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Sample records for acute hereditary angioedema

  1. Hereditary angioedema.

    Science.gov (United States)

    Bracho, Francisco A

    2005-11-01

    Hereditary angioedema is an autosomal-dominant deficiency of C1 inhibitor--a serpin inhibitor of kallikrein, C1r, C1s, factor XII, and plasmin. Quantitative or qualitative deficiency of C1 inhibitor leads to the generation of vasoactive mediators, most likely bradykinin. The clinical syndrome is repeated bouts of nonpruritic, nonpitting edema of the face, larynx, extermities, and intestinal viscera. Recently, investigators, physicians, and industry have demonstrated a renewed interest in the biology and treatment of hereditary angioedema. Investigators have generated a C1INH-/- mouse model that has demonstrated the importance of the contact activation system for hereditary angioedema-related vascular permeability. An interactive database of mutations is available electronically. Investigators have continued exploration into mRNA/protein levels. The proceedings of a recent workshop have been impressive in the scope and depth. Clinicians have produced consensus documents and expert reviews. The pharmaceutical industry has initiated clinical trails with novel agents. Hereditary angioedema is often misdiagnosed and poorly treated. Diagnosis requires careful medical and family history and the measurement of functional C1 inhibitor and C4 levels. Attenuated androgens, anti-fibrinolytics, and C1 inhibitor concentrates are used for long-term and preprocedure prophylaxis, but have significant drawbacks. C1 inhibitor concentrates and fresh frozen plasma are available for acute intervention. The mainstays of supportive care are airway monitoring, pain relief, hydration, and control of nausea. New agents such as recombinant C1 inhibitor, kallikrein inhibitors, and bradykinin inhibitors may offer safer and more tolerable treatments.

  2. Hereditary Angioedema

    Directory of Open Access Journals (Sweden)

    A.P. Volokha

    2014-03-01

    Full Text Available Hereditary angioedema — a rare disease caused by a congenital deficiency of C1-inhibitor. Clinical manifestations of the disease — recurrent episodes of angioedema, which manifest in childhood or adolescence, more often localized in the subcutaneous tissue (limbs, face, trunk, genitals or submucosa (intestine, larynx. Swellings of the larynx are potentially harmful to the patient’s life. Early detection enables to carry out timely appropriate treatment and prevention of angioedema. The paper presents a case of hereditary angioedema with manifestation in early childhood. The case study demonstrates the complexity of diagnosis and treatment of hereditary angioedema.

  3. Hereditary angioedema

    Science.gov (United States)

    ... disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE ... aunt, uncle, or grandparent. Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE ...

  4. Hereditary angioedema

    DEFF Research Database (Denmark)

    Peterson, M P; Bygum, A

    2016-01-01

    We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims of this re......We report a 64-year-old man who suffered from recurrent visible swelling attacks since the age of 20 as well as episodes with severe upper airway edema, resulting in 4 emergency tracheotomies. Eventually after 44 years he was diagnosed with hereditary angioedema (HAE) type II. The aims...

  5. Understanding Hereditary Angioedema

    Science.gov (United States)

    ... Allergy Library ▸ Understanding Hereditary Angioedema Share | Understanding Hereditary Angioedema This article has been reviewed by Thanai Pongdee, MD, FAAAAI Hereditary Angioedema (HAE) is a rare genetic condition. People with ...

  6. Hereditary Angioedema

    DEFF Research Database (Denmark)

    Abdel-Karim, Omar; Dizdarevic, Adis; Bygum, Anette

    2014-01-01

    of life. Most studies have been conducted in adults. We report a 13-year-old boy who quickly learned self-administration, which resulted in reduced frequency and severity of attacks. The aim of this report is to emphasize that children should be considered for self-administration training......Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality...

  7. Genetics Home Reference: hereditary angioedema

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Hereditary angioedema Hereditary angioedema Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hereditary angioedema is a disorder characterized by recurrent episodes of ...

  8. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack...... of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  9. Hereditary Angioedema in Childhood

    DEFF Research Database (Denmark)

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history...

  10. Hereditary angioedema in women

    Directory of Open Access Journals (Sweden)

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  11. [Hereditary angioedema: strange cause of abdominal pain].

    Science.gov (United States)

    Salas-Lozano, Nereo Guillermo; Meza-Cardona, Javier; González-Fernández, Coty; Pineda-Figueroa, Laura; de Ariño-Suárez, Mauricio

    2014-01-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance characterized by sudden attacks of peripheral swelling. Patients also commonly have episodic swelling of the wall of hollow viscera, including the bowel. We present a 33-year-old previously healthy male with a complaint of acute-onset intense abdominal pain localized in the epigastrium. Pain irradiated to the right lower quadrant and was associated with five episodes of vomiting. Computed tomography showed thickening of the duodenal wall with liquid in the subphrenic space. Complementary laboratory tests showed low C4 complement levels (5.5 mg/dl) and 30% complement C1 inhibitor activity. Hereditary angioedema is caused by a deficiency (type I) or dysfunction (type II) in complement C1 inhibitor. Abdominal associated with angioedema may manifest as severe acute-onset abdominal pain or as moderately severe chronic recurrent abdominal pain. Two medications are currently FDA-approved for the treatment of these patients.

  12. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Busse, Paula; Bygum, Anette; Edelman, Jonathan

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typ...

  13. Safety and efficacy of icatibant self-administration for acute hereditary angioedema

    Science.gov (United States)

    Boccon-Gibod, I; Bouillet, L

    2012-01-01

    We evaluated the efficacy and safety of icatibant self-administration in 15 patients with hereditary angioedema (HAE) types I or III, for 55 acute attacks (mostly severe or very severe). Icatibant self-administration was generally effective: first symptom improvement occurred in 5 min–2 h (HAE type I; n = 17) and 8 min–1 h (HAE type III; n = 9) for abdominal attacks and 5–30 min (HAE type I; n = 4) and 10 min–12 h (HAE type III; n = 6) for laryngeal attacks. Complete symptom resolution occurred in 15 min–19 h (HAE type I; n = 8) and 15 min–48 h (HAE type III; n = 9) for abdominal attacks and 5–48 h (HAE type I; n = 3) and 8–48 h (HAE type III; n = 5) for laryngeal attacks. No patient required emergency hospitalization. The only adverse events were mild, spontaneously resolving injection site reactions. Patients reported that carrying icatibant with them gave them greater confidence in managing their condition. PMID:22519593

  14. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  15. Optimum Use of Acute Treatments for Hereditary Angioedema: Evidence-Based Expert Consensus

    Science.gov (United States)

    Longhurst, Hilary

    2018-01-01

    Acute treatment of hereditary angioedema due to C1 inhibitor deficiency has become available in the last 10 years and has greatly improved patients’ quality of life. Two plasma-derived C1 inhibitors (Berinert and Cinryze), a recombinant C1 inhibitor (Ruconest/Conestat alpha), a kallikrein inhibitor (Ecallantide), and a bradykinin B2 receptor inhibitor (Icatibant) are all effective. Durably good response is maintained over repeated treatments and several years. All currently available prophylactic agents are associated with breakthrough attacks, therefore an acute treatment plan is essential for every patient. Experience has shown that higher doses of C1 inhibitor than previously recommended may be desirable, although only recombinant C1 inhibitor has been subject to full dose–response evaluation. Treatment of early symptoms of an attack, with any licensed therapy, results in milder symptoms, more rapid resolution and shorter duration of attack, compared with later treatment. All therapies have been shown to be well-tolerated, with low risk of serious adverse events. Plasma-derived C1 inhibitors have a reassuring safety record regarding lack of transmission of virus or other infection. Thrombosis has been reported in association with plasma-derived C1 inhibitor in some case series. Ruconest was associated with anaphylaxis in a single rabbit-allergic volunteer, but no further anaphylaxis has been reported in those not allergic to rabbits despite, in a few cases, prior IgE sensitization to rabbit or milk protein. Icatibant is associated with high incidence of local reactions but not with systemic effects. Ecallantide may cause anaphylactoid reactions and is given under supervision. For children and pregnant women, plasma-derived C1 inhibitor has the best evidence of safety and currently remains first-line treatment. PMID:29594115

  16. Pediatric Hereditary Angioedema as a Cause of Acute Compartment Syndrome of the Hand and Forearm: A Case Report.

    Science.gov (United States)

    Venditto, Chelsea; Jager, Zachary; LoGiudice, John; Matloub, Hani

    2017-05-01

    Compartment syndrome of the upper extremity is a surgical emergency that, when left untreated, can have dire consequences. Its causes are numerous, one of which is the uncommon entity hereditary angioedema, an autosomal dominant disease resulting in edema in a variety of potential locations, including the extremities. This is only the second time hereditary angioedema has been mentioned in the literature as a cause of compartment syndrome. We present a case of hereditary angioedema leading to hand and forearm compartment syndrome in a 13-year-old pediatric patient. Diagnosis of hereditary angioedema was made by our Rheumatology colleagues with physical exam and a thorough history, and confirmed by laboratory studies. Our patient presented with compartment syndrome of the hand and forearm and underwent hand and volar forearm fasciotomies. She was subsequently worked up for hereditary angioedema with laboratory results confirming the diagnosis. She was discharged after a 5-day hospitalization with prophylactic C1-inhibitor therapy. Hereditary angioedema is a rare but known cause of compartment syndrome of the upper extremity, and must be considered when patients present with compartment syndrome of unknown etiology. This disease can be diagnosed by laboratory studies and symptoms can be controlled with medical therapy.

  17. Disease expression in women with hereditary angioedema

    DEFF Research Database (Denmark)

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle

    2008-01-01

    OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills......-sensitive phenotype for some patients. CONCLUSION: The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management....

  18. New treatments addressing the pathophysiology of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Davis Alvin E

    2008-04-01

    Full Text Available Abstract Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema

  19. Burden of Illness in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen

    2015-01-01

    The objective of the Hereditary Angioedema Burden of Illness Study in Europe was to assess the real-world experience of HAE from the patient perspective. Based on open-ended qualitative interviews with 30 patients from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact...

  20. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  1. Epidemiology of Non-hereditary Angioedema

    DEFF Research Database (Denmark)

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...

  2. Clinical Pattern and Acute and Long-term Management of Hereditary Angioedema Due to C1-Esterase Inhibitor Deficiency.

    Science.gov (United States)

    Gómez-Traseira, C; Pérez-Fernández, E; López-Serrano, M C; García-Ara, M C; Pedrosa, M; López-Trascasa, M; Caballero, T

    2015-01-01

    Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.

  3. Management of hereditary angioedema: 2010 Canadian approach

    Science.gov (United States)

    2010-01-01

    C1-inhibitor (C1-INH) deficiency is a rare blood disorder resulting in angioedema attacks that are debilitating and may be life-threatening. Prophylaxis and therapy of events has changed since our first Canadian Consensus Conference on the diagnosis, therapy and management of HAE. We have formed the Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'Angioédème Héréditaire (RCAH) - http://www.haecanada.com to advance care of patients with this disorder in Canada. We here present a review of management of HAE in Canada. PMID:20667123

  4. Recombinant C1-Inhibitor Effects on Coagulation and Fibrinolysis in Patients with Hereditary Angioedema

    NARCIS (Netherlands)

    Relan, Anurag; Bakhtiari, Kamran; van Amersfoort, Edwin S.; Meijers, Joost C. M.; Hack, C. Erik

    2012-01-01

    Background: Recombinant human C1-inhibitor (rhC1INH; Ruconest (R)) has been developed for treatment of acute angioedema attacks in patients with hereditary angioedema (HAE) due to heterozygous deficiency of C1INH. Previous reports suggest that administration of plasma-derived C1INH products may be

  5. Benefits and risks of danazol in hereditary angioedema

    DEFF Research Database (Denmark)

    Bork, Konrad; Bygum, Anette; Hardt, Jochen

    2008-01-01

    BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine....... In the other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities......, headache, depression, and/or liver adenomas) occurred in 93 of the 118 patients and led to discontinuation of danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in patients with frequent and severe attacks of HAE. Because the risk of adverse effects is high, close monitoring...

  6. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

    Science.gov (United States)

    Cicardi, Marco; Banerji, Aleena; Bracho, Francisco; Malbrán, Alejandro; Rosenkranz, Bernd; Riedl, Marc; Bork, Konrad; Lumry, William; Aberer, Werner; Bier, Henning; Bas, Murat; Greve, Jens; Hoffmann, Thomas K; Farkas, Henriette; Reshef, Avner; Ritchie, Bruce; Yang, William; Grabbe, Jürgen; Kivity, Shmuel; Kreuz, Wolfhart; Levy, Robyn J; Luger, Thomas; Obtulowicz, Krystyna; Schmid-Grendelmeier, Peter; Bull, Christian; Sitkauskiene, Brigita; Smith, William B; Toubi, Elias; Werner, Sonja; Anné, Suresh; Björkander, Janne; Bouillet, Laurence; Cillari, Enrico; Hurewitz, David; Jacobson, Kraig W; Katelaris, Constance H; Maurer, Marcus; Merk, Hans; Bernstein, Jonathan A; Feighery, Conleth; Floccard, Bernard; Gleich, Gerald; Hébert, Jacques; Kaatz, Martin; Keith, Paul; Kirkpatrick, Charles H; Langton, David; Martin, Ludovic; Pichler, Christiane; Resnick, David; Wombolt, Duane; Fernández Romero, Diego S; Zanichelli, Andrea; Arcoleo, Francesco; Knolle, Jochen; Kravec, Irina; Dong, Liying; Zimmermann, Jens; Rosen, Kimberly; Fan, Wing-Tze

    2010-08-05

    Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

  7. The humanistic burden of hereditary angioedema

    DEFF Research Database (Denmark)

    Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette

    2014-01-01

    Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients? lives is not well understood. The study objective was to comprehensively characterize the burden of illness......, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment...

  8. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    DEFF Research Database (Denmark)

    Bygum, Anette

    2014-01-01

    Experiences from a Danish patient cohort with hereditary angioedema are reported with focus on home therapy and burden of illness. Eighty patients have been prospectively followed over 11 years, having experienced a total of 7,809 attacks over 469 patient years. More than half of the patients...... stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...... therapy has profoundly improved the lives of hereditary angioedema patients....

  9. Angioedema attacks in patients with hereditary angioedema : Local manifestations of a systemic activation process

    NARCIS (Netherlands)

    Hofman, Zonne L M; Relan, Anurag; Zeerleeder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to

  10. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process

    NARCIS (Netherlands)

    Hofman, Zonne L. M.; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C. Erik

    2016-01-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to

  11. Anaesthetic management of a patient with hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Nergis Ataol

    2015-12-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal organs. Attacks may occur either spontaneously or following trauma, stress, surgery, infections and hormonal fluctuations. The most common cause of death is asphyxia related to laryngeal edema. Giving C1 esterase inhibitor is the most effective method of treatment. Also fresh frozen plasma, androgen steroids, quinine pathway inhibitors, antifibrinolytics and bradykinin receptor antagonists can be used as treatment. In this paper, the anesthetic management of a patient with hereditary angioedema undergoing inguinal hernia repair surgery is reported.

  12. Hereditary angioedema: what the gastroenterologist needs to know

    Directory of Open Access Journals (Sweden)

    Ali MA

    2014-11-01

    Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

  13. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

    OpenAIRE

    Sergio Duarte Dortas Junior; Solange Oliveira Rodrigues Valle; Soloni Afra Pires Levy; Rosangela P. Tortora; Augusto Tiaqui Abe; Gisele Viana Pires; José Angelo de Souza Papi; Alfeu Tavares França

    2012-01-01

    Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB) is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to par...

  14. Perioperative course in patients with hereditary or acquired angioedema.

    Science.gov (United States)

    MacBeth, Lisa S; Volcheck, Gerald W; Sprung, Juraj; Weingarten, Toby N

    2016-11-01

    Two types of bradykinin-mediated angioedema, hereditary angioedema (HAE) and acquired angioedema (AAE), result from deficiency or dysfunction of C1 esterase inhibitor, leading to an overproduction of bradykinin, which can lead to vascular permeability and life-threatening angioedema of the airway. The objective of this study was to review perioperative outcomes in a series of patients with HAE and AAE and to review current knowledge about anesthetic complications in patients with HAE or AAE. Medical records were retrospectively reviewed for perioperative complications in patients with HAE or AAE who underwent general anesthesia from January 1, 2000, to December 31, 2014, at our institution. Twenty-four patients (13 with HAE, 10 with AAE, and 1 with unspecified angioedema) underwent 38 instances of general anesthesia with airway manipulation. All except 4 received prophylactic therapy. One patient, a 67-year-old woman who was pretreated with stanozolol and fresh frozen plasma required reintubation after postoperative airway edema developed. Life-threatening episodes of angioedema of the airway occur infrequently, but they can occur in patients who received pretreatment and in patients who have previously undergone anesthesia uneventfully. Anesthesiologists must be ready to emergently manage a difficult airway and must be familiar with recommendations provided in consensus guidelines for the treatment of HAE and AAE patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Hereditary angioedema: epidemiology, management, and role of icatibant

    Directory of Open Access Journals (Sweden)

    Ghazi A

    2013-05-01

    Full Text Available Aasia Ghazi, J Andrew GrantUniversity of Texas Medical Branch, Division of Allergy and Clinical Immunology, Galveston, TX, USAAbstract: Hereditary angioedema (HAE is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor® and recombinant (Rhucin® and Ruconest™ C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®, and bradykinin B2 receptor antagonist-icatibant (Firazyr®. Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®, a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial

  16. [Angioedema].

    Science.gov (United States)

    2015-05-11

    Angioedema may be an overlooked common disease. Angioedema comprises the idiopathic, the allergic, pseudo allergic, the physical form as well as the hereditary form. Diagnosis is simple when symptoms are classical (lips, eyes and tongue) but might be missed if symptoms are nonspecific such as dizziness or dyspnoea. However, the most striking observation reviewing the literature is the absence of original research on angioedema considering the high prevalence of the disease. From a patient and physician perspective more information and research on angioedema is needed.

  17. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    DEFF Research Database (Denmark)

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007...... International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). METHODS: The Canadian Hereditary Angioedema Network (CHAEN...... approach. The Consensus document was reviewed at the meeting and then circulated for review. RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. CONCLUSIONS: Consensus approach is only...

  18. Hereditary Angioedema: a Challenging Diagnosis for the Gastroenterologist

    Directory of Open Access Journals (Sweden)

    Gábos Gabriella

    2016-12-01

    Full Text Available Hereditary angioedema (HAE caused by a deficiency of C1 esterase inhibitor enzyme (C1-INH is a very rare, autosomal dominantly inherited genetic disorder, characterized by recurrent peripheral angioedema, painful abdominal attacks and episodes of laryngeal edema. Abdominal attacks are frequent symptoms in adult HAE patients, occurring in more than 90% of the cases. Angioedema in the bowel or abdomen can occur in the absence of cutaneous manifestations and may be easily misdiagnosed unless the clinician has a high degree of awareness to include HAE in the differential diagnosis. Misdiagnosis is associated with inadequate treatments, including unnecessary surgical procedures. Any patient who presents recurrent episodes of swelling should be evaluated for HAE caused by C1-INH deficiency. New therapies could save lives and dramatically improve their quality of life.

  19. Angioedema hereditario en pediatría Hereditary pediatric angioedema

    OpenAIRE

    A. Calvo Gómez-Rodulfo; J.E. García López; J.D. Herrero-Morín; G. Rodríguez García; F. González Guerra

    2009-01-01

    Introducción: El angioedema hereditario es una patología de origen genético causada por la alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH). La prevalencia de esta entidad es baja, lo que dificulta su diagnóstico y manejo adecuado.
    Caso clínico: Se presenta el caso de una paciente con episodios repetidos de edema subcutáneo localizado en las extremidades desde los tres años de vida, añadiendo disfagia y disfonía a partir de la pu...

  20. Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

    Science.gov (United States)

    Lumry, William Raymond

    2018-01-01

    This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

  1. Colorectal intussusception: an unusual gastrointestinal complication of hereditary angioedema.

    Science.gov (United States)

    Witschi, A; Krähenbühl, L; Frei, E; Saltzman, J; Späth, P J; Müller, U R

    1996-09-01

    A 21-year-old man with a history of hereditary angioedema presented with protracted abdominal pain which failed to respond to infusion of C1 inhibitor concentrate. Evaluation by CT scan revealed extensive colorectal intussusception requiring surgical intervention. Under replacement therapy with C1 inhibitor concentrate, both the operation under general anesthesia and the postoperative phase were uneventful. The intraoperative examination suggested initiation of intussusception by local mucosal edema in the transverse colon.

  2. Hereditary angioedema type I: a case report

    Directory of Open Access Journals (Sweden)

    Francisca Muñoz Peralta

    2016-03-01

    Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.

  3. Comparing acquired angioedema with hereditary angioedema (types I/II): findings from the Icatibant Outcome Survey.

    Science.gov (United States)

    Longhurst, H J; Zanichelli, A; Caballero, T; Bouillet, L; Aberer, W; Maurer, M; Fain, O; Fabien, V; Andresen, I

    2017-04-01

    Icatibant is used to treat acute hereditary angioedema with C1 inhibitor deficiency types I/II (C1-INH-HAE types I/II) and has shown promise in angioedema due to acquired C1 inhibitor deficiency (C1-INH-AAE). Data from the Icatibant Outcome Survey (IOS) were analysed to evaluate the effectiveness of icatibant in the treatment of patients with C1-INH-AAE and compare disease characteristics with those with C1-INH-HAE types I/II. Key medical history (including prior occurrence of attacks) was recorded upon IOS enrolment. Thereafter, data were recorded retrospectively at approximately 6-month intervals during patient follow-up visits. In the icatibant-treated population, 16 patients with C1-INH-AAE had 287 attacks and 415 patients with C1-INH-HAE types I/II had 2245 attacks. Patients with C1-INH-AAE versus C1-INH-HAE types I/II were more often male (69 versus 42%; P = 0·035) and had a significantly later mean (95% confidence interval) age of symptom onset [57·9 (51·33-64·53) versus 14·0 (12·70-15·26) years]. Time from symptom onset to diagnosis was significantly shorter in patients with C1-INH-AAE versus C1-INH-HAE types I/II (mean 12·3 months versus 118·1 months; P = 0·006). Patients with C1-INH-AAE showed a trend for higher occurrence of attacks involving the face (35 versus 21% of attacks; P = 0·064). Overall, angioedema attacks were more severe in patients with C1-INH-HAE types I/II versus C1-INH-AAE (61 versus 40% of attacks were classified as severe to very severe; P < 0·001). Median total attack duration was 5·0 h and 9·0 h for patients with C1-INH-AAE versus C1-INH-HAE types I/II, respectively. © 2016 British Society for Immunology.

  4. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group.

    Science.gov (United States)

    Cicardi, M; Aberer, W; Banerji, A; Bas, M; Bernstein, J A; Bork, K; Caballero, T; Farkas, H; Grumach, A; Kaplan, A P; Riedl, M A; Triggiani, M; Zanichelli, A; Zuraw, B

    2014-05-01

    Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Socioeconomic burden of hereditary angioedema: results from the hereditary angioedema burden of illness study in Europe

    Science.gov (United States)

    2014-01-01

    Background Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the patient perspective in Europe. Methods The study was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE via a cross-sectional survey of HAE patients, including direct and indirect resource utilization during and between attacks for patients and their caregivers over the past 6 months. A regression model examined predictors of medical resource utilization. Results Overall, 164 patients had an attack in the past 6 months and were included in the analysis. The most significant predictor of medical resource utilization was the severity of the last attack (OR 2.6; p < 0.001). Among patients who sought medical care during the last attack (23%), more than half utilized the emergency department. The last attack prevented patients from their normal activities an average of 4–12 hours. Patient and caregiver absenteeism increased with attack severity and frequency. Among patients who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. Conclusion HAE poses a considerable burden on patients and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks. PMID:24996814

  6. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

    DEFF Research Database (Denmark)

    Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer

    2009-01-01

    Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed...

  7. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  8. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.

    Science.gov (United States)

    Zeerleder, Sacha; Levi, Marcel

    2016-01-01

    hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age. To date effective therapies for acute and prophylactic treatment are available.

  10. Hereditary Angioedema: The Economics of Treatment of an Orphan Disease

    Directory of Open Access Journals (Sweden)

    William Raymond Lumry

    2018-02-01

    Full Text Available This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

  11. Diagnosis and screening of patients with hereditary angioedema in primary care

    Science.gov (United States)

    Henao, Maria Paula; Kraschnewski, Jennifer L; Kelbel, Theodore; Craig, Timothy J

    2016-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients. PMID:27194914

  12. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Science.gov (United States)

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  13. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    DEFF Research Database (Denmark)

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  14. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Aygören-Pürsün E

    2016-09-01

    Full Text Available Emel Aygören-Pürsün,1 Anette Bygum,2 Kathleen Beusterien,3 Emily Hautamaki,4 Zlatko Sisic,5 Henrik B Boysen,6 Teresa Caballero7 1Angioedema Centre, Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt, Germany; 2Hereditary Angioedema Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; 3Outcomes Research Strategies in Health, Washington, DC, 4Patient Reported Outcomes, Oxford Outcomes Inc., an ICON plc company, Bethesda, MD, USA; 5ViroPharma Incorporated, Chatsworth House, Maidenhead, UK; 6HAEi – Hereditary Angioedema International Patient Organization for C1 Inhibitor Deficiencies, Skanderborg, Denmark; 7Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz, Biomedical Research Network on Rare Diseases U754 (CIBERER, University Hospital La Paz, Madrid, Spain Objective: To estimate health status utility (preference weights for hereditary angioedema (HAE during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health.Study design and methods: The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks.Results: Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation

  15. Disease Severity, Activity, Impact, and Control and How to Assess Them in Patients with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Busse, Paula; Caballero, Teresa

    2017-01-01

    Hereditary angioedema (HAE) is a group of rare, potentially life-threatening, and frequently debilitating diseases characterized by recurrent, and often with an unpredictable onset, of swelling attacks. HAE is heterogeneous, with considerable differences between its subtypes, patients, and even...

  16. Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant.

    Science.gov (United States)

    Krause, Karoline; Metz, Martin; Zuberbier, Torsten; Maurer, Marcus; Magerl, Markus

    2010-04-01

    The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.

  17. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered ica......Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...

  18. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Science.gov (United States)

    2010-01-01

    Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). Methods The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management. PMID:20667127

  19. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Bowen Tom

    2010-07-01

    Full Text Available Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010. Methods The Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

  20. The burden of illness in patients with hereditary angioedema.

    Science.gov (United States)

    Banerji, Aleena

    2013-11-01

    Hereditary angioedema (HAE) is a rare genetic disease characterized by long-term recurrent attacks of subcutaneous or submucosal edema in different parts of the body. A comprehensive review of the literature on burden of illness for patients with HAE is presented. A Boolean search was performed using MEDLINE and EMBASE databases and the Internet. Articles discussing aspects of the burden of illness in HAE were selected. Topics focused on the course of the disease, nature of attacks, treatment, quality of life, and costs. Hereditary angioedema is associated with a significant and multifaceted disease burden. Diagnosis is often delayed for years, with patients receiving ineffective treatment and unnecessary medical procedures before diagnosis. HAE attacks are painful, unpredictable, and debilitating and often require emergency medical attention. Attacks can affect a patient's daily activities, including work or schooling. Depression and anxiety are prevalent in patients with HAE. Recent advances in treatment provide patients with effective and well-tolerated prophylactic and on-demand therapeutic options. However, end points specific to HAE that better measure the impact of treatment on disease burden are lacking. Furthermore, there is a notable paucity of literature directed toward physicians who are instrumental in diagnosing and treating patients with HAE (eg, emergency department). More publications are broadening the understanding of HAE. However, important gaps remain. Effective management of HAE requires a more comprehensive understanding of the disease burden so that disease management can be individualized to meet specific patient needs. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Current state of hereditary angioedema management: A patient survey

    Science.gov (United States)

    Busse, Paula; Christiansen, Sandra C.; Li, Henry; Lumry, William; Davis-Lorton, Mark; Bernstein, Jonathan A.; Frank, Michael; Castaldo, Anthony; Long, Janet F.; Zuraw, Bruce L.; Riedl, Marc

    2015-01-01

    Hereditary angioedema (HAE) is a chronic disease with a high burden of disease that is poorly understood and often misdiagnosed. Availability of treatments, including C1 esterase inhibitor (C1INH) replacement, ecallantide, and icatibant, marks a significant advance for HAE patients. We aimed to better understand the current state of HAE care, from a patient perspective, after the introduction of several novel therapies. One session of the United States Hereditary Angioedema Association 2013 patient summit was devoted to data collection for this study. Patients attending the summit were self-selected, and HAE diagnosis was self-reported. Survey questions assessed patient characteristics, burden of disease, and treatment. Participant responses were captured using an audience response system. We surveyed 149 (80%) type I and II HAE (HAE-C1INH) and 37 (20%) HAE with normal C1INH (HAE-nlC1INH) patients. HAE-C1INH (72%) and HAE-nlCINH patients (76%) equally reported that HAE had a significant impact on quality of life (QOL). A third of HAE-C1INH patients were diagnosed within one year of their first HAE attack, but another third reported a delay of more than 10 years. Most HAE-C1INH (88%) and HAE-nlC1INH (76%) patients had on-demand treatment available. HAE-C1INH patients frequently had an individual treatment plan (76%) compared with 50% of HAE-nlC1INH patients. Most HAE-C1INH patients went to the emergency department (ED) or were hospitalized less than once every six months (80%). Our findings show that HAE management is improving with good access to on-demand and prophylactic treatment options. However, HAE patients still have a significant burden of disease and continued research and educational efforts are needed. PMID:25976438

  2. [Hereditary angioedema in Medellín (Colombia): Clinical evaluation and quality of life appraisal].

    Science.gov (United States)

    Sánchez, María Dulfary; Cuervo, Julián; Rave, Deisi; Clemen, Gustavo; Yepes-Núñez, Juan José; Ortiz-Reyes, Blanca; Sus, Sara; Cardona, Ricardo

    2015-01-01

    Hereditary angioedema is an autosomal dominant primary immunodeficiency caused by a deficiency of the C1 inhibitor protein and characterized by recurrent episodes of subcutaneous and mucosal edema. Unpredictable and frequent crisis of angioedema affect the quality of life of individuals suffering this kind of disorder. To analyze the clinical characteristics of a family with an index case of hereditary angioedema and to determine the impact of this disease on their quality of life. Twenty six members of the family were included in the trial; 25 of them were analyzed for C4 complement and antigenic and functional C1 inhibitor blood levels. Two instruments (SF-365 and KIDSCREEN-27) were used to evaluate adult health quality and children and teenagers quality of life, respectively. Eighty three percent (83%) of individuals reporting symptoms of the condition exhibited serological criteria of hereditary angioedema type I: low levels of both C4 complement and quantitative (antigenic) and qualitative (functional) C1 inhibitor. In relation to patients' psychological and emotional performance, their quality of life was significantly affected by the symptoms of hereditary angioedema. This study provides evidence of the first family in Valle de Aburrá (Colombia) characterized as having hereditary angioedema type I. Despite the use of a generic instrument, the negative impact on the quality of life of individuals suffering this disease was also confirmed.

  3. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

    Directory of Open Access Journals (Sweden)

    Sergio Duarte Dortas Junior

    2012-04-01

    Full Text Available Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.O Angioedema Hereditário é uma doença autossômica dominante. A pesquisa de rotina para autoanticorpos não é recomendada para pacientes com Angioedema Hereditário; entretanto, a prevalência desses anticorpos em pacientes com Angioedema Hereditário não está bem documentada. Objetivamos determinar a prevalência de autoanticorpos para identificar indivíduos sob risco de desenvolver doenças autoimunes. Quinze pacientes com Angioedema Hereditário atendidos no Hospital Universitário Clementino Fraga Filho aceitaram participar do estudo. A prevalência de autoanticorpos foi de 40%. Nossos dados indicam alta prevalência de autoanticorpos em pacientes com Angioedema Hereditário. Estudos de maior escala deveriam ser considerados para determinar a significância desses autoanticorpos no acompanhamento clínico de pacientes com Angioedema Hereditário.

  4. Acute dystonia mimicking angioedema of the tongue

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Pallesen, Kristine A U; Bygum, Anette

    2013-01-01

    We report a case of acute dystonia of the face, jaw and tongue caused by metoclopramide and mimicking angioedema. The patient had attacks for several years before the correct diagnosis was made and we present the first ever published video footage of an attack. This adverse drug reaction is known...

  5. Management of upper airway edema caused by hereditary angioedema

    Directory of Open Access Journals (Sweden)

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

  6. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

    Science.gov (United States)

    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.

  7. Complement factor C4 activation in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Åbom, Anne; Bygum, Anette; Koch, Claus

    2017-01-01

    , that C1-INH-HAE may potentially be overlooked, if screening is performed only by measurement of C4. It has been suggested that measurement of C4 activation products is better suited to avoid false negative results. Our aim was to investigate whether total antigenic C4 or non-functional C4c is a better......Objectives: Low complement factor C4 is usually considered a valuable screening tool for patients with the potentially life-threatening hereditary angioedema with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE). However, there are patients with C1-INH-HAE presenting with normal C4 levels. This means...... measure of the increased C4 activation in C1-INH-HAE patients. Design and methods: Two different monoclonal antibodies (mAb) to human C4 were produced: one had specificity for the β-chain of C4 and would thus react with both functional and non-functional C4, and the other was developed against the factor...

  8. Hereditary angioedema type I in a female patient: a case report

    OpenAIRE

    PRKAČIN, INGRID; BAN, ANA; CAVRIĆ, GORDANA; BARTOLEK HAMP, DUBRAVKA

    2014-01-01

    Hereditary angioedema (HAE) is rare autosomal dominant disease, characterised by spontaneous and recurrent swellings in various parts of the body. The main inflammatory factor in HAE is bradykinin (a key mediator of non-allergic angioedema) and it is responsible for capillary leak. C1 esterase inhibitor (C1-INH) is a protease inhibitor that blocks the activation of the classic complement pathway, but there are also many others biochemical pathways, including kinin. Type I HAE is defi...

  9. Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid

    2014-01-01

    BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding l......BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose......: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems...

  10. Smjernice za dijagnostiku i liječenje hereditarnog angioedema [Guidelines for the diagnosis and treatment of hereditary angioedema

    OpenAIRE

    Stipić Marković, Asja; Rožmanić, Vojko; Anić, Branimir; Aberle, Neda; Račić, Goran; Novak, Srđan; Sunara, Davor; Grdinić, Boris; Karadža-Lapić, Ljerka; Ražov Radas, Melanija; Karanović, Boris; Kvenić, Barbara

    2014-01-01

    Hereditary angioedema (HAE) is a rare but potentially fatal genetic disorder with nonpitting, nonerythematous, and not pruritic swelling which can affect the hands, feet, face, genitals and visceral mucosa. The type, frequency, and severity of the attacks vary between patients, and over the lifetime of an individual patient. Efforts in Croatian counties have identified approximately 100 patients (but there must be more undiagnosed patients). The first global guideline for the management of HA...

  11. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2016-01-01

    OBJECTIVE: To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact...... conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey...

  12. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review*

    OpenAIRE

    Miranda, Amanda Rodrigues; de Ue, Ana Paula Fusel; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; de Souza, Patr?cia Karla; Rotta, Osmar

    2013-01-01

    In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The...

  13. [Hereditary angioedema by C1 inhibitor-deficit: Diagnostic and therapeutic challenges. Case report].

    Science.gov (United States)

    Mayorga, Álvaro José; Ayestas-Moreno, Gerardo José

    2017-01-01

    Hereditary angioedema is a disease which manifests itself with episodes of spontaneous edema on skin, mucosal and airway. Treatment includes acute and prophylactic approach to minimize the attacks and severity. In many parts of the world, androgen derivatives, antifibrinolytic and fresh frozen plasma are the therapies available for prophylaxis. 16 years old teenager of without history of immune decease, has in the course of 1-year repetitive episodes of painless, non-pruritic angioedema, does not respond to antihistamine therapy, corticosteroids or adrenaline; fresh frozen plasma is applied in 1 occasion exacerbating episode with severity. The diagnosis is delayed because of the unavailability of the study in the country, so it is shipped abroad confirming the deficit of C1 Inhibitor (7.1 μg/mL). Initiating prophylactic therapy with Danazol, with subsequent episodes decreased. The delay diagnosis involves considerable risk in these patients; the importance of long-term prophylactic treatment is ratified in the use of androgens, being as an available option in developing countries.

  14. Depression and anxiety in patients with hereditary angioedema.

    Science.gov (United States)

    Fouche, Andrew S; Saunders, Erika F H; Craig, Timothy

    2014-04-01

    Hereditary angioedema (HAE) is characterized by edematous swelling attacks of the face, extremities, abdomen, genitalia, and upper airway. The potential for laryngeal swelling makes the disease life-threatening, and the swelling elsewhere contributes to the significant burden of illness. The increased risk for mental health disorders in HAE is due to the burden of disease and possibly associated activation of the immune system. To determine the prevalence of depression and anxiety in HAE patients and the most high-yield features of depression to target in a clinical encounter. Depression and anxiety symptoms were evaluated using the 29 items of the Hamilton Depression Rating Scale along with the 14-item Hamilton Anxiety Rating Scale. The sample size was 26 participants with a diagnosis of type 1 or 2 HAE drawn from a cohort of 60 adult patients. In addition, a literature search was performed regarding how immune modulation affects depression and anxiety. A total of 39% of participants were identified as experiencing depression of mild (50%), moderate (40%), or severe (10%) levels. Fifteen percent of participants displayed prominent anxiety, half of whom had mild anxiety, 25% moderate anxiety, and 25% severe anxiety. The literature on inflammation and depression suggests a possible link between HAE and depression. Our data and the literature support that depression and anxiety symptoms are common in patients with HAE and may be secondary to chronic disease burden, associated pathophysiologic features, or both. Treatment that addresses the psychosocial and mental health of HAE patients is critical for best practice. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Evidence of impaired sense of smell in hereditary angioedema.

    Science.gov (United States)

    Perricone, C; Agmon-Levin, N; Shoenfeld, N; de Carolis, C; Guarino, M D; Gigliucci, G; Milana, I; Novelli, L; Valesini, G; Perricone, R; Shoenfeld, Y

    2011-01-01

    Hereditary angioedema (HAE) is an autosomal-dominant disorder resulting from C1-inhibitor (C1INH) deficiency. Smell impairments were found in patients affected with systemic lupus erythematosus, that, similarly to HAE, is characterized by the activation of the classical complement pathway with C4 consumption. In this study, we aimed at evaluating the sense of smell in patients with HAE. Thirty patients with HAE and 30 healthy age- and sex-matched controls were evaluated for olfactory functions using the 3-stages Sniffin'-Sticks kit (threshold, discrimination, and identification [TDI]). TDI scores were analyzed according to complement levels (C1INH, C3, C4 and CH50), Beck depression inventory (BDI-II) and danazol treatment. A significant decrease in olfactory function was observed in patients affected with HAE compared with controls in total TDI score (P < 0.001), and in the discrimination (P < 0.001) and identification scores (P = 0.012). Anosmia was present only in patients with HAE (3.3%) who also exhibited more frequently hyposmia (53.3%vs 3.3%, P < 0.0001). Complement levels were reduced in patients with HAE. C4 serum levels showed positive correlation with total TDI score (P < 0.001), and with discrimination (P = 0.002) and identification (P = 0.011) scores. CH50 complement levels showed positive correlation with total TDI score (P < 0.001), and with threshold (P = 0.002) and discrimination (P = 0.011) scores. Sex, age, danazol treatment, BDI-II scores were not different between the patients and controls and did not influence TDI scores significantly. Evidence for an impaired sense of smell was found in patients with HAE. The reduction in olfactory function in these cases seems to correlate with complement C4 and CH50 levels. Immune and genetic mechanisms might play a role in this defect. © 2010 John Wiley & Sons A/S.

  16. Hereditary angioedema: Assessing the hypothesis for underlying autonomic dysfunction.

    Directory of Open Access Journals (Sweden)

    Maddalena A Wu

    Full Text Available Attacks of Hereditary Angioedema due to C1-inhibitor deficiency (C1-INH-HAEare often triggered by stressful events/hormonal changes.Our study evaluates the relationship between autonomic nervous system (ANS and contact/complement system activation.Twenty-three HAE patients (6 males, mean age 47.5±11.4 years during remission and 24 healthy controls (8 males, mean age 45.3±10.6 years were studied. ECG, beat-by-beat blood pressure, respiratory activity were continuously recorded during rest (10' and 75-degrees-head-up tilt (10'. C1-INH, C4, cleaved high molecular weight kininogen (cHK were assessed; in 16 patients and 11 controls plasma catecholamines were also evaluated. Spectral analysis of heart rate variability allowed extraction of low-(LF and high-(HF frequency components, markers of sympathetic and vagal modulation respectively.HAE patients showed higher mean systolic arterial pressure (SAP than controls during both rest and tilt. Tilt induced a significant increase in SAP and its variability only in controls. Although sympathetic modulation (LFnu increased significantly with tilt in both groups, LF/HF ratio, index of sympathovagal balance, increased significantly only in controls. At rest HAE patients showed higher noradrenaline values (301.4±132.9 pg/ml vs 210.5±89.6pg/ml, p = 0.05. Moreover, in patients tilt was associated with a significant increase in cHK, marker of contact system activation (49.5 ± 7.5% after T vs 47.1 ± 7.8% at R, p = 0.01.Our data are consistent with altered ANS modulation in HAE patients, i.e. increased sympathetic activation at rest and blunted response to orthostatic challenge. Tilt test-induced increased HK cleavage suggests a link between stress and bradykinin production.

  17. Angioedema hereditario: Guía de tratamiento Hereditary angioedema: A therapeutic guide

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2012-04-01

    Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a historical asphyxia mortality of 15% to 50%. It is the consequence of functional C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has lead to the development of new drugs for its treatment. HAE management and treatment are agreed by international consensus decision. A therapeutic guide for the treatment of the disease is important to improve diagnosis and treatment. We here describe the pharmacology of drugs available for the treatment of HAE in Argentina: plasma derived C1 Inhibitor, the bradykinin antagonist: icatibant, the attenuated androgen

  18. Gastrointestinal Manifestations of Hereditary Angioedema Diagnosed by Ultrasound in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Christine Riguzzi

    2014-11-01

    Full Text Available Abdominal angioedema is a less recognized type of angioedema, which can occur in patients with hereditary angioedema (HAE. The clinical signs may range from subtle, diffuse abdominal pain and nausea, to overt peritonitis. We describe two cases of abdominal angioedema in patients with known HAE that were diagnosed in the emergency department by point-of-care (POC ultrasound. In each case, the patient presented with isolated abdominal complaints and no signs of oropharyngeal edema. Findings on POC ultrasound included intraperitoneal free fluid and bowel wall edema. Both patients recovered uneventfully after receiving treatment. Because it can be performed rapidly, requires no ionizing radiation,and can rule out alternative diagnoses, POC ultrasound holds promise as a valuable tool in the evaluation and management of patients with HAE. [West J Emerg Med. 2014;15(7:-0.

  19. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    DEFF Research Database (Denmark)

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole

    2013-01-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway...

  20. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Bygum, A; Fagerberg, C R; Ponard, D

    2011-01-01

    Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype...

  1. Clinical characteristics and real-life diagnostic approaches in all Danish children with hereditary angioedema

    DEFF Research Database (Denmark)

    Aabom, Anne; Andersen, Klaus E; Fagerberg, Christina

    2017-01-01

    BACKGROUND: With a potentially early onset, hereditary angioedema (HAE) requires special knowledge also in infancy and early childhood. In children from families with HAE, the diagnosis should be confirmed or refuted early, which can be difficult. Studies of childhood HAE and the diagnostic...

  2. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

    DEFF Research Database (Denmark)

    Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G

    2015-01-01

    BACKGROUND: Hereditary angioedema types I and II are caused by a functional deficiency of C1 inhibitor (C1-INH) leading to overproduction of bradykinin. The current functional diagnostic assays employ inhibition of activated C1s, however, an alternative, more physiologic method, is desirable...

  3. Urticaria and Prodromal Symptoms Including Erythema Marginatum in Danish Patients with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva R; Valente de Freitas, Priscila; Bygum, Anette

    2016-01-01

    Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially...

  4. Angioedema

    Science.gov (United States)

    Angioneurotic edema; Welts; Allergic reaction - angioedema; Hives - angioedema ... symptoms may include: Abdominal cramping Breathing difficulty Swollen eyes and mouth Swollen lining of the eyes ( chemosis )

  5. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema.

    Science.gov (United States)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Boysen, Henrik B; Caballero, Teresa

    2016-01-01

    To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient's life; a score of 0.0 reflects death and 1.0 reflects full health. The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide-ranging personal and social impacts.

  6. Estimation of EuroQol 5-Dimensions health status utility values in hereditary angioedema

    Science.gov (United States)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Boysen, Henrik B; Caballero, Teresa

    2016-01-01

    Objective To estimate health status utility (preference) weights for hereditary angioedema (HAE) during an attack and between attacks using data from the Hereditary Angioedema Burden of Illness Study in Europe (HAE-BOIS-Europe) survey. Utility measures quantitatively describe the net impact of a condition on a patient’s life; a score of 0.0 reflects death and 1.0 reflects full health. Study design and methods The HAE-BOIS-Europe was a cross-sectional survey conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective. Survey items that overlapped conceptually with the EuroQol 5-Dimensions (EQ-5D) domains (pain/discomfort, mobility, self-care, usual activities, and anxiety/depression) were manually crosswalked to the corresponding UK population-based EQ-5D utility weights. EQ-5D utilities were computed for each respondent in the HAE-BOIS-Europe survey for acute attacks and between attacks. Results Overall, a total of 111 HAE-BOIS-Europe participants completed all selected survey items and thus allowed for computation of EQ-5D-based utilities. The mean utilities for an HAE attack and between attacks were 0.44 and 0.72, respectively. Utilities for an acute attack were dependent on the severity of pain of the last attack (0.61 for no pain or mild pain, 0.47 for moderate pain, and 0.08 for severe pain). There were no significant differences across countries. Mean utilities derived from the study approach compare sensibly with other disease states for both acute attacks and between attacks. Conclusion The impacts of HAE translate into substantial health status disutilities associated with acute attacks as well as between attacks, documenting that the detrimental effects of HAE are meaningful from the patient perspective. Results were consistent across countries with regard to pain severity and in comparison to similar disease states. The results can be used to raise awareness of HAE as a serious disease with wide

  7. Shortened Activated Partial Thromboplastin Time May Help in Diagnosing Hereditary and Acquired Angioedema.

    Science.gov (United States)

    Bork, Konrad; Witzke, Günther

    2016-01-01

    To evaluate whether activated partial thromboplastin time (APTT) could be used in the laboratory diagnosis of hereditary or acquired angioedema (HAE or AAE) with and without C1 inhibitor (C1-INH) deficiency. In a prospective investigation, APTT and other coagulation parameters were determined in 149 adult patients with various types of angioedema and in 26 healthy participants (HP). Mean APTT was significantly shortened in HAE-C1-INH type I (p angioedema, 4/30 (13.3%) patients with nonhistaminergic angioedema and in 2/26 (7.7%) HP. Thus, a shortened APTT was obtained in 8-9 times more patients with angioedema due to C1-INH deficiency when compared to patients with various forms of angioedema with normal C1-INH and also to HP. A shortened APTT may help to diagnose HAE-C1-INH and AAE-C1-INH when determination of C1-INH is not yet available. © 2016 S. Karger AG, Basel.

  8. Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting

    DEFF Research Database (Denmark)

    Zanichelli, Andrea; Longhurst, Hilary J; Maurer, Marcus

    2016-01-01

    BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures...... being diagnosed as having C1-INH-HAE. RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185...... patients without (1.7 years; P angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct...

  9. Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance

    Directory of Open Access Journals (Sweden)

    Li HH

    2016-09-01

    Full Text Available Huamin Henry Li Institute for Asthma and Allergy, Chevy Chase, MD, USA Abstract: Hereditary angioedema (HAE is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH. The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE. Keywords: C1-INH concentrate, hereditary angioedema, disease management, first line, prophylaxis, self-administration 

  10. Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings; Angioedema hereditario: una causa infrecuente de abdomen agudo. Hallazgos en la TC e ecografia abdominal

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, R.A. de la; Oliver, J. M.; Bueno, A.; Albillos, J. C. [Fundacion Hospital Alcorcon. Madrid (Spain)

    2002-07-01

    We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs.

  11. Treatment of hereditary angioedema due to C1 inhibitor deficiency in Argentina

    Directory of Open Access Journals (Sweden)

    Eloisa Malbrán

    2017-08-01

    Full Text Available The benefits of the worldwide approval of new drugs for the treatment of acute C1-INH-HAE attacks may still not reach all patients. Identifying the current barriers in the access to medication, as well as conducting a detailed assessment of the progress in this area, is essential to achieve universal treatment. Two hundred and twenty five patients registered in the Argentina Hereditary Angioedema Patient Association (AHAEPA were randomly selected and invited to participate in a web based questionnaire on accessibility to icatibant and pdC1-INH, self-treatment, delay to treatment, and coverage. The data retrieved was compared to our previous reports in 2008 and 2013. We collected 156/225 answers. One hundred and eighteen (76% patients have either pdC1-INH (n = 86, icatibant (n = 10 or both (n = 22, while 38 (24% do not have access to treatment. In 2008, 26% had access while 82% had it in 2013. Thirty-two subjects (22% self-inject themselves, similar to 29% in 2013, even though between studies, widespread self-injection training activities have taken place. However, considering injections by proxy, home treatment reached 56%. Only half of the patients decide to receive treatment early during the attack. Ninety-nine patients (63% have full coverage, thirty (19% have no coverage at all and the rest only obtain partial reimbursement. Twenty-nine families (31% share a single treatment dose of the medication, better than 36% in 2013. Argentina's C1-INH-HAE patients had a sustained improvement in their access to medication. Efforts should continue to further improve accessibility and optimal management of HAE acute attacks to all patients in the country.

  12. Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant

    Science.gov (United States)

    Boccon‐Gibod, Isabelle; Launay, David; Gompel, Anne; Kanny, Gisele; Fabien, Vincent; Fain, Oliver

    2017-01-01

    Abstract Introduction The clinical characteristics and icatibant‐treatment outcomes of patients with hereditary angioedema with normal C1 inhibitor (HAE‐nC1 INH) are limited. Methods We retrospectively analyzed data from French HAE patients enrolled in the Icatibant Outcome Survey registry (from July 2009 to September 2013) to compare disease characteristics and the effectiveness and safety of acute icatibant‐treated angioedema attacks in patients with HAE‐nC1 INH, HAE with C1 INH deficiency (type I), or dysfunction (type II). Results One center in Grenoble contributed 22 patients with HAE‐nC1 INH and a family history of HAE while 15 centers across France contributed 153 patients with HAE type I and seven patients with HAE type II. Patients with HAE‐nC1 INH compared to HAE type I, respectively, were more likely to be female (88.1% vs. 63.4%), older at median age of disease onset (21 years vs. 15 years), and have a greater rate of abdominal (80% vs. 61%) and laryngeal (23% vs. 14%) attacks. Icatibant was effective in both groups though the median time to resolution of attack was significantly longer in the HAE‐nC1 INH group (20.0 h, 37 attacks) versus the HAE type I group (14.0 h, 67 attacks). Icatibant was self‐administered for 96.1% of attacks in patients with HAE‐nC1 INH and 75.8% in patients with HAE type I. No serious adverse side effects related to icatibant were reported. Conclusions These data help further define the disease characteristics of HAE‐nC1 INH in the French population and extend the limited data reporting the safe and effective use of icatibant in acute treatment of angioedema in French patients diagnosed with HAE‐nC1 INH. PMID:28250922

  13. Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema

    DEFF Research Database (Denmark)

    Visy, Beáta; Füst, George; Bygum, Anette

    2007-01-01

    BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks...... in patients with hereditary angioedema (HAE). The present study aimed to reinvestigate the relationship between H. pylori infection and the attack rate in the framework of an international collaborative study. MATERIALS AND METHODS: Within the framework of the PREHAEAT project launched by the European Union......, further 152 patients were studied in seven collaborating centers, and participants of the earlier study were followed up in order to detect any relationship between H. pylori infection and the occurrence of attacks in patients suffered from HAE. RESULTS: The proportion of patients experiencing frequent...

  14. Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.

    Science.gov (United States)

    Hack, C Erik; Relan, Anurag; Baboeram, Aartie; Oortwijn, Beatrijs; Versteeg, Serge; van Ree, Ronald; Pijpstra, Rienk

    2013-04-01

    Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency. The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions. In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system. 130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible. The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.

  15. Treatment of Hereditary Angioedema: items that need to be addressed in practice parameter

    Directory of Open Access Journals (Sweden)

    Dagen Callie

    2010-05-01

    Full Text Available Abstract Background Hereditary Angioedema (HAE is a rare, autosomal dominant (AD disorder caused by a C1 esterase inhibitor (C1-inh deficiency or qualitative defect. Treatment of HAE in many parts of the world fall short and certain items need to be addressed in future guidelines. Objective To identify those individuals who should be on long-term prophylaxis for HAE. Additionally, to determine if prodromal symptoms are sensitive and specific enough to start treatment with C-1 INH and possibly other newly approved therapies. Also, to discuss who is appropriate to self-administer medications at home and to discuss training of such patients. Methods A literature review (PubMed and Google was performed and articles published in peer-reviewed journals, which addressed HAE prophylaxis, current HAE treatments, prodromal symptoms of HAE and self-administration of injected home medications were selected, reviewed and summarized. Results Individuals whom have a significant decrease in QOL or have frequent or severe attacks and who fail or are intolerant to androgens should be considered for long-term prophylaxis with C1INH. Prodromal symptoms are sensitive, but non-specific, and precede acute HAE attacks in the majority of patients. Although the treatment of prodromal symptoms could lead to occasional overtreatment, it could be a viable option for those patients able to adequately predict their attacks. Finally, self-administration, has been shown to be feasible, safe and effective for patients who require IV therapy for multiple other diseases to include, but not limited to, hemophilia. Conclusions Prophylactic therapy, treatment at the time of prodromal symptoms and self-administration at home all should allow a reduction in morbidity and mortality associated with HAE.

  16. Urticaria and angioedema.

    Science.gov (United States)

    Spickett, G

    2014-01-01

    Urticaria, also known as hives, and angioedema, where the swelling occurs below the skin instead of on the skin, are extremely common but there is a misconception that the most likely cause is an allergic reaction. Chronic urticaria in particular is rarely due to allergy. Equally for angioedema, many will consider the exceptionally rare hereditary angioedema (HAE), but in fact other medical causes are the most likely, in particular the use of angiotensin-converting enzyme inhibitor (ACE-I) drugs. Approximately 3-5% of patients receiving ACE-I will develop angioedema at some time in the course of their treatment.1 Stress is a major contributor to both chronic urticaria and recurrent angioedema. Treatment needs to focus on the use of long-acting, non-sedating, antihistamines. Corticosteroids may be used acutely but not long term.

  17. Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings

    Science.gov (United States)

    Aygören-Pürsün, Emel; Soteres, Daniel; Moldovan, Dumitru; Christensen, Jim; Van Leerberghe, Arthur; Hao, James; Schranz, Jennifer; Jacobson, Kraig W.; Martinez-Saguer, Inmaculada

    2017-01-01

    Background Hereditary angioedema (HAE) is a rare genetic disease causing unpredictable and potentially life-threatening subcutaneous and submucosal edematous attacks. Cinryze® (Shire ViroPharma Inc., Lexington, MA, USA), a nanofiltered C1 inhibitor (C1-INH), is approved in Europe for the treatment, preprocedure prevention, and routine prophylaxis of HAE attacks, and for the routine prophylaxis of attacks in the USA. This phase 3 study assessed the safety and efficacy of 2 C1-INH doses in preventing attacks in children aged 6–11 years. Methods A randomized single-blind crossover study was initiated in March 2014. Results for the first 6 patients completing the study are reported here. After a 12-week qualifying observation period, patients were randomly assigned to 1 of 2 C1-INH doses, 500 or 1,000 U, every 3–4 days for 12 weeks and crossed over to the alternative dose for a second 12-week period. The primary efficacy endpoint was the number of angioedema attacks per month. Results Six females with HAE type I and a median age of 10.5 years received 2 doses of C1-INH (500 and 1,000 U). The mean (SD) difference in the number of monthly angioedema attacks between the baseline observation period and the treatment period was −1.89 (1.31) with 500 U and −1.89 (1.11) with 1,000 U. During the treatment periods, cumulative attack severity, cumulative daily severity, and the number of attacks needing acute treatment were lower. No serious adverse events or study drug discontinuations occurred. Conclusions Interim findings from this study indicate that routine prevention with intravenous administration of C1-INH is efficacious, safe, and well tolerated in children ≥6 years of age. PMID:28662509

  18. Depressed activation of the lectin pathway of complement in hereditary angioedema

    DEFF Research Database (Denmark)

    Varga, L; Széplaki, G; Laki, J

    2008-01-01

    ) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured...... by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0.0001) in patients compared with controls. Depressed LP...

  19. The hereditary angioedema burden of illness study in Europe (HAE-BOIS- Europe)

    DEFF Research Database (Denmark)

    Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa

    2012-01-01

    ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation...... of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect...

  20. Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management.

    Science.gov (United States)

    Bork, K; Davis-Lorton, M

    2013-02-01

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a rare, autosomal-dominant disease. HAE-C1-INH is characterized by recurrent attacks of marked, diffuse, nonpitting and nonpruritic skin swellings, painful abdominal attacks, and laryngeal edema. The extremities and the gastrointestinal tract are most commonly affected. Swelling of the upper respiratory mucosa poses the greatest risk because death from asphyxiation can result from laryngealedema. HAE-C1-INH attacks are variable, unpredictable, and may be induced by a variety of stimuli, including stress or physical trauma. Because the clinical presentation of HAE-C1-INH is similar to other types of angioedema, the condition may be a challenge to diagnose. Accurate identification of HAE-C1-INH is critical in order to avoid asphyxiation by laryngeal edema and to improve the burden of disease. Based on an understanding of the underlying pathophysiology of IHAE-C1-INH, drugs targeted specifically to the disease, such as C1-inhibitor therapy, bradykinin B2-receptor antagonists, and kallikrein-inhibitors, have become available for both treatment and prevention of angioedema attacks. This article reviews the clinical features, differential diagnosis, and current approaches to management of HAE-C1-INH.

  1. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Farkas H

    2011-05-01

    Full Text Available Henriette Farkas, Lilian Varga3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryAbstract: Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously, a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.Keywords: hereditary angioedema, C1-inhibitor deficiency, treatment, bradykinin, kallikrein inhibitor, subcutaneous administration

  2. Emerging concepts in the diagnosis and treatment of patients with undifferentiated angioedema

    Science.gov (United States)

    2012-01-01

    Angioedema is a sudden, transient swelling of well-demarcated areas of the dermis, subcutaneous tissue, mucosa, and submucosal tissues that can occur with or without urticaria. Up to 25% of people in the US will experience an episode of urticaria or angioedema during their lifetime, and many will present to the emergency department with an acute attack. Most cases of angioedema are attributable to the vasoactive mediators histamine and bradykinin. Histamine-mediated (allergic) angioedema occurs through a type I hypersensitivity reaction, whereas bradykinin-mediated (non-allergic) angioedema is iatrogenic or hereditary in origin. Although their clinical presentations bear similarities, the treatment algorithm for histamine-mediated angioedema differs significantly from that for bradykinin-mediated angioedema. Corticosteroids, and epinephrine are effective in the management of histamine-mediated angioedema but are ineffective in the management of bradykinin-mediated angioedema. Recent advancements in the understanding of angioedema have yielded pharmacologic treatment options for hereditary angioedema, a rare hereditary form of bradykinin-mediated angioedema. These novel therapies include a kallikrein inhibitor (ecallantide) and a bradykinin β2 receptor antagonist (icatibant). The physician’s ability to distinguish between these types of angioedema is critical in optimizing outcomes in the acute care setting with appropriate treatment. This article reviews the pathophysiologic mechanisms, clinical presentations, and diagnostic laboratory evaluation of angioedema, along with acute management strategies for attacks. PMID:23131076

  3. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Farkas, H; Martinez-Saguer, I; Bork, K

    2017-01-01

    BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagn...

  4. Histaminergic Angioedema.

    Science.gov (United States)

    Busse, Paula J; Smith, Tukisa

    2017-08-01

    Angioedema is frequently categorized into histamine- or bradykinin-mediated disease. It is critical to determine the underlying mediator of symptoms as it directs treatment. Histaminergic angioedema is the most frequent cause of angioedema. It is classified as either acute (lasting 6 weeks). It is further classified into angioedema presenting with or without urticaria. Some patients with acute angioedema may have disease that becomes chronic. Mast cells and basophils are central to the underlying pathophysiology of histamine-mediated angioedema. The underlying treatments of histamine-mediated angioedema are antihistamines, corticosteroids, and epinephrine. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Pediatric Angioedema.

    Science.gov (United States)

    Pattanaik, Debendra; Lieberman, Jay Adam

    2017-08-08

    The aims of this study are to update the clinician on current understanding of angioedema as it presents in the pediatric population and to review proper diagnostic techniques and treatment modalities for various types of angioedema. Angioedema is still best classified by whether it is likely histaminergic or kinin-mediated. New guidelines have been published around the world to help diagnose and treat both forms (urticaria/angioedema and hereditary angioedema). The vast majority of the studies on treatment have been conducted in the adult population; however, there are data available in the pediatric population. In the realm of hereditary angioedema, there are multiple new therapies that have been studied in the pediatric population (down to 2 years in some studies) in recent years and offer the clinician options for treatment. Angioedema (whether occurring with or without urticaria) is common in the pediatric population. The majority of the recent studies has been conducted in hereditary angioedema, and now, the clinician should have various options to treat all forms of angioedema. Many treatment options, especially for hereditary angioedema, are further being examined specifically in the pediatric population.

  6. Breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis are responsive to icatibant

    DEFF Research Database (Denmark)

    Aberer, Werner; Maurer, Marcus; Bouillet, Laurence

    2017-01-01

    BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long......-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. METHODS: Data on LTP use, attacks, and treatments were recorded. Attack...... characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while...

  7. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    OpenAIRE

    Farkas, H.; Martinez?Saguer, I.; Bork, K.; Bowen, T.; Craig, T.; Frank, M.; Germenis, A. E.; Grumach, A. S.; Luczay, A.; Varga, L.; Zanichelli, A.; Aberer, Werner; Andrejevic, Sladjana; Aygoeren?P?rs?n, Emel; Banerji, Alena

    2016-01-01

    BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), ped...

  8. The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity, and depression.

    Science.gov (United States)

    Lumry, William R; Castaldo, Anthony J; Vernon, Margaret K; Blaustein, Marc B; Wilson, David A; Horn, Patrick T

    2010-01-01

    Hereditary angioedema (HAE) is a rare, autosomal dominant disorder characterized by recurrent acute attacks of swelling of the larynx, abdomen, and periphery. This study was designed to assess the humanistic burden of illness associated with HAE. HAE burden was assessed via a web-based survey of patients that solicited information on attack characterization, treatment, side effects, pain, and functional and emotional burden of disease management. In addition to HAE-specific sections, the survey used three standardized instruments to compare HAE patient data to normative (healthy) and chronic disease populations: the 12-Item Short Form (SF-12) Health Survey, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire, and the Hamilton Depression Inventory-Short Form (HDI-SF). A total of 457 HAE patients responded to the survey (response rate, ∼19%). Patients reported significantly poorer health-related quality of life versus population norms, based on the SF-12 Physical Component Summary (mean, 43.7 versus 49.6; p 8.5, indicative of depressive symptomatology. Productivity was also markedly impaired in all WPAI-GH categories, including 34% overall work impairment. Because of their most recent HAE attack, workers lost a mean of 3.3 days; students lost a mean of 1.9 days. HAE results in considerable humanistic burden to patients across physical and mental health domains; negatively impacts education, career, and work productivity; and compounds the substantial economic burdens that are reported separately.

  9. The relationship between anxiety and quality of life in children with hereditary angioedema.

    Science.gov (United States)

    Kessel, Aharon; Farkas, Henriette; Kivity, Shmuel; Veszeli, Nóra; Kőhalmi, Kinga V; Engel-Yeger, Batya

    2017-11-01

    The severe life-threatening characteristics of hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) can affect anxiety levels among pediatric patients. This emotional burden together with the physical restrictions of C1-INH-HAE may decrease children's health-related quality of life (HRQoL). (i) To compare anxiety state and trait between children with C1-INH-HAE and healthy controls; (ii) to examine the relationship between the level of anxiety of children with C1-INH-HAE, their disease activity/affected sites and their HRQoL; and (iii) to predict the HRQoL of children with C1-INH-HAE based on their anxiety level and disease activity/affected sites METHODS: Thirty-three children with C1-INH-HAE (aged 5-18 years) and 52 healthy controls were recruited from Israel and Hungary. All children completed the State-Trait Anxiety Inventory for Children (STAIC), the Pediatric Quality of Life Inventory (Peds-QL) demographic questionnaire and a disease activity and site questionnaire . Disease activity was defined as the number of attacks in last year. Both anxiety state and trait were significantly higher among children with C1-INH-HAE as compared to the controls (44.74±10.56 vs 38.76±10.67, Panxiety state (F 56,2 =4.69, P=.001) and trait (F 56,2 =9.06, Panxiety trait was correlated with the number of angioedema-affected sites (r=.52, P=.003). The presence of HAE attacks and higher anxiety trait predicted a lower HRQoL in children with C1-INH-HAE. C1-INH-HAE children have higher anxiety trait and state, which correlate with reduced HRQoL domains. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  10. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    Science.gov (United States)

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  11. Hereditary angioedema as a metabolic liver disorder: novel therapeutic options and prospects for cure

    Directory of Open Access Journals (Sweden)

    Rohan Ameratuga

    2016-11-01

    Full Text Available Hereditary angioedema (HAE is a rare autosomal dominant disorder caused by mutations of the SERPING1 or the Factor 12 genes. It is potentially fatal, particularly if not identified at an early stage. Apart from androgens, which are contraindicated in children and in pregnant women, a range of effective, albeit very expensive treatments have recently become available for HAE patients. The cost of these new treatments is beyond the reach of most developing countries. At this time, there is no cure for the disorder. In spite of mutations of the SERPING1 gene, autoimmunity and infections are not prominent features of the condition. Here we present the argument that HAE should be viewed primarily as a metabolic liver disorder. This conceptual paradigm shift will stimulate basic research and may facilitate new therapeutic approaches to HAE outlined in this paper. We suggest several novel potential treatment options for HAE from the perspectives of clinical immunology, molecular biology and liver transplantation. Many of these offer the prospect of curing the disorder. The effectiveness of these options are rapidly improving in many cases and their risks are decreasing. Given the very high costs of treating HAE, some of these curative options may become feasible in the next decade.

  12. [Perioperative Management of a Patient with Hereditary Angioedema: A Case Report].

    Science.gov (United States)

    Teranishi, Rie; Makino, Yumi; Amano, Eizou; Shibuya, Hiromi; Okada, Toshiki

    2015-04-01

    Hereditary angioedema (HAE) is a very rare disease that occurs in about 1 in 50,000 to 150,000 people. HAE is caused by low levels or inproper function of the plasma protein C1 inhibitor (C1-INH) which regulates activation of the complement system and the coagulation system. The typical symptom of HAE is regional swellings without pain nor itching, usually triggered by physical trauma or emotional stress. Unlike allergic edema, HAE attacks do not respond to antihistamines, corticosteroids noradrenaline. The swelling attacks against face and throat are potentially life-threatening, and should be treated as a medical emergency. We report a patient with HAE who underwent radical cystectomy of the upper gum under general anesthesia. Because the oral surgery with tracheal intubation is known to be a risk factor of laryngeal edema in a patient with HAE, she was given C1-INH before operation to prevent laryngeal edema according to HAE Guideline 2010 by the Japanese Association for Complement Research. Her pharynx and larynx were checked with Airwayscope before intubation and with bronchofiberscope before extubation, but no edema was recognized. Postoperatively, she was given C1-INH on the next morning again. She was discharged seven days after operation without any complications.

  13. Towards a specific marker for acute bradykinin-mediated angioedema attacks: a literature review.

    Science.gov (United States)

    Deroux, Alban; Vilgrain, Isabelle; Dumestre-Pérard, Chantal; Boccon-Gibod, Isabelle; Bouillet, Laurence

    2015-01-01

    Bradykinin-mediated angioedema (AE) is a rare disease characterised by recurrent angioedema linked to acquired (e.g. angiotensin converting enzyme inhibitor induced AE) or hereditary disorders (e.g. AE type I or II). As the clinical picture can be misleading, diagnosis of this disease is sometimes difficult. A bradykinin-mediated AE attack may be a therapeutic emergency which requires access to effective, but expensive, treatments. Their prescription must therefore be justified. No specific marker of acute bradykinin-mediated AE attacks has yet been identified to facilitate the therapeutic decision but it has been sought in many studies. This article reviews the literature on this type of biomarker, comparing candidate bradykinin-mediated AE markers to candidate markers of mast cell activation. The most interesting biomarkers are those linked to endothelial stress (VE cadherin, E-selectin, endothelin-1, von Willebrand factor and its activity) which is significantly increased during an AE attack. All these markers must now be validated by prospective studies to determine their specificity and utility in diagnosis.

  14. The humanistic burden of hereditary angioedema: results from the Burden of Illness Study in Europe.

    Science.gov (United States)

    Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B

    2014-01-01

    Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients' lives is not well understood. The study objective was to comprehensively characterize the burden of illness and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical and emotional impacts. One hundred eighty-six patients participated; 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common sites of the last attack were the abdomen and extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment physically and emotionally both during and between attacks. A better understanding of these effects may help in the clinical management of HAE patients.

  15. The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe: background and methodology

    Directory of Open Access Journals (Sweden)

    Bygum Anette

    2012-04-01

    Full Text Available Abstract Background Hereditary angioedema (HAE is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe, the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. Methods/Design This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i a survey on individuals’ health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale; and (ii one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients’ health-related quality of life. Discussion The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

  16. The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe): background and methodology.

    Science.gov (United States)

    Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa; Beusterien, Kathleen; Gholizadeh, Shadi; Musingarimi, Patience; Wait, Suzanne; Boysen, Henrik

    2012-04-26

    Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i) a survey on individuals' health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale); and (ii) one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients' health-related quality of life. The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

  17. Patients perception of self-administrated medication in the treatment of hereditary angioedema.

    Science.gov (United States)

    Wang, Adrian; Fouche, Andrew; Craig, Timothy J

    2015-08-01

    Early therapy of hereditary angioedema (HAE) decreases morbidity, improves outcomes, decreases absenteeism, and possibly decreases mortality. This can be accomplished best with self-therapy. Previously, the authors examined barriers to self-therapy from the perspective of the nurse and the physician, but data are lacking on what patients perceive as major barriers to self-administered therapy for HAE. To identify those barriers in a prospective fashion by patient interview. After approval from the institutional review board, a telephone survey was performed of patients with HAE from a database of patients who were recently seen in the clinic. The survey focused on anxiety, depression, stress, concerns regarding method of administration, the ability to inject themselves, and what they perceived as barriers to providing self-care. Ninety-two patients were contacted and 59 agreed to participate. With 69% of those patients currently undergoing self-administered treatment, the results showed minimal depression and anxiety, a high satisfaction with treatment, and significant compliance with treatment. Most of those not yet on self-administered therapy wanted to start despite being satisfied with the care received in the emergency department. They also believed care at home would be optimal. The main concern of the 2 groups was not being able to treat themselves in the event of an HAE attack. From these data, it is obvious that most patients are willing to self-treat. This suggests that physicians should encourage self-treatment of HAE to improve outcomes and quality of life of patients with HAE. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Population pharmacokinetics of recombinant human C1 inhibitor in patients with hereditary angioedema.

    Science.gov (United States)

    Farrell, Colm; Hayes, Siobhan; Relan, Anurag; van Amersfoort, Edwin S; Pijpstra, Rienk; Hack, C Erik

    2013-12-01

    To characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients. Plasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed-effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme. A one-compartment model with Michaelis-Menten elimination kinetics described the data. Baseline C1INH levels were 0.901 [95% confidence interval (CI): 0.839-0.968] and 0.176 U ml(-1) (95% CI: 0.154-0.200) in healthy volunteers and HAE patients, respectively. The volume of distribution of rhC1INH was 2.86 l (95% CI: 2.68-3.03). The maximal rate of elimination and the concentration corresponding to half this maximal rate were 1.63 U ml(-1) h(-1) (95% CI: 1.41-1.88) and 1.60 U ml(-1) (95% CI: 1.14-2.24), respectively, for healthy volunteers and symptomatic HAE patients. The maximal elimination rate was 36% lower in asymptomatic HAE patients. Peak C1INH levels did not change upon repeated administration of rhC1INH. Bodyweight was found to be an important predictor of the volume of distribution. Simulations of the proposed dosing scheme predicted peak C1INH concentrations above the lower level of the normal range (0.7 U ml(-1)) for at least 94% of all patients. The population PK model for C1INH supports a dosing scheme on a 50 U kg(-1) basis up to 84 kg, with a fixed dose of 4200 U above 84 kg. The PK of rhC1INH following repeat administration are consistent with the PK following the first administration. © 2013 The British Pharmacological Society.

  19. Presence of C1-inhibitor polymers in a subset of patients suffering from hereditary angioedema.

    Directory of Open Access Journals (Sweden)

    Daniel Elenius Madsen

    Full Text Available Hereditary angioedema (HAE is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin C1 inhibitor (C1-inh. The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks. Subjects suffering from HAE have been classified in type I patients with decreased functional and antigenic levels of C1-inh, and type II patients with decreased functional but normal antigenic C1-inh levels. However, a few reports have demonstrated that some mutations cause C1-inh polymerization in vitro, and it is speculated that C1-inh polymers may exist in patient plasma, challenging the current classification of HAE patients. To investigate the presence of C1-inh polymers in patient plasma samples, we developed an immunological method, where monoclonal antibodies produced against polymerized C1-inh were applied in native PAGE western blotting. Using this approach we analyzed genuine plasma samples from 31 Danish HAE families, and found that plasma samples from three genotypically distinct HAE type I families (classified upon C1-inh plasma concentrations contained C1-inh polymers. Identical C1-inh polymerization phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del,and one mutation affected helix C (p.Thr167Asn. In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients.

  20. Recombinant human C1-inhibitor in the treatment of acute angioedema attacks

    NARCIS (Netherlands)

    Choi, Goda; Soeters, Maarten R.; Farkas, Henriette; Varga, Lilian; Obtulowicz, Krystyna; Bilo, Barbara; Porebski, Greg; Hack, C. Erik; Verdonk, Rene; Nuijens, Jan; Levi, Marcel

    2007-01-01

    BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the

  1. Angioedema Phenotypes: Disease Expression and Classification.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Perego, Francesca; Zanichelli, Andrea; Cicardi, Marco

    2016-10-01

    Due to marked heterogeneity of clinical presentations, comprehensive knowledge of angioedema phenotypes is crucial for correct diagnosis and choosing the appropriate therapeutic approach. One of the ways to a meaningful clinical distinction can be made between forms of angioedema occurring "with or without wheals." Angioedema with wheals (rash) is a hallmark of urticaria, either acute or chronic, spontaneous or inducible. Angioedema without wheals may still be manifested in about 10 % of patients with urticaria, but it may also occur as a separate entity. Several classifications of angioedema as part of urticaria were published over time, while a latest one, released in 2014 (HAWK group consensus, see below), provided a classification of all forms of "angioedema without wheals" distinct from urticaria, which will be the focus of the present review. At this time, the HAWK consensus classification is the best in terms of covering the pathophysiology, mediators involved, angioedema triggers, and clinical expression. According to this classification, three types of hereditary angioedema (genetic C1-INH deficiency, normal C1-INH with factor XII mutations, and unknown origin) and four types of acquired angioedema (C1-INH deficiency, related to ACE inhibitors intake, idiopathic histaminergic, and idiopathic non-histaminergic) are presented. We will review the distinctive clinical features of each phenotype in details.

  2. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

    DEFF Research Database (Denmark)

    Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence

    2012-01-01

    BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic/obstetri......BACKGROUND: There are a limited number of publications on the management of gynecologic/obstetric events in female patients with hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH). OBJECTIVE: We sought to elaborate guidelines for optimizing the management of gynecologic...... section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...

  3. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea

    2015-01-01

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP...

  4. Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults: HAE-QoL.

    Science.gov (United States)

    Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia; Caminoa, Magdalena; Gómez-Traseira, Carmen; Gayá, Francisco; Aabom, Anne; Aberer, Werner; Betschel, Stephen; Boccon-Gibod, Isabelle; Bouillet, Laurence; Bygum, Anette; Csuka, Dorottya; Farkas, Henriette; Gomide, Maria; Grumach, Anete; Leibovich, Iris; Malbran, Alejandro; Moldovan, Dumitru; Mihaly, Eniko; Obtulowicz, Krystyna; Perpén, Cecilia; Peveling-Oberhag, Adriane; Porebski, Grzegorz; Chavannes, Celine Rayonne; Reshef, Avner; Staubach, Petra; Wiednig, Michaela; Caballero, Teresa

    2016-01-01

    Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) may affect health-related quality of life (HRQoL). A specific HRQoL questionnaire for adult patients with C1-INH-HAE, the HAE-QoL, has recently been developed in Spain. The objective of this study was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft version of the HAE-QoL was pilot tested in 332 patients, and accurate data were obtained from 290 patients from 11 countries. The reduction process resulted in a new version with 25 items and 7 dimensions (treatment difficulties, physical functioning and health, disease-related stigma, emotional role and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0.45 and 0.64, respectively) and with SF-36v2 dimensions (P < .004). HAE-QoL scores discriminated significantly among severity groups (median: asymptomatic 133.5 vs severe 84.0; P < .001); between patients with and without long-term prophylaxis (median: 101 vs 90; P = .001); and between patients with and without psychiatric and/or psychological care (median: 74 vs 103; P ≤ .001). The HAE-QoL, currently available in 18 languages, showed good reliability and validity evidence. Copyright © 2016 American Academy of Allergy

  5. Health-related quality of life in relation to disease activity in adults with hereditary angioedema in Sweden.

    Science.gov (United States)

    Nordenfelt, Patrik; Nilsson, Mats; Lindfors, Anders; Wahlgren, Carl-Fredrik; Björkander, Janne

    2017-11-30

    Health-related quality of life (HR-QoL) is impaired in patients with hereditary angioedema (HAE) but has not yet been satisfactorily described. To study HR-QoL in patients with HAE by combining different HR-QoL instruments with disease activity assessment. All adults in the Swedish HAE registry were invited to take part in this questionnaire study, which used the generic HR-QoL instruments, EuroQol 5 Dimensions 5 Level (EQ-5D-5L) and the RAND Corporation Short Form 36 (RAND-36), the disease-specific Angioedema Quality of Life instrument (AE-QoL), the recently introduced Angioedema Activity Score (AAS) form, and questionnaires on sick leave and prophylactic medication. Sixty-four of 133 adults (26 men, 38 women) between 18 and 91 years old responded. The most affected HR-QoL dimensions in the EQ-5D-5L were pain/discomfort and anxiety/depression; in the RAND-36, energy/fatigue, general health, pain; and, in the AE-QoL, fears/shame and fatigue/mood. Women had lower HR-QoL in the RAND-36 for general health and energy/fatigue (p 0 had significantly impaired HR-QoL. There were significant associations (p depression, and fatigue/mood are important aspects of HAE but the AE-QoL disregards pain. HR-QoL was not significantly affected by prophylaxis. Increased disease activity was associated with impaired HR-QoL, which justifies more active disease management.

  6. Angioedema hereditario: Historia familiar y manifestaciones clínicas en 58 pacientes Hereditary angioedema: Family history and clinical manifestations in 58 patients

    Directory of Open Access Journals (Sweden)

    Diego S. Fernández Romero

    2009-12-01

    Full Text Available El angioedema hereditario (AEH es una enfermedad rara, autosómica dominante, caracterizada por episodios de angioedema que comprometen la piel, el tracto gastrointestinal y la laringe. Analizamos las características epidemiológicas y clínicas en una serie de 58 pacientes, 53 (91% con diagnóstico de AEH tipo I y 5 (9% con tipo II. La edad media al inicio fue de 10.8 ± 9.5 años (0.1 a 59 y de 25.8 ± 16.2 años (2 a 77 en el momento del diagnóstico, con un retraso diagnóstico de 15.3 ± 14.3 años. El promedio de ataques en los 6 meses previos a la consulta fue de 7.4 ± 7.6 (0 a 40. Cincuenta y cuatro (93% presentaron ataques cutáneos, 50 (86% abdominales, 24 (41% laríngeos y 24 (41% cutáneos y abdominales combinados. Veintisiete (46.5% nunca utilizaron medicación preventiva para la enfermedad y 17 (29% recibieron danazol en diferentes dosis por diferentes periodos de tiempo. Durante los ataques, 15 (26% pacientes recibieron C1 inhibidor endovenoso alguna vez, 7 (12% recibieron plasma fresco y 40 (69% tratamiento sintomático. Ansiedad o situaciones de estrés y traumatismos fueron los desencadenantes más frecuentes. Identificamos a 6 (10% pacientes como primera mutación y a 52 (90% con historia familiar previa. Analizamos 20 troncos familiares identificando 205 individuos en riesgo de heredar la enfermedad, 109 (53% de ellos con síntomas o diagnóstico AEH. El total de individuos con síntomas de AEH fue de 145, de los cuales 19 (13% murieron por asfixia. Disminuir el retraso diagnóstico y ofrecer una terapéutica adecuada son desafíos a afrontar en el AEH.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema typically involving the skin, gastrointestinal tract and larynx. We here describe the epidemiologic and clinical characteristic of a series of 58 patients with diagnosis of HAE, 53 (91% type I and 5 (9% type II. The mean age at first symptom was 10.8 ± 9.5 years and the mean

  7. Bradykinin-mediated angioedema.

    Science.gov (United States)

    Obtułowicz, Krystyna

    2016-01-01

    Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life-threatening because of resistance to corticosteroids and antihistamine drugs. C1-INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin-mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes.

  8. Acute dystonic reaction leading to lingual hematoma mimicking angioedema

    Science.gov (United States)

    Sezer, Özgür; Aydin, Ali Attila; Bilge, Sedat; Arslan, Fatih; Arslan, Hasan

    2017-01-01

    Lingual hematoma is a severe situation, which is rare and endangers the airway. It can develop due to trauma, vascular abnormalities, and coagulopathy. Due to its sudden development, it can be clinically confused with angioedema. In patients who applied to the doctor with complaints of a swollen tongue, lingual hematoma can be confused with angioedema, in particular, at the beginning if the symptoms occurred after drug use. It should especially be considered that dystonia in the jaw can present as drug-induced hyperkinetic movement disorder. Early recognition of this rare clinical condition and taking precautions for providing airway patency are essential. In this case report, we will discuss mimicking angioedema and caused by a bite due to dystonia and separation of the tongue from the base of the mouth developing concurrently with lingual hematoma. PMID:29326495

  9. Use of a C1 Inhibitor Concentrate in Adults ≥65 Years of Age with Hereditary Angioedema

    DEFF Research Database (Denmark)

    Bygum, Anette; Martinez-Saguer, Inmaculada; Bas, Murat

    2016-01-01

    BACKGROUND: Treatment of hereditary angioedema (HAE) in 'older adults' (those aged ≥65 years) has not been well studied. The international Berinert Patient Registry collected data on the use of intravenous plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH; Berinert......(®)/CSL Behring) in patients of any age, including many older adults. METHODS: This observational registry, conducted from 2010 to 2014 at 30 US and seven European sites, gathered prospective (post-enrollment) and retrospective (pre-enrollment) usage and adverse event (AE) data on subjects treated with pnfC1-INH....... RESULTS: The registry documented 1701 pnfC1-INH infusions in 27 older adults. A total of 1511 HAE attacks treated with pnfC1-INH administration were reported among 25 of the 27 (92.6 %) older adults. Among the older adults, mean (standard deviation [SD]) (8.8 [4.1] IU/kg) and median (6.4 IU/kg) pnfC1-INH...

  10. [Bradykinin-induced angioedema: Definition, pathogenesis, clinical presentation, diagnosis and therapy].

    Science.gov (United States)

    Hahn, J; Bas, M; Hoffmann, T K; Greve, J

    2015-12-01

    The incidence of bradykinin-induced angioedema is considerably lower than that of histamine-induced forms; however, the same is true for the clinician's knowledge of this condition. Bradykinin-induced angioedemas include hereditary angioedema (HAE), as well as acquired forms induced by drugs or antibody formation, e.g., during the course of oncologic disease. Drug-induced forms affect almost exclusively the head and neck region, and are thus important for the otorhinolaryngologist. Clear differentiation between histamine-induced angioedema (e. g., connected to allergy/urticaria) and bradykinin-induced angioedema is essential for selection of the specific treatment and may be lifesaving. Antihistamines and cortisone derivatives have no relevant effect in bradykinin induced-angioedema, whereas blood-derived C1 esterase inhibitor and bradykinin receptor 2 antagonists represent effective therapeutic options--both for acute and prophylactic treatment.

  11. Health-Related Quality of Life with Subcutaneous C1-Inhibitor for Prevention of Attacks of Hereditary Angioedema.

    Science.gov (United States)

    Lumry, William R; Craig, Timothy; Zuraw, Bruce; Longhurst, Hilary; Baker, James; Li, H Henry; Bernstein, Jonathan A; Anderson, John; Riedl, Marc A; Manning, Michael E; Keith, Paul K; Levy, Donald S; Caballero, Teresa; Banerji, Aleena; Gower, Richard G; Farkas, Henriette; Lawo, John-Philip; Pragst, Ingo; Machnig, Thomas; Watson, Douglas J

    2018-01-31

    Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on

  12. Novelties in the Diagnosis and Treatment of Angioedema.

    Science.gov (United States)

    Cicardi, M; Suffritti, C; Perego, F; Caccia, S

    2016-01-01

    Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. In the present review, we discuss nonallergic angioedema without wheals, which can be divided into 3 acquired and 4 hereditary forms. Histamine is the mediator in acquired angioedema of unknown etiology (idiopathic histaminergic acquired angioedema), whereas in other forms the main mediator is bradykinin. Angioedema can be caused by C1-inhibitor deficiency (C1-INH-hereditary angioedema and C1-INH-acquired angioedema), mutations in coagulation factor XII (FXII-hereditary angioedema), and treatment with angiotensin-converting enzyme inhibitors (ACEI-acquired angioedema). Etiology remains unclear in acquired angioedema (idiopathic nonhistaminergic acquired angioedema) and in 1 type of hereditary angioedema (hereditary angioedema of unknown origin). Several treatments are licensed for hereditary C1-INH deficiency. Plasma-derived and recombinant C1-INHs, the bradykinin receptor blocker icatibant, and the plasma kallikrein inhibitor ecallantide have been approved for on-demand treatment to reverse angioedema symptoms. Attenuated androgen and plasma-derived C1-INH are approved for prophylaxis.

  13. Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective experimental single-cohort study

    Directory of Open Access Journals (Sweden)

    Regis Albuquerque Campos

    Full Text Available CONTEXT AND OBJECTIVE: Hereditary angioedema (HAE with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. It can be lethal due to asphyxia. The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil.DESIGN AND SETTING: Prospective experimental single-cohort study on the efficacy and safety of icatibant for HAE patients.METHODS: Patients with a confirmed HAE diagnosis were enrolled according to symptoms and regardless of the time since onset of the attack. Icatibant was administered in accordance with the protocol that has been approved in Brazil. Symptom severity was assessed continuously and adverse events were monitored.RESULTS: 24 attacks in 20 HAE patients were treated (female/male 19:1; 19-55 years; median 29 years of age. The symptoms were: subcutaneous edema (22/24; abdominal pain (15/24 and upper airway obstruction (10/24. The time taken until onset of relief was: 5-10 minutes (5/24; 20.8%; 10-20 (5/24; 20.8%; 20-30 (8/24; 33.4%; 30-60 (5/24; 20.8%; and 2 hours (1/24; 4.3%. The time taken for complete resolution of symptoms ranged from 4.3 to 33.4 hours. Adverse effects were only reported at injection sites. Mild to moderate erythema and/or feelings of burning were reported by 15/24 patients, itching by 3 and no adverse effects in 6.CONCLUSION: HAE type I patients who received icatibant responded promptly; most achieved improved symptom severity within 30 minutes. Local adverse events occurred in 75% of the patients.

  14. Acute and dramatic saxophone penis

    Directory of Open Access Journals (Sweden)

    Carlota Gutiérrez García-Rodrigo

    2015-01-01

    Full Text Available We present a case of intense genital swelling because of a hereditary angioedema. This rare disease should be included in the differential diagnosis of acute and asymptomatic genital edema, because it may prevent future potentially life-threatening episodes of visceral angioedema.

  15. Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Zahra Habibagahi

    2015-07-01

    Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.

  16. Suspected tartrazine-induced acute urticaria/angioedema is only rarely reproducible by oral rechallenge.

    Science.gov (United States)

    Nettis, E; Colanardi, M C; Ferrannini, A; Tursi, A

    2003-12-01

    Tartrazine has been frequently linked to several diseases. However, a cause-and-effect role for tartrazine in these illnesses, especially in urticaria, has not always been established. The aim of this study is to determine the incidence of intolerance to tartrazine among subjects who experienced an acute episode of urticaria/angioedema following the ingestion of a meal or a product containing this substance. This was a retrospective study based on analysis of data of patients reported to have experienced episodes of urticaria and/or angioedema after ingesting meals or products containing tartrazine. At the first visit to the outpatients clinic, a careful anamnesis had been taken. Patients had then been submitted to the following diagnostic tests: IgE tests to common inhalant allergens and food allergens and a double-blind placebo-controlled challenge with tartrazine. A total of 102 subjects were enrolled in the study: 19 (18.6%) showed at least one relevant positive reaction to an IgE test for food allergy. Only one subject (1%) had reactions after ingestion of 5 mg of tartrazine, given on day 5. She did not have adverse reactions to placebo. This study shows that the percentage of acute urticaria and/or angioedema induced by tartrazine is very low (1%). In view of our results, we suggest that all physicians with patients who have suffered adverse reactions that could be attributed to tartrazine should also carefully evaluate other possible causes.

  17. Recurrent angioedema - a case report

    OpenAIRE

    Martins, Sandrina; Salgado, Miguel; Raposo, Filipa; Pinto, Diana; Martinho, Isabel; Araújo, Ana Rita

    2016-01-01

    Introduction: Hereditary angioedema (HA) is a rare cause of recurrent angioedema caused by a default in the gene that encodes the C1 esterase inhibitor (C1-INH). The oedema involves predominantly the face, limbs and genital and gastrointestinal tract. The involvement of the larynx, although less frequent, is the most severe clinical expression of HA and is potentially fatal. Case report: Clinical report of an eight-year-old female with multiple episodes of angioedema. The...

  18. In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

    Directory of Open Access Journals (Sweden)

    Ceyda Tunakan Dalgıç

    2018-01-01

    Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

  19. Antihistamine-resistant angioedema in women with negative family history: estrogens and F12 gene mutations.

    Science.gov (United States)

    Bork, Konrad; Wulff, Karin; Witzke, Günther; Stanger, Christian; Lohse, Peter; Hardt, Jochen

    2013-12-01

    In women with sporadic recurrent angioedema with an unknown cause who are unresponsive to antihistamines and have normal C1 inhibitor activity and a negative family history of angioedema, it is unclear whether they have idiopathic angioedema or hereditary angioedema with normal C1 inhibitor, and what impact exogenous estrogens have on their angioedema. A cohort of 147 women was analyzed for F12 exon 9 mutations and for the influence of oral contraceptives, hormonal replacement therapy, and pregnancy on their angioedema. A total of 142 women had idiopathic angioedema unresponsive to antihistamines. Five women had an F12 mutation and thereby hereditary angioedema with F12 mutations. Among the women with idiopathic angioedema, 63 had never taken estrogens. There was no estrogen impact in 42 women, a moderate impact in 15 women, and a severe impact in 22 women. The type and dose of estrogens did not differ in women with and without an estrogen impact. In 5 women, idiopathic angioedema disappeared after desogestrel use. Among the 5 women with hereditary angioedema with F12 mutations, angioedema symptoms occurred during 4 pregnancies, whereas no symptoms occurred during any of the 58 pregnancies in women with idiopathic angioedema. Women with recurrent angioedema unresponsive to antihistamines may have idiopathic angioedema or, more rarely, hereditary angioedema with F12 mutations. Both conditions may be provoked or aggravated by exogenous estrogens. In idiopathic angioedema, treatment with progestins may be helpful. Copyright © 2013. Published by Elsevier Inc.

  20. Adverse events reported for hereditary angioedema medications: a retrospective study of spontaneous reports submitted to the EudraVigilance database, 2007-2013

    Directory of Open Access Journals (Sweden)

    Aagaard L

    2016-05-01

    Full Text Available Lise Aagaard,1 Anette Bygum,2 1Section for Clinical Pharmacology, Institute of Public Health, Faculty of Health Sciences, University of Southern Denmark, 2Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark Abstract: Information about long-term safety issues from use of orphan drugs in treatment of hereditary angioedema (HAE is limited and must be studied further. As clinical trials in patients with rare diseases are limited, prescribers and patients have to rely on spontaneous adverse drug reaction (ADR reports for obtaining major information about the serious, rarely occurring, and unknown ADRs. In this study, we aimed to characterize ADRs reported for HAE medications in Europe from 2007 to 2013. ADR reports submitted for C1-inibitors and bradykinin receptor antagonists to the European ADR database, EudraVigilance (EV, were included in this study. The ADR reports were categorized with respect to age and sex of the patients, category of the reporter, type and seriousness of the reported ADRs, and medications. The unit of analysis was one adverse event (AE. Totally, 187 AEs were located in EV, and of these, 138 AEs were reported for Cinryze® (C1-inhibitor (73% of the total and 49 AEs for Firazyr® (icatibant (26% of the total AEs. Approximately 60% of all AEs were serious, including three fatal cases. Less than 5% of AEs were reported in children. In total, 62% of AEs were reported for women and 38% for men. For both Cinryze® and Firazyr®, the majority of reported AEs were of the type “general disorders and administration site conditions”. For Cinryze®, a large number of AEs of the type “HAE” and “drug ineffective” was reported, but only few of these were serious. For Firazyr®, several nonserious reports on injection site reactions were reported. In conclusion, this study showed that in EV, several ADR reports from use of HAE medications were identified, and a large number of these were

  1. Bradykinin-mediated angioedema: factors associated with admission to an intensive care unit, a multicenter study.

    Science.gov (United States)

    Javaud, Nicolas; Floccard, Bernard; Gontier, Florian; Lapostolle, Frédéric; Boccon-Gibod, Isabelle; Martin, Ludovic; Amarger, Stéphanie; Boumedienne, Abdalia; Boubaya, Marouane; Asfar, Pierre; Coppere, Brigitte; Ollivier, Yann; Bouillet, Laurence; Adnet, Frédéric; Fain, Olivier

    2016-06-01

    Bradykinin-mediated angioedema is characterized by transient attacks of localized edema of subcutaneous or submucosal tissues and can be life-threatening when involving the upper airways. The aim of this study was to determine the features of acute attacks that might be associated with admission to an ICU. We carried out a retrospective, multicenter, observational study in consecutive patients attending one of six reference centers in France for acute bradykinin-mediated angioedema attacks. Patients had been hospitalized for an acute episode at least once previously. Acute attacks requiring ICU admission were compared with acute attacks that had not required ICU admission. Overall, 118 acute attacks in 31 patients were analyzed (10 patients with hereditary angioedema, 19 patients with angiotensin-converting enzyme inhibitor-induced angioedema, and two patients with acquired C1-inhibitor deficiency angioedema). In multivariate analysis, upper airway involvement, corticosteroid, and C1-inhibitor concentrate administration were associated with ICU admission. Seven episodes (18%) needed airway protection. The evolution was favorable in 38 of 39 attacks warranting ICU admission: patients were able to get out of the service (mean ICU stay 4±5 days). One death was observed by asphyxiation because of laryngeal swelling. Upper airway involvement is an independent risk factor for ICU admission. Corticosteroid use, which is an ineffective treatment, and C1-inhibitor concentrate use are factors for ICU admission. The presence of upper airway involvement should be a warning signal that the attack may be severe.

  2. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria/angioedema and after aspirin challenge.

    Science.gov (United States)

    Kasperska-Zając, A; Grzanka, A; Czecior, E; Misiolek, M; Rogala, B; Machura, E

    2013-08-01

    Active chronic urticaria, identified as a mast cell- and basophil-dependent inflammatory disorder of the skin is able to elicit acute phase response (APR). However, systemic inflammatory response in different types of urticaria is poorly characterized. To determine APR pattern in a clearly defined group of patients with acute urticaria and/or angioedema - induced by NSAIDs. Plasma IL-6 and serum C-reactive protein (CRP) concentrations were studied in 17 patients with NSAIDs-induced acute urticaria/angioedema (NSAIDsAU) and in 20 healthy controls. Eleven patients who used NSAIDs were presented at the emergency room with acute urticaria/angioedema while the remaining six manifested the symptoms during the aspirin challenge test. Patients were examined in a dynamic manner: during the acute phase, and next, after subsidence of the symptoms. CRP and IL-6 concentrations increased significantly in patients with NSAIDsAU as compared with their asymptomatic period and the healthy subjects. In addition, NSAIDsAU patients showed elevated concentration of the biomarkers following aspirin provocation with the baseline values recovered in the asymptomatic period. These results indicate that an acute systemic inflammatory response is activated in patients with NSAIDs-induced urticaria and/or angioedema. The study supports the evidence proving that up-regulation of CRP and IL-6 in urticaria/angioedema does not necessarily reflect any concomitant infection or other inflammatory processes, but may be due to the disease itself. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  3. Angioedema deaths in the United States, 1979-2010.

    Science.gov (United States)

    Kim, Susan J; Brooks, Jordan C; Sheikh, Javed; Kaplan, Michael S; Goldberg, Bruce J

    2014-12-01

    Hospital admission data indicate that the angioedema incidence has increased during the past several decades. Little is known about mortality trends. To count the number of deaths associated with angioedema in the United States, investigate correlations with age, sex, race, and other contributory causes, and analyze trends from 1979 to 2010. All US death certificates in which angioedema was listed as an underlying or contributing cause of death during 1979 to 2010 were analyzed. Age-adjusted mortality rates were analyzed by age, sex, and race. Other conditions designated as the underlying cause of death were investigated. From 1979 to 2010, there were 5,758 deaths in which angioedema was listed as a contributing cause. The age-adjusted death rate for hereditary angioedema decreased from 0.28 (95% confidence interval [CI] 0.25-0.32) to 0.06 (95% CI 0.05-0.08) per million persons per year. Conversely, mortality for angioedema increased from 0.24 (95% CI 0.21-0.27) to 0.34 (95% CI 0.31-0.37) per million. Blacks constituted 55% of angioedema deaths that were associated with use of angiotensin-converting enzyme inhibitors. On death certificates that listed hereditary angioedema as the underlying cause of death, cancer (frequently lymphoma or leukemia) was the second most commonly listed cause. Angioedema-associated deaths were very rare from 1979 to 2010. Hereditary angioedema deaths became even more so, whereas nonhereditary angioedema deaths increased. Risks associated with angiotensin-converting enzyme inhibitors were higher in blacks. Lack of specific coding for acquired angioedema most likely explains the observed association between cancer and hereditary angioedema. In the future, more granular coding systems may help distinguish hereditary from acquired angioedema. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Icatibant in angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.

    Science.gov (United States)

    Fok, J S; Katelaris, C H; Brown, A F; Smith, W B

    2015-08-01

    Angioedema occurs in up to 2% of those taking angiotensin-converting enzyme (ACE) inhibitors. Upper airway angioedema may potentially require endotracheal intubation or cricothyrotomy, and is usually unresponsive to adrenaline. The bradykinin receptor antagonist icatibant is proven to be effective in the treatment of acute attacks of hereditary angioedema, and has also been reported effective in the treatment of angioedema associated with ACE inhibitors. To describe the use of icatibant for ACE inhibitor-associated airway angioedema. We treated 13 consecutive emergency department (ED) patients, who had not improved with adrenaline and/or corticosteroids, with icatibant 30 mg subcutaneously for ACE inhibitor-associated upper respiratory tract angioedema according to an agreed protocol. Four patients were intubated in the ED either before or after receiving icatibant; three of these were extubated within 24 h of treatment. Eight patients received early icatibant and did not require intubation. The time from onset of airway angioedema to ED presentation ranged from 1 h to 3 days (median 4 h); from ED presentation to receiving icatibant, from 30 minutes to 3 days (median 3 h); and to onset of symptom improvement after icatibant, 15 minutes to 7 h (median 2 h). One patient received a second dose of icatibant. All patients improved after receiving icatibant, consistent with its bradykinin receptor blocking mechanism. Icatibant rapidly reversed symptoms, and appeared to avert the need for intubation or expedite extubation. Timely use of icatibant in ACE inhibitor-associated angioedema may avert the need for invasive airway procedures and intensive care unit admission. © 2015 Royal Australasian College of Physicians.

  5. Lesson of the month 2: The limitations of steroid therapy in bradykinin-mediated angioedema attacks.

    Science.gov (United States)

    Ismail, Sharif; Cheng, Leo; Grigoriadou, Sofia; Laffan, James; Menon, Manoj

    2015-02-01

    Acute angioedema attacks are conventionally treated with antihistamines and steroids, in line with a presumed mechanism of disease involving overwhelming mast-cell degranulation. This approach overlooks a small but important minority of cases in which attacks are bradykinin driven and exhibit poor responsiveness to steroid or anti-histamine therapy. These patients may have a family history of angioedema (hereditary angioedema), or a past medical history including B-cell lymphoproliferative disorders or autoimmune disease (acquired angioedema). Rather than steroid therapy, they respond to administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute, to control acute symptoms and reduce the probability of invasive airway insertion. In the long-term, they require C1 esterase inhibitor sparing therapy and a treat-the-cause approach to reduce the risk of recurrent attacks. We present here a case of a middle-aged woman who presented with recurrent angioedema of initially uncertain aetiology. © 2015 Royal College of Physicians.

  6. ACE inhibitor-induced angioedema.

    Science.gov (United States)

    Baram, Michael; Kommuri, Anand; Sellers, Subhashini A; Cohn, John R

    2013-01-01

    Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed for blood pressure control and renal protection. ACEI angioedema is a common problem in patients who are taking ACEI, although, in most cases, the disorder is self-limited, and spontaneous episodes of apparently unprovoked angioedema stop with the discontinuation of the medication. In a subset of patients, hospitalization and even intubation are required for airway protection. The diagnosis is made clinically. There are no laboratory studies that establish the diagnosis. However, such investigations help exclude alternative diagnoses as the cause for the patient's presentation. Conventional treatment with regimens used to control allergic angioedema is ineffective in this condition. The mechanism of ACEI-induced angioedema is thought to be related to its effect on the kallikrein-kinin system. Kallikrein is a protease that converts high-molecular-weight kininogens into kinins, primarily bradykinin. Medications recently developed, primarily icatibant and ecallantide, to control hereditary angioedema, a disorder also associated with kallikrein-kinin activation, have been used to treat ACEI angioedema with some success. The efficacy of these agents and their optimal use remains to be established by randomized and placebo controlled trials. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. "Nuts and Bolts" of Laboratory Evaluation of Angioedema.

    Science.gov (United States)

    Farkas, Henriette; Veszeli, Nóra; Kajdácsi, Erika; Cervenak, László; Varga, Lilian

    2016-10-01

    Angioedema, as a distinct disease entity, often becomes a clinical challenge for physicians, because it may cause a life-threatening condition, whereas prompt and accurate laboratory diagnostics may not be available. Although the bedside diagnosis needs to be established based on clinical symptoms and signs, family history, and the therapeutic response, later, laboratory tests are available. Currently, only for five out of the nine different types of angioedema can be diagnosed by laboratory testing, and these occur only in a minority of the patient population. Hereditary angioedema with C1-inhibitor (C1-INH) deficiency type I can be diagnosed by the low C1-INH function and concentration, whereas in type II, C1-INH function is low, but its concentration is normal or even elevated. C1q concentration is normal in both forms. Acquired angioedema with C1-INH deficiency type I is characterized by the low C1-INH function and concentration; however, C1q concentration is also low, and autoantibodies against C1-INH cannot be detected. Complement profile of acquired angioedema with C1-INH deficiency type II is similar to that of type I, but in this form, autoantibodies against C1-INH are present. Hereditary angioedema due to a mutation of the coagulation factor XII can be diagnosed exclusively by mutation analysis of FXII gene. Diagnostic metrics are not available for idiopathic histaminergic acquired angioedema, idiopathic non-histaminergic acquired angioedema, acquired angioedema related to angiotensin-converting enzyme inhibitor, and hereditary angioedema of unknown origin; these angioedemas can be diagnosed by medical and family history, clinical symptoms, and therapeutic response and by excluding the forms previously described. Several potential biomarkers of angioedema are used to date only in research. In the future, they could be utilized into the clinical practice to improve the differential diagnosis, therapy, as well as the prognosis of angioedema.

  8. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    NARCIS (Netherlands)

    Levi, Marcel; Choi, Goda; Picavet, Charles; Hack, C. Erik

    2006-01-01

    BACKGROUND: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by C1-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause

  9. Classification, diagnosis, and approach to treatment for angioedema

    DEFF Research Database (Denmark)

    Cicardi, M; Aberer, W; Banerji, A

    2014-01-01

    Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have...... angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired...... and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema....

  10. Socioeconomic burden of hereditary angioedema

    DEFF Research Database (Denmark)

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen

    2014-01-01

    .001). Among patients who sought medical care during the last attack (23%), more than half utilized the emergency department. The last attack prevented patients from their normal activities an average of 4-12 hours. Patient and caregiver absenteeism increased with attack severity and frequency. Among patients...... who were working or in school (n = 120), 72 provided work/school absenteeism data, resulting in an estimated 20 days missing from work/school on average per year; 51% (n = 84) indicated that HAE has hindered their career/educational advancement. CONCLUSION: HAE poses a considerable burden on patients...... and their families in terms of direct medical costs and indirect costs related to lost productivity. This burden is substantial at the time of attacks and in between attacks....

  11. [Angioedema and urticaria].

    Science.gov (United States)

    Boccon-Gibod, I; Bouillet, L

    2014-11-01

    Angiœdema (AE) is the clinical expression of urticaria (U) which occurs when urticaria is located within the subcutis. It is a syndrome characterized by a sudden and limited subcutaneous and/or submucous swelling. The updated classification of urticaria distinguishes acute and chronic urticaria. Chronic urticaria is spontaneous (CSU) or inducible (CIU). Angioedema in chronic urticaria is rarely allergic, but most of the time caused by a non-specific histamine release from activated mast-cell (non IgE mediated reaction). Angioedemas are recurrent, concomitant or not with wheals. They appear skin-coloured, sometimes slightly rosy, non-inflammatory, and more painful than itchy. They are transient, ephemeral, migrant, last most of the time a few hours (Angioedema can be elicited or worsened by physical factors (cold urticaria, exercise, heat, solar, vibratory, aquagenic, delayed pressure urticaria…) and /or drugs (as aspirin, nonsteroid anti-inflammatory drugs, morphine, antibiotics…). The treatment of histaminergic angioedemas of chronic urticaria is based on modern second generation antihistamines (anti H1). In allergic acute urticaria only, additional treatment for anaphylaxis can be used if needed (grade 2 to 4). In chronic urticaria, steroids should be avoided : they can make symptoms worse and long-lasting because of corticosteroid dependence. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Angiotensin Converting Enzyme-induced Angioedema - A Dangerous New Epidemic

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette

    2013-01-01

    Angioedema is a sudden localised and often asymmetric swelling of the skin or mucous membranes caused by transient increased endothelial permeability causing plasma extravasation. In the last decades the incidence of severe angioedema involving the upper airways and even fatal outcome due....... The diagnosis is often delayed and traditional treatment usually ineffective. Complement C1 inhibitor concentrate and bradykinin receptor antagonists, normally used to treat patients with hereditary angioedema, have shown good results when used in patients with bradykinin-mediated angioedema. This review...

  13. Angioedema without urticaria in childhood.

    Science.gov (United States)

    Ertoy Karagol, Hacer I; Yilmaz, Ozlem; Bakirtas, Arzu; Topal, Erdem; Demirsoy, Mehmet S; Turktas, Ipek

    2013-11-01

    There has been no separate study investigating angioedema without urticaria (Aw/oU) exclusively in children so far. The purpose of this study was to investigate the frequency, clinical presentation, etiology, management and follow-up of Aw/oU in children. This is a prospective study that included all consecutive patients with a history of Aw/oU referred to our clinic between January 2011 and May 2012. A standard diagnostic and therapeutic algorithm was applied to all patients. The frequency of Aw/oU was found to be 1.6% during the study period. An etiological factor could be found in only 45 patients (49%). The causes of Aw/oU were infection (21%), allergy (14%), thyroid autoimmunity (TA)-related (8%) and nonsteroid anti-inflammatory drug hypersensitivity (6%), and idiopathic angioedema (51%). There was no hereditary type I, II or acquired type of angioedema or rare syndromes associated with Aw/oU. The median follow-up was 16 months (range: 12-30 months). Antihistamine prophylaxis was initiated at therapeutic doses in 20 patients with frequently recurrent angioedema due to idiopathic and euthyroid TA-related Aw/oU for 3 months. These patients responded to antihistamine prophylaxis for 3 months. Four patients relapsed after cessation of prophylaxis at the end of 3 months. Antihistamine prophylaxis was prolonged to 6 months in three patients and to 9 months in one patient. Angioedema without urticaria in children is a rare condition and no etiology can be identified in half of them. Antihistamine treatment alone is sufficient, and prognosis is good in recurrent non hereditary cases in a short-term follow-up period. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Current treatment options for idiopathic angioedema.

    Science.gov (United States)

    Shroba, Jodi; Hanson, Jill; Portnoy, Jay

    2015-11-01

    Idiopathic angioedema is defined as localized swelling of the cutaneous and mucosal tissue that occurs in episodes without a clear etiology. It can be problematic to treat when the underlying pathophysiology is not well understood. To identify successful treatments of idiopathic angioedema reported in the literature. A literature search was performed using PubMed. Published case reports and articles discussing treatment of idiopathic angioedema were used in the formulation of this review. In addition, 2 case reports are provided. Although there are no approved treatments for idiopathic angioedema, several medications used for the treatment of hereditary angioedema, such as bradykinin receptor antagonists (icatibant), kallikrein inhibitors (ecallantide), and C1 inhibitors, were successful in 10 patients. Anti-IgE monoclonal antibody (omalizumab) proved successful in 5 patients. The most widely used and successful medication was tranexamic acid (154 patients). Despite an unknown etiology, this article highlights viable treatment options for idiopathic angioedema. More clinical trials and better markers identifying the cause of angioedema are needed. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hossein Vakili

    2014-01-01

    Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

  16. Urticaria and Angioedema – More than just Skin Deep!

    African Journals Online (AJOL)

    Hereditary or acquired deficiency, or functional impairment, of the C1 esterase enzyme should be also considered, especially if there is a family history of swelling, airway compromise or surgical complications indicating possible hereditary angioedema. .... Depression, functional and sleep impairment are common and it.

  17. Angioedema due to Systemic Isotretinoin Therapy

    Directory of Open Access Journals (Sweden)

    Pelin Üstüner

    2014-01-01

    Full Text Available Angioedema is the swelling of the mucosal membranes as a variant of urticaria induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne presenting with widespread facial angioedema on the 2nd day of systemic isotretinoin treatment. The patient had taken no drugs other than isotretinoin in the preceding days and had no known food allergy. Her angioedema was resolved after the isotretinoin was discontinued. We want to draw the attention of dermatologists to this rare adverse allergic effect of isotretinoin which is frequently used in the treatment of acne vulgaris.

  18. Chapter 21: Urticaria and angioedema.

    Science.gov (United States)

    Carr, Tara F; Saltoun, Carol A

    2012-01-01

    Urticaria, also known as hives, may affect up to 20% of the population at some time in their lives. Urticaria is characterized by extreme pruritus and described as erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. The pathogenesis of urticaria involves mast cell activation, with subsequent release of histamine and other vasoactive mediators, leading to increased vascular permeability of postcapillary venules and development of edema, erythema, and pruritus. Urticaria is closely associated with angioedema in 40% of individuals; ∼10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized with multiple lesions in no specific distribution; angioedema tends to be localized, commonly affecting the face (periorbital and perioral regions), tongue, uvula, soft palate or larynx, extremities, and genitalia. Urticaria is subdivided into acute and chronic urticaria based on duration of symptoms. Acute urticaria lasts products, medications (aspirin, nonsteroidal anti-inflammatory drugs, and antibiotics), or insect stings. Urticaria lasting >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered idiopathic. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto's disease) and urticaria and angioedema with higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these usually euthyroid patients. Furthermore, studies have revealed a circulating IgG antibody directed against the IgE receptor (F(Cε)RIα) or IgE in 40-60% of patients with chronic urticaria. Histamine 1-receptor antagonists (antihistamines) are initial therapy.

  19. Burden of Illness and Quality-of-Life Measures in Angioedema Conditions.

    Science.gov (United States)

    Caballero, Teresa; Prior, Nieves

    2017-08-01

    Burden of illness studies and evaluation of health-related quality of life using validated questionnaires have become an important task in the comprehensive management of angioedema conditions, mainly angioedema associated with chronic spontaneous urticaria and hereditary angioedema caused by C1-inhibitor deficiency. A review of the principal tools and studies is presented. Both diseases present a higher proportion of psychiatric disorders, impair work and studies productivity, and produce high direct and indirect costs. These assessments also have been useful to evaluate the positive impact of new drugs and interventions. More studies are desirable, especially in other types of angioedema disorders, such as hereditary angioedema with normal C1 inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. [Angioedema and the role of bradykinins: new treatments and implications in patients with heart failure].

    Science.gov (United States)

    Mansi, Marta; Wu, Maddalena Alessandra; Zanichelli, Andrea; Cicardi, Marco

    2016-12-01

    The definition of angioedema is an edema of subcutaneous and submucosal tissues due to increased vascular permeability and fluid extravasation. It can affect different areas, including extremities, genitals, upper airways and intestinal mucosa. The symptoms are disabling and this condition can be fatal if it involves the larynx. We can distinguish different forms of angioedema (hereditary and acquired) with different pathogenetic mechanisms, therefore responding to different treatments. Bradykinin-mediated angioedema (such as hereditary angioedema due to C1-inhibitor deficiency) does not respond to the standard therapy used for histamine-mediated angioedema. These forms should be immediately recognized and specific treatment should be used. In addition, when a patient manifests hypotension not responding to fluid replacement and associated with diffuse edema, hypoalbuminemia and hemoconcentration, we should consider the diagnosis of idiopathic systemic capillary leak syndrome, a very rare but fatal condition.

  1. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death.

    Science.gov (United States)

    Atalay, Eray; Özdemir, Mehmet Tamer; Çiğsar, Gülşen; Omurca, Ferhat; Aslan, Nurullah; Yildiz, Mehmet; Gey, Zehra Bahar

    2015-12-01

    Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

  2. Angioedema: etiology, pathophysiology, current and emerging therapies.

    Science.gov (United States)

    Lewis, Lawrence M

    2013-11-01

    Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%. This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments. Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE. New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Drug-induced angioedema: experience of Italian emergency departments.

    Science.gov (United States)

    Bertazzoni, G; Spina, M T; Scarpellini, M G; Buccelletti, F; De Simone, M; Gregori, M; Valeriano, V; Pugliese, F R; Ruggieri, M P; Magnanti, M; Susi, B; Minetola, L; Zulli, L; D'Ambrogio, F

    2014-06-01

    Acute angioedema represents a cause of admission to the emergency department requiring rapid diagnosis and appropriate management to prevent airway obstruction. Several drugs, including angiotensin-converting enzyme inhibitors (ACE-I), nonsteroidal anti-inflammatory drugs (NSAIDs) and oral antidiabetics, have been reported to induce angioedema. The aim of this prospective observational study conducted in a setting of routine emergency care was to evaluate the incidence and extent of drug-induced non-histaminergic angioedema in this specific clinical setting, and to identify the class of drugs possibly associated with angioedema. Patients admitted to seven different emergency departments (EDs) in Rome with the diagnosis of angioedema and urticaria were enrolled during a 6-month period. Of the 120,000 patients admitted at the EDs, 447 (0.37 %) were coded as having angioedema and 655 (0.5 %) as having urticaria. After accurate clinical review, 62 cases were defined as drug-induced, non-histaminergic angioedema. NSAIDs were the most frequent drugs (taken by 22 out of 62 patients) associated with the angioedema attack. Of the remaining patients, 15 received antibiotic treatment and 10 antihypertensive treatment. In addition, we observed in our series some cases of angioedema associated with drugs (such as antiasthmatics, antidiarrheal and antiepileptics) of which there are few descriptions in the literature. The present data, which add much needed information to the existing limited literature on drug-induced angioedema in the clinical emergency department setting, will provide more appropriate diagnosis and management of this potentially life-threatening adverse event.

  4. The role of icatibant-the B2 bradykinin receptor antagonist-in life-threatening laryngeal angioedema in the ED.

    Science.gov (United States)

    Bartal, Carmi; Zeldetz, Vladimir; Stavi, Vered; Barski, Leonid

    2015-03-01

    Angioedema is a localized, sudden, transient, and often recurrent swelling of the deeper layers of the skin or mucosa with no epidermal component. It is caused by vasoactive substances that produce a transient increase in endothelial permeability. Angioedema involving the laryngeal components is a life-threatening situation for the patient,and it is a challenge for the emergency medicine physician to rapidly achieve a safety airway. Most cases of laryngeal angioedema are induced by histamine release; but 10% are bradykinin induced, which does not respond to the conventional algorithm of treating allergic induced angioedema. We present a case report of an angiotensin converting enzyme (ACE) inhibitor–induced laryngeal angioedema alleviated only after treatment with the new bradykinin receptor inhibitor medication icatibant which was licensed only for use in hereditary angioedema. We reviewed the literature for the use of icatibant in acquired drug-induced angioedema; and because of the similar pathogenesis between the hereditary angioedema and the ACE inhibitor–induced angioedema,we propose an algorithm for careful use of icatibantin life-threatening angioedema in the emergency department.

  5. Fatal laryngeal angioedema: a case report and a workup of angioedema in a forensic setting.

    Science.gov (United States)

    Krizova, Adriana; Gardner, Taylor; Little, D'Arcy L; Arcieri-Piersanti, V; Pollanen, Michael S

    2015-12-01

    Angioedema is an episodic swelling of the deep dermis, subcutis, and/or submucosal tissue due to an increase in local vascular permeability. Swelling may involve skin, respiratory, and gastrointestinal tracts. The most commonly involved areas are the periorbital region and the lips. Here we report a case of a fatal laryngeal obstruction due to angioedema likely caused by an angiotensin-converting-enzyme inhibitor. The decedent, a 58-year-old man, was witnessed developing sudden facial swelling and acute respiratory difficulties quickly followed by unresponsiveness. His past medical history suggested that this was his second episode of angioedema without urticaria. Postmortem examination revealed a complete laryngeal obstruction in the absence of infection, neoplasm, or autoimmune disease. Postmortem computed tomography of the head and neck showed a complete obstruction of the upper airway. Based on the current understanding of the pathophysiology of different types of angioedema, we will suggest a workup of angioedema without urticaria in the forensic setting and offer readers resources they can use in their practice.

  6. Hereditary Pancreatitis

    Science.gov (United States)

    ... E-News Sign-Up Home Hereditary Pancreatitis Hereditary Pancreatitis Hereditary Pancreatitis (HP) is a rare genetic condition characterized by ... of pancreatic attacks, which can progress to chronic pancreatitis . Symptoms include abdominal pain, nausea, and vomiting. Onset ...

  7. Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

    Science.gov (United States)

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

  8. Angioedema Due to Pear: Medical Image

    Directory of Open Access Journals (Sweden)

    Cemil Kavalci

    2014-03-01

    Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 60-years-old female patient presented to our emergency department with dispne and edema in her mouth and lips. It was learned from the history that her symptoms were begun 15 minutes after eating a pear. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  9. Angioedema due to Pomegranate: Original Image

    OpenAIRE

    Meliha Findik

    2014-01-01

     Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  10. Angioedema due to Pomegranate: Original Image

    Directory of Open Access Journals (Sweden)

    Meliha Findik

    2014-03-01

    Full Text Available  Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  11. Angioedema Due to Pear: Medical Image

    OpenAIRE

    Cemil Kavalci

    2014-01-01

      Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 60-years-old female patient presented to our emergency department with dispne and edema in her mouth and lips. It was learned from the history that her symptoms were begun 15 minutes after eating a pear. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  12. Phenotype Standardization of Angioedema in the Head and Neck Region Caused by Agents Acting on the Angiotensin System

    Science.gov (United States)

    Wadelius, M; Marshall, S E; Islander, G; Nordang, L; Karawajczyk, M; Yue, Q-Y; Terreehorst, I; Baranova, E V; Hugosson, S; Sköldefors, K; Pirmohamed, M; Maitland-van der Zee, A-H; Alfirevic, A; Hallberg, P; Palmer, C N A

    2014-01-01

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema. PMID:24960520

  13. Trifluoperazine-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Mugtaba Osman

    2014-01-01

    Full Text Available Angioedema is a serious adverse drug reaction that can rarely be associated with trifluoperazine treatment. We present the case of a 44-year-old male with an established diagnosis of schizoaffective disorder, for which trifluoperazine therapy was considered. He presented to the emergency department with bilateral lower limb oedematous painful erythematous swelling that eased off completely when trifluoperazine was stopped. The possibility of allergic reaction, such as angioedema, should always be kept in mind by psychiatrists and mental health professionals when prescribing trifluoperazine antipsychotic.

  14. Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

    Science.gov (United States)

    Guarneri, Fabrizio; Guarneri, Claudio; Marini, Herbert Ryan

    2014-01-01

    Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation. © 2014 Wiley Periodicals, Inc.

  15. MR imaging of intestinal angioedema related to angiotensin-converting enzyme inhibitors: Report of three cases and review of literature.

    Science.gov (United States)

    Savino, Michael R; Mittal, Pardeep K; Miller, Frank H

    Angioedema is a condition in which an increase in vascular permeability leads to the swelling of body tissues. There are both hereditary and acquired forms of the disease, with the latter often associated with the administration of angiotensin-converting enzyme inhibitor medication. Involvement of the intestinal tract is a rare manifestation of angioedema, and can present with abdominal pain, nausea, and vomiting. It is critical for radiologists to be aware of this entity, as they may have the only opportunity to make the diagnosis. We present three cases of intestinal angioedema diagnosed on MRI with discussion of the imaging findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Angioedema: Clinical and Etiological Aspects

    Directory of Open Access Journals (Sweden)

    Kanokvalai Kulthanan

    2007-01-01

    Full Text Available Angioedema is an abrupt swelling of the skin, mucous membrane, or both including respiratory and gastrointestinal tracts. This study aimed to report an experience of angioedema in a university hospital with respect to etiologies, clinical features, treatment, and outcome. One hundred and five patients were enrolled. About half had angioedema without urticaria. The common sites of involvement were periorbital area and lips. Forty five patients (49% had systemic symptoms. The most common cause of angioedema was allergic angioedema. Nonsteroidal anti-inflammatory drug-induced angioedema and idiopathic angioedema were detected in 20% and 18%, respectively. Among patients with allergic angioedema, 41.7% were caused by food, 39.6% by drugs. Thirty seven patients (39% had recurrent attacks of angioedema. Mean standard deviation (SD number of attacks in patients with recurrent angioedema was 3.9 (2.7 (ranging from 2 to 10 times. Patients who had older age and multiple sites of skin involvement had tendency to have systemic symptoms.

  17. Treatment of angiotensin receptor blocker-induced angioedema: A case series.

    Science.gov (United States)

    Strassen, Ulrich; Bas, Murat; Hoffmann, Thomas K; Knopf, Andreas; Greve, Jens

    2015-07-01

    Angiotensin II receptor antagonists have been proposed as a replacement therapy after the occurrence of either an angiotensin converting enzyme (ACE) inhibitor-induced angioedema or cough. However, recent studies indicate that angioedema is associated with elevated bradykinin levels in a small fraction of patients treated with angiotensin-II-receptor blockers, suggesting a common pathophysiological mechanism. To date, a standard treatment for angiotensin II receptor blocker-induced angioedema does not exist. We present a case series of patients admitted to our hospital due to angioedema induced by an angiotensin II receptor blocker. The patients were either treated with either icatibant (n = 3) or prednisolone-21-hydrogen succinate/clemastine (n = 5). Both patient groups were compared with an untreated patient cohort (n = 3). All patients were previously diagnosed with essential hypertonia. Icatibant was an effective therapy for angiotensin II receptor blocker-induced angioedema. Full symptom recovery was achieved after 5 to 7 hours, whereas symptom remission occurred within 27 to 52 and 24 to 54 hours in patients treated with Solu-Decortin prednisolone/clemastine and untreated patients, respectively. The recovery time for icatibant was similar to that described in previous studies regarding the therapeutic efficacy of icatibant for the treatment of hereditary angioedema and patients suffering from angiotensin converting enzyme inhibitor-induced angioedema. Icatibant is a safe and effective substance for the treatment of angiotensin II receptor blocker-induced angioedema. Although the pathophysiology of angiotensin II receptor blocker-induced angioedema remains unclear, it appears to be associated with the bradykinin pathway. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Hereditary Neuropathies

    Science.gov (United States)

    ... and autonomic neuropathy. The most common type is Charcot-Marie-Tooth disease, one of the hereditary motor and sensory ... and autonomic neuropathy. The most common type is Charcot-Marie-Tooth disease, one of the hereditary motor and sensory ...

  19. Urticaria and angioedema – more than just skin deep! | Holtzhausen ...

    African Journals Online (AJOL)

    Urticaria and angioedema are characterized by pruritic hives and sometimes swelling of deeper mucocutaneous layers. Urticaria is caused by release of histamine and other mediators from mast cells. A cut-off of six weeks distinguishes acute and chronic forms, as these seem to differ regarding etiological and response ...

  20. The Story of Angioedema: from Quincke to Bradykinin.

    Science.gov (United States)

    Reshef, Avner; Kidon, Mona; Leibovich, Iris

    2016-10-01

    The term "swelling" has been used in the old scriptures to illustrate a change of normal figure and, as such, an expression of illness. It should be noted that in ancient times, human diseases were very often regarded a punishment from God. Hence, it is not surprising that one of the oldest tests for infidelity involved swelling as an inflicted punishment. The great Greek physician Hippocrates (377-460 BC), considered one of the most outstanding figures in the history of medicine and "Father of the Western Medicine," already used the term oídēma to describe swelling of organs. It took many centuries later until the first description of angioedema as a distinct medical entity was minted by Quinke in 1882. The historical progression in angioedema research has been characterized by intermittent "leaps" in interest and scientific achievements. As an example, it took 75 years from the accurate description of hereditary angioedema (HAE) by Osler (1888), until a group of researchers headed by Donaldson (1963) disclosed the central role of C1 inhibitor in angioedema pathophysiology. What followed was a result of a collective effort by many researchers and scientific groups who were able to elucidate the intricate connections between the implicated biochemical pathways. Still, scientific progress was hardly translated into effective therapy, and another 45 years had to elapse until the renewed interest in HAE was boosted by studies on the efficacy and safety of novel therapies about 10 years ago. In the twenty-first century, HAE ceased to be an "orphan disease" and its future is far more optimistic. It is better managed now by specialized angioedema centers, harmonized clinical guidelines, educational programs, laboratory services, and continued basic and clinical research. Patient associations worldwide are offering support and guidance, and governments and healthcare systems are gradually addressing patient and family needs.

  1. Current and future therapies for the treatment of histamine-induced angioedema.

    Science.gov (United States)

    James, Christine; Bernstein, Jonathan A

    2017-02-01

    Angioedema, a sudden, self-limited swelling of localized areas of any part of the body that may or may not be associated with urticaria, is thought to be the result of a mast-cell mediated process versus a bradykinin etiology. Understanding the mechanism is key in determining the proper treatment. Areas Covered: Clinical presentation of varying angioedema types may be similar; however, the appropriate treatment algorithm is dependent upon clinicians' knowledge of the underlying pathophysiology and classification of angioedema. Literature review of recent guidelines, available medications, and alternative therapies was completed to provide an overview of options. There are no formal guidelines for treatment of acute or chronic histamine-mediated angioedema, and therefore, algorithms for the treatment of acute and chronic urticaria should be followed until such information becomes available. Differentiating histamine-mediated versus bradykinin mediated angioedema is essential, as treatments and treatment responses are quite different. Further research is needed to better understand idiopathic angioedema that is unresponsive to H1/H2 antagonists, LTMAs, or medications designed to treat bradykinin-mediated angioedema.

  2. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    DEFF Research Database (Denmark)

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...... concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema...

  3. The Clinical Evaluation of Angioedema.

    Science.gov (United States)

    Gill, Parwinder; Betschel, Stephen D

    2017-08-01

    The clinical evaluation of angioedema is reliant on obtaining a thorough patient and family history with an assessment of risk factors and presenting symptoms unique to each subtype. It is important to distinguish between angioedema with and without urticaria as a primary step in the evaluation; thereafter, laboratory parameters and investigations allow for subsequent stratification. There is a significant disease burden associated with angioedema and thus it is essential for health care practitioners to establish a prompt and accurate diagnosis, and a comprehensive care plan that addresses the patient's physical and mental well-being alike. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  4. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Directory of Open Access Journals (Sweden)

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  5. [Management of bradykinin-mediated angioedema].

    Science.gov (United States)

    Floccard, B; Crozon, J; Rimmelé, T; Vulliez, A; Coppere, B; Chamouard, V; Boccon-Gibod, I; Bouillet, L; Allaouchiche, B

    2011-01-01

    Present the clinical signs of bradykinin-mediated angioedema, a disease little known to intensive care anaesthesiologists, and develop their scientific basis with recent data on management in emergency and perioperative care. International recommendations and recent general reviews. Data collection was performed using the Medline database with the keyword: angioedema. Research studies published during the last 10 years were reviewed. Relevant clinical information was extracted and discussed. Angioedema is a clinical syndrome characterized by episodes of transitory recurrent submucosal and subcutaneous oedema, called attacks. During an attack, the oedema may be localized at the level of the skin and/or ENT and digestive tract mucosa. This syndrome is not due to an allergic reaction. It is related to a C1 complement inhibitor deficiency or an increase in factor XII resulting in the excessive release of bradykinin, which leads to capillary permeability. There are hereditary and acquired forms, notably associated with the use of ACE inhibitors and sartans. This rare disease should be recognized by anaesthesiologists and intensive care and emergency physicians because, in the absence of specific treatment, it can be life-threatening due to the appearance of laryngeal oedema. In addition, there is a risk that the patient may have an attack during the perioperatory period, due to surgical trauma. International recommendations exist, and there are new molecules available in France. For moderate attacks, treatment is based on tranexamic acid. For hereditary forms, according to the localization and gravity of the attacks, emergency treatment is based on the use of Icatibant, a bradykinin B2 receptor inhibitor, and C1 inhibitor concentrate. For pregnant women and acquired forms, C1 inhibitor concentrate is the treatment of reference. Antalgic and perfusion treatments should not be neglected, and should be modified as a function of clinical signs. High-risk situations

  6. Factors associated with hospitalization of patients with angiotensin-converting enzyme inhibitor–induced angioedema

    Science.gov (United States)

    Gang, Cheng; Lindsell, Christopher J.; Moellman, Joseph; Sublett, Wesley; Hart, Kim; Collins, Sean

    2013-01-01

    Angiotensin-converting enzyme inhibitor (ACE-I)–induced angioedema can be life-threatening without emergent intervention. The putative mediator is believed to be bradykinin, similar to hereditary angioedema, so these patients respond poorly to corticosteroids and antihistamines. This study was designed to determine characteristics and clinical outcomes of patients presenting to an emergency department (ED) with ACE-I angioedema. This was a retrospective chart review of 100 patients presenting to the ED from 2007 to 2008 with an ICD-9 code of 995.1 (angioedema) or 995.2 (drug-induced angioedema). Two hundred fifty-two patients with these ICD-9 codes were identified and placed in random order, and the first 100 meeting inclusion criteria were included. Statistical analysis was primarily descriptive. All 100 patients had an ICD-9 code of 995.1 (angioedema). Patients presented in every month, with spring months (April–June) having the most presentations (32%). The median age was 59 years, 75% were African American, and 66% were admitted to the hospital. Two patients (2%) required endotracheal intubation. Lisinopril was the most commonly prescribed ACE-I (84%). The most common symptom was moderate lip and tongue swelling (89%) followed by mild difficulty breathing (12%). Tongue swelling was significantly associated with admission. Time from symptom onset to ED presentation was not associated with need for admission. Concomitant medications did not differ between admitted and discharged patients. ACE-I angioedema is associated with significant morbidity and health care use because many patients require hospitalization, suggesting an unmet need for novel therapies targeted to treat this condition. PMID:23676576

  7. A Novel Approach to the Treatment of Orolingual Angioedema After Tissue Plasminogen Activator Administration.

    Science.gov (United States)

    Pahs, Lesley; Droege, Chris; Kneale, Hilary; Pancioli, Arthur

    2016-09-01

    Orolingual angioedema is a rare adverse effect of tissue plasminogen activator (tPA), with an incidence of 1% to 5%. There are currently no published reports describing resolution of tPA-induced orolingual angioedema with complement inhibitor therapy. A 72-year-old man receiving home angiotensin-converting enzyme inhibitor therapy presented to the emergency department with newly developed orolingual angioedema after treatment with tPA for acute ischemic stroke. Therapy was initiated with intravenous methylprednisolone 125 mg, famotidine 20 mg, and diphenhydramine 50 mg, without significant improvement. Because of increased concern for airway protection, plasma-derived C1 esterase inhibitor was administered. Concerns about progressive and airway-threatening orolingual angioedema subsided 2 hours after administration, and invasive airway maneuvers were avoided. Orolingual angioedema is an infrequent, severe adverse effect of tPA for treatment of acute ischemic stroke. Complement inhibitors may be an additional therapeutic option for patients presenting with orolingual angioedema with potential airway compromise that is refractory to standard anaphylactic therapies. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  8. The Humanistic, Societal, and Pharmaco-economic Burden of Angioedema.

    Science.gov (United States)

    Longhurst, Hilary; Bygum, Anette

    2016-10-01

    Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disorder characterized by intermittent and unpredictable episodes of swelling which cause disfigurement, disability, pain, or, in case of laryngeal swelling, risk of death. Historical factors, including the intermittent nature of the disorder, the lack of awareness of this ultra-rare condition amongst medical personnel, lack of specialist centers, and limited treatment options have contributed to under-diagnosis and under-treatment of the condition. Incorrect treatment of attacks has been common, even when medical help is sought. This has lead to reduced health-seeking behavior and alternative coping strategies, sometimes even denial, in many families, while a minority of HAE-affected patients have become serial emergency room attenders with chronic pain and ongoing requirement for opiate-based painkillers. Both strategies have incurred not only physical but also psychological and economic consequences.In the last 10 years, new and effective acute therapies have been made available, some of which have also provided short-term and long-term prophylaxis options, together with a better understanding of older prophylactic drugs. Improved awareness of HAE amongst the general public, family members, and physicians has reduced the long delay in diagnosis and increased the number of patients receiving effective and up-to-date therapies to improve the physical impact of the disorder.Data on the impact of treatment on the psychological outcomes is scarce, but the limited information available suggests that access to specialist advice and treatment leads to psychological as well as physical improvement.HAE also has profound effects on individual and family economic output, directly via absenteeism from school or work and indirectly via lost opportunities. Economic improvements associated with better treatments are offset by the high cost of new acute treatments, resulting in difficult pharmaco

  9. Angioedema related to Angiotensin inhibitors.

    Science.gov (United States)

    Knecht, Stephanie E; Dunn, Steven P; Macaulay, Tracy E

    2014-10-01

    Angiotensin inhibitors have been extensively evaluated in clinical trials and have demonstrated significant reductions in morbidity and mortality following myocardial infarction and stroke, as well as in patients with heart failure or who are at risk of cardiovascular disease. Further, both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are frequently prescribed for the treatment of hypertension and to preserve renal function in patients with diabetes mellitus and chronic kidney disease. Angioedema is a known, but rare, adverse effect of ACEIs and ARBs. Therefore, it is important for clinicians to have a thorough understanding of risks and benefits of prescribing these medications, particularly in patients with a history of angioedema. This review describes the literature evaluating the incidence and cross-reactivity of angioedema with ACEIs and ARBs in order to provide guidance for clinical decision making. © The Author(s) 2014.

  10. Angioedema in progressive muscular dystrophy: a case report.

    Science.gov (United States)

    Dermendzhiev, Svetlan M; Simeonova, Radostina; Murdjeva, Marianna A

    2012-01-01

    Systemic allergic reactions, which include angioedema, are very common in clinical practice. There is great diversity in the etiological factors known to trigger angioedema, and in the pathogenetic mechanisms defining this condition. Beside the broad spectrum of immuno-allergic reactions involved in the angioedemic pathogenesis, this condition is known to also develop on the background of other disorders. These disorders may be of different etiology and have different pathogenesis (either non-immune or immune) but have one common feature referred to as "serological overlap". From research and clinical perspective, it is interesting to explore the combination of some rare neurological diseases, such as myopathies and in particular muscular dystrophies with systemic allergic reactions such as angioedema, urticaria and others. It is known that progressive muscular dystrophies (PMD) are hereditary diseases with different types of inheritance--X-chromosome recessive, X-chromosome dominant, autosomal dominant and others. In some forms, such as Duchenne muscular dystrophy (DMD), an increased expression of perforin in muscle is found which is evidence for involvement of the cellular immune response in the pathogenesis of myopathy. It is in this sense that it is interesting to explore and discuss a clinical case diagnosed as a facioscapulohumeral form of PMD, which also manifests angioedema with urticaria. We present a 41-year-old male hospitalized in the Division of Occupational Diseases and Allergology at St. George University Hospital in Plovdiv who suffered two incidents of massive angioedema on the face, back and chest, accompanied by an itchy urticarial rash. In 1985, after hospitalization to the Clinic of Neurology, he was diagnosed with PMD of facioscapulohumeral type. The medical history could not reveal any of the most common etiologic factors such as drugs, food, insects and other allergens that may be associated with the systemic allergic reactions. The

  11. Recent Advances in Drug-Induced Angioedema

    Directory of Open Access Journals (Sweden)

    Naoko Inomata

    2012-01-01

    Full Text Available Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life- threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and nonsteroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs in the causation of life- threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin- dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

  12. Bowel Angioedema Associated With Iodinated Contrast Media: Incidence and Predisposing Factors.

    Science.gov (United States)

    Seo, Nieun; Chung, Yong Eun; Lim, Joon Seok; Song, Mi Kyung; Kim, Myeong-Jin; Kim, Ki Whang

    2017-09-01

    Bowel angioedema is an acute adverse reaction to iodinated contrast media (CM) that involves the gastrointestinal tract. We aimed to investigate the incidence and predisposing factors of iodinated CM-associated bowel angioedema during computed tomography (CT) examinations. This study was approved by our institutional review board, and informed consent was waived due to its retrospective design. From July 2013 to July 2015, adult patients with a history of adverse reactions to iodinated CM during CT (group A, n = 427) and patients without adverse reactions matched for age and sex with the propensity-score matching method (group B, n = 427) were studied. Contrast media-associated bowel angioedema was determined when bowel wall thickness increased after contrast enhancement compared with the precontrast scan. Potential predisposing factors including patient demographics, symptoms and time of adverse reactions, and CM-related factors were compared between patients with and without angioedema in group A. In addition, the incidence of bowel angioedema was compared between groups A and B. The incidence of CM-associated bowel angioedema in group A was 3.3% (14/427) in the per-patient analysis and 2.6% (15/578) in the per-examination analysis. The CM-associated bowel angioedema involved the distal duodenum and/or proximal jejunum and showed long-segmental circumferential bowel wall thickening on CT. None of the studied predisposing factors was different between patients with and without bowel angioedema (P > 0.05). The incidence of CM-associated bowel angioedema in group B was 1.9% (8/427) and 1.7% (8/458) for per-patient and per-examination analyses, respectively, and these rates were not significantly different between groups A and B (P = 0.346 and P = 0.370, respectively). The incidence of CM-associated bowel angioedema during CT was 1.7% to 3.3%, and none of the studied predisposing factors was associated with bowel angioedema.

  13. Angioedema Due to Lamiaceae Allergy.

    Science.gov (United States)

    Yazıcı, Selçuk; Nacaroglu, Hikmet Tekin; Bahçeci Erdem, Semiha; Karaman, Sait; Can, Demet

    2018-02-01

    We present a 13-year-old male childallergic to three different plants (Salvia officinalis, Mentha piperita and Origanum onites L.) of Lamiaceae family. The patient developed angioedema 20-30 minutes after eating chicken meat with cheddar cheese. There was no history of allergy. Oral food challenge (OFC) with both cheddar cheese and chicken meat was negative. Skin tests for inhalant allergens were negative. 3 weeks later, the patient was admitted with angioedema after drinking sage tea. OFC with sage was applied and angioedema was observed. It was recognized that the first trigger, chicken meat with cheddar cheese, included oregano (Origanum onites L.). OFC for oregano was positive. Prick to prick test for Lamiaceae herbs (oregano, sage, mint) was performed. A positive reaction was observed only to mint. OFC was repeated with fresh mint and angioedema developed after 16 hours. Diagnose of Lamiaceae allergy is complicated and cross-sensitivity is common. Skin prick test (prick to prick)revealed a positive response only to mint but not to oregano and sage. Commercial radioallergosorbent (RAST) tests are available only for a few members of the family. Finally, thediagnose is based mainly on OFC. Spices from Lamiaceae group should be considered as potential triggers of allergic reactions.

  14. An ABC of the Warning Signs of Hereditary Angioedema

    DEFF Research Database (Denmark)

    Grumach, Anete Sevciovic; Ferraroni, Natasha; Olivares, Maria Margarita

    2017-01-01

    are common. HAE attacks may be fatal when upper-airway edema occurs, if proper treatment with a C1 inhibitor concentrate or BK receptor antagonist is not administered or an emergency tracheostomy is not performed. We propose a mnemonic method for the warning signs of HAE for the use as a diagnostic tool, i...

  15. Safety and Usage of C1-Inhibitor in Hereditary Angioedema

    DEFF Research Database (Denmark)

    Riedl, Marc A; Bygum, Anette; Lumry, William

    2016-01-01

    of this study was to describe safety and usage patterns of pnfC1-INH. METHODS: A multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety...... and usage data on subjects receiving pnfC1-INH for any reason. RESULTS: Of 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment......, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...

  16. Use of C1 Inhibitor for Angiotensin-Converting Enzyme (ACE) Inhibitor-Induced Angioedema Decreases Mechanical Ventilation Time.

    Science.gov (United States)

    Urnoski, Eric; Grillo, Angelo; Rosini, Jamie M

    2015-12-01

    Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema is a rare, albeit serious emergency that can result in airway compromise and potentially death if not treated promptly. Currently, there are no agents approved by the Food and Drug Administration to target ACE inhibitor angioedema and to prevent intubation. C1 inhibitors are approved for hereditary angioedema but may show promise in alleviating inflammation associated with ACE inhibitor angioedema. A 41-year-old man presented to the emergency department with swelling of his lips a few days after starting lisinopril for hypertension. Despite receiving diphenhydramine, ranitidine, and methylprednisolone, the swelling progressed to the patient's tongue. A C1 inhibitor was ordered in an effort to prevent intubation. Before the arrival of the medication, the patient was intubated emergently for airway protection. After receipt of the C1 inhibitor, the swelling dramatically improved, and the patient was successfully extubated after less than 18 hours from presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case illustrates a potential role for C1 inhibitors in the emergency setting for treating drug-induced angioedema, which may prevent or minimize mechanical ventilation time. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Tranexamic acid as maintenance treatment for non-histaminergic angioedema: analysis of efficacy and safety in 37 patients

    Science.gov (United States)

    Wintenberger, C; Boccon-Gibod, I; Launay, D; Fain, O; Kanny, G; Jeandel, P Y; Martin, L; Gompel, A; Bouillet, L

    2014-01-01

    Angioedema (AE) is a clinical syndrome characterized by localised swelling lasting several hours. The swelling is often recurring and can be lethal if it is located in the laryngeal region. Much progress has been made recently in the treatment of acute episodes, but no consensus has been reached on maintenance treatment. We have performed a national retrospective observational study to assess the use of tranexamic acid (TA) as maintenance treatment for non-histaminergic AE [hereditary AE (HAE) or idiopathic non-histaminergic AE]. Records for 64 cases were collected from 1 October 2012 to 31 August 2013; 37 of these were included (12 HAE with C1-inhibitor deficiency, six with HAE with normal C1-inhibitor and 19 idiopathic non-histaminergic AE). When treated with TA over six months, the number of attacks was reduced by 75% in 17 patients, 10 patients showed a lower level of reduction and 10 had the same number of attacks. In no instances were symptoms increased. No thromboembolic events were observed, and the main side effects were digestive in nature. Thus, TA, which is well tolerated and inexpensive, appears to be an effective maintenance treatment for some patients with HAE or idiopathic non-histaminergic AE. PMID:24827773

  18. Chronic idiopathic angioedema: a single center experience.

    Science.gov (United States)

    Eli, Magen; Joseph, Mishal; Kuznik, Boris; Menachem, Schlesinger

    2014-10-01

    Chronic idiopathic angioedema (CIA) is defined as three or more episodes of angioedema in a period of > 6 months without a clear etiology. In the study, we tried to explore clinical and laboratory characteristics of patients with CIA unaccompanied by urticaria. We retrospectively reviewed clinical and laboratory characteristics of 1238 patients with chronic urticaria and/or angioedema referred to our allergy clinic. Eight hundred and forty-one (67.9%) subjects had chronic urticaria without angioedema (CU Group), 323 (26.1%) had both urticaria and angioedema (CU + CA group), and 74 (5.9%) had chronic angioedema without urticaria (CA). In 29 (39.2%) cases of CA, no etiologic factor of angioedema was discovered, thus the patients were defined as having chronic idiopathic angioedema (CIA Group). Twenty-two (75.8%) subjects had antihistamine-responsive CIA and seven (24.1%) had antihistamine-unresponsive CIA. There were no statistically significant differences in clinical (except of urticarial eruptions) and laboratory characteristics between CU, CA + CU, and CIA groups. Antihistamine responsive and antihistamine-unresponsive CIA groups had no distinguishable clinical or laboratory features. We suppose that CIA, at least its antihistamine-responsive form, represents a rare form of chronic spontaneous urticaria. The reasons why in CIA there are no other clinical signs of mast cell/basophil activation, such as pruritus, urticarial, and dermatographism, are largely unknown and have to be elucidated in future studies. © 2014 The International Society of Dermatology.

  19. Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients.

    Science.gov (United States)

    Mansi, M; Zanichelli, A; Coerezza, A; Suffritti, C; Wu, M A; Vacchini, R; Stieber, C; Cichon, S; Cicardi, M

    2015-05-01

    The first classification of angioedema without wheals was recently reported and comprises different forms of the disease distinguished by aetiology, mediator of oedema and inheritance. In total, 1725 consecutive patients with angioedema without wheals were examined at our centre between 1993 and 2012. We excluded from the analysis 667 patients because of incomplete data or because angioedema was related to a specific factor. According to the new classification of angioedema, the 1058 patients included in this analysis were diagnosed with hereditary (HAE; n = 377) or acquired angioedema (AAE; n = 681). The former group included HAE with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE; n = 353) and HAE with normal C1-INH levels (n = 24), of which six had a factor XII mutation (FXII-HAE) and 18 had disease of unknown origin (U-HAE). The AAE group included disease with C1-INH deficiency (C1-INH-AAE; n = 49), AAE related to angiotensin-converting enzyme inhibitor treatment (n = 183), idiopathic histaminergic (IH-AAE; n = 379) and idiopathic nonhistaminergic angioedema (InH-AAE; n = 70). We compared hereditary and AAE with uncertain aetiopathogenesis: the FXII-HAE and U-HAE groups pooled (FXII/U-HAE) versus InH-AAE. The median age at onset of FXII/U-HAE and InH-AAE was 26 and 38 years, respectively. In addition, 56% of patients with FXII/U-HAE and 81% of those with InH-AAE reported more than five attacks per year (median duration of 48 h). The location of angioedema in patients with FXII/U-HAE versus those with InH-AAE was the following: face, 70% versus 86%; tongue, oral cavity or larynx, 55% versus 68%; limbs, 70% versus 56%; and gastrointestinal mucosa, 50% versus 20%. Prophylaxis with tranexamic acid was effective in all six patients with U-HAE and in 37 of 38 with InH-AAE who were started on this treatment. Our findings in this cohort of patients with angioedema provide new information on the clinical characteristics, diagnosis and treatment of this

  20. Risk of angioedema following invasive or surgical procedures in HAE type I and II – the natural history

    Science.gov (United States)

    Aygören-Pürsün, E; Martinez Saguer, I; Kreuz, W; Klingebiel, T; Schwabe, D

    2013-01-01

    Background Hereditary angioedema (HAE), caused by deficiency in C1-inhibitor (C1-INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal complications. As surgery can be a trigger for edema episodes, current guidelines recommend preoperative prophylaxis with C1-INH or attenuated androgens in patients with HAE undergoing surgery. However, the risk of an HAE attack in patients without prophylaxis has not been quantified. Objectives This analysis examined rates of perioperative edema in patients with HAE not receiving prophylaxis. Methods This was a retrospective analysis of records of randomly selected patients with HAE type I or II treated at the Frankfurt Comprehensive Care Centre. These were examined for information about surgical procedures and the presence of perioperative angioedema. Results A total of 331 patients were included; 247 underwent 700 invasive procedures. Of these procedures, 335 were conducted in 144 patients who had not received prophylaxis at the time of surgery. Categories representing significant numbers of procedures were abdominal (n = 113), ENT (n = 71), and gynecological (n = 58) procedures. The rate of documented angioedema without prophylaxis across all procedures was 5.7%; in 24.8% of procedures, the presence of perioperative angioedema could not be excluded, leading to a maximum potential risk of 30.5%. Predictors of perioperative angioedema could not be identified. Conclusion The risk of perioperative angioedema in patients with HAE type I or II without prophylaxis undergoing surgical procedures ranged from 5.7% to 30.5% (CI 3.5–35.7%). The unpredictability of HAE episodes supports current international treatment recommendations to consider short-term prophylaxis for all HAE patients undergoing surgery. PMID:23968383

  1. The Angioedema Quality of Life Questionnaire (AE-QoL) - assessment of sensitivity to change and minimal clinically important difference.

    Science.gov (United States)

    Weller, K; Magerl, M; Peveling-Oberhag, A; Martus, P; Staubach, P; Maurer, M

    2016-08-01

    The Angioedema Quality of Life Questionnaire (AE-QoL) has recently been developed and validated as the first specific patient-reported outcome tool to assess quality of life (QoL) impairment in recurrent angioedema patients. As of yet, its sensitivity to change and minimal clinically important difference (MCID) have not been established. Recurrent angioedema patients with chronic spontaneous urticaria or hereditary angioedema were repeatedly asked to complete the AE-QoL along with the SF-12 and other anchors for QoL impairment and disease activity during routine care visits. The sensitivity to change of AE-QoL was determined by correlating changes in its scores over time with changes in the applied anchors. In addition, the MCID was determined using anchor-based and distributional criterion-based approaches. Two hundred and seventy-eight patients contributed data sets for analysis. Baseline AE-QoL values were found to correlate well with SF-12 results as well as all other applied anchors for angioedema-related QoL impairment and disease activity. In addition, AE-QoL score changes over time correlated significantly with changes in the above anchors, thus demonstrating its sensitivity to change. The MCID of the AE-QoL total score was found to be six points. The AE-QoL is a valuable tool to assess changes of QoL impairment in recurrent angioedema patients over time, including changes due to treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Science.gov (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

  3. Drug-Induced Inhibition of Angiotensin Converting Enzyme and Dipeptidyl Peptidase 4 Results in Nearly Therapy Resistant Bradykinin Induced Angioedema: A Case Report.

    Science.gov (United States)

    Hahn, Janina; Trainotti, Susanne; Hoffmann, Thomas K; Greve, Jens

    2017-05-25

    BACKGROUND Bradykinin is an underestimated mediator of angioedema. One subgroup of bradykinin induced angioedema is angioedema triggered by treatment with angiotensin converting enzyme (ACE) inhibitors. Due to its localization in the head and neck region and its unpredictable course, it is a possibly life-threatening condition. There is not an officially approved treatment for ACE inhibitor induced angioedema. CASE REPORT We present a case of an 83-year-old woman, who presented to our ENT department because of acute swelling of the tongue. On admission, there was no pharyngeal or laryngeal edema and no dyspnea. Treatment with glucocorticoids and antihistamines had no response. The patient had ramipril as regular medication, so we assumed ACE inhibitor induced angioedema and treated consequently with C1-inhibitor (human) 1,500 IU. Nevertheless, swelling was progressive and required intubation. Even after the second specific treatment with icatibant, her angioedema subsided extremely slowly. The patient also had regular treatment with saxagliptin, a dipeptidyl peptidase 4 inhibitor, so we assumed that the simultaneous inhibition of two bradykinin degrading enzymes led to a treatment-refractory course of angioedema. CONCLUSIONS General awareness for bradykinin induced angioedema due to regular medication is limited. Our case demonstrated the importance of improving awareness and knowledge about this side effect. We need a better understanding of the pathomechanism to aid in more precise clinical diagnosis. Securing the patient's airway as well as administration of an officially approved therapy is of utmost importance. As the number of patients simultaneously treated with antihypertensive and antidiabetic drugs is likely to increase, the incidence of bradykinin mediated drug induced angioedema is likely to increase as well.

  4. Congenital anomalies, hereditary diseases of the pancreas, acute and chronic pancreatitis; Entwicklungsstoerungen, angeborene Erkrankungen des Pankreas, akute und chronische Pankreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Brambs, Hans-Juergen; Juchems, Markus [Universitaetsklinikum Ulm (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie

    2011-06-15

    The most important congenital anomalies include pancreas divisum, annular pancreas and ectopic pancreas. Patients with pancreas divisum may be more susceptible to acute or chronic pancreatitis and patients with an annular pancreas may develop duodenal stenosis. In pancreas divisum the key finding is the visualization of the main duct draining into the duodenum via the small papilla, separated from the common bile duct. Annular pancreas may show as a well defined ring of pancreatic tissue that encircles the duodenum. Ectopic pancreas is usually asymptomatic but may give rise to abdominal complaints and may be confused with submucosal tumors. Acute pancreatitis is classified as mild or severe. In mild forms ultrasound is the imaging modality of choice whereas in severe forms with extensive pancreatic and peripancreatic necroses computed tomography is the favored method. It is crucial to identify signs and criteria that come along with an increased risk of infection of the necroses. MRI plays an inferior role in the assessment of acute pancreatitis. Chronic pancreatitis is a longstanding inflammatory and fibrosing process causing pain and loss of function. Cross-section imaging is particularly in demand for the detection of complications and the differentiation from pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by lymphoplasmacytic infiltration and fibrosis, and favourable response to corticosteroid treatment. (orig.)

  5. Acute myocardial infarction, ischemic cerebrovascular disease and variceal bleeding due to portal vein thrombosis in a patient with hereditary thrombophilia.

    Science.gov (United States)

    Baran, Bulent; Yilmaz, Yusuf; Algin, Oktay; Keskin, Murat; Kiyici, Murat; Kocamaz, Guzin; Dolar, Enver

    2008-04-01

    We report on a 43-year-old female patient with multiple thrombotic risk factors who, in a few months, developed acute myocardial infarction, an ischemic cerebrovascular event and variceal bleeding due to portal vein thrombosis. The factor V Leiden mutation was carried in heterozygous form, homocysteine was elevated at 19.6 micromol/l, and methylenetetrahydrofolate reductase C677T mutation was carried in homozygous form. Moderately increased plasma homocysteine level and a reduced protein S activity were evident. Anticardiolipin IgG antibodies were mildly positive. We conclude that the presence of multiple genetic and environmental risk factors greatly amplifies the risk of clinical thrombotic events.

  6. A 31-year-old pregnant woman with angioedema.

    Science.gov (United States)

    Speck, Aimee L; Killen, Paul D; Greenhawt, Matthew J

    2015-01-01

    Angioedema is swelling of the deep layers of the dermis and subcutaneous tissue due to an increase in vascular permeability. Angioedema sometimes occurs concomitantly with urticaria and represents an allergic disease. In other cases, angioedema is not associated with an allergic condition. We present the case of a 31-year-old woman with new-onset angioedema in the setting of her first pregnancy. After detailed history, physical examination, and laboratory evaluation, a cause for her angioedema was found that had not been considered previously and had significant implications for future management, particularly in light of her current pregnancy. Because allergists are commonly called on to evaluate and treat angioedema, we should be aware of the many disease processes that can present with this symptom and be well-versed in the workup of new-onset angioedema.

  7. Prognostic factors in outcome of angioedema in the emergency department.

    Science.gov (United States)

    Felder, Sarah; Curtis, R Mason; Ball, Ian; Borici-Mazi, Rozita

    2014-01-01

    Angioedema is a transient, localized swelling caused by two distinct mechanisms, mediated by histamine and bradykinin, respectively, although a proportion of cases remain idiopathic. Studies that characterize undifferentiated angioedema presenting in emergency departments (EDs) are limited. This study investigates the presentation patterns of undifferentiated angioedema in the ED based on the presumed mechanism of swelling. Medical records from all ED visits to two tertiary care hospitals from July 2007 to March 2012 were electronically reviewed. Records with documented visible swelling on general inspection and/or fiberoptic laryngoscopy and a diagnostic code for anaphylactic shock, angioneurotic edema, allergy unspecified, defects in the complement system, or unspecified drug adverse effects were included. Demographic, clinical, and outcome data were collected via a standardized form. Data were analyzed descriptively, including frequencies and percentages for categorical data and means and SDs for continuous data. Predictors for admission were identified using multivariate logistic regression models. ED records from 527 visits for angioedema by 455 patients were included in the study. Annual rate of angioedema was 1 per 1000 ED visits. Urticaria was associated with peripheral (p = 0.008) and lip angioedema (p = 0.001), and the absence of urticaria correlated with tongue angioedema (p = 0.001) and trended toward correlation with pharyngeal angioedema (p = 0.056). Significant predictors of admission included nonsteroidal anti-inflammatory drug-induced angioedema (odds ratio [OR], 15.3), epinephrine treatment (OR, 8.34), hypotension (OR, 15.7), multiple-site angioedema (OR, 4.25), and pharyngeal (OR, 1.23) and tongue angioedema (OR, 4.62). Concomitant urticaria was associated with a significant longer stay in the ED (p angioedema, need for airway management, length of ED visit, and recurrence. A detailed drug and family history, screening blood work for C1 esterase

  8. The Icatibant Outcome Survey: treatment of laryngeal angioedema attacks

    Science.gov (United States)

    Aberer, Werner; Bouillet, Laurence; Caballero, Teresa; Maurer, Marcus; Fabien, Vincent; Zanichelli, Andrea

    2016-01-01

    Objective To characterize the management and outcomes of life-threatening laryngeal attacks of hereditary angioedema (HAE) treated with icatibant in the observational Icatibant Outcome Survey (NCT01034969) registry. Methods This retrospective analysis was based on data from patients with HAE type I/II who received healthcare professional-administered or self-administered icatibant to treat laryngeal attacks between September 2008 and May 2013. Results Twenty centers in seven countries contributed data. Overall, 42 patients with HAE experienced 67 icatibant-treated laryngeal attacks. Icatibant was self-administered for 62.3% of attacks (healthcare professional-administered, 37.7%). One icatibant injection was used for 87.9% of attacks, with rescue or concomitant medication used for 9.0%. The median time to treatment was 2.0 h (n=31 attacks) and the median time to resolution was 6.0 h (n=35 attacks). Conclusions This analysis describes successful use of icatibant for the treatment of laryngeal HAE attacks in a real-world setting. PMID:27116379

  9. The Angiotensin-Converting-Enzyme-Induced Angioedema.

    Science.gov (United States)

    Bas, Murat

    2017-02-01

    The bradykinin B2 receptor antagonist icatibant is effective in angiotensin-converting enzyme inhibitor-induced angioedema. The drug is not approved officially for this indication and has to be administered in an emergency situation off-label. Corticosteroids or antihistamines do not seem to work in this condition. The effectiveness of C1-esterase-inhibitor in angiotensin-converting enzyme-induced angioedema must be verified in a double-blind study. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. [Biological investigation of kinin-mediated angioedema].

    Science.gov (United States)

    Defendi, F; Charignon, D; Ghannam, A; Ponard, D; Drouet, C

    2015-03-01

    Kinin-mediated angioedema results from accumulation of kinins, vasoactive and vasopermeant peptides, on the vascular endothelium. The disease is characterized by sudden episodes of swelling in the subcutaneous and submucosal tissues; the edema may occur spontaneously or it may be precipitated by triggering factors such as physical or emotional stress, or certain medicines. The characterization of kinin formation and catabolism systems helps improve knowledge of the aetiopathogenic mechanisms involved and provides the basis for classification of kinin-mediated angioedema conditions; thus, we may distinguish between angioedema with C1 inhibitor deficiency, whether inherited or acquired, and angioedema with normal C1 inhibitor activity, associated with increased kinin-forming activity or deficiency in kinin catabolism enzymes. In support of the clinical diagnosis, the physician may request laboratory investigation for a functional and molecular definition of the disease. Laboratory diagnosis is based on the characterization of: (1) kinin production control by C1 inhibitor investigation (function, antigen levels and circulating species); (2) kinin production (kininogenase activity, kininogen cleavage species); and (3) kinin catabolism enzymes (aminopeptidase P, carboxypeptidase N, angiotensin-I converting enzyme and dipeptidyl peptidase IV). An abnormal biological phenotype is supported by examination of susceptibility genes (SERPING1, F12 and XPNPEP2) and mutation segregation in the families. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. ACE Inhibitor-Induced Angioedema of the Intestine: Case Report, Incidence, Pathophysiology, Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Gavin Oudit

    2001-01-01

    Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

  12. Angiotensin-converting enzyme inhibitor-induced angioedema may not be a class-related event

    Directory of Open Access Journals (Sweden)

    Hassan A Farhat

    2012-09-01

    Full Text Available Angioedema is a rare but potentially life threatening condition commonly associated with angiotensin-converting enzyme inhibitors (ACEIs. The incidence is approximately 0.1- 0.2% and may occur within the first week to several years of taking an ACEI. We present a case of a 37-year-old African-American male who was uneventfully taking a drug combination of quinapril and hydrochlorothiazide. When his medication was changed to lisinopril he developed an acute swelling of his lower lip and chin on fifth dose. The angioedema subsided within 24 hours after discontinuation of lisinopril. Therefore, this suggests that future treatment with ACEIs, as well as angiotensin receptor blockers (ARBs, is not recommended in this type of patient.

  13. [Facial angioedema after filler injections. Description of five cases].

    Science.gov (United States)

    Cosatti, Micaela; Fernández Romero, Diego S; Juri, María Cecilia; Malbrán, Alejandro

    2010-01-01

    The use of fillers for cosmetic purposes is becoming increasingly frequent. Although initially considered inert, these products produce adverse reactions around the injection site. We present 5 cases of women with a history of filler injections who presented a hard and persistent angioedema followed by local subcutaneous nodules. They were referred to the allergist for suspected allergy related angioedema without response to usual antihistamine treatment. The angioedema episodes initiated 27.6 months (range 1 to 48) after the fillers treatment. The patients underwent exacerbations and remissions of angioedema, partially relieved with oral steroids and, in 2 cases, local triamcinolone injections. Mean time from onset of symptoms to remission of angioedema was 8.75 months (range 1 to 24). Until October 2009 four patients continued into remission after 24.5 months (range 7 to 36) free of symptoms. One patient continued with exacerbations 11 months after the initial symptoms. Fillers may cause angioedema as an adverse event and should be considered in the differential diagnosis of persistent angioedema. They are only sensitive to steroid treatment and in some steroid dependent cases they respond to ciclosporin. The frequency of angioedema after filler injections among patients with angioedema in the Unit of Asthma Allergy and Clinical Immunology was 0.5%.

  14. HEREDITARY BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. M. Bit-Sava

    2013-01-01

    Full Text Available Hereditary breast cancer occurs in 5–20 % of cases and it is associated with inherited mutations in particular genes, such as BRCA1 и BRCA2 in most cases. The CHEK2, PTEN, TP53, ATM, RAD51, BLM, PALB2, Nbs genes are associated with low and median risks ofdeveloping breast cancer. Molecular genetic studies identify germinal mutations underlying hereditary breast cancer. In most cases hereditary breast cancer refers to triple-negative phenotype, which is the most aggressive type of breast cancer, that does not express the genes for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2. The review presents the diagnostic and treatment methods of hereditary breast cancer. Clinical-morphological aspects allow the new diagnostic and treatment methods of hereditary breast cancer to be identified. Poly (ADP-ribose polymerase (PARP inhibitors demonstrate the potential for effective treatment of BRCA-associated breast cancer.

  15. Acetyl salicylic acid induced-urticaria and/or angioedema in atopic children.

    Science.gov (United States)

    Botey, J; Navarro, C; Aulesa, C; Marín, A; Eseverri, J L

    1988-01-01

    From the report of Hirschberg, only 3 years after aspirin synthesis, there have been numerous works dedicated to showing the different types of adverse reactions found following aspirin administration. However, there are few publications on the process of urticaria and/or acute angioedema induced by ASA and few reported cases were found in children. Thus, we present 6 atopic children with urticaria and/or angioedema related with ASA. A carefully detailed history, oral provocation with ASA, oral provocation with other NSAI and HBDT with ASA were done to all of them. The oral provocation with ASA was positive in 5 of the 6 cases. The provocations with the rest of the NSAI and tartrazine and sodium benzoate were negative in all of the patients. The HBDT was positive in 5 of the cases. In conclusion, we insist that aspirin intolerance is not infrequent in infancy and it is not rare to see urticaria and or angioedema, in spite of the fact that asthmatics, atopics or non atopics, usually present as bronchospasm. We also believe that the HBDT can be a method of diagnosis used in these cases.

  16. Cardiovascular and Diabetic Medications That Cause Bradykinin-Mediated Angioedema.

    Science.gov (United States)

    Hudey, Stephanie N; Westermann-Clark, Emma; Lockey, Richard F

    Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Methicillin-resistant Staphylococcus Aureus Lip Infection Mimicking Angioedema.

    Science.gov (United States)

    Lucerna, Alan R; Espinosa, James; Darlington, Anne M

    2015-07-01

    It is rare for angioedema to be misidentified by the experienced clinician or for it to mimic another disease process. As an Emergency Physician, it is important to recognize and treat angioedema immediately. Of equal importance is the recognition and initiation of treatment of facial cellulitis. A case report follows that illustrates methicillin-resistant Staphylococcus aureus (MRSA) lip infection mimicking angioedema. Here, we describe a case of a 21-year-old man who presented with a swollen lower lip, initially diagnosed as angioedema. Further investigation revealed the cause of his lip swelling was actually a MRSA abscess and surrounding cellulitis, an unusual presentation for lip infection, which we discuss below. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Misidentifying MRSA lip infection for angioedema, with a delay in proper treatment, could result in serious morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Refractory Abdominal Pain in a Patient with Chronic Lymphocytic Leukemia: Be Wary of Acquired Angioedema due to C1 Esterase Inhibitor Deficiency

    Directory of Open Access Journals (Sweden)

    Abdullateef Abdulkareem

    2018-01-01

    Full Text Available Acquired angioedema due to C1 inhibitor deficiency (C1INH-AAE is a rare and potentially fatal syndrome of bradykinin-mediated angioedema characterized by episodes of angioedema without urticaria. It typically manifests with nonpitting edema of the skin and edema in the gastrointestinal (GI tract mucosa or upper airway. Edema of the upper airway and tongue may lead to life-threatening asphyxiation. C1INH-AAE is typically under-diagnosed because of its rarity and its propensity to mimic more common abdominal conditions and allergic reactions. In this article, we present the case of a 62-year-old male with a history of recently diagnosed chronic lymphocytic leukemia (CLL who presented to our hospital with recurrent abdominal pain, initially suspected to have Clostridium difficile colitis and diverticulitis. He received a final diagnosis of acquired angioedema due to C1 esterase inhibitor deficiency due to concomitant symptoms of lip swelling, cutaneous nonpitting edema of his lower extremities, and complement level deficiencies. He received acute treatment with C1 esterase replacement and icatibant and was maintained on C1 esterase infusions. He also underwent chemotherapy for his underlying CLL and did not experience further recurrence of his angioedema.

  19. Approaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug-related urticaria and angioedema.

    Science.gov (United States)

    Kowalski, Marek L; Woessner, Katharine; Sanak, Marek

    2015-08-01

    Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. Hereditary fructose intolerance

    Science.gov (United States)

    Fructosemia; Fructose intolerance; Fructose aldolase B-deficiency; Fructose-1, 6-bisphosphate aldolase deficiency ... substances build up in the liver. Hereditary fructose intolerance is inherited, which means it can be passed ...

  1. Learning about Hereditary Hemochromatosis

    Science.gov (United States)

    Skip to main content Learning About Hereditary Hemochromatosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research ...

  2. Hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Green, A

    1999-01-01

    Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early...

  3. Angiotensin-converting enzyme inhibitor-induced angioedema.

    Science.gov (United States)

    Bezalel, Shira; Mahlab-Guri, Keren; Asher, Ilan; Werner, Ben; Sthoeger, Zev Moshe

    2015-02-01

    Angiotensin-converting enzyme inhibitors (ACE-I) are widely used, effective, and well-tolerated antihypertensive agents. The mechanisms by which those agents act can cause side effects such as decreased blood pressure, hyperkalemia, and impaired renal function. ACE-I can induce cough in 5%-35% and angioedema in up to 0.7% of treated patients. Because cough and angioedema are considered class adverse effects, switching treatment to other ACE-I agents is not recommended. Angioedema due to ACE-I has a low fatality rate, although deaths have been reported when the angioedema involves the airways. Here, we review the role of bradykinin in the development of angioedema in patients treated with ACE-I, as well as the incidence, risk factors, clinical presentation, and available treatments for ACE-I-induced angioedema. We also discuss the risk for recurrence of angioedema after switching from ACE-I to angiotensin receptor blockers treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Management of angioedema without urticaria in the emergency department.

    Science.gov (United States)

    Pedrosa, Maria; Prieto-García, Alicia; Sala-Cunill, Anna

    2014-12-01

    Angioedema refers to a localized, transient swelling of the deep skin layers or the upper respiratory or gastrointestinal mucosa. It develops as a result of mainly two different vasoactive peptides, histamine or bradykinin. Pathophysiology, as well as treatment, is different in each case; nevertheless, the resulting signs and symptoms may be similar and difficult to distinguish. Angioedema may occur at any location. When the affected area involves the upper respiratory tract, both forms of angioedema can lead to an imminent upper airway obstruction and a life-threatening emergency. Emergency physicians must have a basic understanding of the pathophysiology underlying this process. Angioedema evaluation in the emergency department (ED) should aim to distinguish between histamine- and bradykinin-induced angioedema, in order to provide appropriate treatment to patients. However, diagnostic methods are not available at the ED setting, neither to confirm one mechanism or the other, nor to identify a cause. For this reason, the management of angioedema should rely on clinical data depending on the particular features of the episode and the patient in each case. The history-taking should be addressed to identify a possible etiology or triggering agent, recording complete information for an ulterior diagnostic study in the outpatient clinic. It is mandatory quickly to recognize and treat a potential life-threatening upper airway obstruction or anaphylaxis. This review focuses on the underlying mechanisms and management of histamine- and bradykinin-induced angioedema at the emergency department and provides an update on the currently available treatments.

  5. Genetics Home Reference: hereditary pancreatitis

    Science.gov (United States)

    ... hereditary pancreatitis: a population-based cohort study in Denmark. Am J Gastroenterol. 2010 Aug;105(8):1876- ... Hammel P, Ruszniewski P, Lévy P. The natural history of hereditary pancreatitis: a national series. Gut. 2009 ...

  6. Glucose Effect in the Acute Porphyrias

    Science.gov (United States)

    ... Porphyria attacks The glucose effect in acute porphyrias Eating behavior and Porphyria A ... porphyrias The disorders Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate ...

  7. Hereditary intestinal polyposis syndromes.

    Science.gov (United States)

    Dean, P A

    1996-01-01

    Colorectal cancer is one of the most common cancers in the world, with overall mortality exceeding 40% even with treatment. Effective efforts for screening and prevention are most likely to succeed in patient groups identified as high risk for colorectal cancer, most notably the hereditary intestinal polyposis syndromes. In these syndromes, benign polyps develop throughout the intestinal tract prior to the development of colorectal cancer, marking the patient and associated family for precancer diagnosis followed by either close surveillance or preventive treatment. This review article was undertaken to discuss the most recent developments in the knowledge of hereditary intestinal polyposis syndromes, emphasizing the clinical approach to diagnosis and treatment relative to preventing the development of cancer. The most common of the hereditary polyposis syndromes is familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon followed at an early age by colorectal cancer. Colorectal cancer can be prevented in this autosomal dominant condition by prophylactic colectomy, though a risk for other tumors, including periampullary cancers, remains throughout life. Variant of FAP associated with fewer and smaller polyps (hereditary flat adenoma syndrome), or even CNS tumors (Turcot's syndrome) also carry this high risk of colorectal cancer. Hereditary hamartomatous polyposis syndromes such as juvenile polyposis and Peutz-Jeghers syndrome (also autosomal dominant) are characterized by less frequent polyps. Though these are generally benign polyps, they are also associated with a significant risk of colorectal and other cancers. Other polyposis syndromes, including neurofibromatosis and Cowden's disease, do not carry this increased risk of colorectal cancer, and therefore affect different treatment strategies. Analysis of genetic factors responsible for these and other hereditary syndromes with

  8. Angioedema por rellenos faciales: Descripción de cinco casos Facial angioedema after filler injections: Description of five cases

    Directory of Open Access Journals (Sweden)

    Micaela A. Cosatti

    2010-12-01

    Full Text Available En los últimos años se ha incrementado la utilización de sustancias de relleno facial con fines estéticos. Estos productos, originalmente considerados inertes, se asocian con diversos efectos adversos localizados alrededor del sitio de la aplicación. Describimos a 5 mujeres con antecedentes de inyecciones de sustancia de relleno facial que presentaron como síntoma inicial angioedema facial duro y persistente seguido por la aparición de nódulos subcutáneos. Todas las pacientes fueron derivadas al servicio de alergia por sospecha de angioedema de causa alérgica sin respuesta al tratamiento con antihistamínicos. El angioedema inició 27.6 meses (1 a 48 luego de la inyección del producto, y las pacientes evolucionaron con brotes y remisiones que fueron tratados con corticoides orales y en 2 oportunidades con inyecciones locales. El tiempo medio desde el inicio de los síntomas hasta la remisión del angioedema fue 8.75 meses (1 a 24. A octubre de 2009 cuatro pacientes se mantuvieron en remisión persistente, luego de un seguimiento clínico de 24.5 meses (7 a 36. Una paciente continúa con exacerbaciones luego de 11 meses de iniciados los síntomas. Las sustancias de relleno facial pueden producir angioedema como evento adverso y deben ser consideradas en el diagnóstico diferencial del angioedema persistente. Sólo responden al tratamiento con esteroides y en algunos casos esteroides dependientes, con ciclosporina. La frecuencia de angioedema por rellenos faciales entre pacientes con angioedema asistidos en la Unidad de Asma, Alergia e Inmunología Clínica fue del 0.5%.The use of fillers for cosmetic purposes is becoming increasingly frequent. Although initially considered inert, these products produce adverse reactions around the injection site. We present 5 cases of women with a history of filler injections who presented a hard and persistent angioedema followed by local subcutaneous nodules . They were referred to the allergist for

  9. Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema.

    Science.gov (United States)

    Culley, Colleen M; DiBridge, Julie N; Wilson, Gregory L

    2016-01-01

    To evaluate the place in therapy of fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA). A literature search was performed using PubMed (1946 through August 2015) and Embase (angioedema, another bradykinin-mediated event, may be effective for use in ACEI-IA. Positive efficacy results were reported with FFP and C1-INH while mixed results have been seen with ecallantide. Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in several cases. These agents were well-tolerated in ACEI-IA. ACEI-IA is typically a self-limiting event. First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine). Symptom progression can be life-threatening and may require interventions such as tracheotomy and intubation. Off-label use of FFP and medications approved for hereditary angioedema have resulted in rapid resolution of symptoms and avoidance of intubation. Among these agents, icatibant has the most supporting evidence and has been incorporated into practice guidelines and algorithms as a second-line agent for serious life-threatening ACE-IA. © The Author(s) 2015.

  10. Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon

    Directory of Open Access Journals (Sweden)

    Rajeev Seecheran

    2017-01-01

    Full Text Available Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant should be considered when there is an absolute indication for antiplatelet therapy.

  11. Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon.

    Science.gov (United States)

    Seecheran, Rajeev; Seecheran, Valmiki; Persad, Sangeeta; Lalla, Sasha; Seecheran, Naveen Anand

    2017-01-01

    Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant) should be considered when there is an absolute indication for antiplatelet therapy.

  12. Emergency department management of patients with ACE-inhibitor angioedema.

    Science.gov (United States)

    Winters, Michael E; Rosenbaum, Steven; Vilke, Gary M; Almazroua, Faisal Y

    2013-11-01

    Angiotensin-converting-enzyme inhibitors (ACEI) are one of the most prescribed medications worldwide. Angioedema is a well-recognized adverse effect of this class of medications, with a reported incidence of ACEI angioedema of up to 1.0%. Of importance to note, ACEI angioedema is a class effect and is not dose dependent. The primary goal of this literature search was to determine the appropriate Emergency Department management of patients with ACEI angioedema. A MEDLINE literature search from January 1990 to August 2012 and limited to human studies written in English for articles with keywords of ACEI angioedema. Guideline statements and non-systematic reviews were excluded. Studies identified then underwent a structured review from which results could be evaluated. Five hundred sixty-two papers on ACEI angioedema were screened and 27 appropriate articles were rigorously reviewed in detail and recommendations given. The literature search did not support any specific treatment protocol with a high level of evidence due to the limited--and limitations of the--available studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Hereditary periodic fever syndromes

    NARCIS (Netherlands)

    McDermott, MF; Frenkel, J

    Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

  14. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  15. Managing hereditary ovarian cancer

    NARCIS (Netherlands)

    Mourits, M. J.; de Bock, G. H.

    2009-01-01

    In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting

  16. Positive impact of omalizumab on angioedema and quality of life in patients with refractory chronic idiopathic/spontaneous urticaria: analyses according to the presence or absence of angioedema.

    Science.gov (United States)

    Maurer, M; Sofen, H; Ortiz, B; Kianifard, F; Gabriel, S; Bernstein, J A

    2017-06-01

    Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL. © 2016 European Academy of Dermatology and Venereology.

  17. Hereditary breast cancer

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  18. [Hereditary transthyretin amyloidosis].

    Science.gov (United States)

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied.

  19. Epidemiology of angioedema without wheals in an allergy and immunology center.

    Science.gov (United States)

    Malbrán, Eloisa; Fernández Romero, Diego; Juri, Maria Cecilia; Larrauri, Blas J; Malbrán, Alejandro

    2015-01-01

    We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.

  20. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    DEFF Research Database (Denmark)

    Elenius Madsen, Daniel; Hansen, Søren Werner Karlskov; Gram, Jørgen Brodersen

    2014-01-01

    phenotypes were observed in four affected family members from one of these families. Genotyping of the families revealed that the polymerogenic mutations of two families were located in proximity to the reactive center loop insertion site in C1-inh (p.Ile271Thr and p.Ser258_Pro260del),and one mutation...... affected helix C (p.Thr167Asn). In conclusion, we demonstrate that C1-inh polymers are present in the plasma of a subgroup of HAE type I patients....

  1. Effectiveness of icatibant for treatment of hereditary angioedema attacks is not affected by body weight

    DEFF Research Database (Denmark)

    Caballero, Teresa; Zanichelli, Andrea; Aberer, Werner

    2018-01-01

    in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant. Methods: Attack and treatment characteristics......) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks......) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P normal). Conclusion: Overall, icatibant was comparatively effective in treating attacks...

  2. Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults

    DEFF Research Database (Denmark)

    Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia

    2016-01-01

    was to perform a cross-cultural validation and psychometric study of the HAE-QoL in an international setting. METHODS: Cross-cultural adaptation of the Spanish HAE-QoL draft version and an international rating phase with experts were performed. The resultant version of the HAE-QoL, a clinical questionnaire......, and Short Form 36-item Health Survey Version 2.0 (SF-36v2) were pilot tested internationally. Item reduction was based on both descriptive and exploratory factor analysis. Psychometric properties were assessed. RESULTS: Cross-cultural adaptation of the HAE-QoL was performed in 18 countries. The draft...... and social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0...

  3. Health-related quality of life in Danish children with hereditary angioedema

    DEFF Research Database (Denmark)

    Aabom, Anne; Nguyen, Dan; Fisker, Niels

    2017-01-01

    -INH-HAE, including possible correlations to disease severity and attack frequency. Methods: All Danish children ages 2-18 years with C1-INH-HAE were invited to complete questionnaires regarding HRQoL; 14 (93%) agreed. Child self-report forms were used for children ages ≥5 years. The instruments used...... scores for healthy children and better than the scores in the only other study dedicated to HRQoL in children. Children with recent attacks had lower scores, whereas HRQoL scores were not correlated to overall disease severity or age. Surprisingly, home therapy was associated with lower HRQoL; however......, home therapy was also correlated to a higher overall severity score and more frequent attacks. There was a strong child-parent agreement in the PedsQL forms, but scores were independent of whether the child had a family history of C1-INH-HAE or sporadic C1-INH-HAE and whether the parent completing...

  4. Angioedema induced by cardiovascular drugs: new players join old friends.

    Science.gov (United States)

    Bas, M; Greve, J; Strassen, U; Khosravani, F; Hoffmann, T K; Kojda, G

    2015-10-01

    During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system (RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Multicentre audit of ACE-inhibitor associated angioedema (MAAAA).

    Science.gov (United States)

    Gandhi, Jimit; Jones, Rachel; Teubner, David; Gabb, Genevieve

    2015-08-01

    Angiotensin-converting enzyme (ACE) inhibitors are a commonly used class of medications that are generally well tolerated. However, angioedema, a rare but potentially life-threatening adverse effect, may occur. A retrospective audit was performed on patients who presented with angioedema to two emergency departments in Adelaide, Australia. Case notes of patients presenting with angioedema who were using an ACE inhibitor were reviewed. This study examined the clinical features of presentation, treatment and outcomes of the patients. A total of 164 patients were identified as having angioedema across the two emergency departments. Fifty-one (31%; 95% CI = 24-39) were found to be on an ACE inhibitor. The two main presenting symptoms were soft tissue swelling in the head and neck (98%), and respiratory distress (33%), both of which usually developed after several hours. Patients were commonly treated with steroids (70%), antihistamines (65%) and adrenaline (35%). Two patients developed airway obstruction. A substantial proportion of emergency department encounters with angioedema in South Australia are from patients who also use an ACE inhibitor. It is important that general practitioners are aware of this problem, to enable rapid recognition and appropriate patient education when prescribing these medications.

  6. How Not to Be Misled by Disorders Mimicking Angioedema

    DEFF Research Database (Denmark)

    Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye

    2016-01-01

    BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subc......BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest...... with subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. METHODS: The review is based on a literature search...... with specific indexing terms in PubMed, a review of bibliographies and the authors' clinical experience. RESULTS: The most essential diseases that mimic angioedema, the so-called pseudoangioedemas, will each be discussed and illustrated by clinical photos, pointing out key features that help clarify...

  7. A Case of Miller Fisher Syndrome, Thromboembolic Disease, and Angioedema: Association or Coincidence?

    Science.gov (United States)

    Salehi, Nooshin; Choi, Eric D; Garrison, Roger C

    2017-01-16

    BACKGROUND Miller Fisher Syndrome is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia, and is considered to be a variant of Guillain-Barre Syndrome. Miller Fisher Syndrome is observed in approximately 1-5% of all Guillain-Barre cases in Western countries. Patients with Miller Fisher Syndrome usually have good recovery without residual deficits. Venous thromboembolism is a common complication of Guillain-Barre Syndrome and has also been reported in Miller Fisher Syndrome, but it has generally been reported in the presence of at least one prothrombotic risk factor such as immobility. A direct correlation between venous thromboembolism and Miller Fisher Syndrome or Guillain-Barre Syndrome has not been previously described. CASE REPORT We report the case of a 32-year-old Hispanic male who presented with acute, severe thromboembolic disease and concurrently demonstrated characteristic clinical features of Miller Fisher Syndrome including ophthalmoplegia, ataxia, and areflexia. Past medical and family history were negative for thromboembolic disease, and subsequent hypercoagulability workup was unremarkable. During the course of hospitalization, the patient also developed angioedema. CONCLUSIONS We describe a possible association between Miller Fisher Syndrome, thromboembolic disease, and angioedema.

  8. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    DEFF Research Database (Denmark)

    Rasmussen, Eva Rye; von Buchwald, Christian; Wadelius, Mia

    2017-01-01

    Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study...... Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995-2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26-86] years. Female...... gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed...

  9. Genetics Home Reference: hereditary fructose intolerance

    Science.gov (United States)

    ... Home Health Conditions Hereditary fructose intolerance Hereditary fructose intolerance Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Hereditary fructose intolerance is a condition that affects a person's ability ...

  10. Epidemiology of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record.

    Science.gov (United States)

    Banerji, Aleena; Blumenthal, Kimberly G; Lai, Kenneth H; Zhou, Li

    Angiotensin-converting enzyme inhibitors (ACEIs) are a common cause of drug-induced angioedema in the United States. Most epidemiologic ACEI angioedema data are from large multicenter clinical trials. The objective of this study was to identify the incidence of and risk factors for ACEI angioedema using a large integrated electronic health record (EHR). We conducted a retrospective cohort study of all ACEI prescriptions in the outpatient setting of a large academic center between January 1, 2000, and September 30, 2008. We determined frequency, timing, and risk factors for ACEI angioedema within 5 years of prescription. All data were derived from EHR sources, with angioedema defined by EHR reactions of angioedema, swelling, edema, or lip, eye, face, tongue, throat or mouth swelling. Among 134,945 patients prescribed an ACEI, 0.7% (n = 888) developed angioedema during the subsequent 5 years. Sex was similar but patients who developed ACEI angioedema were younger (61.5 vs 62.7 years, P = .007). Patients with ACEI angioedema were more likely to have a history of nonsteroidal anti-inflammatory drug allergy compared with patients who did not develop angioedema (7.1% vs 4.2%, P angioedema within 1 month of prescription and a 0.23% incidence during the first year. Incidence of angioedema was relatively constant annually over the subsequent 4 years (0.10% to 0.12%). The incidence of ACEI angioedema within a large EHR is consistent with large clinical trial data. We observed a persistent and relatively constant annual risk; however, angioedema risk factors and underlying genetic and pathophysiological mechanisms require further study. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Angioedema after ovine hyaluronidase injection for treating hyaluronic acid overcorrection.

    Science.gov (United States)

    Andre, Pierre; Fléchet, Marie Laure

    2008-06-01

    Hyaluronic acid injections are becoming popular in aesthetic dermatology, and, sometimes, misplacements and very rarely adverse events have been reported. Hyaluronidase, an enzyme that hydrolyzes hyaluronic acid, is used to treat overcorrection or granulomatous reactions. Allergic reactions are well known except for how frequent they occur. This paper aims to confirm the efficacy of hyaluronidase injections to dissolve hyaluronic acid, but insists on the risk of hypersensitivity with animal-derived products. A case of angioedema due to ovine hyaluronidase is reported, and treatment is discussed. Hyaluronidase is highly effective, but skin test must be done before injection to avoid risk of angioedema and/or Quincke's edema.

  12. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  13. Facial Oedema Is Not Always Angioedema: A Case of Spontaneous Pneumomediastinum with Subcutaneous Emphysema during COPD Exacerbation

    Directory of Open Access Journals (Sweden)

    Sarah Damanti

    2015-10-01

    Full Text Available We report a case of acute facial oedema in an elderly hospitalized patient which was initially misdiagnosed as angioedema secondary to antibiotics in a patient with an allergic diathesis. We describe the differential aetiologies and then the true cause of the oedema, which was an uncommon complication of a very common condition in the elderly: a pneumomediastinum with subcutaneous emphysema probably due to rupture of an emphysematous lung bulla during chronic obstructive pulmonary disease (COPD exacerbation. Lastly, we focus on the therapeutic procedures instituted for the treatment of the pneumomediastinum.

  14. a case report of suspected angioedema in a child after ...

    African Journals Online (AJOL)

    consecutive days.16 Common side effects include: nausea, vomiting while rare side effects include: rash, alopecia, urticaria and angioedema. Adverse effects appear to occur more frequently when higher doses are used.17. A compiled information from Food and Drug administration (FDA) and Facts Med users submissions.

  15. Urticaria and angioedema: a practical approach | Muller | South ...

    African Journals Online (AJOL)

    Urticaria (i.e., pruritic, raised wheals) and angioedema (i.e., deep mucocutaneous swelling) occur in up to 25 percent of the U.S. population. Vasoactive mediators released from mast cells and basophils produce the classic wheal and flare reaction. Diagnosis can be challenging, especially if symptoms are chronic or ...

  16. Fatal angioedema induced by angiotensin conversion enzyme (ACE ...

    African Journals Online (AJOL)

    ACE inhibitors are often prescribed in the treatment of hypertension, heart failure and kidney disease. These drugs are on the Essential Drugs List, and are therefore used at primary to tertiary health care levels in South Africa. Angioedema is considered a rare, but potentially fatal side-effect of this agent, with a reported ...

  17. Angiotensin converting enzyme induced angioedema: The need for ...

    African Journals Online (AJOL)

    Background: Angiotensin converting enzyme (ACE) inhibitor related angioneurotic edema or simply angioedema is a rare but common condition not well noticed in health facilities especially in developing countries. The complication can be life threatening with serious morbidity and mortality if not promptly diagnosed from ...

  18. A case report of suspected angioedema in a child after ...

    African Journals Online (AJOL)

    Children are at a higher risk of developing adverse drug reactions as they seldom express their own drug therapy experiences. Factors that have been implicated include polypharmacy ... Cutaneous drug allergy is a common manifestation of adverse drug reactions. Keywords: Angioedema, Mebendazole, Co-trimoxazole, ...

  19. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  20. Hereditary neuromuscular diseases

    International Nuclear Information System (INIS)

    Oezsarlak, O.; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J.

    2001-01-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible

  1. Hereditary Diffuse Infiltrating Retinoblastoma.

    Science.gov (United States)

    Schedler, Katharina J E; Traine, Peter G; Lohmann, Dietmar R; Haritoglou, Christos; Metz, Klaus A; Rodrigues, Eduardo B

    2016-01-01

    Retinoblastoma is one of the most common childhood cancers. The diffuse infiltrating retinoblastoma is a rare subtype of this neoplasm. The majority of cases of diffuse infiltrating retinoblastoma are unilateral and occur sporadically. Herein we report on a family with three children affected by retinoblastoma, among them one girl with diffuse infiltrating retinoblastoma. This girl was diagnosed at the age of 8 years with a unilateral diffuse infiltrating retinoblastoma. By contrast, the two brothers became clinically apparent in the first 2 years of life with bilateral retinoblastoma. The parents were clinically unremarkable. Genetic analysis of RB1 gene was performed. The girl with diffuse infiltrating RB was found to be heterozygous for an oncogenic mutation in the RB1 gene that was also carried by both brothers and the father of the family. These results show that diffuse infiltrating retinoblastoma can develop on the background of a hereditary predisposition to retinoblastoma.

  2. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  3. [Biologic treatments for hereditary diseases].

    Science.gov (United States)

    Yang, Jing; Xie, Yangli; Chen, Lin

    2015-06-01

    Hereditary disease, especially monogenic disease is one of the major causes for malformation and disability of children. Most hereditary diseases have no effective therapy besides clinical symptomatic treatment. Biological techniques targeting casual genes or related signaling genes, such as transgenic, RNA interfere, genome editing, have been successfully applied in treating some hereditary diseases. However, most biological, treatments were carried out in animals, further confirmation of the effectiveness and safety of these therapies, and development of more therapeutic approaches based on mechanisms are needed before clinical trials.

  4. Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors.

    Science.gov (United States)

    Loftus, Patricia A; Tan, Melin; Patel, Gunj; Lin, Juan; Helman, Sam; Badhey, Arvind; Du, Eugenie; Smith, Richard V; Fried, Marvin P; Ow, Thomas J

    2014-11-01

    To evaluate the etiology and risk factors for severe manifestation and recurrent episodes of angioedema; to evaluate efficacy of short-term and long-term management strategies for angioedema among a high-risk population. Institutional review board-approved retrospective review of a large, urban population. Data from 875 adult patients treated from January 2008 to December 2013 with the diagnosis of angioedema were obtained using the Clinical Looking Glass utility and review of medical records. Demographic and clinicopathologic risk factors were recorded. The major outcomes evaluated were hospital admission, need for airway intervention, and recurrent episodes of angioedema following the first presentation. Initial treatment strategy and follow-up recommendations were also recorded. The most common cause of angioedema was angiotensin converting enzyme inhibitor (ACEi)-induced (496 [56.6%]). Significant risk factors for severe cases of angioedema included older age, Hispanic race, ACEi-induced angioedema type, American Society of Anesthesiologists class III or above, coexistent cardiopulmonary disease, and a positive smoking history. A total of 17.2% of patients experienced recurrent attacks of angioedema; of those patients, 25.9% were still taking an ACEi at subsequent presentation. Risk factors for recurrent episodes included older age, idiopathic angioedema type, and coexistent cardiopulmonary disease. Only 54.1% of patients who experienced ACEi-induced angioedema had electronic medical record documentation of these allergies. Knowledge of risk factors for severe and recurrent episodes of angioedema and improved education for both healthcare providers and patients, specifically related to ACEi use and allergy documentation, may significantly decrease the burden and morbidity of angioedema among high risk populations. 2b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Hereditary iron and copper deposition

    DEFF Research Database (Denmark)

    Aaseth, Jan; Flaten, Trond Peder; Andersen, Ole

    2007-01-01

    Hereditary deposition of iron (primary haemochromatosis) or copper (Wilson's disease) are autosomal recessive metabolic disease characterized by progressive liver pathology and subsequent involvement of various other organs. The prevalence of primary haemochromatosis is approximately 0.5%, about...

  6. Hereditary familial vestibular degenerative diseases.

    NARCIS (Netherlands)

    Sun, J.; Alphen, A.M. van; Wagenaar, M.; Huygen, P.L.M.; Hoogenraad, C.C.; Hasson, T.; Koekkoek, S.K.; Bohne, B.A.; Zeeuw, C.I. de

    2001-01-01

    Identification of genes involved in hereditary vestibular disease is growing at a remarkable pace. Mutant mouse technology can be an important tool for understanding the biological mechanism of human vestibular diseases.

  7. Angiotensin-converting Enzyme Inhibitor Angioedema Requiring Admission to an Intensive Care Unit.

    Science.gov (United States)

    Soo Hoo, Guy W; Lin, Henry K; Junaid, Imran; Klaustermeyer, William B

    2015-07-01

    The purpose of this study was to review consecutive cases of angiotensin-converting enzyme (ACE) inhibitor angioedema admitted to an intensive care unit. Fifty subjects with ACE-inhibitor angioedema admitted from 1998-2011 were reviewed. All 50 subjects were men, 62.8 ± 8.4 years of age, 76% African Americans. Fifteen (30%) required ventilatory support and 2 (4%) required tracheostomy. Over half (56%) had taken ACE inhibitors for over a year. Logistic regression identified dyspnea and tongue involvement with the need for ventilatory support (P angioedema. Angioedema can occur even after extended use. Dyspnea and tongue involvement identified patients requiring ventilatory support. Published by Elsevier Inc.

  8. Angiotensin-converting Enzyme Inhibitor and Other Drug-associated Angioedema.

    Science.gov (United States)

    Stone, Cosby; Brown, Nancy J

    2017-08-01

    Nonsteroidal antiinflammatory agents, β-lactam antibiotics, non-β lactam antibiotics, and angiotensin-converting enzyme inhibitors are the most common classes of drugs that cause angioedema. Drug-induced angioedema is known to occur via mechanisms mediated by histamine, bradykinin, or leukotriene, and an understanding of these mechanisms is crucial in guiding therapeutic decisions. Nonallergic angioedema occurs in patients with genetic variants that affect metabolism or synthesis of bradykinin, substance P, prostaglandins, or leukotrienes, or when patients are taking drugs that have synergistic mechanisms. The mainstay in treatment of nonallergic drug-induced angioedema is cessation of the offending agents. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Angioedema triggered by pulp extirpation--a case report.

    Science.gov (United States)

    Baliga, Mohan; Ramanathan, Arvind; Bhambar, Rohan S

    2011-12-01

    C1-esterase inhibitor deficiency results in episodes of non-allergic edema of parts of the body. Edema of the face may be triggered by dental therapy. We report a case of C1-esterase inhibitor deficiency which was detected in a 42-year-old woman. The patient was completely unaware that she had this disorder or of any related family history, and the patient developed an intense facial angioedema after pulp extirpation of lower premolar tooth. In this case, the diagnosis of angioedema due to C1-esterase inhibitor deficiency was established at a later stage. The differing causes of C1-esterase inhibitor deficiency are briefly discussed and the treatment modalities outlined.

  10. Genetics Home Reference: distal hereditary motor neuropathy, type V

    Science.gov (United States)

    ... Distal hereditary motor neuropathy, type V Distal hereditary motor neuropathy, type V Printable PDF Open All Close All Enable ... link) PubMed OMIM (2 links) NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE VA NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE VB Sources ...

  11. Association between thyroid autoimmunity and recurrent angioedema in children.

    Science.gov (United States)

    Karagol, Hacer Ilbilge Ertoy; Yilmaz, Ozlem; Topal, Erdem; Bideci, Aysun; Bakirtas, Arzu

    2015-01-01

    The association between thyroid autoimmunity (TA) and idiopathic isolated angioedema (or angioedema without urticaria) has not been evaluated in either children or in adults up until now. We, therefore, aimed to investigate underlying or concomitant TA and/or autoimmune thyroid disease in children diagnosed with recurrent idiopathic angioedema. Children who were consecutively diagnosed with recurrent idiopathic histaminergic acquired angioedema (IH-AAE) between January 2011 and January 2014 constituted the case group. A standard diagnostic and therapeutic algorithm was applied to all the patients with recurrent IH-AAE. Thyroid autoantibodies and thyroid function tests were measured in all the patients with recurrent IH-AAE and in healthy control groups. Prophylaxis with an antihistamine was started for patients with frequently recurrent IH-AAE. Eighty consecutive children with recurrent IH-AAE (49 boys; median age, 8.3 years) and 80 healthy children (39 boys; median, 8 years) were enrolled in this prospective, case-control study (p > 0.05 for age and sex). The IH-AAE group was significantly different than the control group with respect to TA (13.7% versus 2.5%, respectively; p = 0.009) but was similar with respect to autoimmune thyroid disease (3.7% versus 0%, respectively; p = 0.2). The median follow-up of the recurrent IH-AAE group was 34 months (range, 12-45 months). Patients with recurrent IH-AAE with and those without TA were not different with respect to either the need or the duration of antihistamine prophylaxis (p > 0.05 for both). Recurrent IH-AAE may be related to or associated with TA and/or autoimmune thyroid diseases in some children. However, exploring to see whether this association is a causal link or just an epiphenomenon deserves further investigation and longer follow-ups.

  12. Recurrent angioedema associated with hypogonadism or anti-androgen therapy.

    Science.gov (United States)

    Pichler, W J; Lehner, R; Späth, P J

    1989-10-01

    Two male patients with hypogonadism and four female patients who received an anti-androgen as contraceptive (cyproteronacetate) and who had recurrent angioedema are described. In one male patient, augmentation of the plasma androgen level resulted in disappearance of symptoms. In the four female patients, recurrent angioedema and urticaria developed after initiation of the anti-androgen treatment. Cessation of cyproteronacetate and a change to another contraceptive resulted in complete resolution of the previously frequent angioedematous attacks. The women are still symptom free after more than 60 patient's months. These cases suggest that an androgen deficit due to either hypogonadism or to anti-androgen treatment may be another cause of angioedema. One of the two male patients was untreated and presented with 40% normal value of C1-INH. Androgen therapy normalized C1-INH concentration in this male patient. Functional C1-INH in the same patient, studied before and after the beginning of androgen therapy, clearly increased when assessed by inhibition of amidolytic activity of C1-esterase. The other male patient with hypogonadism had already been under androgen treatment for 4 years and had C1-INH levels in the normal range. In the female patients, complement profiles were normal before and after cessation of anti-androgen contraception; however, the C1-INH plasma levels were higher after cessation of anti-androgen anticonception. These results indicate an effect of androgen deficit on the level of C1-INH in circulating plasma but do not prove a role of C1-INH in angioedema associated with diminished androgen plasma levels.

  13. [Exercise-induced urticaria and angioedema - case report].

    Science.gov (United States)

    Stelmach, Iwona; Sztafińska, Anna; Lechańka, Joanna; Balcerak, Joanna; Jerzyńska, Joanna

    2014-01-01

    Urticaria is a heterogeneous group of disorders, with various clinical manifestations and intensity of symptoms. Urticaria can be induced with a wide variety of environmental stimuli, such as cold, pressure, vibration, sunlight, exercise, temperature changes, heat, and water. In a select group of patients, exercise can induce a spectrum of urticaria symptoms, ranging from cutaneous pruritus and warmth, generalised urticaria, angioedema, and the appearance of such additional manifestations as collapse, upper respiratory distress, and anaphylaxis. Specific provocation tests should be carried out on an individual basis to investigate the suspected cause and proper diagnosis. Modification of activities and behaviour is the mainstay of treatment in patients with physical urticaria. The aim of this study was to emphasise that primary care paediatricians should be able to recognise physical urticaria, supply a patient with rescue medications, and refer him/her to a specialist. In the article, the authors present a 13-year-old girl with typical urticaria lesions and angioedema after exercise. According to the history, physical examination, and provocation test, exercise-induced urticaria and angioedema were diagnosed.

  14. Diagnosis and Treatment of Urticaria and Angioedema: A Worldwide Perspective

    Science.gov (United States)

    2012-01-01

    Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide. PMID:23282382

  15. Angioedema recorrente – caso clínico

    Directory of Open Access Journals (Sweden)

    Sandrina Martins

    2016-02-01

    Full Text Available Introdução: O Angioedema hereditário (AEH é uma causa rara de angioedema recorrente, resultante de um defeito a nível do gene que codifica o inibidor do C1 esterase (C1 -INH. O edema envolve predominantemente os tecidos da face, membros, trato gastrointestinal e área genital. O envolvimento da laringe, apesar de menos frequente, constitui a expressão clínica mais grave, sendo potencialmente fatal. Caso clínico: Descreve -se o caso clínico de uma criança do sexo feminino de oito anos de idade referenciada à consulta de pediatria por episódios recorrentes de angioedema. O estudo efetuado revelou tratar -se de um caso de AEH. Discussão: O diagnóstico, estabelecido com base no quadro clínico, estudo do complemento e história familiar, é de importância fundamental considerando que o AEH é potencialmente fatal e exige uma terapêutica específica.

  16. Genetic Determinants of C1 Inhibitor Deficiency Angioedema Age of Onset.

    Science.gov (United States)

    Gianni, Panagiota; Loules, Gedeon; Zamanakou, Maria; Kompoti, Maria; Csuka, Dorottya; Psarros, Fotis; Magerl, Markus; Moldovan, Dimitru; Maurer, Marcus; Speletas, Matthaios G; Farkas, Henriette; Germenis, Anastasios E

    2017-01-01

    In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1-428G/A to the disease phenotype. We studied 249 C1-INH-HAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1-428G/A, combined or not with that of the functional F12-46C/T polymorphism. Carriers of the G allele of the KLKB1-428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [p < 0.001], depending on the zygocity status), while carriers of both the KLKB1-428G/A and the F12-46C/T polymorphism displayed an 8.8-year delay in disease onset (p < 0.001) and a 64% lower probability of needing long-term prophylactic treatment (p = 0.019). These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity. © 2017 S. Karger AG, Basel.

  17. Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

    Science.gov (United States)

    Defendi, Federica; Charignon, Delphine; Ghannam, Arije; Habib, Mohammed; Drouet, Christian

    2016-01-01

    Background Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98–175μg/mL, n = 51) and in healthy women (90–176μg/mL, n = 74), while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay. Conclusion As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management. PMID:27685806

  18. Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions.

    Directory of Open Access Journals (Sweden)

    Rémi Baroso

    Full Text Available Angioedema without wheals (AE is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh, but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases.We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker.We retrospectively investigated high molecular weight kininogen (HK cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis.Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98-175μg/mL, n = 51 and in healthy women (90-176μg/mL, n = 74, while HK cleavage was lower (p14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13 or two weeks after AE attack (n = 2, HK cleavage was not fully restored, suggesting its use as a post-attack assay.As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.

  19. Pharmacogenetics of ACE inhibitor-induced angioedema and cough: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Mahmoudpour, Seyed Hamidreza; Leusink, Maarten; van der Putten, Lisa; Terreehorst, Ingrid; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke H.

    2013-01-01

    Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. This study was

  20. Non-myeloablative allogeneic stem cell transplantation: a new treatment option for acquired angioedema?

    NARCIS (Netherlands)

    Zegers, I.H.A.; Aaldering, K.N.; Nieuwhof, C.M.; Schouten, H.C.

    2015-01-01

    INTRODUCTION: Acquired angioedema is a rare disorder causing recurrent life-threatening angioedema, due to decreased activity of C1 esterase inhibitor. CASE REPORT: A 57-year-old man presented to our hospital with recurrent swelling of the hands, lips, tongue, scrotum and throat. Lab examination

  1. Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema

    Science.gov (United States)

    von Buchwald, Christian; Prasad, Sumangali Chandra; Kamaleswaran, Shailajah; Ajgeiy, Kawa Khaled; Authried, Georg; Pallesen, Kristine Appel U.

    2017-01-01

    Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were “DT783 Quincke's oedema” and “DT78.4 Allergy unspecified”. Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor. PMID:28286522

  2. Clinical characteristics and treatment of chronic urticaria and angioedema : Dwelling on swelling, dealing with whealing

    NARCIS (Netherlands)

    van den Elzen, M.T.

    2017-01-01

    The occurrence of wheals, angioedema or both for at least 6 weeks is diagnosed as chronic spontaneous urticaria in (inter) national guidelines - after excluding other illnesses. The underlying mechanism of angioedema without wheals is not entirely known. The objective of this thesis is to increase

  3. Dipeptidyl peptidase-4 inhibitor induced angioedema - an overlooked and potentially lethal adverse drug reaction?

    DEFF Research Database (Denmark)

    Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise

    2018-01-01

    Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl...

  4. Analysis of related factors of orolingual angioedema after rt-PA intravenous thrombolytic therapy.

    Science.gov (United States)

    Wang, Y-X; Li, Y-Q; Chen, Y; Zhang, C-H; Dong, Z; Wang, Z; Zhao, S-N; Li, C-H; Zhang, P-L

    2018-03-01

    Orolingual angioedema (OA) is a rare clinical complication with a potentially fatal risk that occurs after the intravenous application of alteplase (rt-PA) in patients with acute ischemic stroke. The purpose of this work is to investigate the related factors of OA in patients with acute ischemic stroke after the administration of intravenous thrombolytic therapy, to improve the predictive ability of OA during intravenous thrombolytic therapy, and to reduce the prevalence of complications. We recruited 1223 cases of patients with acute ischemic stroke that were treated in the Department of Neurology No. 4 of the Tianjin Huanhu Hospital from June 2014 to April 2015. The clinical manifestations of rt-PA related OA were recorded, the clinical prevalence was counted, related factors of OA after intravenous thrombolytic therapy were analyzed, and the risk assessment of rt-PA related OA was conducted. 14 cases of patients developed OA, with a prevalence rate of 1.14%. Among them, 5 had a history of urticaria, 4 of drug allergy, and 3 of food allergy. Among the 14 cases of patients, 10 developed OA in the process of intravenous thrombolysis and 4 after intravenous thrombolysis, 12 showed lip edema, 9 showed extensive swelling of tongue, 3 showed swelling of lateral tongue, 3 were complicated by respiratory distress, 10 showed infarction in the middle cerebral artery territory, and 6 had previously been given oral ACEI drugs. Orolingual angioedema is a rare complication that occurs after rt-PA intravenous thrombolytic therapy; when serious, it may endanger a patient's life. If patients take an oral hypotension such as ACEI drugs before the onset of OA, they have a history of allergies, or the lesion is an infraction in the dominated area of the middle cerebral artery, the risk of OA after rt-PA intravenous thrombolytic therapy will be increased. The prevalence of OA should be monitored during the rt-PA intravenous thrombolytic therapy process; timely detection and early

  5. Pollen count and presentation of angiotensin-converting enzyme inhibitor-associated angioedema.

    Science.gov (United States)

    Straka, Brittany; Nian, Hui; Sloan, Chantel; Byrd, James Brian; Woodard-Grice, Alencia; Yu, Chang; Stone, Elizabeth; Steven, Gary; Hartert, Tina; Teo, Koon K; Pare, Guillaume; McCarty, Catherine A; Brown, Nancy J

    2013-01-01

    The incidence of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema is increased in patients with seasonal allergies. We tested the hypothesis that patients with ACE inhibitor-associated angioedema present during months when pollen counts are increased. Cohort analysis examined the month of presentation of ACE inhibitor-associated angioedema and pollen counts in the ambulatory and hospital setting. Patients with ACE inhibitor-associated angioedema were ascertained through (1) an observational study of patients presenting to Vanderbilt University Medical Center, (2) patients presenting to the Marshfield Clinic and participating in the Marshfield Clinic Personalized Medicine Research Project, and (3) patients enrolled in The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Measurements include date of presentation of ACE inhibitor-associated angioedema, population exposure to ACE inhibitor by date, and local pollen counts by date. At Vanderbilt, the rate of angioedema was significantly associated with tree pollen months (P = .01 from χ(2) test). When separate analyses were conducted in patients with a history of seasonal allergies and patients without, the rate of ACE inhibitor-associated angioedema was increased during tree pollen months only in patients with a history of seasonal allergies (P = .002). In Marshfield, the rate of angioedema was significantly associated with ragweed pollen months (P = .025). In ONTARGET, a positive trend was observed between the ACE inhibitor-associated angioedema rate and grass season, although it was not statistically significant (P = .057). Patients with ACE inhibitor-associated angioedema are more likely to present with this adverse drug event during months when pollen counts are increased. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Genetics Home Reference: hereditary hemorrhagic telangiectasia

    Science.gov (United States)

    ... Girod S, Bailly S, Plauchu H. Hereditary hemorrhagic telangiectasia: from molecular biology to patient care. J Thromb Haemost. 2010 Jul; ... Bayrak-Toydemir P. Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era. Front Genet. 2015 Jan 26;6:1. doi: ... JA. Hereditary hemorrhagic telangiectasia: ...

  7. Immunophenotyping of hereditary breast cancer

    NARCIS (Netherlands)

    van der Groep, P.

    2009-01-01

    Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may

  8. Graph limits and hereditary properties

    OpenAIRE

    Janson, Svante

    2011-01-01

    We collect some general results on graph limits associated to hereditary classes of graphs. As examples, we consider some classes defined by forbidden subgraphs and some classes of intersection graphs, including triangle-free graphs, chordal graphs, cographs, interval graphs, unit interval graphs, threshold graphs, and line graphs.

  9. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...

  10. How Not to Be Misled by Disorders Mimicking Angioedema: A Review of Pseudoangioedema.

    Science.gov (United States)

    Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye; Bygum, Anette

    2016-01-01

    Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. The review is based on a literature search with specific indexing terms in PubMed, a review of bibliographies and the authors' clinical experience. The most essential diseases that mimic angioedema, the so-called pseudoangioedemas, will each be discussed and illustrated by clinical photos, pointing out key features that help clarify the diagnoses and differentiate these from classic angioedema. A variety of dermatologic conditions can cause swelling that resembles angioedema, some with a potentially fatal outcome if misdiagnosed. Knowledge of pseudoangioedema is fundamental in the emergency setting when handling patients with edema and should be kept in mind when assessing an atypical angioedema case. © 2016 S. Karger AG, Basel.

  11. Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

    Science.gov (United States)

    Owens, Ryan E; Oliphant, Carrie S

    2017-01-01

    Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.

  12. Genetic variants associated with angiotensin-converting enzyme inhibitor-associated angioedema

    Science.gov (United States)

    Pare, Guillaume; Kubo, Michiaki; Byrd, James B.; McCarty, Catherine A.; Woodard-Grice, Alencia; Teo, Koon K.; Anand, Sonia S.; Zuvich, Rebecca L.; Bradford, Yuki; Ross, Stephanie; Nakamura, Yusuke; Ritchie, Marylyn; Brown, Nancy J.

    2013-01-01

    Objective The objective of this study was to identify genetic variants associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Participants and methods We carried out a genome-wide association study in 175 individuals with ACE inhibitor-associated angioedema and 489 ACE inhibitor-exposed controls from Nashville (Tennessee) and Marshfield (Wisconsin). We tested for replication in 19 cases and 57 controls who participated in Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). Results There were no genome-wide significant associations of any single-nucleotide polymorphism (SNP) with angioedema. Sixteen SNPs in African Americans and 41 SNPs in European Americans were associated moderately with angioedema (Pangioedema in the Nashville/Marshfield sample and ONTARGET. In a candidate gene analysis, rs989692 in the gene encoding neprilysin (MME), an enzyme that degrades bradykinin and substance P, was significantly associated with angioedema in ONTARGET and Nashville/Marshfield African Americans. Conclusion Unlike other serious adverse drug effects, ACE inhibitor-associated angioedema is not associated with a variant with a large effect size. Variants in MME and genes involved in immune regulation may be associated with ACE inhibitor-associated angioedema. PMID:23838604

  13. Angioedema: Classification, management and emerging therapies for the perioperative physician

    Science.gov (United States)

    Misra, Lopa; Khurmi, Narjeet; Trentman, Terrence L

    2016-01-01

    Angioedema is a rare condition which manifests as sudden localised, non-pitting swelling of certain body parts including skin and mucous membranes. It is vital that anaesthesiologists understand this condition, as it may present suddenly in the perioperative period with airway compromise. To identify literature for this review, the authors searched the PubMed, Medline, Embase, Scopus and Web of Science databases for English language articles covering a 10-year period, 2006 through 2016. Angioedema can be either mast-cell mediated or bradykinin-induced. Older therapies for histaminergic symptoms are well known to anaesthesiologists (e.g., adrenaline, anti-histamines and steroids), whereas older therapies for bradykinin-induced symptoms include plasma and attenuated androgens. New classes of drugs for bradykinin-induced symptoms are now available, including anti-bradykinin, plasma kallikrein inhibitor and C1 esterase inhibitors. These can be used prophylactically or as rescue medications. Anaesthesiologists are in a unique position to coordinate perioperative care for this complex group of patients. PMID:27601734

  14. Angioedema hereditario: Tratamiento del ataque agudo en la Argentina

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2014-06-01

    Full Text Available En el mundo, el angioedema hereditario (HAE afecta a 1 de cada 50 000 personas. Produce episodios de angioedema cutáneo, abdominal y laríngeos que generan gran incapacidad. La mortalidad por la enfermedad oscila entre 15 y 50%. Aunque en Argentina un concentrado plasmático de C1 inhibidor (pdC1INH ha estado aprobado y disponible por décadas para el tratamiento del ataque agudo, solo 15 (26% de 58 pacientes había recibido pdC1INH alguna vez hasta el año 2008, y solo 2(3.4% lo usaban regularmente. Luego de la aprobación de los nuevos medicamentos para HAE, incluido el icatibant en Argentina y de la publicación de las guías terapéuticas, 42 (82% de 51 pacientes del grupo original tienen pdC1INH para tratar el próximo ataque. Sin embargo, 16 (18% de estos pacientes continúan sin acceso a la medicación y otros 15 (35.7% acceden a través de otro enfermo en forma espuria. Solo 12 (28.6% de los pacientes con el medicamento puede auto tratarse en su domicilio. La mejora en el acceso a la medicación es importante pero debe extenderse a todos los afectados y facilitarse el auto-tratamiento.

  15. Angioedema: Classification, management and emerging therapies for the perioperative physician

    Directory of Open Access Journals (Sweden)

    Lopa Misra

    2016-01-01

    Full Text Available Angioedema is a rare condition which manifests as sudden localised, non-pitting swelling of certain body parts including skin and mucous membranes. It is vital that anaesthesiologists understand this condition, as it may present suddenly in the perioperative period with airway compromise. To identify literature for this review, the authors searched the PubMed, Medline, Embase, Scopus and Web of Science databases for English language articles covering a 10-year period, 2006 through 2016. Angioedema can be either mast-cell mediated or bradykinin-induced. Older therapies for histaminergic symptoms are well known to anaesthesiologists (e.g., adrenaline, anti-histamines and steroids, whereas older therapies for bradykinin-induced symptoms include plasma and attenuated androgens. New classes of drugs for bradykinin-induced symptoms are now available, including anti-bradykinin, plasma kallikrein inhibitor and C1 esterase inhibitors. These can be used prophylactically or as rescue medications. Anaesthesiologists are in a unique position to coordinate perioperative care for this complex group of patients.

  16. On the Hereditary Properties of Modular Nets

    Directory of Open Access Journals (Sweden)

    V. A. Bashkin

    2012-01-01

    Full Text Available Hereditary graph properties are those that can be inherited from the graph to all its subgraphs (such as planarity. Modular nets of active resources is a (Petri nets- powerful formalism with simple modular syntax. Boundedness and liveness are fundamental semantic properties for Petri net models. It is shown that boundedness and liveness, being not hereditary in general, are downward-hereditary (net-to-subnet and upward-hereditary (subnet-to-net for the particular types of AR-subnets. It is also shown that boundedness is downward-hereditary and unboundedness is upward-hereditary for arbitrary subnets after a specific module interface transformation (so-called R-normalization.

  17. Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema

    Directory of Open Access Journals (Sweden)

    Kaur R

    2014-12-01

    Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy

  18. ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

    Directory of Open Access Journals (Sweden)

    R. Mason Curtis

    2016-06-01

    Full Text Available Introduction: Upper airway angioedema is a life-threatening emergency department (ED presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257 of cases. The most common identifiable etiology was AAE (33.1%, n=85, with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54, corticosteroids (50.6%, n=43 and ranitidine (31.8%, n=27. Epinephrine was administered in 21.2% (n=18 of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7% and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management.

  19. Angioedema of the upper aerodigestive tract: risk factors associated with airway intervention and management algorithm.

    Science.gov (United States)

    Brook, Christopher D; Devaiah, Anand K; Davis, Elizabeth M

    2014-03-01

    Angioedema of the upper aerodigestive tract can lead to significant airway obstruction. To date no articles have delineated risk factors for progression after initial evaluation. This article presents the results of a retrospective study of patients with angioedema at a single institution. Patients included were consecutive otolaryngology consultations for angioedema in the emergency department (ED) from 1999 to 2003. All patients were evaluated by an otolaryngologist and underwent fiber-optic laryngoscopy, which was repeated serially depending on findings. Data was collected on demographics, comorbidities, intubation, disposition, and progression of angioedema. A total of 177 patients were included in the study: 32 (18%) patients required intubation; 25 (14%) on initial presentation and 7 (4%) who progressed from an initially stable airway to requiring intervention after reevaluation. Analysis of variance (ANOVA) demonstrated a statistically significant variance between location of edema and rate of intubation, with higher rates in the pharynx and larynx vs the lip and face. Patients who required intubation after progression between serial evaluations were statistically more likely to have edema that involved deeper portions of the aerodigestive tract. Patients who required intubation were statistically more likely to be older (average age 61.8 vs 55.1 years, p = 0.03). In this large series of patients managed for aerodigestive angioedema we demonstrate risk factors associated with airway intervention, and risk factors associated with clinical progression on serial examination to airway intervention. In addition, we demonstrate a successful management algorithm for patients with aerodigestive angioedema. © 2014 ARS-AAOA, LLC.

  20. Elucidating the Mechanism of Gain of Toxic Function From Mutant C1 Inhibitor Proteins in Hereditary Angioedema

    Science.gov (United States)

    2017-10-01

    fact , that the plasma level of C1INH was significantly reduced in 75 PiZZ children compared to 35 control children (14%, p ɘ.01). A similar...constructed all plasmids and performed mutagenesis Funding Support: None Name: Astrid Doerner Project Role: Project Scientist Research

  1. Hereditary & familial colorectal cancer : Identification, characteristics, surveillance

    NARCIS (Netherlands)

    Kallenberg, F.G.J.

    2017-01-01

    Of all colorectal cancer (CRC) cases, 15-20% is related to familial or hereditary factors. Diagnosing familial and hereditary CRC syndromes is important for several reasons. One of these is that surveillance colonoscopies can reduce CRC incidence and mortality importantly. A complete family history

  2. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...

  3. BSACI guideline for the management of chronic urticaria and angioedema.

    Science.gov (United States)

    Powell, R J; Leech, S C; Till, S; Huber, P A J; Nasser, S M; Clark, A T

    2015-03-01

    This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research. © 2015 John Wiley & Sons Ltd.

  4. Andrógenos en el tratamiento de mantenimiento a largo plazo del angioedema hereditario. ¿Es el momento de pensar en otras opciones?

    OpenAIRE

    Frías Iniesta, Jesús

    2016-01-01

    El angioedema hereditario (AEH) es una enfermedad transmitida con un patrón autosómico dominante, caracterizada por la presencia de angioedema recurrente y ocasionada por un defecto de la enzima conocida como inhibidor de C1. El principal mediador involucrado en el desarrollo del angioedema es la bradicinina

  5. The molecular classification of hereditary endocrine diseases.

    Science.gov (United States)

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  6. [Molecular mechanism of hereditary spherocytosis].

    Science.gov (United States)

    Bogusławska, Dzamila M; Heger, Elzbieta; Sikorski, Aleksander F

    2006-01-01

    Hereditary spherocytosis (HS) is a common inherited anaemia in northern Europe characterized by the presence of spherocytic red cells and by heterogeneous clinical presentation, and heterogeneous molecular basis and inheritance. The primary molecular defects reside in the red blood cell membrane, particularly in proteins involved in the vertical interactions between the membrane skeleton and the lipid bilayer. Defects in these interactions lead to the loss of red cell surface area and to the spheroidal shape of the erythrocyte in particular loss of the membrane elasticity and mechanical stability. Severe HS is often associated with a substantial reduction of, and (or) dysfunction of, the affected membrane protein(s). Hereditary spherocytosis stems from mutations in one of the genes encoding ankyrin-1 (ANKI), alpha spectrin (SPTA1) and beta spectrin (SPTB), the anion exchanger 1 (SLC4A 1), and protein 4.2 (EPB42). Inheritance of HS is usually (75%) autosomal, dominant. Recessive and nondominant cases are mostly found in HS associated with ANK1, SPTA1 and SPTB genes.

  7. Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies.

    Science.gov (United States)

    Zazzali, James L; Kaplan, Allen; Maurer, Marcus; Raimundo, Karina; Trzaskoma, Benjamin; Solari, Paul G; Antonova, Evgeniya; Mendelson, Meryl; Rosén, Karin E

    2016-10-01

    Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life. To describe patient-reported angioedema and its management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL). Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine 1 (H 1 )-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H 1 -antihistamines at up to 4 times the approved dose plus H 2 -antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized. At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P angioedema was managed by low-intensity interventions (doing nothing or taking medication). Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes. clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors.

    Science.gov (United States)

    Scalese, Michael J; Reinaker, Travis S

    2016-06-15

    The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema is reviewed. Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial (NCT01919801) will better define the role of icatibant in the management of ACEI-induced angioedema. FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. Hereditary syndromes with enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Lohmann, D.

    2000-01-01

    Sensitivity to ionizing radiation is modified by heritable genetic factors. This is exemplified by heritable disorders that are characterized by predisposition to the development of neoplasms. Cells derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome and ataxia telangiektasia-like disorder show a markedly changed reaction to exposure to ionizing radiation. Correspondingly, at least in patients with ataxia telangiectasia, an enhanced radiosensitivity that is of clinical importance has been observed. In addition to these recessive disorders, some autosomal dominant cancer predisposition syndromes are associated with increased radiosensitivity. As cells from these patients still have a normal allele (that is dominant over the mutant allele), the cellular phenotype is most often normal. Specifically, there is no overtly altered reaction in response to ionizing radiation. Nevertheless, two dominant cancer predisposition syndromes, namely hereditary retinoblastoma and naevoid basal cell carcinoma syndrome, are associated with a enhanced radiosensitivity as indicated by increased development of tumors following radiation therapy. (orig.) [de

  10. Imaging of Hereditary Hemorrhagic Telangiectasia

    International Nuclear Information System (INIS)

    Carette, Marie-France; Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine

    2009-01-01

    This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

  11. Non-myeloablative allogeneic stem cell transplantation: a new treatment option for acquired angioedema?

    Science.gov (United States)

    Zegers, I H A; Aaldering, K N A; Nieuwhof, C M G; Schouten, H C

    2015-10-01

    Acquired angioedema is a rare disorder causing recurrent life-threatening angioedema, due to decreased activity of C1 esterase inhibitor. A 57-year-old man presented to our hospital with recurrent swelling of the hands, lips, tongue, scrotum and throat. Lab examination showed the presence of an IgM kappa monoclonal antibody. Additional analysis showed that in the IgM fraction autoantibody activity against C1 esterase inhibitor was present. This confirmed the diagnosis of acquired angioedema in the presence of lymphoplasmacytic lymphoma. Despite standard therapy, there was an increase in the episodes of laryngeal oedema. Therefore it was decided to perform a non-myeloablative allogeneic haematopoietic stem cell transplantation, with his HLA-identical brother as donor. The post-transplantation course was without complications. Five years following alloSCT he is in complete remission without symptoms and with increased C1 esterase inhibitor activity. In this case all other known treatment options for severe acquired angioedema failed. This is the first case describing treatment of severe acquired angioedema, caused by lymphoplasmacytic lymphoma, with an alloSCT.

  12. [A Case of Life-Threatening Angioedema Occurred During Prolonged Angiotensin-Converting Enzyme Inhibitor Treatment].

    Science.gov (United States)

    Nakamura, Rintaro; Nihei, Shun-Ichi; Arai, Hideaki; Nagata, Keiji; Isa, Yasuki; Harayama, Nobuya; Aibara, Keiji; Kamochi, Msayuki

    2016-03-01

    Although angiotensin-converting enzyme (ACE) inhibitors are widely used as the first choice drug for treating hypertension, we have only a superficial understanding of their relationship to angioedema. We report a case of life-threatening angioedema. The case was a 60-year-old man who had been taking an ACE inhibitor for hypertension for 11 years. He visited his home doctor for dyspnea, and tongue and neck swelling. He was transported to our hospital because of the possibility of airway obstruction. On admission, his tongue and neck swelling became more severe. We performed an intubation using an endoscope and started airway management. We also stopped his ACE inhibitor. The severe tongue and neck swelling improved gradually and he was extubated on day 3. On the fifth day he was discharged. We diagnosed angioedema caused by an ACE inhibitor. Although the risk of airway obstruction with ACE inhibitors is acknowledged, we have only a superficial understanding of how prolonged ACE inhibitor treatment induces angioedema. So we should consider angioedema in cases of taking ACE inhibitors, especially in cases of prolonged treatment.

  13. Angioedema Related to Angiotensin-Converting Enzyme Inhibitors

    Science.gov (United States)

    Javaud, Nicolas; Achamlal, Jallal; Reuter, Paul-George; Lapostolle, Frédéric; Lekouara, Akim; Youssef, Mustapha; Hamza, Lilia; Karami, Ahmed; Adnet, Frédéric; Fain, Olivier

    2015-01-01

    Abstract The number of cases of acquired angioedema related to angiotensin converting enzyme inhibitors induced (ACEI-AAE) is on the increase, with a potential concomitant increase in life-threatening attacks of laryngeal edema. Our objective was to determine the main characteristics of ACEI-AAE attacks and, in doing so, the factors associated with likelihood of hospital admission from the emergency department (ED) after a visit for an attack. A prospective, multicenter, observational study (April 2012–December 2014) was conducted in EDs of 4 French hospitals in collaboration with emergency services (SAMU 93) and a reference center for bradykinin-mediated angioedema. For each patient presenting with an attack, emergency physicians collected demographic and clinical presentation data, treatments, and clinical course. They recorded time intervals from symptom onset to ED arrival and to treatment decision, from ED arrival to specific treatment with plasma-derived C1-inhibitor (C1-INH) or icatibant, and from specific treatment to onset of symptom relief. Attacks requiring hospital admission were compared with those not requiring admission. Sixty-two eligible patients with ACEI-AAE (56% men, median age 63 years) were included. Symptom relief occurred significantly earlier in patients receiving specific treatment than in untreated patients (0.5 [0.5–1.0] versus 3.9 [2.5–7.0] hours; P < 0.0001). Even though icatibant was injected more promptly than plasma-derived C1-INH, there, however, was no significant difference in median time to onset of symptom relief between the 2 drugs (0.5 [0.5–1.3] versus 0.5 [0.4–1.0] hours for C1-INH and icatibant, respectively, P = 0.49). Of the 62 patients, 27 (44%) were admitted to hospital from the ED. In multivariate analysis, laryngeal involvement and progressive swelling at ED arrival were independently associated with admission (Odds ratio [95% confidence interval] = 6.2 [1.3–28.2] and 5.9 [1.3–26

  14. Genetics 101 --The Hereditary Material of Life

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...

  15. Clinical features of Hereditary Haemorrhagic Telangiectasia

    NARCIS (Netherlands)

    Hosman, A.E.

    2017-01-01

    Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease (ROW), is an autosomal dominant disease with multi-systemic vascular dysplasia characterized by mucocutaneous telangiectasia, arteriovenous malformations and recurrent spontaneous epistaxis (nosebleeds). Most cases

  16. Splenic Involvement in Hereditary Hemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Susumu Takamatsu

    2016-01-01

    Full Text Available A 33-year-old man who presented with prolonged epigastric pain was referred to our hospital. He had experienced recurrent epistaxis and had a family history of hereditary hemorrhagic telangiectasia. Computed tomography and magnetic resonance imaging revealed splenomegaly and a 9 cm hypervascular mass in his spleen. Computed tomography also showed a pulmonary arteriovenous malformation and heterogeneous enhancement of the liver parenchyma, suggesting the presence of arteriosystemic shunts and telangiectases. Based on these findings, the patient was definitely diagnosed with hereditary hemorrhagic telangiectasia according to Curaçao criteria. He underwent splenectomy, and his symptoms disappeared after surgery. Pathological examination of the resected specimen revealed that the hypervascular lesion of the spleen was not a tumor but was composed of abnormal vessels associated with hereditary hemorrhagic telangiectasia. Symptomatic splenic involvement may be a rare manifestation of hereditary hemorrhagic telangiectasia but can be revealed by imaging modalities.

  17. Visceral angioedema: an under-recognized complication of angiotensin-converting enzyme inhibitors.

    Science.gov (United States)

    Mutnuri, Sangeeta; Khan, Adnan; Variyam, Easwaran P

    2015-03-01

    Cough and upper airway angioedema are well-recognized adverse reactions of angiotensin-converting enzyme inhibitor (ACEI) therapy. Visceral angioedema is an infrequent and often unrecognized complication of ACEI therapy. We describe a patient in whom the diagnosis was delayed for > 2 years. A 60-year-old woman with hypertension on treatment with enalapril presented with complaints of abdominal pain and diarrhea for 2 days. Physical examination was significant for diffuse abdominal tenderness and hypotension. Laboratory data were normal except for leukocytosis and elevated creatinine. Computed tomography (CT) of the abdomen showed diffuse small bowel wall thickening. ACEI-induced visceral angioedema was considered, enalapril was discontinued and supportive care was provided. Patient's symptoms and CT appearance improved 48 and 72 hours, respectively, after stopping enalapril. She remained symptom-free 1 year after discharge.

  18. Angiodema due to oral acitretin and isotretinoin Angioedema por acitretina e isotretinoína oral

    Directory of Open Access Journals (Sweden)

    Roberto Rheingantz da Cunha Filho

    2011-08-01

    Full Text Available Angioedema may be caused by nonsteroidal antiinflammatory drugs, angiotensin- converting enzyme inhibitors, radiocontrast media, antibiotics, sea food etc. It can involve an allergic (IgE-mediated or non-allergic hypersensitivity reaction, both with a similar clinical presentation. While angioedema due to isotretionin has been described previously, this is the first description of angiodema due to acitretin. We report two uncommon cases of palpebral and labial angiodema due to retinoids, by acitretin and oral isotretinoin respectively: a 48-year-old man with psoriasis and a 24-year-old woman with severe acne resistant to antibiotics and topical drugs. In both cases the reaction persisted through-out treatment with these drugs, but resolved quickly after discontinuation. Reintroduction of the drugs brought on angioedema againAngioedema pode ser causado por diversos fármacos como : antiinflamatórios não-esteroidais, inibidores da ECA, contrastes, antibióticos e frutos do mar, entre outras causas. Pode ser uma reação alérgica, mediada por IgE, ou não-alérgica, com apresentações clínicas semelhantes. Angioedema por isotretinoína já foi relatado, mas não por acitretina. Relatamos dois casos, uma com angioedema palpebral e um labial, por acitretina e isotretinoína, respectivamente: um paciente de 48 anos com psoríase e uma paciente de 24 anos com acne resistente à terapia convencional. Em ambos casos a afecção persistiu durante o tratamento, resolveu com a interrupção e recidivou com reexposição

  19. Hereditary sensory neuropathy type I

    Directory of Open Access Journals (Sweden)

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  20. Mucosal-dominant pemphigus vulgaris in a captopril-taking woman with angioedema.

    Science.gov (United States)

    Gornowicz-Porowska, Justyna; Dmochowski, Marian; Pietkiewicz, Pawel; Bowszyc-Dmochowska, Monika

    2015-01-01

    We describe a 39-year-old woman with an apparent captopril-induced, contact mucosal-dominant pemphigus vulgaris and angioedema, who took captopril during a bout of arterial hypertension. This exposure suggests that captopril and pathophysiology of angioedema stimulated the development of pemphigus vulgaris, which was diagnosed using the novel, indirect immunofluorescence BIOCHIP mosaic, with the modification to detect serum IgG4 autoantibodies. We discuss the patient, who experienced a chain of events leading to the active stage of pemphigus vulgaris, and review concepts of pemphigus vulgaris inducible by drugs and pathological immunity.

  1. Angioedema hereditario: Guía de tratamiento

    Directory of Open Access Journals (Sweden)

    Alejandro Malbrán

    2012-04-01

    Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.

  2. Life Threatening Idiopathic Recurrent Angioedema Responding to Cannabis

    Directory of Open Access Journals (Sweden)

    Amit Frenkel

    2015-01-01

    Full Text Available We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis. Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative. The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks. Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions. The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years. An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship.

  3. Risk of angioedema associated with levetiracetam compared with phenytoin: Findings of the observational health data sciences and informatics research network.

    Science.gov (United States)

    Duke, Jon D; Ryan, Patrick B; Suchard, Marc A; Hripcsak, George; Jin, Peng; Reich, Christian; Schwalm, Marie-Sophie; Khoma, Yuriy; Wu, Yonghui; Xu, Hua; Shah, Nigam H; Banda, Juan M; Schuemie, Martijn J

    2017-08-01

    Recent adverse event reports have raised the question of increased angioedema risk associated with exposure to levetiracetam. To help address this question, the Observational Health Data Sciences and Informatics research network conducted a retrospective observational new-user cohort study of seizure patients exposed to levetiracetam (n = 276,665) across 10 databases. With phenytoin users (n = 74,682) as a comparator group, propensity score-matching was conducted and hazard ratios computed for angioedema events by per-protocol and intent-to-treat analyses. Angioedema events were rare in both the levetiracetam and phenytoin groups (54 vs. 71 in per-protocol and 248 vs. 435 in intent-to-treat). No significant increase in angioedema risk with levetiracetam was seen in any individual database (hazard ratios ranging from 0.43 to 1.31). Meta-analysis showed a summary hazard ratio of 0.72 (95% confidence interval [CI] 0.39-1.31) and 0.64 (95% CI 0.52-0.79) for the per-protocol and intent-to-treat analyses, respectively. The results suggest that levetiracetam has the same or lower risk for angioedema than phenytoin, which does not currently carry a labeled warning for angioedema. Further studies are warranted to evaluate angioedema risk across all antiepileptic drugs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  4. Movement disorders in hereditary ataxias.

    Science.gov (United States)

    Garcia Ruiz, Pedro J; Mayo, David; Hernandez, Jaime; Cantarero, Susana; Ayuso, Carmen

    2002-10-15

    Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA. Copyright 2002 Elsevier Science B.V.

  5. Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature.

    Science.gov (United States)

    Takács, Rozália; Makkos, Zoltán; Kassai-Farkas, Ákos; Pusztai, Ágnes; Ungvári, Gábor S; Gazdag, Gábor

    2014-03-01

    We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings.

  6. [Analysis of 76 patients with urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Japan].

    Science.gov (United States)

    Moriya, Maki; Aihara, Michiko; Hirota, Rie; Hirata, Yuko; Ikinaga, Naoko; Takamura, Naoko; Kunimi, Yuko; Uchida, Takahisa; Ikezawa, Zenro

    2011-06-01

    The pathogenesis of urticaria and angioedema induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still obscure. We analyzed the clinical characteristics of patients with NSAIDs-induced urticaria and angioedema without asthma in Japan. We retrospectively collected the cases of NSAIDs-induced urticaria and angioedema from Japanese medical journals in 2000-2009. Seventy-six patients were analyzed. The male/female ratio was 1:2.5 and the mean age was 38.1 years. Urticaria was most frequent clinical manifestation in 3 groups; urticaria alone, urticaria and angioedema, and angioedema alone. Time interval from drug administration to onset was 5 minutes to 48 hours by aspirin at a dose of 25-1000 mg. Skin prick test was performed with aspirin in 33 patients, and the results were negative in all patients. Meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, and celecoxib, a new selective COX-2 inhibitor, were administered safely in 4 of 6 patients and in 2 of 3 patients with NSAIDs-induced urticaria, respectively. These drugs were administered safely in all administered patients with NSAIDs-induced angioedema. Tiaramidehydrochroride (a basic COX-1 inhibitor) was safely used in 23 administered patients with NSAIDs-induced angioedema. Leukotriene receptor antagonists were effective in 2 of 5 patients administered, but aggravated symptoms in the others. Diversity of NSAIDs-induced urticaria and angioedema was shown in this study. Pathogenesis of NSAIDs-induced urticaria and angioedema without asthma seems to be different from that of NSAIDs-induced asthma.

  7. Abordagem anestésica de doente com angioedema hereditário proposto para cirurgia electiva

    OpenAIRE

    Conceição, Luís; Martinho, Hélder; Azenha, Marta

    2014-01-01

    O angioedema hereditário é uma entidade rara, com transmissão autossómica dominante, causada por deficiência no inibidor de C1. Esta condiciona uma ativação descontrolada da via clássica do complemento e da cascata das cininas, sendo responsável por episódios de angioedema com possível comprometimento da via aérea. Os autores descrevem um caso clínico de um doente com 36 anos com angioedema hereditário tipo I proposto para colecistectomia electiva sob anestesia geral, tendo sido tomadas algum...

  8. Disease: H01006 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01006 Hereditary angioedema Hereditary angioedema (HAE) is a rare genetic disorde...r, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tr...act or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result...6100 PMID:14572810 (description, gene) ... AUTHORS ... Davis AE 3rd ... TITLE ... The pathogenesis of hereditary angioedema... (drug) ... AUTHORS ... Antoniu SA ... TITLE ... Therapeutic approaches in hereditary angioedema. ... JOURNAL ... Clin

  9. Postanesthetic Severe Oral Angioedema in Patient’s Taking Angiotensin-Converting Enzyme Inhibitor

    Directory of Open Access Journals (Sweden)

    Acílio Marques

    2014-01-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors are the leading cause of a drug-induced angioedema. This occurrence is frequently underdiagnosed, but its relapse can be life-threatening. The authors’ intention in reporting this clinical case is to sound a warning about reviewing attitudes and surveillance to try to improve patient perioperative safety.

  10. The effectiveness of a history-based diagnostic approach in chronic urticaria and angioedema

    NARCIS (Netherlands)

    Kozel, M. M.; Mekkes, J. R.; Bossuyt, P. M.; Bos, J. D.

    1998-01-01

    OBJECTIVE: To assess the value of extensive laboratory screening for the identification of causes in patients with chronic urticaria and/or angioedema. DESIGN: In a prospective study involving 220 patients, 2 diagnostic strategies were compared: the combination of detailed history taking and limited

  11. [Quality control of DNA testing in hereditary diseases

    NARCIS (Netherlands)

    Ouweland, A.M.W. van den; Scheffer, H.

    2001-01-01

    The laboratories performing diagnostic studies regarding hereditary diseases and the specialists providing hereditary counselling are housed in clinical genetic centres. The laboratories are subject to the Special Medical Performances Act and have had licenses from the Ministry. The DNA diagnostic

  12. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer.......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... (HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers...

  13. High liver glycogen in hereditary fructose intolerance

    Science.gov (United States)

    Cain, A. R. R.; Ryman, Brenda E.

    1971-01-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance. PMID:5289293

  14. Case-control study evaluating competing risk factors for angioedema in a high-risk population.

    Science.gov (United States)

    Kamil, Rebecca J; Jerschow, Elina; Loftus, Patricia A; Tan, Melin; Fried, Marvin P; Smith, Richard V; Foster, David; Ow, Thomas J

    2016-08-01

    Black race is a risk factor for angioedema. The primary aim was to examine the relationship between race-ethnicity and risk factors for angioedema. Using a retrospective case-control study design, data was extracted with the Clinical Looking Glass utility, a data collection and management tool that captures data from electronic medical record systems within the Montefiore Healthcare System. Cases were emergency department (ED) visits with primary or secondary International Classification of Diseases, Ninth Revision, code diagnoses of angioedema in adults aged ≥ 18 years from January 2008 to December 2013 at three Montefiore centers in Bronx, New York. Controls were a random sampling of adult ED visits during the same period. In primary analyses, angiotensin-converting enzyme inhibitor (ACE-I) and black race were evaluated for synergy. The influence of different risk factors in the development of angioedema was evaluated using logistic regression models. Finally, race-ethnicity was further explored by evaluating for effect modification by stratification of models by race-ethnicity categories. There were 1,247 cases and 6,500 controls randomly selected from a larger control pool. ACE-I use (odds ratio [OR] 3.70, 95% confidence interval [CI] 2.98, 4.60), hypertension (OR 1.88, 95% CI 1.55, 2.29), and black race (OR 2.25, 95% CI 1.86, 2.72) were the strongest risk factors. ACE-I use and black race were not synergistic (OR 1.10, 95% CI 0.80, 1.51). Race-ethnicity was an effect modifier for certain risk factors. Race-ethnicity acts as an effect modifier for particular angioedema risk factors. The two strongest risk factors, ACE-I use and black race, were not synergistic. 3b. Laryngoscope, 126:1823-1830, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Effect of C1-Esterase-inhibitor in angiotensin-converting enzyme inhibitor-induced angioedema.

    Science.gov (United States)

    Greve, Jens; Bas, Murat; Hoffmann, Thomas K; Schuler, Patrick J; Weller, Patrick; Kojda, Georg; Strassen, Ulrich

    2015-06-01

    The study objective was to generate pilot data to evaluate the effectiveness and safety of C1-esterase-inhibitor concentrate (C1-INH) compared to standard treatment in patients with angiotensin-converting enzyme inhibitor (ACEi)-induced angioedema affecting the upper aerodigestive tract. Proof-of-concept case series with historical control. Adult patients with angioedema in the upper aerodigestive tract presenting to the emergency department were included. After establishing the diagnosis of ACEi-induced angioedema based on patient history and thorough clinical examination, all patients were administered 1,000 international units (IU) of C1-INH intravenously. A historical control group consisting of adult patients with ACEi-induced angioedema who had been treated with intravenous corticosteroids and antihistamines at the same institution over the past 8 years was used for comparison. The most important parameters assessed were the time to complete resolution of symptoms and the need for intubation or tracheotomy. Ten patients were included in the C1-INH group and 47 in the corticosteroid/antihistamine group. The time to complete resolution of symptoms was considerably longer in the historical control group (33.1 ± 19.4 hours) than in the C1-INH group (10.1 ± 3.0 hours). No intubation or tracheotomy was needed in the C1-INH group (0/10 patients), whereas three out of the 47 historical controls required tracheotomy and two were intubated (5/47). The results suggest a role for C1-INH as an effective and safe therapeutic option in patients with ACEi-induced angioedema, which needs to be confirmed by further larger and double-blinded studies. 4. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Extramedullary paraspinal hematopoiesis in hereditary spherocytosis

    Directory of Open Access Journals (Sweden)

    Gogia P

    2008-01-01

    Full Text Available Hereditary spherocytosis (HS is a common inherited hemolytic anemia due to red cell membrane defects. Extramedullary hematopoiesis is a compensatory response to insufficient bone marrow blood cell production. The preferred sites of extramedullary hematopoietic involvement are the spleen, liver and lymph nodes; but in HS, the posterior paravertebral mediastinum is also commonly involved. We report a case of a 50-year-old male who presented to us in respiratory distress and with bilateral paravertebral posterior mediastinal masses, which on trucut biopsy were found to be extra-hematopoietic masses; and the patient was found to have hereditary spherocytosis.

  17. Albright hereditary osteodystrophy: A rare case report

    Directory of Open Access Journals (Sweden)

    Goswami M

    2009-09-01

    Full Text Available Albright hereditary osteodystrophy (AHO is a rare hereditary metabolic disorder that may be associated with or without resistant to parathyroid hormone (pseudohypoparathyroidism. It is commonly characterized by a constellation of physical features of short stature, round face, short neck, and small metacarpals and metatarsals, mild mental retardation, osteoporosis, subcutaneous calcification, and sometimes olfactory and hearing functional defect. Hypocalcaemia and hyperphosphatemia are the most important manifestations of the case. We report a clinical case of siblings with AHO with reduced Gs-alpha activity and we discuss their clinical features with oral manifestations, radiographic findings, laboratory tests along with treatment.

  18. Therapeutic Strategies for Hereditary Kidney Cancer.

    Science.gov (United States)

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

  19. Consensus statement on the diagnosis, management, and treatment of angioedema mediated by Bradykinin. Part. II: treatment, follow-up, and special situations

    OpenAIRE

    Caballero, T.; Baeza, M. L.; Cabañas, R.; Campos, A.; Cimbollek, S.; Gómez-Traseira, C.; González-Quevedo, T.; Guilarte, M.; Jurado-Palomo, J.; Larco, J. I.; López-Serrano, M. C.; López-Trascasa, M.; Marcos, C.; Muñoz- Caro, J. M.; Pedrosa, M.

    2011-01-01

    Background: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. Aim: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientifi c evidence and the experience of experts. This statement will serve as a guideline to health professionals. Methods: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish...

  20. Comparison of Clinical Factors Between Patients With Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema and Cough.

    Science.gov (United States)

    Hallberg, Pär; Nagy, Julia; Karawajczyk, Malgorzata; Nordang, Leif; Islander, Gunilla; Norling, Pia; Johansson, Hans-Erik; Kämpe, Mary; Hugosson, Svante; Yue, Qun-Ying; Wadelius, Mia

    2017-04-01

    Angioedema is a rare and serious adverse drug reaction (ADR) to angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common side effect of ACE inhibitors and has been identified as a possible risk factor for angioedema. We compared characteristics between patients with ACE inhibitor-induced angioedema and cough with the aim of identifying risk factors that differ between these adverse events. Data on patients with angioedema or cough induced by ACE inhibitors were collected from the Swedish database of spontaneously reported ADRs or from collaborating clinicians. Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs were used to test for between-group differences. The significance threshold was set to P angioedema and 121 with cough only. Smoking and concomitant selective calcium channel blocker treatment were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI = 2.1-8.9, P = 2.2 × 10 -5 , and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 × 10 -5 . Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4-3.6, P = 1.3 × 10 -4 ) and had longer time to onset and higher doses than those with cough ( P = 3.2 × 10 -10 and P = 2.6 × 10 -4 ). A multiple model containing the variables smoking, concurrent calcium channel blocker treatment, male sex, and time to onset accounted for 26% of the variance between the groups. Smoking, comedication with selective calcium channel blockers, male sex, and longer treatment time were associated with ACE inhibitor-induced angioedema rather than cough.

  1. Autosomal dominant hereditary ataxia in Sri Lanka

    OpenAIRE

    Sumathipala, Dulika S; Abeysekera, Gayan S; Jayasekara, Rohan W; Tallaksen, Chantal ME; Dissanayake, Vajira HW

    2013-01-01

    Background Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. Methods ...

  2. Major and minor form of hereditary hyperekplexia

    NARCIS (Netherlands)

    Tijssen, MAJ; Vergouwe, MN; van Dijk, JG; Rees, M; Frants, RR; Brown, P

    Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied

  3. Revisited diagnostics of hereditary epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    V. I. Albanova

    2014-01-01

    Full Text Available Hereditary epidermolysis bullosa is a big group of hereditary diseases with the main manifestations in the form of blisters on the skin and mucous coat after slight mechanical injuries. It is not always possible to diagnose this disease based on the clinical picture. The article discusses current laboratory diagnostics methods for hereditary epidermolysis bullosa including immunofluorescence antigen mapping (IFM, transmission electron microscopy (TEM and genetic analysis (molecular or DNA diagnostics as well as their advantages and disadvantages. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment. Substantial experience is also needed to analyze the resulting submicroscopic images. IFM determines whether expression of the affected protein related to the disease development is reduced or absent; however, invalid (false positive or false negative results can be obtained in patients with the reduced expression of the affected protein. Genetic analysis plays a key role for prenatal diagnostics. Therefore, to make an exact diagnosis of hereditary epidermolysis bullosa, it is expedient to apply IFM, TEM and genetic analysis. The need to set an exact diagnosis of the disease is related to the fact that the promising treatment methods being currently developed are aimed at treating patients with certain forms of the disease.

  4. Hereditary spherocytosis. | Hassan | Annals of African Medicine

    African Journals Online (AJOL)

    Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. Although a positive family history of spherocytosis increases the risk for this disorder, it may be sporadic in some cases. In severe cases the ...

  5. Presumed hereditary retinal degenerations: Ibadan experience ...

    African Journals Online (AJOL)

    Background: Retinitis pigmentosa (RP) is a hereditary retinal degenerative condition with no known treatment. Associated ocular conditions, such as cataract and glaucoma, when present further worsen vision, but these conditions are often treatable. There are, however, no known reports of cataract or glaucoma surgery in ...

  6. Genetics Home Reference: hereditary cerebral amyloid angiopathy

    Science.gov (United States)

    ... the genes associated with hereditary cerebral amyloid angiopathy APP CST3 ITM2B Related Information What is a gene? What is a gene mutation ... a disorder seems to run in my family? What are the different ways in which a genetic condition can be inherited? More about ... APP-related Genetic Testing Registry: Dementia familial British Genetic ...

  7. Gynecologic screening in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, FEM; Mourits, MJE; Kleibeuker, JH; Hollema, H; van der Zee, AGJ

    2003-01-01

    Objective. In hereditary nonpolyposis colorectal cancer (HNPCC), women with a mismatch repair (MMR) gene mutation have a cumulative lifetime risk of 25-50% for endometrial cancer and 8-12% for ovarian cancer. Therefore, female members of HNPCC families are offered an annual gynecologic and

  8. Hereditary spectrin deficiency in Golden Retriever dogs

    NARCIS (Netherlands)

    Slappendel, Robbert J.; van Zwieten, Rob; van Leeuwen, Martin; Schneijdenberg, Chris T. W. M.

    2005-01-01

    Spectrin deficiency with increased erythrocyte osmotic fragility (OF) is a hallmark of hereditary spherocytosis, which is the most common congenital hemolytic anemia in humans of northern European ancestry. A radioimmunoassay revealed that erythrocyte spectrin concentration was 50-65% of normal in 5

  9. Hereditary hemorrhagic telangiectasia clinical and molecular genetics

    NARCIS (Netherlands)

    Letteboer, T.G.W.

    2010-01-01

    Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber (ROW) syndrome is an autosomal dominant disease characterized by vascular malformations in multiple organ systems. HHT has an age-related penetrance and variable clinical expression. The clinical symptoms are caused by direct

  10. Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder.

    Science.gov (United States)

    Khoury, Paneez; Herold, Jacqueline; Alpaugh, Alexandra; Dinerman, Ellen; Holland-Thomas, Nicole; Stoddard, Jennifer; Gurprasad, Shakuntala; Maric, Irina; Simakova, Olga; Schwartz, Lawrence B; Fong, Juelia; Lee, Chyi-Chia Richard; Xi, Liqiang; Wang, Zengfeng; Raffeld, Mark; Klion, Amy D

    2015-03-01

    Episodic angioedema with eosinophilia (Gleich syndrome) is a rare disorder characterized by episodes of angioedema and eosinophilia that occur at monthly intervals and resolve spontaneously without therapy. Despite the striking periodicity of this disorder, its similarity to other cyclic hematopoietic disorders with multilineage involvement has not been assessed. To characterize the involvement of cell lineages in the etiology and pathogenesis of episodic angioedema with eosinophilia, four subjects were evaluated by blood counts and other analyses over the course of 1-2 months. Surface marker expression was assessed on T cells by flow cytometry and clonality by polymerase chain reaction. Intracellular cytokine evaluation, bone marrow and skin biopsies were performed during different parts of the cycle. Cycling of multiple cell lineages, including neutrophils, lymphocytes and eosinophils, was observed in the four subjects with the disorder with a periodicity of 25-35 days. An aberrant CD3(-)CD4(+) T-cell population was detected in all four subjects, and T-cell receptor rearrangement studies showed a clonal pattern in three subjects. A peak of type II cytokines was detected in the serum of subjects prior to the onset of symptoms and eosinophil cycling and corresponded to ex-vivo type II cytokines detected intracellularly in CD3(+)CD4(+)CD154(+) T cells. Although the etiology of episodic angioedema with eosinophilia is not yet known, multiple lineages, including lymphocytes, neutrophils and mast cells, are involved and may be related to disease pathogenesis. Whether these cells act directly or promote eosinophilia and eosinophil activation remains to be elucidated. All subjects gave informed consent and were evaluated under an Institutional Review Board-approved protocol (NCT00001406). Copyright© Ferrata Storti Foundation.

  11. Idiopathic histaminergic angioedema without wheals: a case series of 31 patients

    Science.gov (United States)

    Boccon‐Gibod, I.; Mansard, C.; Dumestre Perard, C.; Pralong, P.; Chatain, C.; Deroux, A.; Bouillet, L.

    2016-01-01

    Summary Idiopathic histaminergic acquired angioedema (IH‐AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell‐mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH‐AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH‐AAE). Thirty‐one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH‐AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti‐histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three–fourfold in 16·1% (five patients). IH‐AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1‐anti‐histamines may be necessary to control symptoms. PMID:26969870

  12. Idiopathic histaminergic angioedema without wheals: a case series of 31 patients.

    Science.gov (United States)

    Faisant, C; Boccon-Gibod, I; Mansard, C; Dumestre Perard, C; Pralong, P; Chatain, C; Deroux, A; Bouillet, L

    2016-07-01

    Idiopathic histaminergic acquired angioedema (IH-AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell-mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH-AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH-AAE). Thirty-one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH-AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti-histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three-fourfold in 16·1% (five patients). IH-AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1-anti-histamines may be necessary to control symptoms. © 2016 British Society for Immunology.

  13. Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management.

    Science.gov (United States)

    Chan, Norman J; Soliman, Ahmed M S

    2015-02-01

    This study aimed to determine the duration of use, presentation, and management of angiotensin converting enzyme (ACE) inhibitor-related angioedema patients at an urban academic medical center. Retrospective chart review. Eighty-eight patients who presented with ACE inhibitor-related angioedema between January 1, 2012, and December 31, 2012, were identified. They presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About half the patients (50.7%) presented after taking an ACE inhibitor for at least 1 year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six patients were intubated after more than 1 flexible laryngoscopy. The percentage of patients with involvement of the face, lips, tongue, floor of mouth, soft palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%, respectively. Sixty-eight percent of patients with laryngeal edema were intubated. The majority of patients were treated with a corticosteroid and H1 and H2 receptor antagonists. Angioedema can occur at any time after starting ACE inhibitor use, with nearly half occurring after 1 year of use. Laryngeal involvement occurred in a minority of patients, but most of these patients were felt to require airway protection. © The Author(s) 2014.

  14. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria......, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...

  15. Hypogonadotropic hypogonadism in men with hereditary hemochromatosis.

    Science.gov (United States)

    El Osta, Rabih; Grandpre, Nicolas; Monnin, Nicolas; Hubert, Jacques; Koscinski, Isabelle

    2017-01-01

    Hereditary hemochromatosis is a genetic disease that progresses silently. This disease is often diagnosed late when complications appear. Hypogonadotropic hypogonadism (HH) is one of the classical complications of hemochromatosis. Its frequency is declining probably because of earlier diagnosis and better informed physicians. Certain symptoms linked to HH can have an impact on a patient's sexuality, such as decreased libido, erectile dysfunction, and impairment of ejaculation, as well as on his reproductive capacities. This review is based on an online search in English, French and German language publications found in PubMed/Medline, up to 23 September 2016 using the following key word: Male infertility, Hypogonadotropic Hypogonadism, Hereditary Hemochromatosis. Thirty-four papers met these inclusion criteria. This review describes the impact of iron overload on male fertility, resulting in hypogonadotropic hypogonadism and proposes treatment modalities.

  16. Hereditary spastic paraplegia with cerebellar ataxia

    DEFF Research Database (Denmark)

    Nielsen, J E; Johnsen, B; Koefoed, P

    2004-01-01

    Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria...... in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance...... relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations....

  17. [Hereditary ataxia and sensory-motor neuropathy].

    Science.gov (United States)

    Miladinović, Ksenija; Hodzić, Samiha; Zjuzin, Nadezda; Lokmic, Eldan

    2003-01-01

    The authors presented this case because of the determined characteristics in the clinical picture and electrophysiologic finding which refer to spinocerebral degeneration and neuropathia of the hereditary type, and give the possibility of the classification into two nosologic entities. One is Roussey Levy's syndrome, what is the advisable diagnosis of our patient, and another Freidreich's ataxia. Regardless to the impossibility of the establishing of diagnosis by means the specific enzimatic and genetic tests, the authors on the basis of the clinical picture, electromioncurographic findings and data from the literature of the diagnostic ally decided for Freidreich's ataxya. The neuropathy have classified into the hereditary motor sensor neuropathy--HMSN type II and presented its characteristics.

  18. Mania associated with complicated hereditary spastic paraparesis

    OpenAIRE

    Raghavendra B Nayak; Govind S Bhogale; Nanasaheb M Patil; Aditya A Pandurangi

    2011-01-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints ...

  19. Multimodality imaging features of hereditary multiple exostoses

    OpenAIRE

    Kok, H K; Fitzgerald, L; Campbell, N; Lyburn, I D; Munk, P L; Buckley, O; Torreggiani, W C

    2013-01-01

    Hereditary multiple exostoses (HME) or diaphyseal aclasis is an inherited disorder characterised by the formation of multiple osteochondromas, which are cartilage-capped osseous outgrowths, and the development of associated osseous deformities. Individuals with HME may be asymptomatic or develop clinical symptoms, which prompt imaging studies. Different modalities ranging from plain radiographs to cross-sectional and nuclear medicine imaging studies can be helpful in the diagnosis and detecti...

  20. An Unusual Case of Recurrent Hypersensitivity Reaction Associated with Kounis-Like Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Shanker Kundumadam

    2017-01-01

    Full Text Available There have been multiple reports of allergic reactions associated with acute coronary syndromes. This has been classically described as Kounis syndrome. We present an unusual case of 70-year-old male with multiple prior hypersensitivity reactions and history of coronary artery bypass grafting who presented recurrent episode of severe angioedema and anaphylaxis. He responded to epinephrine but subsequently developed a non-ST elevation myocardial infarction with worsening heart failure. Our case is unique in that, unlike classic Kounis syndrome, the acute coronary event in this case did not present concurrently with the allergic reaction; rather it took nearly 48 hours to present. Subsequent angiogram revealed patent grafts and significant decline in the left ventricular systolic function as compared to his own ECHO a year ago. We postulate that slow mediators of inflammation may play a role in delayed development of acute coronary events with associated LV dysfunction following episodes of angioedema and anaphylaxis.

  1. The role of serial physical examinations in the management of angioedema involving the head and neck: A prospective observational study

    Directory of Open Access Journals (Sweden)

    Gary Linkov

    2016-03-01

    Full Text Available Objective: To elucidate the progression of angioedema of the head and neck with routine management and to assess the utility of serial physical exams and fiberoptic laryngoscopy in its management. Methods: This study was a prospective observational research. From 2013 to 2014, a prospective observational study was conducted at a tertiary referral center. Forty patient were approached, 7 refused, 33 (18–90 years old were enrolled. Patients presented with angioedema involving the head and neck over a 12 month period were asked to participate in the study. Physical examination and fiberoptic laryngoscopy were performed at presentation and then repeated at least 1 h later. Results: Thirty-three patients with head and neck angioedema from any cause were enrolled (mean age 58, range 23–89 years. The upper lip was the most commonly involved site (58%. On reevaluation, 82% of patients reported subjective improvement in symptoms. The association between subjective improvement and the physical exam, including fiberoptic laryngoscopy findings, was statistically significant (P < 0.001. Conclusion: In stable patients with angioedema of any head and neck subsite, self-reported symptoms are associated with clinical stability or improvement as assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be an appropriate surrogate to monitor clinical status without the need for routine serial physical examinations or fiberoptic laryngoscopy, though further study is needed. Keywords: Angioedema, Physical examination, Fiberoptic laryngoscopy

  2. Automated detection of hereditary syndromes using data mining.

    Science.gov (United States)

    Evans, S; Lemon, S J; Deters, C A; Fusaro, R M; Lynch, H T

    1997-10-01

    Computer-based data mining methodology applied to family history clinical data can algorithmically create highly accurate, clinically oriented hereditary disease pattern recognizers. For the example of hereditary colon cancer, the data mining's selection of relevant factors to assess for hereditary colon cancer was statistically significant (P recognizer-formulated patterns of hereditary colon cancer were independently confirmed by a clinical expert. Applied to previously analyzed family histories, the recognizer identified the definitive hereditary histories, correctly responded negatively to the putative hereditary histories, and correctly responded negatively to empirically elevated colon cancer risk situations. This capability facilitates patient selection for DNA studies in search of gene mutations. When genetic mutations are included as parameters in a patient database for a genetic disease, the process yields an expert system which characterizes variations in clinical disease presentations in terms of genetic mutations. Such information can greatly improve the efficiency of gene testing.

  3. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... as a control group. Unsupervised cluster analysis identified two distinct subgroups related to genetic complexity. Sporadic and HBOC associated tumors had complex genetic profiles with an average 41% of the genome altered, whereas the mismatch repair defective tumors had stable genetic profiles...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....

  4. Emergency Department Airway Management of Severe Angioedema: A Video Review of 45 Intubations.

    Science.gov (United States)

    Driver, Brian E; McGill, John W

    2017-05-01

    Angioedema is an uncommon but important cause of airway obstruction. Emergency airway management of angioedema is difficult. We seek to describe the course and outcomes of emergency airway management for severe angioedema in our institution. We performed a retrospective, observational study of all intubations for angioedema performed in an urban academic emergency department (ED) between November 2007 and June 2015. We performed a structured review of video recordings of each intubation. We identified the methods of airway management, the success of each method, and the outcomes and complications of the effort. We identified 52 patients with angioedema who were intubated in the ED; 7 were excluded because of missing videos, leaving 45 patients in the analysis. Median time from arrival to the ED to the first intubation attempt was 33 minutes (interquartile range 17 to 79 minutes). Nasotracheal intubation was the most common first method (33/45; 73%), followed by video laryngoscopy (7/45; 16%). Two patients required attempts at more invasive airway procedures (retrograde intubation and cricothyrotomy). The intubating laryngeal mask airway was used as a rescue method 5 times after failure of multiple methods, with successful oxygenation, ventilation, and intubation through the laryngeal mask airway in all 5 patients. All patients were successfully intubated. In this series of ED patients who were intubated because of angioedema, emergency physicians used a range of methods to successfully manage the airway. These observations provide key lessons for the emergency airway management of these critical patients. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  5. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  6. Hereditary History Preserving Bisimilarity Is Undecidable

    DEFF Research Database (Denmark)

    Jurdzinski, Marcin; Nielsen, Mogens

    2000-01-01

    History preserving bisimilarity (hp-bisimilarity) and hereditary history preserving bisimilarity (hhp-bisimilarity) are behavioural equivalences taking into account causal relationships between events of concurrent systems. Their prominent feature is being preserved under action refinement......, an operation important for the top-down design of concurrent systems. We show that-unlike hp-bisimilarity-checking hhp-bisimilarity for finite labelled asynchronous transition systems is not decidable, by a reduction from the halting problem of 2-counter machines. To make the proof more transparent we...

  7. MRI in Leber's hereditary optic neuropathy

    DEFF Research Database (Denmark)

    Matthews, Lucy; Enzinger, Christian; Fazekas, Franz

    2015-01-01

    BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological...... mechanism involving mitochondrial dysfunction. OBJECTIVE: The primary aim was to define MRI features of LMS and LHON, and to assess the proportions of individuals displaying features typical of MS. Secondarily, we investigated the effect of gender on the risk of developing white matter lesions...

  8. Brain abscesses and hereditary hemorrhagic telangiectasia

    International Nuclear Information System (INIS)

    Vives, Daniel A.; Bauni, Carlos E.; Mendoza, Monica E.

    2003-01-01

    Rendu-Osler-Weber disease or Hereditary Hemorrhagic Telangiectasia (HHT) is a generalized familial angiodysplastic disorder. The neurological manifestations of this entity are due to Central Nervous System vascular lesions or to complications of other visceral lesions such as pulmonary arteriovenous fistulae. This report describes two patients (males, 40 and 61 years old), with brain abscesses associated with HHT. The CT, MRI and Angiographic findings as well as the therapeutic approach are analyzed. Patients with brain abscess of unknown origin must be evaluated for the presence of lung vascular malformation in association with HHT. (author)

  9. Hypogonadotropic Hypogonadism Associated with Hereditary Hemorrhagic Telengiectasia

    Science.gov (United States)

    Valentina, Scarano; Daniele, De Santis; Patrizia, Suppressa; Patrizia, Lastella; Mariano, Lenato Gennaro; Vincenzo, Triggiani; Carlo, Sabbà

    2013-01-01

    A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis. PMID:23710379

  10. Skin deposits in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Gudmundsson, G

    1990-01-01

    Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic...... individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17-46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker...

  11. Hereditary thrombophilia and recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Lund, M; Nielsen, H S; Hviid, T V

    2010-01-01

    BACKGROUND: The association among hereditary thrombophilia, recurrent pregnancy loss (RPL) and obstetric complications is yet uncertain. The objective of the study was to assess the prognostic value of the factor V Leiden (FVL) and prothrombin (PT) mutations for the subsequent chance of live birth...... for women with RPL. METHODS: Pregnancy outcome was recorded in a retrospective cohort of 363 women with a minimum of three consecutive pregnancy losses (early miscarriage, late miscarriage or stillbirth/neonatal death) who were not treated with anticoagulation therapy. RESULTS: Of the 363 women, 29 were FVL...

  12. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations

    NARCIS (Netherlands)

    Sijmons, Rolf H.; Hofstra, Robert M. W.

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive

  13. Knowledge regarding basic concepts of hereditary cancers, and the ...

    African Journals Online (AJOL)

    Background. In families with hereditary cancer, at-risk individuals can benefit from genetic counselling and testing. General practitioners (GPs) are ideally placed to identify such families and refer them appropriately. Objective. To assess the practices, knowledge and attitudes of GPs regarding common hereditary cancers.

  14. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    NARCIS (Netherlands)

    C.R.M. Lammens (Chantal); E.M.A. Bleiker (Eveline); N.K. Aaronson (Neil); A.H.J.T. Vriends (Anette); M. Jansweijer (Maaike); M.G.E.M. Ausems (Margreet); A. Wagner (Anja); R.H. Sijmons (Rolf); A.M.W. van den Ouweland (Ans); R.B. van der Luijt (Rob); L. Spruijt (Liesbeth); S. Verhoef (Senno); E.B. Gómez García (Encarna); M.W.G. Ruijs (Marielle)

    2009-01-01

    textabstractThe use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer

  15. Fruit-induced FPIES masquerading as hereditary fructose intolerance.

    Science.gov (United States)

    Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia

    2014-08-01

    Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI. Copyright © 2014 by the American Academy of Pediatrics.

  16. Impairment of autophagy: From hereditary disorder to drug intoxication

    International Nuclear Information System (INIS)

    Aki, Toshihiko; Funakoshi, Takeshi; Unuma, Kana; Uemura, Koichi

    2013-01-01

    At first, the molecular mechanism of autophagy was unveiled in a unicellular organism Saccharomyces cerevisiae (budding yeast), followed by the discovery that the basic mechanism of autophagy is conserved in multicellular organisms including mammals. Although autophagy was considered to be a non-selective bulk protein degradation system to recycle amino acids during periods of nutrient starvation, it is also believed to be an essential mechanism for the selective elimination of proteins/organelles that are damaged under pathological conditions. Research advances made using autophagy-deficient animals have revealed that impairments of autophagy often underlie the pathogenesis of hereditary disorders such as Danon, Parkinson's, Alzheimer's, and Huntington's diseases, and amyotrophic lateral sclerosis. On the other hand, there are many reports that drugs and toxicants, including arsenic, cadmium, paraquat, methamphetamine, and ethanol, induce autophagy during the development of their toxicity on many organs including heart, brain, lung, kidney, and liver. Although the question as to whether autophagic machinery is involved in the execution of cell death or not remains controversial, the current view of the role of autophagy during cell/tissue injury is that it is an important, often essential, cytoprotective reaction; disturbances in cytoprotective autophagy aggravate cell/tissue injuries. The purpose of this review is to provide (1) a gross summarization of autophagy processes, which are becoming more important in the field of toxicology, and (2) examples of important studies reporting the involvement of perturbations in autophagy in cell/tissue injuries caused by acute as well as chronic intoxication

  17. Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial.

    Science.gov (United States)

    Staubach, P; Metz, M; Chapman-Rothe, N; Sieder, C; Bräutigam, M; Canvin, J; Maurer, M

    2016-08-01

    Chronic spontaneous urticaria (CSU) severely impacts quality of life (QoL), especially in patients with wheals and angioedema. Omalizumab is approved as add-on therapy for CSU patients; however, its effect on patients who are double-positive for wheals and angioedema has not been systematically studied. The primary objective was to evaluate the efficacy of omalizumab vs placebo at week 28 using the Chronic Urticaria Quality of Life (CU-Q2oL) questionnaire. Number of angioedema-burdened days, time interval between successive angioedema episodes, disease activity, angioedema-specific and overall QoL impairment were secondary objectives. X-ACT was a phase III, randomized, double-blind study conducted in 24 centres (Germany), which selectively included CSU patients with angioedema and wheals. Patients were randomized (1 : 1) to omalizumab 300 mg or placebo (every 4 weeks up to week 24) (ClinicalTrials.gov number: NCT01723072). Of the 91 patients randomized to omalizumab (n = 44) or placebo (n = 47) at baseline, 68 completed the 28-week treatment phase (omalizumab, 35; placebo, 33). Omalizumab was superior to placebo in improving CU-Q2oL scores at week 28 (P omalizumab (0.3) vs placebo (1.1). The median time to first recurrence of angioedema was 57-63 days with omalizumab and Omalizumab significantly improved angioedema-specific QoL (P omalizumab. Omalizumab was an effective treatment option for patients with moderate-to-severe CSU symptoms and angioedema unresponsive to high doses of antihistamine treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Before and after, the impact of available on-demand treatment for HAE

    DEFF Research Database (Denmark)

    Christiansen, Sandra C; Bygum, Anette; Banerji, Aleena

    2015-01-01

    Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had on their ......Availability of effective treatment for acute attacks is expected to transform the care of hereditary angioedema (HAE) patients. We felt that it would be of interest to test these assumptions by examining the perceptions of HAE patients regarding the impact that these therapies have had...

  19. Transient angioedema of small bowel secondary to intravenous iodinated contrast medium

    Directory of Open Access Journals (Sweden)

    Kirankumar N Kulkarni

    2014-01-01

    Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.

  20. Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report.

    Science.gov (United States)

    Tukenmez Demirci, Gulsen; Kivanc Altunay, Ilknur; Atis, Guldehan; Kucukunal, Asli

    2012-09-01

    Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.

  1. Idiopathic Non-histaminergic Angioedema: Successful Treatment with Omalizumab in Five Patients.

    Science.gov (United States)

    Faisant, Charles; Du Thanh, Aurélie; Mansard, Catherine; Deroux, Alban; Boccon-Gibod, Isabelle; Bouillet, Laurence

    2017-01-01

    Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease characterized by AE resistant to antihistamines and a chronic course. We report five new cases of InH-AAE (two women and three men) with a rapid and dramatic response to the anti-immunoglobulin-E antibody omalizumab. In our literature review, we found 13 other relevant cases with a good response to this treatment. Overall, in 6 out of 18 patients, the doses of omalizumab required to prevent recurrences of attacks were higher than the licensed dose for chronic urticaria. No significant adverse effects have been reported.

  2. [Facial and oropharyngeal angioedema in patient with alimentary fish allergy. Diagnosis and treatment].

    Science.gov (United States)

    Pino Rivero, V; Rodríguez Carmona, M; Iglesias González, R J; del Castillo Beneyto, F

    2007-01-01

    Vegetal or animal food can produce hipersensibility reactions IgE mediated of diverse intensity. We report the case of a 54 years old woman without previous allergic antecedents who after eating frozen fish had to go to Emergencies due to angioedema especially in face and oropharynx. The ENT exploration by fibroscopia descarted laryngeal edema but the patient showed initially respiratory symptoms so she was treated with SC adrenalina and then steroids during her admission. The diagnosis of alimentary alergia would be confirmed after by Allergology with cutaneous test prick type.

  3. HEREDITARY FRUCTOSE INTOLERANCE – CASE REPORT

    Directory of Open Access Journals (Sweden)

    Jernej Brecelj

    2002-03-01

    Full Text Available Background. Hereditary fructose intolerance is a rare inborn error of carbohydrate metabolism that presents with hypoglicemia, metabolic acidosis and liver decompensation when the patient is exposed to fructose. Diagnosis was established by fructose tolerance test in the past and nowadays mostly by determination of deficient enzyme fructose-1phosphate aldolase (aldolase B activity in hepatic tissue or by molecular genetic means if the mutation is known. Treatment involves elimination (in infants or reduction of fructose and sucrose from the diet and results in improvement in the patient’s clinical status and liver disease.Results. This article presents a patient with hereditary fructose intolerance who was diagnosed 18 years ago on the Department of Pediatric Gastroenterology, Ljubljana Children’s Hospital. At that time oral fructose tolerance test was used to diagnose the disorder. When she was 17 we performed liver biopsy. The enzyme determination showed the absence of aldolase B activity.Conclusions. Only cooperation of different experts enables recognition of rare metabolic disorders which must be prompt to prevent further damage.

  4. Leber hereditary optic neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyerson C

    2015-06-01

    Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA

  5. Hereditary ovarian cancer: beyond the usual suspects.

    Science.gov (United States)

    Pennington, Kathryn P; Swisher, Elizabeth M

    2012-02-01

    In the past, hereditary ovarian carcinoma was attributed almost entirely to mutations in BRCA1 and BRCA2, with a much smaller contribution from mutations in DNA mismatch repair genes. Recently, three new ovarian cancer susceptibility genes have been identified: RAD51C, RAD51D, and BRIP1. In addition, germline mutations in women with ovarian carcinoma have been recently identified in many of the previously identified breast cancer genes in the Fanconi anemia (FA)-BRCA pathway. While mutations in genes other than BRCA1 and BRCA2 are each individually rare, together they make up a significant proportion of cases. With at least 16 genes implicated in hereditary ovarian cancer to date, comprehensive testing for ovarian cancer risk will require assessment of many genes. As the cost of genomic sequencing continues to fall, the practice of evaluating cancer susceptibility one gene at a time is rapidly becoming obsolete. New advances in genomic technologies will likely accelerate the discovery of additional cancer susceptibility genes and increase the feasibility of comprehensive evaluation of multiple genes simultaneously at low cost. Improved recognition of inherited risk will identify individuals who are candidates for targeted prevention. In addition, identifying inherited mutations in a variety of FA-BRCA pathway genes may aid in identifying individuals who will selectively benefit from PARP inhibitors. Copyright © 2011. Published by Elsevier Inc.

  6. Pavlodar city children's some hereditary diseases

    International Nuclear Information System (INIS)

    Shajmardanova, B. Kh.; Gorbach, S.V.

    1997-01-01

    Territory of the Pavlodar region directly adjoining to the Semipalatinsk test site is unique object for study of many year tests consequences on population health. Health worsening caused by small doses of radiation on artificial pollution background is defined. Purpose of the work is Pavlodar city children's some hereditary diseases (Downs syndrome, crack of upper lip and/or palate, hemophilia) under study of frequency dynamic of statistical data within period from 1980 by 1995. It is defined: a) tendency to growth Downs syndrome frequency has been distinctly observed beginning of the 1982; b) it is noted Downs syndrome frequency growth stabilization within period from 1988 by 1991; c) among children with Downs syndrome is distinguished low viability; d) there is rather higher correlation rate of Downs syndrome and congenial heart threshold against average statistical index; e) character of frequencies changes of crack of upper lip and/or palate has tendency to growth; f) it is defined that boys predominate among children with this disease; g) congenial crack of soft palate have being revealed as solitary thresholds of development; h) genealogy analysis of hemophilia sick reveals, that it has only hereditary character. 8 refs

  7. Surgical treatment of hereditary lens subluxations.

    Science.gov (United States)

    Ozdek, Sengul; Sari, Ayca; Bilgihan, Kamil; Akata, Fikret; Hasanreisoglu, Berati

    2002-01-01

    To evaluate the effectiveness and results of pars plana vitreolensectomy approach with transscleral fixation of intraocular lens in hereditary lens subluxations. Fifteen eyes of 9 consecutive patients with a mean age of 12.8+/-6.2 years (6-26 years) with hereditary lens subluxation were operated on and the results were evaluated in a prospective study. Surgery was considered if best spectacle corrected visual acuity (BSCVA) was less than 20/70. All eyes underwent a 2-port pars plana vitreolensectomy and transscleral fixation of an intraocular lens (IOL). The mean follow-up period was 12.6+/-7.5 months (6-22 months). There was no major intraoperative complication. Preoperatively, 8 eyes (53.3%) had a BSCVA of counting fingers (CF) and 7 eyes (46.6%) had a BSCVA of 20/200 to 20/70. Postoperatively, 14 eyes (93.3%) had a BSCVA of 20/50 or better. None of the patients had IOL decentration or intraocular pressure (IOP) increase during the follow-up period. There was a macular hole formation in 1 eye postoperatively. The early results of pars plana vitreolensectomy with IOL implantation using scleral fixation technique had shown that it not only promises a rapid visual rehabilitation but it is also a relatively safe method. More serious complications, however, may occur in the long term.

  8. Recommendations regarding splenectomy in hereditary hemolytic anemias.

    Science.gov (United States)

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-08-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. Copyright© 2017 Ferrata Storti Foundation.

  9. Recommendations regarding splenectomy in hereditary hemolytic anemias

    Science.gov (United States)

    Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

    2017-01-01

    Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

  10. Acquired Form of Angioedema of the Head and Neck Related to a Deficiency in C1-Inhibitor: A Case Report with a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Bassel Hallak

    2012-01-01

    Full Text Available Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.

  11. Clinical Evaluation of Inpatients with Acute Urticaria

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    Ayşe Serap

    2011-12-01

    Full Text Available Background and Design: To determine the clinical and etiological features of inpatients with acute urticaria and angioedema and to assess the need for laboratory tests. Material and Methods: We recruited 105 patients with acute urticaria and angioedema who were admitted to our inpatient unit. The lesions and the characteristics of the patients were analyzed. Routine diagnostic tests including complete blood count, thyroid function tests, hepatitis panel, stool parasite, total IgE levels, cultures, erythrocyte sedimentation rate, C-reactive protein, anti-nuclear antibody, and posterior anterior lung X-ray were ordered. A psychiatric consultation was obtained, when needed. The results were analyzed with SPSS 15.0 statistical software.Results: Among 105 patients, 28 (26.7% had urticaria, 7 (6.7% had angioedema, and 70 (66.7% suffered from both urticaria and angioedema. The most common accompanying symptoms were itching (91.4% and burning (34.3%. The most common systemic symptoms were fatigue (15.2% and headache (12.4%. The lesions usually appeared in the evening hours (24.8%. Twenty-five patients were waking up due to itching during the night. Some lesions were associated with physical activities. Systemic diseases accompanied the lesions in 12 patients (11%. In terms of etiological factors, 33 patients (22.5% had infections. Food- related lesions were encountered in 14 (13% patients. Thirty patients (28.5% had history of medication use. Stress was detected in 37.1% of the patients; anxiety was diagnosed in 3% of patients. The stool was positive for parasites in 10 (9% patients. Conclusion: Acute urticaria is a benign disorder. Although the underlying cause of urticaria can not always be identified, infections and medications are the most common causes. A comprehensive and detailed history is very important to discover the underlying cause. The diagnostic tests should be ordered according to the patient’s history. Conducting diagnostic tests

  12. Unilateral angioedema of the tongue and the floor of the mouth as a side-effect of ACE-inhibitors].

    NARCIS (Netherlands)

    de Lange, Jan; de Ruiter, M.H.T.; Smeele, L. E.

    2014-01-01

    Abstract An 80-year-old woman who was medically compromised had recurrent diffuse unilateral swelling of the tongue and the floor of the mouth. The clinical working diagnosis of angioedema as a result of the use of ACE-inhibitors (lisinopril) was made. In consultation with the cardiologist in charge

  13. Phenotype standardization of angioedema in the head and neck region caused by agents acting on the angiotensin system

    NARCIS (Netherlands)

    Wadelius, M.; Marshall, S. E.; Islander, G.; Nordang, L.; Karawajczyk, M.; Yue, Q.-Y.; Terreehorst, I.; Baranova, E. V.; Hugosson, S.; Sköldefors, K.; Pirmohamed, M.; Maitland-van der Zee, A.-H.; Alfirevic, A.; Hallberg, P.; Palmer, C. N. A.

    2014-01-01

    Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient

  14. Angioedema adquirido autoimune de difícil controle em paciente com lúpus eritematoso sistêmico Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Vilson Furlanetto Junior

    2010-02-01

    Full Text Available O angioedema adquirido é causado por diferentes medicamentos e doenças linfoproliferativas, e tem sido raramente relacionado com a presença de doenças autoimunes. Descrevemos aqui uma paciente de 47 anos com lúpus eritematoso sistêmico (LES com envolvimento cutâneo importante que desenvolveu angioedema recorrente localizado em face incluindo lábios e pálpebras, membros superiores e tórax, não acompanhado de urticária e com dosagem do inibidor de C1 esterase reduzida. A utilização de antimaláricos, glicocorticoides e pulsoterapia com metilprednisolona associada ao uso de azatioprina não determinou melhora. A paciente utilizou também danazol sem sucesso, e apresentou resposta clínica somente após ter sido submetida a múltiplas sessões de plasmaferese, ocorrendo inclusive resolução de extenso angioedema na mucosa do trato gastrointestinal.Acquired angioedema is caused by different drugs and lymphoproliferative diseases, and rarely it has also been related to the presence of auto-immune disorders. We report the case of a 47 year old female with systemic lupus erythematosus (SLE and severe cutaneous involvement who developed recurrent localized angioedema of the face, including lips and eye lids, upper limbs, and thorax, not associated with urticaria, and with reduced levels of C1 esterase inhibitor. Treatment with antimalarials, glucocorticoids, and pulse therapy with methylprednisolone associated with azathioprine did not improve her condition. The patient was also unsuccessfully treated with danazol, and she only showed clinical response after several sessions of plasmapheresis, including resolution of the extensive edema of the gastrointestinal tract.

  15. Utility of routine laboratory testing in management of chronic urticaria/angioedema.

    Science.gov (United States)

    Tarbox, James A; Gutta, Ravi C; Radojicic, Cristine; Lang, David M

    2011-09-01

    Laboratory tests are routinely ordered to identify or rule out a cause in patients with chronic urticaria/angioedema (CUA). The results of these tests are usually within normal limits or unremarkable. To investigate the proportion of abnormal test results in patients with CUA leading to a change in management and in outcomes of care. Retrospective analysis of a random sample of adult patients with CUA from 2001-2009. Cases totaled 356: 166 with urticaria and angioedema (AE), 187 with urticaria, and 3 with only AE. Patients were predominately women (69.1%) and white (75.6%), with a mean age of 48 ± 15 years. Abnormalities were commonly seen in complete blood counts (34%) and in complete metabolic panels (9.4%). Among the 1,872 tests that were ordered, results of 319 (17%) were abnormal. Of 356 patients, 30 underwent further testing because of abnormalities in laboratory work. This represented 30 of 1,872 tests (1.60%). Only 1 patient benefited from a subsequent change in management. Laboratory testing in CUA patients referred for an Allergy and Immunology evaluation rarely lead to changes in management resulting in improved outcomes of care. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

    Science.gov (United States)

    Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

    2015-09-01

    Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

  17. Mania associated with complicated hereditary spastic paraparesis

    Directory of Open Access Journals (Sweden)

    Raghavendra B Nayak

    2011-01-01

    Full Text Available Hereditary spastic paraparesis (HSP is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient′s father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  18. Mania associated with complicated hereditary spastic paraparesis.

    Science.gov (United States)

    Nayak, Raghavendra B; Bhogale, Govind S; Patil, Nanasaheb M; Pandurangi, Aditya A

    2011-07-01

    Hereditary spastic paraparesis (HSP) is an inherited group of neurological disorders with progressive lower limb spasticity. HSP can be clinically grouped into pure and complicated forms. Pure HSP is one without any associated neurological/psychiatric comorbidity. Depression is the most common psychiatric comorbidity. Presence of mania or bipolar affective illness with HSP is a rare phenomenon. We report a case of a 17-year-old boy who presented with classical features of HSP with complaints of excessive happiness, irritability, increased self-esteem and decreased sleep since 1 month. The patient also had complex partial seizure ever since he had features of HSP. The patient's father and younger sister suffer from pure HSP. The patient was diagnosed to have first episode mania with complicated HSP. The details of treatment and possible neurobiology are discussed in this case report.

  19. [Hereditary ichthyosis: A diagnostic and therapeutic challenge].

    Science.gov (United States)

    Vega Almendra, Nadia; Aranibar Duran, Ligia

    2016-01-01

    Hereditary ichthyoses are a group of genetic disorders of cornification, which are characterised by hyperkeratosis and scaling. The new classification identifies 36 types of ichthyosis, which are subdivided according to their frequency, pattern of inheritance and extracutaneous involvement. The diagnosis is mainly based on clinical features, since genetic studies are not available in our setting. Treatment is symptomatic and management should be performed by a multidisciplinary team. In this article, the diagnostic and therapeutic aspects of different types of ichthyosis are reviewed, taking into account the nomenclature and modifications presented in the new classification. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Pulmonary vascular complications of hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Circo, Sebastian; Gossage, James R

    2014-09-01

    The purpose of this study is to present the latest advances and recommendations in the diagnosis and treatment of pulmonary vascular complications associated with hereditary haemorrhagic telangiectasia (HHT): pulmonary arteriovenous malformations (PAVMs), pulmonary arterial hypertension (PAH), pulmonary hypertension associated with high output cardiac failure or liver vascular malformations, haemoptysis, haemothorax and thromboembolic disease. Transthoracic contrast echocardiography has been validated as a screening tool for PAVM in patients with suspected HHT. Advancements in genetic testing support its use in family members at risk as a cost-effective measure. Therapy with bevacizumab in patients with high output cardiac failure and severe liver AVMs showed promising results. PAH tends to be more aggressive in HHT type 2 patients. Patients suffering from this elusive disease should be referred to HHT specialized centres to ensure a standardized and timely approach to diagnosis and management.

  1. Dementia in hereditary cystatin C amyloidosis

    DEFF Research Database (Denmark)

    Blöndal, H; Guomundsson, G; Benedikz, Eirikur

    1989-01-01

    Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature...... in seventeen cases of whom two presented with dementia. At the last examination the majority had severe dementia and severely abnormal EEG. Anti-cystatin C positive amyloid vascular and perivascular infiltrates were found. The resulting damage to the microvasculature of the brain and secondary hemorrhages...... and infarctions were considered to be an adequate explanation for the dementia in these cases. Skin biopsies can now probably be used to demonstrate cystatin C positive amyloid deposits conclusively in the tissues of these patients....

  2. Genetics of human isolated hereditary nail disorders.

    Science.gov (United States)

    Khan, S; Basit, S; Habib, R; Kamal, A; Muhammad, N; Ahmad, W

    2015-10-01

    Human hereditary nail disorders constitute a rare and heterogeneous group of ectodermal dysplasias. They occur as isolated and/or syndromic ectodermal conditions where other ectodermal appendages are also involved, and can occur associated with skeletal dysplasia. 'Nail disorder, nonsyndromic congenital' (OMIM; Online Mendelian Inheritance in Man) is subclassified into 10 different types. The underlying genes identified thus far are expressed in the nail bed and play important roles in nail development and morphogenesis. Here, we review the current literature on nail disorders and present a coherent review on the genetics of nail disorders. This review will pave the way to identifying putative genes and pathways involved in nail development and morphogenesis. © 2015 British Association of Dermatologists.

  3. Stroke in hereditary hemorrhagic telangiectasia patients. New evidence for repeated screening and early treatment of pulmonary vascular malformations: two case reports

    Directory of Open Access Journals (Sweden)

    Viader Fausto

    2011-07-01

    Full Text Available Abstract Background Paradoxical embolism due to pulmonary arteriovenous malformations is the main mechanism of brain infarction in patients with hereditary hemorrhagic telangiectasia. International Guidelines have recently been published to clarify the performance of screening tests and the effectiveness of treatment for pulmonary arteriovenous malformations. Case Presentation We present two cases of hereditary hemorrhagic telangiectasia patients of our hospital who experienced an acute stroke secondary to paradoxical embolism. Conclusions These two cases show that the guidelines must be followed to prevent the occurrence of ischemic stroke in patients with hereditary hemorrhagic telangiectasia, and that although they may be adequate in most cases, there are some patients who need a more personalized approach.

  4. Hereditary colon Cancer: Recommendations for prevention

    International Nuclear Information System (INIS)

    Sarroca, C.

    2004-01-01

    Prevention in individuals with hereditary risk of colon cancer, is subject to clinical and molecular facts because their behavior differs to sporadic cancer. Hereditary cancer diseases affecting the colon in particular linked to other locations or that are associated with pre-cancer (polyps, osteoma s, lentigines) phenotypic markers represent a dissimilar to those who present directly in colorectal cancer status or associated conditions. In the first, the presence of previous injury (phenotypes) allows us to identify, while the latter is essential to have other diagnostic pathway (genotypes) .The location of genomic alterations manages to delve into the problem and identify those who will develop disease. The perspective will be different in the general population and those who do not carry mutations in terms suggestions for prevention, both primary and secondary. Not always the mutation is detected and in these high-risk situations, the clinic is sovereign and agrees to keep all members of these events surveillance strict about not being able to characterize those who are carriers of alterations and our condition is different in the proposition of preventive attitudes: set from when control about which organs and often starts, suffer because of accelerated carcinogenesis. The presentation is focused on populations at increased risk of cancer colorectal, regarding the management of the suggestions for primary prevention, secondary prevention while analyzing the early diagnosis of the disease and the suggestion of treatment, compared to the general population management. Primary prevention, including chemo prevention are described. While in secondary prevention is emphasized to management time tracking, optimization diagnostics according to the pathology suspected, the most common therapeutic approaches and findings relating prophylactic surgery

  5. Gender specific issues in hereditary ocular disorders.

    Science.gov (United States)

    Iragavarapu, Saradha; Gorin, Michael B

    2015-02-01

    This review is intended to summarize the current knowledge from basic science and clinical medical literature cited within PubMed that pertain to gender-related factors and affect those individuals with hereditary ocular disorders. We consider gender-related biological factors that (a) affect disease onset and progression, (b) gender differences for major X-linked ocular disorders, (c) gender-specific conditions, (d) medications that may influence genetic eye disorders, and finally, (e) gender-related issues that influence the management and quality of life of these patients. Several studies have demonstrated the manner in which sex-related hormones in animal models are capable of influencing cell pathway and survival that are likely to affect hereditary eye disorders. There are very few clinical studies that provide compelling evidence for gender differences in human ocular conditions, other than for a number of X-linked disorders. Disease expression for X-linked disorders may be impacted by genetic mechanisms such as lyonization or uniparental disomy. Clinical evidence regarding the impact of gender-related medical conditions and therapies on eye conditions is extremely limited and primarily based on anecdotal evidence. Gender-specific factors may play a major role in the underlying biological pathways that influence the onset, rate of progression, and clinical findings associated with ocular genetic conditions. Clinicians need to be aware of the variable phenotypes observed in female carriers of X-linked disorders of gender specific issues, many of which are inadequately addressed in the current literature. Clinicians need to be sensitive to gender differences in social, cultural, and religious systems and they should also be aware of how their own gender biases may influence how they counsel patients. Finally, it is clear that the lack of effective clinical studies in this area creates an opportunity for future research that will have real benefits for these

  6. Recurrent IVF failure and hereditary thrombophilia.

    Science.gov (United States)

    Safdarian, Leila; Najmi, Zahra; Aleyasin, Ashraf; Aghahosseini, Marzieh; Rashidi, Mandana; Asadollah, Sara

    2014-07-01

    The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure.

  7. Reproductive factors in hereditary breast cancer.

    Science.gov (United States)

    Jernström, H C; Johannsson, O T; Loman, N; Borg, A; Olsson, H

    1999-12-01

    An early age at menarche, a short menstrual cycle length, and a high age at first full term pregnancy or nulliparity are known risk factors for breast cancer. These risk factors have previously been reported to differ between breast cancer patients with and without a family history of breast cancer and also between breast cancer patients and controls. Self-administered questionnaires were filled out by 95 women belonging to 24 families with known BRCA1 mutations, 16 women belonging to nine families with known BRCA2 mutations, and 95 women belonging to 65 families with hereditary breast cancer where no BRCA1 or BRCA2 mutations could be detected. Thirty-nine women were BRCA1 mutation carriers and 56 women were BRCA1 negative, 11 women were BRCA2 carriers and five BRCA2 negative. All women were born between 1905 and 1979. Age at menarche, physiological menstrual cycle length at age 30 or at current age in younger women (when not using oral contraceptives), age at first full term pregnancy, and nulliparity did not significantly differ between BRCA1 mutation carriers and BRCA1 negative women. Too few women were BRCA2 negative to serve as a control group. BRCA2 mutation carriers were therefore compared with BRCA1 negative and BRCA2 negative women. None of the above reproductive factors did significantly differ between BRCA2 mutation carriers and from BRCA1 and BRCA2 families. Women from non-BRCA1/BRCA2 hereditary breast cancer families had a higher age at menarche, but this was no longer significant after adjustment for other factors in a multivariate model. Our results suggest that reproductive risk factors of breast cancer are not related to BRCA1 or BRCA2 carrier status. There was also no indication that these factors differ in carriers of unknown susceptibility genes compared with non-carriers from BRCA1 and BRCA2 families.

  8. Hereditary Lymphedema of the Leg – A Case Report

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    Birgit Heinig

    2017-07-01

    Full Text Available Primary of hereditary lymphedema is a rare but progressive disease. It is yet not curable. We present a 48-year-old male patient with hereditary lymphedema of his left leg, that was realised by minor trauma (able twist when he was seven years old. He had never been treated for lymphedema but experienced multiple erysipelas during his life. After diagnostic procedures to exclude other causes of leg swelling, the diagnosis of hereditary lymphedema of the leg, stage III was confirmed. We initialized complex decongestive therapy. During two weeks of intensive treatment, the circumference of the left leg could be reduced by 10 cm. This case illustrates the "natural course" hereditary lymphedema. But it raises the hope that even after decades of ignorance, the patients benefits from complex decongestive treatment. Therapeutic nihilism is unnecessary and poses lymphedema patients to risks of infection and secondary malignancies like Stewart-Trewes syndrome.

  9. Genetics Home Reference: hereditary myopathy with early respiratory failure

    Science.gov (United States)

    ... Canada Muscular Dystrophy UK Resource list from the University of Kansas Medical Center: Muscular Dystrophy / Atrophy GeneReviews (1 link) Hereditary Myopathy with Early Respiratory Failure (HMERF) Scientific Articles on PubMed (1 link) PubMed ...

  10. Genetics Home Reference: infantile-onset ascending hereditary spastic paralysis

    Science.gov (United States)

    ... 2 years of life, the initial symptoms of infantile-onset ascending hereditary spastic paralysis appear. Early symptoms include exaggerated reflexes (hyperreflexia) and recurrent muscle spasms in the legs. As the condition progresses, affected ...

  11. New forms of -compactness with respect to hereditary classes

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    Abdo Mohammed Qahis

    2019-01-01

    Full Text Available A hereditary class on a set X is a nonempty collection of subsets closed under heredity. The aim of this paper is to introduce and study strong forms of u-compactness in generalized topological spaces with respect to a hereditary class, called  SuH-compactness and S- SuH-compactness. Also several of their properties are presented. Finally some eects of various kinds of functions on them are studied.

  12. Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Syed, I; Sunkaraneni, V S

    2015-05-01

    There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis. The Medline and Embase databases were interrogated on 15 November 2013 using the search items 'hereditary haemorrhagic telangiectasia' (title), 'epistaxis' (title) and 'treatment' (title and abstract), and limiting the search to articles published in English. A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3 in vitro studies. There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

  13. Disease: H00106 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available : C1 inhibitor deficiency (hereditary angioedema); C4 binding protein alpha deficiency; C4 binding protein b... subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Genetic deficiency o

  14. Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type

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    Kolokolova A.M.

    2016-09-01

    Full Text Available Aim: to study the value of routine methods (clinical symptoms, electrophysiological findings and results of DNA analysis in diagnostics of hereditary motor sensory neuropathy type IA in outpatient clinics. Material and Methods. The review of foreign literature is represented. The phenotypic polymorphism, genetic heterogeneity and the difficulties of diagnostics are identified. A family with hereditary motor sensory neuropathy of lAtype is presented, which was diagnosed on the base of available methods in outpatient practice (clinical symptoms, genealogical method, electro-physiological findings and DNA analysis results. Results. Routine algorithm (consistent valuation of clinical symptoms, neurophysiologic findings and the results of DNA analysis helped to verify the diagnosis of hereditary motor sensory neuropathy of lAtype in outpatient practice after more than 20 years of the onset of the disease. Conclusion. The neurologists of outpatient clinics and other specialists must be informed about the availability of diagnostics of hereditary diseases of nervous system.

  15. Hereditary and non-hereditary microangiopathies in the young. An up-date.

    Science.gov (United States)

    Ringelstein, E Bernd; Kleffner, Ilka; Dittrich, Ralf; Kuhlenbäumer, Gregor; Ritter, Martin A

    2010-12-15

    In recent years, a considerable number of new sporadic or hereditary small artery diseases of the brain have been detected which preferably occur in younger age, below 45 years. Cerebral microangiopathies constitute an appreciable portion of all strokes. In middle aged patients, hereditary cerebral small vessel diseases have to be separated from sporadic degenerative cerebral microangiopathy which is mainly due to a high vascular risk load. Features of the following disorders and details how to differentiate them, are reviewed here, namely CADASIL, MELAS, AD-RVLC, HEMID, CARASIL, PADMAL, FABRY, COL4A1-related cerebral small vessel diseases and a Portuguese type of autosomal dominant cerebral small vessel disease (SVDB). The symptomatic overlap of the cerebral microangiopathies include also other distinctive non-hereditary diseases like posterior (reversible) encephalopathy and Susac's syndrome which are also described. Some of the microangiopathies described here are not only seen in the young but also in the elderly. The precise diagnosis has direct therapeutic implications in several of these entities. Cerebral microangiopathies cause recurring strokes and diffuse white matter lesions leading to a broad spectrum of gait disturbances and in most of these disorders cognitive impairment or even vascular dementia in the long term. Often, they also involve the eye, the inner ear or the kidney. Several typical imaging findings from illustrative cases are presented. The order in which these diseases are presented here is not dictated by an inner logic principle, because a genetically or pathophysiologically based classification system of all these entities does not exist yet. Some entities are well established and not unusual, whereas others have only been described in a few cases in total. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. C1 Inhibitor Deficiency and Angioedema of the Small Intestine Masquerading as Crohn’s Disease

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    Kelly W Burak

    2000-01-01

    Full Text Available A case of C1 inhibitor deficiency presenting as localized edema of the small intestine is described. A 16-year-old, previously healthy woman presented with recurrent attacks of abdominal pain and vomiting following minor abdominal trauma. Investigations including computed tomography scan and barium studies confirmed localized edema of the jejunum. At laparoscopy, Crohn’s disease was suspected; however, a subsequent enteroscopy was normal. Complement levels revealed a low C4 level, and C1 inhibitor deficiency was later confirmed. Attacks of abdominal pain began after starting oral contraceptives and have not returned since stopping the birth control pill. This rare cause of abdominal pain is examined, and C1 inhibitor deficiency and angioedema are reviewed.

  17. Multimodal Imaging in Hereditary Retinal Diseases

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    Francesco Pichi

    2013-01-01

    Full Text Available Introduction. In this retrospective study we evaluated the multimodal visualization of retinal genetic diseases to better understand their natural course. Material and Methods. We reviewed the charts of 70 consecutive patients with different genetic retinal pathologies who had previously undergone multimodal imaging analyses. Genomic DNA was extracted from peripheral blood and genotyped at the known locus for the different diseases. Results. The medical records of 3 families of a 4-generation pedigree affected by North Carolina macular dystrophy were reviewed. A total of 8 patients with Stargardt disease were evaluated for their two main defining clinical characteristics, yellow subretinal flecks and central atrophy. Nine male patients with a previous diagnosis of choroideremia and eleven female carriers were evaluated. Fourteen patients with Best vitelliform macular dystrophy and 6 family members with autosomal recessive bestrophinopathy were included. Seven patients with enhanced s-cone syndrome were ascertained. Lastly, we included 3 unrelated patients with fundus albipunctatus. Conclusions. In hereditary retinal diseases, clinical examination is often not sufficient for evaluating the patient’s condition. Retinal imaging then becomes important in making the diagnosis, in monitoring the progression of disease, and as a surrogate outcome measure of the efficacy of an intervention.

  18. Episodic neurological dysfunction in hereditary peripheral neuropathy

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    Girish Baburao Kulkarni

    2015-01-01

    Full Text Available Episodic transient neurological symptoms are an important set of problems presenting to a neurologist in his routine practice. Occasionally, detailed clinical history including past and family history supplemented with focused examination can bring out a rare cause for such symptoms. We describe in this report in a young male presenting with episodic focal neurological dysfunction, with family history of similar episodes in mother and brother. Examination showed features of pes cavus and peripheral neuropathy for which patient was asymptomatic. Mother and brother were established cases of hereditary neuropathy. Imaging on multiple occasions showed reversible white matter abnormalities. Clinical suspicion of X-linked Charcot-Marie-Tooth disease type 1 (CMT1X was confirmed with detection of mutation in Gap Junction B1 (GJB1 gene, which codes for connexin 32 protein (c.425G>A; p.R142Q hemizygous mutation. Though this mutation has been already reported in CMTX patients, it has not been associated with transient neurological dysfunctions. This is probably the first reported case of CMTX patient with transient neurological dysfunction from India, whose family members had similar episodes.

  19. Hereditary Spherocytosis and Hereditary Elliptocytosis: Aberrant Protein Sorting during Erythroblast Enucleation

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    Salomao, Marcela; Chen, Ke; Villalobos, Jonathan; Mohandas, Narla; An, Xiuli; Chasis, Joel Anne

    2010-02-08

    During erythroblast enucleation, membrane proteins distribute between extruded nuclei and reticulocytes. In hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), deficiencies of membrane proteins, in addition to those encoded by the mutant gene, occur. Elliptocytes, resulting from protein 4.1R gene mutations, lack not only 4.1R but also glycophorin C, which links the cytoskeleton and bilayer. In HS resulting from ankyrin-1 mutations, band 3, Rh-associated antigen, and glycophorin A are deficient. The current study was undertaken to explore whether aberrant protein sorting, during enucleation, creates these membrane-spanning protein deficiencies. We found that although glycophorin C sorts to reticulocytes normally, it distributes to nuclei in 4.1R-deficient HE cells. Further, glycophorin A and Rh-associated antigen, which normally partition predominantly to reticulocytes, distribute to both nuclei and reticulocytes in an ankyrin-1-deficient murine model of HS. We conclude that aberrant protein sorting is one mechanistic basis for protein deficiencies in HE and HS.

  20. NSAID-induced urticaria/angioedema does not evolve into chronic urticaria: a 12-year follow-up study.

    Science.gov (United States)

    Doña, I; Blanca-López, N; Torres, M J; Gómez, F; Fernández, J; Zambonino, M A; Monteseirín, F J; Canto, G; Blanca, M; Cornejo-García, J A

    2014-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent medicaments involved in drug hypersensitivity reactions, with NSAID-induced urticaria/angioedema (NIUA) being the most frequent clinical entity. The natural evolution of NIUA has been suggested to lead to chronic urticaria (CU) in an important proportion of patients, such that NIUA may therefore precede CU. Our aim was to verify whether these entities are related by following up a large cohort of patients with NIUA as well as a control group over a long period of time. The study comprised three groups: (i) patients with a confirmed history of NIUA (more than two episodes with at least two different NSAIDs or positive drug provocation tests), (ii) patients with more than two episodes of urticaria/angioedema to a single NSAID with good tolerance to a strong COX-1 inhibitor and/or evidence by in vivo tests supporting specific IgE antibodies to the drug (single NSAID-induced urticaria/angioedema, SNIUA), and (iii) controls who tolerated NSAIDs. All cases in the three groups were followed up over a period of 12 years. There were 190 patients with NIUA (64.6% female; mean age 43.71 ± 15.82 years, 110 with SNIUA, and 152 controls. At the 12-year evaluation, 12 patients with NIUA (6.15%) had developed CU over a 1- to 8-year period. Similar proportions were seen in SNIUA and controls. Nonsteroidal anti-inflammatory drugs-induced urticaria/angioedema does not seem to precede the onset of CU over the medium term. Further research including a longer follow-up is necessary to verify this observation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Hereditary neuropathy with liability to pressure palsy: a recurrent and bilateral foot drop case report.

    Science.gov (United States)

    Flor-de-Lima, Filipa; Macedo, Liliana; Taipa, Ricardo; Melo-Pires, Manuel; Rodrigues, Maria Lurdes

    2013-01-01

    Hereditary neuropathy with liability to pressure palsy is characterized by acute, painless, recurrent mononeuropathies secondary to minor trauma or compression. A 16-year-old boy had the first episode of right foot drop after minor motorcycle accident. Electromyography revealed conduction block and slowing velocity conduction of the right deep peroneal nerve at the fibular head. After motor rehabilitation, he fully recovered. Six months later he had the second episode of foot drop in the opposite site after prolonged squatting position. Electromyography revealed sensorimotor polyneuropathy of left peroneal, sural, posterior tibial, and deep peroneal nerves and also of ulnar, radial, and median nerves of both upper limbs. Histological examination revealed sensory nerve demyelination and focal thickenings of myelin fibers. The diagnosis of hereditary neuropathy with liability to pressure palsy was confirmed by PMP22 deletion of chromosome 17p11.2. He started motor rehabilitation and avoidance of stressing factors with progressive recovery. After one-year followup, he was completely asymptomatic. Recurrent bilateral foot drop history, "sausage-like" swellings of myelin in histological examination, and the results of electromyography led the authors to consider the diagnosis despite negative family history. The authors highlight this rare disease in pediatric population and the importance of high index of clinical suspicion for its diagnosis.

  2. Hereditary Neuropathy with Liability to Pressure Palsy: A Recurrent and Bilateral Foot Drop Case Report

    Directory of Open Access Journals (Sweden)

    Filipa Flor-de-Lima

    2013-01-01

    Full Text Available Hereditary neuropathy with liability to pressure palsy is characterized by acute, painless, recurrent mononeuropathies secondary to minor trauma or compression. A 16-year-old boy had the first episode of right foot drop after minor motorcycle accident. Electromyography revealed conduction block and slowing velocity conduction of the right deep peroneal nerve at the fibular head. After motor rehabilitation, he fully recovered. Six months later he had the second episode of foot drop in the opposite site after prolonged squatting position. Electromyography revealed sensorimotor polyneuropathy of left peroneal, sural, posterior tibial, and deep peroneal nerves and also of ulnar, radial, and median nerves of both upper limbs. Histological examination revealed sensory nerve demyelination and focal thickenings of myelin fibers. The diagnosis of hereditary neuropathy with liability to pressure palsy was confirmed by PMP22 deletion of chromosome 17p11.2. He started motor rehabilitation and avoidance of stressing factors with progressive recovery. After one-year followup, he was completely asymptomatic. Recurrent bilateral foot drop history, “sausage-like” swellings of myelin in histological examination, and the results of electromyography led the authors to consider the diagnosis despite negative family history. The authors highlight this rare disease in pediatric population and the importance of high index of clinical suspicion for its diagnosis.

  3. Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.

    Science.gov (United States)

    Faisant, Charles; Armengol, Guillaume; Bouillet, Laurence; Boccon-Gibod, Isabelle; Villier, Céline; Lévesque, Hervé; Cottin, Judith; Massy, Nathalie; Benhamou, Ygal

    2016-01-01

    Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database. The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB. 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment. Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.

  4. The prevalence of depression in hereditary spastic paraplegia.

    Science.gov (United States)

    Vahter, L; Braschinsky, M; Haldre, S; Gross-Paju, K

    2009-09-01

    To evaluate the prevalence of depression and sensitivity and specificity of the single-item interview 'Are you depressed?' for people with hereditary spastic paraplegia in Estonia. Single-item interview 'Are you depressed?' was used as a screening question for depression; all participants then completed the Beck Depression Inventory. People with hereditary spastic paraplegia identified from the epidemiological database who agreed to participate in the study. Beck Depression Inventory, clinical interview. The epidemiological database consisted of 59 patients with clinically confirmed diagnosis of hereditary spastic paraplegia. Forty-eight of these consented to participate in the study. The Beck Depression Inventory score was higher than cut-off point in 58% (28/48) and lower in 42% (20/48). Of the study group, 44% (21/48) had mild, 13% (6/48) moderate and one person revealed severe depression. There was a statistically significant correlation between Beck Depression Inventory score and level of mobility; no other significant correlations with other measures were detected. Of the participants, 54% (26/48) had subjective complaints about depression and answered 'Yes' to the single-item interview 'Are you depressed?'. The sensitivity of the one-item interview in the hereditary spastic paraplegia group was 75% and specificity 75%. Our results show that mild depression is prevalent among people with hereditary spastic paraplegia. Although the single question may be helpful, it cannot be relied upon entirely when assessing a person for depression.

  5. Outcomes of Lensectomy in Hereditary Lens Subluxation

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    Mohammad-Hossein Dehghan

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the results of pars plana lensectomy in patients with hereditary lens subluxation. METHOD: Hospital records of patients with hereditary lens subluxation who had undergone pars plana lensectomy at Labbafinejad Medical Center, Tehran-Iran from 1996 to 2003 were reviewed. Patients with more than 6 months of follow up were included. Underlying disorders, best corrected visual acuity (BCVA before and after surgery, intraocular pressure (IOP, postoperative refraction and complications were evaluated. RESULTS: Overall, records of 87 eyes of 49 patients including 27 male and 22 female subjects were reviewed. Mean follow up duration was 20±18 months. Underlying disorders leading to lens subluxation included Marfan syndrome (79.5%, Weill-Marchesani syndrome (8.2%, simple ectopia lentis (8.2%, and homocystinuria (4.1%. The most common indication for surgery was non-correctable refractive error (92.1%. Mean BCVA was 1.13 LogMAR (20/250 preoperatively, which improved to 0.26 LogMAR (20/30-20/40 postoperatively (P < 0.001. BCVA better than 20/40 was achieved in 82.8% of cases after surgery. Angle-supported anterior chamber intraocular lens (ACIOL was implanted in

  6. Angioedema as the first presentation of B-cell non-Hodgkin lymphoma--an unusual case with normal C1 esterase inhibitor level: a case report.

    Science.gov (United States)

    Gunatilake, Sonali Sihindi Chapa; Wimalaratna, Harith

    2014-08-07

    Acquired angioedema is a rare but recognized manifestation of lymphoproliferative disorders due to deficiency in C1 esterase inhibitor. Normal level of C1 esterase inhibitor proteins in association with angioedema due to lymphoproliferative disease is a rare and an uncommon finding caused by antibodies produced from the underlying disease. Antibodies cause inactivation of C1 esterase inhibitor, thus resulting in C1 esterase inhibitor dysfunction despite of normal quantity of C1 esterase inhibitor. A 50-year-old Sri Lankan male presented with first episode of angioedema without any family history. Physical examination revealed mild pallor with swelling of tongue, lips and perioral region. On investigations, erythrocyte sedimentation rate was persistently high and bone marrow with immunohistochemistry revealed infiltration with B-cell type low grade non-Hodgkin lymphoma. Computed tomography scan of the chest and abdomen showed paratracheal and subcarinal lymphadenopathy and splenomegaly, with the findings being compatible with lymphoma. He had normal C1 esterase inhibitor protein level with reduced activity and low C1q, C4 levels indicating antibodies against C1 esterase inhibitor causing dysfunctional C1 esterase inhibitor. Adult onset angioedema should prompt physicians to suspect underlying lymphoproliferative disorder despite of C1 esterase inhibitor protein level being normal. Though uncommon, presence of antibodies against C1 esterase inhibitor secondary to lymphoproliferative disorder should be considered in the presence of normal C1 esterase inhibitor protein levels with low functional capacity in the background of acquired angioedema.

  7. Hereditary stomatocytosis: First case report from Valley of Kashmir

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    Javid Rasool

    2015-01-01

    Full Text Available Stomatocytes are erythrocytes with a central slit or mouth-shaped (stoma area of central pallor when examined on dried smears. In wet preparations, they are uniconcave rather than biconcave, giving them a bowllike appearance. In vitro, stomatocytes are produced by drugs that intercalate into the inner half of the lipid bilayer, thereby expanding the inner lipid surface area relative to that of the outer half of the bilayer. Hereditary stomatocytosis (also known as hereditary hydrocytosis, or overhydrated stomatocytosis refers to a heterogeneous group of autosomal dominant hemolytic anemias caused by altered sodium permeability of the red cell membrane. We present the first case report of hereditary stomatocytosis in a 10-year-old male from the valley of Kashmir. Only eight families with this condition have been described worldwide.

  8. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert [Helsingfors, FI; Vogelstein, Bert [Baltimore, MD; Kinzler, Kenneth W [Baltimore, MD

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  9. [Hereditary hemachromatosis: clinical case report and literature review].

    Science.gov (United States)

    Prochazka, Ricardo; Tagle, Martín

    2006-01-01

    Hemachromatosis is a hereditary condition, producing progressive iron overload as a result of the mutation in proteins that regulate intestinal iron absorption. It is a systemic disease with several manifestations including cirrhosis, diabetes mellitus, cardiomyopathy, joint disease and a proportion of asymptomatic patients. When it is diagnosed and treatment with phlebotomies is initiated before any organ damage is developed, the prognosis is very good, with normal survival free of manifestations. This condition is common in European populations. We report the case of a Peruvian patient of European ancestry who is asymptomatic, but has high levels of aminotransferases and elevated iron markers. Genetic testing confirmed the patient's diagnosis of hereditary hemachromatosis.

  10. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    Energy Technology Data Exchange (ETDEWEB)

    Githu, Tangayi [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Radiology of Huntsville, P.C., Huntsville, AL (United States); Merrow, Arnold C.; Lee, Jason K. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Garrison, Aaron P. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States); Akron Children' s Hospital, Pediatric Surgery, Akron, OH (United States); Brown, Rebeccah L. [Cincinnati Children' s Hospital Medical Center, Department of Surgical Services, Division of Pediatric General and Thoracic Surgery, Cincinnati, OH (United States)

    2014-03-15

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  11. Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation

    International Nuclear Information System (INIS)

    Githu, Tangayi; Merrow, Arnold C.; Lee, Jason K.; Garrison, Aaron P.; Brown, Rebeccah L.

    2014-01-01

    Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of congenital bowel obstruction. The morbidity and mortality of this disease differ significantly from those of isolated intestinal atresias and non-hereditary forms of multiple intestinal atresia. Most notably, despite successful operative repairs of the atresias found in this disease, HMIA maintains a 100% lethality rate from continued post-operative intestinal failure and an associated severe immunodeficiency. We present a case of HMIA evaluated with fetal MRI and subsequently diagnosed by a combination of corroborative postnatal imaging with surgical exploration and pathological examination. (orig.)

  12. Clinical features of pure hereditary spastic paraplegia

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    WEI Qian-qian

    2013-07-01

    Full Text Available Objective To study the clinical features and diagnostic methods of patients with pure hereditary spastic paraplegia (HSP. Methods Patients diagnosed with pure HSP from October 2006 to February 2013 admitted to Department of Neurology, West China Hospital, Sichuan University were included. The patients were assessed by the Spastic Paraplegia Rating Scale and the clinical features were reviewed. Results Thirty-three HSP patients (21 men and 12 women were included in the study. Thirteen patients (39.39% had family history of HSP and the most common genetic mode of the familial cases were autosomal dominant inheritance (11/13. The mean age of onset were (20.35 ± 15.55 years and the mean disease duration were (12.77 ± 9.83 years. All of the included patients presented with signs of impairment of the pyramidal tract such as increased muscular tone, tendon hyperreflexia and positive Babinski's sign of the lower limbs. Impairment of the pyramidal tract also presented in the upper limbs in some patients. Scissors gait appeared in 29 patients and feet deformity in 5 patients. Atrophy of thoracic cord on MRI were presented in 5 patients while 2 patients complicated with peripheral nerve damage. Four patients had a novel exon 10-17 deletion in SPG4 gene. There were no differences in onset age, disease duration and mean score of the Spastic Paraplegia Rating Scale between male and female patients as well as between patients with and without family history (P > 0.05, for all. Conclusion The onset age of pure HSP is variational and males are more common than females. The most common inheritance mode is autosomal dominant and most of the cases are characterized by impairment of the pyramidal tract of the lower limbs and occasionally bladder dysfunction and peripheral nerve damage. Gender and family history do not affect the clinical features. Clinical features, family history and spinal cord MRI will assist the correct diagnosis, and making a definite

  13. Effectiveness of omalizumab in a patient with a life-threatening episode of bronchospasm and larynx angioedema after exposure to house dust.

    Science.gov (United States)

    Kupryś-Lipińska, Izabela; Korczyńska, Paulina; Tworek, Damian; Kuna, Piotr

    2014-02-01

    Omalizumab is a monoclonal antibody against IgE, nowadays approved for the treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated asthma but there is also some evidence (case reports and four published clinical trials) on the effectiveness of this medication in urticaria and angioedema. The case of a 42-year-old woman suffering from severe allergic asthma and severe chronic urticaria with concomitant angioedema is presented in the article. She had a life-threatening episode of bronchospasm and larynx edema after exposure to house dust recorded in her medical history. The patient did not respond to standard therapy. The improvement in asthma control and remission of chronic urticaria and angioedema was achieved after introducing the therapy with omalizumab.

  14. Type I anaphylactic reaction due to contrast induced angioedema causing neck swelling: the role of sitting fiberoptic bronchoscopy in emergent intubation

    Directory of Open Access Journals (Sweden)

    Ali Dabbagh

    2016-07-01

    Full Text Available Contrast induced angioedema is a rapidly progressive state involving a number of organ systems including the upper airway tract; which is usually a type I anaphylactic reaction also known as immediate hypersensitivity reaction. Prompt preservation of the respiratory tract is the cornerstone of this situation. The use of fiberoptic bronchoscope for tracheal intubation though very helpful, has some special considerations due to the anatomic distortions created by edema.This manuscript describes a patient with contrast induced angioedema managed successfully. Serum levels of IgE were highly increased during the first hours after the event; while serum levels of complement were normal. However, rapid airway management and prophylactic intubation saved the patient and prevented the possible aftermath of airway obstruction.Keywords: airway management; type I anaphylactic reaction, angioedema; fiberoptic bronchoscope.Conflict of interest: none of the authors has any conflict of interest.

  15. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53).

  16. Acute laryngeal obstruction in children. A fifty-year review.

    Science.gov (United States)

    Davison, F W

    1978-01-01

    When dealing with acute laryngeal obstruction, the first important consideration is the differential diagnosis of the cause. The author considers the following six types: acute laryngotracheobronchitis, acute epiglottitis, diphtheria, supraglottic allergic edema (angioedema), subglottic allergic edema (spasmodic croup) and foreign body in the larynx or trachea. He traces the development of the treatments that have in 50 years lowered the mortality rate from 70% to practically zero. High humidity, best supplied by an ultrasonic nebulizer, antibiotics, and corticosteroids in very high dose have been the prime effective measures. There still is controversy about the choice between tracheostomy and nasotracheal intubation if medical therapy is delayed or ineffective. The primary physician must know when and where to send these children in order to prevent the fatalities so frequent in previous years.

  17. Note on generalized topological spaces with hereditary classes

    Directory of Open Access Journals (Sweden)

    V. Renukadevi

    2014-01-01

    Full Text Available In this paper, we extend the study of $\\Psi_\\mathcal{H}$ operator  introduced and studied in [5] and rectify the errors in the paper. Moreover, characterizations of $\\mu-$codense and strongly $\\mu-$codense hereditary classes in generalized topological spaces are also given.

  18. Leber's hereditary optic neuropathy and vitamin B12 deficiency

    NARCIS (Netherlands)

    Pott, Jan Willem R.; Wong, Kwok H.

    2006-01-01

    Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON. Methods: A case series was observed. Results: Three

  19. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic ...

  20. Hereditary Ovarian Cancer: Not Only BRCA 1 and 2 Genes

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2015-01-01

    Full Text Available More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

  1. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

  2. [The spectrum of hereditary skeletal-muscle channelopathies

    NARCIS (Netherlands)

    Trip, J.; Drost, G.; Ginjaar, H.B.; Engelen, B.G.M. van; Faber, C.G.

    2005-01-01

    Channelopathies are a heterogeneous group of genetic diseases in which a defective ion channel is responsible for the symptoms. They manifest as diseases of the heart, brain or skeletal muscle. Hereditary skeletal-muscle channelopathies are characterised by myotonia, periodic paralysis or a

  3. Mutations in TITF-1 are associated with benign hereditary chorea

    NARCIS (Netherlands)

    G.J. Breedveld (Guido); A. Guala (Andrea); B.A. Oostra (Ben); A.K. Percy; L.S. Dure; P. Harper; W.F.M. Arts (Willem Frans); L.P. Lazarou; H. van der Linde; B.B.A. de Vries (Bert); M. Joosse (Marijke); M.E. MacDonald; H. Krude; A. Grüters (Annette); J.W.F. van Dongen (Jeroen); C. Danesino (Cesare); P. Heutink (Peter)

    2002-01-01

    textabstractBenign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder

  4. Mutations in TITF-1 are associated with benign hereditary chorea.

    NARCIS (Netherlands)

    Breedveld, G.J.; Dongen, J.W. van; Danesino, C.; Guala, A.; Percy, A.K.; Dure, L.S.; Harper, P.; Lazarou, L.P.; Linde, H. van der; Joosse, M.; Gruters, A.; MacDonald, M.E.; Vries, L.B.A. de; Arts, P.J.W.; Oostra, B.A.; Krude, H.; Heutink, P.

    2002-01-01

    Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental

  5. Clinical and genetic heterogeneity in benign hereditary chorea.

    NARCIS (Netherlands)

    Breedveld, G.J.; Percy, A.K.; MacDonald, M.E.; Vries, L.B.A. de; Yapijakis, C.; Dure, L.S.; Ippel, E.F.; Sandkuijl, L.A.; Heutink, P.; Arts, P.J.W.

    2002-01-01

    BACKGROUND: Benign hereditary chorea (BHC) is an autosomal dominant disorder that can be distinguished from Huntington disease by its early onset, stable or only slightly progressive course, and absence of mental deterioration. The variation in clinical features is such that its very existence has

  6. Rare hereditary cause of chronic pancreatitis in a young male ...

    African Journals Online (AJOL)

    Hereditary chronic pancreatitis associated with a mutation in the serine protease inhibitor, Kazal Type-1 (SPINK-1 gene) is extremely rare. The SPINK1 mutation results in trypsinogen activation which predisposes to chronic pancreatitis predominately when combined with CFTR gene mutations. It presents as either chronic ...

  7. Calf enlargement in hereditary motor and sensory neuropathy

    NARCIS (Netherlands)

    de Visser, M.; Hoogendijk, J. E.; Ongerboer, B. W.; Verbeeten, B. J.

    1990-01-01

    Six members originating from two families with hereditary motor and sensory neuropathy (hypertrophic and neuronal types) were noted to have enlarged calf muscles. Muscle computed tomography revealed that muscle enlargement in the propositus of the family with the hypertrophic type of HMSN was due to

  8. Hereditary primary open angle glaucoma: case study of a Nigerian ...

    African Journals Online (AJOL)

    Objective: To present a case of hereditary primary open angle glaucoma in a Nigerian family. Method: Six members of an Ibo family from Delta State, Nigeria were interviewed and examined by the authors. Information on age, gender, tribe, history of blindness, eye disease and other medical conditions was recorded.

  9. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

    NARCIS (Netherlands)

    Swinkels, D.W.; Janssen, M.C.H.; Bergmans, J.; Marx, J.J.M.

    2006-01-01

    Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for

  10. Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

    Science.gov (United States)

    ... is found in the cells of the nervous system, including sensory neurons. The mutations involved in HSAN2A result in ... Samuels M, Rouleau GA. Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II. J Clin Invest. 2008 Jul; ...

  11. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.

    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised

  12. Positional cloning of a gene involved in hereditary multiple exostoses

    NARCIS (Netherlands)

    Wuyts, W.; van Hul, W.; Wauters, J.; Nemtsova, M.; Reyniers, E.; van Hul, E. V.; de Boulle, K.; de Vries, B. B.; Hendrickx, J.; Herrygers, I.; Bossuyt, P.; Balemans, W.; Fransen, E.; Vits, L.; Coucke, P.; Nowak, N. J.; Shows, T. B.; Mallet, L.; van den Ouweland, A. M.; McGaughran, J.; Halley, D. J.; Willems, P. J.

    1996-01-01

    Hereditary multiple exostosis (EXT) is an autosomal dominant condition mainly characterized by the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been

  13. Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

    Science.gov (United States)

    Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

    2010-01-01

    The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

  14. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S.; Jaspers, Jan P C

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors

  15. Motor activation in SPG4-linked hereditary spastic paraplegia

    DEFF Research Database (Denmark)

    Scheuer, KH; Nielsen, JE; Krabbe, Katja

    2006-01-01

    OBJECTIVE: The aim of this study was to investigate the extent of motor cortical functional reorganisation in patients with SPG4-linked hereditary spastic paraplegia by exploring cortical motor activation related to movements of clinically affected (lower) and unaffected (upper) limbs. METHODS: T...

  16. Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis.

    NARCIS (Netherlands)

    Darghouth, D.; Koehl, B.; Heilier, J.F.; Madalinski, G.; Bovee, P.H.; Bosman, G.J.C.G.M.; Delaunay, J.; Junot, C.; Romeo, P.H.

    2011-01-01

    Overhydrated hereditary stomatocytosis, clinically characterized by hemolytic anemia, is a rare disorder of the erythrocyte membrane permeability to monovalent cations, associated with mutations in the Rh-associated glycoprotein gene. We assessed the red blood cell metabolome of 4 patients with this

  17. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  18. RB1 mutations and second primary malignancies after hereditary retinoblastoma

    NARCIS (Netherlands)

    Dommering, Charlotte J.; Marees, Tamara; van der Hout, Annemarie H.; Imhof, Saskia M.; Meijers-Heijboer, Hanne; Ringens, Peter J.; van Leeuwen, Flora E.; Moll, Annette C.

    2012-01-01

    Survivors of hereditary retinoblastoma have a high risk of second primary malignancies, but it has not been investigated whether specific RB1 germline mutations are associated with greater risk of second primary malignancies in a large cohort. We conducted a retrospective cohort study of 199

  19. Hereditary atypical retinitis pigmentosa: case report | Omoti | Annals ...

    African Journals Online (AJOL)

    This report presents four generations of hereditary atypical (pericentric) retinitis pigmentosa in an Itsekiri family of Warri, Delta state of Nigeria. The patients presented with nyctalopia, waxy disc pallor, arteriolar attenuation, pigment deposits around the optic nerve and visual field loss. The cases were typically mild with ...

  20. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Directory of Open Access Journals (Sweden)

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  1. Genetics Home Reference: hereditary sensory neuropathy type IA

    Science.gov (United States)

    ... Houlden H, King R, Blake J, Groves M, Love S, Woodward C, Hammans S, Nicoll J, Lennox G, O'Donovan DG, Gabriel C, Thomas PK, Reilly MM. Clinical, pathological and genetic characterization of hereditary sensory and autonomic neuropathy type 1 (HSAN I). Brain. 2006 Feb;129(Pt 2):411-25. Epub ...

  2. The neuropathology of hereditary congenital facial palsy vs Mobius syndrome.

    NARCIS (Netherlands)

    Verzijl, H.T.F.M.; Zwaag, B. van der; Lammens, M.M.Y.; Donkelaar, H.J. ten; Padberg, G.W.A.M.

    2005-01-01

    OBJECTIVE: To characterize the neuropathology of hereditary congenital facial palsy. METHODS: The authors compared brainstem pathology of three members of one family with autosomal dominant congenital facial palsy to that in three age-matched controls. The neuropathologic findings of the familial

  3. Dementia with non-hereditary cystatin C angiopathy

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Blöndal, H; Jóhannesson, G

    1989-01-01

    Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral...

  4. ENG mutational mosaicism in a family with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Kjeldsen, Anette D; Ousager, Lilian Bomme

    2018-01-01

    BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder caused by mutations in ENG, ACVRL1, or SMAD4. Around 90% of HHT patients present with a heterozygous pathogenic genetic variation. Almost all cases of HHT have a family history. Very few cases are de...

  5. Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Kjeldsen, J

    2000-01-01

    Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population....

  6. Treatment for dysphagia (swallowing difficulties) in hereditary ataxia.

    Science.gov (United States)

    Vogel, Adam P; Keage, Megan J; Johansson, Kerstin; Schalling, Ellika

    2015-11-13

    Hereditary ataxias are a heterogeneous group of disorders resulting in progressive inco-ordination. Swallowing impairment, also known as dysphagia, is a common and potentially life threatening sequel of disease progression. The incidence and nature of dysphagia in these conditions is largely unknown. The loss of an effective and safe swallow can dramatically affect the health and well-being of an individual. Remediation of difficulties of eating and drinking is an important goal in the clinical care of people with hereditary ataxia. To assess the effects of interventions for swallowing impairment (dysphagia) in people with hereditary ataxias. We searched the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, PsycINFO, and the Education Resources Information Center (ERIC) on 14 September 2015. We also searched Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts, and Trials Registries on 24 September 2015. We considered all randomised controlled trials (RCTs) and quasi-RCTs that compared treatments for hereditary ataxia with placebo or no treatment. We only included studies measuring dysphagia. Three review authors (ES, KJ, MK) independently screened all titles and abstracts. In the event of any disagreement or uncertainty over the inclusion of a particular paper, the review authors planned to meet and reach consensus. We identified no RCTs from the 519 titles and abstracts screened. We excluded papers primarily for not including participants with a hereditary ataxia (that is, being focused on other neurological conditions), being theoretical reviews rather than intervention studies, or being neither randomised nor quasi-randomised trials.We identified five papers of various design that described treatment for dysphagia, or improvement to swallow as a by-product of treatment, in people with hereditary ataxia. None of these studies were RCTs or

  7. Computational modeling of tracheal angioedema due to swelling of the submucous tissue layer.

    Science.gov (United States)

    Gou, Kun; Pence, Thomas J

    2017-10-01

    Angioedema is a tissue-swelling pathology due to rapid change in soft tissue fluid content. Its occurrence in the trachea is predominantly localized to the soft mucous tissue that forms the innermost tracheal layer. The biomechanical consequences, such as airway constriction, are dependent upon the ensuing mechanical interactions between all of the various tissues that comprise the tracheal tube. We model the stress interactions by treating the trachea organ as a three-tissue system consisting of swellable mucous in conjunction with nonswelling cartilage and nonswelling trachealis musculature. Hyperelastic constitutive modeling is used by generalizing the standard anisotropic, incompressible soft tissue framework to incorporate the swelling effect. Finite element stress analysis then proceeds with swelling of the mucous layer providing the driving factor for the mechanical analysis. The amount of airway constriction is governed by the mechanical interaction between the three predominant tissue types. The detailed stress analysis indicates the presence of stress concentrations near the various tissue junctions. Because of the tissue's nonlinear mechanical behavior, this can lead to material stiffness fluctuations as a function of location on the trachea. Patient specific modeling is presented. The role of the modeling in the interpretation of diagnostic procedures and the assessment of therapies is discussed. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Red blood cell vesiculation in hereditary hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Amr eAlaarg

    2013-12-01

    Full Text Available Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterised by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely asessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary

  9. Red blood cell vesiculation in hereditary hemolytic anemia

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

    2013-01-01

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID

  10. Development and validation of the angiotensin-converting enzyme inhibitor (ACEI) induced angioedema investigator rating scale and proposed discharge criteria.

    Science.gov (United States)

    Bonner, Nicola; Panter, Charlotte; Kimura, Alan; Sinert, Rich; Moellman, Joseph; Bernstein, Jonathan A

    2017-05-22

    The use of angiotensin-converting enzyme inhibitors (ACEI) has been associated with the development of bradykinin-mediated angioedema. With ever-widening indications for ACEI in diseases including hypertension, congestive heart failure and diabetic nephropathy, a concomitant increase in ACEI-Angioedema (ACEI-A) has been reported. At present there is no validated severity scoring or discharge criteria for ACEI-A. We sought to develop and validate an investigator rating scale with corresponding discharge criteria using clinicians experienced in treating ACEI-A. In-depth, 60-min qualitative telephone interviews were conducted with 12 US-based emergency physicians. Beforehand, clinicians were sent four case studies describing patients experiencing different severities of angioedema attacks. Clinicians were initially asked open-ended questions about their experience of patients' symptoms, treatment and discharge decisions. Clinicians then rated each patient case study and discussed patient diagnoses, ratings of symptom severity and discharge evaluation. The ratings were used to assess inter-rater reliability of the scale using the intra-class correlation coefficient (ICC) using IBM SPSS analysis Version 19 software. The findings provide support focusing on four key symptoms of airway compromise scored on a 0-4 scale: 1) Difficulty Breathing, 2) Difficulty Swallowing, 3) Voice Changes and 4) Tongue Swelling and the corresponding discharge criteria of a score of 0 or 'No symptoms' for Difficulty Breathing and Difficulty Swallowing and a score of 0 or 1 indicating mild or absence of symptoms for Voice Change and Tongue Swelling. Eleven clinicians agreed the absence of standardized discharge criteria supported the use of this scale. All physicians concurred with the recommended discharge criteria. The clinician ratings provided evidence of strong inter-rater reliability for the rating scale (ICC > 0.80). The investigator rating scale and discharge criteria are

  11. Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema of the Small Bowel-A Surgical Abdomen Mimic.

    Science.gov (United States)

    Bloom, Adam S; Schranz, Craig

    2015-06-01

    Angioedema is an infrequent complication of the use of angiotensin-converting enzyme inhibitors (ACEi) that has an incidence of up to 0.5%. The oropharynx is most commonly affected. Angioedema of the small bowel is a much rarer occurrence; it uniformly presents with abdominal pain of variable duration. A 51-year-old man presented to the emergency department (ED) with generalized abdominal pain, emesis, diarrhea, and bloating. Medical history was significant for hypertension and medications included captopril, metoprolol and aspirin. Vital signs and laboratory tests were unremarkable. Due to the presence of significant abdominal tenderness with guarding on examination, a FAST (focused assessment with ultrasound in trauma) examination was performed and revealed free fluid in the abdomen. A computed tomography scan of the abdomen was quickly obtained, which revealed a large amount of simple-appearing free fluid within the abdomen and mucosal edema throughout the small bowel. The patient underwent an emergent diagnostic laparoscopy and was ultimately diagnosed with angioedema of the small bowel, deemed secondary to captopril usage. Captopril was discontinued and symptoms gradually resolved with supportive care. When imaging is obtained in cases such as this one, small bowel submucosal edema and ascites are often present. Supportive care and cessation of ACEi usage are the cornerstones of treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients on ACEi, it is important to keep this diagnosis in mind to potentially avoid an unneeded surgical intervention, as the condition is self-limiting and can be treated primarily with supportive measures. Published by Elsevier Inc.

  12. Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults.

    Science.gov (United States)

    Teplitsky, Valery; Huminer, David; Zoldan, Joseph; Pitlik, Silvio; Shohat, Mordechai; Mittelman, Moshe

    2003-12-01

    Transcobalamin II is a serum transport protein for vitamin B12. Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects. Complete absence of TC-II or total functional abnormality causes tissue vitamin B12 deficiency resulting in a severe disease with megaloblastic anemia and immunologic and intestinal abnormalities in the first months of life. This condition was described in hereditary autosomal-recessive form. Low serum TC-II without any symptoms or clinical significance was noted in relatives of affected homozygotes. To study 23 members of a four-generation family with hereditary vitamin B12 deficiency and neurologic disorders. Thorough neurologic, hematologic and family studies were supplemented by transcobalamin studies in 20 family members. Partial TC-II deficiency was found in 19 subjects. Apo TC-II (free TC-II unbound to vitamin B12) and total unsaturated B12 binding capacity were low in all tested individuals but one, and holo TC-II (TC-II bound by vitamin B12) was low in all family members. The presentation of the disease was chronic rather than acute. Early signs in children and young adults were dyslexia, decreased IQ, vertigo, plantar clonus and personality disorders. Interestingly, affected children and young adults had normal or slightly decreased serum vitamin B12 levels but were not anemic. Low serum B12 levels were measured in early adulthood. In mid-late adulthood megaloblastic anemia and subacute combined degeneration of the spinal cord were diagnosed. Treatment with B12 injections resulted in a significant improvement. The pedigree is compatible with an autosomal-dominant transmission. This family study suggests a genetic heterogeneity of TC-II deficiency. We report the first family with a hereditary transmitted condition of low serum TC-II (partial TC-II deficiency) associated with neurologic and mental manifestations in childhood. Partial TC-II deficiency may decrease

  13. The impact of age and gender on reporting of cough and angioedema with RAS inhibitors: A case/non-case in VigiBase

    NARCIS (Netherlands)

    Alharbi, Fawaz F.; Kholod, Anzhelika A.V.; Souverein, Patrick C.; Meyboom, Ron H.; de Groot, Mark; De Boer, Anthonius; Klungel, Olaf H.

    2016-01-01

    Background: Little is known about the effect of age and gender on reporting of cough/ angioedema with renin angiotensin system (RAS) inhibitors (angiotensin- converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aliskiren, a direct renin inhibitor (DRI). Objectives: To assess

  14. Alteration of the erythrocyte membrane skeletal ultrastructure in hereditary spherocytosis, hereditary elliptocytosis, and pyropoikilocytosis.

    Science.gov (United States)

    Liu, S C; Derick, L H; Agre, P; Palek, J

    1990-07-01

    The membrane skeleton of normal erythrocytes is largely organized into a hexagonal lattice of junctional complexes (JC) crosslinked by spectrin tetramers, and occasional double tetramers and hexamers. To explore possible skeletal alterations in hereditary spherocytosis (HS), elliptocytosis (HE), and pyropoikilocytosis (HPP), we have studied the ultrastructure of the spread membrane skeletons from a subpopulation of HS patients with a partial spectrin deficiency ranging from 43% to 86% of normal levels, and in patients with HPP who, in addition to a mild spectrin deficiency, also carried a mutant spectrin that was dysfunctional, thus reducing the ability of spectrin dimers to assemble into tetramers. Membrane skeletons derived from Triton-treated erythrocyte ghosts were examined by negative staining electron microscopy. HS membrane skeletons contained structural elements, consisting of JC and spectrin filaments similar to the normal skeleton. However, less spectrin filaments interconnected the JC, and the decrease of spectrin filaments attached to JC appeared to correlate with the severity of spectrin deficiency. Only in severe HS associated with severe spectrin deficiency was the loss of spectrin sufficient enough to disrupt the overall skeletal architecture. In contrast, membrane skeletons prepared from red blood cells (RBCs) of subjects with HPP were strikingly different from HS RBCs with a comparable degree of spectrin deficiency. Although HPP RBCs were only mildly deficient in spectrin, their skeletal lattice was grossly disrupted, in contrast to only mild ultrastructural abnormalities of HS membrane skeletons with a nearly identical degree of spectrin deficiency. Skeletons from patients with common mild HE or asymptomatic carriers, carrying the mutant spectrin but having normal spectrin content, exhibited a moderate disruption of the skeletal lattice. We propose that the above differences in skeletal ultrastructure may underlie differences in the biomechanical

  15. The impact of age and sex on the reporting of cough and angioedema with renin-angiotensin system inhibitors: a case/noncase study in VigiBase.

    Science.gov (United States)

    Alharbi, Fawaz F; Kholod, Anzhelika A V; Souverein, Patrick C; Meyboom, Ronald H; de Groot, Mark C H; de Boer, Anthonius; Klungel, Olaf H

    2017-12-01

    The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting. © 2017 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

  16. The burden of angioedema on United States emergency departments: 2006-2010.

    Science.gov (United States)

    Smith, Aaron; Ray, Meredith; Jain, Nikhita; Zhang, Hongmei; Sebelik, Merry

    2017-04-01

    Angioedema (AE) is a condition that may prompt a visit to an emergency department (ED), and can quickly progress to airway obstruction. To optimize treatment of AE, it is necessary to understand epidemiology and practice patterns. This study measured the magnitude of AE ED visits and characterized demographics, management, frequency of airway interventions, and mortality. Analysis of two national data sets. From the Nationwide Emergency Department Sample and National Hospital Ambulatory Medical Care Survey, we identified all patients presenting from 2006 to 2010 with a primary diagnosis of AE, characterized by the International Classification of Diseases, Ninth Edition, Clinical Modification code 995.1. The discharges were weighted and stratified by comorbidities, age, treatments, and region. χ 2 , t test, and linear regression were employed for comparisons. Total discharges increased from 87,481 (29.3 of 100,000 people) to 111,116 (35.8 of 100,000 people). More females were afflicted (57%), and 41.1% were African American. The majority (83%) of patients were discharged from the ED. Twelve percent of cases were attributed to antihypertensive adverse reaction, and these patients were older (P < .0001, odds ratio [OR] = 1.02), and had more comorbidities (P < .0001, OR = 5.66), hospital admissions (P < .0001, OR = 4.83), and intubations (P < .03, OR = 2.07). Overall, patients required intubation infrequently (<1%) and mortality was low (0.08%). The AE burden on EDs has increased over time. Patients with adverse reactions to antihypertensives are older, have more comorbidities, and require admission and intubation more frequently. Further investigation is needed to better delineate causation and outcome predictors, and to understand regional practice variance. 2c. Laryngoscope, 127:828-834, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Management of women with a hereditary predisposition for breast cancer.

    Science.gov (United States)

    Jatoi, Ismail; Benson, John R

    2016-10-01

    Women with a hereditary breast cancer predisposition have three management options: screening, chemoprevention (risk-reducing medication) and risk-reducing surgery. However, no randomized trials have addressed the effect of these strategies in mutation carriers. In the general population, randomized trials failed to demonstrate a benefit for screening in premenopausal women. Moreover, although chemoprevention reduces breast cancer incidence in high-risk populations, this benefit is potentially confined to estrogen receptor-positive tumors. Finally, observational studies suggest that prophylactic mastectomy and even prophylactic salpingo-ophorectomy reduces breast cancer risk in BRCA mutation carriers, but there are systematic biases associated with such studies. Therefore, women with a hereditary predisposition for breast cancer should be informed of the three risk-reducing strategies, and that their benefits are not fully understood.

  18. CLINICAL AND MORPHOLOGICAL FEATURES OF HEREDITARY OVARIAN CANCER

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    K. B. Kotiv

    2017-01-01

    Full Text Available Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27% patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11% of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy. 

  19. Management of Hereditary Breast and Ovarian Cancer. The Asian Experience

    Directory of Open Access Journals (Sweden)

    Ava Kwong

    2017-02-01

    Full Text Available BRCA1/BRCA2 mutations are the most common high penetrant genes associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC. Although genetic testing is standard of care in Western developed countries, there are still variations in availability of genetic testing and risk assessment for HBOC in Asia. Depending on the countries, there are variations in the clinical strategies and cancer management. The Asian BRCA Consortium has grouped together 14 Asian countries and reviewed genetic counselling/testing uptake rates and clinical management options in these countries. Moreover economic factors, healthcare and legal frameworks, and cultural issues affecting the genetic service availability in Asia were discussed. Mutation spectrum, and VUS rates and the increase use of NGS gene panel testing poses more decisional issues in the clinical management of Hereditary Breast cancer in Asia. These will be discussed. Keywords: BRCA1/BRCA2, germline, HBOC, Asia BRCA Consortium, NGS

  20. Iron in hereditary retinal degeneration: PIXE microanalysis Preliminary results

    International Nuclear Information System (INIS)

    Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J.C.

    1999-01-01

    Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented

  1. Could Ossification of the Achilles Tendon Have a Hereditary Component?

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    Chawki Cortbaoui

    2013-01-01

    Full Text Available Ossification of the Achilles tendon (OTA is an unusual clinical condition. It is characterized by the presence of an ossified mass within the fibrocartilaginous substance of the Achilles tendon. The etiology of the ossification of the Achilles tendon is unknown. Review of the literature suggests that its etiology is multifactorial. The major contributing factors are trauma and surgery with other minor causes such as systemic diseases, metabolic conditions, and infections. To our knowledge, no previous reports suggest any genetic/hereditary predisposition in OAT. We report 3 siblings who have OAT with no history of any of the aforementioned predisposing factors. Could OAT have a hereditary component as one of its etiologies?

  2. Spinal Exostosis in a Boy with Multiple Hereditary Exostoses

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    Ali Al Kaissi

    2013-01-01

    Full Text Available We report on a 13-year-old boy who presented with multiple hereditary exostosis and had development of back pain, associated with neurological deficits, and was found to have exostoses in the spinal canal. Spine radiograph showed a cauliflower-like abnormality of multiple exostoses of the posterior arch (pedicle of the thoracic vertebrae (T3–5. Reformatted CT scanning revealed the simultaneous development of intra- and extraspinal osteochondromatosis of T3–5. The spinal cord was compressed by the intraspinal exostosis. Our patient was surgically treated for intraspinal exostoses and showed cessation of neurological deficits. We report what might be a rare association of spinal cord compression in a patient with multiple hereditary exostoses.

  3. [Hereditary haemorrhagic telangiectasia diagnosed in connection with a traffic accident].

    Science.gov (United States)

    Sivapalan, Pradeesh; Demény, Ann Kathrin; Almind, Merete; Kjeldsen, Anette Drøhse

    2014-02-17

    Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular dysplasia and haemorrhage. It is manifested by mucocutaneous telangiec-tases and arteriovenous malformations in organs such as lungs, liver and brain. We present a case of HHT. A 16-year-old patient with a history of recurrent epistaxis was admitted to the local hospital with chest pain and desaturation. A CT scan revealed pulmonary arteriovenous malformations.

  4. HEREDITARY INTRAVENTRICULAR CONDUCTION DISORDERS IN THE FAMILY FROM KRASNOYARSK

    Directory of Open Access Journals (Sweden)

    A. A. Chernova

    2011-01-01

    Full Text Available Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG, echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

  5. Moyamoya disease in a patient with hereditary spherocytosis.

    Science.gov (United States)

    Holz, A; Woldenberg, R; Miller, D; Kalina, P; Black, K; Lane, E

    1998-02-01

    Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by occlusion of the supraclinoid portion of the internal carotid artery and proximal portions of the anterior and middle cerebral arteries. Patients develop an extensive collateral network of parenchymal, transdural and leptomeningeal vessels to supply the compromised brain. These collateral channels, also known as "moyamoya vessels," may be seen in a number of disorders which lead to intracranial vascular occlusion. We report a case of MMD in a child with hereditary spherocytosis.

  6. Review: Clinical aspects of hereditary DNA Mismatch repair gene mutations.

    Science.gov (United States)

    Sijmons, Rolf H; Hofstra, Robert M W

    2016-02-01

    Inherited mutations of the DNA Mismatch repair genes MLH1, MSH2, MSH6 and PMS2 can result in two hereditary tumor syndromes: the adult-onset autosomal dominant Lynch syndrome, previously referred to as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the childhood-onset autosomal recessive Constitutional Mismatch Repair Deficiency syndrome. Both conditions are important to recognize clinically as their identification has direct consequences for clinical management and allows targeted preventive actions in mutation carriers. Lynch syndrome is one of the more common adult-onset hereditary tumor syndromes, with thousands of patients reported to date. Its tumor spectrum is well established and includes colorectal cancer, endometrial cancer and a range of other cancer types. However, surveillance for cancers other than colorectal cancer is still of uncertain value. Prophylactic surgery, especially for the uterus and its adnexa is an option in female mutation carriers. Chemoprevention of colorectal cancer with aspirin is actively being investigated in this syndrome and shows promising results. In contrast, the Constitutional Mismatch Repair Deficiency syndrome is rare, features a wide spectrum of childhood onset cancers, many of which are brain tumors with high mortality rates. Future studies are very much needed to improve the care for patients with this severe disorder. Copyright © 2016. Published by Elsevier B.V.

  7. Morphological clues to the appropriate recognition of hereditary renal neoplasms.

    Science.gov (United States)

    Moch, Holger; Ohashi, Riuko; Gandhi, Jatin S; Amin, Mahul B

    2018-02-14

    An important emerging role of the surgical pathologist besides the traditional tasks of establishment of the diagnosis and documentation of prognostic and predictive factors, is to recognize the possibility of a hereditary condition in cases where the histology is suggestive for a familial cancer syndrome. In recent years, the knowledge regarding all of the above roles, including the role of recognition of familial cancer, has particularly expanded in renal neoplasms with the close scrutiny to morphology, molecular correlates and clinical features of the different sub-types of renal cell carcinoma. Awareness of these clinically distinctive sub-types and their associated histologic clues will prompt the pathologist for further immunohistochemical or molecular work up, to look for clinical information to support the suspected diagnosis of familial cancer, to alert managing physician/s to look for stigmata of history of familial cancer, which will permit triaging patients and their families for appropriate genetic counseling. This review provides a comprehensive review of the known sub-types of renal cell carcinoma that have a predilection to occur in the setting of hereditary disease; examples include renal cancers occurring in the background of von Hippel Lindau disease, hereditary leiomyomatosis and renal cell carcinoma syndrome, tuberous sclerosis, Birt Hogg Dube syndrome and succinate dehydrogenase deficiency. Herein we focus on diagnostic clues for renal tumors occurring in a non-pediatric setting that should prompt their correct recognition and reiterate the importance of the correct diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).

    Science.gov (United States)

    DiNardo, Courtney D; Bannon, Sarah A; Routbort, Mark; Franklin, Anna; Mork, Maureen; Armanios, Mary; Mace, Emily M; Orange, Jordan S; Jeff-Eke, Meselle; Churpek, Jane E; Takahashi, Koichi; Jorgensen, Jeffrey L; Garcia-Manero, Guillermo; Kornblau, Steve; Bertuch, Alison; Cheung, Hannah; Bhalla, Kapil; Futreal, Andrew; Godley, Lucy A; Patel, Keyur P

    2016-07-01

    Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Referral reasons included (1) bone marrow failure or myelodysplastic syndrome in patients ≤ 50 years, (2) evaluation for germ-line inheritance of identified RUNX1, GATA2, or CEBPA mutations on targeted next-generation sequencing panels, and (3) strong personal and/or family history of malignancy. Cultured skin fibroblasts were utilized for germ-line DNA in all patients with hematologic malignancy. Eight patients (12%) were clinically diagnosed with a HCS: 4 patients with RUNX1-related familial platelet disorder (FPD)/acute myeloid leukemia (AML), and 1 patient each with dyskeratosis congenita, Fanconi anemia, germ-line DDX41, and Li-Fraumeni syndrome (LFS). Two patients with concern for FPD/AML and LFS, respectively, had RUNX1 and TP53 variants of unknown significance. Additionally, 4 patients with prior HCS diagnosis (1 LFS, 3 FPD/AML) were referred for further evaluation and surveillance. In this HHMC-referred hematologic malignancy cohort, HCS was confirmed in 12 patients (18%). HCS identification provides insight for improved and individualized treatment, as well as screening/surveillance opportunities for family members. The HHMC has facilitated HCS diagnosis; with increased clinical awareness of hematologic malignancy predisposition syndromes, more patients who may benefit from evaluation can be identified. Mutation panels intended for prognostication may provide increased clinical suspicion for germ-line testing. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 'Mass allergy': acute scombroid poisoning in a deployed Australian Defence Force health facility.

    Science.gov (United States)

    Ward, David Ian

    2011-02-01

    On the last night of disaster relief operations in Sumatra, Indonesia, a mass casualty event occurred that involved deployed Australian Defence Force personnel. Symptoms of acute urticaria, angioedema, wheeze and gastrointestinal upset were experienced to varying degrees by 16% of the deployed element. The present report describes a presumed scombroid poisoning cluster and demonstrates the difficulties of operating in a deployed environment, the confusion that might be associated with evolving non-kinetic mass casualties, and provides a learning opportunity for an unusual mass casualty incident. © 2011 The Author. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  10. Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria.

    Science.gov (United States)

    Schmitt, Caroline; Gouya, Laurent; Malonova, Eva; Lamoril, Jérôme; Camadro, Jean-Michel; Flamme, Magali; Rose, Christian; Lyoumi, Said; Da Silva, Vasco; Boileau, Catherine; Grandchamp, Bernard; Beaumont, Carole; Deybach, Jean-Charles; Puy, Hervé

    2005-10-15

    Hereditary coproporphyria (HCP), an autosomal dominant acute hepatic porphyria, results from mutations in the gene that encodes coproporphyrinogen III oxidase (CPO). HCP (heterozygous or rarely homozygous) patients present with an acute neurovisceral crisis, sometimes associated with skin lesions. Four patients (two families) have been reported with a clinically distinct variant form of HCP. In such patients, the presence of a specific mutation (K404E) on both alleles or associated with a null allele, produces a unifying syndrome in which hematological disorders predominate: 'harderoporphyria'. Here, we report the fifth case (from a third family) with harderoporphyria. In addition, we show that harderoporphyric patients exhibit iron overload secondary to dyserythropoiesis. To investigate the molecular basis of this peculiar phenotype, we first studied the secondary structure of the human CPO by a predictive method, the hydrophobic cluster analysis (HCA) which allowed us to focus on a region of the enzyme. We then expressed mutant enzymes for each amino acid of the region of interest, as well as all missense mutations reported so far in HCP patients and evaluated the amount of harderoporphyrin in each mutant. Our results strongly suggest that only a few missense mutations, restricted to five amino acids encoded by exon 6, may accumulate significant amounts of harderoporphyrin: D400-K404. Moreover, all other type of mutations or missense mutations mapped elsewhere throughout the CPO gene, lead to coproporphyrin accumulation and subsequently typical HCP. Our findings, reinforced by recent crystallographic results of yeast CPO, shed new light on the genetic predisposition to HCP. It represents a first monogenic metabolic disorder where clinical expression of overt disease is dependent upon the location and type of mutation, resulting either in acute hepatic or in erythropoietic porphyria.

  11. Genetic testing and counseling for hereditary forms of colorectal cancer.

    Science.gov (United States)

    Petersen, G M; Brensinger, J D; Johnson, K A; Giardiello, F M

    1999-12-01

    The discovery of genes responsible for inherited forms of colorectal cancer have the potential to improve cancer risk assessment and counseling. Germline mutations (nonsense, frameshift) of APC are associated with familial adenomatous polyposis, an autosomal dominant syndrome, clinically characterized by young onset, hundreds of adenomatous polyps in the colon, and increased risk for extracolonic tumors. Mutations in APC are also associated with forms of attenuated familial adenomatous polyposis. Germline mutations in five mismatch repair related genes (hMSH2, hMLH1, hMSH6, hPMS1, and hPMS2) cause hereditary nonpolyposis colorectal cancer and are associated with increased risk of somatic genetic alterations and high DNA microsatellite instability. Hereditary nonpolyposis colorectal cancer is characterized by young onset colorectal cancer, proximal colon location, and increased risk of extracolonic cancers. A missense mutation in APC (I1307K) is associated with some familial colorectal cancer in Ashkenazic Jews. For persons at risk for hereditary forms of colorectal cancer, testing algorithms and gene test interpretations depend on identification of the pedigree germline gene mutation. Careful evaluation of the kindred for characteristic aggregation of tumor types among affected individuals and the availability of affected persons for testing are important issues in implementing genetic testing and follow-up management. Case reports illustrate the importance of genetic counseling as a component of cancer genetic risk assessment. The genetic counseling process includes exploration of patient risk perception, sources of anxiety related to cancer risk, patient education (specific cancer-related issues, prevention/intervention options), discussion of possible gene test options, test limitations, and consequences of various gene test outcomes.

  12. [The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

    Science.gov (United States)

    He, J X; Jiang, Y F

    2017-08-06

    Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

  13. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

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    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions

  14. Repetitive Transcranial Magnetic Stimulation in Patients with Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Mehmet Ağırman

    2011-06-01

    Full Text Available Hereditary spastic paraplegia (HSPP is a heterogeneous genetic disease characterized by progressive spasticity of lower extremities. Spasticity is a major cause of long-term disability in HSPP and significantly affects the functional life of patients. Repetitive transcranial magnetic stimulation (rTMS is widely used in diagnosis and treatment of many neurological and psychiatric diseases. Although the positive impacts of rTMS for spasticity have been reported, no study has been found on HSPP. We present two HSPP patients treated with low frequency rTMS (20 minutes at a frequency of 1 Hz (1200 pulses, for a period of 10 treatment sessions.

  15. Current concepts in the treatment of hereditary ataxias

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    Pedro Braga Neto

    2016-03-01

    Full Text Available ABSTRACT Hereditary ataxias (HA represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

  16. Hereditary properties of Amenability modulo an ideal of Banach algebras

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    Hamidreza Rahimi

    2014-10-01

    Full Text Available In this paper we investigate some hereditary properties of amenability modulo an ideal of Banach algebras. We show thatif $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity modulo $I$ of a Banach algebra $A$ and $X$ is a neo-unital modulo $I$, then $(e_{\\alpha}_{\\alpha}$ is a bounded approximate identity for $X$. Moreover we show that amenability modulo an ideal of a Banach algebra $A$ can be only considered by the neo-unital modulo $I$ Banach algebra over $A$

  17. Hypogonadotropic hypogonadism associated with hereditary hemorrhagic telangiectasia [corrected].

    Science.gov (United States)

    Scarano, Valentina; Valentina, Scarano; De Santis, Daniele; Daniele, De Santis; Suppressa, Patrizia; Patrizia, Suppressa; Lastella, Patrizia; Patrizia, Lastella; Lenato, Gennaro Mariano; Mariano, Lenato Gennaro; Triggiani, Vincenzo; Vincenzo, Triggiani; Sabbà, Carlo; Carlo, Sabbà

    2013-01-01

    A 65-year-old man was referred to our clinic for the rehabilitation of right hemiparesis caused by ischaemic stroke. Hypertension, postphlebitic syndrome of lower limbs, frequent nose bleeding, and anemia were present in his history; in his adolescence, he was treated for idiopathic hypogonadotropic hypogonadism. Further investigations have revealed also microsomia, suggesting a clinical diagnosis of Kallmann syndrome, that is, an association, possible in males and females, of hypogonadotropic hypogonadism with olfactory deficits. A definite diagnosis of hereditary hemorrhagic telangiectasia was made based on clinical criteria and confirmed by genetic analysis.

  18. [Hereditary hemorrhagic telangiectasia presenting with hematuria and severe anemia].

    Science.gov (United States)

    Paz, A; Goren, E; Segal, M

    1995-07-01

    A patient with hereditary hemorrhagic telangiectasia was admitted with hematuria and severe anemia after mild recurrent episodes of epistaxis. Telangiectasias were found in the skin and buccal and nasal mucosa. No defect in the coagulation mechanism was found; thrombocyte count and function were normal. On cystoscopy, tortuous engorged vessels, some actively bleeding, were seen in the trigonal mucosa. Biopsy showed enlarged vessels in the lamina propria. Electrocoagulation of the bleeding vessels stopped hematuria, but 6 months later it recurred. This time Nd-YAG laser was used to stop the bleeding after electrocoagulation was ineffective.

  19. Automated imaging dark adaptometer for investigating hereditary retinal degenerations

    Science.gov (United States)

    Azevedo, Dario F. G.; Cideciyan, Artur V.; Regunath, Gopalakrishnan; Jacobson, Samuel G.

    1995-05-01

    We designed and built an automated imaging dark adaptometer (AIDA) to increase accuracy, reliability, versatility and speed of dark adaptation testing in patients with hereditary retinal degenerations. AIDA increases test accuracy by imaging the ocular fundus for precise positioning of bleaching and stimulus lights. It improves test reliability by permitting continuous monitoring of patient fixation. Software control of stimulus presentation provides broad testing versatility without sacrificing speed. AIDA promises to facilitate the measurement of dark adaptation in studies of the pathophysiology of retinal degenerations and in future treatment trials of these diseases.

  20. Predisposing genes in hereditary breast and ovarian cancer

    OpenAIRE

    Huusko, P. (Pia)

    1999-01-01

    Abstract In the present study, mutations in BRCA1 and BRCA2, the two major genes predisposing individuals to hereditary breast and ovarian cancer, were screened in Finnish and Turkish cancer families. Germline BRCA1 mutations were found in 7% (6/88) and BRCA2 mutations in 6% (5/88) of the Finnish families studied in Oulu. Two distinct BRCA1 (3745delT, 4216nt-2A→G) and three BRCA2 (999delTCAAA, 6503delTT, 9346nt-2A→G) mutations were identified, all of which are recurrently found in Finland....