Therapeutic success of sodium thiosulfate in treating cutaneous calciphylaxis in a patient with hyperphosphataemic familial tumoral calcinosis.

Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Topical sodium thiosulfate has been successfully reported for cutaneous calcification associated with connective tissue diseases and calciphylaxis in patients with chronic kidney disease. We provide a case report of a patient with HFTC and calciphylaxis who was treated with topical sodium thiosulfate with a rapid and complete response with no side effects.

Palliative Nerve Block for Penile Calciphylaxis: A Case Report on Ultrasound-Guided Phenol Neurolysis.

A 78-year-old man with uncontrolled diabetes, heart failure, and hemodialysis-dependent end-stage renal disease presented with intractable penile pain secondary to calciphylaxis and necrosis of his glans penis. Given pain refractory to pharmacologic management and refusal of surgery, treatment entailed an ultrasound-guided dorsal penile nerve block with 5 mL of aqueous 4% phenol bilaterally. The patient reported immediate relief and died pain-free 3 months later. While phenol nerve blocks are increasingly uncommon due to local tissue toxicity, the precision of ultrasound leverages phenol's denaturing and axonal demyelinating properties to facilitate long-term targeted neurolysis to palliate chronic nonmalignant pain.

Calciphylaxis in Stage 3 Chronic Kidney Disease on Apixaban Successfully Treated With Sodium Thiosulfate: A Case Report.

INTRODUCTION: Calciphylaxis is a serious condition that often occurs in patients with end-stage renal failure undergoing hemodialysis, with potential comorbidities of hyperparathyroidism and chronic kidney disease (CKD). It is a result of progressive calcification in small- and medium-sized arteries. Causing ischemia in multiple organs and skin ulcers, calciphylaxis has a poor prognosis. No definitive therapeutic or diagnostic guideline exists to prevent the devastating consequences of calciphylaxis. Association of warfarin with calciphylaxis has been reported in the literature, but, to the authors' knowledge, there are no literature reports of patients with CKD who were not on dialysis or warfarin developing calciphylaxis. OBJECTIVE: The authors report an unusual case of calciphylaxis in a patient with stage 3 CKD who was not on dialysis, warfarin, or insulin. CASE REPORT: A 72-year-old female with a history of type 2 diabetes mellitus, who was not taking subcutaneous insulin and had stage 3 CKD, was diagnosed with calciphylaxis by skin biopsy. She was treated with intravenous sodium thiosulfate twice weekly for 2 months with complete resolution of skin lesions. CONCLUSIONS: This case illustrates that early diagnosis, intervention, and a multidisciplinary approach are of utmost importance in the management of calciphylaxis. Sodium thiosulfate, when used in the correct setting, can improve prognosis in patients. Serious consideration should be given to sodium thiosulfate as a practical measure of treatment.

Multidisciplinary management of calciphylaxis: a series of 5 patients at a single facility.

Calciphylaxis is a rare and severe disease that manifests with painful skin ulceration and necrosis. Herein, we report five patients of hemodialysis patients with skin biopsy-proven calciphylaxis at a single facility. One patient had undergone parathyroidectomy (PTx) due to severe secondary hyperparathyroidism, four had been treated with vitamin D receptor activators, and two were on warfarin therapy. All patients had hyperphosphatemia, and one had hypercalcemia. The intact parathyroid hormone level at diagnosis was 2 pg/ml in the patient after PTx, while three patients were within the target range. The average period after diagnosis of calciphylaxis was 2 months. Skin lesions were present on the thighs and lower legs in two patients, and on the dorsum of the foot in one patient. In skin biopsy, calcification was found in the arteriolar media in four patients, and calcium (Ca) was deposited in the dermal lesion in one patient. All patients received local cures, surgical debridement, antibiotics to control infectious diseases, and strict control of serum Ca and phosphate. Calcimimetics were used in all patients except one who had undergone PTx one month before, sodium thiosulfate was used in 4 patients, and low Ca dialysate was used in three patients. The average follow-up period was 7.4 months. Four patients were cured, and one died due to infection. We suggest that multidisciplinary management for infectious diseases, surgical debridement, strict control of mineral and bone markers from the early stage, and elimination of risk factors may improve the course of calciphylaxis, which is a life-threatening disease.

Successful Treatment of Single Infected Calciphylaxis Lesion With Intralesional Injection of Sodium Thiosulfate at High Concentration.

INTRODUCTION: Calciphylaxis is a very complicated disease that usually presents in patients with end-stage renal disease (ESRD). Treatment for calciphylaxis is not well standardized and typically involves a multidisciplinary approach. One of the common medications used in calciphylaxis treatment is sodium thiosulfate (STS). However, its intravenous injection is associated with multiple side effects. CASE REPORT: The authors present a case report of an intralesional injection of STS followed by a literature review of the common treatment modalities and possible further use of intralesional injections. A 51-year-old man with ESRD on peritoneal dialysis presented with a right calf biopsy-proven calciphylaxis lesion measuring 3.1 cm x 3.9 cm. About the same time, he had Pseudomonas-associated peritoneal catheter peritonitis. The calciphylaxis lesion was treated with bimonthly intralesional injections of STS. The lesion had a complete resolution by week 9. CONCLUSIONS: The authors believe a higher local concentration of STS leading to a faster resolution and requiring less frequent injections needs to be further evaluated. Following additional studies, they also propose a greater use of intralesional STS injections in a select set of patients in the future.

Non-uremic calciphylaxis in a patient with multiple rheumatologic diseases.

Non-uremic calciphylaxis is a rare, life-threatening condition characterized clinically by cutaneous necrosis and histologically by calcium deposition in small vessel walls. The etiology of non-uremic calciphylaxis remains the subject of ongoing speculation and debate. Herein we present a patient with calciphylaxis who had normal kidney function and numerous rheumatologic diseases, namely systemic lupus erythematosus (SLE), Sjogren syndrome (SS), and myasthenia gravis (MG). We review the pathophysiology, possible mechanisms, and management for non-uremic calciphylaxis.

The color of skin: black diseases of the skin, nails, and mucosa.

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have.

Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report / Tiosulfato de sodio y pamidronato para el tratamiento de calcifilaxis: reporte de caso

Abstract Introduction: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. Clinical Case: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. Treatment and Outcome: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. Conclusion: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

Resumen: Introducción: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. Caso Clínico: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. Tratamiento y resultado: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. Conclusión: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

Calcifilaxia idiopática: relato de caso / Idiopathic calciphylaxis: case report

A calcifilaxia é uma vasculopatia obliterativa caracterizada por necrose isquêmica cutânea, com instalação aguda e progressiva, secundária à calcificação de vasos sanguíneos de pequeno ou médio calibre. Habitualmente, é uma complicação observada nos pacientes com hiperparatireoidismo secundário à insuficiência renal crônica. Sua patogênese ainda é desconhecida e, provavelmente, multifatorial. Este estudo descreve o caso de um paciente com calcifilaxia idiopática submetido ao tratamento clínico, desbridamento cirúrgico e curativos, com resolução completa após 6 meses. Apesar de ser uma afecção rara e grave na população em geral, o diagnóstico e o tratamento precoce da calcifilaxia permitem a evolução clínica favorável e a melhoria da qualidade de vida do paciente.(AU)

The calciphylaxis is an obliterative vasculopathy characterized by cutaneous ischemic necrosis, with acute and progressive installation, secondary to calcification of small or medium-sized blood vessels. Usually, is a complication observed in patients with hyperparathyroidism secondary to chronic renal failure. Its pathogenesis is still unknown and probably multifactorial. This study describes a case of a patient with idiopathic calciphylaxis, which was submitted to clinical treatment, surgical debridement and dressings, with complete resolution after 6 months. Although being a rare and serious disease in the general population, the early diagnosis and treatment of calciphylaxis allow favorable clinical evolution and improvement of patient's quality of life.(AU)

Penile calciphylaxis in a patient on combined peritoneal dialysis and hemodialysis.

Calciphylaxis presents with painful purpura and intractable skin ulcers on the trunk and particularly the distal extremities, and it mainly occurs in patients on chronic dialysis. A 66-year-old man with renal failure due to diabetic nephropathy was on peritoneal dialysis alone for 1 year, followed by peritoneal dialysis combined with hemodialysis for 3 years. He developed calciphylaxis of the penis, which was diagnosed from the skin biopsy findings and clinical observation. To treat this condition, PD was stopped and HD was performed three times a week. In addition, warfarin therapy was discontinued and infusion of sodium thiosulfate was performed. The penile ulcers decreased in size and pain was markedly improved, so the patient was discharged from hospital. Following discharge, PD was resumed after changing the peritoneal dialysis fluid to bicarbonate-buffered dialysate. The penile ulcers eventually resolved completely. There have been very few reports about calciphylaxis in patients on combined dialysis modalities. In our patient, penile calciphylaxis progressed when lactate-buffered peritoneal dialysis fluid was used and resolved after switching to bicarbonate-buffered fluid together with cessation of warfarin therapy and infusion of sodium thiosulfate.

Sodium thiosulfate and pamidronate for treatment of calciphylaxis: case report.

INTRODUCTION: Calciphylaxis is an infrequent disease that almost exclusively affects patients with chronic kidney disease, although cases have been observed in patients without renal function impairment. The diagnosis is mainly made by clinical manifestations and subsequently confirmed by radiological and histological study. The optimal treatment is not known, although there is a consensus that a multifactorial approach is required. CLINICAL CASE: A 68-year-old woman on hemodialysis for 2 years, who presented a painful nodular lesion in the left thigh, a skin biopsy was performed resulting in a diagnosis of calciphylaxis. TREATMENT AND OUTCOME: Treatment was started with intravenous sodium thiosulfate. Pamidronate is added intravenously, three months later, due to an unfavorable evolution. After 6 months of treatment, improvement in nodular lesions and healing of the ulcerated lesion was observed to be generally well tolerated treatment. CONCLUSION: The combined treatment of sodium thiosulfate, pamidronate and calcitomimetics has been effectiveand safe for the treatment of calciphylaxis, inducing complete remission.

INTRODUCCIÓN: La calcifilaxis es una enfermedad infrecuente que afecta casi exclusivamente a pacientes con insuficiencia renal, aunque se han observado casos en pacientes sin deterioro de la función renal. El diagnóstico es clínico confirmándose con estudio radiológico e histológico. No se conoce con exactitud el tratamiento óptimo, aunque hay consenso en que se requiere un abordaje multifactorial. CASO CLÍNICO: Mujer de 68 años en hemodiálisis desde hace 2 años, que presenta una lesión nodular dolorosa en muslo izquierdo, resultando un diagnostico compatible con calcifilaxis, tras biopsia cutánea. TRATAMIENTO Y RESULTADO: Inicia tratamiento con tiosulfato de sodio vía venosa. Tres meses más tarde y ante la evolución desfavorable, se añade al tratamiento pamidronato vía intravenosa. Tras 6 meses de tratamiento se observa mejoría de las lesiones nodulares y cicatrización de la lesión ulcerada, habiéndose experimentado buena tolerancia. CONCLUSIÓN: El tratamiento combinado de tiosulfato de sodio, pamidronato y calcimiméticos ha resultado efectivo y seguro para el tratamiento de la calcifilaxis, induciendo su remisión completa.

A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma.

Cardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of biomarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.

Benefits of intralesional injections of sodium thiosulfate in the treatment of calciphylaxis.

Calciphylaxis (CPX) is a rare calcifying thrombotic vasculopathy responsible for painful necrotic ulcers, with a high mortality rate, and its management is often difficult. Recently, intravenous infusions of sodium thiosulfate (STS) have shown efficacy. The aim of this study was to assess the efficacy of intralesional STS (IL STS) in four patients. Our aim was to assess the efficacy of IL STS in a prospective mono-centric open study that included four patients with a biopsy-proven cutaneous CPX. Four women (55-84 years old, mean age: 71·2 years) with a uremic (n = 1) or non-uremic CPX (n = 3) and primary hyperparathyroidism induced by teriparatide or after the initiation of oral anti-vitamin K were treated by IL STS (250 mg/ml). The injections were performed around the ulcers, on the active borders, once or twice a week and then at 1-2 weeks intervals. The injected quantity varied from 1·5 to 15 ml. Pain usually improved after two series of injections. Clinical response was visible after 2 weeks. Three patients (75%) healed completely or almost completely. A failure was observed in the last patient who also had lower limb arteriopathy. The main side effect was the pain during injections. IL STS is an interesting alternative therapeutic option in the management of CPX necrotic ulcers with limited side effects. Larger studies are warranted to precisely define its place, its administration procedure and the patients who could benefit from it.

Premature diagnosis of calciphylaxis without pathological indications finally diagnosed as cutaneous small-vessel vasculitis: a post-mortem case report.

A man in his fifties with diabetes had a past history of myocardial infarction and ventricular septal perforation. He underwent hemodialysis about a year ago and was taking amiodarone. He presented with sores and purpura on the lower limbs.-Skin biopsy showed immunofluorescence-negative leukocytoclastic vasculitis. Skin lesions were treated with ointments, which ameliorated the symptoms to some extent, but ulceration relapsed and deteriorated in both number and size. Calciphylaxis was suspected, and a second skin biopsy was performed. No calcium detection,on the arteries was observed, but leukocytoclastic vasculitis was seen. Antineutrophil cytoplasmic antibody-related vasculitis, cryoglobulin vasculitis, or anti-phospholipid syndrome were ruled out by negative findings for autoantibodies. Although he was treated with 30 mg prednisolone, his systemic condition deteriorated, and he died of disseminated intravascular coagulation. Autopsy findings showed no vasculitis in the lung, kidney or intestine, and perimyocardial patch infection was observed.Although calciphylaxis was clinically suspected, his condition was diagnosed finally as cutaneous small-vessel vasculitis.

Successful Treatment of Lung Calciphylaxis With Sodium Thiosulfate in a Patient With Sickle Cell Disease: A Case Report.

Calciphylaxis is a small vessel vasculopathy, characterized by medial wall calcification that develops in a few patients with chronic renal failure. The prognosis of skin calciphylaxis has improved considerably since the introduction of sodium thiosulfate (STS), but it remains unclear whether this therapy is effective against organ lesions related to calciphylaxis. Pulmonary calciphylaxis is a usually fatal medical condition that may occur in association with skin involvement in patients with end-stage renal disease.We report here the case of a 49-year-old woman homozygous sickle cell disease patient on chronic hemodialysis with biopsy-proven systemic calciphylaxis involving the lungs and skin. On admission, ulcerative skin lesions on the lower limbs and bilateral pulmonary infiltrates on chest computerized tomography scan were the main clinical and radiological findings. Skin and bronchial biopsies demonstrated calciphylaxis lesions. The intravenous administration of STS in association with cinacalcet for 8 consecutive months led to a clear improvement in skin lesions and thoracic lesions on chest computerized tomography scan.This case suggests for the first time that organ lesions related to calciphylaxis, and particularly lung injury, are potentially reversible. This improvement probably resulted from the combination of 3 interventions (more frequent dialysis, cinacalcet, and STS), rather than the administration of STS alone.

Use of Becaplermin for nondiabetic ulcers: pyoderma gangrenosum and calciphylaxis.

Large difficult to heal ulcers of various etiologies carry a high morbidity and mortality rate. Becaplermin is a recombinant platelet-derived growth factor approved for treatment of diabetic ulcers. In this two-case series, we report the use of becaplermin in the treatment of ulcers due to (i) calciphylaxis, an often fatal condition resulting from systemic calcification and thrombosis of vessels and (ii) pyoderma gangrenosum (PG), a neutrophilic dermatosis. We also report that topical collagenase worsened PG ulcers, consistent with pathergy. Becaplermin can be used to help treat ulcers resulting from calciphylaxis and PG. These encouraging results lend support for the utilization of becaplermin in the treatment of nondiabetic chronic ulcers of various etiologies.