Full Text Available Calciphylaxis is a devastating disorder with a mortality rate of 80% due to sepsis and organ failure. Hallmarks of this rare disease are arteriolar media calcification, thrombotic cutaneous ischemia, and necrotic ulcerations. Different mechanisms of vascular calcification can lead to calciphylaxis. Early diagnosis by deep cutaneous ulcer biopsy is most important for prognosis. Here, dermatologists play a significant role although treatment usually needs an interdisciplinary approach. Surgical procedures had been the cornerstone of treatment in the past including parathyroidectomy, but recently new medical treatments emerged aiming to normalize disturbances of minerals to reduce the serum concentration of sodium phosphate and to prevent precipitation and calcification. Multimodal therapy is warranted but only aggressive surgical debridement of cutaneous ulcers has shown significant outcome improvement.
Gupta, Nancy; Haq, Khwaja F; Mahajan, Sugandhi; Nagpal, Prashant; Doshi, Bijal
BACKGROUND Calciphylaxis is associated with a high mortality that approaches 80%. The diagnosis is usually made when obvious skin lesions (painful violaceous mottling of the skin) are present. However, visceral involvement is rare. We present a case of calciphylaxis leading to lower gastrointestinal (GI) bleeding and rectal ulceration of the GI mucosa. CASE REPORT A 66-year-old woman with past medical history of diabetes mellitus, hypertension, end-stage renal disease (ESRD), recently diagnosed ovarian cancer, and on hemodialysis (HD) presented with painful black necrotic eschar on both legs. The radiograph of the legs demonstrated extensive calcification of the lower extremity arteries. The hospital course was complicated with lower GI bleeding. A CT scan of the abdomen revealed severe circumferential calcification of the abdominal aorta, celiac artery, and superior and inferior mesenteric arteries and their branches. Colonoscopy revealed severe rectal necrosis. She was deemed to be a poor surgical candidate due to comorbidities and presence of extensive vascular calcifications. Recurrent episodes of profuse GI bleeding were managed conservatively with blood transfusion as needed. Following her diagnosis of calciphylaxis, supplementation with vitamin D and calcium containing phosphate binders was stopped. She was started on daily hemodialysis with low calcium dialysate bath as well as intravenous sodium thiosulphate. The clinical condition of the patient deteriorated. The patient died secondary to multiorgan failure. CONCLUSIONS Calciphylaxis leading to intestinal ischemia/perforation should be considered in the differential diagnosis in ESRD on HD presenting with abdominal pain or GI bleeding.
Oda, Tomoko; Sawada, Yu; YAMAGUCHI, TAKASHI; Ohmori, Shun; Omoto, Daisuke; Haruyama, Sanehito; Yoshioka, Manabu; Okada, Etsuko; Nakamura, Motonobu
Background Calciphylaxis following acute renal failure is rare. Findings We report A 57-year-old male with an acute renal failure associated with necrotizing fasciitis. We also review the cases of calciphylaxis due to acute renal disorder further. Conclusions It should be kept in mind that calciphylaxis is observed in patient with not only chronic renal disease but also acute renal failure.
Full Text Available Abstract Introduction Calciphylaxis occurring after kidney transplantation is rare and rarely reported. It results in chronic non-healing wounds and is associated with a poor prognosis and is often fatal. We present a case of proximal lower limb calciphylaxis that occurred early after kidney transplantation. The patient had no classic associated risk factors. He had previously had a total parathyroidectomy but had normal serum calcium-phosphate product and parathyroid hormone levels. The clinical outcome of this case was favorable and highlights some fundamental issues relating to management. Case presentation A 70-year-old British Caucasian man with end-stage renal failure secondary to IgA nephropathy presented six months post kidney transplantation with cutaneous calciphylaxis lesions involving the medial aspect of the thigh bilaterally. Conclusion To the best of our knowledge, this is the first reported case of rapid onset cutaneous calciphylaxis occurring soon after kidney transplantation that was associated with a favorable outcome. Cutaneous calciphylaxis lesions should be promptly managed with meticulous wound care, antimicrobial therapy and the correction of calcium-phosphate product where indicated.
Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard
Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies.
Full Text Available Tumoral calcinosis and calciphylaxis are uncommon but severe complications in ure-mic patients. They occur generally after long-term hemodialysis (HD treatment explained by ad-vanced secondary hyperparathyroidism and longstanding high calcium phosphorus product (Ca × P. Other factors such granulomatous diseases may worsen the calcium phosphate homeostasis alterations. We report a young male patient treated by HD for 6 years who developed tuberculosis in addition to tumoral calcinosis and calciphylaxis.
Shah, Surbhi; Larson, Andrew; Datta, Yvonne
Antiphospholipid antibody syndrome (APS) is a multisystem disorder characterized by vascular thrombosis and presence of circulating autoantibodies. The presence of APS can predispose to macrovascular as well as microvascular thrombotic events. Renal involvement is a common occurrence especially in the background of systemic lupus erythematosus. Skin appears to be another frequent target organ and a significant proportion of patients may present with skin lesions at the time of diagnosis. We present the case of a patient who presented with skin necrosis secondary to antiphospholipid antibody syndrome despite being on therapeutic anticoagulation and then developed dystrophic calcification secondary to her renal insufficiency. This complex skin condition eventually leads to her demise, as she was not a candidate for surgical management of these lesions. Why is this important? This case brings to our attention the need to consider calciphylaxis as a cause of ecchymotic-appearing skin lesions in dialysis patients on warfarin in patients with antiphospholipid antibody syndrome.
Full Text Available Although soft tissue and vascular calcifications are common in CKD and progress as an independent risk factor of all-cause mortality, tumour calcification and calciphylaxis are uncommon in patients with end-stage renal disease (ESRD. Here, we discuss a rare case of a patient with tumour calcification complicated with calciphylaxis developed septic shock from infection. Our patient is a 57-year-old man in his late stage of renal disease who presented with a huge mass at the right hip and necrotic cutaneous ulcers on the lower legs followed by local and systemic infection and death due to septic shock.
Kingi, Lawrence; Grech, Roger; Lam, Michael; Dissanayake, Ajith; Otter, Simon
This case history describes a rare complaint - Calciphylaxis, seen in a New Zealand Maori patient undergoing renal dialysis. This condition causes non-healing tissue ulceration, typically with sepsis and is associated with a very high mortality rate. The need for vigilance among health professionals is highlighted, including the risk factors that may faciliate an early diagnosis; together with the value associated with a multi-disciplinary team approach to management.
Malak Itani, MD
Full Text Available Calciphylaxis is a rare devastating medical condition commonly associated with end-stage renal disease and characterized by extensive microvascular calcifications. We describe a case of calciphylaxis presenting on Tc-99m MDP bone scan imaging with asymmetric radiotracer uptake within the lower extremities corresponding to extensive soft tissue calcifications on Computed tomography. Familiarity with the classic clinical presentation and imaging features of this rare entity may help its early identification and treatment.
Manzoor A. Shah
Full Text Available Temporal artery calciphylaxis has rarely been described in chronic kidney disease patients on dialysis. We report a case of 72-year-old Caucasian man with multiple comorbidities and end-stage renal disease on dialysis who presented with temporal artery calcification leading to bilateral loss of vision followed by extensive skin lesions including one on glans penis. While on peritoneal dialysis, he developed anterior ischemic optic neuropathy, had no improvement on high dose steroids, and temporal artery biopsy showed marked calcification without any evidence of vasculitis. Few weeks later on hemodialysis, he developed widespread cutaneous lesions on extremities and penile necrosis with skin biopsy revealing calciphylaxis. On literature review of calciphylaxis in chronic kidney disease, we found only four cases of temporal artery calciphylaxis leading to anterior ischemic optic neuropathy and blindness. We believe this is the first case in which the rare temporal artery calciphylaxis and the uncommon penile necrosis are being described together. The objective is to emphasize the need to recognize this condition early in the CKD patients on dialysis presenting with visual symptoms as the different treatment strategies may help prevent complete loss of vision and also modify or prevent a full blown calciphylaxis.
Ramy Magdy Hanna
Full Text Available Calciphylaxis has seldom been reported in patients with acute renal failure or in pre-dialysis patients. It also has been reported at lower calcium phosphorous products and in patients with adynamic bone disease. We report a pre-hemodialysis (HD patient with acute renal failure and biopsy-proven calciphylaxis involving multiple cutaneous sites with calcification of the perineal area resulting in dry gangrene of the penis that necessitated a partial penectomy. The patient had elevated serum calcium, phosphorous and parathyroid hormone level of 612 pg/mL. The same patient suffered subsequently from a calcium embolus that occluded his left ophthalmic artery and resulted in left eye blindness. Calciphylaxis is a devastating phenomenon and physicians should have a high clinical suspicion for it in HD patients as well as in patients with late stages of chronic kidney disease.
Full Text Available Calciphylaxis, or calcific uremic arteriolopathy, commonly affects people with end-stage renal disease and carries with it a high rate of morbidity and mortality. Here, we present the unusual case of a 56-year-old woman, with extensive medical problems, who developed calciphylaxis in the presence of primary hyperparathyroidism. Our patient initially presented with bilateral, exquisitely tender thigh lesions. The diagnosis of calciphylaxis was rendered histologically by extensive calcification of the subcutaneous blood vessels. Subsequent parathyroidectomy identified the presence of a hyperactive mediastinal parathyroid adenoma, weighing 0.62 grams. Postoperatively, the patient had normalization of hypercalcemia and parathyroid hormone levels, with subsequent healing of her thigh wounds. Currently, there have been sixteen cases described in the English literature, with only nine being offered a potentially therapeutic parathyroidectomy. It is contingent upon the vigilant physician to diagnose and properly manage this difficult yet treatable condition.
Jee Eun Park
Full Text Available Warfarin skin necrosis (WSN is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.
Nahm, Walter K; Badiavas, Evangelos; Touma, Dany J; Wilkel, Caroline S; Falanga, Vincent
Calciphylaxis is an ill-defined syndrome that is commonly associated with chronic renal failure. Its heterogeneous clinical features include painful livedo reticularis-like purpuric patches and plaques, vesicles, irregularly shaped ulcers, and black eschars. Despite demonstration of extensive vascular arteriolar calcification in this syndrome, its exact pathogenesis remains unknown. Here, we report a case of calciphylaxis presenting with indurated plaques without the usual clinical picture of livedo reticulate purpura, ulcers or necrotic eschars. This case provides an opportunity to review the clinical spectrum of calciphylaxis and to discuss the therapeutic approaches and pathogenesis of this syndrome from deep intra-wall vascular calcification to the resulting infarctions of adjacent tissues.
Sandhu, Gagangeet; Gini, Marcelo Barrios; Ranade, Aditi; Djebali, David; Smith, Steven
Calciphylaxis or calcific uremic arteriolopathy is a life-threatening condition that predominantly affects patients with end-stage renal disease on hemodialysis. A prevalence of up to 4% and a 6-month mortality rate of up to 80% have been reported in those with proximal disease (thighs, abdomen wall, and buttocks). Penile calciphylaxis is very rare but has a mortality rate of 69% within 6 months. Its treatment is controversial. For small lesions, conservative treatment with local wound care and debridement may suffice. Partial or complete penectomy may be needed for more extensive lesions, and especially those associated with signs of local infection. In addition to surgical intervention, as with any other case of calcific uremic arteriolopathy, the cornerstones of therapy should be to keep serum phosphorus sodium thiosulfate was used in addition to the standard medical and surgical therapy. Two months after surgery, the patient's wound completely healed and he has experienced no new lesions over the past 11 months.
Chi, Mijung; Kim, H Jane; Basham, Ryan; Yoon, Michael K; Vagefi, Reza; Kersten, Robert C
Mucormycosis is a rare often fatal opportunistic fungal infection. It is typically described in patients with diabetes in ketoacidotic status and is rare in renal transplant recipients. Calciphylaxis is a rare and highly morbid disease of vascular calcification affecting patients with end-stage renal disease (ESRD). The first case of a renal transplant recipient who was inflicted with both rhinoorbitocerebral mucormycosis and calciphylaxis is reported. A 45-year-old man presented with 2-day history of left upper blepharoptosis, periorbital pain, left-sided headache, binocular diplopia, and left V2 numbness. He had undergone renal transplant for ESRD 7 months earlier with resultant immunosuppressive therapy. MRI and nasal biopsy confirmed rhinoorbitocerebral mucormycosis. Immunosuppressive therapy was stopped and antifungal therapy begun. He had orbital exenteration for progressive rhinoorbitocerebral mucormycosis. Two months later, the patient reported new-onset intermittent bitemporal headache and bilateral swollen, tender temporal arteries. Temporal artery biopsy revealed features consistent with calciphylaxis. Clinical presentation, treatment course, and follow up are discussed.
Full Text Available Background: Calciphylaxis is a rare, yet life-threatening disease mainly occurring in dialysis patients. Traditional options of treatment remain unsatisfactory. Methods: Here we present a novel, combined approach, treating calciphylaxis with IV sodium thiosulfate, cinacalcet and sevelamer. In a case series five hemodialysis patients, have been successfully treated with this regimen. Treatment and survival data were analyzed using descriptive statistics. Results: In all patients, a rapid decrease in pain, improvement of general condition and wound healing within six months occurred. Side effects were low. Drug dosages: IV sodium thiosulfate initial dose 119.4 +/- 84.9 g/m2/week, maintenance dose 40.6 +/- 9 g/m2/week; cinacalcet: maintenance dose 36 +/- 32.9 mg/d and sevelamer maintenance dose 3320 +/-1671 mg/d. One and two year survivals were 100 % and 80 %, respectively. We also report on long-term application of IV sodium thiosulfate of up to 52 months. Patient survival after diagnosis was 52, 84, 21, 36 and 30 months, respectively. Survival since initiation of hemodialysis was 76, 136, 89, 36 and 35 months, respectively. Conclusion: This novel combined approach, a multi-modal treatment of calciphylaxis with persistent hyperparathyroidism, using IV sodium thiosulfate, cinacalcet and sevelamer seems to improve the outcome of this devastating disease.
Bennis, Y; Becquart, C; Aljudaibi, N; Patenotre, P; Guerreschi, P; Delaporte, E; Duquennoy-Martinot, V
Calciphylaxis or calcific arteriolopathy is a rare, life-threatening obstructive pathology of the small cutaneous and subcutaneous vessels. It mainly affects patients with chronic renal failure but it also has been described in patients with normal renal function. The principal risks factors apart from renal failure and phosphocalcic metabolism imbalance are: the female sex, obesity, peripheral vascular disease, diabetes and oral anti-coagulation. We present a very rare case of abdominal, mammarian and upper thighs calciphylaxis in a patient with normal renal function. She presented a severe obesity with a recent important loss of weight and had been treated by oral anticoagulants for a long time. She benefited of a multidisciplinary approach with dermatologists, plastic surgeons and anesthesists permitting a recovery in fourteen weeks. Multidisciplinary approach is necessary but the place of the surgery is not well defined. We report a case in which early and wide surgical approach permitted to obtain a favourable evolution of the pathology. Then, we propose a therapeutic strategy after review of the literature.
Ecto-5' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients – Data from the German Calciphylaxis Registry
Brandenburg, Vincent; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Ketteler, Markus; Wanner, Christoph
Introduction Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. Methods We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD). 144 dialysis patients from the German calciphylaxis registry were compared with 370 dialysis patients without history of CUA. Genotyping was performed using iPLEX Gold MassARRAY(Sequenom, San Diego, USA), KASP genotyping chemistry (LGC, Teddington, Middlesex, UK) or sequencing. Statistical analysis comprised logistic regression analysis with adjustment for age and sex. Results 165 SNPs were finally analyzed and 6 SNPs were associated with higher probability for calciphylaxis (OR>1) in our cohort. Nine SNPs of three genes (CD73, FGF23 and Vitamin D receptor) reached nominal significance (p< 0.05), but did not reach statistical significance after correction for multiple testing. Of the CD73 gene, rs4431401 (OR = 1.71, 95%CI 1.08–2.17, p = 0.023) and rs9444348 (OR = 1.48, 95% CI 1.11–1.97, p = 0.008) were associated with a higher probability for CUA. Of the FGF23 and VDR genes, rs7310492, rs11063118, rs13312747 and rs17882106 were associated with a higher probability for CUA. Conclusion Polymorphisms in the genes encoding CD73, vitamin D receptor and FGF23 may play a role in calciphylaxis development. Although our study is the largest genetic study on calciphylaxis, it is limited by the low sample sizes. It therefore requires replication in other cohorts if available. PMID:28212442
Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate
Sowers James R
Full Text Available Abstract Background Vascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling. The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall. Results The pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. Conclusion A discussion of sodium thiosulfate's dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.
Lourdes Bolla de Lezcano
Full Text Available Resumen La calcifilaxis es un síndrome clínico caracterizado por una calcificación vascular progresiva que ocasiona la aparición de lesiones violáceas, frecuentemente dolorosas, en la piel de pacientes con insuficiencia renal crónica, diálisis o trasplante renal, asociado usualmente a niveles elevados de hormona paratiroidea. Se presenta el caso clínico de una mujer de 44 años, diabética con insuficiencia renal crónica, en hemodiálisis desde hace 2 años, que fue diagnosticada de calcifilaxis tras sospecha clínica y biopsia de lesiones cutáneas. Abstract Calciphylaxis is a clinical syndrome characterized by progressive vascular calcification that causes the appearance of purplish lesions, often painful, in the skin of patients with chronic renal failure, dialysis or kidney transplantation, usually associated with elevated levels of parathyroid hormone. We report a case of a 44-year-old diabetic woman with chronic renal failure on hemodialysis for 2 years. She was diagnosed with calciphylaxis after clinical suspicion and biopsy of skin lesions.
Mayank Mohan Agarwal
Full Text Available Penile gangrene associated with chronic renal failure is very uncommon. A 52-year-old man with diabetes mellitus, diffuse atherosclerosis, ischemic cardiomyopathy and end-stage renal disease presented with blackening of distal penis for 10 days. His general condition was poor and gangrene of prepuce and glans was noted. Doppler and magnetic-resonance angiography revealed bilateral internal iliac artery obstruction. He underwent trocar suprapubic cystostomy and was planned for partial penectomy. But he died of severe diabetic complications in the interim period. Penile gangrene is a manifestation of widespread vascular calcifications associated with end-stage renal disease and is a marker of poor prognosis.
Martínez-Martínez, Marco Ulises; Román-Acosta, Susana; Alvarez-Reyes, Juan Manuel; Oros-Ovalle, Cuauhtémoc; Abud-Mendoza, Carlos
Introducción: la gota es una artropatía inflamatoria que frecuentemente se asocia con obesidad, consumo de alcohol, hipertensión e hipertrigliceridemia. La calcifilaxis se caracteriza por la calcificación metastásica de los vasos de mediano y pequeño calibre. En forma independiente ambas se asocian con mortalidad elevada. Cuando la hiperuricemia y la calcifilaxis están presentes, el riesgo de muerte es de 80%. Caso clínico: hombre de 51 años de edad, con antecedentes de alcoholismo e hipertensión arterial sistémica, quien desarrolló úlceras en extremidades, edema generalizado y síndrome urémico. Tres semanas después de su ingreso falleció debido a sepsis ocasionada por Staphylococcus aureus. El diagnóstico fue calcifilaxis asociada con síndrome metabólico, comorbilidades, factores de riesgo cardiovascular y de insuficiencia renal. Conclusiones: la hiperuricemia es parte del complejo que conforma el síndrome metabólico, resultante de factores genéticos y ambientales. Se reconoce que es un factor asociado con la mortalidad cardiovascular, lo que obliga a considerar a la hiperuricemia en las guías de práctica clínica en la prevención y tratamiento de enfermedades con alta mortalidad debido a las complicaciones que se presentan.
Kjaerskov, Mette Wanscher; Comstedt, Lisbeth Rosholm; Bygum, Anette;
A 64-year-old diabetic man on peritoneal dialysis developed painful necrotic ulcers of the glans penis over a period of six months. On suspicion of atherosclerotic necrosis, a partial resection of his penis was performed. Histological examination showed calciphylaxis. This vasculopathy...... with calcification and intimal fibrosis in small blood vessels is mostly seen in patients with end-stage renal disease. The condition is characterized by painful livedoid and infiltrated plaques and ulcers. Involvement of the penis is rare, but probably underdiagnosed. Udgivelsesdato: 2009-May-25...
Landis, W. J.
High-voltage electron-microscopic tomographic (3D) studies of the ultrastructural interaction between mineral and organic matrix in a variety of calcified tissues reveal different crystal structural and organizational features in association with their respective organic matrices. In brittle or weak pathologic or ectopic calcifications, including examples of osteogenesis imperfecta, calciphylaxis, calcergy, and dermatomyositis, hydroxyapatite crystals occur in various sizes and shapes and are oriented and aligned with respect to collagen in a manner which is distinct from that found in normal calcified tissues. A model of collagen-mineral interaction is proposed which may account for the observed crystal structures and organization. The results indicate that the ultimate strength, support, and other mechanical properties provided by a calcified tissue are dependent in part upon the molecular structure and arrangement of its constituent mineral crystals within their organic matrix.
Fatma, Lilia Ben; El Ati, Zohra; Azzouz, Haifa; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hédi Ben; Béji, Soumaya; Zouaghi, Karim; Zitouna, Moncef; Moussa, Fatma Ben
Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD) for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcutaneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin) that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadroparin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calciphylaxis, outcome is favorable.
Lilia Ben Fatma
Full Text Available Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcu-taneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadro-parin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calci-phylaxis, outcome is favorable.
Chen, Neal X., E-mail: email@example.com [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); O’Neill, Kalisha; Akl, Nader Kassis [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Moe, Sharon M. [Divison of Nephrology, Indiana University School of Medicine, Indianapolis, IN (United States); Roudebush VA Medical Center, Indianapolis, IN (United States)
Highlights: • High phosphorus can induce calcification of adipocytes, even when fully differentiated. • Adipocytes can induce vascular calcification in an autocrine manner. • Sodium thiosulfate inhibits adipocyte calcification. - Abstract: Background: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. Methods: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. Results: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. Conclusion: High phosphorus induced calcification of mature adipocytes, and
by a multistaged approval process. During the early phases, exposure is limited in order to accumulate preliminary data on pharmacology and toxicity. In the Critical Appraisal CME series, Muglia and DiGiovanna describe early testing processes in Phase 1 clinical trials. Calciphylaxis is a severe disease associated with calcification of the skin, subcutaneous tissue and potentially, internal organs. While the disease itself is relatively uncommon, the manifestations are quite distinctive. In this issue of the Journal, we have a review of calciphylaxis from Richard Worth, as well as a preamble by Dr. Goodall and a case report by Kalaaji et al. illustrating the consequences of this rare but distinctive entity.
Haak, Daniel; Gehlen, Johan; Jonas, Stephan; Deserno, Thomas M.
Imaging and image-based measurements nowadays play an essential role in controlled clinical trials, but electronic data capture (EDC) systems insufficiently support integration of captured images by mobile devices (e.g. smartphones and tablets). The web application OpenClinica has established as one of the world's leading EDC systems and is used to collect, manage and store data of clinical trials in electronic case report forms (eCRFs). In this paper, we present a mobile application for instantaneous integration of images into OpenClinica directly during examination on patient's bed site. The communication between the Android application and OpenClinica is based on the simple object access protocol (SOAP) and representational state transfer (REST) web services for metadata, and secure file transfer protocol (SFTP) for image transfer, respectively. OpenClinica's web services are used to query context information (e.g. existing studies, events and subjects) and to import data into the eCRF, as well as export of eCRF metadata and structural information. A stable image transfer is ensured and progress information (e.g. remaining time) visualized to the user. The workflow is demonstrated for a European multi-center registry, where patients with calciphylaxis disease are included. Our approach improves the EDC workflow, saves time, and reduces costs. Furthermore, data privacy is enhanced, since storage of private health data on the imaging devices becomes obsolete.
Kurt M. Sowers
Full Text Available Calcific uremic arteriolopathy (CUA/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.
Full Text Available Background. Roux-en-Y gastric bypass (RYGB can result in calcium and vitamin D deficiency. Parathyroid surgery carries the risk of immediate and long-term hypocalcemia. Methods and Results. We describe a 54-year-old woman with history of end-stage renal disease and gastric bypass surgery who developed calciphylaxis requiring a 3.5-gland parathyroidectomy. Seven weeks later, she presented with weakness, perioral numbness, leg cramps, a positive Chvostek's sign, hypotension, prolonged QT-interval, and serum calcium of 5.4 mg/dL. Oral and intravenous calcium, calcitriol, and high calcium bath hemodialysis were given. She required 18 days of intravenous calcium and an outpatient maintenance regimen of calcitriol 6 mcg/day, calcium carbonate 8 grams/day, calcium citrate 1.2 grams/day, and ergocalciferol 50,000 IU/week. Conclusion. The patient's life-threatening prolonged hypocalcemia and large requirements of calcium and calcitriol were due to a combination of malabsorption, hypoparathyroidism, and renal failure. Special considerations should be given to bariatric surgery patients undergoing neck exploration.
Connor-Stroud, Fawn R; Hopkins, William D; Preuss, Todd M; Johnson, Zachary; Zhang, Xiaodong; Sharma, Prachi
Spontaneous vascular mineralization (deposition of iron or calcium salts) has been observed in marble brain syndrome, mineralizing microangiopathy, hypothyroidism, Fahr syndrome, Sturge–Weber syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and calciphylaxis in humans and as an aging or idiopathic lesion in the brains of horses, cats, nonhuman primates, mice, rats, cattle, white-tailed deer, and dogs. Here we present a 27-y-old, adult male chimpanzee (Pan troglodytes) with spontaneous, extensive vascular mineralization localized solely to the brain. The chimpanzee exhibited tremors and weakness of the limbs, which progressed to paralysis before euthanasia. Magnetic resonance brain imaging in 2002 and 2010 (immediately before euthanasia) revealed multiple hypointense foci, suggestive of iron- and calcium-rich deposits. At necropsy, the brain parenchyma had occasional petechial hemorrhage, and microscopically, the cerebral, cerebellar and brain stem, gray and white matter had moderate to severe mural aggregates of a granular, basophilic material (mineral) in the blood vessels. In addition, these regions often had moderate to severe medial to transmural deposition of mature collagen in the blood vessels. We ruled out common causes of brain mineralization in humans and animals, but an etiology for the mineralization could not be determined. To our knowledge, mineralization in brain has been reported only once to occur in a chimpanzee, but its chronicity in our case makes it particularly interesting. PMID:24956215
Fein, P A; Madane, S J; Jorden, A; Babu, K; Mushnick, R; Avram, M M; Grosman, I
Protein malnutrition is now well established as an important contributory factor to the high mortality in peritoneal dialysis (PD) patients. Low dietary protein calorie intake is one of the factors leading to protein malnutrition. If PD patients develop difficulty eating, percutaneous endoscopic gastrostomy (PEG) feeding may prove beneficial in providing adequate nutrition. Studies on the effectiveness of PEG feeding in PD patients are limited to pediatric patients. The objective of the present study was to assess the outcome of PEG feeding in adult patients with end-stage renal disease (ESRD) on PD. We retrospectively reviewed charts from May 1992 to February 2000 of 10 consecutive patients in our center who had had feeding tubes inserted. The patients' ages ranged from 37 to 81 years, with mean age of 65. Of the 10 patients, 7 were male, 5 were diabetic, and 1 was infected with the human immunodeficiency virus. Two patients had cerebrovascular accident (CVA) with dysphagia, 3 had multi-infarct dementia, 2 had anoxic encephalopathy, 2 had dementia, and 1 had calciphylaxis with anorexia. Of the 10 patients, 9 failed to eat because of neurologic disorders. Two patients who had functioning PEG feedings before starting PD had no complications. Only 2 of 8 patients already on PD continued with long-term PD after a PEG was inserted. Both patients whose PD was not interrupted at the time of PEG placement immediately developed peritonitis. Of the 6 patients who were maintained on hemodialysis (HD), 2 developed peritonitis within one week of starting PEG feedings. The other 4 had no complications from PEG feedings while being maintained on HD, but 1 developed peritonitis when PD was resumed. Of the 5 patients who developed peritonitis, 3 experienced fungal peritonitis. In PD patients, PEG feeding is associated with frequent complications. However, PEG placement prior to PD initiation appears to be safe. Maintaining patients on HD for at least 6 weeks appears to decrease