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  1. Fabry Disease

    Science.gov (United States)

    ... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Fabry disease is caused by the lack of or faulty ... severe symptoms similar to males with the disorder. × Definition Fabry disease is caused by the lack of or faulty ...

  2. Autonomic skin responses in females with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming W.; Feldt-Rasmussen, Ulla

    2009-01-01

    Fabry disease is a genetic lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system and with neuropathy as a prominent manifestation. Neurological symptoms include pain and autonomic...... dysfunction. This study examined peripheral autonomic nerve function in 19 female patients with Fabry disease and 19 sex and age-matched controls by measuring (1) sweat production following acetylcholine challenge; (2) the sympathetically mediated vasoconstrictor responses to inspiratory gasp, stress......, and the cold pressor test; and (3) cutaneous blood flow following capsaicin. The vasoconstrictor response to inspiratory gasp was increased in Fabry patients compared to controls (p = 0.03), while the response to cold and mental stress did not change. Female patients with Fabry disease had a reduced sweat...

  3. Fabry's disease.

    Science.gov (United States)

    Adam, Tatiana; Alexandrescu, Luana; Voinea, F; Toringhibel, M; Hâncu, Anca

    2006-01-01

    Fabry's disease is a rare X-linked, recessive, glycolipid storage disorder. It is caused by the deficient activity of a lysosomal enzyme, alpha-galactosidase A. Deficiency of alpha-GAL causes an inability to catabolize the lipids with cellular accumulation of its most abundant substrate, globotriaosylceramide (GL-3), and other neutral glycosphingolipids in the vascular endothelium and numerous tissues throughout the body. This progressive glycosphingolipid accumulation leads to life-threatening clinical sequelae in renal, cardiac and cerebrovascular systems. Heterozygous Fabry's disease is less studied. We present a patient, 43 years old, with cardiac (hypertrophic cardiomyopathy), neurological (sensitive-motive polyneuropathy), digestive (chronic diarrheea), renal and cutaneous involvements.

  4. [Fabry disease].

    Science.gov (United States)

    Stephan, F; Haber, R

    2017-02-01

    Fabry disease, also known as Anderson-Fabry disease or angiokeratoma corporis diffusum universale, is an X-linked recessive form of sphingolipidosis caused by total or partial deficiency of the lysosomal hydrolase, alpha-galactosidase A. From the youngest age, it results in a gradual ubiquitous build-up of glycosphingolipids that are not degraded by the missing enzyme. Cutaneous, neurological, nephrologic, cardiac, gastrointestinal, ophthalmological, respiratory, cochleovestibular and haematological involvement are responsible for increased mortality and significant impairment of quality of life in subjects affected by the disease. Angiokeratomas are the most common cutaneous sign of this disease, although they are not specific to it and must be distinguished from angiokeratomas either occurring in isolation or associated with systemic diseases. Other cutaneous signs encountered in this disease include hyperhidrosis, oral lesions, lower limb oedemas, etc. The diagnosis is mainly clinical and should be considered in the presence of a personal and/or familial history; it is confirmed by assay of enzyme activity within leucocytes or by molecular studies. Management is multidisciplinary and involves symptomatic treatment as well as specific treatment, resulting in improved survival and enhanced quality of life for patients presenting the disease. Enzyme replacement therapy with alpha-galactosidase A forms the cornerstone of specific treatment and may be associated with other types of treatments such as galactose and molecular chaperones. Gene therapy is now also used extensively. At present, these marked therapeutic advances, which closely involve dermatologists, could help transform the prognosis for patients presenting Fabry disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Fabry disease

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2010-11-01

    Full Text Available Abstract Fabry disease (FD is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain, cutaneous (angiokeratoma, renal (proteinuria, kidney failure, cardiovascular (cardiomyopathy, arrhythmia, cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with

  6. Is it Fabry disease?

    NARCIS (Netherlands)

    Schiffmann, Raphael; Fuller, Maria; Clarke, Lorne A.; Aerts, Johannes M. F. G.

    2016-01-01

    Fabry disease is caused by mutations in the GLA gene that lower alpha-galactosidase A activity to less than 25-30% of the mean normal level. Several GLA variants have been identified that are associated with relatively elevated residual alpha-galactosidase A. The challenge is to determine which GLA

  7. Fabry disease in children

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Feldt-Rasmussen, U; Rasmussen, AK

    2013-01-01

    Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational...... retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow......-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also...

  8. Fabry disease, respiratory symptoms, and airway limitation

    DEFF Research Database (Denmark)

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    BACKGROUND: Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A, resulting in accumulation of glycosphingolipids in multiple organs, primarily heart, kidneys, skin, CNS, and lungs. MATERIALS AND METHOD: A systematic literature search was performed...... using the PubMed database, leading to a total number of 154 hits. Due to language restriction, this number was reduced to 135; 53 papers did not concern Fabry disease, 19 were either animal studies or gene therapy studies, and 36 papers did not have lung involvement in Fabry disease as a topic....... The remaining 27 articles were relevant for this review. RESULTS: The current literature concerning lung manifestations describes various respiratory symptoms such as dyspnoea or shortness of breath, wheezing, and dry cough. These symptoms are often related to cardiac involvement in Fabry disease as respiratory...

  9. Genetics Home Reference: Fabry disease

    Science.gov (United States)

    ... Page National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet Educational Resources (9 links) Children Living With Inherited Metabolic Diseases (CLIMB) (UK): Fabry Disease Fact Sheet (PDF) Disease InfoSearch: ... Trait Profile National Kidney Foundation Orphanet: ...

  10. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    . Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...... treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry...

  11. Clinical heterogeneity in Fabry disease

    Directory of Open Access Journals (Sweden)

    G. N. Salogub

    2015-01-01

    Full Text Available Fabry disease is an X-linked, lysosomal storage disease (OMIM: 301500, caused by α-galactosidase A deficiency, resulting in accumulation of its substrates, glycosphingolipids, primarily – globotriaosylceramide, in the lysosomes of multiple cell types with multi-system clinical manifestations, even within the same family, including abnormalities of the central and peripheral nervous system, kidneys, heart, gastrointestinal tract, lungs, organ of vision. Clinical heterogeneity is often the reason of the delayed diagnosis. Nowadays enzyme replacement therapy has proved its efficiency in the treatment of Fabry disease. Including Fabry disease in the differential diagnosis of a large range of disorders is important because of its wide clinical heterogeneity and the possibility of an earlier intervention with a beneficial treatment.

  12. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme a-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  13. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  14. Electroneuromyographic Features in Fabry Disease: A Retrospective Review.

    Science.gov (United States)

    Akpinar, Çetin Kürşad; Türker, Hande; Bayrak, Oytun; Cengiz, Nilgün

    2015-09-01

    . Quantitative sensory test, autonomic tests (R-R interval and sympathetic skin response) and skin biopsy should be performed in such cases. In our country, pediatric physicians work on Fabry disease more than physicians dealing with Fabry disease in adults. Therefore, in this retrospective study, we aimed to draw adult and pediatric neurologists' attention to Fabry disease.

  15. Redefining the Pulvinar Sign in Fabry Disease.

    Science.gov (United States)

    Cocozza, S; Russo, C; Pisani, A; Olivo, G; Riccio, E; Cervo, A; Pontillo, G; Feriozzi, S; Veroux, M; Battaglia, Y; Concolino, D; Pieruzzi, F; Mignani, R; Borrelli, P; Imbriaco, M; Brunetti, A; Tedeschi, E; Palma, G

    2017-12-01

    The pulvinar sign refers to exclusive T1WI hyperintensity of the lateral pulvinar. Long considered a common sign of Fabry disease, the pulvinar sign has been reported in many pathologic conditions. The exact incidence of the pulvinar sign has never been tested in representative cohorts of patients with Fabry disease. The aim of this study was to assess the prevalence of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease cohort, determining whether relaxometry changes could be detected in this region independent of the pulvinar sign positivity. We retrospectively analyzed brain MR imaging of 133 patients with Fabry disease recruited through specialized care clinics. A subgroup of 26 patients underwent a scan including 2 FLASH sequences for relaxometry that were compared with MRI scans of 34 healthy controls. The pulvinar sign was detected in 4 of 133 patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53, 7.5% of the entire male population) with renal failure and under enzyme replacement therapy. When we tested for discrepancies between Fabry disease and healthy controls in quantitative susceptibility mapping and relaxometry maps, no significant difference emerged for any of the tested variables. The pulvinar sign has a significantly lower incidence in Fabry disease than previously described. This finding, coupled with a lack of significant differences in quantitative MR imaging, allows hypothesizing that selective involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease. © 2017 by American Journal of Neuroradiology.

  16. Cochleovestibular Manifestations in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  17. Fabry Disease: A Disorder of Childhood Onset.

    Science.gov (United States)

    Schiffmann, Raphael; Ries, Markus

    2016-11-01

    Fabry disease, an X-linked disorder of glycosphingolipids, markedly increases the risk of systemic vasculopathy, ischemic stroke, small-fiber peripheral neuropathy, cardiac dysfunction, and chronic kidney disease. We performed an extensive PubMed search on the topic of Fabry disease and drew from our cumulative 43 years of experience. Most of these complications are nonspecific in nature and clinically indistinguishable from similar abnormalities that occur in the context of more common disorders in the general population. This disease is caused by variants of the GLA gene, and its incidence may have been underestimated. However, one must also guard against overdiagnosis of Fabry disease and unjustified enzyme replacement therapy, because some of the gene variants are benign. Specific therapy for Fabry disease has been developed in the last few years, but its clinical effect has been modest. Novel therapeutic agents are being developed. Standard "nonspecific" medical and surgical therapy is necessary and effective in slowing deterioration or compensating for organ failure in patients with Fabry disease. Fabry disease is a treatable and modifiable genetic risk factor for a myriad of clinical organ complications. Fabry disease may be frequently overlooked but on occasion overdiagnosed. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Biomarkers for diagnosing and staging of Fabry disease.

    Science.gov (United States)

    Krämer, Johannes; Weidemann, Frank

    2017-06-16

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient activity of α -galactosidase A which leads to progressive intracellular accumulation of globotriaosylceramide in tissues and organs including heart, kidney, vascular endothelium, the nervous system, the eyes and the skin. Cardiac involvement is common, leads to fatal complications and is mainly responsible for reduced life expectancy in Fabry disease. The exact staging of disease progression and timely initiation of treatment is essential in Fabry disease. Therefore it is essential to use the possibilities of specific biomarkers for early detection of organ involvement or early diagnosis. By the use of Pubmed all relevant papers for biomarkers in Fabry disease were screened. The quality of retrieved papers was appraised using standard tools. Finally 56 peer reviewed paper were included. In the past biomarkers for Fabry disease biomarkers did not have clinical relevance. Nowadays, a lot of research is focusing on identification of new biomarkers and their clinical relevance. Only two biomarkers reached clinical applicability. Lyso-GB3 for identification of atypical FD variants and hsTNT for identification of cardiac involvement, which should indicate further diagnostics. Treatment response to ERT can be monitored by lyso-GB3 but data for long-time outcome are missing. A lot of GB3-related analogues are identified in urine and plasma, some of which might play an important role for managing Fabry disease in future. In conclusion, we suggest to measure lyso-GB3 and hsTNT at least once a year. The routinely measurement of these two biomarkers will help now for the staging of every individual patient and in addition, will help for a better general understanding of Fabry disease . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Renal complications of Fabry disease in children.

    Science.gov (United States)

    Najafian, Behzad; Mauer, Michael; Hopkin, Robert J; Svarstad, Einar

    2013-05-01

    Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis, and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges, and needs to better approach renal complications of Fabry disease in children.

  20. Fabry disease presenting with sudden hearing loss and otosclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Felisati Giovanni

    2012-04-01

    Full Text Available Abstract Introduction Fabry disease is an X-linked lysosomal storage disorder resulting in a multiple-system disorder with a wide spectrum of physical signs and symptoms, predominantly affecting the central and peripheral nervous systems, skin, heart, kidneys, and eyes. Case presentation We describe the case of a 26-year-old European Caucasian man who had Fabry disease and who presented with episodic sudden unilateral hearing loss and was treated with glucocorticoids, pentoxifylline, hyperbaric oxygen, and fluoride because of concomitant audiometric evidence of otosclerosis. This case demonstrates the partial and transient beneficial effect of standard treatment for sudden hearing loss not related to Fabry disease and analyzes the possible connection between typical Fabry disease inner-ear lesions and otosclerosis. Whereas hearing loss has been described in connection with Fabry disease, otosclerosis-associated hearing loss in Fabry disease has not yet been described. Conclusions Although progressive hearing loss in patients with Fabry disease seems to be influenced by replacement therapy, few data concerning treatment of sudden hearing loss are available. The lack of literature concerning the pathogenesis of the otological involvement in Fabry disease makes it impossible to identify a connection between the latter and otosclerosis. Therefore, this report may help to reinforce the importance of a thorough evaluation of hearing in patients with Fabry disease and may be of help with therapeutic decision-making.

  1. No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy.

    Science.gov (United States)

    de Greef, Bianca T A; Hoeijmakers, Janneke G J; Wolters, Emma E; Smeets, Hubertus J M; van den Wijngaard, Arthur; Merkies, Ingemar S J; Faber, Catharina G; Gerrits, Monique M

    2016-01-01

    Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy. Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations. 725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished α-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease. In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions.

  2. No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy.

    Directory of Open Access Journals (Sweden)

    Bianca T A de Greef

    Full Text Available Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy.Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations.725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished α-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease.In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions.

  3. Vertebrobasilar Dolichoectasia in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Juan Politei

    2014-06-01

    Full Text Available Introduction: Fabry disease (FD is a lysosomal storage disorder associated with marked cerebrovascular involvement. Conventional magnetic resonance imaging (MRI shows different abnormalities, like white matter lesions that may already be present at an early stage in the disease. Aim: To present observations from a series of brain MRIs performed among a cohort of patients with FD and the relationship of imaging abnormalities with the presence of cardiovascular risk factors (CVRFs. Methods: A total of 70 patients with FD (43 women were enrolled. The cardiac, renal, ophthalmic, and peripheral nerve functioning was assessed. The MRI evaluation included assessment for evidence of ischemia, microbleeds, pulvinar sign, Arnold-Chiari type 1 malformation, and vertebrobasilar dolichoectasia (VBD. The presence or absence of CVRFs was examined for all patients. Results: Renal involvement was found in 60%, cardiac compromise in 30%, cornea verticillata in 91.4%, and acroparesthesias in 87.1% of patients. Brain MRI analysis found evidence of cerebral ischemic injury in 25.9% of men and 30.2% of women. Vertebrobasilar dolichoectasia was observed in imaging from 55.5% of men and 34.8% of women. The logistic regression analysis adjusted for cardiovascular risks factors, using ischemia or VBD as a dependent variable, showed no statistically significant results. Discussion: Our results have demonstrated cerebrovascular involvement before the third decade in many patients with FD. This study is further evidence confirming that women are not just carriers of FD and should be followed clinically and evaluated comprehensively to monitor for disease burden and progression. Although silent brain ischemias in MRI should be included as a key feature for the diagnoses of FD, VBD is an earlier and frequent sign.

  4. Fabry disease and incidence of cancer.

    Science.gov (United States)

    Bird, Sarah; Hadjimichael, Efthymios; Mehta, Atul; Ramaswami, Uma; Hughes, Derralynn

    2017-09-06

    Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α-galactosidase A and the resulting accumulation of the glycosphingolipid globotriaosylceramide (Gb3) and its derivatives, including globotriaosylsphingosine (Lyso-Gb3). Increased cellular and plasma levels of Gb3 and Lyso-Gb3 affect multiple organs, with specific clinical consequences for the kidneys, heart and brain. There is growing evidence that alterations in glycosphingolipids may have an oncogenic role and this prompted a review of cases of cancer and benign lesions in a large single centre cohort of Fabry patients. We also explored whether there is a difference in the risk of cancer in Fabry patients compared to the general population. Our results suggest that Fabry patients may have a marginally reduced rate of all cancer (incidence rate ratio 0.61, 95% confidence interval 0.37 to 0.99) but possibly increased rates of melanoma, urological malignancies and meningiomas. Greater knowledge and awareness of cancer in patients with Fabry disease may help identify at-risk individuals and elucidate cancer mechanisms in this rare inherited disease, which may potentially be relevant to the wider cancer population.

  5. Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST).

    Science.gov (United States)

    Saito, Osamu; Kusano, Eiji; Akimoto, Tetsu; Asano, Yasushi; Kitagawa, Teruo; Suzuki, Ken; Ishige, Nobuyuki; Akiba, Takashi; Saito, Akira; Ishimura, Eiji; Hattori, Motoshi; Hishida, Akira; Guili, Chu; Maruyama, Hiroki; Kobayashi, Masahisa; Ohashi, Touya; Matsuda, Ichiro; Eto, Yoshikatsu

    2016-04-01

    In Fabry disease, progressive glycolipid accumulation leads to damage in kidney and other organs. This study was designed to determine the prevalence rate of Fabry disease in Japanese dialysis patients. All dialysis patients agreeing to Japan Fabry disease screening study (J-FAST) with informed consent were selected except for Fabry disease. The screening was performed by a method of measuring plasma and/or leukocytes lysosomal α-galactosidase A protein level and α-galactosidase A activity. If positive, genetic analysis was carried out upon patient's agreement. J-FAST dealt with 8547 patients (male 5408, female 3139). At the tertiary examination, 26 out of 8547 patients were found to be positive. Six out of 26 patients could not accept genetic analysis because of death. Remaining 20 patients agreed with genetic analysis; then 2 patients (male 2, female 0) had a variation of the α-Gal gene and 11 patients showed E66Q variations. Therefore, the frequency of Fabry disease in J-FAST was 0.04 % (2/5408) in males and 0 % (0/3139) in females, and then 0.02 % (2/8547) in all patients. The presumptive clinical diagnoses of end-stage kidney disease (ESKD) were 10 chronic glomerulonephritis, 7 diabetic nephropathy, 3 unknown etiology, 3 nephrosclerosis, 1 gouty nephropathy, 1 autosomal dominant polycystic kidney disease and 1 renal tuberculosis among 26 tertiary positive patients. Two male Fabry patients were initially diagnosed as nephrosclerosis and chronic glomerulonephritis. The prevalence rate of Fabry disease in J-FAST was 0.02 %. Moreover, Fabry disease could not be ruled out as the clinical diagnosis of ESKD.

  6. Enzyme Replacement Therapy for Fabry Disease

    Directory of Open Access Journals (Sweden)

    Maria Dolores Sanchez-Niño PhD

    2016-11-01

    Full Text Available Fabry disease is a rare X-linked disease caused by the deficiency of α-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human α-galactosidase A (agalsidase are available in most markets: agalsidase-α and agalsidase-β, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-α. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-α is 0.2 mg/kg/2 weeks, while the dose for agalsidase-β is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-β is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death. In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.

  7. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  8. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    OpenAIRE

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for ...

  9. Multiple parapelvic cysts in Fabry disease.

    Science.gov (United States)

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Fabry disease in light of recent review

    International Nuclear Information System (INIS)

    Uyama, Eiichiro

    2008-01-01

    Fabry disease is a lysosomal storage disorder that is caused by mutations in the gene encoding α-galactosidase A on Xq22.1. Typically hemizygous male patients exhibit classic phenotypes such as angiokeratoma, acroparesthesias, episodic pain ''crises,'' hypohidrosis, and whorl-shaped corneal opacities from childhood. However, during adulthood, they gradually develop kidney failure, heart disease, and strokes resulting in early death between 40 to 50 years of age. However, recent studies have indicated a high prevalence of disabling clinical symptoms in heterozygous females patients. Patients having the cardiac variant of Fabry's disease exhibit only left ventricular hypertrophy, while patients having the renal variant exhibit only kidney failure. Individuals affected by these variants show higher residual enzyme activity of α-galactosidase A than individuals affected by the classic form of Fabry's disease due to missense mutations of the GLA gene. The cerebrovascular involvement in Fabry disease is not rare in both adult hemizygotes and heterozygotes. Infarctions caused by the occlusions of small vessels involving mostly the vertebrobasilar region in approximately two-thirds of the cases, and that is associated with the deposition glycosphingolipids including GL-3 in the walls of these vessels. In Caucasian patients, elongated, ectatic, and tortuous vertebral and basilar arteries are frequently observed on MR angiography (MRA)s. Life-threatening megadolichobasilar anomaly with thrombosis has been identified in a large Hungarian family in which the family members share L16P mutation. On performing MRI, an increased signal intensity was observed in the pulvinar in T 1 -weighted images; this is the characteristic so-called ''pulvinar sign''. Enzyme replacement therapy has been approved in Japan since 2004 and 2007 for agalsidase β and agalsidase α, respectively. This treatment modestly improves the small-fiber neuropathy, hypohidrosis, hypertrophic cardiomyopathy

  11. Chloroquine-induced lipidosis mimicking Fabry disease.

    Science.gov (United States)

    Albay, Diana; Adler, Sharon G; Philipose, Jaya; Calescibetta, C C; Romansky, Stephen G; Cohen, Arthur H

    2005-05-01

    Intracellular accumulation of phospholipids may be a consequence of inherited or acquired metabolic disorders. In Fabry disease, deficiency of alpha-galactosidase A results in storage of globotriasylceramide in numerous cells including endothelium, striated muscle (skeletal, cardiac), smooth muscle, and renal epithelium among others; the ultrastructural appearance of the inclusions is of whorled layers of alternating dense and pale material ('zebra bodies' or myeline figures). Chloroquine therapy may result in storage of biochemically and ultrastructurally similar inclusions in many of the same cells as Fabry disease and often results in similar clinical manifestations. We report a 56-year-old woman with rheumatoid arthritis treated with chloroquine, who developed muscle weakness and renal insufficiency; information regarding therapy was not emphasized at the time of renal biopsy, leading to initial erroneous interpretation of Fabry disease. Following muscle biopsy, genetic and enzyme evaluation, and additional studies on the kidney biopsy, a diagnosis of chloroquine toxicity was established. One year following cessation of chloroquine, renal and muscle dysfunction greatly improved. In chloroquine toxicity, inclusions in glomeruli are not only in visceral epithelial, endothelial and mesangial cells but are in infiltrating monocytes/macrophages, which are most commonly present in the mesangium. Curvilinear bodies, the ultrastructural features of chloroquine toxicity in striated muscle, are not present in renal cells. This report documents differences in appearance, cells affected and morphological differential diagnostic features to distinguish these two entities.

  12. Fabry disease: A case report and algorithmic approach to angiokeratomas

    Directory of Open Access Journals (Sweden)

    Aslı Aksu Çerman

    2014-12-01

    Full Text Available Fabry disease is an x-linked recessive metabolic storage disorder due to the deficiency of lysosomal α-galactosidase A, and the subsequent accumulation of glycosphingolipids, throughout the body. The presence of diffuse angiokeratomas in Fabry disease is a cutaneous hallmark but it is not a specific one. In this case report, we observed the features of a case of Fabry disease and reviewed the diagnostic approach to angiokeratomas.

  13. Parkinson's disease prevalence in Fabry disease: A survey study.

    Science.gov (United States)

    Wise, Adina H; Yang, Amy; Naik, Hetanshi; Stauffer, Chanan; Zeid, Natasha; Liong, Christopher; Balwani, Manisha; Desnick, Robert J; Alcalay, Roy N

    2018-03-01

    Recent research has suggested a possible link between Parkinson's disease (PD) and Fabry disease. To test this relationship, we administered a self-report and family history questionnaire to determine the prevalence of PD in Fabry disease patients and family members with likely pathogenic alpha-galactosidase A (GLA) mutations. A total of 90 Fabry patients (77 from the online survey and 13 from the Icahn School of Medicine at Mount Sinai (ISMMS)) were included in the analysis. Two of the Fabry disease patients who completed the online survey were diagnosed with PD (2/90, 2.2%). Among probands older than 60, 8.3% (2/24) were diagnosed with PD. Using Kaplan Meier survival analysis, the age-specific risk of PD by age 70 was 11.1%. Family history was available on 72 Fabry families from the online study and 9 Fabry families from ISMMS. Among these 81 families, 6 (7.4%) had one first degree relative who fit the criteria for a conservative diagnosis of PD. The results of this study suggest that there may be an increased risk of developing PD in individuals with GLA mutations, but these findings should be interpreted with caution given the limitations of the study design.

  14. Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study.

    Science.gov (United States)

    Arends, Maarten; Wanner, Christoph; Hughes, Derralynn; Mehta, Atul; Oder, Daniel; Watkinson, Oliver T; Elliott, Perry M; Linthorst, Gabor E; Wijburg, Frits A; Biegstraaten, Marieke; Hollak, Carla E

    2017-05-01

    Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype ( P Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients. Copyright © 2017 by the American Society of Nephrology.

  15. Non-specific gastrointestinal features: Could it be Fabry disease?

    Science.gov (United States)

    Hilz, Max J; Arbustini, Eloisa; Dagna, Lorenzo; Gasbarrini, Antonio; Goizet, Cyril; Lacombe, Didier; Liguori, Rocco; Manna, Raffaele; Politei, Juan; Spada, Marco; Burlina, Alessandro

    2018-03-01

    Non-specific gastrointestinal symptoms, including pain, diarrhoea, nausea, and vomiting, can be the first symptoms of Fabry disease. They may suggest more common disorders, e.g. irritable bowel syndrome or inflammatory bowel disease. The confounding clinical presentation and rarity of Fabry disease often cause long diagnostic delays and multiple misdiagnoses. Therefore, specialists involved in the clinical evaluation of non-specific upper and lower gastrointestinal symptoms should recognize Fabry disease as a possible cause of the symptoms, and should consider Fabry disease as a possible differential diagnosis. When symptoms or family history suggest Fabry disease, in men, low alpha-galactosidase A enzyme levels, and in women, specific Fabry mutations confirm the diagnosis. In addition to symptomatic treatments, disease-specific enzyme replacement therapy with recombinant human alpha-galactosidase A enzyme or chaperone therapy (migalastat) in patients with amenable mutations can improve the disease, including gastrointestinal symptoms, and should be initiated as early as possible after Fabry disease has been confirmed; starting enzyme replacement therapy at as young an age as possible after diagnosis improves long-term clinical outcomes. Improved diagnostic tools, such as a modified gastrointestinal symptom rating scale, may facilitate diagnosing Fabry disease in patients with gastrointestinal symptoms of unknown cause and thus assure timely initiation of disease-specific treatment. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Fabry disease in children: a federal screening programme in Russia.

    Science.gov (United States)

    Namazova-Baranova, Leyla Seymurovna; Baranov, Alexander Alexandrovich; Pushkov, Aleksander Alekseevich; Savostyanov, Kirill Victorovich

    2017-10-01

    Our objective was to examine the prevalence of Fabry disease in Russian children with chronic pain in the distal limbs. This non-interventional, multi-centre study included children 2-18 years of age with chronic recurrent unilateral or bilateral pain, burning, or acroparesthesia in the hands or feet. The presence of Fabry disease was defined by abnormal alpha-galactosidase A activity in males or alpha-galactosidase gene (GLA) mutation in females. Among 214 patients (110 males), 84.1% had bilateral limb pain and 31.8% had unilateral limb pain recorded at some time point; 61 (28.5%) patients had a positive family history possibly associated with Fabry disease. Alpha-galactosidase A activity was within the normal range in all 109 of the male patients tested. One female patient had a GLA mutation (C937G > T) and alpha-galactosidase A activity within the normal range. We did not find definitive evidence of Fabry disease in these children with a history of chronic recurrent unilateral or bilateral limb pain or acroparesthesia. The presence of chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that key early signs and symptoms of Fabry disease are not specific to the disease. What is Known: • Signs and symptoms of Fabry disease are seen in children Fabry disease was not diagnosed in this population of Russian children with a history of chronic limb pain. • The presence of acroparesthesia or chronic limb pain does not appear to be highly predictive of a diagnosis of Fabry disease in Russian children and adolescents, suggesting that these early symptoms of Fabry disease are not specific to the disease.

  17. Elevated globotriaosylsphingosine is a hallmark of Fabry disease

    NARCIS (Netherlands)

    Aerts, Johannes M.; Groener, Johanna E.; Kuiper, Sijmen; Donker-Koopman, Wilma E.; Strijland, Anneke; Ottenhoff, Roelof; van Roomen, Cindy; Mirzaian, Mina; Wijburg, Frits A.; Linthorst, Gabor E.; Vedder, Anouk C.; Rombach, Saskia M.; Cox-Brinkman, Josanne; Somerharju, Pentti; Boot, Rolf G.; Hollak, Carla E.; Brady, Roscoe O.; Poorthuis, Ben J.

    2008-01-01

    Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, and neuropathology usually are ascribed to

  18. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry

    NARCIS (Netherlands)

    Wanner, Christoph; Oliveira, João P.; Ortiz, Alberto; Mauer, Michael; Germain, Dominique P.; Linthorst, Gabor E.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Cianciaruso, Bruno; Vujkovac, Bojan; Lemay, Roberta; Beitner-Johnson, Dana; Waldek, Stephen; Warnock, David G.

    2010-01-01

    These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement

  19. Fabry Disease: A Turkish Case with a Novel Mutation and Dermatological Manifestations

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2015-03-01

    Full Text Available Fabry disease is a rare, X-linked disease, caused by the deficiency of lysosomal and #945;-galactosidase. Clinical fetaures are; acroparesthesia, unexplained fever, hypohidrosis and angiokeratomas. Untreated cases die early from cardiac complications, renal insuffiency or stroke. Currently there is no cure for Fabry disease, enzyme replacement therapy is the only choice in this progressive disease. A 9-year-old boy admitted to the Dermatology Clinic with reddish papular skin lesions, joint pain and anhydrosis. Hystological examination of the skin biopsy revealed angiokeratoma. There was no renal dysfunction or proteinuria. Biochemical confirmation of Fabry disease was made by determining the deficient leukocyte and #945;-galactosidase activity. Subsequently, the patient's molecular analysis was identified a novel nonsense mutation c. 785G>T in the GLA gene. Enzyme replacement therapy with agalsidase beta was started. He is on enzyme replacement therapy for 8 years, significant improvement was obtained in severity and frequency of pain crisis and fatigue. We report this case to emphasize the importance of early diagnosis of Fabry disease restricted to dermatological findings, especially before renal and cardiac involvement occurs, while enzyme replacement therapy is now available. Also this patient is one of the first Fabry patients under enzyme replacement therapy in Turkey. [Cukurova Med J 2015; 40(Suppl 1: 156-160

  20. Fabry disease: a rare cause of neuropathic pain

    NARCIS (Netherlands)

    Biegstraaten, Marieke; Linthorst, Gabor E.; van Schaik, Ivo N.; Hollak, Carla E. M.

    2013-01-01

    Fabry disease is characterized by burning or shooting pains in hands and feet, which have a severe impact on the quality of life of patients. It is therefore of importance that Fabry patients receive adequate diagnosis, counseling, treatment and follow up. This review describes neuropathic pain in

  1. Neuropathic pain in a Fabry disease rat model.

    Science.gov (United States)

    Miller, James J; Aoki, Kazuhiro; Moehring, Francie; Murphy, Carly A; O'Hara, Crystal L; Tiemeyer, Michael; Stucky, Cheryl L; Dahms, Nancy M

    2018-03-22

    Fabry disease, the most common lysosomal storage disease, affects multiple organs and results in a shortened life span. This disease is caused by a deficiency of the lysosomal enzyme α-galactosidase A, which leads to glycosphingolipid accumulation in many cell types. Neuropathic pain is an early and severely debilitating symptom in patients with Fabry disease, but the cellular and molecular mechanisms that cause the pain are unknown. We generated a rat model of Fabry disease, the first nonmouse model to our knowledge. Fabry rats had substantial serum and tissue accumulation of α-galactosyl glycosphingolipids and had pronounced mechanical pain behavior. Additionally, Fabry rat dorsal root ganglia displayed global N-glycan alterations, sensory neurons were laden with inclusions, and sensory neuron somata exhibited prominent sensitization to mechanical force. We found that the cation channel transient receptor potential ankyrin 1 (TRPA1) is sensitized in Fabry rat sensory neurons and that TRPA1 antagonism reversed the behavioral mechanical sensitization. This study points toward TRPA1 as a potentially novel target to treat the pain experienced by patients with Fabry disease.

  2. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy.

    Science.gov (United States)

    Fall, Brent; Scott, C Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.

  3. Gastrointestinal involvement in Fabry disease. So important, yet often neglected.

    Science.gov (United States)

    Politei, J; Thurberg, B L; Wallace, E; Warnock, D; Serebrinsky, G; Durand, C; Schenone, A B

    2016-01-01

    Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms-abdominal pain, nausea, diarrhea and diverticular disease--are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. FabryScan: a screening tool for early detection of Fabry disease

    NARCIS (Netherlands)

    Arning, Kathrin; Naleschinski, Dennis; Maag, Rainer; Biegstraaten, Marieke; Kropp, Peter; Lorenzen, Jürgen; Hollak, Carla E. M.; van Schaik, Ivo N.; Harten, Pontus; Zeuner, Rainald A.; Binder, Andreas; Baron, Ralf

    2012-01-01

    Fabry disease, an X-linked lipid storage disorder, is associated early morbidity and mortality. Since enzyme replacement therapy is available, accurate detection of unrecognized cases is important. Characteristic early symptoms are recurrent episodes of burning and lancinating pain in the distal

  5. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

    Directory of Open Access Journals (Sweden)

    Hoffmann Björn

    2009-10-01

    Full Text Available Abstract Background In Fabry disease (α-galactosidase A deficiency accumulation of Globotriaosylceramide (Gb3 leads to progressive organ failure and premature death. The introduction of enzyme replacement therapy (ERT was the beginning of a new era in this disorder, and has prompted a broad range of research activities. This review aims to summarize recent developments and progress with high impact for Fabry disease. Methods A Pubmed analysis was performed using the search terms "Fabry disease", "Anderson-Fabry disease", "alpha-galactosidase A" and "Gb3". Of the given publications by 31st January 2009 only original articles recently published in peer reviewed journals were included for this review. Case reports were included only when they comprised a new aspect. In addition we included relevant conference abstracts when the results had not already been published as original articles. Results Apart from Gb3-accumulation cellular and organ specific damages may be related also to inflammatory and immunological consequences. It will be interesting whether this may lead to new therapeutic strategies in the treatment of Fabry disease. Since newborn screening is still difficult in Fabry disease, detection of patients in populations at risk is of great importance. Undiagnosed patients with Fabry disease may still be found in cohorts of subjects with renal diseases, cardiomyopathy and TIA or stroke. Efforts should be undertaken to identify these individuals and initialise ERT in order to hault disease progression. It has also been demonstrated that Gb3-accumulation leads to pre-clinical damages and it is believed that early treatment may be the only possibility so far to prevent irreversible organ damage.

  6. [Fabry disease: clinic and enzymatic diagnosis of homozygous and heterozygous. New therapeutic prospects].

    Science.gov (United States)

    Peces, R; Olea, T

    2002-01-01

    Fabry disease is an X-linked recessive lysosomal storage disorder caused by a partial or complete deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of Fabry disease. The finding of a marked decreased activity of (alpha-galactosidase A in plasma, white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. The recently completed double-blind, placebo-controlled trials of intravenous infusions of (alpha-galactosidase A in patients with Fabry disease demonstrated the safety and efficacy of this treatment. We report a family with Fabry disease composed of hemicygous and heterocygous. The propositus developed chronic renal failure and received a cadaver renal transplant, which remained with adequate renal function during 15 years.

  7. Agalsidase beta treatment is associated with improved quality of life in patients with Fabry disease: findings from the Fabry Registry

    DEFF Research Database (Denmark)

    Watt, Torquil; Burlina, Alessandro P; Cazzorla, Chiara

    2010-01-01

    To evaluate the effect of agalsidase beta on longitudinal health-related quality of life in patients with Fabry disease.......To evaluate the effect of agalsidase beta on longitudinal health-related quality of life in patients with Fabry disease....

  8. Arterial Wall Properties and Womersley Flow in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Dimitriadis Emilios

    2002-01-01

    Full Text Available Abstract Background Fabry disease is an X-linked recessive lysosomal storage disease resulting in the cellular accumulation of globotriaosylceramide particularly globotriaosylceramide. The disease is characterized by a dilated vasculopathy with arterial ectasia in muscular arteries and arterioles. Previous venous plethysomographic studies suggest enhanced endothelium-dependent vasodilation in Fabry disease indicating a functional abnormality of resistance vessels. Methods We examined the mechanical properties of the radial artery in Fabry disease, a typical fibro-muscular artery. Eight control subjects and seven patients with Fabry disease had a right brachial arterial line placed allowing real time recording of intra-arterial blood pressure. Real time B-mode ultrasound recordings of the right radial artery were obtained simultaneously allowing calculation of the vessel wall internal and external diameter, the incremental Young's modulus and arterial wall thickness. By simultaneously measurement of the distal index finger-pulse oximetry the pulse wave speed was calculated. From the wave speed and the internal radial artery diameter the volume flow was calculated by Womersley analysis following truncation of the late diastolic phase. Results No significant difference was found between Fabry patients and controls for internal or external arterial diameters, the incremental Young's modulus, the arterial wall thickness, the pulse wave speed and the basal radial artery blood flow. Further, no significant difference was found for the radial artery blood flow in response to intra-arterial acetylcholine or sodium nitroprusside. Both drugs however, elevated the mean arterial flow. Conclusions The current study suggests that no structural or mechanical abnormality exists in the vessel wall of fibro-muscular arteries in Fabry disease. This may indicate that a functional abnormality downstream to the conductance vessels is the dominant feature in

  9. Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

    Science.gov (United States)

    Namer, Barbara; Ørstavik, Kirstin; Schmidt, Roland; Mair, Norbert; Kleggetveit, Inge Petter; Zeidler, Maximillian; Martha, Theresa; Jorum, Ellen; Schmelz, Martin; Kalpachidou, Theodora; Kress, Michaela; Langeslag, Michiel

    2017-01-01

    The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0). The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons. PMID:28769867

  10. Changes in Ionic Conductance Signature of Nociceptive Neurons Underlying Fabry Disease Phenotype

    Directory of Open Access Journals (Sweden)

    Barbara Namer

    2017-07-01

    Full Text Available The first symptom arising in many Fabry patients is neuropathic pain due to changes in small myelinated and unmyelinated fibers in the periphery, which is subsequently followed by a loss of sensory perception. Here we studied changes in the peripheral nervous system of Fabry patients and a Fabry mouse model induced by deletion of α-galactosidase A (Gla−/0. The skin innervation of Gla−/0 mice resembles that of the human Fabry patients. In Fabry diseased humans and Gla−/0 mice, we observed similar sensory abnormalities, which were also observed in nerve fiber recordings in both patients and mice. Electrophysiological recordings of cultured Gla−/0 nociceptors revealed that the conductance of voltage-gated Na+ and Ca2+ currents was decreased in Gla−/0 nociceptors, whereas the activation of voltage-gated K+ currents was at more depolarized potentials. Conclusively, we have observed that reduced sensory perception due to small-fiber degeneration coincides with altered electrophysiological properties of sensory neurons.

  11. A case of Fabry's disease with congenital agammaglobulinemia.

    Science.gov (United States)

    Lee, Ki-Yeol; Jeon, Su-Young; Hong, Jin-Woo; Kim, Sung-Eun; Song, Ki-Hoon; Kim, Young-Hun; Kim, Ki-Ho

    2011-07-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.

  12. Early Renal Involvement in a Girl with Classic Fabry Disease.

    Science.gov (United States)

    Perretta, Fernando; Antongiovanni, Norberto; Jaurretche, Sebastián

    2017-01-01

    Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis). This would explain why women (heterozygotes) present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.

  13. Apical left ventricular hypertrophy and mid-ventricular obstruction in fabry disease.

    Science.gov (United States)

    Cianciulli, Tomás F; Saccheri, María C; Fernández, Segundo P; Fernández, Cinthia C; Rozenfeld, Paula A; Kisinovsky, Isaac

    2015-05-01

    We report the case of a rare cardiac presentation of Fabry disease. Although concentric left ventricular hypertrophy is a major cardiac finding in Fabry disease, there is no case report of dynamic obstruction at mid-left ventricular level. We describe a 59-year-old-woman suffering from a severe form of Fabry disease, mimicking an apical hypertrophic cardiomyopathy with mid-ventricular obstruction. Differentiation of Fabry disease from hypertrophic cardiomyopathy is crucial given the therapeutic and prognostic differences. Fabry disease should always be suspected in an adult, independently of the pattern of left ventricular hypertrophy. © 2015, Wiley Periodicals, Inc.

  14. Fabry's Disease: Case Series and Review of Literature | Wani ...

    African Journals Online (AJOL)

    Fabry's disease is an X‑linked lysosomal storage disorder caused by a deficiency of alpha‑galactosidase A enzyme with the progressive accumulation of globotriaosylceramide in vascular endothelial cells leading to cardiovascular, renal, gastrointestinal, neuropathic, lenticular, and dermatological manifestations. It is a rare ...

  15. Pain in Fabry Disease: Practical Recommendations for Diagnosis and Treatment.

    Science.gov (United States)

    Politei, Juan M; Bouhassira, Didier; Germain, Dominique P; Goizet, Cyril; Guerrero-Sola, Antonio; Hilz, Max J; Hutton, Elspeth J; Karaa, Amel; Liguori, Rocco; Üçeyler, Nurcan; Zeltzer, Lonnie K; Burlina, Alessandro

    2016-07-01

    Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. © 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

  16. Prevalence of Anderson-Fabry disease in patients with hypertrophic cardiomyopathy: the European Anderson-Fabry Disease survey

    NARCIS (Netherlands)

    Elliott, Perry; Baker, Robert; Pasquale, Ferdinando; Quarta, Giovanni; Ebrahim, Hatim; Mehta, Atul B.; Hughes, Derralynn A.; Anastasakis, Aristides; Autore, Camillo; Musumeci, Maria Beatrice; Frenneaux, Michael; Gimeno, Juan; Tiina, Heliö; Kuusisto, Johanna; Aalto-Setäla, Katriina; McKeown, Pascal; Monserrat, Lorenzo; Fernandez, Xusto; Pacileo, Giuseppe; Limongelli, Giuseppe; Rapezzi, Claudio; Biagini, Elena; ten Cate, Folkert J.; Wilde, Arthur A. M.; Pinto, Yigal M.; Christiaans, Imke; Zachara, Elisabetta

    2011-01-01

    The prevalence of Anderson-Fabry disease (AFD) in patients presenting with unexplained left ventricular hypertrophy (LVH) is controversial. The aim of this study was to determine the prevalence of AFD in a large, consecutive cohort of patients with hypertrophic cardiomyopathy (HCM) using rapid

  17. Fabry disease, do we think enough about this multisystemic disorder?: A presentation of three cases in a Serbian family

    Directory of Open Access Journals (Sweden)

    Sakač Dejan

    2012-01-01

    Full Text Available Background. Fabry Disease is a rare, X-chromosomal inherited lysosomal storage disease with a consequent intracellular accumulation of neutral glycosphingolipids in various tissues. This can cause skin and ocular lessions, progressive renal, cardiac or cerebrovascular disorders. If a person in a family has Fabry disease, other family members including even extended relatives, may also be at risk. Case report. We presented three cases pointed out various manifestation of Fabry disease, that illustrate a possible cause for otherwise unexplained cardiac hypertrophy and various rhythm and conduction abnormalities. Conclusion. Although most symptoms begin in childhood, various manifestations often lead to misdiagnosis and clinical diagnosis is frequently delayed for many years, even decades. Enzyme replacement therapy has become available, pointing out the importance of early diagnosis so that treatment can be initiated before irreversible organ damage.

  18. Teenager male with burning pain in extremities--suspect Fabry disease, 2 case reports.

    Science.gov (United States)

    Patil, Rajesh B; Joglekar, V K

    2014-01-01

    We present 2 cases of teenager males presented with burning pain in extremities and turned out to be cases of Fabry disease.The purpose of presenting this case is to highlight the fact that suspicion of Fabry disease in patients presenting with these symptoms will lead to early diagnosis and treatment of this condition before occurrences of complications. A 14-year-old male presented with severe burning pain in both hands and feet since last 4 yrs which persisted despite consumption of painkillers and becoming more disabling and without having any family history for such condition. On general examination patient had small reddish coloured lesions around the umbilicus, appearing like angiokeratomas. Skin biopsy confirmed the lesion. On enzyme assay his alpha galactosidase activity found to be '0' nmol/hr/mg of protein, confirming his diagnosis. Patient's creatinine and 2 D ECHO were normal and urine had 1+ proteinuria. Patient started on carbamazepine tablets for pain and referred to higher centre for genetic diagnosis and enzyme replacement therapy. CASE REPORT 2: An 18-year-old male referred to our hospital by general practitioner for fatigue and pedal oedema with deranged renal function tests. On history taking patient gave history of severe burning pain in both hands and feet since age of 9 yrs. Patient's general examination revealed hypertension with pallor, pedal oedema along with angiokeratomas in bathing suit distribution. Patient's ultrasonography of kidney revealed bilaterally normal sized kidneys with altered echotexture and urine examination showed fine granular foamy cells with sub nephrotic range proteinuria. 2 D ECHO revealed concentric left ventricular hypertrophy. Skin biopsy report supported the diagnosis of Fabry disease. Patient advised to undergo renal biopsy to confirm Fabry nephropathy but patient denied any further diagnostic workup for nephropathy or Fabry disease. Patient started on conservative treatment and carbamazepine in renal dose

  19. Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

    International Nuclear Information System (INIS)

    Gruber, S.; Bogner, W.; Stadlbauer, A.; Krssak, M.; Bodamer, O.

    2011-01-01

    Objective: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. Methods: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. Results: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). Conclusions: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

  20. Time of Anderson-Fabry Disease Detection and Cardiovascular Presentation

    Directory of Open Access Journals (Sweden)

    K. Selthofer-Relatic

    2018-01-01

    Full Text Available Background. Anderson-Fabry disease is an X-linked inherited disease, which manifests in a different manner depending on gender and genotype. Making a working diagnosis of Anderson-Fabry disease is difficult because of several reasons: (a that it is a multiorgan disease with wide variety of phenotypes, (b different timelines of presentation, (c gender differences, and (d possible coexistence with other comorbidities. Late-onset/cardiac type of presentation with minimal involvement of other organs can additionally make diagnosis difficult. Aim. To describe different cardiac manifestations at different time points in the course of the disease: (1 72-year-old female (echocardiography detection, heterozygote, significant left and mild right ventricular hypertrophy; (2 62-year-old male (echocardiography detection, hemizygote, left ventricular hypertrophy, implanted cardiac pacemaker, a performed percutaneous coronary intervention after myocardial infarction, degenerative medium degree aortic valve stenosis; (3 45-year-old female (asymptomatic/family screening, heterozygote, thickened mitral papillary muscle, mild left ventricular hypertrophy, first degree diastolic dysfunction; and (4 75-year-old female (symptomatic/family screening, heterozygote, cardiomyopathy with reduced left ventricular ejection fraction after heart surgery (mitral valve annuloplasty and plastic repair of the tricuspid valve. Conclusion. All patients have Anderson-Fabry disease but with different clinical presentations depending on the gender, the type of mutation, and the time of detection. All these features can make the patients’ profiles unique and delay the time of detection.

  1. The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

    Science.gov (United States)

    Turkmen, Kultigin; Guclu, Aydın; Sahin, Garip; Kocyigit, Ismail; Demirtas, Levent; Erdur, Fatih Mehmet; Sengül, Erkan; Ozkan, Oktay; Emre, Habib; Turgut, Faruk; Unal, Hilmi; Karaman, Murat; Acıkel, Cengiz; Esen, Hasan; Balli, Ebru; Bıtırgen, Gulfidan; Tonbul, Halil Zeki; Yılmaz, Mahmut Ilker; Ortiz, Alberto

    2016-01-01

    Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. © 2016 The Author(s) Published by S. Karger AG, Basel.

  2. The Impact of Fabry Disease on Reproductive Fitness

    OpenAIRE

    Laney, Dawn A.; Clarke, Virginia; Foley, Allison; Hall, Eric W.; Gillespie, Scott E.; Holida, Myrl; Simmons, Morgan; Wadley, Alexandrea

    2017-01-01

    Fabry disease (FD) is a pan-ethnic, X-linked, progressive lysosomal storage disorder caused by pathogenic mutations in the GLA gene. Published case reports and abstracts suggest that decreased reproductive fitness may occur in males with FD. In order to understand the impact of FD on reproductive fitness and increase the accuracy of reproductive genetic counseling, this study examines a large, multi-centered population of individuals with FD to determine if males have reduced reproductive fit...

  3. Early Renal Involvement in a Girl with Classic Fabry Disease

    Directory of Open Access Journals (Sweden)

    Fernando Perretta

    2017-01-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis. This would explain why women (heterozygotes present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.

  4. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    ... a serious case, you might need medical help. Impetigo —A skin infection caused by bacteria. Usually the ... and form a thick crust. You can treat impetigo with antibiotics. Melanoma © 2008 Logical Images, Inc. Melanoma — ...

  5. Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease

    Science.gov (United States)

    Üçeyler, Nurcan; Homola, György A.; Guerrero González, Hans; Kramer, Daniela; Wanner, Christoph; Weidemann, Frank; Solymosi, László; Sommer, Claudia

    2014-01-01

    A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males – females; normal – impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13%) and 5/57 (9%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1%). Male Fabry patients had a larger basilar artery (p3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87%, specificity: 86%, pFabry disease independent of disease severity. PMID:24475221

  6. Avascular necrosis of bilateral femoral heads in a patient with Fabry's disease.

    LENUS (Irish Health Repository)

    O'Neill, Francis

    2012-07-13

    The underlying cause of avascular necrosis (AVN) of the femoral head is often not apparent. We report the case of a 26 year old builder with a four month history of bilateral hip pain, and a diagnosis of bilateral femoral head avascular necrosis. Fabry\\'s disease was identified as the probable cause. Since 2001, enzyme replacement therapy for Fabry\\'s disease has become available, with a potential to influence the disease process, and this is of potential importance to clinicians treating AVN.

  7. Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS--the Fabry Outcome Survey

    NARCIS (Netherlands)

    Hughes, Derralynn A.; Barba Romero, Miguel-Ángel; Hollak, Carla E. M.; Giugliani, Roberto; Deegan, Patrick B.

    2011-01-01

    Fabry disease (α-galactosidase A deficiency) is an X-linked disorder. Women who are heterozygous for disease-causing mutations often manifest signs and symptoms of Fabry disease, but most studies of the effects of enzyme replacement therapy (ERT) have included only men. To date, no direct comparison

  8. Compromiso cardiovascular en la enfermedad de Fabry Cardiovascular involvement in Fabry disease

    Directory of Open Access Journals (Sweden)

    Ana M Barón O

    2008-06-01

    Full Text Available La enfermedad de Fabry es una patología de origen genético que se produce por el depósito, a nivel lisosomal, de diferentes productos como globotriazolceramida, glicoesfingolípidos neurales y diagalactosilceramida a nivel sistémico, como consecuencia de la actividad deficiente de la enzima alfa-galactosidasa A. Las manifestaciones clínicas se inician desde la infancia pero son sutiles y suelen confundirse con otras patologías, razón por la cual en la mayoría de los casos la enfermedad se detecta en grados avanzados. En los adultos los órganos más afectados son corazón, riñones y cerebro. El compromiso cardiaco es de gran importancia por tratarse de una de las principales causas de morbi-mortalidad. El depósito de estas moléculas ocurre en todos sus componentes celulares. Genera hipertrofia e isquemia y remodelación miocárdica, o ambas. En la actualidad existe tratamiento específico con agalasidasa A y B recombinante, con el cual se logra una disminución en los depósitos lisosomales. Se recomienda aumentar la vigilancia de la enfermedad para detectar los casos e iniciar el tratamiento lo más temprano posible.Fabry disease is a genetic condition that causes lysosomal storage of products like glotriaosylceramide, neural glycosphingolipids and diagalactosylceramide, as a consequence of alpha-galactosidase A enzyme deficiency. Clinical manifestations begin in childhood, but they are subtle, and can mimic other pathologies, delaying the diagnosis until the second or third decade of life, when the disease is in an advanced stage. In adults the most affected organs are heart, kidneys and brain. Cardiac involvement is one of the most important causes of morbidity and mortality. Deposits of these molecules occur in every component of the heart, leading to hypertrophy, ischemia and myocardial remodeling. Nowadays there is specific enzyme replacement therapy with recombinant agalacidase A and B that decreases lysosomal deposits and

  9. Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry.

    Science.gov (United States)

    Auray-Blais, Christiane; Blais, Catherine-Marie; Ramaswami, Uma; Boutin, Michel; Germain, Dominique P; Dyack, Sarah; Bodamer, Olaf; Pintos-Morell, Guillem; Clarke, Joe T R; Bichet, Daniel G; Warnock, David G; Echevarria, Lucia; West, Michael L; Lavoie, Pamela

    2015-01-01

    Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. A UPLC-MS/MS was used for biomarker analysis. Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease.

    Science.gov (United States)

    Mignani, Renzo; Pieruzzi, Federico; Berri, Francesco; Burlina, Alessandro; Chinea, Benito; Gallieni, Maurizio; Pieroni, Maurizio; Salviati, Alessandro; Spada, Marco

    2016-10-01

    Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R (2) = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

  11. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    Science.gov (United States)

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into account that they are based on retrospective comparisons with previously published data.

  12. Enzyme replacement therapy in Fabry Disease: the importance of dose

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2017-04-01

    Full Text Available Fabry disease is a rare X-linked inherited disorder due to deficient or absent lysosomal α-galactosidase A activity, resulting in an excessive glycosphingolipid deposit, mainly globotriaosylceramide (gl3 and mortality due renal, cardiac and neurological cause. Current treatment available is enzyme replacement therapy, where the deficient enzyme is substituted. In Latinamerica and Europe two different formulations of agalsidase (alfa and beta are available. Food and Drug Administration in United States did not approve agalsidasa Alfa. The main difference among these formulations is the licensed dose: 0.2 mg/kg every other week for Alfa and 1 mg/kg every other week for Beta. Recent studies suggest a dose-dependent response, making 0.2 mg/kg every other week not sufficient in some patients. However there are no tools to predict which patients need a higher dose for preventing or decreasing the disease progression. This review, summarize the current knowledge about the impact of different dose and its efficacy in Fabry disease.

  13. Enfermedad de Fabry: Comunicación de ocho casos Fabry disease: Report of eight cases

    Directory of Open Access Journals (Sweden)

    M Palombo

    2011-12-01

    Full Text Available La Enfermedad de Fabry (EF constituye una alteración hereditaria del metabolismo de los glicoesfingolípidos, debida a la deficiencia parcial o completa de la enzima alfa-galactosidasa A. Es una enfermedad de transmisión genética ligada a X, que afecta universalmente a todas las etnias humanas con una incidencia comunicada de 1 cada 100.000 nacimientos, aunque es probable que esta cifra subestime la real prevalencia de la enfermedad, especialmente por el gran número de casos no diagnosticados. La EF se manifiesta en su forma más florida, en varones homocigotas que carecen completamente de actividad alfa-galactosidasa A, provocando una miríada de alteraciones, incluyendo anomalías renales (proteinuria progresiva e insuficiencia renal, cardiovasculares (cardiopatías, arritmias, accidentes cerebrovasculares, neurológicas (dolor acral y abdominal, y cocleo-vestibulares, entre las más importantes. Sin embargo, la afectación cutánea constituye la alteración más específica de la enfermedad y es en general, la que conduce a la sospecha diagnóstica. La EF no tratada reduce francamente la expectativa de vida de acuerdo a la severidad de la afectación renal y cardiovascular, si bien la terapia con reemplazo enzimático puede modificar e incluso detener el curso de la enfermedad. En 2010, una paciente de 28 años oriunda de la Provincia de Santa Fe, consultó porangioqueratomas, que condujeron al diagnóstico de enfermedad de Fabry. Desde entonces hemos estudiado y tratado a toda la familia, con ocho casos confirmados a la fecha y otros tantos en evaluación.Fabry disease (Online Mendelian Inheritance in Man No. 301500 is an X-linked inherited condition due to absence or reduction of ɑ galactosidase activity in lysosomes that results in accumulation of globotriaosylceramide and related neutral glycosphingolipids (storage disorder. It is estimated to occur in 1 in 40.000 to 117.000 live male births, although a more recent screening study in

  14. Cognitive impairment and Fabry Disease: a case report with mutation S126G

    Directory of Open Access Journals (Sweden)

    Razza, Grazia

    2016-11-01

    Full Text Available Anderson-Fabry Disease is a lysosomal storage disease, multisystem, progressive, hereditary, linked to the X-chromosome. Specifically, it is characterized by a glycosphingolipid metabolism due to the reduction or absence of Alpha-galactosidase, an enzyme activity lisosomile gene mutation GLA (Xq21.3-q22, which encodes the enzyme. The decreased activity causes the accumulation of globotriaosylceramide (Gb3 within lysosomes, which in turn sets off a cascade of cellular events. The clinical picture presents a wide spectrum of manifestations of multiple systems: neurological, skin, kidney, cardiovascular disease, auditory and vestibular and cerebrovascular. Despite the recent interest in the involvement of cognitive studies in literature have not yet produced enough results to outline a possible neuropsychological profile of course. Also, not all researchers agree on the existence of a specific cognitive deficit of Fabry Disease (FD. The case discussed here is a example of a neuropsychological profile in patient with FD (mutation p.S126G.

  15. A thermodynamic assay to test pharmacological chaperones for Fabry disease.

    Science.gov (United States)

    Andreotti, Giuseppina; Citro, Valentina; Correra, Antonella; Cubellis, Maria Vittoria

    2014-03-01

    The majority of the disease-causing mutations affect protein stability, but not functional sites and are amenable, in principle, to be treated with pharmacological chaperones. These drugs enhance the thermodynamic stability of their targets. Fabry disease, a disorder caused by mutations in the gene encoding lysosomal alpha-galactosidase, represents an excellent model system to develop experimental protocols to test the efficiency of such drugs. The stability of lysosomal alpha-galactosidase under different conditions was studied by urea-induced unfolding followed by limited proteolysis and Western blotting. We measured the concentration of urea needed to obtain half-maximal unfolding because this parameter represents an objective indicator of protein stability. Urea-induced unfolding is a versatile technique that can be adapted to cell extracts containing tiny amounts of wild-type or mutant proteins. It allows testing of protein stability as a function of pH, in the presence or in the absence of drugs. Results are not influenced by the method used to express the protein in transfected cells. Scarce and dispersed populations pose a problem for the clinical trial of drugs for rare diseases. This is particularly true for pharmacological chaperones that must be tested on each mutation associated with a given disease. Diverse in vitro tests are needed. We used a method based on chemically induced unfolding as a tool to assess whether a particular Fabry mutation is responsive to pharmacological chaperones, but, by no means is our protocol limited to this disease. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Adaptive pathway development for Fabry disease: a clinical approach.

    Science.gov (United States)

    Schuller, Yvonne; Arends, Maarten; Körver, Simon; Langeveld, Mirjam; Hollak, Carla E M

    2018-02-15

    Fabry disease (FD) is a rare X-chromosome-linked lysosomal storage disorder. Although initial expectations of enzyme replacement therapy (ERT) were high, it is now clear that real-world effectiveness is disappointing and evidence gathering has been inadequate. In retrospect, development of ERT for FD had several shortcomings. Little convincing evidence on the effectiveness existed at time of authorization. Also, post-marketing evaluation failed to generate sufficient and relevant data for adequate evaluation on effectiveness. Adaptive pathways might have benefitted ERT development by: (i) involving healthcare professionals, patients, health technology assessment bodies and payers in the development process; (ii) iterative development, starting with initial authorization in classical males; (iii) a clear real-world data collection plan; (iv) an independent disease registry; and (v) prescription control. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. A male Fabry disease patient treated with intravenous thrombolysis for acute ischemic stroke.

    Science.gov (United States)

    Saarinen, Jukka T; Sillanpää, Niko; Kantola, Ilkka

    2015-02-01

    The use of intravenous thrombolytic therapy for acute ischemic stroke is associated with improved outcomes. Fabry disease is an X-linked glycosphingolipid storage disease with vascular endothelial deposits. Affected males with the classic phenotype develop renal, cardiac, and cerebrovascular disease and die prematurely. However, Fabry disease is rare in young men with first ischemic stroke of undetermined cause. We report a 38-year-old man with acute aphasia and a left M2 segment of the middle cerebral artery thrombus with no recanalization who was finally diagnosed with Fabry disease after left ventricular hypertrophy of undetermined cause had been identified. A gene test revealed a R227X mutation typical of Fabry disease with the classical phenotype. To our knowledge our patient is the first reported male Fabry patient who was given intravenous thrombolytic therapy and the first reported Fabry patient who received intravenous thrombolytic therapy between 3 and 4.5 hours of the symptom onset. Despite favorable prognostic indicators on admission imaging, our patient suffered a significant stroke and had an unfavorable clinical outcome. Fortunately, the episode was not complicated by intracranial hemorrhage. Further studies are needed to evaluate the efficacy and safety of intravenous thrombolytic therapy in treating patients with Fabry disease and acute ischemic stroke. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    Purpose of review: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. Recent findings: Advances in computing and high-throughput sequencing

  19. Prevalence of Fabry disease in young patients with cryptogenic ischemic stroke.

    Science.gov (United States)

    Dubuc, Véronique; Moore, David F; Gioia, Laura C; Saposnik, Gustavo; Selchen, Daniel; Lanthier, Sylvain

    2013-11-01

    A German study diagnosed 4% of young cryptogenic ischemic stroke patients with Fabry disease, an X-linked lysosomal storage disease caused by mutations in the alpha-galactosidase A (α-GAL-A) gene resulting in an accumulation of glycosphingolipids. A lower prevalence was found in other geographic regions. To determine the prevalence of Fabry disease in a Canadian population of young cryptogenic ischemic stroke patients. Patients with cryptogenic ischemic stroke at age 16-55 were retrospectively identified in our institutional stroke database and underwent a focused clinical evaluation. We sequenced the α-GAL-A gene and measured the levels of blood globotriaosylsphingosine in subjects with mutations of undetermined pathogenicity. Fabry disease was diagnosed in patients with pathogenic mutations or increased levels of blood globotriaosylsphingosine. Ninety-three of 100 study subjects had normal α-GAL-A gene polymorphisms. Seven had mutations of undetermined pathogenicity, including one with increased globotriaosylsphingosine (prevalence, 1%; 95% confidence interval, ischemic stroke presentation as the first clinical manifestation of Fabry disease. Both Fabry patients experienced recurrent ischemic stroke. Fabry disease accounts for a small proportion of young Canadians with cryptogenic ischemic stroke. Identification of Fabry biomarkers remains a research priority to delineate stroke patients disserving routine screening. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Occupational skin diseases

    DEFF Research Database (Denmark)

    Mahler, V; Aalto-Korte, K; Alfonso, J H

    2017-01-01

    in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks......BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal...... diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment...

  1. Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

    Science.gov (United States)

    Yeniçerioğlu, Yavuz; Akdam, Hakan; Dursun, Belda; Alp, Alper; Sağlam Eyiler, Funda; Akın, Davut; Gün, Yelda; Hüddam, Bülent; Batmazoğlu, Mehmet; Gibyeli Genek, Dilek; Pirinççi, Serhat; Ersoy, İsmail Rıfkı; Üzüm, Atilla; Soypaçacı, Zeki; Tanrısev, Mehmet; Çolak, Hülya; Demiral Sezer, Sibel; Bozkurt, Gökay; Akyıldız, Utku Oğan; Akyüz Ünsal, Ayşe İpek; Ünübol, Mustafa; Uslu, Meltem; Eryılmaz, Ufuk; Günel, Ceren; Meteoğlu, İbrahim; Yavaşoğlu, İrfan; Ünsal, Alparslan; Akar, Harun; Okyay, Pınar

    2017-11-01

    Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 μmol/L/h. A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m 2 , 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 μmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 μmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

  2. Diagnostic and therapeutic dilemmas in Fabry and Gaucher disease

    NARCIS (Netherlands)

    Smid, B.E.

    2015-01-01

    De ziekte van Fabry en Gaucher zijn erfelijke lysosomale stapelingsziekten met een wisselend fenotype. Mutaties in het Fabry gen kunnen leiden tot een ernstig, of een milder fenotype, of kunnen asymptomatisch zijn. Om potentieel behandelbare patiënten op te sporen worden in toenemende mate

  3. Anaesthesiologic protocol for kidney transplantation in two patients with Fabry Disease: a case series

    Science.gov (United States)

    Sorbello, Massimiliano; Veroux, Massimiliano; Cutuli, Melania; Morello, Gianluigi; Paratore, Annalaura; Sidoti, Mirko Tindaro; Maugeri, Jessica Giuseppina; Gagliano, Massimiliano; Giuffrida, Giuseppe; Corona, Daniela; Veroux, Pierfrancesco

    2008-01-01

    Fabry's Disease is a rare genetic syndrome, with a classic X-linked alpha -galactosidase A deficiency phenotype, responsible for glico-sphyngolypids metabolism impairment with clinical effects in several organs and functions. We describe the anaesthesiologic implications of two patients with Fabry disease who underwent a kidney transplantation from a deceased donor. We recommend careful preoperative evaluation, including cardiac sonography study and spirometry for Fabry disease patients, and according to our experience, we recommend advanced haemodynamic monitoring during surgery. Careful airway examination should be further performed, with particular attention to patient ventilability prediction and available alternative strategies for airway management in case of difficulties. A nephroprotective strategy and a particular care to the associated end-stage organ disease may significantly improve the long-term outcome of patients with Fabry Disease. PMID:19014714

  4. [Clinical courses of two male siblings on hemodialysis for Fabry disease ].

    Science.gov (United States)

    Itoh, Kazuko; Tanaka, Motoko; Matsushita, Kazutaka; Miyamura, Nobuhiro; Nishida, Kenroh; Araki, Eiichi; Nonoguchi, Hiroshi; Tomita, Kimio

    2005-01-01

    Fabry disease is an X-linked recessive disease resulting from a deficiency of the lysosomal hydrolase alpha-galactosidase A. In male patients with the classic hemizygous form, acroparesthesias, hypohidrosis, corneal opacities, and dysfunction of the heart, brain, and kidney are observed. Recently, it was reported that 0.5-1.2% of male chronic hemodialysis (HD) patients were diagnosed as having Fabry disease based on the measurement of alpha-galactosidase A activity. Fabry disease is thought to be an important cause of end-stage renal disease. There are a few reports of patients with Fabry disease on long-term HD. Here we report two male siblings with classical type Fabry disease on HD. They had acroparesthesias, and hypohidrosis. Their mother had severe heart failure due to a heterozygous form of Fabry disease. Case 1 is a 44-year-old male. He had mid-cerebral apoplexy at 30 years of age. He started maintenance HD in 2000. Remarkable left ventricular hypertophy and conduction disorders of the heart were found. In 2004, he collapsed and ventricular-tachycardia and severe hypoxic brain damage were found. Now his consciousness level has been in the range of 100 to 300 on the Japan Coma Scale. Case 2 is a 40-year-old male. He started maintenance HD in 1993. Malnutrition due to chronic diarrhea and severe ischemic change in the brain were found. In 1998, he had severe joint pain of shoulders and fingers with ectopic calcifications detected by X ray. The ectopic calcifications were extended to the whole body. In 2004, his dementia by ischemic change in the brain has rapidly progressed. In conclusion, cardiovascular complications, cerebrovascular manifestations, painful ectopic carcifications, and chronic diarrheas in our patients were considered to be specific symptoms of Fabry disease. Young HD patients with these symptoms will need to be examined for Fabry disease.

  5. Newborn screening for Fabry disease in the north-west of Spain.

    Science.gov (United States)

    Colon, Cristobal; Ortolano, Saida; Melcon-Crespo, Cristina; Alvarez, Jose V; Lopez-Suarez, Olalla E; Couce, Maria L; Fernández-Lorenzo, José R

    2017-08-01

    Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy is available to treat patients, who often experience delayed diagnosis. A newborn screening for Fabry disease was performed to study the prevalence of the pathology and to evaluate the possibility to implement the test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males and 7025 females) and carried out a diagnostic study by fluorometric measurement of α-galactosidase A enzymatic activity and GLA gene sequencing. We detected one patient with a mutation in GLA associated with classical Fabry Disease (M290I), ten subjects carrying genetic variants of uncertain diagnosis (S126G, R118C, A143T), and a girl with the non-characterized variant F18Y, which was not previously described. Additional 25 samples presented nucleotide substitutions described as polymorphisms (D313Y, rs2071225, and rs2071397). The estimated prevalence for Fabry disease in north-western Spanish males is of 0.013%. These results confirm that the prevalence of Fabry disease is underestimated and systematic screening is feasible; however, further characterization of variants of uncertain clinical significance is necessary to establish protocols of patients' management. What is Known: • Fabry disease is a rare disease of delayed diagnosis, whose prevalence is underestimated. However, early diagnosis is important for better efficiency of the current available treatment. What is New: • This newborn screening for Fabry disease performed on Spanish population reveals a prevalence of genetic alterations in GLA of 0.1% in males (0.013% with classic Fabry disease) and also characterizes these modifications in order to discriminate between pathogenic mutations and genetic variants of unknown significance.

  6. Prevalence of Fabry disease and GLA c.196G>C variant in Japanese stroke patients.

    Science.gov (United States)

    Nagamatsu, Kiyoshiro; Sekijima, Yoshiki; Nakamura, Katsuya; Nakamura, Kimitoshi; Hattori, Kiyoko; Ota, Masao; Shimizu, Yusaku; Endo, Fumio; Ikeda, Shu-Ichi

    2017-07-01

    Fabry disease is an important underlying disease in young cryptogenic stroke patients. However, little is known regarding the frequency of Fabry disease in the general stroke population, especially in elderly patients. A total of 588 stroke patients (61.7% men; average age 74.1±12.5 years) were enrolled in this prospective study. Blood samples were obtained to produce blood spots to determine α-galactosidase A (α-GalA) activity and for GLA gene analysis. One 65-year-old female patient had a known GLA gene mutation, c.2T>C (p.M1T), causing Fabry disease. Five male patients and two female patients had GLA c.196G>C (p.E66Q) variant, which is not associated with the full clinical manifestations of Fabry disease. The allele frequency of GLA c.196G>C was significantly higher in male patients with small-vessel occlusion (odds ratio 3.95, P=0.048) and non-cardioembolism (odds ratio 4.08, P=0.012) than that in the general Japanese population. Fabry disease is rare in the general Japanese stroke population. However, screening identified one elderly female patient with Fabry disease. GLA c.196G>C variant is a genetic risk factor for cerebral small-vessel occlusion and non-cardioembolism in Japanese males but not in females.

  7. Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy

    DEFF Research Database (Denmark)

    Madsen, Christoffer Valdorff; Bundgaard, Henning; Rasmussen, Åse Krogh

    2017-01-01

    OBJECTIVES: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long...... significantly in the ERT group, whereas no differences were observed within the non-ERT group. DISCUSSION: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research....

  8. The management and treatment of children with Fabry disease: A United States-based perspective.

    Science.gov (United States)

    Hopkin, Robert J; Jefferies, John L; Laney, Dawn A; Lawson, Victoria H; Mauer, Michael; Taylor, Matthew R; Wilcox, William R

    2016-02-01

    Fabry disease is an inherited X-linked disorder that presents during childhood in male and female patients. Young patients may initially experience pain, hypohidrosis, and gastrointestinal symptoms. Other manifestations of Fabry disease, such as renal and cardiac disease, manifest later in adolescence or adulthood. In the pediatric population, renal damage is typically subclinical and identifiable only through biopsy. Specialists from the United States with expertise in Fabry disease convened during 2013-2014 in order to develop these consensus guidelines about the management and treatment of children with Fabry disease. The presence of symptoms in boys and girls of any age is an indication to begin therapy. Early treatment before the onset of potentially irreversible vital organ pathology is ideal. Asymptomatic children with Fabry mutations should be followed closely for the development of renal, cardiac, neurological, or gastrointestinal signs, symptoms, or laboratory changes, which would warrant treatment initiation. A comprehensive care plan should be implemented by the treating physicians to guide the management of children with Fabry disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Cardiac magnetic resonance imaging in patients with Fabry's disease.

    Science.gov (United States)

    Małek, Lukasz A; Chojnowska, Lidia; Spiewak, Mateusz; Kłopotowski, Mariusz; Miśko, Jolanta; Petryka, Joanna; Miłosz, Barbara; Ruzyłło, Witold

    2010-08-01

    Fabry's disease (FD) is a rare hereditary disorder caused by the loss of alpha galactosidase A activity leading to accumulation of glycosphingolipids in various organs including hypertrophy of the heart. Most reports on cardiac involvement in FD focus on the left ventricular hypertrophy (LVH) and its relation to diastolic function. However, recent studies demonstrated large subset of patients with FD and right ventricle (RV) hypertophy. The accurate depiction of RV volumes, function and mass is possible with cardiovascular magnetic resonance (CMR). The CMR study can be also used to identify typically localised regions of intramyocardial fibrosis (infero-lateral segments of the LV), which have been shown to be a marker of inefficacious response to enzyme replacement therapy. We present series of 8 patients with genetically confirmed FD who underwent CMR study. We demonstrated a typical concentric and diffuse pattern of LVH with RV involvement in patients with the most severe LVH without significant impact on RV function and volumes. We showed that myocardial fibrosis can be observed not only in LV but also in RV. In 2 patients FD coexisted with symptomatic coronary artery disease with evidence of subendocardial myocardial fibrosis typical for ischaemic origin in one patient. The CMR confirmation of the presence of FD in one patient at an early stage of the disease, before the onset of advanced hypertrophy or failure of other organs, supports the value of this imaging technique in differential diagnosis of concentric and diffuse LVH.

  10. Continuous cardiac troponin I release in Fabry disease.

    Science.gov (United States)

    Feustel, Andreas; Hahn, Andreas; Schneider, Christian; Sieweke, Nicole; Franzen, Wolfgang; Gündüz, Dursun; Rolfs, Arndt; Tanislav, Christian

    2014-01-01

    Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD. cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females) regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI). Three patients (21%) without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: gadolinium enhancement (LGE) in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01). Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3) in cardiomyocytes. Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD.

  11. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.

    2006-01-01

    affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically......Fabry disease is a rare X-linked lysosomal storage disorder. The mutations result in a deficiency of the lysosomal enzyme α-galactosidase A causing accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. Given the X-linked inheritance, male patients are severely....... The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p...

  12. Arrhythmia and Clinical Cardiac Findings in Children With Anderson-Fabry Disease.

    Science.gov (United States)

    Wilson, Hunter C; Hopkin, Robert J; Madueme, Peace C; Czosek, Richard J; Bailey, Laurie A; Taylor, Michael D; Jefferies, John L

    2017-07-15

    Anderson-Fabry Disease (AFD) is a lysosomal storage disorder that results in progressive cardiovascular hypertrophy, scarring, and arrhythmia burden; yet, the early cardiac phenotype of AFD is still poorly defined. To further characterize early cardiac features in AFD, we evaluated electrocardiographic and clinical findings contained in a local cohort of pediatric AFD patients and arrhythmia data in children enrolled in the Fabry Registry. Twenty-six local patients aged Fabry Registry, sinus bradycardia, defined as heart rate Fabry cardiomyopathy. Bradycardia, common in adults, is frequent even among children with AFD. Given the potential for early initiation of enzyme replacement therapy to reduce cardiovascular morbidity, continued work to develop paradigms of therapy and longitudinal cardiovascular surveillance is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease.

    Science.gov (United States)

    Seydelmann, Nora; Liu, Dan; Krämer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; Störk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2016-05-31

    High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; PFabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease

    Directory of Open Access Journals (Sweden)

    Fernando C Fervenza

    2008-11-01

    Full Text Available Fernando C Fervenza1, Roser Torra2, David G Warnock31Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Department of Nephrology, Fundació Puigvert, Barcelona, Spain; 3Division of Nephrology, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Kidney involvement with progressive loss of kidney function (Fabry nephropathy is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed.Keywords: agalsidase, enzyme replacement therapy, Fabry nephropathy, anti-proteinuric therapy

  15. Smoking and skin disease

    DEFF Research Database (Denmark)

    Thomsen, S F; Sørensen, L T

    2010-01-01

    suggest that tobacco smoking is a contributing factor in systemic lupus erythematosus, psoriasis, palmoplantar pustulosis, cutaneous squamous cell carcinoma, hidradenitis suppurativa, and genital warts. In contrast, smoking may confer some protective effects and mitigate other skin diseases, notably......Tobacco smoking is a serious and preventable health hazard that can cause or exacerbate a number of diseases and shorten life expectancy, but the role of smoking as an etiologic factor in the development of skin disease is largely unknown. Although epidemiological evidence is sparse, findings...... pemphigus vulgaris, pyoderma gangrenosum, aphthous ulcers, and Behçet's disease. Various degenerative dermatologic conditions are also impacted by smoking, such as skin wrinkling and dysregulated wound healing, which can result in post-surgical complications and delayed or even arrested healing of chronic...

  16. Smoking and skin disease

    DEFF Research Database (Denmark)

    Thomsen, S F; Sørensen, L T

    2010-01-01

    Tobacco smoking is a serious and preventable health hazard that can cause or exacerbate a number of diseases and shorten life expectancy, but the role of smoking as an etiologic factor in the development of skin disease is largely unknown. Although epidemiological evidence is sparse, findings...... suggest that tobacco smoking is a contributing factor in systemic lupus erythematosus, psoriasis, palmoplantar pustulosis, cutaneous squamous cell carcinoma, hidradenitis suppurativa, and genital warts. In contrast, smoking may confer some protective effects and mitigate other skin diseases, notably...... pemphigus vulgaris, pyoderma gangrenosum, aphthous ulcers, and Behçet's disease. Various degenerative dermatologic conditions are also impacted by smoking, such as skin wrinkling and dysregulated wound healing, which can result in post-surgical complications and delayed or even arrested healing of chronic...

  17. Neuro-otological and peripheral nerve involvement in Fabry disease

    Directory of Open Access Journals (Sweden)

    Sergio Carmona

    2017-07-01

    Full Text Available Fabry disease (FD is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain, vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%, vertigo (27.8% or both (25%. An involvement of either cochlear or vestibular function was identified in most patients (75%. In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neurootological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

  18. Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease.

    Directory of Open Access Journals (Sweden)

    Michael Mauer

    Full Text Available Fabry disease. an X-linked deficiency of α-galactosidase A coded by the GLA gene, leads to intracellular globotriaosylceramide (GL-3 accumulation. Although less common than in males, chronic kidney disease, occurs in ∼ 15% of females. Recent studies highlight the importance of podocyte injury in Fabry nephropathy development and progression. We hypothesized that the greater the % of podocytes with active wild-type GLA gene (due to X-inactivation of the mutant copy the less is the overall podocyte injury.Kidney biopsies from 12 treatment-naive females with Fabry disease, ages 15 (8-63, median [range], years were studied by electron microscopy and compared with 4 treatment-naive male patients.In females, 51 (13-100% of podocytes (PC per glomerulus had no GL-3 inclusions, this consistent with a non-Fabry podocyte phenotype (NFPC. In PC with GL-3 inclusions [Fabry podocyte phenotype (FPC], GL-3 volume density per podocyte was virtually identical in females and males, consistent with little or no cross-correction between FPC and NFPC. %NFPC per glomerulus (%NFPC/glom correlated with age in females (r = 0.65, p = 0.02, suggesting a survival disadvantage for FPC over time. Age-adjusted %NFPC/glom was inversely related to foot process width (FPW (r = -0.75, p = 0.007, an indicator of PC injury. GL-3 volume density in FPC in females correlated directly with FPW.These findings support important relationships between podocyte mosaicism and podocyte injury in female Fabry patients. Kidney biopsy, by providing information about podocyte mosaicism, may help to stratify females with Fabry disease for kidney disease risk and to guide treatment decisions.

  19. Prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in Fabry disease: a cross-sectional study.

    Science.gov (United States)

    Deshayes, Samuel; Auboire, Laurent; Jaussaud, Roland; Lidove, Olivier; Parienti, Jean-Jacques; Triclin, Nathalie; Imbert, Bernard; Bienvenu, Boris; Aouba, Achille

    2015-05-01

    Fabry disease (FD) is a lysosomal disorder leading to progressive systemic involvement, including microvascular damage that leads to neurological and cardiovascular disorders. We hypothesize that the latter could be documented at an early stage by performing a microcirculation study with nailfold capillaroscopy and evaluation of Raynaud phenomenon.The objective was to measure the prevalence of Raynaud phenomenon and nailfold capillaroscopic abnormalities in FD.This cross-sectional study included a standardized questionnaire and a nailfold capillaroscopy that assessed previously reported patterns in FD (dystrophic and giant capillaries, avascular fields, irregular architecture, dilatation and density of capillaries, hemorrhage), and was conducted on 32 Fabry patients and 39 controls. Capillaroscopic photographs were reviewed by 2 independent blinded investigators.Twelve Fabry patients (38%) suffered from Raynaud phenomenon, 5 were males (ie, 50% of male Fabry patients), compared with 2 controls (13%) (P Raynaud phenomenon was concomitant or before the occurrence of pain in the extremities in 42% of Fabry patients.More ramified capillaries were significantly observed in Fabry patients (12/32, 38%) than in controls (5/39, 13%, P = 0.016).Secondary Raynaud phenomenon should lead to screening for FD, especially in men. By extension, in high-risk populations for FD, the presence of Raynaud phenomenon and ramified capillaries should be assessed.

  20. Continuous cardiac troponin I release in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Andreas Feustel

    Full Text Available Fabry disease (FD is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD.cTNI values were determined at least twice per year in 14 FD-patients (6 males and 8 females regularly followed-up in our centre. The data were related to other parameters of heart function including cardiac magnetic resonance imaging (cMRI.Three patients (21% without specific vascular risk factors other than FD had persistent cTNI-elevations (range 0.05-0.71 ng/ml, normal: <0.01. cMRI disclosed late gadolinium enhancement (LGE in all three individuals with cTNI values ≥0.01, while none of the 11 patients with cTNI <0.01 showed a pathological enhancement (p<0.01. Two subjects with increased cTNI-values underwent coronary angiography, excluding relevant stenoses. A myocardial biopsy performed in one during this procedure demonstrated substantial accumulation of globotriaosylceramide (Gb3 in cardiomyocytes.Continuous cTNI elevation seems to occur in a substantial proportion of patients with FD. The high accordance with LGE, reflecting cardiac dysfunction, suggests that cTNI-elevation can be a useful laboratory parameter for assessing myocardial damage in FD.

  1. The neurocognitive impact of Fabry disease on pediatric patients.

    Science.gov (United States)

    Bugescu, Nicolle; Alioto, Andrea; Segal, Summer; Cordova, Matthew; Packman, Wendy

    2015-04-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder that results in progressive multisystemic organ complications. Several studies have examined neurocognitive impairments in adults; however, there is a paucity of research examining neurocognitive functioning in children with FD. This is the first exploratory study to examine the neurocognitive functioning of pediatric patients with FD and to evaluate the effects of enzyme replacement therapy (ERT) on neurocognitive functioning within this population. Families attending a national conference with at least one child with FD and one parent affected by FD comprised the sample (n = 48; 24 pediatric patients, 24 parents). Pediatric participants (10 males, 14 females) between the ages of 6 and 18 years and their parent(s) were involved in the study. Data from a demographic questionnaire and two neurocognitive self-report and parent-report measures were analyzed. Parent reports of neurocognitive functioning were also compared to a sample of children with and without head injury and to a sample of children who had undergone liver transplant (LT). Children with FD had poorer cognitive and executive functioning than healthy peers, and were comparable to children with head injury and LT. In addition, children using ERT had higher scores on measures of overall cognitive functioning, as well as fewer problems with attention/working memory and executive functioning. Results of this study suggest that children with FD may exhibit poorer cognitive and executive functioning relative to healthy peers. The use of ERT may mitigate the negative impact of FD on neurocognitive functioning in pediatric patients. © 2015 Wiley Periodicals, Inc.

  2. Prevalence of Fabry disease among Turkish dialysis patients: Data from hemodialysis centers in Bursa province.

    Science.gov (United States)

    Sayilar, Emel Isiktas; Ayar, Yavuz; Yavuz, Mahmut

    2016-03-01

    Detection of potential Fabry disease patients before appearance of life-threatening findings is of great importance, particularly in high-risk populations. This study was designed to determine prevalence of Fabry disease among Turkish patients undergoing peritoneal dialysis and hemodialysis for chronic renal failure (CRF). A total of 1,527 patients (mean (SD) age: 60.2 (14.2) years, 55.5% were males) on hemodialysis (n = 1,435) or peritoneal dialysis (n = 92) for CRF were included in this multicenter study conducted at 17 dialysis centers across Bursa province, Turkey. Prevalence of the disease was determined using combined enzymatic and genetic strategy with measuring the activity of α-galactosidase A (α-Gal A) and Sanger sequence analysis based genotyping in α-galactosidase A gene (GLA) in dried blood samples (DBS). Overall α-Gal A activity was determined to be below the reference value in 130 (8.5%) of 1,527 patients. GLA genotyping confirmed the diagnosis of Fabry disease in 5 (0.3%) patients with low α-Gal A activity. All Fabry-positive patients were males corresponding to a 0.6% prevalence of disease in this gender. In conclusion, our findings, which were based on the use of DBS for both enzymatic activity and genotyping analyses, revealed the diagnosis of Fabry disease in 5 males corresponding to overall 0.3% prevalence of disease in the cohort and 0.6% prevalence among males. Our results support the likelihood of unrecognized Fabry disease in a nonnegligible number of patients on dialysis and thus emphasize the value of screening studies in terms of detection of new cases and improved prognosis of the disease via early diagnosis and treatment.

  3. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic

    2015-01-01

    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed...... of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations....

  4. Cardiac involvement in genotype-positive Fabry disease patients assessed by cardiovascular MR.

    Science.gov (United States)

    Kozor, Rebecca; Grieve, Stuart M; Tchan, Michel C; Callaghan, Fraser; Hamilton-Craig, Christian; Denaro, Charles; Moon, James C; Figtree, Gemma A

    2016-02-15

    Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR. Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0-46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m(2), p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, pgadolinium enhancement (LGE) was present in 15 Fabry subjects (9/21 males and 6/23 females). The most common site for LGE was the basal inferolateral wall (93%, 14/15). There was a positive association between LVM index and LGE. Despite this, there were two males and three females with no LVH that displayed LGE. Of Fabry subjects who were not on enzyme replacement therapy at enrolment (n=28), six were reclassified as having cardiac involvement (four LVH-negative/LGE-positive, one LVH-positive/LGE-positive and one LVH-positive/LGE-negative). CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Fabry disease: the importance of the enzyme replacement therapy (TRE, treating quickly and efficiently

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2014-06-01

    Full Text Available Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase A enzyme that causes a pathological accumulation of glycosphingolipids mainly in the endothelial cells, vascular smooth muscle cells and podocytes among others. Enzyme replacement therapy is the only option for a specific treatment at present. Increasing knowledge of the physiopathological mechanisms has changed the management of the disease and above all, when treatment should begin. At present, beginning treatment at an early age seems to be a way of preventing and in some cases reverting some of the signs and symptoms of Fabry disease.

  6. The coincidence of IgA nephropathy and Fabry disease

    Directory of Open Access Journals (Sweden)

    Maixnerová Dita

    2013-01-01

    Full Text Available Abstract Background IgA nephropathy (IgAN is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD. Case presentation A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient’s plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted. The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Conclusions Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic

  7. Identification of Fabry Disease in a Tertiary Referral Cohort of Patients with Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Maron, Martin S; Xin, Winnie; Sims, Katherine B; Butler, Rita; Haas, Tammy S; Rowin, Ethan J; Desnick, Robert J; Maron, Barry J

    2018-02-01

    Fabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease-specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy. We studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene. In 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy. These observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease-affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

    NARCIS (Netherlands)

    Warnock, David G.; Ortiz, Alberto; Mauer, Michael; Linthorst, Gabor E.; Oliveira, João P.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Vujkovac, Bojan; Beitner-Johnson, Dana; Lemay, Roberta; Cole, J. Alexander; Svarstad, Einar; Waldek, Stephen; Germain, Dominique P.; Wanner, Christoph

    2012-01-01

    Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of

  9. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate

    NARCIS (Netherlands)

    Tøndel, Camilla; Ramaswami, Uma; Aakre, Kristin Moberg; Wijburg, Frits; Bouwman, Machtelt; Svarstad, Einar

    2010-01-01

    Studies on renal function in children with Fabry disease have mainly been done using estimated creatinine-based glomerular filtration rate (GFR). The aim of this study was to compare estimated creatinine-based GFR (eGFR) with measured GFR (mGFR) in children with Fabry disease and normal renal

  10. The central nervous system manifestation and CT findings of Fabry's disease

    International Nuclear Information System (INIS)

    Toyonaga, Kazutaka; Nishihira, Takeo

    1983-01-01

    A case of Fabry's disease with central nervous system dysfunction is reported. This 27-year-old man had recurrent episodes of pains in the extremities when he was a child. Spontaneous clinical remission occured around puberty. He had been well until age 22 when he experienced transient weakness of the left arm. The following year he developed transient blindness of the right eye. Then, he developed weakness in the extremities, dysphagia, dysarthria, and was brought to the hospital in unconscious state. Several members of his family are affected with the same disease presenting leg pains, kidney disease and angiokeratoma. Physical examination disclosed an optic atrophy, pseudobulbar palsy with spastic weakness in the all extremities and multiple angiokeratoma in the flank, buttocks and thighs. Abnormal laboratory findings included leukocytosis, increased ESR and strongly positive CRP. Biopsy of the skin disclosed dilated capilaries with numerous vacuoles in the cytoplasm of the epithelial cells. Thin-layer chromatography of the urine sediment showed a marked increase in ceramide trihexoside. Leukocyte alphagalactosidase level was abnormally low. CT scan showed diffuse cerebral atrophy and multiple low density areas in the thalamus, ventral pons and centrum semiovale. The CT findings and possible mechanism of the response to predonisolone were also discussed. (author)

  11. Central nervous system manifestation and CT findings of Fabry's disease. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Toyonaga, Kazutaka; Nishihira, Takeo (Okinawa Central Hospital (Japan))

    1983-11-01

    A case of Fabry's disease with central nervous system dysfunction is reported. This 27-year-old man had recurrent episodes of pains in the extremities when he was a child. Spontaneous clinical remission occured around puberty. He had been well until age 22 when he experienced transient weakness of the left arm. The following year he developed transient blindness of the right eye. Then, he developed weakness in the extremities, dysphagia, dysarthria, and was brought to the hospital in unconscious state. Several members of his family are affected with the same disease presenting leg pains, kidney disease and angiokeratoma. Physical examination disclosed an optic atrophy, pseudobulbar palsy with spastic weakness in the all extremities and multiple angiokeratoma in the flank, buttocks and thighs. Abnormal laboratory findings included leukocytosis, increased ESR and strongly positive CRP. Biopsy of the skin disclosed dilated capilaries with numerous vacuoles in the cytoplasm of the epithelial cells. Thin-layer chromatography of the urine sediment showed a marked increase in ceramide trihexoside. Leukocyte alphagalactosidase level was abnormally low. CT scan showed diffuse cerebral atrophy and multiple low density areas in the thalamus, ventral pons and centrum semiovale. The CT findings and possible mechanism of the response to predonisolone were also discussed.

  12. Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry Registry.

    Science.gov (United States)

    Wilcox, William R; Feldt-Rasmussen, Ulla; Martins, Ana Maria; Ortiz, Alberto; Lemay, Roberta M; Jovanovic, Ana; Germain, Dominique P; Varas, Carmen; Nicholls, Katherine; Weidemann, Frank; Hopkin, Robert J

    2018-01-01

    Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase, GLA. In patients with Fabry disease, glycosphingolipids accumulate in various cell types, triggering a range of cellular and tissue responses that result in a wide spectrum of organ involvement. Although variable, gastrointestinal symptoms are among the most common and significant early clinical manifestations; they tend to persist into adulthood if left untreated. To further understand the effects of sustained enzyme replacement therapy (ERT) with agalsidase beta on gastrointestinal symptoms in heterozygotes, a data analysis of female patients enrolled in the Fabry Registry was conducted. To be included, females of any age must have received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5 years. Measured outcomes were self-reported gastrointestinal symptoms (abdominal pain, diarrhea). Outcomes at baseline and last follow-up, and their change from baseline to last follow-up, were assessed. Relevant data were available for 168 female patients. Mean age at the start of ERT was 43 years and mean treatment duration 5.7 years. Baseline pre-treatment abdominal pain was reported by 45% of females and diarrhea by 39%. At last follow-up, 31% reported abdominal pain (p Fabry Registry analysis suggest that while on sustained treatment with agalsidase beta (1.0 mg/kg every 2 weeks), both abdominal pain and diarrhea improved in many female patients with Fabry disease.

  13. Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for establishing the diagnosis in women

    DEFF Research Database (Denmark)

    Havndrup, Ole; Christiansen, Michael; Stoevring, Birgitte

    2010-01-01

    , a male with ASH and multiple episodes of ventricular tachycardia, was hemizygous for a missense mutation (p.A156T). His daughter was heterozygous, but had normal enzyme activity. The third proband was a female with ASH, and no other indices of Fabry disease. She was heterozygous for a GLA missense...... without sarcomere gene mutations. GLA mutations were found in 3/90 (3%) of HCM families and in 2/20 (10%) of females without sarcomere-gene mutations. None of the probands presented other indices of Fabry disease. This, in combination with putative reversibility of cardiac changes by enzyme replacement...

  14. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three...

  15. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three...

  16. The D313Y variant in the GLA gene - no evidence of a pathogenic role in Fabry disease.

    Science.gov (United States)

    Hasholt, Lis; Ballegaard, Martin; Bundgaard, Henning; Christiansen, Michael; Law, Ian; Lund, Allan M; Norremolle, Anne; Krogh Rasmussen, Ase; Ravn, Kirstine; Tumer, Zeynep; Wibrand, Flemming; Feldt-Rasmussen, Ulla

    2017-12-01

    Fabry disease is an X- linked inherited lysosomal storage disease caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A (α-Gal A). The possible pathological significance of the D313Y variant in the GLA gene has not been verified and it may be a Fabry variant. Our aim was to elucidate whether the presence of the D313Y variant influenced the α-Gal A activity or resulted in Fabry symptoms or Fabry organ involvement. In two Danish families the presence of the D313Y variant did not result in reduced α-Gal A activity or clinical Fabry manifestations in males, and the presence in Fabry females did not significantly enhance the phenotype of a known causative mutation in the GLA gene (G271S). Our findings indicate that the D313Y variant is not causative to nor enhancing Fabry disease phenotype. The D313Y variant in the GLA gene was not disease causative in 2 Danish families. Investigating male family members were crucial in excluding the Fabry phenotype, and thus very important for proper genetic counceling of all family members, as well as overdiagnosing a devastating genetic disease.

  17. [Screening Test of Fabry Disease in Patients with Renal Replacement Therapy in the City of Modena].

    Science.gov (United States)

    Alfano, Gaetano; Ganda, Nicola; Cerami, Caterina; Mori, Giacomo; Fontana, Francesco; Cappelli, Gianni

    2018-03-01

    Fabry disease is a rare genetic lysosomal storage disease, inherited in an X-linked manner, characterized by lysosomal deposition of globotriaosylceramide due to deficient activity of the enzyme α-galactosidase A. Because the prevalence of this genetic disorder is unknown in the Emilia Romagna region, we conducted a screening study to assess the prevalence of Fabry disease in the city of Modena, Italy. A screening study has been conducted in patients on renal replacement therapy at University Hospital of Modena. Screening tests have been performed using dried blood spot method. Alpha-galactosidase A activity and Lyso-Gb3 levels were evaluated in peripheral blood of all men. In women test based on genetic analysis; Lyso-Gb3 was measured only in patients with mutation of gene GLA. Screening tests have been performed on 388 subjects: 181 maintenance hemodialysis patients, 166 kidney transplant recipients and 41 peritoneal dialysis patients. About 40% of the patients did not had etiological diagnosis of renal disease. Lyso-Gb3 was more specific test than α- galactosidase A (100% vs. 82.5%) to diagnose Fabry disease. We found two different mutations: c.13 A >G p.(Asn5Asp), a variant likely benign and c.937 G >T p.(Asp313Tyr) a variant of uncertain significance. Both the patients carrying these genetic mutations had no symptoms or medical history compatible with Fabry disease. Identification of variant of uncertain significance such as c.937G >Tp.(Asp313Tyr) showed the limits of genetic analysis to diagnose an inherit disease. Further studies are need to assess the diagnostic value of Lyso-Gb3 for screening for Fabry disease. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

  18. Mutations of alpha-galactosidase A gene in two unusual cases of Fabry disease

    NARCIS (Netherlands)

    Beyer, EM; Kopishinskaya, SV; Van Amstel, JKP; Tsvetkova, [No Value

    1999-01-01

    The mutation analysis of alpha-galactosidase A gene was carried out in two families with Fabry disease described by us earlier. In the family P. a new point mutation E341K (a G to A transition at position 10999 of the gene) was identified. The mutation causes a Glu341Lys substitution in

  19. Diagnostic dilemmas in Fabry disease: a case series study on GLA mutations of unknown clinical significance

    NARCIS (Netherlands)

    Smid, B. E.; Hollak, C. E. M.; Poorthuis, B. J. H. M.; van den Bergh Weerman, M. A.; Florquin, S.; Kok, W. E. M.; Lekanne Deprez, R. H.; Timmermans, J.; Linthorst, G. E.

    2015-01-01

    Fabry disease' (FD) phenotype is heterogeneous: alpha-galactosidase A gene mutations (GLA) can lead to classical or non-classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non-classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a

  20. Prevalence of symptoms in female Fabry disease patients: a case-control survey

    NARCIS (Netherlands)

    Bouwman, Machtelt G.; Rombach, Saskia M.; Schenk, Erica; Sweeb, Annelies; Wijburg, Frits A.; Hollak, Carla E. M.; Linthorst, Gabor E.

    2012-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by a deficiency of alpha-galactosidase A. Several studies demonstrated that heterozygotes have symptoms such as acroparesthesia, abdominal pain and chronic fatigue. However, as these symptoms are aspecific and relatively common in

  1. Lipid profile in adult patients with Fabry disease - Ten-year follow up.

    Science.gov (United States)

    Stepien, Karolina M; Hendriksz, Chris J

    2017-12-01

    Fabry disease, an X-linked genetic condition, results from alpha-galactosidase deficiency and increased accumulation of glycosphingolipids in cardiovascular tissues. Clinical manifestation includes vasculature associated complications. Hyperlipidaemia is one of the cardiovascular risk factors however it has never been well defined in Fabry disease. Enzyme Replacement Therapy (ERT) is available but its effect on serum cholesterol is unknown. The aim of this project was to assess the influence of long-term ERT on lipid profile in a large cohort of adult patients with Fabry disease. This was a retrospective analysis of lipid profile results. Patients with Fabry disease were on ERT for 10 years, were not treated with statins and had no severe renal impairment. All patients had lipid profile measured before ERT was commenced and 6, 12, 24, 36, 48, 60, 120 months later. Statistical analysis included ANOVA, Student t -test and descriptive statistics. Among 72 patients, 40 were females (median age 45; range 29-75), 32 males (median age 46; range 20-69). There was no significant difference in total cholesterol or HDL-cholesterol measured at baseline before ERT was commenced and 6, 12, 24, 36, 48, 60 and 120 months after ERT was commenced in 72 patients (ANOVA; P  = 0.673 and P  = 0.883, respectively). Female patients on ERT had higher mean HDL-cholesterol as compared to female patients with Fabry disease who were asymptomatic and not treated ( P  ≥ 0.05). Total cholesterol between treated and non-treated female patients was comparable. Female patients on ERT have higher total cholesterol and HDL-cholesterol when compared to lipid results in male patients on ERT. Total cholesterol/HDL-cholesterol ratio was low in female and male patients on ERT over 10 years. Adult patients with Fabry disease have remarkably elevated HDL-cholesterol and as a result, elevated total cholesterol. It is possible that elevated HDL-cholesterol has a cardioprotective effect in patients

  2. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    John Marshall

    Full Text Available Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal. This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3 in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT. Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638 was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.

  3. Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy.

    Science.gov (United States)

    Heo, Sun Hee; Kang, Eungu; Kim, Yoon-Myung; Go, Heounjeong; Kim, Kyung Yong; Jung, Jae Yong; Kang, Minji; Kim, Gu-Hwan; Kim, Jae-Min; Choi, In-Hee; Choi, Jin-Ho; Jung, Sung-Chul; Desnick, Robert J; Yoo, Han-Wook; Lee, Beom Hee

    2017-11-01

    Fabry disease is characterised by the progressive accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in vascular endothelial cells. Enzyme replacement therapy (ERT) clears this accumulation. We analysed plasma proteome profiles before and after ERT to characterise its molecular pathology. Two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight tandem mass spectrometry (MALDI-TOF MS) and tandem mass spectrometry (MS/MS) were done using plasma samples before and after ERT in eight patients with classical Fabry disease RESULTS: After short-term ERT (4-12 months), the levels of 15 plasma proteins involved in inflammation, oxidative and ischaemic injury, or complement activation were reduced significantly. Among them, β-actin (ACTB), inactivated complement C3b (iC3b), and C4B were elevated significantly in pre-ERT Fabry disease plasma compared with control plasma. After longer-term ERT (46-96 months), iC3b levels gradually decreased, whereas the levels of other proteins varied. The gradual reduction of iC3b was comparable to that of Gb3 levels. In addition, iC3b increased significantly in pre-ERT Fabry disease mouse plasma, and C3 deposits were notable in renal tissues of pre-enzyme replacement therapy patients. These results indicated that C3-mediated complement activation might be altered in Fabry disease and ERT might promote its stabilisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study.

    Science.gov (United States)

    Rolfs, Arndt; Fazekas, Franz; Grittner, Ulrike; Dichgans, Martin; Martus, Peter; Holzhausen, Martin; Böttcher, Tobias; Heuschmann, Peter U; Tatlisumak, Turgut; Tanislav, Christian; Jungehulsing, Gerhard J; Giese, Anne-Katrin; Putaala, Jukaa; Huber, Roman; Bodechtel, Ulf; Lichy, Christoph; Enzinger, Christian; Schmidt, Reinhold; Hennerici, Michael G; Kaps, Manfred; Kessler, Christof; Lackner, Karl; Paschke, Eduard; Meyer, Wolfgang; Mascher, Hermann; Riess, Olaf; Kolodny, Edwin; Norrving, Bo

    2013-02-01

    Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov.Unique identifier: NCT00414583.

  5. Priapism in a Fabry disease mouse model is associated with upregulated penile nNOS and eNOS expression.

    Science.gov (United States)

    Meng, Xing-Li; Arning, Erland; Wight-Carter, Mary; Day, Taniqua S; Jabbarzadeh-Tabrizi, Siamak; Chen, Shuyuan; Ziegler, Robin J; Bottiglieri, Teodoro; Schneider, Jay W; Cheng, Seng H; Schiffmann, Raphael; Shen, Jin-Song

    2018-03-01

    Fabry disease is a glycosphingolipidosis caused by deficient activity of α-galactosidase A; it is one of a few diseases that are associated with priapism, an abnormal prolonged erection of the penis. The goal of this study was to investigate the pathogenesis of Fabry disease-associated priapism in a mouse model of the disease. We found that Fabry mice develop late-onset priapism. Neuronal nitric oxide synthase (nNOS), which was predominantly present as the 120-kDa N-terminus-truncated form, was significantly upregulated in the penis of 18-month-old Fabry mice compared to wild type controls (~fivefold). Endothelial NOS (eNOS) was also upregulated (~twofold). NO level in penile tissues of Fabry mice was significantly higher than wild type controls at 18 months. Gene transfer-mediated enzyme replacement therapy reversed abnormal nNOS expression in the Fabry mouse penis. The penile nNOS level was restored by antiandrogen treatment, suggesting that hyperactive androgen receptor signaling in Fabry mice may contribute to nNOS upregulation. However, the phosphodiesterase-5A expression level and the adenosine content in the penis, which are known to play roles in the development of priapism in other etiologies, were unchanged in Fabry mice. In conclusion, these data suggested that increased nNOS (and probably eNOS) content and the consequential elevated NO production and high arterial blood flow in the penis may be the underlying mechanism of priapism in Fabry mice. Furthermore, in combination with previous findings, this study suggested that regulation of NOS expression is susceptible to α-galactosidase A deficiency, and this may represent a general pathogenic mechanism of Fabry vasculopathy.

  6. Assessment of Renal Pathology and Dysfunction in Pediatric Patients with Fabry Disease

    OpenAIRE

    Ramaswami, Uma; Najafian, Behzad; Schieppati, Arrigo; Mauer, Michael; Bichet, Daniel G.

    2010-01-01

    Overt renal disease often first presents in males with Fabry disease in early-to-mid adulthood, but proteinuria and reduced glomerular filtration rate may occur in adolescents and in young children. More recently, kidney biopsy data have shown early renal histological changes in pediatric patients. Renal investigations and their timing in children remain poorly defined. A consensus on renal investigations is necessary to understand the natural progression of the disease and to evaluate the ef...

  7. Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    Lukas Hofmann

    Full Text Available Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3 due to α-galactosidase A (α-Gal A deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO and compared results with those of age-matched male wildtype (WT littermates. Young (3 months and old (≥ 18 months mice were tested in the naïve state and after i.pl. injection of complete Freund`s adjuvant (CFA as an inflammatory pain model. We used the elevated plus maze (EPM, the light-dark box (LDB and the open field test (OF to investigate anxiety-like behavior. The forced swim test (FST and Morris water maze (MWM were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in naïve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05. After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05 and naïve young Fabry KO mice (p<0.05 in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05. Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.

  8. The D313Y variant in the GLA gene - no evidence of a pathogenic role in Fabry disease

    DEFF Research Database (Denmark)

    Hasholt, Lis; Ballegaard, Martin; Bundgaard, Henning

    2017-01-01

    Fabry disease is an X- linked inherited lysosomal storage disease caused by mutations in the GLA gene encoding the lysosomal enzyme alpha-galactosidase A (α-Gal A). The possible pathological significance of the D313Y variant in the GLA gene has not been verified and it may be a Fabry variant. Our...... aim was to elucidate whether the presence of the D313Y variant influenced the α-Gal A activity or resulted in Fabry symptoms or Fabry organ involvement. In two Danish families the presence of the D313Y variant did not result in reduced α-Gal A activity or clinical Fabry manifestations in males......, and the presence in Fabry females did not significantly enhance the phenotype of a known causative mutation in the GLA gene (G271S). Our findings indicate that the D313Y variant is not causative to nor enhancing Fabry disease phenotype. The D313Y variant in the GLA gene was not disease causative in 2 Danish...

  9. Characterization of a chemically modified plant cell culture expressed human α-Galactosidase-A enzyme for treatment of Fabry disease.

    Science.gov (United States)

    Kizhner, Tali; Azulay, Yaniv; Hainrichson, Mariana; Tekoah, Yoram; Arvatz, Gil; Shulman, Avidor; Ruderfer, Ilya; Aviezer, David; Shaaltiel, Yoseph

    2015-02-01

    Fabry disease is an X-linked recessive disorder caused by the loss of function of the lysosomal enzyme α-Galactosidase-A. Although two enzyme replacement therapies (ERTs) are commercially available, they may not effectively reverse some of the Fabry pathology. PRX-102 is a novel enzyme for the therapy of Fabry disease expressed in a BY2 Tobacco cell culture. PRX-102 is chemically modified, resulting in a cross-linked homo-dimer. We have characterized the in-vitro and in-vivo properties of PRX-102 and compared the results with the two commercially produced α-Galactosidase-A enzymes. Results show that PRX-102 has prolonged in-vitro stability in plasma, after 1h incubation it retains 30% activity compared with complete inactivation of the commercial enzymes. Under lysosomal-like conditions PRX-102 maintains over 80% activity following 10 days of incubation, while commercial enzymes become inactive after 2days. Pharmacokinetic profile of PRX-102 measured in male Fabry mice shows a 10 fold increase in t1/2 in mice (581min) compared to approved drugs. The enzyme has significantly different kinetic parameters to the alternative ERTs available (p-valueFabry fibroblasts. The repeat administration of the enzyme to Fabry mice caused significant reduction (p-valueFabry disease. Copyright © 2014. Published by Elsevier Inc.

  10. Plasma mutant α-galactosidase A protein and globotriaosylsphingosine level in Fabry disease

    Directory of Open Access Journals (Sweden)

    Takahiro Tsukimura

    2014-01-01

    Full Text Available Fabry disease is an X-linked genetic disorder characterized by deficient activity of α-galactosidase A (GLA and accumulation of glycolipids, and various GLA gene mutations lead to a wide range of clinical phenotypes from the classic form to the later-onset one. To investigate the biochemical heterogeneity and elucidate the basis of the disease using available clinical samples, we measured GLA activity, GLA protein and accumulated globotriaosylsphingosine (Lyso-Gb3, a biomarker of this disease, in plasma samples from Fabry patients. The analysis revealed that both the enzyme activity and the protein level were apparently decreased, and the enzyme activity was well correlated with the protein level in many Fabry patients. In these cases, a defect of biosynthesis or excessive degradation of mutant GLAs should be involved in the pathogenesis, and the residual protein level would determine the accumulation of Lyso-Gb3 and the severity of the disease. However, there are some exceptional cases, i.e., ones harboring p.C142Y, p.R112H and p.M296I, who exhibit a considerable amount of GLA protein. Especially, a subset of Fabry patients with p.R112H or p.M296I has been attracted interest because the patients exhibit almost normal plasma Lyso-Gb3 concentration. Structural analysis revealed that C142Y causes a structural change at the entrance of the active site. It will lead to a complete enzyme activity deficiency, resulting in a high level of plasma Lyso-Gb3 and the classic Fabry disease. On the other hand, it is thought that R112H causes a relatively large structural change on the molecular surface, and M296I a small one in a restricted region from the core to the surface, both the structural changes being far from the active site. These changes will cause not only partial degradation but also degeneration of the mutant GLA proteins, and the degenerated enzymes exhibiting small and residual activity remain and probably facilitate degradation of Lyso-Gb3

  11. Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Feldt-Rasmussen, Ulla; Granqvist, Henrik

    2015-01-01

    also inspected visually and severity of white matter lesions (WMLs) was graded using a visual rating scale. RESULTS: In 28 patients brain-FDG-PET was normal; in 23 of these 28 patients brain MRI was normal--of the remaining five patients in this group, four patients had WMLs and one patient never had...... risk of cerebrovascular disease at a young age in addition to heart and kidney failure. OBJECTIVE: The objective of this study was to assess brain function and structure in the Danish cohort of patients with Fabry disease in a prospective way using 18-fluoro-deoxyglucose (F-18 FDG) positron emission...... tomography (PET) and magnetic resonance imaging (MRI). PATIENTS: Forty patients with Fabry disease (14 males, 26 females, age at inclusion: 10-66 years, median: 39 years) underwent a brain F-18-FDG-PET-scan at inclusion, and 31 patients were followed with FDG-PET biannually for up to seven years. All...

  12. Screening for Fabry's disease in young patients with ischemic stroke in a Chinese population.

    Science.gov (United States)

    Song, Xiaowei; Xue, Sufang; Zhao, Jingyan; Wu, Jian

    2017-04-01

    Fabry disease is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. Data regarding Fabry disease and ischemic stroke has been lacking in China. In this study, we investigated the prevalence of Fabry disease and the distribution of the alpha-galactosidase A (α-GalA) gene - GLA mutations in young stroke patients in the Chinese population and its association with stroke subtypes. A total of 357 ischemic stroke patients admitted to Xuanwu Hospital of Capital Medical University, aged 18-55 years old, including 293 patients with cerebral infarction and 64 patients with transient ischemic attack, were enrolled in this study. Mutations in the GLA gene were screened by Sanger sequencing. Enzyme levels were measured to further confirm the disease in patients with the gene mutation. The mutation frequency was compared among different stroke subtypes and further compared with the control group individually. No pathogenic mutations in the coding regions of the GLA gene were identified in this group of patients and thus no Fabry disease was found in our study. However, the frequency of an intronic polymorphism c.-10C>T was significantly different among different Trial of Org 10172 in Acute Stroke Treatment subtypes (p T polymorphism in patients with stroke due to other causes and undetermined causes was much higher than that in the control group (OR = 3.18, 95% CI: 1.29-7.83, p stroke patients. In addition, our results suggested that the c.-10C>T polymorphism may be a risk factor for ischemic stroke of other and undetermined causes. Further study is required to confirm our findings.

  13. Prevalence of Fabry Disease and Outcomes in Young Canadian Patients With Cryptogenic Ischemic Cerebrovascular Events.

    Science.gov (United States)

    Lanthier, Sylvain; Saposnik, Gustavo; Lebovic, Gerald; Pope, Karen; Selchen, Daniel; Moore, David F

    2017-07-01

    Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA). We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation. α-galactosidase-A gene was sequenced for Fabry diagnosis. National Institutes of Health Stroke Scale score was measured at presentation to quantify stroke severity. Modified Rankin Scale determined functional outcomes ≤7 days after presentation and 6 months later. We enrolled 365 patients with IS and 32 with TIA. α-galactosidase-A sequencing identified a single carrier of a genetic variant of unknown significance (p.R118C) and no well-recognized pathogenic variants. Mean National Institutes of Health Stroke Scale score was 3.1. Proportion of patients with modified Rankin Scale of 0 to 2 was 70.7% at ≤7 days and 87.4% at 6 months. National Institutes of Health Stroke Scale score at presentation and diabetes mellitus predicted 6-month modified Rankin Scale. Thirteen patients experienced 5 recurrent IS and 9 TIA during follow-up. No patient died. Most patients (98.7%) returned home. Among previous workers, 43% had residual working limitations. In this Canadian cohort of patients with cryptogenic IS or TIA, the prevalence of Fabry was 0.3% if p.R118C variant is considered as pathogenic. This suggests that more cost-effective methods should be applied for diagnosis of Fabry rather than systematic genetic screening in this population. Overall, cryptogenic IS in young adults is associated with favorable outcomes. © 2017 American Heart Association, Inc.

  14. Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model.

    Science.gov (United States)

    Lakomá, Jarmila; Rimondini, Roberto; Ferrer Montiel, Antonio; Donadio, Vincenzo; Liguori, Rocco; Caprini, Marco

    2016-01-01

    Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(-/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(-/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(-/0) mice displayed a ≈2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(-/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(-/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(-/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life. © The Author(s) 2016.

  15. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    International Nuclear Information System (INIS)

    Baptista, Ana; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio

    2015-01-01

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m 2 for women or ≥ 116 g/m 2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m 2 (± 28.5; 99.2 to 228.5 g/m 2 ] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  16. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

    2015-08-15

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  17. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Directory of Open Access Journals (Sweden)

    Ana Baptista

    2015-01-01

    Full Text Available Abstract Background: Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. Objective: To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. Methods: The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m2 for women or ≥ 116 g/m2 for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. Results: A total of 47 patients with a mean left ventricular mass index of 141.1 g/m2 (± 28.5; 99.2 to 228.5 g/m2] were included. Most of the patients were females (51.1%. Nine (19.1% showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5, a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. Conclusion: In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5.

  18. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed. © 2013 Elsevier Inc. All rights reserved.

  19. Prevalence of Cardiac Abnormalities in Fabry Disease: a large CMR study in Argentina

    OpenAIRE

    Laura Dragonetti; Marcelo Pietrani; Carlos Rivas; Diego Pérez de Arenaza; Eduardo Eyheremendy; Rebeca Kozzor; Ricardo García Mónaco; James Moon

    2016-01-01

    Background: Cardiovascular magnetic resonance (CMR) can measure cardiac structure, function and characterize myocardial tissue. The full potential of CMR for Fabry disease (FD) is yet to be defined. The objective of the present work was to assess the clinical utility of CMR for the detection and classification of cardiac involvement in patients with FD. Methods This is retrospective observational study of CMR scans performed in 99 unique FD patients from 2 hospitals in Argentina between...

  20. Blood group does not correlate with disease severity in patients with Fabry disease (alpha-galactosidase A deficiency)

    NARCIS (Netherlands)

    Linthorst, Gabor E.; Folman, Claudia C.; Aerts, Johannes M. F. G.; Hollak, Carla E. M.

    2003-01-01

    Blood groups B and P1 are substrates for the lysosomal enzyme alpha-galactosidase A. Therefore, patients with alpha-Gal A deficiency and blood groups B or P1 may exhibit more severe disease. In 48 Fabry patients distribution of blood group was not different from that in the Dutch population. No

  1. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  2. Fabry disease: Four case reports of meningioma and a review of the literature on other malignancies

    Directory of Open Access Journals (Sweden)

    Beth L. Thurberg, MD, PhD

    2017-06-01

    Full Text Available Fabry disease (FD is an X-linked lysosomal storage disorder caused by loss of function mutations in the GLA gene at Xq22 with subsequent functional deficiency of alpha-galactosidase A, resulting in the accumulation of globotriaosylceramide (GL-3 or Gb3 in multiple cells types throughout the body. As with other rare metabolic disorders, little is known about the incidence of malignancies in these populations and the relationship to the underlying disease, if any. We report the occurrence of meningioma in four female patients with Fabry disease. Two of the cases are from the same family and shared the same GLA mutation. All four patients underwent surgical excision of their tumor. High resolution light microscopy and electron microscopy examination of one case revealed extensive involvement of tumor cells and associated blood vessels by GL-3 accumulation. Because of the small number of Fabry-associated cancer cases reported in the literature, questions about a possible link between lysosomal storage disorders and the development of malignancy remain open.

  3. Successful salvage therapy with Daptomycin for osteomyelitis caused by methicillin-resistant Staphylococcus aureus in a renal transplant recipient with Fabry-Anderson disease

    Directory of Open Access Journals (Sweden)

    Polilli Ennio

    2012-03-01

    Full Text Available Abstract Daptomycin is licensed in adults for the management of Staphylococcus aureus methicillin-resistant infections, including bone and skin complicated infections. We describe for the first time its use in a renal transplant recipient for Fabry-Anderson Disease with right heel osteomyelitis. The patient was unresponsive to first-line Teicoplanin and second-line Tigecycline, whereas he was successfully treated with third-line Daptomycin monotherapy at 4 mg/Kg/qd for 4 weeks. Local debridement was performed in advance of each line of treatment.

  4. Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla.

    Science.gov (United States)

    Petritsch, B; Köstler, H; Weng, A M; Horn, M; Gassenmaier, T; Kunz, A S; Weidemann, F; Wanner, C; Bley, T A; Beer, M

    2016-10-28

    Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1 H magnetic resonance spectroscopy (MRS) at 3 Tesla. Myocardial lipid content was quantified in vivo by 1 H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1 H-MRS with cardiac cine imaging and LGE MRI in a single examination. Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1 H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1 H-MRS; T 1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.

  5. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

    DEFF Research Database (Denmark)

    Torvin, Moller A.; Winther, Bach F.; Feldt-Rasmussen, U.

    2009-01-01

    Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme alpha-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until...... and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation...

  6. [Role of cardiac magnetic resonance in cardiac involvement of Fabry disease].

    Science.gov (United States)

    Serra, Viviana M; Barba, Miguel Angel; Torrá, Roser; Pérez De Isla, Leopoldo; López, Mónica; Calli, Andrea; Feltes, Gisela; Torras, Joan; Valverde, Victor; Zamorano, José L

    2010-09-04

    Fabry disease is a hereditary disorder. Clinical manifestations are multisystemic. The majority of the patients remain undiagnosed until late in life, when alterations could be irreversible. Early detection of cardiac symptoms is of major interest in Fabry's disease (FD) in order to gain access to enzyme replacement therapy. Echo-Doppler tissular imaging (TDI) has been used as a cardiologic early marker in FD. This study is intended to determine whether the cardiac magnetic resonance is as useful tool as TDI for the early detection of cardiac affectation in FD. Echocardiography, tissue Doppler and Cardio magnetic resonance was performed in 20 patients with confirmed Fabry Disease. Left ventricular hypertrophy was defined as septum and left ventricular posterior wall thickness ≥12 mm. An abnormal TDI velocity was defined as (Sa), (Ea) and/or (Aa) velocities gadolinium-enhanced images sequences were obtained using magnetic resonance. Twenty patients included in the study were divided into three groups: 1. Those without left ventricular hypertrophy nor tissue Doppler impairment 2. Those without left ventricular hypertrophy and tissue Doppler impairment 3. Those with left ventricular hypertrophy and Tissue Doppler impairment. Late gadolinium enhancement was found in only one patient, who has already altered DTI and LVH. Tissue Doppler imaging (TDI) is the only diagnostic tool able to provide early detection of cardiac affectation in patients with FD. Magnetic resonance provides information of the disease severity in patients with LVH, but can not be used as an early marker of cardiac disease in patients with FD. However MRI could be of great value for diagnostic stratification. Copyright © 2009 Elsevier España, S.L. All rights reserved.

  7. Skin Diseases and the Adolescent

    Science.gov (United States)

    Bauer, Marjorie

    1970-01-01

    Discusses such concerns as acne, syphilis, drug abuse, and tatoos. Indicates need for physician not only to treat skin diseases but to help adolescents to accept themselves and find constructive directions. (CJ)

  8. Skin Manifestations of Endocrine Diseases.

    Science.gov (United States)

    Demirkesen, Cuyan

    2015-01-01

    Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

  9. Tandem mass spectrometry multiplex analysis of methylated and non-methylated urinary Gb3 isoforms in Fabry disease patients.

    Science.gov (United States)

    Abaoui, Mona; Boutin, Michel; Lavoie, Pamela; Auray-Blais, Christiane

    2016-01-15

    Fabry disease is a lysosomal storage disorder leading to the accumulation of glycosphingolipids in biological fluids and tissues. Globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are currently used for Fabry screening and diagnosis. However, these biomarkers are not always increased in Fabry patients with residual enzyme activity. We recently identified 7 urinary methylated Gb3-related isoforms. The aims of this study were (1) to develop and validate a novel LC-MS/MS method for the relative quantification of methylated and non-methylated Gb3 isoforms normalized to creatinine, (2) to evaluate these biomarkers in Fabry patients and healthy controls, and (3) to assess correlations between biomarker urinary excretion with age, gender, treatment and genotype of patients. Urine samples from 150 Fabry patients and 95 healthy controls were analyzed. Samples were purified and injected in the tandem mass spectrometer working in positive electrospray ionization. Relative quantification was performed for 15 methylated and non-methylated Gb3 isoforms. Significant correlations (pFabry patients with late-onset cardiac variant mutations. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease.

    Science.gov (United States)

    Kanai, Takahiro; Ito, Takane; Odaka, Jun; Saito, Takashi; Aoyagi, Jun; Betsui, Hiroyuki; Yamagata, Takanori

    2016-03-01

    Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels. This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.

  11. Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Frits A Wijburg

    Full Text Available This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.Males aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years were studied, including cellular globotriaosylceramide (GL-3 accumulation in skin (n = 31 and kidney biopsy (n = 6; median age 15 years; range 13-17 years, renal function, and glycolipid levels (plasma, urine.Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients and deep vessel endothelial cells (23/29 patients. The mean glomerular filtration rate (GFR, measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2 (range 90.4-161.0 mL/min/1.73 m(2 and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g. On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells, as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced

  12. Separation and Analysis of Lactosylceramide, Galabiosylceramide, and Globotriaosylceramide by LC-MS/MS in Urine of Fabry Disease Patients.

    Science.gov (United States)

    Boutin, Michel; Menkovic, Iskren; Martineau, Tristan; Vaillancourt-Lavigueur, Vanessa; Toupin, Amanda; Auray-Blais, Christiane

    2017-12-19

    Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A (α-GAL A) deficiency. This enzyme contributes to the cellular recycling of glycosphingolipids such as galabiosylceramide (Ga 2 ), globotriaosylceramide (Gb 3 ), and globotriaosylsphingosine (lyso-Gb 3 ) by hydrolyzing the terminal α-galactosyl moiety. Urine and plasma α-GAL A substrates are currently analyzed as biomarkers for the detection, monitoring, and follow-up of Fabry disease patients. The sensitivity of the analysis of Ga 2 is decreased by the co-analysis of its structural isomer, lactosylceramide (LacCer), which is not an α-GAL A substrate. A normal-phase ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) methodology, allowing the baseline separation of 12 Ga 2 isoforms/analogues from their lactosylceramide counterparts, was developed and validated in urine. The method was multiplexed with the analysis of 12 Gb 3 isoforms/analogues having the same fatty acid moieties as those of Ga 2 for comparison, and with creatinine for sample normalization. Urine samples were studied from 34 untreated and 33 Fabry males treated by enzyme replacement therapy (ERT) and 54 untreated and 19 ERT-treated Fabry females, along with 34 male and 25 female healthy controls. The chromatographic separation of Ga 2 from LacCer increased the sensitivity of analysis, especially in women. One untreated Fabry female and two treated Fabry females presented abnormal levels of Ga 2 but normal levels of Gb 3 , supporting the importance of analyzing Ga 2, in addition to Gb 3 . Our results show that urine LacCer levels from females were significantly higher than those from males. Moreover, LacCer levels were not affected by Fabry disease for both males and females.

  13. Gender aspects in skin diseases.

    Science.gov (United States)

    Chen, W; Mempel, M; Traidl-Hofmann, C; Al Khusaei, S; Ring, J

    2010-12-01

    Gender differences in medicine have been recognized in anatomy, physiology, as well as in epidemiology and manifestations of various diseases. With respect to skin disorders, males are generally more commonly afflicted with infectious diseases while women are more susceptible to psychosomatic problems, pigmentary disorders, certain hair diseases, and particularly autoimmune as well as allergic diseases. Significantly, more female sex-associated dermatoses can be identified than the male sex-associated dermatoses. Dermatoses in the genital area differ between men and women. Gender differences also exist in the occurrence and prognosis of certain skin malignancies. The mechanisms underlying gender differences in skin diseases remain largely unknown. Differences in the skin structure and physiology, effect of sex hormones, ethnic background, sociocultural behaviour and environmental factors may interact to exert the influences. A better understanding of gender differences in human health and diseases will allow the development of novel concepts for prevention, diagnosis and therapy of skin diseases. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

  14. Focal Reduction in Cardiac 123I-Metaiodobenzylguanidine Uptake in Patients With Anderson-Fabry Disease.

    Science.gov (United States)

    Yamamoto, Saori; Suzuki, Hideaki; Sugimura, Koichiro; Tatebe, Shunsuke; Aoki, Tatsuo; Miura, Masanobu; Yaoita, Nobuhiro; Sato, Haruka; Kozu, Katuya; Ota, Hideki; Takanami, Kentaro; Takase, Kei; Shimokawa, Hiroaki

    2016-11-25

    It remains to be elucidated whether cardiac sympathetic nervous activity is impaired in patients with Anderson-Fabry disease (AFD).Methods and Results:We performed 123 I-meta-iodobenzylguanidine (MIBG) scintigraphy and gadolinium-enhanced cardiovascular magnetic resonance (CMR) in 5 AFD patients. MIBG uptake in the inferolateral wall, where wall thinning and delayed enhancement were noted on CMR, was significantly lower compared with the anteroseptal wall. The localized reduction in MIBG uptake was also noted in 2 patients with no obvious abnormal findings on CMR. Cardiac sympathetic nervous activity is impaired in AFD before development of structural myocardial abnormalities. (Circ J 2016; 80: 2550-2551).

  15. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease

    DEFF Research Database (Denmark)

    Hughes, Derralynn A.; Nicholls, Kathleen; Shankar, Suma P.

    2017-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement......, to receive 18 months open-label migalastat or remain on ERT. Four patients had nonamenable mutant forms of α-Gal based on the validated cell-based assay conducted after treatment initiation and were excluded from primary efficacy analyses only. Migalastat and ERT had similar effects on renal function. Left...

  16. Social preference weights for treatments in Fabry disease in the UK: a discrete choice experiment.

    Science.gov (United States)

    Lloyd, Andrew J; Gallop, Katy; Ali, Shehzad; Hughes, Derralynn; MacCulloch, Alasdair

    2017-01-01

    Fabry disease is a rare inherited lysosomal storage disorder caused by deficiency of α-galactosidase A. Effective enzyme replacement therapies are available that are administered intravenously. However, a new oral treatment is being developed as an alternative option for patients with amenable mutations. This study was designed to understand the value that people place on the different features of treatments for Fabry disease. A discrete choice experiment (DCE) was designed to assess the importance of different aspects of treatments for Fabry disease. The attributes included overall survival, mode of administration, treatment related reactions, treatment related headaches and risk of antibody formation. Attributes were combined using a published orthogonal array into choice sets. A research panel was used to survey the UK general public. The mixed logit model was used to estimate strength of preference for the attributes and marginal rates of substitution (MRSs). Disutilities were estimated from the DCE data for changes in each attribute. The sample (n = 506) was broadly representative of UK demographics. The logit model revealed that all attributes were significant predictors of choice. Participants were significantly more likely to choose a treatment which meant an increase in their life expectancy by 1 year (odds ratio = 1.574; 95% CI = 1.504-1.647) and significantly less likely to choose self-administered intravenous (IV) treatment compared to an every other day tablet (OR = 0.426 95% CI = 0.384-0.474). Estimated disutilities were -0.0543 (self-administered infusion), treatment related headaches 12 times a year (-0.0361) and infusion reactions six times a year (-0.0202). The survey revealed a significant preference for oral treatment compared with IV even in the context of a treatment that can extend overall survival. MRSs were used as a basis for estimating disutilities associated with changes in attribute levels which could be used to weight QALYs. It is

  17. Fabry's Disease: Case Series and Review of Literature

    African Journals Online (AJOL)

    cells causing suspicion of a metabolic disease (e.g., FD). Subsequent enzymatic and pedigree analysis confirmed the diagnosis of FD in the recipient and one of his brothers with the possibility of their mother being an affected carrier. Four years posttransplant, the patient continues to have progressively worsening serum ...

  18. Guidelines to start enzyme replacement therapy in classic Fabry Disease patients in Latin America

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2017-01-01

    Full Text Available Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. Conclusion: We believe that the importance of this guideline relies on the participation of experts from ten Latin American countries. However, as it deals with a systemic disease whose physiopathological mechanisms and complications are still being described, some manifestations have not been included in the criteria, making it necessary to revise this guideline in order to report any changes that may arise in the future.

  19. Human Alpha Galactosidases Transiently Produced in Nicotiana benthamiana Leaves: New Insights in Substrate Specificities with Relevance for Fabry Disease

    NARCIS (Netherlands)

    Kytidou, Kassiani; Beenakker, Thomas J. M.; Westerhof, Lotte B.; Hokke, Cornelis H.; Moolenaar, Geri F.; Goosen, Nora; Mirzaian, Mina; Ferraz, Maria J.; de Geus, Mark; Kallemeijn, Wouter W.; Overkleeft, Herman S.; Boot, Rolf G.; Schots, Arjen; Bosch, Dirk; Aerts, Johannes M. F. G.

    2017-01-01

    Deficiency of α-galactosidase A (α-GAL) causes Fabry disease (FD), an X-linked storage disease of the glycosphingolipid globtriaosylcerammide (Gb3) in lysosomes of various cells and elevated plasma globotriaosylsphingosine (Lyso-Gb3) toxic for podocytes and nociceptive neurons. Enzyme replacement

  20. Recombinant enzyme therapy for Fabry disease: Absence of editing of human alpha-galactosidase A mRNA

    NARCIS (Netherlands)

    Blom, Daniël; Speijer, Dave; Linthorst, Gabor E.; Donker-Koopman, Wilma G.; Strijland, Anneke; Aerts, Johannes M. F. G.

    2003-01-01

    For more than a decade, protein-replacement therapy has been employed successfully for the treatment of Gaucher disease. Recently, a comparable therapy has become available for the related lipid-storage disorder Fabry disease. Two differently produced recombinant alpha-galactosidase A (alpha-gal A)

  1. Accidente cerebro-vascular en la enfermedad de Fabry: Algo más que una simple estenosis Stroke in Fabry disease: More than a simple stenosis

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2006-10-01

    Full Text Available Se analiza la evidencia existente a la fecha sobre los mecanismos fisiopatológicos que pueden generar accidentes cerebrovasculares en la enfermedad de Fabry. Esta entidad es el resultado de la deficiencia de a-galactosidasa A, lo que resulta en depósito patológico de glicoesfingilípidos en distintas poblaciones celulares. Asociados a la insuficiencia renal y cardíaca, los accidentes cerebrovasculares pueden derivar en la muerte de los pacientes. Durante mucho tiempo el único mecanismo generador de daño vascular informado fue la oclusión vascular por depósito lipídico a nivel endotelial. En la actualidad se describen otros mecanismos. El advenimiento de la terapia de reemplazo enzimático ha generado gran expectativa en cuanto la posibilidad de reversión de estos mecanismos. Si bien la evidencia es escasa y son necesarios más estudios a largo plazo, algunos informes demuestran que luego de meses, el tratamiento ha logrado revertir algunos de los mecanismos implicados.The objective is to analyze the updated evidence on the physiopathological mechanisms that can generate cerebrovascular damage in Fabry disease. Fabry disease is the result of the deficiency of a-galactosidasa A, which causes pathological storage of glycosphingolipids, in different cells. Associated to renal and cardiac insufficiency, cerebrovascular complications can derive in the death of the patients. During a long time the only reported mechanism was the vascular occlusion by deposit of lipids at endothelial level. At the present time, other mechanisms are postulated. The arrival of enzyme replacement therapy has generated great expectation on the possibility of reversion of these alterations. Although the evidence is scarce and more long term studies are necessary, some reports demonstrate that after months, the treatment has managed to revert some of the mechanisms involved.

  2. Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta

    DEFF Research Database (Denmark)

    Wilcox, William R; Feldt-Rasmussen, Ulla; Martins, Ana Maria

    2018-01-01

    of organ involvement. Although variable, gastrointestinal symptoms are among the most common and significant early clinical manifestations; they tend to persist into adulthood if left untreated. To further understand the effects of sustained enzyme replacement therapy (ERT) with agalsidase beta......Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase, GLA. In patients with Fabry disease, glycosphingolipids accumulate in various cell types, triggering a range of cellular and tissue responses that result in a wide spectrum...... on gastrointestinal symptoms in heterozygotes, a data analysis of female patients enrolled in the Fabry Registry was conducted. To be included, females of any age must have received agalsidase beta (average dose 1.0 mg/kg every 2 weeks) for at least 2.5 years. Measured outcomes were self-reported gastrointestinal...

  3. Long time enzyme replacement therapy stabilizes obstructive lung disease and alters peripheral immune cell subsets in Fabry patients.

    Science.gov (United States)

    Odler, Balázs; Cseh, Áron; Constantin, Tamás; Fekete, György; Losonczy, György; Tamási, Lilla; Benke, Kálmán; Szilveszter, Bálint; Müller, Veronika

    2017-11-01

    Fabry disease is an X-linked lysosomal storage disorder, causing accumulation of globotriaosylceramid in different organs. Glycolipids are activators of different immune cell subsets the resulting inflammation is responsible for organ damage. Pulmonary involvement leads to airway inflammation; however, data on severity, as well as the effect of enzyme replacement therapy on lung function parameters and changes in peripheral immune cell subsets on lung involvement are sparse. Seven Fabry patients and four carriers underwent detailed clinical examinations screening for pulmonary manifestations. Repetitive measurements were performed on five patients on ERT (average follow-up 5 years). Patients with Fabry disease and control volunteers were included into peripheral blood cell measurements. Lung involvement was present in all patients. Symptoms suggestive for lung disease were mild, however, obstructive ventilatory disorder, dominantly affecting small airways accompanied by hyperinflation was demonstrated in all affected patients. ERT resulted in small improvement of FEV1 in most treated patients. Decreased ratio of myeloid DC, Th17 cells while increase in T helper (Th)1 cells, and no change in Th2 and regulatory T (Treg) cells were detected in Fabry patients. Fabry disease results mainly in mild symptoms related to lung involvement, characterized by moderate non-reversible obstructive ventilatory disorder. Stabilization of airway obstruction during follow-up was observed using ERT in most patients, emphasizing the importance of this treatment in respect of pulmonary manifestations. Changes of immune cell subsets in the peripheral blood might play a role in inflammatory process, including small airways in Fabry patient's lung. © 2016 John Wiley & Sons Ltd.

  4. Enzyme replacement therapy for Fabry disease: some answers but more questions

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2011-02-01

    Full Text Available Majid Alfadhel1, Sandra Sirrs21Division of Biochemical Diseases, Department of Paediatrics, BC Children’s and Women’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, CanadaAbstract: Fabry disease (FD is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.Keywords: Fabry disease, agalsidase α, agalsidase β, Replagal, Fabrazyme, critical appraisal, evidence-based medicine

  5. The skin in Parkinson's disease.

    Science.gov (United States)

    Flint, A

    1977-09-01

    The characteristic oily skin in individuals with parkinsonism has long been observed by clinicians. The oiliness seems to be associated with periods when the disease is most active. This seborrhea has been observed particularly in post-encephalitic parkinsonism, as well as in idiopathic paralysis agitans. It also occurs in phenothiazine-induced parkinsonism.

  6. Malassezia skin diseases in humans.

    Science.gov (United States)

    Difonzo, E M; Faggi, E; Bassi, A; Campisi, E; Arunachalam, M; Pini, G; Scarfì, F; Galeone, M

    2013-12-01

    Although Malassezia yeasts are a part of the normal microflora, under certain conditions they can cause superficial skin infection, such as pityriasis versicolor (PV) and Malassezia folliculitis. Moreover the yeasts of the genus Malassezia have been associated with seborrheic dermatitis and dandruff, atopic dermatitis, psoriasis, and, less commonly, with confluent and reticulated papillomatosis, onychomycosis, and transient acantholytic dermatosis. The study of the clinical role of Malassezia species has been surrounded by controversy due to the relative difficulty in isolation, cultivation, and identification. This review focuses on the clinical, mycologic, and immunologic aspects of the various skin diseases associated with Malassezia. Moreover, since there exists little information about the epidemiology and ecology of Malassezia species in the Italian population and the clinical significance of these species is not fully distinguished, we will report data about a study we carried out. The aim of our study was the isolation and the identification of Malassezia species in PV-affected skin and non-affected skin in patients with PV and in clinically healthy individuals without any Malassezia associated skin disease.

  7. Fabry disease: renal sphingolipid distribution in the alpha-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging

    Czech Academy of Sciences Publication Activity Database

    Kuchař, L.; Faltýsková, Helena; Ledvinová, J.; Krásný, Lukáš; Dobrovolný, R.; Hůlková, H.; Volný, Michael; Strohalm, Martin; Lemr, Karel; Kryšpínová, L.; Asfaw, B.; Rybová, J.; Desnick, R.J.; Havlíček, Vladimír

    2015-01-01

    Roč. 407, č. 8 (2015), s. 2283-2291 ISSN 1618-2642 R&D Projects: GA MŠk(CZ) LD13038; GA ČR(CZ) GAP206/12/1150 Institutional support: RVO:61388971 Keywords : Fabry disease * Kidney * Glycosphingolipids Subject RIV: CE - Biochemistry Impact factor: 3.125, year: 2015

  8. Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

    NARCIS (Netherlands)

    Biegstraaten, Marieke; van Schaik, Ivo N.; Wieling, Wouter; Wijburg, Frits A.; Hollak, Carla E. M.

    2010-01-01

    ABSTRACT: BACKGROUND: Fabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and

  9. Effective clearance of GL-3 in a human iPSC-derived cardiomyocyte model of Fabry disease.

    Science.gov (United States)

    Itier, Jean-Michel; Ret, Gwénaëlle; Viale, Sandra; Sweet, Lindsay; Bangari, Dinesh; Caron, Anne; Le-Gall, Françoise; Bénichou, Bernard; Leonard, John; Deleuze, Jean-François; Orsini, Cécile

    2014-11-01

    Fabry disease, a rare X-linked α-galactosidase A deficiency, causes progressive lysosomal accumulation of globotriaosylceramide (GL-3) in a variety of cell types. As the disease progresses, renal failure, left ventricular hypertrophy, and strokes may occur. Enzyme replacement therapy (ERT), with recombinant α-galactosidase A, is currently available for use to reduce GL-3 deposits. However, although it improves cardiac function and decreases left ventricular mass, GL-3 clearance upon ERT has been demonstrated in cardiac capillary endothelium but not in cardiomyocytes of patients. Relevant models are needed to understand the pathogenesis of cardiac disease and explore new therapeutic approaches. We generated induced pluripotent stem cells (iPSC) from Fabry patients and differentiated them into cardiomyocytes. In these cells, GL-3 accumulates in the lysosomes over time, resulting in phenotypic changes similar to those found in cardiac tissue from Fabry patients. Using this human in vitro model, we demonstrated that substrate reduction therapy via glucosylceramide synthase inhibition was able to prevent accumulation and to clear lysosomal GL-3 in cardiomyocytes. This new in vitro model recapitulates essential features of cardiomyocytes from patients with Fabry disease and therefore provides a useful and relevant tool for further investigations of new therapy.

  10. In Patients with an α-Galactosidase A Variant, Small Nerve Fibre Assessment Cannot Confirm a Diagnosis of Fabry Disease

    NARCIS (Netherlands)

    van der Tol, Linda; Verhamme, Camiel; van Schaik, Ivo N.; van der Kooi, Anneke J.; Hollak, Carla E. M.; Biegstraaten, Marieke

    2016-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by an α-galactosidase A enzyme deficiency due to pathogenic variants in the α-galactosidase A gene (GLA). An increasing number of individuals with a GLA variant, but without characteristic FD features, are identified. A definite

  11. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Thaneas Prabakaran

    Full Text Available Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs.

  12. The management of Fabry nephropathy

    Directory of Open Access Journals (Sweden)

    Renzo Mignani

    2016-09-01

    Full Text Available A case of an adult female with Fabry disease is described with discussion based on the following key questions: 1. What is the natural history of Fabry nephropathy? 2. What are the indications to perform kidney biopsy in Fabry disease? 3. How to perform the workout of the patient in recognition of systemic organ damage? 4. Is the missed recognition of Fabry disease frequent in dialysis patients? 5. When and which patients are eligible to start enzyme replacement therapy? 6. Is enzyme replacement therapy effective in Fabry nephropathy? 7. What is the outcome of the patient who underwent a kidney transplantation? 8. Is the supportive therapy important in Fabry disease nephropathy? 9. What are the future therapeutic perspectives?

  13. Myocardial fibrosis as the first sign of cardiac involvement in a male patient with Fabry disease: report of a clinical case and discussion on the utility of the magnetic resonance in Fabry pathology.

    Science.gov (United States)

    Sechi, Annalisa; Nucifora, Gaetano; Piccoli, Gianluca; Dardis, Andrea; Bembi, Bruno

    2014-07-16

    Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging is increasingly used to assess myocardial involvement in patients with Fabry disease, an X linked lipid storage disorder. However, it is often proposed as an optional tool. A different cardiomyopathic disease progression between male and female patients was hypothesised in previous studies, as in female myocardial fibrosis was found without left ventricular (LV) hypertrophy, while myocardial fibrosis was always detected in association to LV hypertrophy in men. A male Caucasian patient, 19 years old, diagnosed through a family-based molecular screening, presented with LGE of the LV inferolateral wall evidenced at the CMR, without LV hypertrophy, or other clinical signs of the disease. This is the first report of cardiac fibrosis as the first sign of organ involvement in a male patient with Fabry disease. This finding stresses the importance of performing CMR with LGE imaging for the initial staging and monitoring of Fabry patients of both genders.

  14. Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

    Science.gov (United States)

    Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

    2017-10-01

    Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

  15. Skin diseases in Turkish soldiers

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2011-06-01

    Full Text Available This study aimed to determine the prevalence of skin diseases among soldiers who were assigned duties in Kahramanmaras, a province of east Mediterranean region of Turkey. One hundred eighty-eight soldiers were assessed for skin diseases by a complete dermatological examination and the findings were recorded to a form. Apart from the low number of older ones, the soldiers were of 20–22 years. The diagnosis of superficial fungal infections was made by the use of potassium hydroxide preparations in addition to clinical appearance. On completion of the study period, the data were evaluated, and patients were grouped. Pitted keratolysis was the primary dermatologic disease in 34.5% of the soldiers, 29.2% were diagnosed with oral candidiasis, and 25.5% suffered from tinea pedis. Among the soldiers suffering from a cutaneous disease, dyshidrotic eczema (18.6%, intertrigo (excluding candidal intertrigo (17%, acne (17%, seborrheic dermatitis (14.9%, plantar hyperkeratosis (14.3%, contact dermatitis (13.8%, and folliculitis (12.2% were the other most frequent dermatoses. Other less frequent dermatoses were asteatotic eczema, callus, onychomycosis, traumatic onychodystrophy, and so on. We conclude that the prevalence of skin diseases in soldiers is very high and is one of the major public health problems that have a significant burden on our nation.

  16. Skin disorders in Parkinson's disease

    DEFF Research Database (Denmark)

    Ravn, Astrid-Helene; Thyssen, Jacob P; Egeberg, Alexander

    2017-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, characterized by a symptom triad comprising resting tremor, rigidity, and akinesia. In addition, non-motor symptoms of PD are well recognized and often precede the overt motor manifestations. Cutaneous manifestations...... with bullous pemphigoid. Moreover, a 2-fold increase in risk of new-onset PD has been observed in patients with rosacea. Besides the association between PD and various dermatological disorders, the skin may be useful in the diagnosis of PD. Early PD pathology is found not only in the brain but also in extra......-neuronal tissues. Thus, the protein α-synuclein, which is genetically associated with PD, is present not only in the CNS but also in the skin. Hence, higher values of α-synuclein have been observed in the skin of patients with PD. Furthermore, an increased risk of PD has been found in the Cys/Cys genotype, which...

  17. Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease.

    Science.gov (United States)

    Huang, Ju; Khan, Aneal; Au, Bryan C; Barber, Dwayne L; López-Vásquez, Lucía; Prokopishyn, Nicole L; Boutin, Michel; Rothe, Michael; Rip, Jack W; Abaoui, Mona; Nagree, Murtaza S; Dworski, Shaalee; Schambach, Axel; Keating, Armand; West, Michael L; Klassen, John; Turner, Patricia V; Sirrs, Sandra; Rupar, C Anthony; Auray-Blais, Christiane; Foley, Ronan; Medin, Jeffrey A

    2017-06-16

    Fabry disease is a rare lysosomal storage disorder (LSD). We designed multiple recombinant lentivirus vectors (LVs) and tested their ability to engineer expression of human α-galactosidase A (α-gal A) in transduced Fabry patient CD34 + hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34 + hematopoietic cells produced even higher levels of α-gal A activity than normal CD34 + hematopoietic cells. We successfully transduced Fabry patient CD34 + hematopoietic cells with "near-clinical grade" LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34 + hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF) mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA) to Health Canada and opening of a "first-in-the-world" gene therapy trial for Fabry disease.

  18. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    Science.gov (United States)

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P adaptive functioning. Decreased social-adaptive functioning in this study was not statistically significantly associated to disease severity, pain, or level of vitality. This study shows for the first time that FD patients, particularly women, are affected by decreased social-adaptive functioning. Comprehensive treatment plans for FD should consider assessments and interventions to evaluate and improve social, occupational, and psychological functioning. Attention to the behavioral aspects of FD could lead to improved treatment outcome and improved quality of life. Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.

  19. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease

    OpenAIRE

    Moon, J. C.; Sheppard, M.; Reed, E.; Lee, P.; Elliott, P. M.; Pennell, D. J.

    2006-01-01

    Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic d...

  20. Morgellons Disease: Managing a Mysterious Skin Condition

    Science.gov (United States)

    Morgellons disease: Managing an unexplained skin condition Morgellons disease is a controversial, unexplained skin condition. Here you'll find answers to common questions about Morgellons and suggestions for coping with it. ...

  1. Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy

    Directory of Open Access Journals (Sweden)

    Ruiz de Garibay AP

    2012-10-01

    Full Text Available Aritz Pérez Ruiz de Garibay, Diego Delgado, Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez GascónPharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy Faculty, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainPurpose: Gene-mediated enzyme replacement is a reasonable and highly promising approach for the treatment of Fabry disease (FD. The objective of the present study was to demonstrate the potential applications of solid lipid nanoparticle (SLN-based nonviral vectors for the treatment of FD.Methods: SLNs containing the pR-M10-αGal A plasmid that encodes the α-Galactosidase A (α-Gal A enzyme were prepared and their in vitro transfection efficacy was studied in Hep G2 cells. We also studied the cellular uptake of the vectors and the intracellular disposition of the plasmid.Results: The enzymatic activity of the cells treated with the vectors increased significantly relative to the untreated cells, regardless of the formulation assayed. When the SLNs were prepared with protamine or dextran and protamine, the activity of the α-Gal A enzyme by the transfected Hep G2 cells increased up to 12-fold compared to that of untreated cells.Conclusion: With this work we have revealed in Hep G2 cells the ability of a multicomponent system based on SLNs to act as efficient nonviral vectors to potentially correct low α-Gal A activity levels in FD with gene therapy.Keywords: solid lipid nanoparticles, Fabry disease, nonviral vectors, gene therapy

  2. Fabry or not Fabry: From genetics to diagnosis

    NARCIS (Netherlands)

    van der Tol, L.

    2015-01-01

    Fabry disease is a lysosomal storage disorder with an X-linked pattern of inheritance. Fabry disease is caused by impaired degradation and accumulation of the glycosphingolipid globotriaosylceramide, due to a deficiency of the enzyme α-Galactosidase A. Both males and females can be affected,

  3. Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro.

    Science.gov (United States)

    Brogden, Graham; Shammas, Hadeel; Maalouf, Katia; Naim, Samara L; Wetzel, Gabi; Amiri, Mahdi; von Köckritz-Blickwede, Maren; Das, Anibh M; Naim, Hassan Y

    2017-04-30

    It is still not entirely clear how α-galactosidase A (GAA) deficiency translates into clinical symptoms of Fabry disease (FD). The present communication investigates the effects of the mutation N215S in FD on the trafficking and processing of lysosomal GAA and their potential association with alterations in the membrane lipid composition. Abnormalities in lipid rafts (LRs) were observed in fibroblasts isolated from a male patient with FD bearing the mutation N215S. Interestingly, LR analysis revealed that the distribution of cholesterol and flotillin-2 are distinctly altered in the Fabry fibroblasts when compared with that of the wild-type cells. Furthermore, increased levels of glycolipid globotriaosylceramide 3 (Gb3) and sphingomyelin (SM) were observed in non-raft membrane fractions of Fabry cells. Substrate reduction with N -butyldeoxynojirimycin (NB-DNJ) in vitro was capable of reversing these abnormalities in this patient. These data led to the hypothesis that alterations of LRs may contribute to the pathophysiology of Morbus Fabry. Furthermore, it may be suggested that substrate reduction therapy with NB-DNJ might be a promising approach for the treatment of GAA deficiency at least for the selected patients. © 2017 The Author(s).

  4. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

    2014-01-01

    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...

  5. Evaluation of oxidative stress markers and cardiovascular risk factors in Fabry Disease patients

    Directory of Open Access Journals (Sweden)

    Karen B. Müller

    2012-01-01

    Full Text Available Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle.

  6. Optical coherence tomography for imaging of skin and skin diseases

    DEFF Research Database (Denmark)

    Mogensen, Mette; Thrane, Lars; Jørgensen, Thomas Martini

    2009-01-01

    Optical coherence tomography (OCT) is an emerging imaging technology based on light reflection. It provides real-time images with up to 2-mm penetration into the skin and a resolution of approximately 10 μm. It is routinely used in ophthalmology. The normal skin and its appendages have been studied......, as have many diseases. The method can provide accurate measures of epidermal and nail changes in normal tissue. Skin cancer and other tumors, as well as inflammatory diseases, have been studied and good agreement found between OCT images and histopathological architecture. OCT also allows noninvasive...... monitoring of morphologic changes in skin diseases and may have a particular role in the monitoring of medical treatment of nonmelanoma skin cancer. The technology is however still evolving and continued technological development will necessitate an ongoing evaluation of its diagnostic accuracy. Several...

  7. Expert System For Diagnosis Of Skin Diseases

    Directory of Open Access Journals (Sweden)

    A.A.L.C. Amarathunga

    2015-01-01

    Full Text Available Abstract Dermatology is a one of major session of medicine that concerned with the diagnosis and treatment of skin diseases. Skin diseases are the most common form of disease in humans. Recently many of researchers have advocated and developed the imaging of human vision or in the loop approach to visual object recognition. This research paper presents a development of a skin diseases diagnosis system which allows user to identify diseases of the human skin and to provide advises or medical treatments in a very short time period. For this purpose user will have to upload an image of skin disease to our system and answer questions based on their skin condition or symptoms. It will be used to detect diseases of the skin and offer a treatment recommendation. This system uses technologies such as image processing and data mining for the diagnosis of the disease of the skin. The image of skin disease is taken and it must be subjected to various preprocessing for noise eliminating and enhancement of the image. This image is immediately segmentation of images using threshold values. Finally data mining techniques are used to identify the skin disease and to suggest medical treatments or advice for users. This expert system exhibits disease identification accuracy of 85 for Eczema 95 for Impetigo and 85 for Melanoma.

  8. A novel mutation of α-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family.

    Science.gov (United States)

    Ge, Wei; Wei, Bin; Zhu, Hao; Miao, Zhigang; Zhang, Weimin; Leng, Cuihua; Li, Jizhen; Zhang, Dan; Sun, Miao; Xu, Xingshun

    2017-05-01

    Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern. Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed. Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c.139T>C (p.W47R) of GLA was identified in a male proband as well as two female carriers in this family. Enzyme assay of α-galactosidase A activity showed deficient enzyme activity in male patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of α-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p.W47R of GLA is the cause of Fabry disease. Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.

  9. Atypical Distribution of Late Gadolinium Enhancement of the Left Ventricle on Cardiac Magnetic Resonance in Classical Anderson-Fabry Disease

    OpenAIRE

    Kasuya, Shusuke; Suzuki, Masayo; Inaoka, Tsutomu; Odashima, Masayuki; Nakatsuka, Tomoya; Ishikawa, Rumiko; Tokuyama, Wataru; Terada, Hitoshi

    2016-01-01

    Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. Approximately 50% of patients with AFD may have cardiac involvement. Gadolinium-enhanced cardiac magnetic resonance (CMR) is useful for the diagnosis of cardiac involvement of AFD by recognizing typical late gadolinium enhancement (LGE) patterns. We report a 48-year-old man with cardiac involvement in classical AFD, showing atypical distribution of the LGE at the mid-lateral...

  10. The Challenge of Diagnosis and Indication for Treatment in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Marco A. Curiati MD

    2017-01-01

    Full Text Available Fabry disease, caused by deficient alpha-galactosidase A lysosomal enzyme activity, remains challenging to health-care professionals. Laboratory diagnosis in males is carried out by determination of alpha-galactosidase A activity; for females, enzymatic activity determination fails to detect the disease in about two-thirds of the patients, and only the identification of a pathogenic mutation in the GLA gene allows for a definite diagnosis. The hurdle to be overcome in this field is to determine whether a mutation that has never been described determines a “classic” or “nonclassic” phenotype, because this will have an impact on the decision-making for treatment initiation. Besides the enzymatic determination and GLA gene mutation determination, researchers are still searching for a good biomarker, and it seems that plasma lyso-Gb3 is a useful tool that correlates to the degree of substrate storage in organs. The ideal time for treatment initiation for children and nonclassic phenotype remains unclear.

  11. High?Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease

    OpenAIRE

    Seydelmann, Nora; Liu, Dan; Kr?mer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; St?rk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2016-01-01

    Background High?sensitivity troponin (hs?TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs?TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow?up study to assess longitudinal hs?TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs?TNT from 75 consecutive patients with genetically confirm...

  12. Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.

    Science.gov (United States)

    Germain, Dominique P; Brand, Eva; Burlina, Alessandro; Cecchi, Franco; Garman, Scott C; Kempf, Judy; Laney, Dawn A; Linhart, Aleš; Maródi, László; Nicholls, Kathy; Ortiz, Alberto; Pieruzzi, Federico; Shankar, Suma P; Waldek, Stephen; Wanner, Christoph; Jovanovic, Ana

    2018-04-12

    The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%). p.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  13. The Frequency of Fabry Disease among Young Cryptogenic Stroke Patients in the City of Sakarya.

    Science.gov (United States)

    Gündoğdu, Aslı Aksoy; Kotan, Dilcan; Alemdar, Murat

    2017-06-01

    Fabry disease (FD) is known as a rare cause of stroke. Recent studies suggested that FD is an underdiagnosed entity among young stroke patients. We aimed to investigate the frequency of FD in young cryptogenic stroke patients who lived in the City of Sakarya and to define the clinical features that help in recognizing patients with FD. Acute ischemic stroke patients aged 18-55 years who were admitted to our hospital between October 2013 and September 2016 were evaluated for inclusion. Patients with other recognized causes of stroke were excluded. The screening was performed for alpha-galactosidase A (α-Gal A) activity on dried blood spot, and DNA was sequenced for GLA mutation in patients with low plasma α-Gal A activity. Among the 484 acute ischemic stroke patients, 54 (24 male, 44.4%) young cryptogenic stroke patients were enrolled. The α-Gal A activity was detected as low in 3 patients. c.[680G > A] p.[R227Q] missense mutation was identified in 2 male patients. The frequency of FD was calculated as 3.7%. Our research is the first FD screening study in Turkish stroke patients. Our results underlined the importance of considering FD during the etiologic evaluation of young cryptogenic stroke patients as it is a rare but potentially treatable entity. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    International Nuclear Information System (INIS)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico; Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio; Russo, Camilla; Feriozzi, Sandro; Veroux, Massimiliano; Battaglia, Yuri; Concolino, Daniela; Pieruzzi, Federico; Tuttolomondo, Antonino; Caronia, Aurelio; Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo

    2017-01-01

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  15. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

    2017-06-15

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  16. Enzyme replacement therapy for Fabry disease: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Taciane Alegra

    2012-01-01

    Full Text Available The specific treatment available for Fabry disease (FD is enzyme replacement therapy (ERT with agalsidase alfa or beta. A systematic review and meta-analysis was conducted to assess the efficacy and safety of ERT for FD. Only double-blind, randomized clinical trials (RCTs comparing agalsidase alfa or beta and placebo were included. ERT with either agalsidase alfa or beta was considered similar for the purposes of analysis. Ten RCTs were identified, which showed improvements in neuropathic pain, in heart abnormalities and in globotriaosylceramide (GL-3 levels. A meta-analysis showed increased odds for fever, rigors, development of IgG antibodies to agalsidase, and no significant association with development of hypertension or reduction in the QRS complex duration on electrocardiogram. The RCTs included in this comparison enrolled few patients, were highly heterogeneous, and were focused mainly on surrogate endpoints, limiting any conclusions as to the real effect of ERT for FD. The available evidence suggests that response to ERT is variable across patient subgroups and that agalsidase may slow progression of FD, with slight improvement of existing changes. Nevertheless, many uncertainties remain, and further studies are necessary.

  17. Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype.

    Science.gov (United States)

    Choi, Jin-Ho; Lee, Beom Hee; Heo, Sun Hee; Kim, Gu-Hwan; Kim, Yoo-Mi; Kim, Dae-Seong; Ko, Jung Min; Sohn, Young Bae; Hong, Yong Hee; Lee, Dong-Hwan; Kook, Hoon; Lim, Han Hyuk; Kim, Kyung Hee; Kim, Woo-Shik; Hong, Geu-Ru; Kim, Su-Hyun; Park, Sang Hyun; Kim, Chan-Duck; Kim, So Mi; Seo, Jeong-Sook; Yoo, Han-Wook

    2017-07-01

    Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males. Each diagnosis was based on an enzyme assay and GLA gene mutation analysis.The mean age at presentation was 24 years (range, 5-65 years); however, the diagnoses were delayed by 21 ± 19 years after the onset of symptoms. Those patients with late-onset Fabry disease were diagnosed by family screening or milder symptoms at a later age. Forty different mutations were identified: 20 missense (50%), 10 nonsense (25%), 8 frameshift (20%), and 2 splice site (5%) mutations. Five of them were novel. IVS4+919G>A (c.936+919 G>A) was not detected among the 6505 alleles via newborn screening using dried blood spots. Enzyme replacement therapy (ERT) was performed in all the males and pediatric patients, whereas 75% of the symptomatic females underwent ERT for 4.2 ± 3.6 years.This study described the demographic data, wide clinical spectrum of phenotypes, and GLA mutation spectrum of Fabry disease in Korea. Most of the patients had classical Fabry disease, with a 4 times higher incidence than that of late-onset Fabry disease, indicating an underdiagnosis of mild, late-onset Fabry disease.

  18. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.

    Science.gov (United States)

    Moon, James C; Sheppard, Mary; Reed, Emma; Lee, Phillip; Elliott, Perry M; Pennell, Dudley J

    2006-01-01

    Anderson-Fabry Disease (AFD) is a storage disease that mimics hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance occurs in approximately 50% of patients in the basal inferolateral LV wall, but how an intracellular storage disease causes focal LGE is unknown. We present a whole-heart histological validation that LGE is caused by focal myocardial collagen scarring. This scarring may be the substrate for electrical re-entry and sudden arrhythmic death. The reasons for this distribution of fibrosis are unclear, but may reflect inhomogeneous left ventricular wall stress.

  19. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  20. Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease

    Directory of Open Access Journals (Sweden)

    Ju Huang

    2017-06-01

    Full Text Available Fabry disease is a rare lysosomal storage disorder (LSD. We designed multiple recombinant lentivirus vectors (LVs and tested their ability to engineer expression of human α-galactosidase A (α-gal A in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease.

  1. Myocardial fibrosis as the first sign of cardiac involvement in a male patient with Fabry disease: report of a clinical case and discussion on the utility of the magnetic resonance in Fabry pathology

    OpenAIRE

    Sechi, Annalisa; Nucifora, Gaetano; Piccoli, Gianluca; Dardis, Andrea; Bembi, Bruno

    2014-01-01

    Background Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging is increasingly used to assess myocardial involvement in patients with Fabry disease, an X linked lipid storage disorder. However, it is often proposed as an optional tool. A different cardiomyopathic disease progression between male and female patients was hypothesised in previous studies, as in female myocardial fibrosis was found without left ventricular (LV) hypertrophy, while myocardial fibr...

  2. Cardiac sympathetic neuronal damage precedes myocardial fibrosis in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Imbriaco, Massimo; Piscopo, Valentina; Ponsiglione, Andrea; Nappi, Carmela; Puglia, Marta; Dell' Aversana, Serena; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Petretta, Mario [University Federico II, Department of Translational Medical Sciences, Naples (Italy); Riccio, Eleonora; Pisani, Antonio [University of Naples Federico II, Department of Public Health, Naples (Italy)

    2017-12-15

    Cardiac sympathetic denervation may be detectable in patients with Anderson-Fabry disease (AFD), suggesting its usefulness for early detection of the disease. However, the relationship between sympathetic neuronal damage measured by {sup 123}I-metaiodobenzylguanidine (MIBG) imaging with myocardial fibrosis on cardiac magnetic resonance (CMR) is still unclear. Cardiac sympathetic innervation was assessed by {sup 123}I-MIBG single-photon emission computed tomography (SPECT) in 25 patients with genetically proved AFD. Within one month from MIBG imaging, all patients underwent contrast-enhanced CMR. MIBG defect size and fibrosis size on CMR were measured for the left ventricle (LV) and expressed as %LV. Patients were divided into three groups according to MIBG and CMR findings: (1) matched normal, without MIBG defects and without fibrosis on CMR (n = 10); (2) unmatched, with MIBG defect but without fibrosis (n = 5); and (3) matched abnormal, with MIBG defect and fibrosis (n = 10). The three groups did not differ with respect to age, gender, α-galactosidase, proteinuria, glomerular filtration rate, and troponin I, while New York Heart Association class (p = 0.008), LV hypertrophy (p = 0.05), and enzyme replacement therapy (p = 0.02) were different among groups. Although in patients with matched abnormal findings, there was a significant correlation between MIBG defect size and area of fibrosis at CMR (r{sup 2} = 0.98, p < 0.001), MIBG defect size was larger than fibrosis size (26 ± 23 vs. 18 ± 13%LV, p = 0.02). Sympathetic neuronal damage is frequent in AFD patients, and it may precede myocardial damage, such as fibrosis. Thus, {sup 123}I-MIBG imaging can be considered a challenging technique for early detection of cardiac involvement in AFD. (orig.)

  3. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study.

    Science.gov (United States)

    Arends, Maarten; Biegstraaten, Marieke; Wanner, Christoph; Sirrs, Sandra; Mehta, Atul; Elliott, Perry M; Oder, Daniel; Watkinson, Oliver T; Bichet, Daniel G; Khan, Aneal; Iwanochko, Mark; Vaz, Frédéric M; van Kuilenburg, André B P; West, Michael L; Hughes, Derralynn A; Hollak, Carla E M

    2018-02-07

    Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, Pbeta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease

    OpenAIRE

    Wagner, Martin; Krämer, Johannes; Blohm, Elisabeth; Vergho, Dorothee; Weidemann, Frank; Breunig, Frank; Wanner, Christoph

    2015-01-01

    Background Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD. Methods In 96 patients (53% female; age 40???12?yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were na?ve to enzyme replacement ther...

  5. Skin diseases among schoolchildren in Africa

    NARCIS (Netherlands)

    Hogewoning, Adriaan Anne

    2012-01-01

    Many skin diseases among schoolchildren in sub-Sahara Africa cause disturbing complaints like itch and pain and several of them are contagious.This high prevalence causes a major public health problem.Although in several countries and also in our studies skin diseases present in large numbers, they

  6. PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology.

    Science.gov (United States)

    Del Pino, M D; Ortiz, A; Torra, R; Hernandez, D

    2016-01-01

    Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights

  7. Changes in plasma and urine globotriaosylceramide levels do not predict Fabry disease progression over 1 year of agalsidase alfa.

    Science.gov (United States)

    Schiffmann, Raphael; Ries, Markus; Blankenship, Derek; Nicholls, Kathy; Mehta, Atul; Clarke, Joe T R; Steiner, Robert D; Beck, Michael; Barshop, Bruce A; Rhead, William; West, Michael; Martin, Rick; Amato, David; Nair, Nitin; Huertas, Pedro

    2013-12-01

    Globotriaosylceramide concentrations were assessed as potential predictors of change from baseline after 12 months by estimated glomerular filtration rate and left-ventricular mass index using pooled data from three randomized, placebo-controlled agalsidase alfa trials and open-label extensions of patients with Fabry disease. Males (aged 18 years or older) with Fabry disease received agalsidase alfa (0.2 mg/kg every other week for 12 months). A backward-elimination approach evaluated potential predictors (baseline estimated glomerular filtration rate and left-ventricular mass index; age at first dose; baseline and change from baseline at 12 months of globotriaosylceramide (urine, plasma); urine protein excretion; and systolic and diastolic blood pressure). Subgroups included patients randomized to placebo or agalsidase alfa (double-blind phase), then to agalsidase alfa (open-label extensions; placebo→agalsidase alfa or agalsidase alfa→agalsidase alfa, respectively) and stage 2/3 chronic kidney disease patients. Baseline estimated glomerular filtration rate, age at first dose, baseline urine globotriaosylceramide excretion, and baseline and change from baseline urine protein excretion significantly predicted change from baseline estimated glomerular filtration rate in the analysis population (N = 73; all P<0.05), although not in all subgroups. Change from baseline urine and plasma globotriaosylceramide (baseline and change from baseline) concentrations did not predict change from baseline estimated glomerular filtration rate. No predictors of left-ventricular mass index were significant. Changes in globotriaosylceramide concentrations do not appear to be useful biomarkers for prediction of Fabry disease-related changes in estimated glomerular filtration rate or left-ventricular mass index.

  8. Non-invasive determination of myocardial lipid content in Fabry disease by {sup 1}H-MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Petritsch, B.; Koestler, H.; Machann, W.; Horn, M.; Weng, A.M.; Goltz, J.P.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik im ZOM; Niemann, M.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I

    2012-11-15

    Purpose: In Fabry disease (FD), a progressive deposition of sphingolipids is reported in different organs. The present study applied {sup 1}H magnetic resonance spectroscopy (MRS) to investigate the myocardial lipid content in FD. Materials and Methods: In patients (PTS, n = 15) with genetically proven FD, {sup 1}H MRS of the heart was acquired in the same examination as routine cardiac cine and late enhancement MR imaging. Healthy volunteers (n = 11) without history of cardiac disease served as control (CTL). Myocardial triglycerides in vivo were quantified in {sup 1}H MRS. Left ventricular (LV) ejection fraction (EF) and late enhancement were assessed for the determination of LV systolic function, and onset or absence of myocardial fibrosis. Results: All {sup 1}H MRS revealed resonances for intramyocardial triglycerides. Clinical parameters, e.g. EF (PTS 64 {+-} 2 % vs. CTL 61 {+-} 1 %) were similar in PTS and CTL or showed a non-significant trend (LV mass). Apart from a single patient with elevated myocardial triglycerides, no significant impact of Fabry disease on the triglyceride/water resonance ratio (PTS 0.47 {+-} 0.11 vs. CTL 0.52 {+-} 0.11 %) was observed in our patient cohort. Conclusion: A comprehensive cardiac evaluation of morphology, function as well as metabolism in Fabry PTS with suspected cardiac involvement is feasible in a single examination. No significant effect of myocardial triglyceride deposition could be observed in patients. The remarkably high myocardial triglyceride content in one patient with advanced FD warrants further studies in PTS with an extended history of the disease. (orig.)

  9. Periostin in Skin Tissue Skin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Yukie Yamaguchi

    2014-01-01

    Recently, periostin—a matricellular protein—has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD, attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

  10. Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

    Directory of Open Access Journals (Sweden)

    Maria Köping

    Full Text Available Fabry disease (FD is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3 in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.To examine hearing loss in patients with FD depending on cardiac and renal function.Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA6 (0.5, 1, 2, 4, 6, 8 and HF-PTA (6, 8 kHz. Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05.High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.

  11. Later Onset Fabry Disease, Cardiac Damage Progress in Silence: Experience With a Highly Prevalent Mutation.

    Science.gov (United States)

    Hsu, Ting-Rong; Hung, Sheng-Che; Chang, Fu-Pang; Yu, Wen-Chung; Sung, Shih-Hsien; Hsu, Chia-Lin; Dzhagalov, Ivan; Yang, Chia-Feng; Chu, Tzu-Hung; Lee, Han-Jui; Lu, Yung-Hsiu; Chang, Sheng-Kai; Liao, Hsuan-Chieh; Lin, Hsiang-Yu; Liao, Tsan-Chieh; Lee, Pi-Chang; Li, Hsing-Yuan; Yang, An-Hang; Ho, Hui-Chen; Chiang, Chuan-Chi; Lin, Ching-Yuang; Desnick, Robert J; Niu, Dau-Ming

    2016-12-13

    Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement. The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD. To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults. LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes. Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Thromboembolic events in Fabry disease and the impact of factor V Leiden.

    Science.gov (United States)

    Lenders, Malte; Karabul, Nesrin; Duning, Thomas; Schmitz, Boris; Schelleckes, Michael; Mesters, Rolf; Hense, Hans-Werner; Beck, Michael; Brand, Stefan-Martin; Brand, Eva

    2015-03-10

    Although several reports suggest an increased thromboembolic event rate, especially regarding strokes and TIAs at early age in patients with Fabry disease (FD), the risk for patients with FD to experience these events, the clinical relevance of additional risk factors including the concurrence of factor V Leiden (FVL), and the benefit of enzyme replacement therapy (ERT) regarding these events remain unclear. Three hundred four consecutively recruited patients with FD were evaluated for their lifetime occurrence of thromboembolic events such as stroke, TIA, deep vein thrombosis, and pulmonary embolism. The thromboembolic risk was determined in patients with FD and concurrent FVL, and the impact of ERT was assessed. The 304 patients with FD had a median age of 41 years and 53 (17.4%) had experienced at least one thromboembolic event during their lifetime. Among 226 patients with FD screened for FVL, 16 gene carriers were identified (7.1%). The occurrence of thromboembolic events in patients with FD and concurrent FVL was significantly increased compared to those without FVL (hazard ratio = 5.45, 95% confidence interval 2.29-12.99; p risk of thromboembolic events compared to those without ERT (hazard ratio = 0.362, 95% confidence interval 0.132-0.992; p = 0.0422). This observational study confirms that patients with FD have a high risk of clinically relevant thromboembolic events, which could be aggravated by a concurrence of FVL. ERT might be of benefit in preventing vascular events in patients with FD. The latter observation needs confirmation, however, by randomized and controlled clinical trials. © 2015 American Academy of Neurology.

  13. Bullous Skin Diseases: Classical Types of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Jan Damoiseaux

    2013-01-01

    Full Text Available The prototypic bullous skin diseases, pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid, are characterized by the blister formation in the skin and/or oral mucosa in combination with circulating and deposited autoantibodies reactive with (hemidesmosomes. Koch’s postulates, adapted for autoimmune diseases, were applied on these skin diseases. It appears that all adapted Koch’s postulates are fulfilled, and, therefore, these bullous skin diseases are to be considered classical autoimmune diseases within the wide and expanding spectrum of autoimmune diseases.

  14. Control of proteinuria with increased doses of agalsidase alfa in a patient with Fabry disease with atypical genotype–phenotype expression

    Directory of Open Access Journals (Sweden)

    Christos Paliouras

    2015-11-01

    Full Text Available Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipids, caused by the partial or complete deficiency of the lysosomal enzyme alpha-galactosidase A (a-Gal A. The missense mutation pN215S usually causes a milder form of the disease with isolated cardiac involvement. We report a case of a male Fabry patient with the pN215S mutation and a generalized disease. He suffered a relapse in proteinuria which responded to increased doses of the administered recombinant enzyme. Individualization of enzyme replacement therapy must be considered in selected cases characterized by clinical deterioration.

  15. Crohn’s disease and skin

    OpenAIRE

    Gravina, AG; Federico, A; Ruocco, E; Lo Schiavo, A; Romano, F; Miranda, A; Sgambato, D; Dallio, M; Ruocco, V; Loguercio, C; Romano, M

    2015-01-01

    Crohn’s disease is a chronic inflammatory bowel disease potentially involving any segment of the gastrointestinal tract. Extra-intestinal manifestations may occur in 6%–40% of patients, and disorders of the skin are among the most common. This manuscript will review skin manifestations associated to Crohn’s disease, with a particular focus on lesions associated to anti-tumour necrosis factor therapy.

  16. Auditing the frequency and the clinical and economic impact of testing for Fabry disease in patients under the age of 70 with a stroke admitted to Saint Vincent's University Hospital over a 6-month period.

    Science.gov (United States)

    Lambe, J; Noone, I; Lonergan, R; Tubridy, N

    2018-02-01

    Fabry disease is an X-linked recessive lysosomal storage disorder that provokes multi-organ morbidity, including early-onset stroke. Worldwide prevalence may be greater than previously estimated, with many experiencing first stroke prior to diagnosis of Fabry disease. The aim of this study is to screen a cohort of stroke patients under 70 years of age, evaluating the clinical and economic efficacy of such a broad screening programme for Fabry disease. All stroke patients under 70 years of age who were entered into the Saint Vincent's University Hospital stroke database over a 6-month period underwent enzyme analysis and/or genetic testing as appropriate for Fabry disease. Patients' past medical histories were analysed for clinical signs suggestive of Fabry disease. Cost-effectiveness analysis of testing was performed and compared to overall economic impact of young stroke in Ireland. Of 22 patients tested for Fabry disease, no new cases were detected. Few clinical indicators of Fabry disease were identified at the time of testing. Broad screening programmes for Fabry disease are highly unlikely to offset the cost of testing. The efficacy of future screening programmes will depend on careful selection of an appropriate patient cohort of young stroke patients with multi-organ morbidity and a positive family history.

  17. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

    Science.gov (United States)

    Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

    2003-12-01

    Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

  18. Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease.

    Science.gov (United States)

    Lenders, Malte; Schmitz, Boris; Stypmann, Jörg; Duning, Thomas; Brand, Stefan-Martin; Kurschat, Christine; Brand, Eva

    2017-12-01

    Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT). A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed. Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex. In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  19. Intraoperative Diagnosis of Anderson-Fabry Disease in Patients With Obstructive Hypertrophic Cardiomyopathy Undergoing Surgical Myectomy.

    Science.gov (United States)

    Cecchi, Franco; Iascone, Maria; Maurizi, Niccolò; Pezzoli, Laura; Binaco, Irene; Biagini, Elena; Fibbi, Maria Laura; Olivotto, Iacopo; Pieruzzi, Federico; Fruntelata, Ana; Dorobantu, Lucian; Rapezzi, Claudio; Ferrazzi, Paolo

    2017-10-01

    Diagnostic screening for Anderson-Fabry cardiomyopathy (AFC) is performed in the presence of specific clinical red flags in patients with hypertrophic cardiomyopathy (HCM) older than 25 years. However, left ventricular outflow tract obstruction (LVOTO) has been traditionally considered an exclusion criteria for AFC. To examine a series of patients diagnosed with HCM and severe basal LVOTO undergoing myectomy in whom the diagnosis of AFC was suspected by the cardiac surgeon intraoperatively and confirmed by histological and genetic examinations. This retrospective analysis of patients undergoing surgical septal reduction strategies was conducted in 3 European tertiary referral centers for HCM from July 2013 to December 2016. Patients with a clinical diagnosis of obstructive HCM referred for surgical management of LVOTO were observed for at least 18 months after the procedure (mean [SD] follow-up, 33 [14] months). Etiology of patients with HCM who underwent surgical myectomy. From 2013, 235 consecutive patients with a clinical diagnosis of HCM underwent septal myectomy. The cardiac surgeon suspected a storage disease in 3 patients (1.3%) while inspecting their heart samples extracted from myectomy. The mean (SD) age at diagnosis for these 3 patients was 42 (4) years; all were male. None of the 3 patients presented with extracardiac features suggestive of AFC. All patients showed asymmetrical left ventricular hypertrophy, with maximal left ventricular thickness in the basal septum (19-31 mm), severe basal LVOTO (70-120 mm Hg), and left atrial dilatation (44-57 mm). Only 1 patient presented with late gadolinium enhancement on cardiovascular magnetic resonance at the right ventricle insertion site. The mean (SD) age at surgical procedure was 63 (5) years. On tactile sensation, the surgeon felt a spongy consistency of the surgical samples, different from the usual stony-elastic consistency typical of classic HCM, and this prompted histological examinations. Histology

  20. Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.

    Science.gov (United States)

    Lukas, Jan; Giese, Anne-Katrin; Markoff, Arseni; Grittner, Ulrike; Kolodny, Ed; Mascher, Hermann; Lackner, Karl J; Meyer, Wolfgang; Wree, Phillip; Saviouk, Viatcheslav; Rolfs, Arndt

    2013-01-01

    Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalactonojirimycin (DGJ) as a tool to analyse the influence of individual mutations on subcellular organelle-trafficking and stability. We analysed a significant number of mutations and correlated the obtained properties to the clinical manifestation related to the mutation in order to improve our knowledge of the identity of functional relevant amino acids. Additionally, we illustrate the consequences of different mutations on plasma lyso-globotriaosylsphingosine (lyso-Gb3) accumulation in the patients' plasma, a biomarker proven to reflect the impaired substrate clearance caused by specific mutations. The established system enables us to provide information for the clinical relevance of PC therapy for a given mutant. Finally, in order to generate reliable predictions of mutant GLA defects we compared the different data sets to reveal the most coherent system to reflect the clinical situation.

  1. Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low...

  2. Uncertain diagnosis of fabry disease in patients with neuropathic pain, angiokeratoma or cornea verticillata: consensus on the approach to diagnosis and follow-up

    NARCIS (Netherlands)

    Tol, L. van der; Cassiman, D.; Houge, G.; Janssen, M.C.; Lachmann, R.H.; Linthorst, G.E.; Ramaswami, U.; Sommer, C.; Tondel, C.; West, M.L.; Weidemann, F.; Wijburg, F.A.; Svarstad, E.; Hollak, C.E.M.; Biegstraaten, M.

    2014-01-01

    INTRODUCTION: Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the

  3. Abnormal expression and processing of uromodulin in Fabry disease reflects tubular cell storage alteration and is reversible by enzyme replacement therapy

    Czech Academy of Sciences Publication Activity Database

    Vyleťal, P.; Hůlková, H.; Živná, M.; Berná, L.; Novák, Petr; Elleder, M.; Kmoch, S.

    2008-01-01

    Roč. 31, č. 4 (2008), s. 508-517 ISSN 0141-8955 Institutional research plan: CEZ:AV0Z50200510 Keywords : uromodulin * fabry disease * tubular cell Subject RIV: EE - Microbiology, Virology Impact factor: 2.691, year: 2008

  4. Uncertain Diagnosis of Fabry Disease in Patients with Neuropathic Pain, Angiokeratoma or Cornea Verticillata: Consensus on the Approach to Diagnosis and Follow-Up

    NARCIS (Netherlands)

    van der Tol, L.; Cassiman, David; Houge, Gunnar; Janssen, Mirian C.; Lachmann, Robin H.; Linthorst, Gabor E.; Ramaswami, Uma; Sommer, Claudia; Tøndel, Camilla; West, Michael L.; Weidemann, Frank; Wijburg, Frits A.; Svarstad, Einar; Hollak, Carla E. M.; Biegstraaten, Marieke

    2014-01-01

    Introduction: Individuals with neuropathic pain, angiokeratoma (AK) and/or cornea verticillata (CV) may be tested for Fabry disease (FD). Classical FD is characterised by a specific pattern of these features. When a patient presents with a non-specific pattern, the pathogenicity of a variant in the

  5. Pathophysiological Mechanisms in Sclerosing Skin Diseases

    Directory of Open Access Journals (Sweden)

    Beate Eckes

    2017-08-01

    Full Text Available Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches.

  6. Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment.

    Science.gov (United States)

    Mauer, Michael; Sokolovskiy, Alexey; Barth, Jay A; Castelli, Jeffrey P; Williams, Hadis N; Benjamin, Elfrida R; Najafian, Behzad

    2017-11-01

    Deficiency of α-galactosidase A (αGal-A) in Fabry disease leads to the accumulation mainly of globotriaosylceramide (GL3) in multiple renal cell types. Glomerular podocytes are relatively resistant to clearance of GL3 inclusions by enzyme replacement therapy (ERT). Migalastat, an orally bioavailable small molecule capable of chaperoning misfolded αGal-A to lysosomes, is approved in the European Union for the long-term treatment of patients with Fabry disease and amenable GLA (α-galactosidase A enzyme) mutations. We aimed to examine if migalastat reduces GL3 content of podocytes in Fabry disease. We compared paired renal biopsies of eight adult men with amenable Fabry disease mutations at baseline and after 6 months of treatment with 150 mg migalastat every other day using quantitative unbiased electron microscopic morphometric methods. Migalastat treatment led to a reduction in mean total GL3 inclusion volume per podocyte in renal biopsies from baseline to 6 months. This reduction correlated precisely with reduced mean podocyte volume. There was also a direct relationship between reduction in podocyte foot process width and the reduction in mean total podocyte GL3 content following 6 months of migalastat treatment, suggestive of reduced podocyte injury. Migalastat treatment of 6 months duration in eight male patients with Fabry disease demonstrated effective GL3 clearance from the podocyte, an important and relatively ERT-resistant glomerular cell. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Comparison of left atrial size and function in hypertrophic cardiomyopathy and in Fabry disease with left ventricular hypertrophy.

    Science.gov (United States)

    Saccheri, María Cristina; Cianciulli, Tomás Francisco; Challapa Licidio, Wilde; Lax, Jorge A; Beck, Martín A; Morita, Luis A; Gagliardi, Juan A

    2018-02-19

    Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) are two diseases with a different pathophysiology, both cause left ventricular hypertrophy (LVH) and myocardial fibrosis. Although remodeling and systolic dysfunction of the left atrium (LA) are associated with atrial fibrillation and stroke in HCM, changes in the size and function of the LA have not been well studied in FD with LVH. The following groups were studied prospectively, and their respective findings compared: 19 patients with non-obstructive HCM (Group I), 20 patients with a diagnosis of Fabry cardiomyopathy (Group II), and 20 normal subjects matched for sex and age (Group III). Left ventricular mass index was measured using Devereux' formula, left atrial volume with Simpson's biplane method and left atrial mechanical function, including strain and strain rate, was measured using the speckle tracking technique. Strain and strain rate of the reservoir were measured during the three phases: reservoir (SR S), passive conduit (SR E) and atrial contraction (SR A). Patients with HCM had a larger left atrial volume than patients with FD (48.16 ± 14.3 mL/m 2 vs 38.9 ± 14.9 mL/m 2 respectively, P cardiomyopathy, affecting the three phasic functions of the LA. Although in patients with HCM left atrial volume is larger than in patients with FD, both disorders exhibit severe decrease in left atrial function. These findings should be considered, given the potentially serious complications that can occur with the two diseases. © 2018 Wiley Periodicals, Inc.

  8. Human Alpha Galactosidases Transiently Produced in Nicotiana benthamiana Leaves: New Insights in Substrate Specificities with Relevance for Fabry Disease

    Directory of Open Access Journals (Sweden)

    Kassiani Kytidou

    2017-06-01

    Full Text Available Deficiency of α-galactosidase A (α-GAL causes Fabry disease (FD, an X-linked storage disease of the glycosphingolipid globtriaosylcerammide (Gb3 in lysosomes of various cells and elevated plasma globotriaosylsphingosine (Lyso-Gb3 toxic for podocytes and nociceptive neurons. Enzyme replacement therapy is used to treat the disease, but clinical efficacy is limited in many male FD patients due to development of neutralizing antibodies (Ab. Therapeutic use of modified lysosomal α-N-acetyl-galactosaminidase (α-NAGAL with increased α-galactosidase activity (α-NAGALEL has therefore been suggested. We transiently produced in Nicotiana benthamiana leaves functional α-GAL, α-NAGAL, and α-NAGALEL enzymes for research purposes. All enzymes could be visualized with activity-based probes covalently binding in their catalytic pocket. Characterization of purified proteins indicated that α-NAGALEL is improved in activity toward artificial 4MU-α-galactopyranoside. Recombinant α-NAGALEL and α-NAGAL are not neutralized by Ab-positive FD serum tested and are more stable in human plasma than α-GAL. Both enzymes hydrolyze the lipid substrates Gb3 and Lyso-Gb3 accumulating in Fabry patients. The addition to FD sera of α-NAGALEL, and to a lesser extent that of α-NAGAL, results in a reduction of the toxic Lyso-Gb3. In conclusion, our study suggests that modified α-NAGALEL might reduce excessive Lyso-Gb3 in FD serum. This neo-enzyme can be produced in Nicotiana benthamiana and might be further developed for the treatment of FD aiming at reduction of circulating Lyso-Gb3.

  9. Skin diseases of the vulva

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2017-01-01

    A multitude of infectious diseases of viral (genital herpes, herpes zoster, genital warts and molluscum contagiosum), bacterial (syphilis, chancroid, lymphogranuloma venereum, donovanosis, erysipelas, cellulitis and necrotising fasciitis, folliculitis, impetigo, bartholin gland abscess...

  10. Malassezia species and their associated skin diseases.

    Science.gov (United States)

    Harada, Kazutoshi; Saito, Mami; Sugita, Takashi; Tsuboi, Ryoji

    2015-03-01

    Malassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture-independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases. © 2015 Japanese Dermatological Association.

  11. Influence of skin diseases on fingerprint recognition.

    Science.gov (United States)

    Drahansky, Martin; Dolezel, Michal; Urbanek, Jaroslav; Brezinova, Eva; Kim, Tai-hoon

    2012-01-01

    There are many people who suffer from some of the skin diseases. These diseases have a strong influence on the process of fingerprint recognition. People with fingerprint diseases are unable to use fingerprint scanners, which is discriminating for them, since they are not allowed to use their fingerprints for the authentication purposes. First in this paper the various diseases, which might influence functionality of the fingerprint-based systems, are introduced, mainly from the medical point of view. This overview is followed by some examples of diseased finger fingerprints, acquired both from dactyloscopic card and electronic sensors. At the end of this paper the proposed fingerprint image enhancement algorithm is described.

  12. Skin disorders in Parkinson's disease

    DEFF Research Database (Denmark)

    Ravn, Astrid-Helene; Thyssen, Jacob P; Egeberg, Alexander

    2017-01-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, characterized by a symptom triad comprising resting tremor, rigidity, and akinesia. In addition, non-motor symptoms of PD are well recognized and often precede the overt motor manifestations. Cutaneous manifestations...

  13. The Microbiome in Skin Health and Disease

    Indian Academy of Sciences (India)

    Souvik Mukherjee

    Crohn's disease & IBD. Almost Absent. Higher Abundance. The healthy skin microbiome is well characterised in Western populations (Grice et al. Science 2009, Zeeuwen et al. Genome Biol. 2012, Flores et al. Genome. Biol. 2014, Oh et al. Nature 2014). No study had been performed on Asian populations. Studying the ...

  14. Managing Amphibian Disease with Skin Microbiota.

    Science.gov (United States)

    Woodhams, Douglas C; Bletz, Molly; Kueneman, Jordan; McKenzie, Valerie

    2016-03-01

    The contribution of emerging amphibian diseases to the sixth mass extinction is driving innovative wildlife management strategies, including the use of probiotics. Bioaugmentation of the skin mucosome, a dynamic environment including host and microbial components, may not provide a generalized solution. Multi-omics technologies and ecological context underlie effective implementation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 9 CFR 311.6 - Diamond-skin disease.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diamond-skin disease. 311.6 Section... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.6 Diamond-skin disease. Carcasses of hogs affected with diamond-skin disease when localized and not associated with systemic change...

  16. Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages.

    Science.gov (United States)

    Krämer, Johannes; Lenders, Malte; Canaan-Kühl, Sima; Nordbeck, Peter; Üçeyler, Nurcan; Blaschke, Daniela; Duning, Thomas; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Gottschling, Timo; Störk, Stefan; Wanner, Christoph; Sommer, Claudia; Brand, Eva; Weidemann, Frank

    2017-11-23

    Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6  ±  9.1 mL/min/1.73 m2 (P risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in the re-switch group after change of the therapy regimen (P < 0.05). After switch to agalsidase-alfa, Fabry patients experienced a continuous decline in eGFR, while this decline was attenuated in patients who were re-switched to agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment response in the latter group. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  17. Skin Diseases: Skin and Sun—Not a good mix

    Science.gov (United States)

    ... Americans spend billions of dollars each year on skin care products that promise to erase wrinkles, lighten age spots, and eliminate itching, flaking, or redness. As you age, your skin changes. It becomes thinner and loses fat, making ...

  18. Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping.

    Science.gov (United States)

    Sado, Daniel M; White, Steven K; Piechnik, Stefan K; Banypersad, Sanjay M; Treibel, Thomas; Captur, Gabriella; Fontana, Marianna; Maestrini, Viviana; Flett, Andrew S; Robson, Matthew D; Lachmann, Robin H; Murphy, Elaine; Mehta, Atul; Hughes, Derralynn; Neubauer, Stefan; Elliott, Perry M; Moon, James C

    2013-05-01

    Anderson-Fabry disease (AFD) is a rare but underdiagnosed intracellular lipid disorder that can cause left ventricular hypertrophy (LVH). Lipid is known to shorten the magnetic resonance imaging parameter T1. We hypothesized that noncontrast T1 mapping by cardiovascular magnetic resonance would provide a novel and useful measure in this disease with potential to detect early cardiac involvement and distinguish AFD LVH from other causes. Two hundred twenty-seven subjects were studied: patients with AFD (n=44; 55% with LVH), healthy volunteers (n=67; 0% with LVH), patients with hypertension (n=41; 24% with LVH), patients with hypertrophic cardiomyopathy (n=34; 100% with LVH), those with severe aortic stenosis (n=21; 81% with LVH), and patients with definite amyloid light-chain (AL) cardiac amyloidosis (n=20; 100% with LVH). T1 mapping was performed using the shortened modified Look-Locker inversion sequence on a 1.5-T magnet before gadolinium administration with primary results derived from the basal and midseptum. Compared with health volunteers, septal T1 was lower in AFD and higher in other diseases (AFD versus healthy volunteers versus other patients, 882±47, 968±32, 1018±74 milliseconds; Pgadolinium enhancement (1001±82 versus 891±38 milliseconds; P<0.0001). Noncontrast T1 mapping shows potential as a unique and powerful measurement in the imaging assessment of LVH and AFD.

  19. Co-existence of Phenylketonuria and Fabry disease on a 3 year-old boy: case report

    Directory of Open Access Journals (Sweden)

    Bonapace Giuseppe

    2010-05-01

    Full Text Available Abstract Background The co-existence of two genetically distinct metabolic disorders in the same patient has rarely been reported. Phenylketonuria (PKU is an inborn error of the metabolism resulting from a phenylalanine hydroxylase deficiency. Fabry disease (FD is an X-linked lysosomal storage disorder due to a deficiency of the enzyme alpha-galactosidase A. Case presentation We report a case of a 3 year- old boy affected by classic PKU and FD, both confirmed by molecular data. The FD was suspected at the age of 21 months on the presence of non-specific GI symptoms (severe abdominal pain and periodically appearance of not specific episodes of gastroenteritis apparently non related to PKU. Conclusion This is the first report of co-existence of FD and PKU, two different congenital inborn of metabolism and in consideration of the prevalence of each disease this chance association is a very unusual event. The co-existence of this diseases made very difficult the correct interpretation of clinical symptoms as lack of appetite, severe abdominal pain and non-specific gastroenteritis episodes. Furthermore, this case report helps to define the early clinical phenotype of FD.

  20. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease.

    Directory of Open Access Journals (Sweden)

    Valentina Citro

    Full Text Available Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay.

  1. A survey of skin disease and skin-related issues in Arab Americans.

    Science.gov (United States)

    El-Essawi, Dina; Musial, Joseph L; Hammad, Adnan; Lim, Henry W

    2007-06-01

    There is a paucity of knowledge relating to dermatologic conditions in Arab Americans. To assess common skin diseases and concerns and to evaluate access to dermatologic care and perception of skin in Arab Americans. Arab Americans from 3 Southeast Michigan locations (community health center [n = 207], mosque [n = 95], and church [n = 99]) completed a survey questionnaire. The most common self-reported skin conditions were acne, eczema/dermatitis, warts, fungal skin infections, and melasma. The most pressing skin concerns were uneven skin tone, skin discoloration, dry skin, acne, and facial hair. Significant associations exist between socioeconomic status and having seen a dermatologist. Attitudes surrounding skin perception were related to the number of years of residence in the United States. The skin condition data were gathered from a self-reported survey. Skin conditions and other related issues that affect Arab Americans are similar to those which affect other skin-of-color populations.

  2. Ten-year-long enzyme replacement therapy shows a poor effect in alleviating giant leg ulcers in a male with Fabry disease

    Directory of Open Access Journals (Sweden)

    Jun Okada

    2018-03-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A, leading to the progressive accumulation of glycosphingolipids. Classical hemizygous males usually present symptoms, including pain and paresthesia in the extremities, angiokeratoma, hypo- or anhidrosis, abdominal pain, cornea verticillata, early stroke, tinnitus, and/or hearing loss, during early childhood or adolescence. Moreover, proteinuria, renal impairment, and cardiac hypertrophy can appear with age. Enzyme replacement is the most common therapy for Fabry disease at present which has been approved in Japan since 2004. We report a case involving a 27-year-old male with extreme terminal pain, anhidrosis, abdominal pain, tinnitus, hearing impairment, cornea verticillata, and recurrent huge ulcers in the lower extremities. At the age of 16 years, he was diagnosed with Fabry disease with a positive family history and very low α-gal A activity. He then received enzyme replacement therapy (ERT with recombinant human agalsidase beta at 1 mg/kg every 2 weeks for 10 years. Throughout the course of ERT, his leg ulcers recurred, and massive excretion of urinary globotriaosylceramide and plasma globotriaosylsphingosine was observed. Electron microscopy of the venous tissue in the regions of the ulcer showed massive typical zebra bodies in the vascular wall smooth muscle cells.

  3. Patients of Skin Diseases Hospital, Maiduguri, Borno State

    African Journals Online (AJOL)

    ADOWIE PERE

    Retrospective Study of Epidermal Parasitic Skin Diseases amongst Out- Patients of ... Epidermal Parasitic Skin Diseases (EPSD) among out-patients from the skin diseases hospital in Maiduguri, Borno state. ... accorded to the risk factors such as lack of adequate sanitation, poor hygiene and overcrowding which when.

  4. Myocardial deformation imaging and rare cardiomyopathies with hypertrophic phenotype: a review focused on Fabry disease, Friedreich ataxia and amyloidosis

    Directory of Open Access Journals (Sweden)

    Bahaa Fadel

    2013-06-01

    Full Text Available Tissue Doppler and deformation imaging, including Doppler-derived strain and speckle tracking, have significantly improved our understanding of cardiac mechanics in both physiological and pathological states. The various modes of left ventricular deformation (longitudinal, circumferential, radial and twist leading to systolic contraction can nowadays be quantified. One of the best applications of deformation imaging is in the area of hypertrophic cardiomyopathies. Deformation imaging allows the evaluation of global and regional myocardial performance and the noninvasive characterization of abnormal intramural myocardial mechanics. In this review, we discuss the role of myocardial deformation imaging derived by echocardiography in the assessment of rare hypertrophic phenotype including Fabry disease, Friedreich ataxia and amyloidosis. Deformation imaging allows for early identification of myocardial dysfunction in many hypertrophic disorders, at an earlier stage than that provided by standard imaging or echocardiographic techniques. This allows for the implementation of appropriate therapy before significant disease progression has occurred and prior to the development of advanced myocardial fibrosis. Thus therapy would likely be more effective and may potentially lead to improvement in patient outcome. Additionally strain imaging allows to better monitoring the efficacy of therapy by assessing the progression and regression of myocardial involvement. Finally, findings on strain imaging carry important prognostic information in many hypertrophic disorders.

  5. Global skin diseases on Instagram hashtags.

    Science.gov (United States)

    Braunberger, Taylor; Mounessa, Jessica; Rudningen, Kyle; Dunnick, Cory A; Dellavalle, Robert P

    2017-05-15

    Recently named one of the most influential phone applications, Instagram continues to grow in popularity [1]. Instagram consists of images and video posts, making it ideal for education and communication within the visual field of dermatology. In this study, we seek to determine the presence of dermatology-related content with regard to the most common cutaneous diseases of the world. We searched the account types and hashtags associated with the eight most common skin diseases globally as identified by the Global Burden of Disease (GBD) study by Hollenstein et al.: eczema, psoriasis, acne,pruritus, alopecia, decubitus ulcer, urticaria, andscabies [9]. The majority of Instagram accounts included patient experiences (n=73), private accounts(n=52), and disease advocacy and awareness groups(n=20), (total n=221). We further investigated over 2 million skin disease hashtags. The greatest numbersof hashtags were the following: #acne (n = 1,622,626),#alopecia (n = 317,566), and #eczema (n = 196,115). Our results demonstrate that patients interact withone another through Instagram. As social networking platforms become more frequently used as a source of information for patients and patient support, medical professionals must gain awareness of content available through Instagram and consider it as a means to educate the public.

  6. Skin Manifestations of Inflammatory Bowel Disease.

    Science.gov (United States)

    Greuter, Thomas; Navarini, Alexander; Vavricka, Stephan R

    2017-12-01

    Inflammatory bowel disease (IBD) with its two main subtypes Crohn's disease and ulcerative colitis is not restricted to the gastrointestinal tract. Indeed, so-called extraintestinal manifestations (EIMs) are frequent and considerably affect morbidity and mortality. The prevalence of EIMs ranges from 6 to 47%. In up to one quarter of the patients, EIMs can present even before an IBD diagnosis is established. The pathophysiology of EIMs remains elusive, although data from clinical trials demonstrating anti-tumor necrosis factor (TNF) efficacy suggest a common pathogenic link between intestinal and extraintestinal disease activity. However, not all EIMs parallel intestinal disease. Skin lesions are usually classified based on their pathophysiological association with the underlying intestinal disease into four categories: (1) specific, (2) reactive, (3) associated, and (4) treatment-induced manifestations. Cutaneous manifestations include erythema nodosum (EN), pyoderma gangrenosum (PG), Sweet's syndrome, and oral lesions, with EN being the most commonly reported and PG showing the most debilitating disease course. Anti-TNF-induced skin reactions are a new, but increasingly recognized phenomenon, which can be eventually misinterpreted as psoriatic lesions. Medical treatment modalities are limited with topical and systemic steroids being the most frequently employed agents. If EIMs parallel intestinal disease activity, the therapeutic cornerstone usually is the management of underlying intestinal disease activity rather than direct treatment of the EIMs. However, increasing evidence for anti-TNF agents' efficacy in EIM management has changed the approach to complicating and debilitating disease courses. In the case of anti-TNF-induced lesions, topical steroids are usually sufficient and discontinuation of anti-TNF is seldom warranted. In this review, we summarize current knowledge on cutaneous EIMs, their diagnostic criteria and clinical presentation, natural history

  7. Occupational skin disease in Victoria, Australia.

    Science.gov (United States)

    Cahill, Jennifer L; Williams, Jason D; Matheson, Melanie C; Palmer, Amanda M; Burgess, John A; Dharmage, Shyamali C; Nixon, Rosemary L

    2016-05-01

    To describe the characteristics of patients with occupational skin disease (OSD) in a tertiary referral clinic in Victoria, Australia. A retrospective review was conducted of records from patients seen at the Occupational Dermatology Clinic in Melbourne, Australia between 1 January 1993 and 31 December 2010. Of the 2894 people assessed in the clinic during the 18-year period, 44% were women and 56% were men. In all, 2177 (75%) were diagnosed with occupational skin disease (OSD). Of the patients with a work-related skin condition, 45% (n = 979) were considered to be atopic. The most common diagnosis in those with OSD was irritant contact dermatitis (ICD) (44%), followed by allergic contact dermatitis (33%) and endogenous eczema (11%). Women were significantly more likely to have soaps and detergents (P care workers (21 per 100 000). We confirm the importance of occupational contact dermatitis as the most common cause of OSD, with ICD being the most common diagnosis. There are differences in the causes of ICD between our group of male and female workers. For the first time in Australia, rates of OSD in certain industries have been calculated. © 2015 The Australasian College of Dermatologists.

  8. Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice.

    Science.gov (United States)

    Baig, Shanat; Edward, Nicky C; Kotecha, Dipak; Liu, Boyang; Nordin, Sabrina; Kozor, Rebecca; Moon, James C; Geberhiwot, Tarekegn; Steeds, Richard P

    2017-10-17

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

  9. Occupational skin diseases in automotive industry workers.

    Science.gov (United States)

    Yakut, Yunus; Uçmak, Derya; Akkurt, Zeynep Meltem; Akdeniz, Sedat; Palanci, Yilmaz; Sula, Bilal

    2014-03-01

    Studies on occupational skin diseases in workers of the automotive industry are few. To investigate the prevalence of occupational skin diseases in workers of the automotive industry. Between September and December 2011, a total of 405 workers from the automotive repair industry in Diyarbakır were interviewed. They were active workers in the repair industry who had been employed for at least six months. Business owners, sellers of spare parts and accounting officers were not included. The employees were examined at their workplaces and the working conditions were observed. Detailed dermatological examination was performed. The mean age of the 405 workers who participated in the study was 27.7 ± 10.3. The mean working time of employees was 13.3 ± 10.4 years. All of the employees were male. Dermatological diseases were not detected in 144 out of 405 workers (35.6%) and at least one condition was diagnosed in 261 (64.4%). The most frequent diagnosis was callus, hyperkeratosis, clavus (27.7%), followed by nail changes (16.8%) and superficial mycoses (12.1%). Contact dermatitis was seen at a rate of 5.9%. Traumatic lesions such as hyperkeratotic lesions and nail changes were found most frequently. Traumatic lesions were common among individuals who did not use gloves. Most nail changes were localized leuconychia, a finding not reported in the studies on automotive industry workers. In accordance with the literature, irritant contact dermatitis was observed in patients with a history of atopy and who had been working for a long time. Occupational skin diseases comprise an important field in dermatology, deserving much attention. Further studies on occupational dermatology are necessary.

  10. De novo Diagnosis of Fabry Disease among Italian Adults with Acute Ischemic Stroke or Transient Ischemic Attack.

    Science.gov (United States)

    Romani, Ilaria; Borsini, Walter; Nencini, Patrizia; Morrone, Amelia; Ferri, Lorenzo; Frusconi, Sabrina; Donadio, Vincenzo Angelo; Liguori, Rocco; Donati, Maria Alice; Falconi, Serena; Pracucci, Giovanni; Inzitari, Domenico

    2015-11-01

    Cerebrovascular complications are often the first cause of hospitalization in patients with Fabry disease (FD). Screenings for FD among stroke patients have yielded discrepant results, likely as a result of heterogeneous or incomplete assessment. We designed a study to identify FD among adults 60 years of age or younger who were consecutively admitted for acute ischemic stroke or transient ischemic attack (TIA) to a stroke neurology service in Italy. Patients with first-ever or recurrent events were included, irrespective of gender, risk factors, or stroke type. We screened male patients using α-galactosidase A enzyme assay, and female patients using DNA sequencing. FD was eventually established after a broad multidisciplinary discussion. We screened 108 patients (61% males, median age: 48 years); 84% of these patients had stroke. De novo FD diagnosis was established in 3 patients (2.8%; 95% confidence interval, .57-8.18): a 59-year-old man with recurrent lacunar-like strokes and multiple risk factors; a 42-year-old woman with recurrent cryptogenic minor strokes; and a 32-year-old woman with recurrent strokes previously attributed to Behçet's disease. Screened patients were systematically asked for typical FD symptoms; each of the de novo patients reported one or more of the following: episodes of hand/foot pain during fever, angiokeratoma, and family history of heart disease. In all of the patients events were recurrent, and lacunar-like infarcts characterized their brain imaging. Prevalence of FD among nonselected adults 60 years of age or younger with acute ischemic stroke or TIA is not negligible. A systematic search for FD in a stroke setting, using a comprehensive clinical, biochemical, and genetic screening protocol, may be worthwhile. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

    Science.gov (United States)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

    2017-08-01

    The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

  12. Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

    Science.gov (United States)

    San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

    2014-06-06

    Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Bodies in skin: a philosophical and theological approach to genetic skin diseases.

    Science.gov (United States)

    Walser, Angelika

    2010-03-01

    This contribution evolved from my work in a European network and is dedicated to the rare genetic skin diseases. To gain a deeper knowledge about the question, what it means to suffer from a genetic skin disease, I have discussed the concepts of skin in philosophical and theological anthropology. Presuming that ancient interpretations of skin diseases (moral and cultical impurity) are still relevant today, feminist Christian theology shows the ways of deconstructing stigmatizing paradigma by using the body as a hermeneutic category. Skin becomes the "open borderline" of the human being, pointing out both the social vulnerability and the transcendent capacity of the human person.

  14. The Psychological Burden of Skin Diseases

    DEFF Research Database (Denmark)

    Dalgard, Florence J; Gieler, Uwe; Tomas-Aragones, Lucia

    2015-01-01

    The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational...... with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants--3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1...

  15. A Missense Mutation of the α-Galactosidase A Gene in a Chinese Family of Fabry Disease with Renal Failure

    Directory of Open Access Journals (Sweden)

    Chunli Wang

    2013-06-01

    Full Text Available Background: Fabry disease (FD is a rare disease due to an X-linked recessive inborn error of glycosphingolipid metabolism resulting from the mutations of the α-galactosidase A (α-gal A gene. FD is rare in Chinese and the data on clinic and genetic features of FD is still limited. Methods: In this study, the α-gal A gene of a Chinese family diagnosed with FD was analyzed for mutations and the genetic features of FD in this family were presented. Results: The α-gal A activity of the proband in this family was 0.03 nmol/ml/h in the whole blood. By PCR amplification and sequencing of the α-gal A gene exons, a single C-to-T transition was identified in codon 112 of exon 2. This C-to-T transition, mapping to position 334 in the cDNA of the α-gal A gene, was a missense mutation predicting a substitution of arginine to cysteine (p.R112C, which disrupts the normal activity of α-gal A enzyme. No further mutations were found in other exons of the α-gal A gene. In contrast to previous reports, in this family, all of the five male patients developed end-stage renal failure due to this missense mutation. Conclusions: These findings suggest that the missense mutation, p.R112C, in α-gal A gene ablates its activity and results in the development of FD with the renal damage.

  16. Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" α-galactosidase a large deletion

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of a-galactosidase A (a-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased a-Gal A activity. However, in female heterozygotes, the a-Gal A activity can range from low...... on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas....

  17. Skin manifestations of chronic kidney disease.

    Science.gov (United States)

    Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

    2015-10-01

    Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  18. PEMPHIGUS: A DISEASE STAMPED IN THE SKIN

    Directory of Open Access Journals (Sweden)

    Aline Bicalho Matias

    2013-11-01

    Full Text Available Introduction: Pemphigus are autoimmune blistering diseases that affect the skin and mucous membranes. The blisters characteristics of pemphigus tend to break, causing painful erosions that easily bleed. This study aimed to identify the experiences involved in the triggering of pemphigus and how patients face the illness and treatment. Material and Methods: The study included 31 patients diagnosed with pemphigus foliaceus and vulgaris, under a standardized pulsetherapy treatment. Data collection was through semi-structured interviews, which were audio-recorded, transcribed and analyzed using a qualitative approach. Results: During the journey in search of the phenomenon, were defined two thematic categories, subdivided into eleven subcategories. Months before the triggering of the illness, patients experienced feelings of losses, familiar conflicts and concerns; also showed an experience permeated by heartache and disappointments. After the first signs of pemphigus, patients experienced a long journey until the correct diagnose; worsening of the lesions after the communication of the diagnosis; feelings of isolation, shame and prejudgment; interruptions of the future plans; lack of information about the disease and treatment; difficult adherence to the pulsetherapy and the appearance of new lesions or worse by stressful events. Discussion: It might be observed that the disease is not just a biological deviation, but also a social deviance, which explicit the need to adapt to the new reality of the disease and face the isolation, prejudgment and shame of living with a stigmatizing disease.

  19. Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.

    Science.gov (United States)

    Deva, Djeven Parameshvara; Hanneman, Kate; Li, Qin; Ng, Ming Yen; Wasim, Syed; Morel, Chantal; Iwanochko, Robert M; Thavendiranathan, Paaladinesh; Crean, Andrew Michael

    2016-03-31

    Although it is known that Anderson-Fabry Disease (AFD) can mimic the morphologic manifestations of hypertrophic cardiomyopathy (HCM) on echocardiography, there is a lack of cardiovascular magnetic resonance (CMR) literature on this. There is limited information in the published literature on the distribution of myocardial fibrosis in patients with AFD, with scar reported principally in the basal inferolateral midwall. All patients with confirmed AFD undergoing CMR at our center were included. Left ventricular (LV) volumes, wall thicknesses and scar were analyzed offline. Patients were categorized into 4 groups: (1) no wall thickening; (2) concentric hypertrophy; (3) asymmetric septal hypertrophy (ASH); and (4) apical hypertrophy. Charts were reviewed for clinical information. Thirty-nine patients were included (20 males [51%], median age 45.2 years [range 22.3-64.4]). Almost half (17/39) had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three quarters of these (13/17) had typical inferolateral midwall scar. A quarter (9/39) had both concentric wall thickening and typical inferolateral scar. A subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall thickness, total LV scar, apical scar and mid-ventricular scar than those with concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and sustained ventricular tachycardia (p = 0.008). Concentric thickening and inferolateral mid-myocardial scar are the most common manifestations of AFD, but the spectrum includes cases morphologically identical to apical and ASH subtypes of HCM and these have more apical and mid-ventricular LV scar. Significant LVH is associated with ventricular arrhythmia.

  20. Reduced Right Ventricular Native Myocardial T1 in Anderson-Fabry Disease: Comparison to Pulmonary Hypertension and Healthy Controls.

    Directory of Open Access Journals (Sweden)

    Joseph J Pagano

    Full Text Available Anderson-Fabry disease (AFD is characterized by progressive multiorgan accumulation of intracellular sphingolipids due to α-galactosidase A enzyme deficiency, resulting in progressive ventricular hypertrophy, heart failure, arrhythmias, and death. Decreased native (non-contrast left ventricular (LV T1 (longitudinal relaxation time with MRI discriminates AFD from healthy controls or other presentations of concentric hypertrophy, but the right ventricle (RV has not been studied. The aims of the current study were to evaluate native RV T1 values in AFD, with a goal of better understanding the pathophysiology of RV involvement.Native T1 values were measured in the inferior RV wall (RVI, interventricular septum (IVS, and inferior LV (LVI in patients with AFD, patients with pulmonary hypertension, who provided an alternative RV pathological process for comparison, and healthy controls. A minimum wall thickness of 4 mm was selected to minimize partial volume errors in tissue T1 analysis. T1 analysis was performed in 6 subjects with AFD, 6 subjects with PH, and 21 controls. Native T1 values were shorter (adjusted p<0.05 for all comparisons, independent of location, in subjects with AFD (RVI-T1 = 1096±49 ms, IVS-T1 = 1053±41 ms, LVI-T1 = 1072±44 ms compared to both PH (RVI-T1 = 1239±41 ms, IVS-T1 = 1280±123 ms, LVI-T1 = 1274±57 ms and HC (IVS-T1 = 1180±60 ms, LVI-T1 = 1183±45 ms. RVI measurements were not possible in controls due to insufficient wall thickness.Native T1 values appear similarly reduced in the left and right ventricles of individuals with AFD and RV wall thickening, suggesting a common pathology. In contrast, individuals with PH and thickened RVs showed increased native T1 values in both ventricles, suggestive of fibrosis.

  1. Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease.

    Science.gov (United States)

    Mills, K; Morris, P; Lee, P; Vellodi, A; Waldek, S; Young, E; Winchester, B

    2005-01-01

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A. This deficiency leads to the progressive accumulation, in lysosomes of visceral tissues and in body fluids of hemizygotes, of the glycosphingolipids globotriaosylceramide (CTH, Gb(3) or GL-3) and galabiosylceramide (CDH) and to a lesser extent the blood group AB and B related glycolipids. Elevated levels of the glycosphingolipids are found in the urine of hemizygous males with the classic phenotype, but it is not known whether all symptomatic or asymptomatic heterozygotes have elevated levels. We have therefore measured CTH and CDH quantitatively in a multiplex assay using tandem mass spectrometry in urine from a large cohort (44) of genetically proven or obligate heterozygotes including four with the N215S mutation, from classic hemizygotes (28), from cardiac variant hemizygotes with the N215S mutation (6) and from normal controls. The levels of CTH and CDH were related to both creatinine and sphingomyelin. Urinary CTH was elevated in all 28 classic hemizygotes but only in 4/6 of the cardiac variants. The level was within or just above the normal reference range in the four individuals heterozygous for the N215S mutation but was elevated in 38/40 of the other heterozygotes. Similar results were obtained for CDH, except that only 34/40 heterozygotes had an elevated level. The level of CDH was not elevated in the four heterozygotes and 4/6 of the hemizygotes for the N215S mutation. Combining the levels of CTH and CDH did not improve the discrimination of heterozygotes from controls. The ratio of CDH to CTH was higher in heterozygotes than in hemizygotes. Measurement of urinary CTH gave the best discrimination of heterozygotes from controls.

  2. Analogs of human genetic skin disease in domesticated animals

    Directory of Open Access Journals (Sweden)

    Justin Finch, MD

    2017-09-01

    The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.

  3. OCT imaging of skin cancer and other dermatological diseases

    DEFF Research Database (Denmark)

    Mogensen, Mette; Thrane, Lars; Jørgensen, Thomas Martini

    2009-01-01

    Optical coherence tomography (OCT) provides clinicians and researchers with micrometer-resolution, in vivo, cross-sectional images of human skin up to several millimeter depth. This review of OCT imaging applied within dermatology covers the application of OCT to normal skin, and reports on a lar...... number of applications in the fields of non-melanoma skin cancer, malignant melanomas, psoriasis and dermatitis, infestations, bullous skin diseases, tattoos, nails, haemangiomas, and other skin diseases. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)...

  4. The prevalent deep intronic c. 639+919 G>A GLA mutation causes pseudoexon activation and Fabry disease by abolishing the binding of hnRNPA1 and hnRNP A2/B1 to a splicing silencer

    DEFF Research Database (Denmark)

    Palhais, Bruno; Dembic, Maja; Sabaratnam, Rugivan

    2016-01-01

    Fabry disease is an X-linked recessive inborn disorder of the glycosphingolipid metabolism, caused by total or partial deficiency of the lysosomal α-galactosidase A enzyme due to mutations in the GLA gene. The prevalent c.639+919 G>A mutation in GLA leads to pathogenic insertion of a 57bp...... oligonucleotide (SSO) mediated blocking of the pseudoexon 3'ss and 5'ss effectively restores normal GLA splicing. This indicates that SSO based splicing correction may be a therapeutic alternative in the treatment of Fabry disease....

  5. Occupational skin diseases in hairdressing apprentices - has anything changed?

    DEFF Research Database (Denmark)

    Hougaard, Majken G; Winther, Lone; Søsted, Heidi

    2015-01-01

    BACKGROUND: Hairdressers are at risk for occupational skin diseases. Since 2008, an educational programme has been conducted in Danish hairdressing schools to prevent occupational skin diseases. Its effect is unknown. OBJECTIVE: To examine the current frequency of self-reported hand eczema and co...

  6. Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

    Science.gov (United States)

    Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells. © 2016 Asian Pacific Society of Nephrology.

  7. Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy: a nationwide Danish cohort study.

    Science.gov (United States)

    Madsen, Christoffer Valdorff; Bundgaard, Henning; Rasmussen, Åse Krogh; Sørensen, Søren Schwartz; Petersen, Jørgen Holm; Køber, Lars; Feldt-Rasmussen, Ulla; Petri, Helle

    2017-08-01

    In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT. We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring. We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p Fabry disease and stress the need for further research.

  8. Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

    Directory of Open Access Journals (Sweden)

    Chassaing Augustin

    2002-10-01

    Full Text Available Abstract Background Fabry disease (FD, OMIM 301500 is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement. Methods We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19–64 years, mean 39 affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy. Results A total of 12 patients (54.5% with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32% experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P tinnitus aurium was also found in six patients (27%. Conclusion This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s of the cochlear involvement deserves further studies.

  9. Analogs of human genetic skin disease in domesticated animals ?

    OpenAIRE

    Finch, Justin; Abrams, Stephanie; Finch, Amy

    2017-01-01

    Genetic skin diseases encompass a vast, complex, and ever expanding field. Recognition of the features of these diseases is important to ascertain a correct diagnosis, initiate treatment, consider genetic counseling, and refer patients to specialists when the disease may impact other areas. Because genodermatoses may present with a vast array of features, it can be bewildering to memorize them. This manuscript will explain and depict some genetic skin diseases that occur in both humans and do...

  10. Global skin disease morbidity and mortality an update from the global burden of disease study 2013

    NARCIS (Netherlands)

    C. Karimkhani (Chante); R.P. Dellavalle (Robert P.); L.E. Coffeng (Luc); C. Flohr (Carsten); R.J. Hay (Roderick J.); S.M. Langan (Sinéad M.); E.O. Nsoesie (Elaine O.); A. Ferrari (Andrea); H. Erskine (Holly); J. Silverberg; T. Vos (Theo); M. Naghavi (Morteza)

    2017-01-01

    markdownabstractIMPORTANCE Disability secondary to skin conditions is substantial worldwide. The Global Burden of Disease Study 2013 includes estimates of global morbidity and mortality due to skin diseases. OBJECTIVE To measure the burden of skin diseases worldwide. DATA SOURCES For nonfatal

  11. Incidence of skin and respiratory diseases among Danish hairdressing apprentices

    DEFF Research Database (Denmark)

    Foss-Skiftesvik, Majken H.; Winther, Lone; Johnsen, Claus R.

    2017-01-01

    Background: Hairdressing is one of the professions with the highest risk of occupational skin and respiratory diseases. The incidence of these diseases in hairdressing apprentices has been studied only sparsely. Objective: To determine the incidence of skin and respiratory diseases in hairdressing.......8% of the hairdressing apprentices had left the trade, and 70.3% of these had left because of health complaints. The most frequently reported reasons for leaving were musculoskeletal pain (47.4%) and skin diseases (47.4%), followed by respiratory symptoms (23.7%). Conclusions: Hairdressing apprentices are at increased...

  12. Quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging in patients with Fabry disease and hypertrophic cardiomyopathy.

    Science.gov (United States)

    Morsbach, F; Gordic, S; Gruner, C; Niemann, M; Goetti, R; Gotschy, A; Kozerke, S; Alkadhi, H; Manka, R

    2016-08-15

    This study aims to determine whether the quantification of myocardial fibrosis in patients with Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) using a late gadolinium enhancement (LGE) singlebreath-hold three-dimensional (3D) inversion recovery magnetic resonance (MR) imaging sequence is comparable with a clinically established two-dimensional (2D) multi-breath-hold sequence. In this retrospective, IRB-approved study, 40 consecutive patients (18 male; mean age 50±17years) with Fabry disease (n=18) and HCM (n=22) underwent MR imaging at 1.5T. Spatial resolution was the same for 3D and 2D images (field-of-view, 350×350mm(2); in-plane-resolution, 1.2×1.2mm(2); section-thickness, 8mm). Datasets were analyzed for subjective image quality; myocardial and fibrotic mass, and total fibrotic tissue percentage were quantified. There was no significant difference in subjective image quality between 3D and 2D acquisitions (P=0.1 and P=0.3) for either disease. In patients with Fabry disease there were no significant differences between 3D and 2D acquisitions for myocardial mass (P=0.55), fibrous tissue mass (P=0.89), and total fibrous percentage (P=0.67), with good agreement between acquisitions according to Bland-Altman analyses. In patients with HCM there were also no significant differences between acquisitions for myocardial mass (P=0.48), fibrous tissue mass (P=0.56), and total fibrous percentage (P=0.67), with good agreement according to Bland-Altman analyses. Acquisition time was significantly shorter for 3D (25±5s) as compared to the 2D sequence (349±62s, PFabry disease and HCM, 3D LGE imaging provides equivalent diagnostic information in regard to quantification of myocardial fibrosis as compared with a standard 2D sequence, but at superior acquisition speed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Potential role of vitamin D deficiency on Fabry cardiomyopathy

    NARCIS (Netherlands)

    Drechsler, C.; Schmiedeke, B.; Niemann, M.; Schmiedeke, D.; Kramer, J.; Turkin, I.; Blouin, K.; Emmert, A.; Pilz, S.; Obermayer-Pietsch, B.; Weidemann, F.; Breunig, F.; Wanner, C.

    2014-01-01

    Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study

  14. The psychosocial and occupational impact of chronic skin disease.

    Science.gov (United States)

    Hong, Judith; Koo, Bonnie; Koo, John

    2008-01-01

    Chronic skin diseases, particularly psoriasis and atopic dermatitis, have a negative impact on patients' quality of life. Patients often experience significant psychological and social distress such as increased levels of depression and fear of stigma. Skin diseases can also impact patients' occupational lives by causing them to miss work or be less productive. Quality of life instruments provide important information for healthcare professionals, the general public, and those involved in distribution of healthcare resources, which helps prevent chronic skin disease from being overlooked amidst other medical conditions.

  15. The Influence of Patient-Reported Joint Manifestations on Quality of Life in Fabry Patients.

    Science.gov (United States)

    Ivleva, Alexandra; Weith, Ekaterina; Mehta, Atul; Hughes, Derralynn A

    2018-01-30

    Fabry disease, a lysosomal storage disorder, is a rare inborn error of metabolism caused by deficiency of the enzyme alpha galactosidase A and resulting accumulation of globotriaosylceramide. The symptoms of Fabry disease are heterogeneous including renal failure, cardiac hypertrophy, and stroke and may not be well recognized by non-specialist physicians. Patients with milder, later onset of disease often have a delay in diagnosis.Fabry patients may suffer significant neuropathic pain in the extremities (acroparasthesia) but the degree to which musculoskeletal symptoms contribute to total pain and disability is unknown. Here, we present a questionnaire study focusing on joint manifestations and their impact on daily life of patients with Fabry disease.Seventy-seven patients with Fabry disease and age-matched healthy controls (49 female and 28 male) took part in a survey focused on joint problems, pain, disability, and quality of life. Joint pain and swelling were reported by 43% of male and 39% of female Fabry patients. Analysis by age group showed higher prevalence of joint problems and decreased quality of life, in terms of mobility, activity, pain, and anxiety, in Fabry patients younger than 50 years compared to healthy controls. Female Fabry patients had higher fatigue scores compared to control subjects. Fabry patients reported problems with vigorous daily activities and gripping.Musculoskeletal symptoms are common in Fabry patients and contribute to overall pain and decreased quality of life. Awareness of Fabry disease by physicians may be raised to ensure timely diagnosis of this rare disease.

  16. Prevalence of major skin diseases of cattle and associated risk ...

    African Journals Online (AJOL)

    Across-sectional study was conducted on 384 cattle to identify skin diseases and associated risk factors in cattle in and around Ambo town, Ethiopia. Thorough clinical examination was made followed by collection of skin scrapping and visible ecto-parasites for laboratory identification. The overall prevalence was 73.7%, ...

  17. The Diagnostic Value of Skin Disease Diagnosis Expert System.

    Science.gov (United States)

    Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Arabkermany, Zahra; Gilasi, Hamidreza

    2016-02-01

    Evaluation is a necessary measure to ensure the effectiveness and efficiency of all systems, including expert systems. The aim of this study was to determine the diagnostic value of expert system for diagnosis of complex skin diseases. A case-control study was conducted in 2015 to determine the diagnostic value of an expert system. The study population included patients who were referred to Razi Specialized Hospital, affiliated to Tehran University of Medical Sciences. The control group was selected from patients without the selected skin diseases. Data collection tool was a checklist of clinical signs of diseases including pemphigus vulgaris, lichen planus, basal cell carcinoma, melanoma, and scabies. The sample size formula estimated 400 patients with skin diseases selected by experts and 200 patients without the selected skin diseases. Patient selection was undertaken with randomized stratified sampling and their sign and symptoms were logged into the system. Physician's diagnosis was determined as the gold standard and was compared with the diagnosis of expert system by SPSS software version 16 and STATA. Kappa statistics, indicators of sensitivity, specificity, accuracy and confidence intervals were calculated for each disease. An accuracy of 90% was considered appropriate. Comparing the results of expert system and physician's diagnosis at the evaluation stage showed an accuracy of 97.1%, sensitivity of 97.5% and specificity of 96.5% The Kappa test indicated a high agreement of 93.6%. The expert system can diagnose complex skin diseases. Development of such systems is recommended to identify all skin diseases.

  18. Pattern of skin diseases among Central African refugees in Chad

    Directory of Open Access Journals (Sweden)

    Ahmed Fawzi Ismael

    2015-08-01

    Full Text Available Aim: to describe the pattern of skin diseases among refugees attending the dermatology clinic in refugee camps in southern Chad. Methods: A descriptive clinic-based cross-sectional study was done in two refugee camps of people from Republic of Central Africa in Southern Chad. Diagnosis of skin diseases was done through clinical examination by a single dermatologist along with the help of hand lens provided with illumination. Lack of investigations and other skin diagnostic tools prevented further confirmation of diagnosis. Data was manually analyzed and diagnosis was presented as number and percent using the ICD -10 of the World Health Organization. Results: A total of 366 dermatologic diseases were diagnosed in 361 patients. Certain infectious and parasitic diseases and dermatitis/ eczema were the commonest diagnostic categories (39.9% and 22.45; respectively followed by disorders of skin appendices (15% and infections of skin and subcutaneous tissues (13.1%. Tinea barbae /capitis, ringworm and impetigo are the commonest recorded infections (11.5%, 10.1% and 7.9%; respectively. Miliaria and acne vulgaris were the most frequent disorders of skin appendages. Conclusions: Infectious skin diseases are common among refugees. There are urgent needs for health education and promotion of personal hygiene with adequate sanitation as well as availability of diagnostic tests [TAF Prev Med Bull 2015; 14(4.000: 324-328

  19. The role of antimicrobial peptides in chronic inflammatory skin diseases

    Directory of Open Access Journals (Sweden)

    Małgorzata Marcinkiewicz

    2016-02-01

    Full Text Available Antimicrobial peptides (AMPs are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases.

  20. Pattern of skin disease in Hail region of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Fawwaz Al Shammrie

    2017-07-01

    Conclusion: Dermatitis, acne, vitiligo, alopecia, viral wart and psoriasis are the most common top six skin diseases in hail region compared to other previous study in Hail region. The prevalence of skin disease in any community depends upon various factors, namely the genetic, racial constitution, the social and hygienic standards, customs and occupations, the nutritional status, age structure of the community, climatic factors and state of industrialization.

  1. Mortality from nonneoplastic skin disease in the United States.

    Science.gov (United States)

    Lott, Jason P; Gross, Cary P

    2014-01-01

    The mortality burden from nonneoplastic skin disease in the United States is unknown. We sought to estimate mortality from nonneoplastic skin disease as underlying and contributing causes of death. Population-based death certificate data detailing mortality from nonneoplastic skin disease for years 1999 to 2009 were used to calculate absolute numbers of death and age-adjusted mortality by year, patient demographics, and 10 most commonly reported diagnoses. Nonneoplastic skin diseases were reported as underlying and contributing causes of mortality for approximately 3948 and 19,542 patients per year, respectively. Age-adjusted underlying cause mortality (per 100,000 persons) were significantly greater (P deaths occurred in patients ages 65 years and older (34,248 total deaths). Common underlying causes of death included chronic ulcers (1789 deaths/y) and cellulitis (1348 deaths/y). Errors in death certificate data and inability to adjust for patient-level confounders may limit the accuracy and generalizability of our results. Mortality from nonneoplastic skin disease is uncommon yet potentially preventable. The elderly bear the greatest burden of mortality from nonneoplastic skin disease. Chronic ulcers and cellulitis constitute frequent causes of death. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  2. Recurrent outbreaks of lumpy skin disease and its economic impact ...

    African Journals Online (AJOL)

    Lumpy skin disease (LSD) is an acute, severe and economically important transboundary disease of cattle caused by LSD virus (LSDV). Suspected outbreaks of LSD are frequently reported in Nigeria, but laboratory diagnosis is seldom carried out and the economic impact of the disease is unknown. This study investigated ...

  3. Disease management for chronic skin cancer

    NARCIS (Netherlands)

    S. van der Geer-Rutten (Simone)

    2012-01-01

    textabstractWorldwide non-melanoma skin cancer (NMSC) is a rapidly rising problem. In this thesis we show that an enormous gap exists between the official first primary figures available at cancer registries and the actual burden in a dermatology practice. NMSC needs to be regarded as a chronic

  4. A comprehensive Fabry-related pain questionnaire for adult patients.

    Science.gov (United States)

    Üçeyler, Nurcan; Magg, Barbara; Thomas, Phillip; Wiedmann, Silke; Heuschmann, Peter; Sommer, Claudia

    2014-11-01

    Pain may be the earliest symptom in Fabry disease and presents with a distinct phenotype including triggerable pain attacks, evoked pain, pain crises, and chronic pain. Current pain questionnaires do not reflect the special phenotype of Fabry disease-associated pain, which hampers its systematic evaluation as the basis of correct diagnosis and effective treatment. A questionnaire specifically designed to assess Fabry disease-associated pain is thus urgently needed. At the Würzburg Fabry Center for Interdisciplinary Therapy (FAZIT), Germany, we developed and validated the first face-to-face Fabry Pain Questionnaire (FPQ) for adult patients. The initial version of the FPQ was tested in a pilot study with 20 consecutive Fabry disease patients. The performance of the revised FPQ was assessed in a first (n=56) and second (n=20) validation phase in consecutive Fabry disease patients. For this, patients were interviewed at baseline and 2 weeks later. We determined the test-retest reliability and validity of the FPQ in comparison to data obtained with the Neuropathic Pain Symptom Inventory. The FPQ contains 15 questions on the 4 pain phenotypes of Fabry disease (pain attacks, pain crises, evoked pain, chronic pain) in childhood and adulthood, on pain development during life with and without enzyme replacement therapy, and on everyday life impairment due to pain. This first disease-specific questionnaire is a valuable tool for baseline and follow-up assessment of pain in Fabry disease patients and may guide treatment in this distinct pain phenotype. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Pathologies of the skin and its appendages in endocrine diseases

    Directory of Open Access Journals (Sweden)

    Hubert Arasiewicz

    2016-05-01

    Full Text Available Patients suffering from endocrine disorders often present a wide profile of skin lesions. In hyperthyroidism we observe hair loss, lower leg myxedema and onycholysis or, in the case of hormone deficiency, generalized swelling of the skin, which becomes cold and pale. Primary hyperparathyroidism is revealed by pruritus, presence of chronic urticaria or deposition of amorphous calcium salts. In hypoparathyroidism, the skin is dry while the nails become very brittle. Skin lesions in diabetes include necrobiosis lipoidica, granuloma annulare, scleroderma-like diabetic edema and acanthosis nigricans. Overactive pituitary gland is often manifested as acromegaly with hypertrophy of soft tissue thickening and hypertrichosis. The skin in the early stages of hypopituitarism feels swollen, is pale yellow and oily, and finally becomes alabaster and dry. The characteristic features of Cushing syndrome are central obesity, lunar face, buffalo hump, and striae. In Addison’s disease we observe hyperpigmentation. Hyperandrogenism in women leads to acne, hirsutism and virilization.

  6. Efficacy and safety of enzyme-replacement-therapy with agalsidase alfa in 36 treatment-naïve Fabry disease patients.

    Science.gov (United States)

    Tsuboi, Kazuya; Yamamoto, Hiroshi

    2017-06-07

    Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis. The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation. All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low. The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT. The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291 ) on May 19th, 2017.

  7. Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

    Science.gov (United States)

    El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

    2017-01-01

    Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, pregression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

  8. Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience.

    Science.gov (United States)

    Thofehrn, Scheila; Netto, Cristina; Cecchin, Cláudia; Burin, Maira; Matte, Ursula; Brustolin, Sílvia; Nunes, Ane Cláudia Fernandes; Coelho, Janice; Tsao, Marylin; Jardim, Laura; Giugliani, Roberto; Barros, Elvino José Guardão

    2009-01-01

    Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/ 1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >or= 90 mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73 m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73 m(2), and stage V as < 15 mL/min/1.73 m(2). Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions

  9. Implementation of Nearest Neighbor using HSV to Identify Skin Disease

    Science.gov (United States)

    Gerhana, Y. A.; Zulfikar, W. B.; Ramdani, A. H.; Ramdhani, M. A.

    2018-01-01

    Today, Android is one of the most widely used operating system in the world. Most of android device has a camera that could capture an image, this feature could be optimized to identify skin disease. The disease is one of health problem caused by bacterium, fungi, and virus. The symptoms of skin disease usually visible. In this work, the symptoms that captured as image contains HSV in every pixel of the image. HSV can extracted and then calculate to earn euclidean value. The value compared using nearest neighbor algorithm to discover closer value between image testing and image training to get highest value that decide class label or type of skin disease. The testing result show that 166 of 200 or about 80% is accurate. There are some reasons that influence the result of classification model like number of image training and quality of android device’s camera.

  10. Primary skin fibroblasts as a model of Parkinson's disease

    NARCIS (Netherlands)

    Auburger, G.; Klinkenberg, M.; Droste, J.A.H.; Marcus, K.; Morales-Gordo, B.; Kunz, W.S.; Brandt, U.; Broccoli, V.; Reichmann, H.; Gispert, S.; Jendrach, M.

    2012-01-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts

  11. Farber disease overlapping with stiff skin syndrome: Expanding the ...

    African Journals Online (AJOL)

    Background: Farber Disease (MIM 228000)1 is a rare AR disorder fi rst described by Sidney Farber in 19522. Farber disease is usually recognized by the presence of three symptoms: Painful and progressively deformed joints, nodules under the skin and progressive hoarseness. Other organ systems may also be involved.

  12. Transmission dynamics of lumpy skin disease in Ethiopia

    NARCIS (Netherlands)

    Molla, W.; Frankena, Klaas; Jong, de Mart

    2017-01-01

    Lumpy skin disease (LSD) is a severe disease of cattle caused by a Capripoxvirus and often caused epidemics in Ethiopia and many other countries. This study was undertaken to quantify the transmission between animals and to estimate the infection reproduction ratio in a predominantly mixed

  13. The skin in autoimmune diseases-Unmet needs.

    Science.gov (United States)

    Kuhn, A; Landmann, A; Bonsmann, G

    2016-10-01

    Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Switch to agalsidase alfa after shortage of agalsidase beta in Fabry disease: a systematic review and meta-analysis of the literature.

    Science.gov (United States)

    Pisani, Antonio; Bruzzese, Dario; Sabbatini, Massimo; Spinelli, Letizia; Imbriaco, Massimo; Riccio, Eleonora

    2017-03-01

    In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-analysis of existing data. Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects. The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.Genet Med 19 3, 275-282.

  15. Skin

    International Nuclear Information System (INIS)

    Hunter, R.D.

    1985-01-01

    Malignant disease involving the skin represents a significant work load to the general radiotherapist and can involve interesting diagnostic and therapeutic decisions. Primary skin cancer is also relatively common and there is a need to provide an efficient service in which the first treatment is successful in the majority of patients. The reward for careful attention to technique is very considerable both in terms of clinical cancer control and functional results. Squamous cell carcinoma, basal cell carcinoma, and intra-epidermal carcinoma constitute the majority of the lesions dealt with clinically, but metastatic disease, lymphomas, and malignant melanomas are also referred regularly for opinions and may require radiotherapy. The general principle of the techniques of assessment and radiotherapeutic management to be described are equally applicable to any malignant skin tumour once the decision has been made to accept it for radiotherapy. Dosage and fractionation may have to be adjusted to allow for the nature of the disease process and the intent of the treatment

  16. Fabry cardiomyopathy presenting with a high defibrillation threshold: A short case report

    Directory of Open Access Journals (Sweden)

    Takashi Kanda, MD

    2015-06-01

    Full Text Available Fabry disease is an X-linked recessive glycosphingolipid storage disorder caused by a deficiency of lysosomal enzyme α-galactosidase A. It is recognized that Fabry disease patients often have ventricular arrhythmias. Although the effectiveness of implantable cardioverter-defibrillator (ICD therapy in patients with ventricular fibrillation is established, there is little evidence regarding ICD therapy for Fabry disease. Here, we report the case of patient with Fabry disease who was treated with an ICD and presented with high defibrillation thresholds.

  17. Occupational skin hazards and prevalence of occupational skin diseases in shoe manufacturing workers in Indonesia.

    Science.gov (United States)

    Febriana, Sri Awalia; Soebono, Hardyanto; Coenraads, Pieter-Jan

    2014-02-01

    Shoe manufacturing workers are exposed daily to an extensive range of potential physical and chemical occupational hazards. Shoe manufacturing in Indonesia is one of the industrial sectors that has shown sustained growth amongst the newly industrialized countries (NICs). In this study, we investigated the possible potential exposure of the workers to physical and occupational hazards and determined the prevalence of occupational skin diseases at a shoe manufacturing factory in Indonesia. A cross-sectional study on the observation of the working process and an inventory and risk assessment of exposure to the chemicals used. Classification of chemicals as potential sensitizers/irritants and qualitative assessments of these chemicals were done. Workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. The risk of Occupational skin diseases (OSD) at the shoe factory was mainly related to the exposure of the workers' skin to potential physical and chemical hazards in hot and humid environmental conditions. From a total of 514 workers, 8.5 % reported current OSD and 4.8 % reported a history of OSD. Occupational skin diseases were diagnosed in 29 % of the workers by dermatologists and 7.6 % had an occupational contact dermatitis (OCD). Of the 39 workers with contact dermatitis, 33 consented to being patch tested, 14 (3 %) workers showed a positive results and considered as having an occupational allergic contact dermatitis (OACD) and 25 (4.9 %) had an occupational irritant contact dermatitis (OICD). We observed a repeated and prolonged exposure of the workers to numerous physical and chemical skin hazards at this factory.

  18. Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

    Science.gov (United States)

    2014-01-01

    Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

  19. Skin Manifestations Associated with Autoimmune Liver Diseases: a Systematic Review.

    Science.gov (United States)

    Terziroli Beretta-Piccoli, Benedetta; Invernizzi, Pietro; Gershwin, M Eric; Mainetti, Carlo

    2017-12-01

    Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often associated with extrahepatic autoimmune diseases. However, the association with cutaneous diseases is less well described. In the present article, we provide a systematic literature review on skin manifestations linked to each of these four autoimmune liver diseases, excluding skin manifestations of systemic diseases. The association of autoimmune hepatitis with vitiligo is well known, with a particular striking association with type 2 autoimmune hepatitis, a condition occurring almost entirely in children and adolescents, much rarer and more aggressive than type 1 autoimmune hepatitis; probable associations are also identified with alopecia areata, psoriasis, and pyoderma gangrenosum. Primary biliary cholangitis is not linked to lichen planus as previously assumed, but to vitiligo, psoriasis and the very rare amicrobial pustulosis of the folds. The proposed diagnostic criteria for this latter condition include the presence of anti-mitochondrial autoantibodies, the serological hallmark of primary biliary cholangitis. The very strong association of primary sclerosing cholangitis with inflammatory bowel diseases hampers the search for an association with skin diseases, since inflammatory bowel diseases have a strong association with various dermatological condition, including neutrophilic dermatoses and erythema nodosum. Nevertheless, a probable association of primary sclerosing cholangitis with psoriasis is identified in this review. Variant syndromes, also called overlap syndromes, are likely associated with vitiligo as well, which is not surprising, since autoimmune hepatitis is a feature of these conditions and they may share regions of the MHC.

  20. Clinical and genetic investigation of a Japanese family with cardiac fabry disease. Identification of a novel α-galactosidase A missense mutation (G195V).

    Science.gov (United States)

    Nakagawa, Naoki; Maruyama, Hiroki; Ishihara, Takayuki; Seino, Utako; Kawabe, Jun-ichi; Takahashi, Fumihiko; Kobayashi, Motoi; Yamauchi, Atsushi; Sasaki, Yukie; Sakamoto, Naka; Ota, Hisanobu; Tanabe, Yasuko; Takeuchi, Toshiharu; Takenaka, Toshihiro; Kikuchi, Kenjiro; Hasebe, Naoyuki

    2011-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A gene (GLA), and the disease is a relatively prevalent cause of left ventricular hypertrophy mimicking idiopathic hypertrophic cardiomyopathy. We assessed clinically 5 patients of a three-generation family and also searched for GLA mutations in 10 family members. The proband had left ventricular hypertrophy with localized thinning in the basal posterior wall and late gadolinium enhancement (LGE) in the near-circumferential wall in cardiovascular magnetic resonance images and her sister had vasospastic angina pectoris without organic stenosis of the coronary arteries. LGE notably appeared in parallel with decreased α-galactosidase A activity and increased NT-pro BNP in our patients. We detected a new GLA missense mutation (G195V) in exon 4, resulting in a glycine-to-valine substitution. Of the 10 family members, 5 family members each were positive and negative for this mutation. These new data extend our clinical and molecular knowledge of GLA gene mutations and confirm that a novel missense mutation in the GLA gene is important not only for a precise diagnosis of heterozygous status, but also for confirming relatives who are negative for this mutation.

  1. Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans.

    Science.gov (United States)

    Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K

    2016-05-01

    Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.

  2. Epidemiology of skin diseases in University of Nigeria Teaching ...

    African Journals Online (AJOL)

    Background: Several studies have been carried out to determine the patterns of skin diseases across Nigeria and results have shown changing patterns with the trend reflecting a higher tendency for allergic dermatoses in a majority of these studies. This study was carried out to evaluate the current clinical picture of patients ...

  3. WILDE,OSCAR SKIN-DISEASE - ALLERGIC CONTACT-DERMATITIS

    NARCIS (Netherlands)

    NATER, JP

    During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly

  4. Television depictions about dermatology and skin diseases in Seinfeld.

    Science.gov (United States)

    Vickers, Jennifer L; Uchida, Tatsuo; Wagner, Richard F

    2010-12-15

    The iconic television situation comedy Seinfeld frequently referenced dermatologists and topics involving the integument, using satire for comedic effect. However, selecting satire to portray an already misunderstood and unknown subject matter may perpetuate incorrect public beliefs and stereotypes about those with skin diseases and diminish cultural sensitivity towards people who have dermatologic conditions and their caregivers.

  5. Epidemiology of skin diseases in university of Nigeria Teaching ...

    African Journals Online (AJOL)

    Background: Several studies have been carried out to determine the patterns of skin diseases across Nigeria and results have shown changing patterns with the trend reflecting a higher tendency for allergic dermatoses in a majority of these studies. This study was carried out to evaluate the current clinical picture of patients ...

  6. Getting Under the Skin: The Inscription of Dermatological Disease ...

    African Journals Online (AJOL)

    8; Papadopoulos, Bor & Legg, 1999, p. 107). Chronic cutaneous disease is often visible to others so that social factors in coping and adjustment are thus highly relevant (Papadopoulos, et al., 1999, p. 107). Psychological factors tend, however, to be overlooked in the dermatological treatment domain when the skin problem ...

  7. The nature and consequence of Karl Marx's skin disease.

    Science.gov (United States)

    Shuster, S

    2008-01-01

    From an analysis of the original correspondence, it has been possible to establish that Karl Marx's incapacitating skin disease was hidradenitis suppurativa, not 'boils' as was universally assumed at the time and since; the psychological effect of this illness on the man and his work appears to have been considerable.

  8. Prevalence of Skin Diseases in Nigerian Children: - (The University ...

    African Journals Online (AJOL)

    Background: Skin diseases are frequently encountered in the tropics and are a serious cause of morbidity, disfigurement and distress in all age groups. The aim of this study is to determine prevalence and common dermatological conditions encountered in UPTH. Methods: Children aged 0-16 years attending the ...

  9. Immunoglobulin G4-related disease and its skin manifestations.

    Science.gov (United States)

    Takayama, Ryoko; Ueno, Takashi; Saeki, Hidehisa

    2017-03-01

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4 + plasma cells and an elevated serum IgG4 level. It usually occurs in middle-aged or older patients, with male predominance, and can involve multiple organs synchronously or metachronously. Patients with IgG4-RD generally respond to steroid therapy. IgG4-related skin lesions are typically erythematous and itchy plaques, subcutaneous nodules, or papules like prurigo nodularis located on the head and neck areas. Histologically, lymphoplasmacytic infiltrates with abundant IgG4+ plasma cells are seen in the dermis and/or subcutaneous tissue. The skin condition of IgG4-RD does not necessarily exhibit infiltration of IgG4 + plasma cells, which is a prerequisite for IgG4-related skin disease, but such skin lesions without infiltration by IgG4 + plasma cells can be included in the skin manifestations of IgG4-RD. © 2017 Japanese Dermatological Association.

  10. The family impact of skin diseases: the Greater Patient concept.

    Science.gov (United States)

    Basra, M K A; Finlay, A Y

    2007-05-01

    Although the impact of skin disease on patients' health-related quality of life (HRQoL) is well known, little work has been carried out to determine the secondary impact of a patient's skin disease on the patient's family or partner. The aim of this study was to identify the different aspects of a family member's QoL that may be affected by having a family member with skin disease. Qualitative interviews were conducted with 50 family members/partners of patients attending the outpatient clinic of a university hospital, with a wide range of dermatological conditions (n = 21). Subjects were invited to discuss in detail all the ways that their lives were affected by living with a patient with skin disease. The mean age of subjects (M = 19; F = 31) was 48.1 years (SD = 15.7) most were either parents (44%) or spouses/partners (44%) of the patients. Patients' ages (M = 16; F = 34) ranged from 5 months to 84 years. Fifty-nine aspects of QoL of family members were identified that were adversely affected by the patients' skin disease. These were categorized into 18 main topic areas: Emotional distress (98%), Burden of care (54%), Effect on housework (42%), Social life (48%), Holidays (46%), Financial aspect (30%), Physical well-being (22%), Job/study (40%), Leisure activities (26%), Sleep (20%), Food/drink (12%), Restriction of liked activities (14%), Need for support (12%), People's attitude (10%), Dissatisfaction with medical care (14%), Effect on sex life (8%), Role of religious faith (8%) and Miscellaneous (16%). There was no significant difference between male and female subjects regarding main QoL areas affected. The median number of main topic areas reported per family member was five (mean = 5.2, range = 1-10, SD = 2.64). This study has demonstrated that skin diseases can significantly impair the HRQoL of the patient's family in very diverse ways. Asking family members about this impact is greatly appreciated by them. We propose the 'Greater Patient' concept to

  11. The Counterbalance of Skin Metabolism on Orbits and Diseases

    Directory of Open Access Journals (Sweden)

    Li-Fan Chuang

    2015-05-01

    Full Text Available Human organ functions are regulated by the nervous system. When human cells receive a message, this message is transmitted to the nervous system through a series of signal transmission processes. Skin conditions that occur after applying skin cream are closely related to signal transmission and nervous regulation. We determined the connection between signal regulation and natural rhythmic operations. The diurnal variations resulting from the earth’s rotation and indicate the relative relationships between the sympathetic nervous system and the parasympathetic nerve system. A spectrum was developed to assess neural transmission conditions by using skin signals which from Fourier transformation of the waves and established the association between the spectrum and diseases. The results could explain the relationships between the neurological illnesses and established spectrum. The objective was to promote the use of this spectrum as a new tool for conducting the nervous system tests in the future.

  12. The skin microbiota: composition and function in health and disease

    DEFF Research Database (Denmark)

    Brüggemann, Holger

    2016-01-01

    conflicting properties, some of which are mutualistic with potential beneficial effects for skin health while others are potentially harmful for the host, such as P. acnes’ pro-inflammatory activity. Analysis of the population structure of P. acnes highlighted its multiphyletic composition; together...... protective function or its immunomodulatory properties. The skin microbiota of the face and upper back is dominated by species of the genera Staphylococcus and Propionibacterium. In particular, the species Propionibacterium acnes (P. acnes) predominately colonizes sebaceous areas. This species has several...... with comparative genomics data that revealed phylotype-specific differences, the hypothesis arose that certain lineages of P. acnes are health-beneficial while others are drivers of disease. This talk will introduce properties and host-interacting activities of P. acnes and other skin microbes. The talk...

  13. The skin microbiota: composition and function in health and disease

    DEFF Research Database (Denmark)

    Brüggemann, Holger

    2016-01-01

    protective function or its immunomodulatory properties. The skin microbiota of the face and upper back is dominated by species of the genera Staphylococcus and Propionibacterium. In particular, the species Propionibacterium acnes (P. acnes) predominately colonizes sebaceous areas. This species has several...... conflicting properties, some of which are mutualistic with potential beneficial effects for skin health while others are potentially harmful for the host, such as P. acnes’ pro-inflammatory activity. Analysis of the population structure of P. acnes highlighted its multiphyletic composition; together...... with comparative genomics data that revealed phylotype-specific differences, the hypothesis arose that certain lineages of P. acnes are health-beneficial while others are drivers of disease. This talk will introduce properties and host-interacting activities of P. acnes and other skin microbes. The talk...

  14. THE FREQUENT SKIN DISEASES DIAGNOSED AT UNIVERSITY STUDENTS

    Directory of Open Access Journals (Sweden)

    Yesim KAYMAK

    2005-12-01

    Full Text Available The incidence of some skin diseases are increasing at adolescent and early adulthood period. The most frequent disease at this period is acne vulgaris whereas fungal diseases, dermatitis, dermatosis which are due to stress and other reasons, oral mucosal lesions and herpetic lesions of perioral region are also frequent. In this research we aim to determine the frequent dermatologic diseases of university students and 147 female, 74 male, a total of 221 students are included. We questioned the dermatologic complaints of students, then examined dermatologically in detail and registered ages, sexes, findings of the dermatological examination and dermatological diagnostic informations. As a result it is found out that the most frequent diseases are acne vulgaris (34.1%, allergic and pruritic dermatosis (16.6%, fungal diseases ( 13.0%, and eritamatous-squamous disease (8.3%. [TAF Prev Med Bull 2005; 4(6.000: 313-320

  15. Mesenchymal Stem Cells for the Treatment of Skin Diseases

    Directory of Open Access Journals (Sweden)

    Toshio Hasegawa

    2017-08-01

    Full Text Available Mesenchymal stem cell (MSC-based therapy involving both autologous and allogeneic MSCs shows great promise in treating several conditions. MSCs promote wound healing, and can differentiate into multiple cell lineages, including keratinocytes. Therefore, MSCs can be used for the treatment of congenital or acquired skin defects. Because of their immunomodulatory properties, MSCs may be useful for the treatment of inflammatory and autoimmune skin diseases. In particular, MSCs might be effective for the treatment of large vitiligo lesions as immunosuppressant or cultured grafts. MSCs can also be a novel cell source for regenerating hair in the treatment of scarring alopecia and androgenic alopecia. MSCs might also be an effective treatment for alopecia areata, which is associated with autoimmunity. Stem cell therapies with topical administration of MSCs and bone marrow transplantation were shown to alleviate recessive dystrophic epidermolysis bullosa in both animal models and human subjects. In addition to cell transplantation, the mobilization of endogenous MSCs has been attempted for skin regeneration. Overall, this review highlights the great potential of MSCs for the treatment of skin diseases in the near future.

  16. View and practices of dermatologists regarding preventable skin diseases

    International Nuclear Information System (INIS)

    Raza, N.; Seir, F.; Qadir, S.N.R.

    2014-01-01

    To find out views and practice of dermatologists regarding prevention of preventable skin diseases. Study Design: Cross-sectional study. Place and Duration of Study: The study was set up in Apr-May 2010 at PAF Hospital Faisal, Karachi, Pakistan. Material and Methods: A close-ended questionnaire was sent to 100 dermatologists through resource persons at different places throughout the country. It included basic information about them, their views and practice regarding prevention of these diseases. Data was managed and analyzed using SPSS-17. Results: Fifty dermatologists thought that frequency of preventable skin diseases in their clinical practice is 26-50%. Fifty-six observed educated community as the most important link for prevention, 46 held governments responsible and 42 consider busy schedule as barrier to educate community. Thirty dermatologists delivered talk to general public, 11 at schools, colleges and factories, 07 appeared on mass media and 08 prepared leaflets, pamphlets and brochures regarding preventive aspects of skin diseases at least once during last one year. Conclusion: Dermatologists in Pakistan are aware of magnitude of the problem and understand importance of public education; however only a few dermatologists have endeavored to take up this task. (author)

  17. Skin diseases associated with Malassezia yeasts: facts and controversies.

    Science.gov (United States)

    Gaitanis, Georgios; Velegraki, Aristea; Mayser, Peter; Bassukas, Ioannis D

    2013-01-01

    The implication of the yeast genus Malassezia in skin diseases has been characterized by controversy, since the first description of the fungal nature of pityriasis versicolor in 1846 by Eichstedt. This is underscored by the existence of Malassezia yeasts as commensal but also by their implication in diseases with distinct absence of inflammation despite the heavy fungal load (pityriasis versicolor) or with characteristic inflammation (eg, seborrheic dermatitis, atopic dermatitis, folliculitis, or psoriasis). The description of 14 Malassezia species and subsequent worldwide epidemiologic studies did not reveal pathogenic species but rather disease-associated subtypes within species. Emerging evidence demonstrates that the interaction of Malassezia yeasts with the skin is multifaceted and entails constituents of the fungal wall (melanin, lipid cover), enzymes (lipases, phospholipases), and metabolic products (indoles), as well as the cellular components of the epidermis (keratinocytes, dendritic cells, and melanocytes). Understanding the complexity of their interactions will highlight the controversies on the clinical presentation of Malassezia-associated diseases and unravel the complexity of skin homeostatic mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Nappi, Carmela; Altiero, Michele; Imbriaco, Massimo; Giudice, Caterina Anna; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Nicolai, Emanuele; Aiello, Marco; Diomiaiuti, Claudio Tommaso [IRCCS SDN, Naples (Italy); Pisani, Antonio [University Federico II, Department of Public Health, Naples (Italy)

    2015-03-26

    Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients. Thirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of {sup 18}F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart. Six patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01). PET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted. (orig.)

  19. Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up.

    Science.gov (United States)

    Siegenthaler, M; Huynh-Do, U; Krayenbuehl, P; Pollock, E; Widmer, U; Debaix, H; Olinger, E; Frank, M; Namdar, M; Ruschitzka, F; Nowak, A

    2017-12-15

    Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort. A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59-155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04-2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25-0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07-18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95-17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS. CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Preventing Occupational Skin Disease: A Review of Training Programs.

    Science.gov (United States)

    Zack, Bethany; Arrandale, Victoria H; Holness, D Linn

    Occupational contact dermatitis (OCD) is a common occupational disease that impacts a variety of worker groups. Skin protection and disease prevention training programs have shown promise for improving prevention practices and reducing the incidence of OCD. This review details the features of training programs for primary prevention of OCD and identifies gaps in the literature. Twelve studies were identified for in-depth review: many studies included wet workers employed in health care, hairdressing, cleaning, and food preparation; 1 program featured manufacturing workers. Few programs provided content on allergic contact dermatitis, and only 1 was evaluated for long-term effectiveness. Effective programs were similar in content, delivery method, and timing and were characterized by industry specificity, multimodal learning, participatory elements, skin care resource provision, repeated sessions, and management engagement. Long-term effectiveness, generalizability beyond OCD, workplace health and safety culture impact, and translation of programs in the North American context represent areas for future research.

  1. Body image satisfaction and anxiety of a Turkish sample of university students with skin diseases.

    Science.gov (United States)

    Kaymak, Yeşim; Ulutaş, Ilkay; Taner, Ender; Bakir, Bilal; Simşek, Isil

    2007-04-01

    The aim of this study was to evaluate perception of body image and anxiety of 221 university students presenting to the dermatology outpatient clinic with a skin disease and 205 students without skin disease. Analysis of anxiety and body image scores yielded differences by sex and age in both groups. The group with skin disease had lower scores on body image. Acne vulgaris seems to be the most disturbing among the skin diseases, and this was more prominent in younger patients.

  2. Diseases of the Skin in the Production of Caprolactam,

    Science.gov (United States)

    As a result of the refinement of chemical technology in the production of caprolactam , workers are subjected to the effect of very low concentrations...clinical signs of a skin disease, is evident. In industrial contact with caprolactam and products of its synthesis, the barrier-protective function...in industries for the production of caprolactam include hygiene and preventive medical measures. Preliminary and periodic medical examinations by a physician-dermatologist are required.

  3. Mutational analysis of the GLA gene in Mexican families with Fabry ...

    Indian Academy of Sciences (India)

    EcoTILLING and HRM technology. BMC Res. Notes 6, 323. Desnick R. J. and Wasserstein M. P. 2001 Fabry disease: clini- cal features and recent advances in enzyme replacement therapy. Adv. Nephrol. Necker. Hosp. 31, 317–313. Desnick R. J. and Brady R. O. 2004 Fabry disease in childhood. J. Pediatr. 144, S20–S26.

  4. AB018. Revisited later-onset cardiac type Fabry disease—cardiac damages progressed in silence—experiences from an extremely high prevalent area, Taiwan

    OpenAIRE

    Niu, Dau-Ming; Hsu, Ting-Rong; Yang, Chia-Feng; Chu, Tzu-Hung; Chiang, Chuan-Chi; Ho, Hui-Chen

    2015-01-01

    All of the current newborn screening studies of Fabry disease revealed that the incidences of later-onset Fabry disease in their studied populations were much higher than the previous expectancy. It reveals that later-onset Fabry disease could be an important hidden health issue in some populations or even a lot of populations. However, the natural course of later-onset Fabry disease is still largely unknown. A total of 792,247 newborns have been screened for Fabry disease by our team in Taiw...

  5. Skin diseases and tattoos: a five-year experience.

    Science.gov (United States)

    Napolitano, Maddalena; Megna, Matteo; Cappello, Milena; Mazzella, Caterina; Patruno, Cataldo

    2017-05-16

    Decorative tattooing as a body art form underwent an exponential increase during the last two decades, particularly among teenagers and young adults. Consequently, the number of reported adverse reactions after tattooing has increased. The most frequent reported skin reactions to tattoo include infectious (bacterial, viral, fungal) or inflammatory (allergic contact dermatitis and granulomatous reaction) diseases. Moreover, tattoos can also induce the development of typical skin lesions of pre-existing dermatoses, a phenomenon known as isomorphism reactive or Koëbner phenomenon, which commonly occurs in patients with psoriasis, vitiligo, or lichen planus. A retrospective study analyzing records data of patients attending the Department of Dermatology, University of Naples "Federico II" during 2011-2015 was performed. All cases of tattoorelated or closely located dermatitis were selected. We observed 19 patients (mean age: 26.4 year-old) showing cutaneous conditions related to the practice of tattooing. Allergic contact dermatitis was reported as the most common cutaneous disease linked to tattooing (31.6%), followed by granulomatous reactions (26.3%). These data are consistent with those already reported in literature. Our results highlight the need to develop detailed regulations regarding tattoos practice, used materials, as well as execution procedures in order to limit the outbreak of tattooing related skin diseases.

  6. Infectious Skin Diseases in Children in General Practice: epidemiology and management

    NARCIS (Netherlands)

    R.S.A. Mohammedamin (Robbert)

    2007-01-01

    textabstractThe increasing proportion of skin diseases, especially infectious and allergic skin diseases, encountered in general practice represents a substantial part of the morbidity in children. Only limited information is available about the epidemiology of skin diseases in children in

  7. Gaps in Workplace Education For Prevention of Occupational Skin Disease.

    Science.gov (United States)

    Gupta, Tanya; Arrandale, Victoria H; Kudla, Irena; Holness, D Linn

    2018-02-13

    Occupational contact dermatitis (OCD) is a common occupational disease. Evidence suggests that education and training are effective prevention strategies. In spite of these known prevention strategies, workers continue to develop OCD. Little is reported regarding the actual training experience of workers. To examine the training experience of workers with contact dermatitis to identify areas for improvement. Participants were workers being assessed for contact dermatitis in an occupational health clinic. The anonymous survey collected demographics, workplace characteristics, and education and prevention practices. Approximately 80% reported general occupational health and safety training; however, only 49% reported skin-specific training (SST). For workers reporting SST, most received information regarding exposure avoidance, hand washing, and glove use. This content was reported as helpful by at least 50%. Workers who did not receive SST indicated the most important content would be warning signs of skin problems, how to avoid exposure and skin care while using gloves. While the study was anonymous and used self-reported of training experience, the study suggests there are gaps in skin protection training. Addressing these gaps may lead to improved prevention and reduction in OCD. © The Author(s) 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  8. Pattern of skin diseases in Bantwal Taluq, Dakshina Kannada

    Directory of Open Access Journals (Sweden)

    Kuruvilla Maria

    2000-01-01

    Full Text Available A survey was conducted to find out the pattern of skin diseases among patients who attended the fortnightly medical camp held in Bantwal Taluq, a rural area. Infective disorders were found in 42.68% and non infective in 41.58%. Among the infective disorders fungal infections were most common (24.08%. Among the non infective dermatoses eczemas were most common (33.93%. On comparing the proportional infectivity rate of infectious diseases among males and females it was found that in scabies males were more affected than females.

  9. Pattern of skin diseases in Bantwal Taluq, Dakshina Kannada.

    Science.gov (United States)

    Kuruvilla, M; Sridhar, K S; Kumar, P; Rao, G S

    2000-01-01

    A survey was conducted to find out the pattern of skin diseases among patients who attended the fortnightly medical camp held in Bantwal Taluq, a rural area. Infective disorders were found in 42.68% and non infective in 41.58%. Among the infective disorders fungal infections were most common (24.08%). Among the non infective dermatoses eczemas were most common (33.93%). On comparing the proportional infectivity rate of infectious diseases among males and females it was found that in scabies males were more affected than females.

  10. Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by {sup 123}I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Letizia; Giudice, Caterina Anna; Imbriaco, Massimo; Trimarco, Bruno; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Pisani, Antonio; Riccio, Eleonora [University Federico II, Department of Public Health, Naples (Italy); Salvatore, Marco [IRCCS SDN, Naples (Italy)

    2016-04-15

    Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and {sup 123}I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95 % confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction. (orig.)

  11. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    Science.gov (United States)

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

  12. The role of Toll-like receptors in skin diseases

    Directory of Open Access Journals (Sweden)

    Joanna Bacharewicz

    2014-09-01

    Full Text Available The innate immune system has the ability to recognize pathogens through Toll-like receptors (TLRs, which are transmembrane glycoproteins on the cell surface. These receptors present on the surface of immunological cells – macrophages, dendritic cells, mast cells and some populations of lymphocytes – play an important role in the defense against bacterial, viral and fungal infections. The connection of a Toll-like receptor with the microbial cell component known as pathogen associated molecular pattern (PAMP induces intracellular mechanisms leading to the synthesis of proinflammatory cytokines. Depending on the kind of the recognized ligand, TLRs are classified into subfamilies. So far, 13 TLRs have been described in mice and 11 in humans. These receptors may be expressed extracellularly (TLRs 1, 2, 4, 5, 6, 10, 11 or intracellularly, located in endosomes (TLRs 3, 7, 8, 9. Recent studies also indicate their role in the development of many dermatoses. Occurrence of these receptors has been found on the surface of epidermal and dermal cells: keratinocytes, Langerhans cells, fibroblasts, endo-thelial cells, melanocytes and adipocytes. This paper presents the structure and function of Toll-like receptors and their role in the pathogenesis of some infectious skin diseases, autoimmune and allergic dermatoses as well as skin neoplasms. The knowledge about the role of Toll-like receptors in the development of skin diseases creates the possibility to use them in treatment in the future.

  13. Permanent disability pension due to skin diseases in Denmark 2003-2008

    DEFF Research Database (Denmark)

    Ibler, K.S.; Jemec, G.B.E.

    2011-01-01

    in the understanding of how skin diseases affect patients and in arguments for continued specialist services. An approach to explore the societal impact of skin diseases is to investigate the incidence of permanent disability pensions granted due to skin diseases. The present study evaluated the number of permanent...... disability pensions granted due to skin diseases in Denmark during the 2003-2008 period and related them to previous findings. In view of the high prevalence of skin diseases in the society, and particularly their role in occupational medicine, only a low number of disability pensions are granted. This may...

  14. Direct immunofluorescence for immunobullous and other skin diseases.

    Science.gov (United States)

    Ghanadan, Alireza; Saghazadeh, Amene; Daneshpazhooh, Maryam; Rezaei, Nima

    2015-05-01

    A swift glance at ample evidence currently available about the assay clearly illustrates that the development of direct immunofluorescence (DIF), in which direct fluorescent antibodies are utilized to identify the target antigen, has been of immense importance. The immunoreactant deposits have been delineated by the DIF assay in three main locations, including throughout the epidermis, at the dermoepidermal junction (also known as the basement membrane zone) and in and/or around blood vessel walls. DIF testing can be conducted on several specimen sources, which are categorized according to feasibility of collection into invasive (e.g., skin) and non-invasive (e.g., hair). This review was intended to indicate that inspection of immunoreactant deposits via DIF is highly instrumental in diagnosing and monitoring the immunobullous and other diseases of the skin.

  15. Fabry Disease: prevalence of affected males and heterozygotes with pathogenicGLAmutations identified by screening renal, cardiac and stroke clinics, 1995-2017.

    Science.gov (United States)

    Doheny, Dana; Srinivasan, Ram; Pagant, Silvere; Chen, Brenden; Yasuda, Makiko; Desnick, Robert J

    2018-01-12

    Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A ( GLA ) mutations, results in two major subtypes, the early-onset Type 1 'Classic' and the Type 2 'Later-Onset' phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised 'benign/likely-benign' variants, thereby inflating prevalence estimates. Online databases were searched for all FD screening studies in high-risk clinics (1995-2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined. Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype. Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

  16. Issues in the use of costume and its relationship to skin diseases in ...

    African Journals Online (AJOL)

    This article focuses on the fundamental issues in the use of costumes and its relationship to skin diseases in the Nigerian theatre. It examines skin diseases that can be contracted through the use of contaminated costumes which can bring infections to the human skin. In the Nigerian theatre, like other theatre traditions ...

  17. Permanent disability pension due to skin diseases in Denmark 2003-2008

    DEFF Research Database (Denmark)

    Ibler, K.S.; Jemec, G.B.E.

    2011-01-01

    Skin diseases are common in the society. The majority of papers published on the impact of skin diseases are focused on clinical consequences of the quality of life, depression and anxiety. The overall societal perspective on skin disease is only poorly described but is important in the understan...... reflect that skin diseases either have less impact on the individual or are not considered by the authorities as debilitating as other high prevalence diseases such as musculoskeletal, psychiatric or circulatory diseases.......Skin diseases are common in the society. The majority of papers published on the impact of skin diseases are focused on clinical consequences of the quality of life, depression and anxiety. The overall societal perspective on skin disease is only poorly described but is important...... in the understanding of how skin diseases affect patients and in arguments for continued specialist services. An approach to explore the societal impact of skin diseases is to investigate the incidence of permanent disability pensions granted due to skin diseases. The present study evaluated the number of permanent...

  18. The Malassezia Genus in Skin and Systemic Diseases

    Science.gov (United States)

    Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D.; Velegraki, Aristea

    2012-01-01

    Summary: In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis. PMID:22232373

  19. The Malassezia genus in skin and systemic diseases.

    Science.gov (United States)

    Gaitanis, Georgios; Magiatis, Prokopios; Hantschke, Markus; Bassukas, Ioannis D; Velegraki, Aristea

    2012-01-01

    In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis, M. japonica, M. yamatoensis, M. nana, M. caprae, M. equina, and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia-synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.

  20. Distribution and degradation of albumin in extensive skin disease

    DEFF Research Database (Denmark)

    Worm, Anne-Marie; Taaning, E; Rossing, N

    1981-01-01

    The distribution and degradation of albumin were determined in twelve patients with extensive skin disease and in ten control subjects by measuring the metabolic turnover and transcapillary escape of 132 I-labelled albumin. The ratio of intravascular to total mass of albumin was normal. Thus...... the observed hypoalbuminaemia and the low intravascular mass reflect a reduced mass of total body albumin. The rate of synthesis was normal, but the transcapillary escape rate reflecting the microvascular leakiness to macromolecules, and the fractional disappearance rate were significantly higher...

  1. Isolation of lumpy skin disease virus from cattle in and around ...

    African Journals Online (AJOL)

    ... Lumpy Skin Disease was found to be a serious disease in the study area. So, further investigation is needed on identification of the causative agents and Molecular characterization of Lumpy Skin Disease Virus and risk factors of the disease in South Wollo Zone. Keywords: Cattle, Dessie and Kombolcha, LSD, LSDV, ...

  2. Son dönem böbrek yetmezliğinin nadir bir nedeni: Fabry hastalığı

    OpenAIRE

    ESEN, Bennur; ATAY, Ahmet Engin; GÖKMEN, Emel; YILDIRIM, Süleyman; ŞİT, Dede

    2015-01-01

    Fabry disease is the second most common lysosomal storage disease after Gaucher disease. Although there are many systemic symptoms, generally diagnosis of Fabry disease is delayed. Having a family history of Fabry disease with symptoms is important for diagnosis. In this report, a 23-year-old male patient diagnosed as Farby disease by genetic analysis is presented who had mitral insufficiency, cardiomyopathy and end stage renal failure requiring hemodialysis.

  3. Occupational skin diseases and prevention among sanitation workers in China.

    Science.gov (United States)

    Yan, Yuehua; Wang, Xinggang; Wu, Jianbo; Xu, Li

    2015-09-01

    Little research has been focused on the health status or the occupational protection awareness of sanitation workers. The policy recommendations on the occupational safety and health of sanitation workers based on the scientific research are also insufficient in developing countries like China. To study the incidence of dermatoses and the relevance with occupational exposure, protection awareness and protective measures among sanitation workers for better management and protection of the sanitation workers. 273 sanitation workers and 113 administrative staff from 11 streets of Wuhan were recruited. Dermatological problems were evaluated and recorded by physical examination. Occupational exposure, protection awareness, the use of protective equipments and personal history of skin disease were assessed by questionnaires. Compared with administrative staff, sanitation workers had much more occupational dermatological problems and had a much higher rate of harmful ultraviolet ray exposure. Young sanitation workers were more aware of occupational self-protection and a relatively higher rate of them using protective equipments compared with old ones. Exposure to multiple health hazards and the poor use of protective equipments are related to skin diseases in sanitation workers. Prejob training of self-protection and the use of protective equipments are recommended.

  4. Automation Diagnosis of Skin Disease in Humans using Dempster-Shafer Method

    Science.gov (United States)

    Khairina, Dyna Marisa; Hatta, Heliza Rahmania; Rustam; Maharani, Septya

    2018-02-01

    Skin disease is an infectious disease that is common in people of all ages. Disorders of the skin often occur because there are factors, among others, are climate, environment, shelter, unhealthy living habits, allergies and others. Skin diseases in Indonesia are mostly caused by bacterial, fungal, parasitic, and allergies. The objective of the research is to diagnose skin diseases in humans by using the method of making decision tree then performing the search by forward chaining and calculating the probability value of Dempster-Shafer method. The results of research in the form of an automated system that can resemble an expert in diagnosing skin disease accurately and can help in overcoming the problem of skin diseases.

  5. Changes in Bacteria Induce Inflammatory Skin Diseases | Center for Cancer Research

    Science.gov (United States)

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that manifests as dry skin with a relentless itch and eczema. AD is considered an allergic disease in which the skin inflammation manifests in response to chronic exposure to contact allergens. However, identification of a responsible allergen is uncommon. Meanwhile, analyses have demonstrated that the surface of the human body is colonized by large numbers of diverse bacteria. This observation has led researchers to examine the roles these bacteria play in healthy and diseased skin. In a variety of genetic and chronic inflammatory skin diseases, including in patients with AD or with cancer who receive epidermal growth factor receptor (EGFR) inhibitors, Staphylococcus aureus and Corynebacterium species are the predominant bacteria isolated from the skin. However, the cause-and-effect relationship between this microbial imbalance and skin inflammation has not been determined.

  6. Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy.

    Science.gov (United States)

    Godel, Tim; Bäumer, Philipp; Pham, Mirko; Köhn, Anja; Muschol, Nicole; Kronlage, Moritz; Kollmer, Jennifer; Heiland, Sabine; Bendszus, Martin; Mautner, Victor-Felix

    2017-09-19

    To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy. In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls. Dorsal root ganglia of patients with Fabry disease were symmetrically enlarged by 78% (L3), 94% (L4), 122% (L5), 115% (S1), and 119% (S2) ( p Fabry disease and controls ( p = 0.7). The sciatic nerve of patients with Fabry disease at the thigh level showed an increase in cross-sectional area by 48% ( p Fabry disease have severely enlarged dorsal root ganglia with dysfunctional perfusion. This may be due to glycolipid accumulation in the dorsal root ganglia mediating direct neurotoxic effects and decreased neuronal blood supply. These alterations were less pronounced in peripheral nerve segments. Thus, the dorsal root ganglion might play a key pathophysiologic role in the development of neuropathy and pain in Fabry disease. © 2017 American Academy of Neurology.

  7. Skin and Diet: An Update on the Role of Dietary Change as a Treatment Strategy for Skin Disease.

    Science.gov (United States)

    Katta, Rajani; Kramer, Mary Jo

    2018-01-01

    An increasing body of research indicates that dietary change may serve as a component of therapy for certain skin conditions. This includes conditions such as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain nutrients, foods, or dietary patterns may act as disease "triggers", while others may prove beneficial. Avoidance or elimination diets may be helpful in some conditions, although testing may be recommended first. In terms of beneficial effects, an eating pattern that emphasizes the consumption of whole foods over highly processed foods may help in the treatment of certain skin conditions, and will certainly help in the prevention of associated co-morbidities.

  8. Plasma lyso-Gb3: a biomarker for monitoring fabry patients during enzyme replacement therapy.

    Science.gov (United States)

    Sakuraba, Hitoshi; Togawa, Tadayasu; Tsukimura, Takahiro; Kato, Hiroshi

    2017-12-29

    Recently, globotriaosylsphingosine (lyso-Gb3) has attracted interest as a biomarker of Fabry disease. However, little is known regarding its utility for the evaluation of the therapeutic efficacy. We measured plasma lyso-Gb3 concentration in Japanese healthy subjects and Fabry patients by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). We determined the reference interval in Japanese (UMIN000016854), and examined the effect of enzyme replacement therapy (ERT) with recombinant α-galactosidase A (GLA) and the influence of antibodies against the enzyme on the plasma lyso-Gb3 level in Fabry patients (UMIN000017152). The reference interval was determined to be 0.35-0.71 nmol/L, this being almost the same as the normal range in a non-Japanese population previously reported. The analysis revealed that the plasma lyso-Gb3 level was strikingly increased in classic Fabry males, and to a lesser extent in later-onset Fabry males and Fabry females. The elevation of the plasma lyso-Gb3 level was related to renal involvement in the Fabry females. ERT gave a rapid reduction in the elevated plasma lyso-Gb3 level in the classic Fabry males, and a gradual one or stabilization in most of the later-onset Fabry males and Fabry females. However, formation of antibodies against the recombinant GLA had a negative effect on the reduction of plasma lyso-Gb3. Regular observation of plasma lyso-Gb3 and antibodies is useful for monitoring of Fabry patients during ERT.

  9. Skin as a marker of general feline health: Cutaneous manifestations of systemic disease.

    Science.gov (United States)

    Vogelnest, Linda J

    2017-09-01

    Practical relevance: Although most skin lesions occur due to diseases primarily affecting the skin, some reflect important systemic diseases. Such lesions may relate directly to the systemic disease, or may occur due to secondary skin diseases that develop because of immunosuppression. Early recognition of skin changes as a marker of systemic disease will maximise patient outcomes. Clinical challenges: In older or clearly debilitated cats presenting with skin disease, the potential for underlying systemic disease is often readily apparent. Similarly, cats presenting with severe ulcerative or multifocal nodular skin lesions, or with concurrent signs of systemic illness, will more instinctively prompt systemic evaluation. More challenging is the cat presenting with alopecic, scaling, erythemic and/or mildly crusted skin disease, with or without pruritus; hypersensitivities and infectious dermatoses are the most common considerations, but occasionally systemic disease underlies the skin changes. Knowing when screening laboratory testing, body imaging or other systemic diagnostics are indicated is not always straightforward. Evidence base: This article reviews cutaneous presentations of systemic diseases reported in the veterinary literature, and discusses important differential diagnoses. The author draws on clinical experience, published data on disease prevalence and case evaluations, and expert opinions on approach to common systemic problems to provide guidance on when investigation for underlying systemic disease is most appropriate.

  10. Skin diseases among children attending the out patient clinic of the ...

    African Journals Online (AJOL)

    The commonest skin condition was pyoderma (29.81%) seen mainly in those below 5 years, followed by scabies (13.55%). Approximately 1/3 (33.3%) of the patients were referred to the dermatology clinic. Conclusion: Infectious skin diseases constitute a high percentage of skin disorders encountered in paediatrics. Almost ...

  11. Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

    Science.gov (United States)

    Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

    2013-01-01

    Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (pFabry disease, as well as for those with the classic type. PMID:23864212

  12. Electron microscopic examination of skin and conjunctival biopsy specimens in neuronal storage diseases.

    Science.gov (United States)

    Yamano, T; Shimada, M; Okada, S; Yutaka, T; Yabuuchi, H; Nakao, Y

    1979-01-01

    Skin and conjunctival biopsy specimens from fourteen patients with neuronal storage diseases were investigated using an electron microscope. The diseases were Tay-Sachs disease, ceroid-lipofuscinosis (Jansky-Bielschowsky type), Niemann-Pick disease (type B), highly suspected adrenoleukodystrophy, I-cell disease, mucolipidosis of the beta-galactosidase deficient type, Hurler disease, Hunter disease and Morquio disease. This examination provided valuable diagnostic information on some neuronal storage diseases but not on Morquio disease or highly suspected adrenoleukodystrophy. False negative results may sometimes occur using this examination method. However, this examination suggests the usefulness of skin and conjunctival biopsy specimens as a diagnostic tool in some neuronal storage diseases.

  13. Soil Correlates and Mortality from Giraffe Skin Disease in Tanzania.

    Science.gov (United States)

    Bond, Monica L; Strauss, Megan K L; Lee, Derek E

    2016-10-01

    Giraffe skin disease (GSD) is a disorder of undetermined etiology that causes lesions on the forelimbs of Masai giraffe ( Giraffa camelopardalis tippelskirchi) in Tanzania, East Africa. We examined soil correlates of prevalence of GSD from 951 giraffe in 14 sites in Tanzania, and estimated mortality using 3 yr of longitudinal mark-recapture data from 382 giraffe with and without GSD lesions, in Tarangire National Park (TNP). Spatial variation in GSD prevalence was best explained by soil fertility, measured as cation exchange capacity. We found no mortality effect of GSD on adult giraffe in TNP. Based on our findings, GSD is unlikely to warrant immediate veterinary intervention, but continued monitoring is recommended to ensure early detection if GSD-afflicted animals begin to show signs of increased mortality or other adverse effects.

  14. Skin disease among farmers using wastewater in rice cultivation in Nam Dinh, Vietnam

    DEFF Research Database (Denmark)

    Do, Thuy Trang; van der Hoek, Wim; Nguyen, Dang Tuan

    2007-01-01

    OBJECTIVE: To assess the risk of skin disease among farmers occupationally exposed to wastewater. METHODS: One-year follow-up study with monthly assessments of wastewater exposure and skin disease in Nam Dinh, northern Vietnam, in two adjacent communes with contrasting levels of wastewater use....... In each commune, 200 households were randomly selected. RESULTS: Of the 1103 individuals aged > or =15 years, 381 reported a skin problem at baseline or at any of the monthly visits, primarily dermatitis (eczema) and superficial fungal infections. Among the 874 subjects who were free from skin disease...... at baseline and who could be followed up > or =11 months, 183 developed a new skin disease (cumulative incidence 21%). Exposure to wastewater was a major risk factor for skin disease with a relative risk (RR) of 1.89 [95% confidence interval (CI) 1.39-2.57] in multivariable analysis. Other risk factors...

  15. Prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases in general practice.

    NARCIS (Netherlands)

    Verhoeven, E.W.M.; Kraaimaat, F.W.; Kerkhof, P.C.M. van de; Weel, C. van; Duller, P.; Valk, P.G.M. van der; Hoogen, H.J.M. van den; Bor, J.H.J.; Schers, H.J.; Evers, A.W.M.

    2007-01-01

    BACKGROUND: Physical symptoms of skin diseases have been shown to negatively affect patients' wellbeing. Although insight into physical symptoms accompanying skin diseases is relevant for the management and treatment of skin diseases, the prevalence of physical symptoms among patients with skin

  16. Understanding the Effects of Host Evolution and Skin Bacteria Composition on Disease Vector Choices

    Science.gov (United States)

    2016-04-14

    Distribution Unlimited UU UU UU UU 14-04-2016 1-Sep-2014 31-Dec-2015 Final Report: Understanding the effects of host evolution and skin bacteria...reviewed journals: Final Report: Understanding the effects of host evolution and skin bacteria composition on disease vector choices Report Title Here...SECURITY CLASSIFICATION OF: Here we sought to understand how host biology influences the composition of skin microbes, how skin microbes influence

  17. Presymptomatic diagnosis of Fabry's disease

    DEFF Research Database (Denmark)

    Hasselbalch, Rasmus Bo; Lav Madsen, Per; Bundgaard, Henning

    2016-01-01

    differential diagnoses in patients presenting with cardiac hypertrophy. In boys, onset has been reported in early childhood with complaints initially comprising neuropathic pain, reduced sweat production, and gastrointestinal symptoms. Later the cardiac, renal, and central nervous systems may become affected...... inheritable cardiomyopathies. The specific - precise - diagnosis may be crucial for the patient as well as the relatives....

  18. Quality of life assessment among patients with peristomal skin disease

    DEFF Research Database (Denmark)

    Nybaek, Hanne; Knudsen, Dorte Bang; Laursen, Troels Nørgaard

    2010-01-01

    No data exist to describe how a skin problem may additionally affect the quality of life (QOL) in ostomates. We have studied the QOL in patients with peristomal skin problems and the variables that may affect it.......No data exist to describe how a skin problem may additionally affect the quality of life (QOL) in ostomates. We have studied the QOL in patients with peristomal skin problems and the variables that may affect it....

  19. Skin Examination: An Important Diagnostic Tool in Renal Failure Patients.

    Science.gov (United States)

    Van de Velde-Kossmann, Karen M

    2018-01-26

    Renal failure is common in the United States with an estimated prevalence of 660,000 treated end-stage renal disease patients in 2015 [1]. Causes of renal failure are many, and complications from renal failure, underlying disease, and treatment are not infrequent. Examples of common skin manifestations include xerosis, pigmentary change, and nail dystrophies. Frequent disease-specific skin changes may be helpful in the diagnosis of primary disorders leading to renal disease or severity of disease including bullosis diabeticorum, sclerodactyly, or leukoctoclastic vasculitis. Some cutaneous changes, such as the multiple angiokeratomas of Fabry disease or the plexiform neurofibromas of neurofibromatosis, are pathognomonic of genetic disorders, which often lead to renal failure. Careful examination of the skin can provide crucial clues to diagnosis of renal failure causation and aid in monitoring complications. © 2018 S. Karger AG, Basel.

  20. Genetic deletion of amphiregulin restores the normal skin phenotype in a mouse model of the human skin disease tylosis

    Directory of Open Access Journals (Sweden)

    Vishnu Hosur

    2017-08-01

    Full Text Available In humans, gain-of-function (GOF mutations in RHBDF2 cause the skin disease tylosis. We generated a mouse model of human tylosis and show that GOF mutations in RHBDF2 cause tylosis by enhancing the amount of amphiregulin (AREG secretion. Furthermore, we show that genetic disruption of AREG ameliorates skin pathology in mice carrying the human tylosis disease mutation. Collectively, our data suggest that RHBDF2 plays a critical role in regulating EGFR signaling and its downstream events, including development of tylosis, by facilitating enhanced secretion of AREG. Thus, targeting AREG could have therapeutic benefit in the treatment of tylosis.

  1. Awareness of occupational skin disease in the service sector.

    Science.gov (United States)

    Holness, D L; Kudla, I; Brown, J; Miller, S

    2017-06-01

    Occupational skin disease (OSD) is a common occupational disease. Although primary prevention strategies are known, OSDs remain prevalent in a variety of work environments including the service sector (restaurant/food services, retail/wholesale, tourism/hospitality and vehicle sales and service). To obtain information about awareness and prevention of OSD in the service sector. Focus groups and a survey were conducted with two groups. The first consisted of staff of the provincial health and safety association for the service sector and the second group comprised representatives from sector employers. Focus groups highlighted key issues to inform the survey that obtained information about perceptions of awareness and prevention of OSD and barriers to awareness and prevention. Both provincial health and safety association staff and sector employer representatives highlighted low awareness and a low level of knowledge of OSD in the sector. Barriers to awareness and prevention included a low reported incidence of OSD, low priority, lack of training materials, lack of time and cost of training, lack of management support and workplace culture. A starting point for improving prevention of OSD in the service sector is increased awareness. Identification of the barriers to awareness and prevention will help to shape an awareness campaign and prevention strategies. Building on existing experience in Europe will be important. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  2. In vitro culture of skin-homing T lymphocytes from inflammatory skin diseases

    DEFF Research Database (Denmark)

    Bang, Karen; Lund, Marianne; Mogensen, Søren C

    2005-01-01

    was for AD 1.20, MF 0.65 and psoriasis 0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+ cells in vitro. Our findings indicate a changed homeostasis among skin-homing lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes leads to a prominent cellular...

  3. 78 FR 70312 - National Institute of Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-25

    ... Arthritis and Musculoskeletal and Skin Diseases; Notice of Closed Meeting Pursuant to section 10(d) of the... meeting. The meeting will be closed to the public in accordance with the provisions set forth in sections... Arthritis and Musculoskeletal and Skin Diseases Special Emphasis Panel; Small Business Innovation Research...

  4. The significance of gender in the pattern of skin diseases in Zaria ...

    African Journals Online (AJOL)

    Background: Skin diseases are common worldwide, although their frequency of occurrence varies from region to region. This is a histopathologic analysis with the aim of establishing possible gender difference in the occurrence of skin diseases in a tropical hospital. Patients and Method: A 14-year histopathological analysis ...

  5. The efficacy of pulsed dye laser treatment for inflammatory skin diseases: A systematic review

    NARCIS (Netherlands)

    Erceg, A.; Jong, E.M.G.J. de; Kerkhof, P.C.M. van de; Seyger, M.M.B.

    2013-01-01

    BACKGROUND: The position of the pulsed dye laser (PDL) in the treatment of inflammatory skin diseases is still unclear. Evidence-based recommendations are lacking. OBJECTIVES: We sought to systematically review all available literature concerning PDL treatment for inflammatory skin diseases and to

  6. Occupational skin diseases in Czech healthcare workers from 1997 to 2009.

    Science.gov (United States)

    Machovcová, A; Fenclová, Z; Pelclová, D

    2013-04-01

    The healthcare sector ranked in second place among economic sectors in the Czech Republic, with about 11.4 % of all occupational diseases in 2009. Skin diseases constituted about 20 % of all occupational diseases. The aim of this study was to analyze the causes and trends in allergic and irritant-induced skin diseases in the healthcare sector. The data concerning occupational skin diseases (Chapter IV of the Czech List of Occupational Diseases, non-infectious skin illnesses) in the healthcare sector were analyzed from the Czech National Registry of Occupational Diseases from 1997 until 2009. The trends in the total counts and most frequent causes were evaluated. During the past 13 years, a total of 545 skin diseases were acknowledged in healthcare workers. Allergic contact dermatitis was diagnosed in 464 (85 %), irritant contact dermatitis in 71 (13 %) and contact urticaria in 10 subjects (2 %). Ninety-five percent of the patients were females. The overall incidence in individual years varied between 1.0 and 2.9 cases per 10,000 full-time employees per year. Disinfectants were the most frequent chemical agents causing more than one third of all allergic skin diseases (38 %), followed by rubber components (32 %) and cleaning agents (10 %). A general downward trend of diagnosed cases of occupational skin diseases in heath care workers in the Czech Republic over the past 13 years was demonstrated.

  7. Skin manifestations of growth hormone-induced diseases.

    Science.gov (United States)

    Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

    2016-09-01

    The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

  8. Skin diseases in workers at a perfume factory.

    Science.gov (United States)

    Schubert, Hans-Jürgen

    2006-08-01

    The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.

  9. Disease-related and drug-induced skin manifestations in inflammatory bowel disease.

    Science.gov (United States)

    Hindryckx, Pieter; Novak, Gregor; Costanzo, Antonio; Danese, Silvio

    2017-03-01

    Skin manifestations are common in patients with inflammatory bowel diseases (IBD) and can be part of a concomitant illness with a shared genetic background, an extra-intestinal manifestation of the disease, or a drug side-effect. Areas covered: We provide a practical overview of the epidemiology, pathogenesis, diagnosis, therapeutic approach and prognosis of the most frequent disease-related and drug-induced cutaneous manifestations in IBD, illustrated by cases encountered in our clinical practice. Among the most frequently encountered IBD-related lesions are erythema nodosum, pyoderma gangrenosum and Sweet's syndrome. Common skin manifestations with a strong association to TNF antagonists are local injection site reactions, psoriasiform lesions, cutaneous infections, vasculitides and lupus-like syndromes. In addition, we discuss the relation of thiopurines and TNF antagonists with the risk of skin cancer. Expert commentary: We hope this review will help caretakers involved in the management of IBD patients to recognize the lesions and to manage them in close collaboration with a dedicated dermatologist.

  10. Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats

    Directory of Open Access Journals (Sweden)

    Alison Diesel

    2017-05-01

    Full Text Available Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly “feline atopic syndrome” when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

  11. Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic Skin Disease in Cats.

    Science.gov (United States)

    Diesel, Alison

    2017-05-09

    Feline allergic skin disease presents a unique set of challenges to the veterinary practitioner. Although there is some similarity to what is seen in the allergic canine patient, cutaneous hypersensitivity dermatoses in cats can manifest with strikingly different clinical signs, treatment options and outcomes, and secondary complications/disease entities. Additionally, less is known about the pathogenesis of feline allergic skin diseases, particularly "feline atopic syndrome" when compared to dogs or people. This article aims to review what is currently known in regards to allergic skin disease in the feline patient, with focus on non-flea, non-food hypersensitivity dermatitis.

  12. SOME DISEASES INVOLVING THE EYE AND THE SKIN

    African Journals Online (AJOL)

    1971-04-10

    Apr 10, 1971 ... balanitis, urethritis and arthritis. Occasionally there are skin lesions only, erosions of the mouth and dull red macules (on the skin and soles of feet and palms of hands) which develop into cone-shaped hyperkeratosis (kerato- derma blenorrhagica). 5. Auto-immune Disorders. The ophthalmologist may be ...

  13. White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up Lesões da substância branca na doença de Fabry antes e depois da terapia de reposição enzimática: um seguimento de 2 anos

    Directory of Open Access Journals (Sweden)

    Laura B. Jardim

    2006-09-01

    Full Text Available PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS findings of patients with Fabry disease (FD during 24 months of enzyme replacement therapy (ERT with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML were evaluated as well as their relation to age, symptoms and neurological examination (CNS score. RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.OBJETIVO: Relatar os achados neurológicos e de imagem do sistema nervoso central (SNC, observados durante 24 meses de tratamento de reposição enzimática (ERT com agalsidase-alfa, em pacientes com a doença de Fabry (FD. MÉTODO: 8 pacientes foram incluídos; 6 completaram 24 meses de ERT. Os dados foram obtidos aos 0, 12 e 24 meses de ERT. Lesões de substância branca (WML foram avaliadas assim como sua relação com a idade e o exame neurológico (escore SNC. RESULTADOS: Os achados de ressonância nuclear magnética foram estáveis em 3 pacientes. As WML e o escore SNC pioraram em um caso; flutuaram em um outro caso; e melhoraram no sexto paciente. No todo, havia 15 WML antes da ERT e 19 WML depois de 24 meses de ERT. Em dois anos, 4 lesões desapareceram e 8 novas surgiram. CONCLUSÕES: Viu-se um padrão difuso de WML assintomáticas, na FD. Em dois anos, algumas WML surgiram, enquanto outras desapareceram. Resta demonstrar se esses fenômenos fazem parte da história natural da doença.

  14. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    Directory of Open Access Journals (Sweden)

    Goláň L

    2015-07-01

    Full Text Available Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC, Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW. Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643 in treatment-naïve adults (≥18 years with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New

  15. Microscopic Study of Skin Diseases in Horses from the Bogota Savanna, Colombia

    Directory of Open Access Journals (Sweden)

    Iovana Castellanos Londoño

    2014-06-01

    Full Text Available Horses hold third place in number of cases of skin disease after cats and dogs; however, there is little information about the demographic aspects of dermatological diseases in this species in Colombia. The purpose of this work was to carry out a preliminary study in order to determine the dermatological diseases that affect horses in the Bogota Savanna, through biopsy, skin scraping and trichogram, in order to approach the diagnosis and thus to establish therapeutic and prophylactic measures that benefit the animal’s health and productivity in commercial farms. Thirty-nine skin biopsies, thirty-nine cutaneous scraping and thirtyseven samples of hairy peel from horses with some kind of skin disease were received, all of which were processed by the Histopathology Laboratory from La Salle University. The inflammatory injuries were sorted taking into account the histological patterns of inflammatory skin disease and tumors, according to the classification by the World Health Organization (WHO. Allergic dermatitis was the most common pathology (46% and neoplasia was observed in 13% of the cases; fungal spores in ectothrix position were found in 10% of the cutaneous scrapes. Mites of the type Psoroptes spp were identified in one of the trichograms. This is the first report of microscopic diagnosis of skin diseases of horses in the country with the goal of contributing with the demographic knowledge of skin diseases in the Bogota Savanna.

  16. [Results of the experiment of skin disease reduction in military personnel of Air-Force troops].

    Science.gov (United States)

    Samtsov, A V; Glad'ko, V V; Goriachev, A I; Kalachev, O V; Deriabin, V F; Adon'ev, V S; Ustinov, M V

    2010-11-01

    The article reflects the results of the experiment of skin disease reduction in the Airborne troops. Some aspects of skin disease in the individual armed services are revealed, the reasons of its increase in comparison with the analogous data in the Armed Forces of the Russian Federation in whole, concrete measures to reduce the number of diseases are offered. The most effective interventions are clothing exchange and bath operations 2 times a week, as well as the use of personal hygiene kits.

  17. A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

    Science.gov (United States)

    Munk, Adiel; Man, Joshua; Schaffer, Andras; Tung, Thomas; Mann, Caroline

    2017-01-01

    Dendritic cells (DCs) are important in regulating immunity and tolerance and consist of functionally distinct subsets that differentially regulate T lymphocyte function. The underlying basis for this subset specificity is lacking, particularly in humans, where the classification of tissue DCs is currently incomplete. Examination of healthy human epidermal Langerhans cells and dermal skin cells revealed a tissue CD5-expressing DC subtype. The CD5+ DCs were potent inducers of cytotoxic T cells and Th22 cells. The products of these T cells, IL-22 and IFN-γ, play a key role in the pathogenesis of psoriasis. Remarkably, CD5+ DCs were significantly enriched in lesional psoriatic skin compared with distal tissues, suggesting their involvement in the disease. We show that CD5+ DCs can be differentiated from hematopoietic progenitor cells independently of the CD5– DCs. A progenitor population found in human cord blood and in the dermal skin layer, marked as CD34–CD123+CD117dimCD45RA+, was an immediate precursor of these CD11c+CD1c+CD5+ DCs. Overall, our discovery of the CD5-expressing DC subtype suggests that strategies to regulate their composition or function in the skin will represent an innovative approach for the treatment of immune-mediated disorders in and beyond the skin. PMID:28931765

  18. Skin manifestations in course of celiac disease: case report and review of the literature.

    Science.gov (United States)

    Skroza, Nevena; Proietti, Ilari; Bernardini, Nicoletta; Giorgio, La Viola; Mancini, Maria Teresa; Nicolucci, Francesca; Pampena, Riccardo; Tolino, Ersilia; Zuber, Sara; Potenza, Concetta

    2014-01-01

    Skin and gut represent physical and immunological barriers between internal and external environment. Some affections involving the intestine, such as celiac disease, are reported to be associated with several different cutaneous diseases, like dermatitis herpetiforme or psoriasis. This could be better explained if gut and skin are taken as complex structures that share physio-pathological and immunological aspects. As a proof, we present the case of a woman affected by celiac disease who presented with three different skin manifestations strongly related in terms of onset, response to therapy and improvement during gluten-free diet.

  19. Glycosphingolipid storage in Fabry mice extends beyond globotriaosylceramide and is affected by ABCB1 depletion

    Science.gov (United States)

    Kamani, Mustafa A; Provençal, Philippe; Boutin, Michel; Pacienza, Natalia; Fan, Xin; Novak, Anton; Huang, Tonny C; Binnington, Beth; Au, Bryan C; Auray-Blais, Christiane; Lingwood, Clifford A; Medin, Jeffrey A

    2016-01-01

    Aim: Fabry disease is caused by α-galactosidase A deficiency leading to accumulation of globotriaosylceramide (Gb3) in tissues. Clinical manifestations do not appear to correlate with total Gb3 levels. Studies examining tissue distribution of specific acyl chain species of Gb3 and upstream glycosphingolipids are lacking. Material & methods/Results: Thorough characterization of the Fabry mouse sphingolipid profile by LC-MS revealed unique Gb3 acyl chain storage profiles. Storage extended beyond Gb3; all Fabry tissues also accumulated monohexosylceramides. Depletion of ABCB1 had a complex effect on glycosphingolipid storage. Conclusion: These data provide insights into how specific sphingolipid species correlate with one another and how these correlations change in the α-galactosidase A-deficient state, potentially leading to the identification of more specific biomarkers of Fabry disease. PMID:28116130

  20. Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry

    NARCIS (Netherlands)

    Gold, Henrik; Mirzaian, Mina; Dekker, Nick; Joao Ferraz, Maria; Lugtenburg, Johan; Codée, Jeroen D. C.; van der Marel, Gijs A.; Overkleeft, Herman S.; Linthorst, Gabor E.; Groener, Johanna E. M.; Aerts, Johannes M.; Poorthuis, Ben J. H. M.

    2013-01-01

    BACKGROUND: Biochemical markers that accurately reflect the severity and progression of disease in patients with Fabry disease and their response to treatment are urgently needed. Globotriaosylsphingosine, also called lysoglobotriaosylceramide (lysoGb3), is a promising candidate biomarker. METHODS:

  1. Biological response modifiers and their potential use in the treatment of inflammatory skin diseases

    DEFF Research Database (Denmark)

    Villadsen, Louise S; Skov, Lone; Baadsgaard, Ole

    2003-01-01

    In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectivene......, recombinant cytokines, or fusion proteins may be effective. Several biological response modifiers have already shown positive results in phase II/III clinical trials in skin diseases, and many new biological response modifiers are in progress.......In recent years, a more detailed understanding of the pathogenesis of several inflammatory skin diseases, combined with the developments within biotechnology, has made it possible to design more selective response modifiers. Biological response modifiers hold the potential for greater effectiveness...... and fewer side-effects than the current systemic therapies now used for severe psoriasis, contact dermatitis and atopic dermatitis. In the pathogenesis of inflammatory skin diseases, the immune system plays a pivotal role, and this is where biological response modifiers such as monoclonal antibodies...

  2. Autoimmune bullous diseases with skin and eye involvement: Cicatricial pemphigoid, pemphigus vulgaris, and pemphigus paraneoplastica.

    Science.gov (United States)

    Broussard, Karen C; Leung, Theresa G; Moradi, Ahmadreza; Thorne, Jennifer E; Fine, Jo-David

    2016-01-01

    Autoimmune blistering diseases are a heterogeneous group of disorders that mostly affect the skin and mucous membranes. Occasionally, other organ systems may be involved, depending on the unique pathophysiology of each disease. Cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus are distinct entities, but all have the potential to have cutaneous and ocular involvement. Awareness and early recognition of ocular involvement in these diseases is important given the increased risk for vision loss and blindness with delay in management. Several skin diseases may be associated with involvement of the external eye. The most common autoimmune diseases are cicatricial pemphigoid, pemphigus vulgaris, and paraneoplastic pemphigus. Copyright © 2016. Published by Elsevier Inc.

  3. Infliximab-induced skin manifestations in patients with inflammatory bowel disease.

    Science.gov (United States)

    Hellström, Alec Eligius; Färkkilä, Martti; Kolho, Kaija-Leena

    2016-01-01

    The use of infliximab in rheumatoid and inflammatory bowel diseases (IBD) has been associated with a variety of adverse skin reactions, including paradoxical psoriatic lesions. The prevalence and possible predictors for these lesions were under observation in our cross-sectional prospective study. Nurses screened the skin of 118 adult patients with IBD during infliximab infusions between 4 September 2013 and 30 September 2014 based on the structured questionnaire. Data on skin manifestations, concomitant medications, extraintestinal manifestations and inflammatory markers were collected for analysis. Non-infectious skin manifestations were observed in 27 (22.9%) patients during the study period, of which eight (29.6%) were new-onset, eight (29.6%) were exacerbations of existing lesions and 11 (40.7%) were baseline lesions that did not worsen during the study. Scaling eczema was the most commonly described skin manifestation (n = 8; 29.6%), followed by exacerbated atopic eczema (n = 5; 18.5%) and plausible infliximab-induced psoriasiform lesions (n = 5; 18.5%). The strongest associating factor for skin manifestations was Crohn's disease, in nearly 80% of afflicted patients. Anti-TNF-α therapy is frequently associated with newly onset skin reactions, most commonly in patients with Crohn's disease. Non-infectious skin manifestations can be treated topically and do not require cessation of anti-TNF-α therapy.

  4. Psoriasis and other Th17-mediated skin diseases.

    Science.gov (United States)

    Tokura, Yoshiki; Mori, Tomoko; Hino, Ryosuke

    2010-12-01

    T helper (Th) 17 cells have crucial functions in host defense, and dysregulated Th17 responses mediate a variety of autoimmune and inflammatory conditions. Th17 cells coexpress interleukin (IL)-22, and its receptor is expressed on epidermal keratinocytes. IL-17 and IL-22 cooperatively enhance some immunological responses. A close relationship between IL-17 and the cutaneous milieu has been suggested by a number of observations. IL-17 induces the production of certain cytokines, chemokines and antimicrobial peptides by keratinocytes, and its cooperation with IL-22 has been documented. Recent findings have suggested that Th17 cells profoundly participate in the pathogenesis of certain skin disorders, in particular, psoriasis. The concept of the subsets of T cells responsible for psoriasis has been modified in the order of Th1, T cytotoxic 1, and again Thl, and Thl7 cells. IL-22 is the strongest cytokine in the keratinocyte-proliferative ability. Since IL-22 is produced by Th17 cells, they are crucial for the proliferation of keratinocytes. Furthermore, IL-22 with the help of IL-17 can induce the critical events of psoriasis, including signal transducer and activator of transcription 3 (STAT3) activation, cytokine/chemokine (IL-8 etc.) production, and antimicrobial peptide elaboration. For maintaining Th17 cells, IL-23 is required and is released from tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthetase (iNOS)-producing dendritic cells (TIP-DCs). TIP-DCs are activated via an autocrine mechanism by virtue of TNF-alpha. The above cytokine network in the pathogenesis of psoriasis has been proven by the therapeutic effectiveness of cytokine-blocking biologics. Antibodies against TNF-alpha or its soluble receptor have already been widely used in the treatment of psoriasis. The involvement of Th17 cells has also been shown in allergen-specific immune responses. The percentage of Th17 cells is increased in the peripheral blood of patients with atopic

  5. Repair of DNA damage in light sensitive human skin diseases

    Energy Technology Data Exchange (ETDEWEB)

    Horkay, I.; Varga, L.; Tam' asi P., Gundy, S.

    1978-12-01

    Repair of uv-light induced DNA damage and changes in the semiconservative DNA synthesis were studied by in vitro autoradiography in the skin of patients with lightdermatoses (polymorphous light eruption, porphyria cutanea tarda, erythropoietic protoporphyria) and xeroderma pigmentosum as well as in that of healthy controls. In polymorphous light eruption the semiconservative DNA replication rate was more intensive in the area of the skin lesions and in the repeated phototest site, the excision repair synthesis appeared to be unaltered. In cutaneous prophyrias a decreased rate of the repair incorporation could be detected. Xeroderma pigmentosum was characterized by a strongly reduced repair synthesis.

  6. [The assessment of the occupational risk for skin diseases in workers at the Storgoziia Plant, Pleven].

    Science.gov (United States)

    Madzhunov, N; Nosko, M

    1993-01-01

    A dermatological examination is performed on 95 workers (43 men and 52 women). In order to differentiate the type of contact dermatitis in connection with the expert examination of the skin changes in 20 workers was carried out epicutaneous test by specialized series PVH dust (pure), PVH--dust, containing dyes, by titanium oxide, with lead stearat and with paraloid, which is on acrylic base--all in concentrations 2% in carrier oil. It is established that in 26.3% of the examined are registered general skin diseases. In 7.4% are proved occupational skin diseases and in 3.2% allergic, in 4.2%--irritative.

  7. miRNAs in inflammatory skin diseases and their clinical implications

    DEFF Research Database (Denmark)

    Løvendorf, Marianne B; Skov, Lone

    2015-01-01

    miRNAs are a class of non-coding RNA molecules that modulate gene expression post-transcriptionally. They have a major impact on several physiological and pathological cellular processes including modulation of the innate and the adaptive immune system. The role of miRNAs in skin biology is still...... incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental...

  8. Filaggrin genotype and skin diseases independent of atopic dermatitis in childhood

    DEFF Research Database (Denmark)

    Bager, Peter; Wohlfahrt, Jan; Thyssen, Jacob Pontoppidan

    2016-01-01

    BACKGROUND: Filaggrin gene (FLG) mutations compromise skin barrier functions and increase risk of atopic dermatitis. We aimed to study effects on other skin diseases using unique data from the Danish registers. METHODS: FLG genotyping of a population-based sample of 1547 children with extracted D...... mutations may predispose to skin disease in young children including urticaria, and rash not recognized as atopic dermatitis although equally frequent. In clinical practice, FLG genotyping may help indicate the use of moisturizers to reduce skin problems.......BACKGROUND: Filaggrin gene (FLG) mutations compromise skin barrier functions and increase risk of atopic dermatitis. We aimed to study effects on other skin diseases using unique data from the Danish registers. METHODS: FLG genotyping of a population-based sample of 1547 children with extracted DNA...... and information on skin diseases from the Danish National Birth Cohort and Health Register, with 18 years follow-up during years 1996-2013. Odds ratios (OR) and hazard ratios (HR) were estimated using logistic regression and Cox regression, respectively, and adjusted for physician-diagnosed atopic dermatitis...

  9. Altered manifestations of skin disease at sites affected by neurological deficit.

    Science.gov (United States)

    Azimi, E; Lerner, E A; Elmariah, S B

    2015-04-01

    The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that an intact neural component is required for the conventional clinical manifestations of many inflammatory skin diseases. To investigate the relationship between nerve damage and skin disease. Previous individual reports since 1966 were collected systematically and the clinical observations described therein were placed within current concepts of neurogenic inflammation. We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only four cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor or combined sensory and motor deficits. These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses. © 2014 British Association of Dermatologists.

  10. Transcriptomic Analysis of Host Immune Response in the Skin of Chickens Infected with Marek's Disease Virus

    Science.gov (United States)

    Marek’s disease virus, a highly cell-associated oncogenic 'alpha-herpesvirus, is the causative agent of a T cell lymphoma and neuropathic disease called Marek’s disease. The skin is the only anatomical site where infectious enveloped cell-free virions are produced and shed into the environment. Stud...

  11. Bovine lumpy skin disease: epidemiology, economic impact and control opportunities in Ethiopia

    NARCIS (Netherlands)

    Abebe, Wassie Molla

    2018-01-01

    Lumpy skin disease (LSD) is a serious pox disease of cattle caused by LSD virus of the genus Capripoxvirus, subfamily Chordopoxvirinae and family Poxviridae. It is economically an important disease due to its effect on productivity, fertility, animal survival, hide quality, and trade. LSD is an

  12. Bovine lumpy skin disease: epidemiology, economic impact and control opportunities in Ethiopia

    NARCIS (Netherlands)

    Abebe, Wassie Molla

    2018-01-01

    Lumpy skin disease (LSD) is a serious pox disease of cattle caused by LSD virus of the genus Capripoxvirus, subfamily Chordopoxvirinae and family Poxviridae. It is economically an important disease due to its effect on productivity, fertility, animal survival, hide

  13. Benefits of optical coherence tomography for imaging of skin diseases

    Directory of Open Access Journals (Sweden)

    Utz S.R.

    2015-09-01

    Full Text Available Aim: working out the methods of visualization of information obtained during optical coherent tomography in normal skin and in series of inflammatory disorders. Materials and Methods. OCS1300SS (made in Thorlabs, USA was used in which the source of emission of radiation was a super-luminiscent diode with mean wavelength of 1325 nm. 12 patients with different skin conditions and 5 virtually healthy volunteers were examined with ОСТ procedure in OPD and IPD settings. High resolution USG numerical system DUB (TPM GmbH, Germany was used for comparative USG assessment. Results. ОСТ demonstrated considerably more detailed picture of the objects scanned compared to USG investigation. Image obtained with the help of ОСТ contains vital information about sizes of macro-morphological elements, status of vascular elements and their density in different depths of the skin. Conclusion. Additional results obtained from ОСТ of the skin lesions in plane section improves attraction for ОСТ in practical dermatology.

  14. The impact of pediatric skin disease on self-esteem

    Directory of Open Access Journals (Sweden)

    K.L. Vivar, MD

    2018-03-01

    Conclusion: Pediatric dermatologic disorders impact self-esteem throughout childhood. In addition to the surgical and medical management of these disorders, clinicians can also take an active role in the assessment and improvement of the psychosocial impact of these skin disorders.

  15. Ambient humidity and the skin: the impact of air humidity in healthy and diseased states.

    Science.gov (United States)

    Goad, N; Gawkrodger, D J

    2016-08-01

    Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further

  16. Skin autofluorescence is a predictor of cardiovascular disease in chronic kidney disease patients.

    Science.gov (United States)

    Furuya, Fumihiko; Shimura, Hiroki; Takahashi, Kazuya; Akiyama, Daiichiro; Motosugi, Ai; Ikegishi, Yukinobu; Haraguchi, Kazutaka; Kobayashi, Tetsuro

    2015-02-01

    Accelerated formation and tissue accumulation of advanced glycation end products (AGEs), reflecting cumulative glycemic and oxidative stress, occurs in age-related and chronic diseases like diabetes mellitus (DM) and renal failure, and contributes to vascular damage. Skin autofluorescence (AFR), a noninvasive measurement method, reflects tissue accumulation of AGEs. AFR has been reported to be an independent predictor of mortality in Caucasian hemodialysis patients. We assessed the relationship between levels of AFR and the prevalence of cardiovascular disease (CVD), and clarified the prognostic usefulness of skin AFR levels in Asian (non-Caucasian) hemodialysis (HD) patients. AFR was measured with an autofluorescence reader in 64 HD patients. Overall and cardiovascular mortality was monitored prospectively during the 3-year follow-up. During follow-up, CVD events occurred in 21 patients. The deaths of 10 HD patients were associated with CVD. Multivariate logistic regression analyses showed that initial AFR was an independent risk factor for de novo CVD in HD patients with or without diabetes. When patients were classified on the basis of AFR tertiles, Cochran-Armitage analysis demonstrated that the highest tertile of AFR level showed an increased odds ratio for the prevalence of CVD. These findings suggest that AFR levels can be used to detect the prevalence of CVD in HD patients with or without diabetes. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

  17. [Expression of promyelocytic leukaemia protein in Bowen's disease, skin squamous cell carcinoma and basal cell carcinoma].

    Science.gov (United States)

    Wang, Qiongyu; Ma, Huiqun; Wang, Shijie; Ma, Yunyun; Zou, Xingwei; Li, Ruilian

    2013-07-01

    To investigate the expression of promyelocytic leukaemia (PML) protein of PML protein in Bowen's disease (BD), skin squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) and explore the role of PML in the pathogenesis of these diseases. PML protein in normal skin tissues and lesions of Bowen's disease, SCC and BCC were detected with immunohistochemistry. Normal skin tissues did not express PML protein. In BCC, PML showed rather low expressions in the skin lesions (8.69% in cell nuclei and 4.35% in cytoplasm). The lesions in BD and SCC (grade I and II) showed obvious overexpression of PML protein in the cell nuclei and cytoplasm, and its expression in the cell nuclei of these lesions was significantly higher than that in grade III-IV SCC. PML protein may play an important role in the early stage of SCC, and its overexpression may contribute to the carcinogenesis and metastasis of SCC.

  18. Prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases in general practice.

    Science.gov (United States)

    Verhoeven, E W M; Kraaimaat, F W; van de Kerkhof, P C M; van Weel, C; Duller, P; van der Valk, P G M; van den Hoogen, H J M; Bor, J H J; Schers, H J; Evers, A W M

    2007-06-01

    Physical symptoms of skin diseases have been shown to negatively affect patients' wellbeing. Although insight into physical symptoms accompanying skin diseases is relevant for the management and treatment of skin diseases, the prevalence of physical symptoms among patients with skin diseases is a rather unexplored territory. The goal of the present study was to examine the prevalence of physical symptoms of itch, pain and fatigue in patients with skin diseases. On the basis of a systematic morbidity registration system in primary care, questionnaires were sent to 826 patients with skin diseases. Eventually, questionnaires from 492 patients were suitable for our analyses. Results indicated that patients with skin diseases particularly experience symptoms of itch and fatigue. Approximately 50% of all patients report experiencing these symptoms and about 25% experience these symptoms as relatively severe. Pain was relatively less frequently reported by 23% of all patients, and was on average somewhat less intense. The physical symptoms showed relatively strong correlations with disease-related quality of life and self-reported disease severity. In contrast, only moderate correlations were found with comorbidity and demographic variables, which suggests that the physical symptoms of itch, pain and fatigue are consequences of the skin diseases. Itch and fatigue and, to a somewhat lesser extent, pain have a high prevalence among patients with skin diseases. Clinicians should be encouraged to carefully assess itch, pain and fatigue in patients with skin diseases, and where appropriate focus treatment to these symptoms.

  19. Pattern of skin diseases in patients visiting a tertiary care health facility at hyderabad, pakistan

    International Nuclear Information System (INIS)

    Memon, K.N.; Soomro, R.A.

    2011-01-01

    Background: The morbidity associated with skin diseases makes them an important public health problem. Very scanty literature is found on the problem which is either disease-based, community based or a specified population group-based. objective of this study was to assess the pattern of skin diseases in patients and to determine their relation with demographic characteristics. Methods: This descriptive study was conducted at dermatology out-patient department of liaquat university hospital, jamshoro, pakistan for the period from 10th january to 10th february 2008. Four hundred and eleven patients were enrolled during the study period. The study population comprised of newly diagnosed cases as well as relapsing cases presenting at the facility. The criterion for registering the patients was clinical diagnosis although few cases were supported by investigations, too. The data was collected through a pre-designed questionnaire and analysed through spss-12. Result: Skin problems are fairly common among children and women. in children of less than 10 years age, 82.5% visiting the facility suffer from infectious skin diseases. among the infectious diseases, scabies is highly prevalent disease (45.5%). the majority of the patients belong to rural or slum areas (77.2%), low socio-economic strata (68.9%), and living in overcrowded families (82%). a strong association between skin infections and water inadequacy (p=0.016) was found, and scabies shows a strong statistical association with overcrowding (p=0.025). Conclusion: The skin diseases involve every age strata of our population but it is fairly common in younger age group, women, and people who do not practice hygiene. Out-reach services for the rural and slum communities and health education will give good results on prevention of skin diseases. (author)

  20. Pattern of skin diseases in paediatric age group and adolescents

    Directory of Open Access Journals (Sweden)

    Sayal S

    1998-01-01

    Full Text Available A total of 300 patients from first day of life to 17 years of age were analysed for pattern of skin disorders. School going children formed majority (41.3% of cases followed by preschool children (32%. Infections formed the commonest disorder (31 % followed by eczemas (24%, papulosquamous disorders (12%, infestation (8.6% and urticaria (5.3% while vitiligo, acne vulgaris, alopecia areata and genodermatoses were seen in 2.7% cases each.

  1. Revisiting Amazonian Plants for Skin Care and Disease

    Directory of Open Access Journals (Sweden)

    Bruno Burlando

    2017-07-01

    Full Text Available This review concerns five species of trees and palm trees that occur as dominant plants in different rainforest areas of the Amazon region. Due to their abundance, these species can be exploited as sustainable sources of botanical materials and include Carapa guianensis Aubl., family Meliaceae; Eperua falcata Aubl., family Fabaceae; Quassia amara L., family Simaroubaceae; and Attalea speciosa Mart. and Oenocarpus bataua Mart., family Arecaceae. For each species, the general features, major constituents, overall medicinal properties, detailed dermatological and skin care applications, and possible harmful effects have been considered. The major products include seed oils from A. speciosa and C. guianensis, fruit oil from O. bataua, and active compounds such as limonoids from C. guianensis, flavonoids from E. falcata, and quassinoids from Q. amara. The dermatologic and cosmetic applications of these plants are growing rapidly but are still widely based on empiric knowledge. Applications include skin rehydration and soothing; anti-inflammatory, antiage, and antiparasite effects; hair care; burn and wound healing; and the amelioration of rosacea and psoriasis conditions. Despite a limited knowledge about their constituents and properties, these species appear as promising sources of bioactive compounds for skin care and health applications. An improvement of knowledge about their properties will provide added value to the exploitation of these forest resources.

  2. Steroid synthesis by primary human keratinocytes; implications for skin disease

    International Nuclear Information System (INIS)

    Research highlights: → Primary keratinocytes express the steroid enzymes required for cortisol synthesis. → Normal primary human keratinocytes can synthesise cortisol. → Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. → StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3βHSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7- 3 H]-pregnenolone through each steroid intermediate to [7- 3 H]-cortisol in cultured PHK. Trilostane (a 3βHSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra

  3. Steroid synthesis by primary human keratinocytes; implications for skin disease

    Energy Technology Data Exchange (ETDEWEB)

    Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Michael, Anthony E. [Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, 3rd Floor, Lanesborough Wing, St. George' s, University of London, Cranmer Terrace, Tooting, London SW17 0RE (United Kingdom); Jaulim, Adil [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom); Bhogal, Ranjit [Life Science, Unilever R and D Colworth House, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Burrin, Jacky M. [Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ (United Kingdom); Philpott, Michael P. [Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT (United Kingdom)

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  4. The impact of skin diseases on quality of life: A multicenter study.

    Science.gov (United States)

    Sanclemente, G; Burgos, C; Nova, J; Hernández, F; González, C; Reyes, M I; Córdoba, N; Arévalo, Á; Meléndez, E; Colmenares, J; Ariza, S; Hernández, G

    2017-04-01

    To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. To determine the impact in quality of life of skin diseases in a Colombian population. This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p=0.37), symptoms (p=0.71) and emotions (p=0.32) domains, whereas statistical differences were found in the function domain (p=0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. A case study of infant physiologic response to skin-to-skin contact following surgery for complex congenital heart disease

    Science.gov (United States)

    Harrison, Tondi M.; Ludington-Hoe, Susan

    2014-01-01

    Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374

  6. Interferon and biologic signatures in dermatomyositis skin: specificity and heterogeneity across diseases.

    Directory of Open Access Journals (Sweden)

    David Wong

    Full Text Available BACKGROUND: Dermatomyositis (DM is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. METHODOLOGY AND FINDINGS: We analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin. CONCLUSIONS AND SIGNIFICANCE: As in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.

  7. Puffy skin disease (PSD) in rainbow trout, Oncorhynchus mykiss (Walbaum): a case definition.

    Science.gov (United States)

    Maddocks, C E; Nolan, E T; Feist, S W; Crumlish, M; Richards, R H; Williams, C F

    2015-07-01

    Puffy skin disease (PSD) is a disease that causes skin pathology in rainbow trout, Oncorhynchus mykiss (Walbaum). Incidence of PSD in UK fish farms and fisheries has increased sharply in the last decade, with growing concern from both industry sectors. This paper provides the first comprehensive case definition of PSD, combining clinical and pathological observations of diseased rainbow trout from both fish farms and fisheries. The defining features of PSD, as summarized in the case definition, were focal lateral flank skin lesions that appeared as cutaneous swelling with pigment loss and petechiae. These were associated with lethargy, poor body condition, inappetance and low level mortality. Epidermal hyperplasia and spongiosis, oedema of the dermis stratum spongiosum and a mild diffuse inflammatory cellularity were typical in histopathology of skin. A specific pathogen or aetiology was not identified. Prevalence and severity of skin lesions was greatest during late summer and autumn, with the highest prevalence being 95%. Atypical lesions seen in winter and spring were suggestive of clinical resolution. PSD holds important implications for both trout aquaculture and still water trout fisheries. This case definition will aid future diagnosis, help avoid confusion with other skin conditions and promote prompt and consistent reporting. © 2014 John Wiley & Sons Ltd.

  8. Commercial Essential Oils as Potential Antimicrobials to Treat Skin Diseases

    Science.gov (United States)

    Orchard, Ané

    2017-01-01

    Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman's literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils. PMID:28546822

  9. Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated.

    Science.gov (United States)

    Almeida, Beverley; Campanilho-Marques, Raquel; Arnold, Katie; Pilkington, Clarissa A; Wedderburn, Lucy R; Nistala, Kiran

    2015-09-01

    The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P-CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P-CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met the other 3 criteria. Incorporating PGA as

  10. Occupational Skin Disease Prevention: An Educational Intervention for Hairdresser Cosmetology Students.

    Science.gov (United States)

    Haughtigan, Kara; Main, Eve; Bragg-Underwood, Tonya; Watkins, Cecilia

    2017-11-01

    Cosmetologists frequently develop occupational skin disease related to workplace exposures. The purpose of this study was to evaluate an educational intervention to increase cosmetology students' occupational skin disease knowledge and use of preventive practices. A quasi-experimental design was used to evaluate students' knowledge, behaviors, intentions, expectancies, and expectations. A 20-minute verbal presentation and printed two-page educational handout were provided for participants. Statistically significant increases in knowledge, frequency of glove use, and frequency of moisturizer use were found, but the frequency of handwashing did not increase. In addition, the Behavioral Strategies subscale, the Intention subscale, and the Expectancies subscale showed statistically significant improvements. The results of this study suggest an educational intervention can increase cosmetology students' knowledge of occupational skin diseases and their use of preventive strategies.

  11. Breast disease with skin thickening: differential diagnosis with mammography and ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Young Rok; Kim, Hak Hee; Cha, Eun Suk; Park, Hye Seong; Kim, Ki Tae; Shinn, Kyung Sub [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    1999-02-01

    Diffuse skin thickening of the breast is produced by lymphedema usually secondary to obstruction of the axillary lymphatics. On physical examination, the affected breast is, due to increased fluid content, larger, heavier, and of higher overall density. Mammography reveals an increased coarse reticular pattern. Thickening of the skin can have many causes. It may be a result of tumor invasion or a tumor in the dermal lymphatics ; or because of lymphatic congestion through obstruction of lymphatic drainage within the breast, in the axilla, or centrally in the mediastinum. Further causes may be congestive heart failure, benign inflammation, primary skin processes such as psoriasis, or systemic diseases which involve the skin. Mammographic appearance is known to be nonspecific. Ultrasound can demonstrate skin thickening directly, but despite some reports suggesting that the cause of skin thickening can be inferred from the results of ultrasound, this is not usually of practical importance. The purpose of this study is to review the causes of skin thickening of the breast and to use mammography and US to differentiate the causes.

  12. Exposure to ambient bioaerosols is associated with allergic skin diseases in Greater Taipei residents.

    Science.gov (United States)

    Kallawicha, Kraiwuth; Chuang, Ying-Chih; Lung, Shih-Chun Candice; Han, Bor-Cheng; Ting, Yi-Fang; Chao, Hsing Jasmine

    2016-09-01

    Allergic skin diseases may result from various types of chemical and biological allergens. This study investigated the association between ambient bioaerosol exposure and allergic skin diseases by using the exposure data obtained from land use regression models and interpolated data. Data on daily average outpatient visits for atopic dermatitis (ICD-9-CM 691.8) and contact dermatitis and other eczema (ICD-9-CM 692.9) between November 2011 and August 2012 were obtained from the National Health Insurance Research Database. A generalized estimating equation was used to analyze the associations between the skin diseases and ambient bioaerosol levels. The results indicated that during the study period, contact dermatitis and other eczema were more prevalent than atopic dermatitis in the study area. Most cases were observed in districts of Taipei City and 3 major districts of New Taipei City, namely Xinzhuang, Banqiao, and Xindian. In univariate analysis, most bioaerosols were positively associated with both skin diseases. After adjustment for air pollution and sociodemographic factors, exposure to total fungal spores was significantly associated with atopic dermatitis in males (relative risk [RR] = 1.12; 95% confidence interval [CI] = 1.05-1.19). Contact dermatitis and other eczema had significant relationships with Cladosporium in males (RR = 1.07; 95% CI = 1.02-1.14) and with Aspergillus/Penicillium in females (RR = 1.04; 95% CI = 1.02-1.07). Meteorological parameters, namely wind speed, temperature, and rainfall, were also significantly associated with skin diseases. Our findings reveal that exposure to ambient bioaerosols is a significant and independent risk factor for allergic skin diseases. Copyright © 2016. Published by Elsevier Ltd.

  13. Skin Lesions (non Neoplastic and Non Hansen Disease in Jabalpur Area

    Directory of Open Access Journals (Sweden)

    J C Gupta

    1978-01-01

    Full Text Available The paper deals with 588 cases of skin diseases studied histopathologically between 1968 and 1974. Neoplastic and Hansens′s diseases have not been included in this study. The diseases have been studied with emphasis on their incidence, types and clinicopathological features. Psoriasis, lichen planus, vitiligo, chronic dermatitis, eczema, lupus vulgaris, mofluscum contagiosum etc. are reported in this paper. The results are presented and discussed.

  14. Cell-Type-Specific Differentiation and Molecular Profiles in Skin Transplantation: Implication of Medical Approach for Genetic Skin Diseases

    OpenAIRE

    Oyama, Noritaka; Kaneko, Fumio

    2011-01-01

    Skin is highly accessible and valuable organ, which holds promise to accelerate the understanding of future medical innovation in association with skin transplantation, engineering, and wound healing. In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture. These local events are more unlikely to be regulated by the host imm...

  15. Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.

    Science.gov (United States)

    Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki

    2017-11-01

    Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double-edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin-derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Appearance self-esteem in systemic sclerosis--subjective experience of skin deformity and its relationship with physician-assessed skin involvement, disease status and psychological variables.

    NARCIS (Netherlands)

    Lankveld, W.G.J.M. van; Vonk, M.C.; Teunissen, H.; Hoogen, F.H.J. van den

    2007-01-01

    OBJECTIVES: To determine the importance of skin deformity in systemic sclerosis (SSc) relative to other disease stressors and to find psychological correlates of appearance self-esteem (ASE) after controlling for disease status. METHODS: Disease-related stressors, symptoms, physical and

  17. Appearance self-esteem in systemic sclerosis--subjective experience of skin deformity and its relationship with physician-assessed skin involvement, disease status and psychological variables.

    Science.gov (United States)

    van Lankveld, W G J M; Vonk, M C; Teunissen, H; van den Hoogen, F H J

    2007-05-01

    To determine the importance of skin deformity in systemic sclerosis (SSc) relative to other disease stressors and to find psychological correlates of appearance self-esteem (ASE) after controlling for disease status. Disease-related stressors, symptoms, physical and psychological functioning, social support, coping styles, cognitions and ASE were assessed in 123 patients with SSc. A rheumatologist determined disease duration, SSc subtype, presence of organ involvement and skin-thickness scores. Stepwise hierarchical regression analysis of disease-related cognitions on ASE was performed after controlling for selected variables. Skin deformities proved a core stressor of the disease, only preceded by fatigue. Physician-assessed disease status, including modified Rodnan skin score, was unrelated to ASE. Sex, self-reported functioning and symptoms were related to ASE and used as control variables. Both acceptance and anxiety correlated strongly with ASE. The stepwise regression procedure only identified the disease-related cognition acceptance. In SSc, ASE proved unrelated to the extent of skin thickness. Psychological interventions aimed at boosting ASE should primarily target the psychological factors acceptance and anxiety.

  18. Fabry-Perot interferometry for microplasma diagnostics

    International Nuclear Information System (INIS)

    Hojo, H.; Mase, A.

    2006-01-01

    A new method for determining the electron density of a thin plasma by means of Fabry-Perot interferometry is proposed. The interferometer consists of two plasma layers and dielectric material surrounded by two plasma layers. The transmittance of electromagnetic waves across the interferometer is calculated, and Fabry-Perot resonances are demonstrated. It is shown that the electron density can be determined from the measurement of the Fabry-Perot resonance frequencies. This method can also be applied to the measurement of conduction electron density in semiconductor films

  19. Discrimination of skin diseases using the multimodal imaging approach

    Science.gov (United States)

    Vogler, N.; Heuke, S.; Akimov, D.; Latka, I.; Kluschke, F.; Röwert-Huber, H.-J.; Lademann, J.; Dietzek, B.; Popp, J.

    2012-06-01

    Optical microspectroscopic tools reveal great potential for dermatologic diagnostics in the clinical day-to-day routine. To enhance the diagnostic value of individual nonlinear optical imaging modalities such as coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) or two-photon excited fluorescence (TPF), the approach of multimodal imaging has recently been developed. Here, we present an application of nonlinear optical multimodal imaging with Raman-scattering microscopy to study sizable human-tissue cross-sections. The samples investigated contain both healthy tissue and various skin tumors. This contribution details the rich information content, which can be obtained from the multimodal approach: While CARS microscopy, which - in contrast to spontaneous Raman-scattering microscopy - is not hampered by single-photon excited fluorescence, is used to monitor the lipid and protein distribution in the samples, SHG imaging selectively highlights the distribution of collagen structures within the tissue. This is due to the fact, that SHG is only generated in structures which lack inversion geometry. Finally, TPF reveals the distribution of autofluorophores in tissue. The combination of these techniques, i.e. multimodal imaging, allows for recording chemical images of large area samples and is - as this contribution will highlight - of high clinically diagnostic value.

  20. [Value of adjuvant basic therapy in chronic recurrent skin diseases. Neurodermatitis atopica/psoriasis vulgaris].

    Science.gov (United States)

    Schöpf, E; Mueller, J M; Ostermann, T

    1995-07-01

    Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.

  1. Clinical combination of multiphoton tomography and high frequency ultrasound imaging for evaluation of skin diseases

    Science.gov (United States)

    König, K.; Speicher, M.; Koehler, M. J.; Scharenberg, R.; Elsner, P.; Kaatz, M.

    2010-02-01

    For the first time, high frequency ultrasound imaging, multiphoton tomography, and dermoscopy were combined in a clinical study. Different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond-laser multiphoton tomograph DermaInspectTM and (iii) dermoscopes. Dermoscopy provides two-dimensional color imaging of the skin surface with a magnification up to 70x. Ultrasound images are generated from reflections of the emitted ultrasound signal, based on inhomogeneities of the tissue. These echoes are converted to electrical signals. Depending on the ultrasound frequency the penetration depth varies from about 1 mm to 16 mm in dermatological application. The 100-MHz-ultrasound system provided an axial resolution down to 16 μm and a lateral resolution down to 32 μm. In contrast to the wide-field ultrasound images, multiphoton tomography provided horizontal optical sections of 0.36×0.36 mm2 down to 200 μm tissue depth with submicron resolution. The autofluorescence of mitochondrial coenzymes, melanin, and elastin as well as the secondharmonic- generation signal of the collagen network were imaged. The combination of ultrasound and multiphoton tomography provides a novel opportunity for diagnostics of skin disorders.

  2. IgG4-related skin disease may have distinct systemic manifestations: a systematic review.

    Science.gov (United States)

    Bennett, Adam E; Fenske, Neil A; Rodriguez-Waitkus, Paul; Messina, Jane L

    2016-11-01

    IgG4-related disease (IgG4-RD) is an increasingly prevalent protean multisystem disorder characterized by single or multi-organ infiltration of IgG4-bearing plasma cells. Skin involvement has been recognized and is relevant to proper diagnosis. A systematic literature review of 50 cases involving the skin reveals that patients with IgG4-related skin disease show predominant involvement of the head and neck and have a distinct pattern of systemic involvement, also favoring the head and neck - lymphatics, orbit, salivary, and lacrimal glands - but generally lacking pancreaticobiliary involvement (16% of cases), which by contrast is a predominant manifestation in systemic IgG4-RD (60% with pancreaticobiliary involvement). We summarize clinical and pathologic descriptive data from this systematic review. We review differential diagnosis and propose a diagnostic scheme for stratifying probability of disease based upon comprehensive integration of clinical, histopathologic, and laboratory data. Plasmacyte infiltration and storiform fibrosis are prominent in IgG4-related skin disease, but obliterative venulitis is less common than in the prototypical IgG4-related disease manifestation of autoimmune pancreatitis. IgG4 tissue and serum values, with a mean (±95% CI) in the reviewed cases of 132.8 ± 32.6 IgG4-positive plasma cells per high-power field and 580 ± 183.8 mg/dl, respectively, are incorporated into the suggested criteria. The distinct set of manifestations identified by this systematic review and the proposed diagnostic considerations, while requiring further validation in prospective studies, highlight the need to consider that IgG4-related skin disease defines a unique systemic disease complex along the spectrum of IgG4-RD. © 2016 The International Society of Dermatology.

  3. Knowledge Acquisition for Diagnosis of Skin Diseases as an Initial Platform for an Expert System

    Directory of Open Access Journals (Sweden)

    Fatemeh Rangraz Jeddi

    2018-04-01

    Full Text Available Background: The diagnosis of skin diseases, especially in patients suffering from more than one disease or having similar symptoms, is very complex and access to the knowledge of skin diseases makes the design of an expert system easier. This research aimed to design a knowledge base used for diagnosis of complex skin diseases, selected by experts. Methods: This applied developmental research was conducted in 2015. The study population included 10 dermatologists of Razi Hospital, affiliated to Tehran University of Medical Sciences. Data collection was conducted through a questionnaire and a checklist. The questionnaire had face and content validity and was based on Likert scale according to the twelfth chapter of the International Classification of Diseases (Tenth revision. The questionnaires were administered to participants and collected after completion. A checklist of knowledge acquisition was designed for each disease based on the semiology book of skin diseases with “agree-disagree” options and completed by interviews. Signs and symptoms had an agreement with at least 70% of the experts, and symptoms that were added according to the experts’ proposal entered the checklist and was given to experts for consensus in future evaluations. The software used in this research was Clementine and its statistical method used was Stata. The data were analyzed using SPSS, 16. Results: The diseases including pemphigus vulgaris, lichen planus, basal cell carcinoma, melanoma, and scabies were selected to design the expert system. Confirmed signs and symptoms of the diseases selected by the experts included 106 causes. Conclusion: The choice of the selected diseases needed by specialists in the knowledge system is a very vital component needed in designing the expert knowledge base system to meet international standards based on international classification and according to the needs of specialists.

  4. ORIGINAL ARTICLE Farber disease overlapping with stiff skin ...

    African Journals Online (AJOL)

    salah

    Sewell AC, Roggendorf W, Kuster- mann Kuhn B, et al. A case of com- bined Farber and Sandhoff disease. Eur.J.Pediatr. 1989;148(6):558-62. Schnabel D, Schroder M, Furst W,. 14. Klein A, Hurwitz R, Zenk T, et al. Simultaneous deficiency of sphin- golipid activator proteins 1 and 2 is caused by a mutation in the initiation.

  5. Patient reported outcomes in chronic skin diseases: eHealth applications for clinical practice

    NARCIS (Netherlands)

    van Cranenburgh, O.D.

    2016-01-01

    The overall aim of this thesis was to examine and integrate patient reported outcomes (PROs) in dermatological care. In part I, we specifically examined health-related quality of life (HRQoL), treatment satisfaction, and experiences with care in patients with chronic skin diseases. Our results

  6. Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands.

    NARCIS (Netherlands)

    Meeuwis, K.A.P.; Hullu, J.A. de; Jager, M.E.A. de; Massuger, L.F.A.G.; Kerkhof, P.C.M. van de; Rossum, M.M. van

    2010-01-01

    BACKGROUND: Psoriatic lesions may involve nearly all sites of the body. Involvement of the genital skin is frequently classified as part of intertriginous psoriasis without special awareness and treatment for this presentation of the disease. Gaining knowledge about the frequency of the involvement

  7. The Occurrence and Prevalence of Giraffe Skin Disease in Protected Areas of Northern Tanzania.

    Science.gov (United States)

    Lee, Derek E; Bond, Monica L

    2016-07-01

    Giraffe skin disease (GSD) is a disorder of undetermined etiology that causes lesions on the forelimbs of Masai giraffe ( Giraffa camelopardalis tippelskirchi). We estimated occurrence and prevalence of GSD in six wildlife conservation areas of Tanzania. The disjunct spatial pattern of occurrence implies that environmental factors may influence GSD.

  8. Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease

    NARCIS (Netherlands)

    Noordzij, Marjon J.; Lefrandt, Joop D.; Loeffen, Erik A. H.; Saleem, Ben R.; Meerwaldt, Robbert; Lutgers, Helen L.; Smit, Andries J.; Zeebregts, Clark J.

    Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was

  9. The Greek moulages: a picture of skin diseases in former times.

    Science.gov (United States)

    Worm, A-M; Hadjivassiliou, M; Katsambas, A

    2007-04-01

    Medical moulages are three-dimensional wax figures made for teaching in the beginning of the last century. A rather unknown hospital museum in Athens, Greece, stores 1660 moulages depicting skin and venereal diseases prevalent at that time such as syphilis, lepra and tuberculosis. The historical background behind the Greek moulages and the art of moulaging are described.

  10. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients.

    Science.gov (United States)

    Alharbi, Fahad J; Geberhiwot, Tarekegn; Hughes, Derralynn A; Ward, Douglas G

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish. Graphical Abstract ᅟ.

  11. Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

    Science.gov (United States)

    Amber, Kyle T; Murrell, Dedee F; Schmidt, Enno; Joly, Pascal; Borradori, Luca

    2018-02-01

    Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies

  12. Laser treatment of medical skin disease in women

    Directory of Open Access Journals (Sweden)

    C. LaRosa, MD

    2017-09-01

    Full Text Available Laser treatment is a relatively new and increasingly popular modality for the treatment of many dermatologic conditions. A number of conditions that predominantly occur in women and that have a paucity of effective treatments include rosacea, connective tissue disease, melasma, nevus of Ota, lichen sclerosus (LS, notalgia paresthetica and macular amyloidosis, and syringomas. Laser therapy is an important option for the treatment of patients with these conditions. This article will review the body of literature that exists for the laser treatment of women with these medical conditions.

  13. Self-administered version of the Fabry-associated pain questionnaire for adult patients.

    Science.gov (United States)

    Magg, Barbara; Riegler, Christoph; Wiedmann, Silke; Heuschmann, Peter; Sommer, Claudia; Üçeyler, Nurcan

    2015-09-17

    Fabry-associated pain may be the first symptom of Fabry disease (FD) and presents with a unique phenotype including mostly acral burning triggerable pain attacks, evoked pain, pain crises, and permanent pain. We recently developed and validated the first Fabry Pain Questionnaire (FPQ) for adult patients. Here we report on the validation of the self-administered version of the FPQ that no longer requires a face-to-face interview but can be filled in by the patients themselves allowing more flexible data collection. At our Würzburg Fabry Center for Interdisciplinary Treatment, Germany, we have developed the self-administered version of the FPQ by adapting the questionnaire to a self-report version. To do this, consecutive Fabry patients with current or past pain history (n = 56) were first interviewed face-to-face. Two weeks later patients' self-reported questionnaire results were collected by mail (n = 55). We validated the self-administered version of the FPQ by assessing the inter-rater reliability agreement of scores obtained by supervised administration and self-administration of the FPQ. The FPQ contains 15 questions on the different pain phenotypes, on pain development during life with and without therapy, and on impairment due to pain. Statistical analysis showed that the majority of questions were answered in high agreement in both sessions with a mean AC1-statistic of 0.857 for 55 nominal-scaled items and a mean ICC of 0.587 for 9 scores. This self-administered version of the first pain questionnaire for adult Fabry patients is a useful tool to assess Fabry-associated pain without a time-consuming face-to-face interview but via a self-reporting survey allowing more flexible usage.

  14. Systematic mapping review about costs and economic evaluations of skin conditions and diseases in the aged.

    Science.gov (United States)

    Lichterfeld-Kottner, Andrea; Hahnel, Elisabeth; Blume-Peytavi, Ulrike; Kottner, Jan

    2017-02-01

    Skin conditions and dermatological diseases associated with advanced age (e.g. fungal infection, dry skin and itch) receive increasingly attention in clinical practice and research. Cost and economic evaluations are important sources to inform priority setting and ressource allocation decisions in healthcare. The economics of skin conditions in aged populations has not been systematically reviewed so far. The aim of this mapping review was to summarize the economic evidence of selected skin conditions in the aged (65 + years). A mapping literature review and evidence summary was conducted. Searches were conducted in data bases Medline and Embase via OVID. Cinahl was searched using EBSCO. References lists of potential eligible studies, reviews, guidelines or other sources were screened for additional literature. For evaluation of methodological quality of full economic analyses the Consensus on Health Economic Criteria (CHEC) checklist was used. Database searches resulted in 1388 records. A total of 270 articles were read in full-text. Thirty-five publications were finally included in the data analysis reporting 38 economic analyses. Ten cost of illness analyses and 26 cost-effectiveness analyses reporting about pressure ulcers, skin tears, pressure ulcers, incontinence associated dermatitis and intertrigo/contact dermatitis/candidiasis treatment and prevention and onychomycosis testing were identified. Limited evidence indicated that low air loss beds were more cost effective than standard beds for prevention of pressure ulcers. Standardized skin care regimens seem to lower the incidence of pressure ulcers, skin tears and IAD but a cost saving effect was not always observed. Findings of this mapping review indicate that there is a paucity of high quality evidence regarding the economic impact of age-associated skin conditions and diseases. Substantial heterogeneity in terms of study design, evaluation perspective, time period, and way of cost estimation was

  15. Senescent phenotypes of skin fibroblasts from patients with Tangier disease

    International Nuclear Information System (INIS)

    Matsuura, Fumihiko; Hirano, Ken-ichi; Ikegami, Chiaki; Sandoval, Jose C.; Oku, Hiroyuki; Yuasa-Kawase, Miyako; Tsubakio-Yamamoto, Kazumi; Koseki, Masahiro; Masuda, Daisaku; Tsujii, Ken-ichi; Ishigami, Masato; Nishida, Makoto; Shimomura, Iichiro; Hori, Masatsugu; Yamashita, Shizuya

    2007-01-01

    Tangier disease (TD) is characterized by a deficiency of high density lipoprotein (HDL) in plasma and patients with TD have an increased risk for coronary artery disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and flattened morphology, which is often observed in senescent cells. On the other hand, data have accumulated to show the relationship between cellular senescence and development of atherosclerotic CAD. The aim of the present study was to investigate whether TD fibroblasts exhibited cellular senescence. The proliferation of TD fibroblasts was gradually decreased at population doubling level (PDL) ∼10 compared with control cells. TD cells practically ceased proliferation at PDL ∼30. DNA synthesis was markedly decreased in TD fibroblasts. TD cells exhibited a higher positive rate for senescence-associated β-galactosidase (SA-β-gal), which is one of the biomarkers of cellular senescence in vitro. These data showed that TD cells reached cellular senescence at an earlier PDL compared with controls. Although, there was no difference in the telomere length of fibroblasts between TD and controls at the earlier passage (PDL 6), the telomere length of TD cells was shorter than that of controls at the late passage (PDL 25). Taken together, the current study demonstrates that the late-passaged TD fibroblasts showed senescent phenotype in vitro, which might be related to the increased cardiovascular manifestations in TD patients

  16. [Active search for leprosy and other skin diseases in school children from Agua de Dios, Colombia].

    Science.gov (United States)

    Rodríguez, Gerzaín; González, Rosalba; Gonzalez, Deysy; Granados, Carolina; Pinto, Rafael; Herrera, Hilda; Gutiérrez, Luisa F; Hernández, Elkin; López, Fernando; Gómez, Yenny

    2007-01-01

    Actively searching for leprosy, other skin diseases and BCG vaccination scars amongst school children from Agua de Dios, the municipality having the highest prevalence of leprosy in Colombia. A clinical examination of the children was carried out by nurses, interns, general practitioners and experts on leprosy. Skin smear tests and skin biopsies were performed when the clinical findings suggested leprosy. Anti-phenolic glycolipid antibodies in blood were determined in special cases. 86 % of the 2 844 school children were examined; 833 had skin diseases and 16 % of these required evaluation by specialists. Four new cases of paucibacillary leprosy, two indeterminate and two primary polyneuritic cases were found. Pediculosis capitis, pityriasis alba, tinea versicolor, hypopigmented nevus, insect bites and miliaria were frequently detected. BCG vaccination scars were absent in 387 children; following several logistical problems, they were vaccinated. Four children had signs of childhood abuse. An 11-year-old girl presented hypopigmented mycosis fungoides. All diseases and conditions found were treated. The community received information regarding the results, emphasising the importance of an early diagnosis of leprosy. The incidence of leprosy found (16/10,000) was 123 times higher than the rest of the country's incidence. It is advisable to continue clinical examinations in Agua de Dios and research into risk factors for acquiring leprosy.

  17. Treatment of skin and subcutaneous cancer diseases by hyperthermic methods

    Directory of Open Access Journals (Sweden)

    Zviad Kovziridze

    2015-03-01

    Full Text Available Purpose: The present work pursues perfection of highly efficient anticancer, principally new methodology and technology. It deals with the comparative study of anticancer activity of controlled local hyperthermia in animals and determination-de- velopment of optimal regimes and schemes. Furthermore, it also presents the work on new clinical device of high anticancer effect. Methods: Authors used controlled local hyperthermia for this study. In our experiments, we used 3 to 3.5 months-old non-pedigree (nonlinear white mice (mass: 18-30 gram. After mice selection for the experiments, animals were placed in vivarium, in quarantine regime for 10 to 4 days. Individual protocols were drawn for each animal. Similar feeding and handling regimes were created for all animals. Transplantable malignant cancer strain, Erlich adenocarcinoma, was used. Results: Experiments on animals were successful. There are positive conclusions of pathological-anatomy laboratory “PathGeo”: Form # IV -200- 6A, for the examination # 3119-12 and # 15/02 and macro-morphological and micro-morphological description of the study # 15272-13. On the basis of the results of morphological study, it was proved that liver and lungs (the main target bodies were intact, and secondary cancer injuries were not fixed. After three sessions of hyperthermia treatment, the decrease in sizes of cancer formations and necrosis of diseased sections were visualized, while massive necrosis was observed after seven sessions. In all cases, necrosis and ulceration of diseased places were observed, which refers to transition of cancer into phase of healing. After eight-ten sessions, necrosis of cancer and ulceration were observed, which refers to irreversibility of the process and efficiency of the applied method of hyperthermia. Conclusion: Anticancer effect of hyperthermia conditioned by temperature fields was proved, which was expressed in inhibition of cancer growth, resorption and increase of

  18. Skin in health and diseases in ṛgveda saṃhiṭa: an overview.

    Science.gov (United States)

    Mukhopadhyay, Amiya Kumar

    2013-11-01

    Ṛgveda is the oldest religious book of the Aryans. It picturises the early lives of the Aryans. We get mention of various diseases in this Veda. Skin - both in health and diseases had caught attention of the Vedic sages. Skin was not merely an organ of attraction and look but its colour was important socially. Mentions of various diseases like leprosy, guinea worm, jaundice etc., are interesting. Mention of different disorders of the nails and hair are also there, though in a very primitive and mystic form. Management strategy was consisted of herbs, amulates, chanting of mantras, touching the body, uses of water and sunrays etc. This may be presumed that this Veda founded the base for the Āyurveda of the later period.

  19. Skin in health and diseases in Ṛgveda saṃhiṭa: An overview

    Directory of Open Access Journals (Sweden)

    Amiya Kumar Mukhopadhyay

    2013-01-01

    Full Text Available Ṛgveda is the oldest religious book of the Aryans. It picturises the early lives of the Aryans. We get mention of various diseases in this Veda. Skin - both in health and diseases had caught attention of the Vedic sages. Skin was not merely an organ of attraction and look but its colour was important socially. Mentions of various diseases like leprosy, guinea worm, jaundice etc., are interesting. Mention of different disorders of the nails and hair are also there, though in a very primitive and mystic form. Management strategy was consisted of herbs, amulates, chanting of mantras, touching the body, uses of water and sunrays etc. This may be presumed that this Veda founded the base for the Βyurveda of the later period.

  20. Prevalence of and Risk Factors for Skin Diseases Among Army Personnel and Flood Victims During the 2011 Floods in Thailand.

    Science.gov (United States)

    Thongtaeparak, Wittaya; Pratchyapruit, Walai-Orn; Kotanivong, Settha; Sirithanakit, Nimit; Thunyaharn, Sudaluck; Rangsin, Ram; Chaikaew, Phachara; Wongyongsin, Pitee; Pinyoboon, Pongpak; Sutthiwan, Phatcharaphan; Theethansiri, Witchwaree; Janthayanont, Dusit; Mungthin, Mathirut

    2016-08-01

    This study aimed to determine the prevalence of and risk factors for skin problems among flood victims and army personnel during the 2011 floods in Thailand. To determine the prevalence of and risk factors for skin symptoms, standardized questionnaires were used to collect demographic data, current skin symptoms, history of water exposure, and sanitary behaviors. A certified dermatologist evaluated those who presented with skin problems and provided diagnoses. Univariate and multivariate analyses were performed to assess independent risk factors for skin symptoms. The most prevalent skin disease was irritant contact dermatitis. Flood victims showed a higher prevalence of skin symptoms compared with army personnel. Development of skin symptoms after exposure to floodwater was also observed earlier among flood victims. Having a history of skin diseases and delayed skin cleaning after exposure were also significant risk factors for the development of skin symptoms. This information might be used as guidelines for protecting military personnel and to educate the general public regarding flood disaster management. (Disaster Med Public Health Preparedness. 2016;10:570-575).

  1. The impact of obesity on skin disease and epidermal permeability barrier status.

    Science.gov (United States)

    Guida, B; Nino, M; Perrino, N R; Laccetti, R; Trio, R; Labella, S; Balato, N

    2010-02-01

    Obese subjects frequently show skin diseases. However, less attention has been paid to the impact of obesity on skin disorders until now. The purposes of this study are: to highlight the incidence of some dermatoses in obese subjects and to study the water barrier function of the obese skin using transepidermal water loss (TEWL). Sixty obese subjects and 20 normal weight volunteers were recruited. Obese group was further divided into three body mass index (BMI) classes: class I (BMI 30-34.9 kg/m(2)), class II (BMI 35-39.9 kg/m(2)) and class III (BMI 40 g/m(2)). All subjects attended dermatological examination for skin diseases. To assess barrier function, TEWL measurements were performed on the volar surface of the forearm using a tewameter. The results of this study showed that: (i) obese subjects show a higher incidence of some dermatoses compared with normal-weight controls; in addition the dermatoses are more, frequent as BMI increases; (ii) the rate of TEWL is lower in obese subjects, than in the normal-weight subjects, particularly in patients with intra-abdominal obesity. Specific dermatoses as skin tags, striae distensae and plantar hyperkeratosis, could be considered as a cutaneous stigma of severe obesity. The low permeability of the skin to evaporative water loss is observed in obese subjects compared with normal weight control. Although the physiological mechanisms are still unknown, this finding has not been previously described and we believe that this may constitute a new field in the research on obesity.

  2. DNA damage in Fabry patients: An investigation of oxidative damage and repair.

    Science.gov (United States)

    Biancini, Giovana Brondani; Moura, Dinara Jaqueline; Manini, Paula Regina; Faverzani, Jéssica Lamberty; Netto, Cristina Brinckmann Oliveira; Deon, Marion; Giugliani, Roberto; Saffi, Jenifer; Vargas, Carmen Regla

    2015-06-01

    Fabry disease (FD) is a lysosomal storage disorder associated with loss of activity of the enzyme α-galactosidase A. In addition to accumulation of α-galactosidase A substrates, other mechanisms may be involved in FD pathophysiology, such as inflammation and oxidative stress. Higher levels of oxidative damage to proteins and lipids in Fabry patients were previously reported. However, DNA damage by oxidative species in FD has not yet been studied. We investigated basal DNA damage, oxidative DNA damage, DNA repair capacity, and reactive species generation in Fabry patients and controls. To measure oxidative damage to purines and pyrimidines, the alkaline version of the comet assay was used with two endonucleases, formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). To evaluate DNA repair, a challenge assay with hydrogen peroxide was performed. Patients presented significantly higher levels of basal DNA damage and oxidative damage to purines. Oxidative DNA damage was induced in both DNA bases by H2O2 in patients. Fabry patients presented efficient DNA repair in both assays (with and without endonucleases) as well as significantly higher levels of oxidative species (measured by dichlorofluorescein content). Even if DNA repair be induced in Fabry patients (as a consequence of continuous exposure to oxidative species), the repair is not sufficient to reduce DNA damage to control levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Genetic diseases associated with an increased risk of skin cancer development in childhood.

    Science.gov (United States)

    Fogel, Alexander L; Sarin, Kavita Y; Teng, Joyce M C

    2017-08-01

    Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals. In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis. The sonic hedgehog (SHH) pathway inhibitor vismodegib was shown in a placebo-controlled phase III randomized trial to reduce the tumor burden in patients with BCNS. Epidermolysis bullosa (EB) has been classified into four major types and more than 30 subtypes based partly on specific mutations, and best clinical practice guidelines for the management of cutaneous squamous cell carcinoma in EB have been developed. Oculocutaneous albinism (OCA) has been associated with new mutations in genes named OCA5, OCA6, and OCA7, bringing to the total number of culprit genes to seven (OCA1-OCA7). Advances in our understanding of genetic conditions that predispose to childhood skin cancer include new disease classification systems, management guidelines, and treatment options.

  4. Potential of IL-1, IL-18 and Inflammasome Inhibition for the Treatment of Inflammatory Skin Diseases

    Directory of Open Access Journals (Sweden)

    Gabriele Fenini

    2017-05-01

    Full Text Available In 2002, intracellular protein complexes known as the inflammasomes were discovered and were shown to have a crucial role in the sensing of intracellular pathogen- and danger-associated molecular patterns (PAMPs and DAMPs. Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1β and IL-18. Several autoinflammatory disorders such as cryopyrin-associated periodic syndromes and Familial Mediterranean Fever have been associated with mutations of genes encoding inflammasome components. Moreover, the importance of IL-1 has been reported for an increasing number of autoinflammatory skin diseases including but not limited to deficiency of IL-1 receptor antagonist, mevalonate kinase deficiency and PAPA syndrome. Recent findings have revealed that excessive IL-1 release induced by harmful stimuli likely contributes to the pathogenesis of common dermatological diseases such as acne vulgaris or seborrheic dermatitis. A key pathogenic feature of these diseases is IL-1β-induced neutrophil recruitment to the skin. IL-1β blockade may therefore represent a promising therapeutic approach. Several case reports and clinical trials have demonstrated the efficacy of IL-1 inhibition in the treatment of these skin disorders. Next to the recombinant IL-1 receptor antagonist (IL-1Ra Anakinra and the soluble decoy Rilonacept, the anti-IL-1α monoclonal antibody MABp1 and anti-IL-1β Canakinumab but also Gevokizumab, LY2189102 and P2D7KK, offer valid alternatives to target IL-1. Although less thoroughly investigated, an involvement of IL-18 in the development of cutaneous inflammatory disorders is also suspected. The present review describes the role of IL-1 in diseases with skin involvement and gives an overview of the relevant studies discussing the therapeutic potential of modulating the secretion and activity of IL-1 and IL-18 in such diseases.

  5. A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts.

    Science.gov (United States)

    Schueler, Ulrike; Kaneski, Christine; Remaley, Alan; Demosky, Stephen; Dwyer, Nancy; Blanchette-Mackie, Joan; Hanover, John; Brady, Roscoe

    2016-01-01

    Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal-lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal-lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.

  6. Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003–2015

    OpenAIRE

    IGISSINOV, Nurbek; KULMIRZAYEVA, Dariyana; BILYALOVA, Zarina; AKPOLATOVA, Gulnur; MAMYRBAYEVA, Marzya; ZHUMAGALIYEVA, Galina

    2017-01-01

    Background: Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. Methods: This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003–2015. Results: The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. T...

  7. Deep axial reflux, an important contributor to skin changes or ulcer in chronic venous disease.

    Science.gov (United States)

    Danielsson, Gudmundur; Eklof, Bo; Grandinetti, Andrew; Lurie, Fedor; Kistner, Robert L

    2003-12-01

    We undertook this cross-sectional study to investigate the distribution of venous reflux and effect of axial reflux in superficial and deep veins and to determine the clinical value of quantifying peak reverse flow velocity and reflux time in limbs with chronic venous disease. Four hundred one legs (127 with skin changes, 274 without skin changes) in 272 patients were examined with duplex ultrasound scanning, and peak reverse flow velocity and reflux time were measured. Both parameters were graded on a scale of 0 to 4. The sum of reverse flow scores was calculated from seven venous segments, three in superficial veins (great saphenous vein at saphenofemoral junction, great saphenous vein below knee, small saphenous vein) and four in deep veins (common femoral vein, femoral vein, deep femoral vein, popliteal vein). Axial reflux was defined as reflux in the great saphenous vein above and below the knee or in the femoral vein to the popliteal vein below the knee. Reflux parameters and presence or absence of axial reflux in superficial or deep veins were correlated with prevalence of skin changes or ulcer (CEAP class 4-6). The most common anatomic presentation was incompetence in all three systems (superficial, deep, perforator; 46%) or in superficial or perforator veins (28%). Isolated reflux in one system only was rare (15%; superficial, 28 legs; deep, 14 legs; perforator, 18 legs). Deep venous incompetence was present in 244 legs (61%). If common femoral vein reflux was excluded, prevalence of deep venous incompetence was 52%. The cause, according to findings at duplex ultrasound scanning, was primary in 302 legs (75%) and secondary in 99 legs (25%). Presence of axial deep venous reflux increased significantly with prevalence of skin changes or ulcer (C4-C6; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.56-4.67). Of 110 extremities with incompetent popliteal vein, 81 legs had even femoral vein reflux, with significantly more skin changes or ulcer, compared

  8. Skin condition and its relationship to systemic inflammation in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Majewski S

    2017-08-01

    Full Text Available Sebastian Majewski,1,2 Anna Pietrzak,3 Damian Tworek,4 Karolina Szewczyk,5 Anna Kumor-Kisielewska,1 Zofia Kurmanowska,5 Paweł Górski,1,2 Anna Zalewska-Janowska,3,* Wojciech Jerzy Piotrowski1,2,* 1Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland; 2Healthy Ageing Research Centre (HARC, Lodz, Poland; 3Department of Psychodermatology, Medical University of Lodz, Lodz, Poland; 4Department of General and Oncological Pulmonology, Medical University of Lodz, Lodz, Poland; 5Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland *These authors contributed equally to this work Background: The systemic (extrapulmonary effects and comorbidities of chronic obstructive pulmonary disease (COPD contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. Materials and methods: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP, interleukin-6 (IL-6, and tumor necrosis factor α (TNF-α, were measured in serum using commercially available enzyme-linked immunosorbent assays. Results: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P<0.05, but not for transepidermal water loss and erythema index. No significant

  9. Elevated numbers of SCART1+ gammadelta T cells in skin inflammation and inflammatory bowel disease

    DEFF Research Database (Denmark)

    Fink, Dorte Rosenbek; Holm, Dorte; Schlosser, Anders

    2010-01-01

    models of human diseases: skin inflammation and inflammatory bowel disease. In the skin inflammation model, an 8.6-fold increase in SCART1(+) cells was observed. Finally, recombinant SCART1 protein was found not to bind to selected bacterial or fungal components or to whole bacteria. Our results show......The members of the scavenger receptor cysteine-rich (SRCR) superfamily group B have diverse functions, including roles in the immune system. For years it has been known that the WC1 protein is expressed on the surface of bovine gammadelta T cells, and more recent studies indicate that WC1......(+) gammadelta T cells respond to stimulation with bacterial antigens by producing interferon-gamma. The SRCR proteins CD5, CD6, Sp alpha, CD163, and DMBT1/gp-340 are also involved in the immune response, since they are pattern recognition receptors capable of binding directly to bacterial and/or fungal...

  10. ALThe incidence of sexually transmitted infections and contagious skin diseases in the Saratov region

    Directory of Open Access Journals (Sweden)

    Schnaider D.A.

    2014-09-01

    Full Text Available Objective: Clinical and epidemiological analysis of the incidence of sexually transmitted infections (STI and the most frequently reported infectious skin diseases in the Saratov region. To estimate the contribution of immigrants to the formation and number of episodes of infections with sexually transmission in the region. Materials and methods. Retrospective evaluation of the incidence and manifestations of the epidemiological process conducted by evaluating data obtained from the forms of state statistical reporting (№ 9 and № 34, annual report of Saratov regional dermatovenerologic dispensary (2009-2013. Results. We carried out a comparative analysis of the incidence of STI and the most common infectious skin diseases of the population of Saratov region and noted resistant dynamics to decrease. Conclusion. Population displacement within the country and the influx of immigrants from the former CIS countries, have a significant impact on the epidemiological situation in the Saratov region

  11. Recurrence of skin disease in a nursery: ineffectuality of hexachlorophene bathing.

    Science.gov (United States)

    Gehlbach, S H; Gutman, L T; Wilfert, C M; Brumley, G W; Katz, S L

    1975-03-01

    An outbreak of streptococcal and staphylococcal skin disease was discovered in a full-term nursery after the discontinuation of bathing infants with hexachlorophene. The epidemic was only temporarily controlled by conventional means and recurred despite reinstitution of hexachlorophene bathing. Measures that decreased infants' exposure to visitors and hospital personnel and enforced aseptic techniques in the nursery were more important than use of hexachlorophene soap in achieving and maintaining control.

  12. Diet and Dermatology: The Role of Dietary Intervention in Skin Disease

    OpenAIRE

    Katta, Rajani; Desai, Samir P.

    2014-01-01

    For decades, it was thought that many common dermatological conditions had no relationship to diet. Studies from recent years, however, have made it clear that diet may influence outcome. In this review, the authors focus on conditions for which the role of diet has traditionally been an underappreciated aspect of therapy. In some cases, dietary interventions may influence the course of the skin disease, as in acne. In others, dietary change may serve as one aspect of prevention, such as in s...

  13. Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease.

    Science.gov (United States)

    Karbach, Susanne; Croxford, Andrew L; Oelze, Matthias; Schüler, Rebecca; Minwegen, Daniel; Wegner, Joanna; Koukes, Lija; Yogev, Nir; Nikolaev, Alexei; Reißig, Sonja; Ullmann, Alexander; Knorr, Maike; Waldner, Maximilian; Neurath, Markus F; Li, Huige; Wu, Zhixiong; Brochhausen, Christoph; Scheller, Jürgen; Rose-John, Stefan; Piotrowski, Carolin; Bechmann, Ingo; Radsak, Markus; Wild, Philipp; Daiber, Andreas; von Stebut, Esther; Wenzel, Philip; Waisman, Ari; Münzel, Thomas

    2014-12-01

    Interleukin (IL)-17A is regarded as an important cytokine to drive psoriasis, an inflammatory skin disease marked by increased cardiovascular mortality. We aimed to test the hypothesis that overproduction of IL-17A in the skin leading to dermal inflammation may systemically cause vascular dysfunction in psoriasis-like skin disease. Conditional overexpression of IL-17A in keratinocytes caused severe psoriasis-like skin inflammation in mice (K14-IL-17A(ind/+) mice), associated with increased reactive oxygen species formation and circulating CD11b(+) inflammatory leukocytes in blood, with endothelial dysfunction, increased systolic blood pressure, left ventricular hypertrophy, and reduced survival compared with controls. In K14-IL-17A(ind/+) mice, immunohistochemistry and flow cytometry revealed increased vascular production of the nitric oxide/superoxide reaction product peroxynitrite and infiltration of the vasculature with myeloperoxidase(+)CD11b(+)GR1(+)F4/80(-) cells accompanied by increased expression of the inducible nitric oxide synthase and the nicotinamide dinucleotide phosphate (NADPH) oxidase, nox2. Neutrophil depletion by anti-GR-1 antibody injections reduced oxidative stress in blood and vessels. Neutralization of tumor necrosis factor-α and IL-6 (both downstream of IL-17A) reduced skin lesions, attenuated oxidative stress in heart and blood, and partially improved endothelial dysfunction in K14-IL-17A(ind/+) mice. Dermal overexpression of IL-17A induces systemic endothelial dysfunction, vascular oxidative stress, arterial hypertension, and increases mortality mainly driven by myeloperoxidase(+)CD11b(+)GR1(+)F4/80(-) inflammatory cells. Depletion of the GR-1(+) immune cells or neutralization of IL-17A downstream cytokines by biologicals attenuates the vascular phenotype in K14-IL-17A(ind/+) mice. © 2014 American Heart Association, Inc.

  14. Mutational analysis of the GLA gene in Mexican families with Fabry ...

    Indian Academy of Sciences (India)

    Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal Adeficiency leads to Gb3 accumulation in tissues and cells in the body. This pathology is likely ...

  15. Mutational analysis of the GLA gene in Mexican families with Fabry ...

    Indian Academy of Sciences (India)

    PRONAF CP 32315, Ciudad Juárez, Chihuahua, México. Abstract. Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal A deficiency leads to Gb3 ...

  16. Patterns of skin disease in a sample of the federal prison population: a retrospective chart review.

    Science.gov (United States)

    Gavigan, Geneviève; McEvoy, Alana; Walker, James

    2016-01-01

    Dermatology in vulnerable populations is under-researched. Our objective was to analyze the most commonly referred skin diseases affecting the Correctional Service Canada inmates in Ontario. An observational, cross-sectional, retrospective chart review of inmate patients seen from 2008 until 2013 was performed. Two groups of patients were included in the analysis: those assessed in-person, and those evaluated by e-consult. In the in-person patient group, the 3 most common diagnoses were acne, psoriasis and other superficial mycoses. For the e-consult group, the 3 most frequent diagnoses were acne, psoriasis and rosacea. There was a clear bias toward more inmates being seen in-person where the service was provided (Collins Bay Institution) than from other correctional institutions in Eastern Ontario. Most of the skin diseases that affected the incarcerated population studied were common afflictions, similar to those affecting the general population, which is in agreement with other studies. Future studies investigating skin diseases in male and female inmates across Canada would bestow more generalizable data.

  17. The role of interleukin 16 in the pathogenesis of selected skin diseases

    Directory of Open Access Journals (Sweden)

    Dorota Purzycka-Bohdan

    2014-03-01

    Full Text Available Interleukin-16 (IL-16 is a proinflammatory cytokine with a pleiotropic impact on cells of the immune system. Based on its biological properties including activation of CD4+ T cell migration and proliferation and also stimulation of proinflammatory cytokine synthesis, it could be postulated that IL-16 may play an important role in the pathogenesis of many diseases associated with immunological disturbances. Interleukin-16 acts as a chemoattractant not only for T CD4+ lymphocytes, but also for other cells, which have specific receptors on their surface. Moreover, IL-16 acts as a cell cycle regulator. This cytokine is produced by cells of the immune system, i.e. T CD4+ and T CD8+ lymphocytes, eosinophils, mast cells, dendritic cells and also fibroblasts and epithelial cells. The mechanism of action of IL-16 may suggest its significant role in the pathogenesis of skin disorders associated with an inflammatory reaction and infiltration composed of T CD4+ lymphocytes. Both this interleukin and anti-IL-16 antibodies may be useful in diagnosis and therapy of many skin diseases. Further detailed studies on the release of IL-16 and its biological functions are needed to reveal the role of this cytokine in the complex immunological process. The aim of this article is a current literature review of the relationship between IL-16 and the development of selected skin diseases: atopic dermatitis, systemic lupus erythematosus, bullous pemphigoid, cutaneous T-cell lymphomas and psoriasis.

  18. Puffy Skin Disease Is an Emerging Transmissible Condition in Rainbow Trout Oncorhynchus mykiss Walbaum.

    Science.gov (United States)

    Cano, Irene; Verner-Jeffreys, David W; van Aerle, Ronny; Paley, Richard K; Peeler, Edmund J; Green, Matthew; Rimmer, Georgina S E; Savage, Jacqueline; Joiner, Claire L; Bayley, Amanda E; Mewett, Jason; Hulland, Jonathan; Feist, Stephen W

    2016-01-01

    The transmission of puffy skin disease (PSD) to rainbow trout Oncorhynchus mykiss Walbaum was tested in the laboratory by conducting co-habitation challenges with puffy skin (PS)-affected fish (Trojans) collected from the field. Two separate challenges were conducted using Trojans sourced from two different sites and diploid (first trial) or triploid (second trial) naïve fish. PSD-specific clinical signs were observed in both groups of naïve fish, with 66% of the fish sampled during the challenges showing signs of varying severity. The first clinical features of PSD were presented as white oval skin patches on one or both flanks 15-21 days post-challenge (dpc). The extent of the lesions ranged from 10 to 90% of the body surface, depending on the severity of the lesion. Both the severity and number of affected fish increased during the challenge. Macroscopically, oedema of the skin and multifocal petechial haemorrhaging were observed towards the end of the trials. Abnormal fish behaviour consisting of "flashing" and excessive mucous production was noted from 15 dpc onwards. Fish with severe PSD lesions also displayed inappetence and associated emaciation. Rodlet cells were observed in 41% of the fresh skin scrapes analysed from the second trial. Histologically epidermal oedema was observed in 31% of the naive fish showing gross pathology, with additional 12% displaying epidermal hyperplasia, mostly observed at the end of the challenge. Other concomitant features of the PSD lesions in challenged fish were epithelial erosion and sloughing, and occasionally mild or focal inflammation. No consistent pathology of internal organs was observed. The parasites Ichthyophthirius multifiliis and Ichthyobodo necator were observed in skin samples of a proportion of naïve challenged fish and in Trojans but not in control fish. The presence of these and other known fish pathogens in the skin of PSD-fish was confirmed by high-throughput sequencing analysis. In summary, we have

  19. RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.

    Science.gov (United States)

    Zhu, Huiyuan; Lou, Fangzhou; Yin, Qianqian; Gao, Yuanyuan; Sun, Yang; Bai, Jing; Xu, Zhenyao; Liu, Zhaoyuan; Cai, Wei; Ke, Fang; Zhang, Lingyun; Zhou, Hong; Wang, Hong; Wang, Gang; Chen, Xiang; Zhang, Hongxin; Wang, Zhugang; Ginhoux, Florent; Lu, Chuanjian; Su, Bing; Wang, Honglin

    2017-05-01

    Retinoic acid inducible-gene I (RIG-I) functions as one of the major sensors of RNA viruses. DDX58 , which encodes the RIG-I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG-I by 5'ppp-dsRNA, its synthetic ligand, directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice. Repeated injections of IL-23 to the ears failed to induce IL-23 production and a full psoriasis-like skin phenotype, in either germ-free or RIG-I-deficient mice. RIG-I is also critical for a full development of skin inflammation in imiquimod (IMQ)-induced psoriasis-like mouse model. Furthermore, RIG-I-mediated endogenous IL-23 production was mainly confined to the CD11c + dendritic cells (DCs) via nuclear factor-kappa B (NF-κB) signaling, and stimulated RIG-I expression in an auto-regulatory feedback loop. Thus, our data suggest that the dysregulation in the antiviral immune responses of hosts through the innate pattern recognition receptors may trigger the skin inflammatory conditions in the pathophysiology of psoriasis. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  20. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    Directory of Open Access Journals (Sweden)

    Miri Kim

    2015-09-01

    Full Text Available Photodynamic therapy (PDT uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects.

  1. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    Science.gov (United States)

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  2. Chronic tattoo reactions cause reduced quality of life equaling cumbersome skin diseases

    DEFF Research Database (Denmark)

    Carlsen, Katrina Hutton; Serup, Jørgen

    2015-01-01

    Tattoos are often associated with mild complaints, but some people develop complications that may require medical treatment, and the burden of these events has hitherto been neglected. To understand the dimensions and the psychological symptomatology of adverse events both the sensory and affective...... applied to patients with chronic tattoo reactions, tattoo complaints and impact on quality of life that were comparable to patients presenting cumbersome dermatological disease such as psoriasis, eczema and pruritus, which often show widespread effects to the skin, were uncovered. In conclusion, chronic...... tattoo reactions should be ranked as a cumbersome dermatological disease and, accordingly, given priority attention and qualified treatment by the public health care system....

  3. Changes in skin test reactivity among adults with atopic disease: a 3-year prospective study

    DEFF Research Database (Denmark)

    Aslund, N.; Thomsen, S.F.; Molgaard, E.

    2008-01-01

    Background: Our knowledge about longtudinal predictors of atopy is limited. Objectives: To describe changes in skin test reactivity during a 3-year period in a sample of adolescents and adults with atopic disease and to identify factors of importance for these changes. Methods: From a sample of 1...... sensitizations, and 12 (4%) both gained and lost sensitizations. Female sex (odds ratio = 1.90 [1.02-3.57] P =.04) significantly predicted incidence of 1 or more sensitizations. Conclusions: Four of 10 adults with atopic disease will have changes in SPT status during a 3-year period, and most will gain new...

  4. Clinical significance of skin rash in dengue fever: A focus on discomfort, complications, and disease outcome.

    Science.gov (United States)

    Huang, Hsin-Wei; Tseng, Han-Chi; Lee, Chih-Hung; Chuang, Hung-Yi; Lin, Shang-Hung

    2016-07-01

    To assess whether the cutaneous features in patients with dengue fever are associated with abnormal blood biochemistry, complications, and poor disease outcome. Forty five patients with dengue fever were identified at a medical center in Kaohsiung, Taiwan, from September to November 2014. All cases were exclusively caused by type 1 dengue virus. Patients were classified into two groups, based on the presence or absence of skin rash, and their rash was subclassified into maculopapular, morbilliform, and petechial types. Clinical symptoms, laboratory data, disease outcome, and complications were compared between the two groups. Thirty two patients with dengue fever developed skin rash (SP group, n = 32) while the rest of 13 did not (SN group, n = 13). The patient numbers in the maculopapular, morbilliform, and petechial group were 4, 21, and 7, respectively. The SP group was younger (P = 0.001), experienced more pruritus (P = 0.008) and more swollen palms/soles (P = 0.015) than the SN group. However, the SN group had greater genital mucosa involvement (P = 0.008), higher platelet transfusion rate (P = 0.003), and lower hemoglobin and hematocrit levels (P = 0.030) than the SP group. Patients with morbilliform lesions had a higher incidence of palm/sole swelling, less genital mucosal involvement, and a lower platelet transfusion rate than did patients with maculopapular or petechial lesions. Cutaneous manifestations provide an important clue to dengue fever. In patients with dengue fever, those with skin rash tend to have itching and swelling of the palms/soles, however, those without skin rash tend to have more complications and poor disease outcomes. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  5. Systematic Review and Meta-Analysis of Human Skin Diseases Due to Particulate Matter

    Directory of Open Access Journals (Sweden)

    Le Thi Nhu Ngoc

    2017-11-01

    Full Text Available This study investigated the effects of particulate matter (PM on human skin diseases by conducting a systematic review of existing literature and performing a meta-analysis. It considered articles reporting an original effect of PM on human skin. From among 918 articles identified, 13 articles were included for further consideration after manual screening of the articles resulted in the exclusion of articles that did not contain data, review articles, editorials, and also articles in languages other than English. Random-effects models and forest plots were used to estimate the effect of PM on the skin by Meta-Disc analysis. According to people’s reports of exposure and negative skin effects (atopic dermatitis (AD, eczema, and skin aging, etc. due to air pollution, the summary relative risk (odds ratio of PM10 was determined to be 0.99 (95% confidence interval (CI 0.89–1.11 whereas PM2.5 was determined to be 1.04 (95% CI 0.96–1.12. Simultaneously, there was a different extent of impact between PM10 and PM2.5 on atopic dermatitis (AD for those of young age: the odds ratio of PM10 and PM2.5 were 0.96 (95% CI 0.83–1.11; I2 = 62.7% and 1.05 (95% CI 0.95–1.16; I2 = 46%, respectively. Furthermore, the results suggest an estimated increase of disease incidence per 10 μg/m3 PM of 1.01% (0.08–2.05 due to PM10 and 1.60% (0.45–2.82 due to PM2.5. Following the results, PM10 and PM2.5 are associated with increased risks of human skin diseases, especially AD, whose risk is higher in infants and school children. With its smaller size and a high concentration of metals, PM2.5 is more closely related to AD in younger people, compared to PM10.

  6. Characterization of skin blister fluids from children with Epstein-Barr virus-associated lymphoproliferative disease.

    Science.gov (United States)

    Wada, Taizo; Toma, Tomoko; Miyazawa, Hanae; Koizumi, Eiko; Shirahashi, Tetsujiro; Matsuda, Yusuke; Yachie, Akihiro

    2018-01-20

    Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids. © 2018 Japanese Dermatological Association.

  7. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins.

    Science.gov (United States)

    Zenz, Rainer; Eferl, Robert; Kenner, Lukas; Florin, Lore; Hummerich, Lars; Mehic, Denis; Scheuch, Harald; Angel, Peter; Tschachler, Erwin; Wagner, Erwin F

    2005-09-15

    Psoriasis is a frequent, inflammatory disease of skin and joints with considerable morbidity. Here we report that in psoriatic lesions, epidermal keratinocytes have decreased expression of JunB, a gene localized in the psoriasis susceptibility region PSORS6. Likewise, inducible epidermal deletion of JunB and its functional companion c-Jun in adult mice leads (within two weeks) to a phenotype resembling the histological and molecular hallmarks of psoriasis, including arthritic lesions. In contrast to the skin phenotype, the development of arthritic lesions requires T and B cells and signalling through tumour necrosis factor receptor 1 (TNFR1). Prior to the disease onset, two chemotactic proteins (S100A8 and S100A9) previously mapped to the psoriasis susceptibility region PSORS4, are strongly induced in mutant keratinocytes in vivo and in vitro. We propose that the abrogation of JunB/activator protein 1 (AP-1) in keratinocytes triggers chemokine/cytokine expression, which recruits neutrophils and macrophages to the epidermis thereby contributing to the phenotypic changes observed in psoriasis. Thus, these data support the hypothesis that epidermal alterations are sufficient to initiate both skin lesions and arthritis in psoriasis.

  8. The Neil Smith Memorial Lecture: John Laws Milton. The Founder of St John's Hospital for Diseases of the Skin.

    Science.gov (United States)

    Black, M M

    2003-01-01

    John Laws Milton, a 19th-Century surgeon, founded the St John's Hospital for Diseases of the Skin close to Leicester Square in London in 1863. This article reviews his single-minded effort to establish dermatology as a medical subspeciality and to create a proper skin diseases hospital. The review also details his many contributions to the medical and dermatological literature, including his insightful description of the pregnancy dermatosis, herpes (pemphigoid) gestationis.

  9. Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits.

    Science.gov (United States)

    Svarstad, Einar; Leh, Sabine; Skrunes, Rannveig; Kampevold Larsen, Kristin; Eikrem, Øystein; Tøndel, Camilla

    2018-01-01

    A previous case report found stereomicroscopic changes typical for Fabry disease in a kidney biopsy. This case series evaluates an expanded diagnostic capacity of the method. Bedside stereomicroscopy was performed in a cross-sectional prospective study of 31 consecutive enzyme-treated or treatment-naïve male (n = 14) and female Fabry disease patients. The burden of glomerular storage material was scored semiquantitatively on a visual analog scale (range 0-3) and a blinded comparison was done with a reference histologic method. Significant correlations (p Fabry disease was finally discarded. Bedside stereomicroscopy of kidney biopsies is an easily available, low-cost microscopy method handled by the clinician. The method carries a high diagnostic sensitivity for Fabry disease, reducing the risk of misdiagnosis in previously unknown cases. An expanded yield of the method is suggested, including the grading of the podocyte Gb3 burden and assessment of effectiveness of enzyme replacement therapy. We recommend the method as complementary to current standard histologic evaluation of Fabry kidney biopsies. © 2017 The Author(s) Published by S. Karger AG, Basel.

  10. Risk of Flood-Related Diseases of Eyes, Skin and Gastrointestinal Tract in Taiwan: A Retrospective Cohort Study.

    Science.gov (United States)

    Huang, Ling-Ya; Wang, Yu-Chun; Wu, Chin-Ching; Chen, Yi-Chun; Huang, Yu-Li

    2016-01-01

    Floods are known to cause serious environmental damage and health impacts. Studies on flood-related diseases have been primarily on individual events, and limited evidence could be drawn on potential health impacts from floods using large population data. This study used reimbursement records of one million people of the Taiwan National Health Insurance program to compare incident diseases of the eyes, skin and gastrointestinal (GI) tract associated with floods. Incidence rates for the selected diseases were calculated according to outpatient/emergency visit data. The incidence rates were evaluated by flood status: in 10 days before floods, during floods and within 10 days after the floods receded. Outpatient/emergency visit rates for the eye, skin and GI tract diseases were highest after floods and lowest during floods. Results from multivariate Poisson regression analyses showed that, when compared with the incidence in 10 days before floods, the incidence rate ratios (IRR) of diseases within 10 days after floods were 1.15 (95% confidence interval (CI) = 1.10-1.20) for eyes, 1.08 (95% C.I. = 1.05-1.10) for skin, and 1.11 (95% CI = 1.08-1.14) for GI tract, after controlling for covariates. All risks increased with ambient temperature. V-shaped trends were found between age and eye diseases, and between age and GI tract diseases. In contrast, the risk of skin diseases increased with age. In conclusion, more diseases of eyes, skin and GI tract could be diagnosed after the flood.

  11. Effects of the German skin cancer screening programme on melanoma incidence and indicators of disease severity.

    Science.gov (United States)

    Trautmann, F; Meier, F; Seidler, A; Schmitt, J

    2016-11-01

    In Germany a nationwide melanoma screening programme for adults aged ≥ 35 years was introduced in July 2008. Evidence on utilization and effects is limited. To examine the uptake and effects of the German nationwide screening programme. This analysis is based on pseudonymized outpatient routine data of a German health insurance company covering data of > 2 million individuals from Saxony for the years 2005-2012. Cases of melanoma and nonmelanoma skin cancer (NMSC) were identified using an algorithm based on the International Classification of Diseases, 10th Revision. Cross-sectional and longitudinal analyses were applied to determine the utilization of the screening programme and effects on skin cancer incidence and disease severity as a proxy for prognosis. Overall, 38·0% of eligible persons (≥ 35 years) were screened at least once between July 2008 and December 2012. The annual participation rate was 12·4%. Out of 533 393 persons screened, melanoma and NMSC were diagnosed in 0·3% and 2·5%, respectively. The 6-month melanoma incidence per 100 000 insured persons decreased from 12·8 before screening introduction (January to June 2008) to 10·2 after introduction (July to December 2008). NMSC incidence increased from 173·8 to 175·5 per 100 000. The numbers of screening participants receiving interferon alpha and/or being diagnosed with lymph node and/or distant metastasis (8·6%, 5·9%, 1·5%, respectively) were lower than in nonparticipants (11·2%, 8·5%, 3·5%). These differences were not significant. The results suggest that the introduction of a generic skin cancer screening programme in Germany was not associated with significant changes in incidence. No firm conclusions regarding the effects of skin cancer screening on prognosis can be drawn. Longer follow-up and linkage with clinical registry data are necessary to clarify the effect of screening participation on incidence and prognosis. © 2016 British Association of Dermatologists.

  12. Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands.

    Science.gov (United States)

    Meeuwis, K A P; de Hullu, J A; de Jager, M E A; Massuger, L F A G; van de Kerkhof, P C M; van Rossum, M M

    2010-12-01

    Psoriatic lesions may involve nearly all sites of the body. Involvement of the genital skin is frequently classified as part of intertriginous psoriasis without special awareness and treatment for this presentation of the disease. Gaining knowledge about the frequency of the involvement of genital skin in these patients will improve the overall care for patients with psoriasis. We studied the prevalence of genital psoriasis in the Netherlands and epidemiological characteristics of this specific presentation of the disease. Furthermore, we studied the relation between flexural and genital psoriasis. A self-administered questionnaire was sent to all 5300 members of the Dutch Psoriasis Society. Sociodemographic patient characteristics and disease-related data (such as localization of psoriatic lesions, involvement of the genitalia, age at onset of genital psoriasis and severity of genital psoriatic lesions) were collected and analysed. A response rate of 37% was achieved. Almost 46% of the responding patients with psoriasis, that is 16.5% of all potential responders (n = 5300), report genital involvement at some time during the course of their disease. The genitalia can become affected at any age. Many patients with current genital involvement (38%) do not have the flexural skin affected. A large part of patients with psoriasis suffer from genital psoriasis, which was not associated with flexural involvement in at least one third of them. More attention to the genital region is required in the current standard treatment of both male and female psoriatic patients at any age. © 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.

  13. Diagnosing skin disease in primary care: a qualitative study of GPs' approaches.

    Science.gov (United States)

    Rübsam, Marie-Luise; Esch, Maximilian; Baum, Erika; Bösner, Stefan

    2015-10-01

    Skin diseases are a common reason for consulting a GP. This regular occurrence happens despite most GPs' lack of knowledge and training in skin disease. We aimed to explore different diagnostic approaches of GPs in patients presenting with a dermatological problem. In addition, we aimed to identify strategies used by GPs to handle diagnostic uncertainty in these patients. We conducted interviews (20-40 minutes) with 14 GPs using a semi-structured guideline. Recalling encounters with patients with skin disease, GPs described their individual diagnostic strategies. Interviews were taped and transcribed verbatim. Qualitative analysis was conducted by two independent raters using a deductive-inductive approach. We identified several aspects of a complex decision-making process in GPs' diagnostic management of patients with dermatological problems. In the general diagnostic workup, GPs used a broad spectrum of different strategies such as spot diagnosis, stepwise refinement, pattern recognition trigger or test of treatment. GPs reduced diagnostic uncertainty through the identification of red flags, the application of the test of time, therapeutic trials and asking for further advice, including patient referral. GPs encounter a broad range of dermatological problems in their daily work using a variety of strategies in the workup of these patients. However, in a significant number of patients, there remains diagnostic uncertainty that is mainly reduced by specialist referral. Regular training in the diagnosis and treatment of common dermatological diseases should be offered to all GPs. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Primary care and pattern of skin diseases in a mediterranean island

    Directory of Open Access Journals (Sweden)

    Lyronis Ioannis

    2006-01-01

    Full Text Available Abstract Background In Greece where primary health care services are not fully developed, patients with simple or minor conditions have to attend to hospitals to be treated. We analysed the data of patients with cutaneous disorders attending the tertiary referral hospital on the Island of Crete, with the aim to identify the most common conditions that patients complain of, in order to define the areas where the education of General Practitioners in Dermatology must focus. Methods All patients attending the Dermatology ambulatory office in the Emergency Department of the University General Hospital of Heraklion from January 2003 to December 2003 were included in this retrospective analysis. The medical records of the patients (history, physical examination and laboratory investigations were analysed to ascertain the diagnosis and the management of cases. All patients were evaluated by qualified dermatologists. Results A total of 3715 patients attended the Dermatology Clinic. Most patients were young adults in the age group 21–40 years (38.4%, and the male to female ratio was 1 to 1.2. Allergic skin diseases, mostly dermatitis and urticaria (35.7% were the most common for attendance, followed by infectious diseases (26.1% and insect bites (10.2%. Inflammatory and autoimmune disorders accounted for 7.9% of the cases. Pruritus of unknown origin was diagnosed in 6.3% of patients. Skin tumors were detected in 2.7%. The management of the vast majority of cases (85.0% consisted of advice with or without a prescription, while only 4.8% of patients required admission. Conclusion Allergic and infectious skin diseases were the most common cutaneous diseases in patients attending this tertiary University hospital, while the management of most patients did not require specialised care. On the basis of the present data, the training of primary health care providers in Dermatology should emphasize these common conditions, with the aim of improving primary

  15. Quality of life in patients with skin diseases in central Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Abolfotouh MA

    2012-07-01

    Full Text Available Mostafa A Abolfotouh,1 Mohammad S Al-Khowailed,1 Wijdan E Suliman,1 Deema A Al-Turaif,1 Eman Al-Bluwi,2 Hassan S Al-Kahtani21King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, 2Dermatology Department, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi ArabiaBackground: Previous national and international studies of quality of life (QoL in patients with skin diseases have revealed different levels of QoL impairment. The aims of this study were to assess QoL in patients with skin diseases in central Saudi Arabia using the newly validated Skindex-16 instrument and to determine the association between QoL in patients with skin disease, sociodemographic data, and disease characteristics.Methods: A cross-sectional study was conducted in 283 adult patients who visited the outpatient dermatology clinics of King Abdulaziz Medical City, Riyadh, Saudi Arabia, over 3 months. The patients were interviewed using a pretested Arabic version of the Skindex-16 to measure the effect of skin disorders on their QoL during the previous 7 days. Patient characteristics, medical history, and clinical findings were collected. Multiple linear regression analyses were used to relate the demographic and clinical characteristics to the percentage mean QoL score, and P # 0.05 was considered to be statistically significant.Results: QoL was good in 69% of the respondents, with a total percent mean score of 31.80 ± 20.16. The emotional domain was the most affected (mean percentage score 44.27 ± 27.06, followed by symptoms (31.45 ± 28.40 and functioning (14.61 ± 22.75. After adjustment for potential confounders, poorer QoL was significantly associated with female gender (P = 0.03, older age (P = 0.003, rural origin (P = 0.03, positive family history of the same lesion(s (P = 0.01, shorter duration of ≤ 6 months (P = 0.02, generalized spread (P ≤ 0.02, and lack of isotretinoin treatment (P = 0.02.Conclusion: The

  16. Demonstration of characteristic skin surface contours of extramammary Paget's disease and parapsoriasis en plaque by image analysis of negative impression replicas.

    Science.gov (United States)

    Kikuchi, Katsuko; Aiba, Setsuya; O'Goshi, Ken-ichiro; Yanai, Motohiro; Takahashi, Motoji; Kasai, Hidefumi; Tagami, Hachiro

    2002-10-01

    The surface contours of lesional skin of certain skin diseases, such as parapsoriasis en plaque (PEP) and extramammary Paget's disease (EMPD), in which there is a massive infiltration by non-epidermal cells, looks somewhat different from that of the adjacent normal skin, needless to state that they are apparently different from that of ordinary chronic inflammatory dermatoses where we found acanthotic epidermis accompanied by hyperkeratosis. We attempted to objectively characterize these unique skin surface changes qualitatively and quantitatively using non-invasive methods. Negative impression replicas were taken from the lesional skin of patients with EMPD or PEP as well as from the adjacent uninvolved skin. The findings were confirmed histologically. The replicas were examined by using computerized image analysis. Several parameters were analyzed that correlate with the changes in the anisotropy of the skin furrows (VC1), average skin roughness (KSD), average length of skin furrows (LEN), and number of skin furrows (NUM). There were significant decreases in KSD and NUM in EMPD, indicating a smoother skin surface in the lesional skin than in the adjacent normal skin. In contrast, the PEP lesion had an increase in VC1 and LEN and a decrease in NUM, which suggests larger skin ridges in the lesional skin than in the uninvolved skin. Thus the unique skin surface of the cutaneous disorders accompanied by epidermal invasion by non-epidermal cells, such as EMPD and PEP, was characterized both qualitatively and quantitatively using computerized image analysis of negative impression replicas.

  17. Neurological aspects of Gaucher and Fabry disease

    NARCIS (Netherlands)

    Biegstraaten, M.

    2011-01-01

    Momenteel zijn er meer dan vijftig stapelingsziekten bekend, waarvan de ernst zeer uiteen loopt. Sommige aandoeningen worden gekenmerkt door ernstige mentale retardatie, neurologische problemen en overlijden op kinderleeftijd; andere vormen hebben nauwelijks een lagere levensverwachting. Ook in de

  18. Molecular characterisation of lumpy skin disease virus and sheeppox virus based on P32 gene

    Directory of Open Access Journals (Sweden)

    P.M.A.Rashid

    2017-06-01

    Full Text Available Lumpy skin disease virus (LSDV and sheeppox virus (SPV have a considerable economic impact on the cattle and small ruminant industry. They are listed in group A of contagious disease by the World Organization for Animal Health (OIE. This study addressed molecular characterisation of first LSDV outbreak and an endemic SPV in Kurdistan region of Iraq based on P32 gene. The results indicated that P32 gene can be successfully used for diagnosis of LSDV. The phylogenic and molecular analysis showed that there may be a new LSDV isolate circulating in Kurdistan which uniquely shared the same characteristic amino acid sequence with SPV and GPV, leucine at amino acid position 51 in P32 gene as well as few genetically distinct SPV causing pox disease in Kurdistan sheep. This study provided sequence information of P32 gene for several LSDV isolates, which positively affects the epidemiological study of Capripoxvirus

  19. Evaluation of structured patient education in occupational skin diseases: a systematic assessment of the disease-specific knowledge.

    Science.gov (United States)

    Wilke, Annika; Gediga, Kathrin; John, Swen Malte; Wulfhorst, Britta

    2014-11-01

    The aim of this study was to evaluate the effectiveness of patient education in occupational skin diseases (OSD) regarding changes of the disease-specific knowledge. One hundred and five patients participated in structured patient education as part of an interdisciplinary outpatient prevention measure. In a prospective one-group pre-post-design, the disease-specific knowledge was assessed with the validated "Occupational Skin Diseases Knowledge Questionnaire" (OSD-KQ) before (T0) and after the intervention (T1). A subcohort (n = 68) was examined 2-3 months later (T2). The mean OSD-KQ score significantly improved from 38.5 (59.2% of correct answers, T0) to 55.6 (85.5% of correct answers, T1). A pronounced heterogeneity was observed among the participants regarding the pre-interventional knowledge (10.8-84.6% of correct answers, T0) and the individual knowledge gain. Patients who worked in health-related occupations scored significantly higher. Age and sex did not influence the knowledge. In a subcohort, a significantly improved disease-specific knowledge of 52.3 (80.5% of correct answers) could still be found 2-3 months after the intervention (T2). Structured patient education significantly improves the disease-specific knowledge in patients with OSD. The study indicates not only positive short- but also sustainable long-term effects on the knowledge gain. The OSD-KQ can serve as a tool to evaluate and improve patient education. Health educators need to be aware of the heterogeneity regarding the participants' knowledge and take this into account during educational practice. Additional counseling may be necessary to meet the individual learners' needs.

  20. The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy.

    Science.gov (United States)

    Malakouti, Mona; Brown, Gabrielle E; Leon, Argentina; Wang, Eva; Naegeli, April N; Edson-Heredia, Emily; Levin, Ethan; Koo, John Y M

    2017-06-01

    Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.

  1. [Epidemiology of skin diseases in 10,000 patients of pediatric age].

    Science.gov (United States)

    Ruiz-Maldonado, R; Tamayo Sánchez, L; Velázquez, E

    1977-01-01

    Ten thousand new patients were seen between January 1971 and January 1975 at the Department of Pediatric Dermatology, "Hospital del Niño IMAN" in Mexico City. The patients were between 0 and 18 years old. They represented 10.4% of the entire pediatric population attending the general out-patient clinic of the hospital. The results of our study showed no significant difference among the sexes of patients. The highest proportion of patients in the sample were under one year of age. The most frequently observed groups of dermatoses were: parasitic, cutaneous reactions, viral and bacterial. The ten diseases most frequently observed were: papular urticaria (16.3%); atopic dermatitis (12.9%); scabies (10.4%); viral warts (8.4%); impetigo (6.8%); pitiriasis alba (6.6%); vitiligo (2.6%); acne (2.5%); dermatophytosis (2.4%) and numular eczema (2.3%). The 20 skin diseases most frequently recorded accounted for 85.8% of the sample. The ten most frequent skin diseases in each group of age were also recorded. The monthly and annual frequency for the more frequent dermatoses was studied. The present study provides epidemiological information for a rational development of programs on care, education and investigation in pediatric dermatology in Mexico.

  2. [Photodynamic diagnosis and therapy in dermatology. Experience with use of TPPS4 in skin diseases].

    Science.gov (United States)

    Jirásková, M; Jirásek, L; Stork, J; Vosmík, F; Jirsa, M

    2003-08-01

    Some skin lesions e.g. basal cell carcinomas are sometimes difficult to remove completely and frequent relapses can develop after their imperfect removal. In case the patient refuses to undergo a radical surgical intervention, more painful alternative like cryotherapy comes into consideration as a method of tumour destruction. Not even such a procedure does guarantee complete destruction of all tumour cells. During the last years new diagnostics and therapeutic methods like photodynamic diagnostic and photodynamic therapy have been developed and they became subjects of our interest. Lesions were treated with photosensitizer (meso-tetra-para-sulphonato-phenyl-porfine-TPPS4) administered in an injection or in the ointment under occlusion. Six to 24 hours later we checked presence of photosensitizer in the lesions and in positive cases we irradiated the lesions with light of suitable wave length (630 nm). PDD and PDT were used for diagnostics and treatment of different dermatoses (basal cell carcinomas, malignant melanoma metastases, verrucae vulgares, keratoacanthomas, solitary lesions of T lymphoma--mycosis fungoides, m. Bowen, psoriasis vulgaris, pustulosis palmoplantaris, solar keratoma) with very good medical and cosmetic effect. Results are presented in the table. Authors do not consider the PDT to be the only and miraculous method relevant to treatment of all skin tumours or other skin diseases. They are of the opinion that this technique, when properly used, can extend the scale of therapeutic methods. The advantage of PDT is its selectivity, good tolerance and generally good cosmetic effect.

  3. Dermatologist-diagnosed skin diseases among immigrant Latino poultry processors and other manual workers in North Carolina, USA.

    Science.gov (United States)

    Pichardo-Geisinger, Rita; Muñoz-Ali, Diana; Arcury, Thomas A; Blocker, Jill N; Grzywacz, Joseph G; Mora, Dana C; Chen, Haiying; Schulz, Mark R; Feldman, Steve R; Quandt, Sara A

    2013-11-01

    Immigrant Latino workers represent an expanding workforce in rural areas of the USA, where their employment is concentrated in occupations such as poultry processing that entail chemical, infectious, and mechanical skin exposures. Occupation-related skin illnesses in this vulnerable population are not well characterized. This study was designed to describe the prevalences of skin diseases among immigrant Latino poultry processors and other manual workers in North Carolina. Community-based sampling was used to recruit 742 immigrant Latino workers, 518 of whom underwent a physical examination supervised by a board-certified dermatologist. The presence or absence of skin disease on the face, neck, arms, hands, and feet was recorded. Workers ranged in age from 18 years to 68 years. Slightly over half of the sample were male (52.6%). Poultry workers represented 55.8% of the study sample. Infectious skin diseases were the most common diagnosis, present in 52.3% of workers. Inflammatory skin diseases were present in 28.2% and pigmentary disorders in 21.8% of workers. The most common skin conditions were tinea pedis (37.6%), onychomycosis (31.9%), scars (13.7%), acne (11.8%), and melasma (9.3%). Age, sex, first language, and work as a poultry processor accounted in part for the prevalence of these diseases. Several skin diseases are highly prevalent in immigrant Latino workers and may relate to work environment. These may impair the quality of life of these workers and predispose them to further illness. © 2013 The International Society of Dermatology.

  4. Evidence-based Danish guidelines for the treatment of Malassezia-related skin diseases

    DEFF Research Database (Denmark)

    Hald, Marianne; Arendrup, Maiken C; Svejgaard, Else L

    2015-01-01

    Internationally approved guidelines for the diagnosis and management of Malassezia-related skin diseases are lacking. Therefore, a panel of experts consisting of dermatologists and a microbiologist under the auspices of the Danish Society of Dermatology undertook a data review and compiled...... guidelines for the diagnostic procedures and management of pityriasis versicolor, seborrhoeic dermatitis and Malassezia folliculitis. Main recommendations in most cases of pityriasis versicolor and seborrhoeic dermatitis include topical treatment which has been shown to be sufficient. As first choice....... Maintenance therapy is often necessary to prevent relapses. In the treatment of Malassezia folliculitis systemic antifungal treatment is probably more effective than topical treatment but a combination may be favourable....

  5. Ethnomedicobotany of Uttara Kannada District in Karnataka, India--plants in treatment of skin diseases.

    Science.gov (United States)

    Harsha, V H; Hebbar, S S; Shripathi, V; Hegde, G R

    2003-01-01

    Present paper deals with the herbal remedies for skin diseases in Uttara Kannada district of Karnataka--a Southern State in India, which is located in the hearts of Western Ghats. In an ethnobotanical exploration of this area 52 herbal preparations from 31 plants belonging to 21 families have been recorded. This also includes 17 new claims to the ethnomedical knowledge. The parts used and methods of preparation are discussed along with the family and local name for all the plants. Copyright 2002 Elsevier Science Ireland Ltd.

  6. A review of nicotinamide: treatment of skin diseases and potential side effects.

    Science.gov (United States)

    Rolfe, Heidi M

    2014-12-01

    Nicotinamide, also known as niacinamide, is the amide form of vitamin B3. It is a precursor of essential coenzymes for numerous reactions in the body including adenosine triphosphate (ATP) production. Nicotinic acid, also known as niacin, is converted into nicotinamide in the body. The use of topical nicotinamide in the treatment of acne vulgaris; melasma; atopic dermatitis; rosacea; and oral nicotinamide in preventing nonmelanoma skin cancer is discussed. The possible side effects and consequences of excessive nicotinamide exposure are reviewed, including suggestions nicotinamide might have a role in the development of diabetes, Parkinson's disease, and liver damage. © 2014 Wiley Periodicals, Inc.

  7. Imperfect pathogen detection from non-invasive skin swabs biases disease inference

    Science.gov (United States)

    DiRenzo, Graziella V.; Grant, Evan H. Campbell; Longo, Ana; Che-Castaldo, Christian; Zamudio, Kelly R.; Lips, Karen

    2018-01-01

    1. Conservation managers rely on accurate estimates of disease parameters, such as pathogen prevalence and infection intensity, to assess disease status of a host population. However, these disease metrics may be biased if low-level infection intensities are missed by sampling methods or laboratory diagnostic tests. These false negatives underestimate pathogen prevalence and overestimate mean infection intensity of infected individuals. 2. Our objectives were two-fold. First, we quantified false negative error rates of Batrachochytrium dendrobatidis on non-invasive skin swabs collected from an amphibian community in El Copé, Panama. We swabbed amphibians twice in sequence, and we used a recently developed hierarchical Bayesian estimator to assess disease status of the population. Second, we developed a novel hierarchical Bayesian model to simultaneously account for imperfect pathogen detection from field sampling and laboratory diagnostic testing. We evaluated the performance of the model using simulations and varying sampling design to quantify the magnitude of bias in estimates of pathogen prevalence and infection intensity. 3. We show that Bd detection probability from skin swabs was related to host infection intensity, where Bd infections disease systems, particularly those with similar objectives, biology, and sampling decisions. 4. Uncertainty in pathogen detection is an inherent property of most sampling protocols and diagnostic tests, where the magnitude of bias depends on the study system, type of infection, and false negative error rates. Given that it may be difficult to know this information in advance, we advocate that the most cautious approach is to assume all errors are possible and to accommodate them by adjusting sampling designs. The modeling framework presented here improves the accuracy in estimating pathogen prevalence and infection intensity.

  8. Malassezia yeasts produce a collection of exceptionally potent activators of the Ah (dioxin) receptor detected in diseased human skin.

    Science.gov (United States)

    Magiatis, Prokopios; Pappas, Periklis; Gaitanis, George; Mexia, Nikitia; Melliou, Eleni; Galanou, Maria; Vlachos, Christophoros; Stathopoulou, Konstantina; Skaltsounis, Alexios Leandros; Marselos, Marios; Velegraki, Aristea; Denison, Michael S; Bassukas, Ioannis D

    2013-08-01

    Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10- to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients' extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin- and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development.

  9. Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4: An Emerging Biomarker for Skin Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Kenji Izuhara

    2018-04-01

    Full Text Available Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4, members of the ovalbumin serpin (ov-serpin/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various kinds of squamous cell carcinomas. Recently, our understanding of the underlying mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover, it has been shown that SCCA1/2 are involved in the pathogenesis of several inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD. IL-22 and IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13, signature cytokines of type 2 inflammation, both of which are positively correlated with the pathogenesis of psoriasis and allergic diseases, respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or keratinocytes, leading to high expression of SCCA1/2 in these diseases. Based on these findings, several trials have been performed to examine the potential of applying SCCA1/2 to biomarkers for these diseases. The findings show that SCCA2 is useful to aid diagnosis, estimate clinical severity and disease type, and assess responses to treatment in psoriasis and AD. These results suggest that SCCA2 has emerged as a novel biomarker for skin inflammatory diseases.

  10. Association Between Allergic Diseases and Food Allergens Based on Skin Prick Test in Bushehr Province

    Directory of Open Access Journals (Sweden)

    Saman Keshvari

    2017-04-01

    Full Text Available Background: The Frequency of allergic diseases is growing in recent years. Identification of frequency of food allergens in different areas play an important role in diagnosis and treatment of these diseases. The aim of this study was to determine frequency and association of common food allergens in patients with allergic diseases based on Skin Prick Test in Bushehr province. Material and Methods: In this descriptive cross-sectional study, 1100 patients were enrolled with allergic diseases which had a sensitivity to at least one allergen.  This test was carried out with 21 common food allergens extract. Results: In all patients, association between the severity of the reaction prick allergy test and severity of allergic diseases with shrimp, cow's Milk and peanuts were (P= 0.01, (P= 0.02 and (P=0.04 respectively. In this study, the frequency of allergic rhinitis, asthma, chronic and acute urticaris and atopic eczema were 54.2%, 23%, 12.4%, 4.1% and 12%, respectively. While the the most common food allergens were peanuts (46.6%, egg yolk (43.1% and shrimp (42% respectively. Conclusion: This study indicated that food allergens such as shrimp, cow's Milk and peanuts have a greater role in severity of allergic diseases and this food allergens showed the highest frequency in patients.

  11. Immunological, hematological, biochemical, and histopathological studies on cows naturally infected with lumpy skin disease

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    Ahmed N. F. Neamat-Allah

    2015-09-01

    Full Text Available Aim: Lumpy skin disease (LSD is an infectious viral disease of cattle caused by an LSD virus (LSDV of the family Poxviridae characterized by skin nodules covering all parts of the body. There are many aspects of LSD remaining unknown, thus immunological, hematological, and biochemical parameters were estimated. Materials and Methods: During an outbreak of LSD in Sharkia governorate from Egypt, 211 cows aging (2-4 years were examined clinically for the presence of LSD lesions during the period from July to November 2014. A total of 134 cows from those showed lesions suspected to be LSD. Results: Recorded clinical signs were pyrexia with the development of skin nodules of varying sizes which ranged from a few to several hundred sometimes coalesced together enlargements of the peripheral lymph nodes. Intracytoplasmic inclusion bodies were noticed in the histopathological examination. Immunological studies revealed a significant decrease of lymphocyte transformation rate, phagocytic % and killing % which was marked within 2 weeks postinfection. LSD resulted in non-significant in hemogram in 1st-2nd day post-infection while a macrocytic hypochromic anemia within 10-14th days post-infection. Leucopenia and lymphopenia were recorded 1st-2nd day post-infection while at 10-14th showed granulocytic leukocytosis. Biochemical analysis revealed hypoproteinemia, hypoalbuminemia, and hyperglobulinemia especially gamma globulins. The significant increase in serum alanine aminotransferase, aspartate aminotransferase activities, creatinine level, blood urea nitrogen and creatine phosphokinase Conclusion: LSDV infected cows in early stages revealed leucopenia. Immunosuppressive effect was pronounced later. In late stage revealed hemolytic anemia, leukocytosis and increase of serum CK, which could aid in diagnosis. Disturbance in liver and kidney function tests have been occurred.

  12. Imperfect pathogen detection from non-invasive skin swabs biases disease inference

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    DiRenzo, Graziella V.; Grant, Evan H. Campbell; Longo, Ana; Che-Castaldo, Christian; Zamudio, Kelly R.; Lips, Karen

    2018-01-01

    1. Conservation managers rely on accurate estimates of disease parameters, such as pathogen prevalence and infection intensity, to assess disease status of a host population. However, these disease metrics may be biased if low-level infection intensities are missed by sampling methods or laboratory diagnostic tests. These false negatives underestimate pathogen prevalence and overestimate mean infection intensity of infected individuals. 2. Our objectives were two-fold. First, we quantified false negative error rates of Batrachochytrium dendrobatidis on non-invasive skin swabs collected from an amphibian community in El Copé, Panama. We swabbed amphibians twice in sequence, and we used a recently developed hierarchical Bayesian estimator to assess disease status of the population. Second, we developed a novel hierarchical Bayesian model to simultaneously account for imperfect pathogen detection from field sampling and laboratory diagnostic testing. We evaluated the performance of the model using simulations and varying sampling design to quantify the magnitude of bias in estimates of pathogen prevalence and infection intensity. 3. We show that Bd detection probability from skin swabs was related to host infection intensity, where Bd infections < 10 zoospores have < 95% probability of being detected. If imperfect Bd detection was not considered, then Bd prevalence was underestimated by as much as 16%. In the Bd-amphibian system, this indicates a need to correct for imperfect pathogen detection caused by skin swabs in persisting host communities with low-level infections. More generally, our results have implications for study designs in other disease systems, particularly those with similar objectives, biology, and sampling decisions. 4. Uncertainty in pathogen detection is an inherent property of most sampling protocols and diagnostic tests, where the magnitude of bias depends on the study system, type of infection, and false negative error rates. Given that it may

  13. Intelligent Diagnostic Assistant for Complicated Skin Diseases through C5’s Algorithm

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    Jeddi, Fatemeh Rangraz; Arabfard, Masoud; Kermany, Zahra Arab

    2017-01-01

    Introduction: Intelligent Diagnostic Assistant can be used for complicated diagnosis of skin diseases, which are among the most common causes of disability. The aim of this study was to design and implement a computerized intelligent diagnostic assistant for complicated skin diseases through C5’s Algorithm. Method: An applied-developmental study was done in 2015. Knowledge base was developed based on interviews with dermatologists through questionnaires and checklists. Knowledge representation was obtained from the train data in the database using Excel Microsoft Office. Clementine Software and C5’s Algorithms were applied to draw the decision tree. Analysis of test accuracy was performed based on rules extracted using inference chains. The rules extracted from the decision tree were entered into the CLIPS programming environment and the intelligent diagnostic assistant