Kalziphylaxie

Calciphylaxis is a rare disease associated with thrombotic cutaneous ischemia and necrosis. Lesions are usually located on the lower extremities, buttocks and the abdomen. Calciphylaxis is recognized by medial calcification, inflammation and subintimal fibrosis of cutaneous arterioles. Calcification, thrombus formation and occlusion occur sequential before tissue necrosis. The disease is usually observed in patients with end-stage renal disease and hyperparathyroidism. In end-stage renal disease, an elevated parathyroid hormone level, hypercalcemia and hyperphosphatemia direct to vascular mineralization. Calciphylaxis affects about 4% of hemodialysis patients. The clinical syndrome is characterized by a high mortality rate. The most important measure is an active multidisciplinary management approach, with intention to wound care and prevention of sepsis.     

Cutaneous calciphylaxis treated by autologous keratinocytes graft and subtotal parathyroidectomy

BACKGROUND: Cutaneous calciphylaxis, seen most often in dialysis patients, is characterised by skin necrosis, and is a disabling and lifethreatening disease. Despite intensive topical treatment, recourse to parathyroidectomy is often necessary. We report the case of a female patient with skin necrosis due to calciphylaxis: pain and necrotic lesions were controlled by grafting of cultured autologous keratinocytes (Epibase). CASE REPORT: A 75-year-old woman with a 5-year history of dialysis-dependent chronic renal failure secondary to nephroangiosclerosis presented a very painful necrotic ulceration on her left leg. In spite of an autologous patch grafts, the lesions rapidly deteriorated. Laboratory data showed high levels of calcium, phosphate and parathyroid hormone and imaging suggested parathyroidal adenoma. Although cutaneous biopsy was not performed, the diagnosis of cutaneous necrosis due to calciphylaxis with tertiary hyperparathyroidism was established. Treatment consisted of a low-calcium and low-phosphorus diet with autologous keratinocytes grafts (Epibase). After the third application of keratinocytes, the pain disappeared, necrosis ceased and wound healing began. Subtotal parathyroidectomy was performed two months after the start of grafts. At three months, the patient was cured. DISCUSSION:. Calciphylaxis is an obstructive vascular disease secondary to calcification of the arterioles leading to ischemic tissue necrosis. Prompt diagnosis is essential since this disease is disabling and life-threatening due to sepsis and ischemic complications. In our case, autologous keratinocyte grafts allowed pain relief to be achieved within large expanses of cutaneous necrosis after correction of calcium and phosphorus levels, thereby allowing parathyroidectomy to be performed under optimal conditions.     

Calciphylaxis in a patient without renal failure or elevated parathyroid hormone: possible aetiological role of chemotherapy

Calciphylaxis is a rare, often fatal disease characterized clinically by progressive cutaneous necrosis and ulceration, and histologically by vascular calcification and thrombosis. It has been described in association with end-stage renal disease, after initiation of dialysis, following renal transplantation, and in patients with hyperparathyroidism. We present the first case of calciphylaxis occurring in a patient with both normal renal function and parathyroid hormone level and discuss the possible aetiological role of chemotherapy-induced functional protein C and protein S deficiency.     

Calciphylaxis of the breast: a rare disease in the differential diagnosis of breast cancer

Calciphylaxis is a rare, but potentially life-threatening condition usually observed in patients with end-stage chronic renal disease and characterized by small- and medium-sized blood vessel calcification leading to tissue ischemia. The clinical features are primarily cutaneous, consisting of skin necrosis and ulceration, mostly located in the lower extremities. We report a case of a 56-year-old woman with a previous history of renal disease and atypical lobular hyperplasia of the right breast, who developed painful skin necrosis on both breasts. Differential diagnosis comprises acute bacterial infection with ulceration, cutaneous vasculitis, cancer and calciphylaxis.     

Nonuraemic calciphylaxis: response to treatment with pamidronate and negative pressure therapy

Calciphylaxis is a rare cause of skin ulcerations and necrosis in patients with both normal renal and parathyroid function. Although calciphylaxis appears to be on the increase, treatments are mainly empirical, especially for wound care. The lesions in calciphylaxis are typically very painful and carry a high risk of infection, with sepsis being the leading cause of death in this serious disease. We report two cases of nonuraemic calciphylaxis, which responded to treatment with pamidronate and wound management by negative pressure system.     

Fulminant and relentless cutaneous necrosis with excruciating pain caused by calciphylaxis developing in a patient undergoing peritoneal dialysis

A 50-year-old Japanese female with chronic renal failure who had been on continuous ambulatory peritoneal dialysis developed fulminant systemic cutaneous necrosis that began as painful livedo reticularis-like skin lesions on her thighs. Because of disseminated vascular calcification within the muscular layer of her lower limbs, we eventually diagnosed her with calciphylaxis. The skin necrosis progressed rapidly, and she died of sepsis and pneumonia on the 53rd hospital day. In addition to her long-lasting severe hyperparathyroidism and extremely elevated serum phosphorus and calcium levels, mechanical, frictional stimulation inflicted on the local skin and administration of corticosteroids were suspected to have precipitated the calciphylaxis. Our lack of awareness of this disease in its early stages resulted in our missing the chance to do a parathyroidectomy that might have changed the course. It is important to know the clinical features of this rare disease in order to make a diagnosis as early as possible.     

Widespread cutaneous and systemic calcification (calciphylaxis) in patients with the acquired immunodeficiency syndrome and renal disease.

BACKGROUND: Calciphylaxis is a form of widespread calcification that may occur in patients with renal disease and hyperparathyroidism. The skin is often affected secondary to vascular compromise and ischemia. Patients infected with the human immunodeficiency virus (HIV) are predisposed to renal failure and thus may develop this serious complication. OBJECTIVE: The purpose of this article is to describe two cases of fatal calciphylaxis in patients with the acquired immunodeficiency syndrome and renal disease. METHODS: Two patients were examined clinically and through the performance of serologic studies and skin biopsies. RESULTS: Both patients had a widespread livedo reticularis-like eruption, which rapidly progressed to cutaneous gangrene. Patient 1 had elevated serum calcium and phosphorus levels whereas patient 2 had normal values but had markedly elevated serum parathyroid hormone levels. Biopsy specimens in both cases showed vascular thrombosis and soft tissue calcification. CONCLUSION: Widespread calcification may develop in patients with HIV infection and renal failure and, in some cases, calcium and phosphorus levels may be normal.     

Cutaneous calciphylaxis

Calciphylaxis represents a dermatological emergency with a mortality of up to 80%. The disease is characterized by a triad of arteriolar medial calcification, thrombotic cutaneous ischemia and necrotic ulcerations. Recently several mechanisms of vascular calcification have been identified. This may led to preventive measures in the future. Early diagnosis is important to avoid complications such as sepsis. The dermatologist plays an important role in early diagnosis based on the recognition of clinical presentation and histopathology. Patients with end-stage renal disease are most commonly affected by calciphylaxis. The most frequent non-uremic predisposing conditions are primary hyperparathyroidism, malignancies, alcohol-induced liver disease, and autoimmune connective tissue diseases. Medical treatment aims to normalize mineral metabolism to reduce the serum concentration of sodium phosphate and thus to prevent precipitation and calcification. Newer compounds are bisphosphonates, non-sodium/non-aluminium phosphate binders, cinacalcet, paricalcitrol, and sodium thiosulfate. Among the surgical procedures parathyroidectomy did not result in a significant survival benefit. An aggressive surgical debridement of necrotic ulcerations, on the other hand, improved survival. Early diagnosis and a multidisciplinary treatment approach including re-vascularization by the vascular surgeon, repeated surgical debridement and split skin transplantation support wound healing and insure limb conservation.     

Kutane Kalziphylaxie

Calciphylaxis represents a dermatological emergency with a mortality of up to 80%. The disease is characterized by a triad of arteriolar medial calcification, thrombotic cutaneous ischemia and necrotic ulcerations. Recently several mechanisms of vascular calcification have been identified. This may led to preventive measures in the future. Early diagnosis is important to avoid complications such as sepsis. The dermatologist plays an important role in early diagnosis based on the recognition of clinical presentation and histopathology. Patients with end-stage renal disease are most commonly affected by calciphylaxis. The most frequent non-uremic predisposing conditions are primary hyperparathyroidism, malignancies, alcohol-induced liver disease, and autoimmune connective tissue diseases. Medical treatment aims to normalize mineral metabolism to reduce the serum concentration of sodium phosphate and thus to prevent precipitation and calcification. Newer compounds are bisphosphonates, non-sodium/non-aluminium phosphate binders, cinacalcet, paricalcitrol, and sodium thiosulfate. Among the surgical procedures parathyroidectomy did not result in a significant survival benefit. An aggressive surgical debridement of necrotic ulcerations, on the other hand, improved survival. Early diagnosis and a multidisciplinary treatment approach including re-vascularization by the vascular surgeon, repeated surgical debridement and split skin transplantation support wound healing and insure limb conservation.     

Five cases of calciphylaxis and a review of the literature

Calciphylaxis is a rare phenomenon of cutaneous necrosis that typically occurs in association with renal failure and has a poor prognosis. We report 5 new cases of calciphylaxis that illustrate the important clinical and histopathologic features of the disease. All patients had end-stage renal failure at the time that purpuric plaques and nodules were noted; these subsequently progressed to necrotic ulcers with eschars. All skin biopsy specimens showed varying degrees of calcification of the medial layer of blood vessel walls in the dermis and subcutaneous fat. Neither the product of serum calcium and phosphorus concentrations nor parathyroid hormone levels correlated temporally with the clinical observations in every case, emphasizing the importance of clinical-histopathologic correlation. Although certain features of calciphylaxis in humans resemble the animal model originally proposed, there are also some crucial differences. We review the pathogenesis, epidemiology, clinical and histopathologic features, and treatment of this disease. (J Am Acad Dermatol 1999;40: 979-87.)     

Calciphylaxis in a patient with end-stage renal disease.

Calciphylaxis is a rare and life-threatening condition of progressive cutaneous necrosis secondary to small and medium-sized vessel calcification. It is seen almost exclusively in patients with end-stage renal disease and secondary hyperparathyroidism. We experienced a case of 67-year-old man with calciphylaxis that manifested with characteristic skin lesions, pathologic findings, and laboratory changes. His skin lesions began as painful erythematous patches and subsequently progressed to necrotic ulcers with eschars on the distal aspect of the extremities. Pathologically, calcification was found in small and medium-sized blood vessels in the deep dermis and subcutaneous tissue. His serum calcium was 9.5 mg/dL, phosphorus was 7.8 mg/dL, and nPTH was 99.9 pg/mL. The patient had been treated with surgical debridement and other supportive treatment. However, he eventually underwent an amputation below the right knee and died from sepsis.     

Calciphylaxis with a Protracted Course in a Patient with End-Stage Renal Failure

Calciphylaxis is a rare condition with a high mortality involving mural calcification of small vessels and occurring primarily in patients with end-stage renal disease. Most cases are characterized by rapid progression of tender subcutaneous nodules or cutaneous plaques to epidermal necrosis, with death in the majority of cases occurring from sepsis. The condition is still poorly understood and the pathogenesis not known. We report a case of calciphylaxis following an unusually benign course. Our patient was a 63-year-old Chinese woman with end-stage renal failure undergoing peritoneal dialysis who presented with itchy pruriginous rashes on her limbs and trunk with subsequent development of eschars and ulceration. Biopsy confirmed the presence of calcification within vessel walls in the subcutis. She was managed conservatively and refused a parathyroidectomy. Surprisingly, her disease did not worsen but remained stable. She died from an acute myocardial infarction 5 months after presenting to our clinic.     

Fulminant metastatic calcinosis with cutaneous necrosis in a child with end-stage renal disease and tertiary hyperparathyroidism

Summary Metastatic calcinosis is a common feature of chronic renal failure. Its first manifestations are bone demineralization and non-visceral and/or visceral calcification with mostly mural deposits in arteries and arterioles. It is initially characterized by hyperphosphataemin followed by secondary or tertiary hyperparathyroidism. Cutaneous involvement is a rare complication. Histologically, the lesions show vascular calcification with ischaemic skin necrosis. Extreme cases may produce calcinosis cuits (calciphylaxis), i.e. disseminated calcification of the subcutaneous tissue and dermis in the form of hard painful cutaneous nodules and plaques with subsequent ulceration. Metastatic calcinosis is a disease affecting adults. While the dystrophic or idiopathic type can develop in children. We present the case of a 6-year-old boy with end-stage renal disease, attributed to congenital renal hypoplasia, and accompanied by secondary hyperparathyroidism. He developed fulminant tertiary hyper- parathyroidism and metastatic caleinosis of the lungs, as well as cutaneous neerosis of the buttocks and legs, subsequent to calcification of arteries and arterioles. A maternal renal transplant failed to function. The serum parathormone, calcium and phosphate levels could not be controlled by maintenance dialysis, phosphate binders and calcitriol. Total parathyroldectomy without auto-transplantation of parathyroid tissue rapidly returned the serum parathormone, calcium and phosphate levels to normal. In addition, topical treatment using merbromine solution and hydro- colloid dressings, healed the ulcers with significant scar formation, within 2.5 months after para- thyroidectomy. A renewed increase of the calcium x phosphate product, 2 months after parathyroidectomy, was attributed to mobilization of calcium compounds from the viseera, as confirmed by a chest X-ray.     

Unusual case of calciphylaxis associated with metastatic breast carcinoma

Calciphylaxis is a relatively rare disorder associated with calcification of small- and medium-sized blood vessels, progressive ischemic skin necrosis, and ulcerations. It is usually seen in patients with end-stage renal disease with secondary hyperparathyroidism and is occasionally seen in primary hyperparathyroidism, hypercalcemia of malignancy, and end-stage liver disease. We report an unusual case of calciphylaxis seen in association with metastatic breast carcinoma in the absence of end-stage renal or parathyroid disease. A 73-year-old woman presented with painful leg ulcers. Serum calcium levels and parathormone levels were within normal limits. Skin biopsies from the ulcers revealed small- to medium-sized subcutaneous arteries with calcification of the media. Some of the arteries were narrowed by fibrointimal hyperplasia and fibrin thrombi. Calcification of the subcutaneous fat, fat necrosis, and suppuration were also seen. Calciphylaxis associated with metastatic osteolytic breast carcinoma is rare. Although end stage renal disease with secondary hyperparathyroidism is the most common cause of calciphylaxis, this case demonstrates that less common conditions with normal serum calcium and parathormone levels may also cause it.     

Conservative management of distal leg necrosis in lung transplant recipients

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI.In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience.     

Warfarin‐induced calciphylaxis successfully treated with sodium thiosulphate

Calciphylaxis is a rare life‐threatening form of skin necrosis. Although traditionally observed in patients with end‐stage renal disease and/or hyperparathyroidism, calciphylaxis has also been reported to occur in ‘non‐traditional’ patients with normal renal and parathyroid function. We report a case of warfarin‐induced calciphylaxis treated successfully with sodium thiosulphate and discuss the role of Vitamin K2 as a potential therapeutic option in the management of warfarin‐induced calciphylaxis.     

Metastatic calcification

Calciphylaxis is a rare, painful, and debilitating disease of widespread metastatic calcification that progresses to ischemic tissue necrosis. It occurs almost exclusively in patients with end-stage renal disease and secondary hyperparathyroidism. Reticulated, violaceous, mottled patches commonly appear on the lower extremities and progress to cordlike nodules and necrotic ulcers with overlying eschars. Septicemia, which may occur after secondary infection of the ulcers, is the most common cause of death. Treatment with phosphate-binding antacids, total or partial parathyroidectomy, and avoidance of local tissue trauma remain the mainstays of therapy, although a uniform cure for calciphylaxis remains elusive. Prognosis for patients with calciphylaxis is dismal, even after surgical intervention. Early diagnosis and treatment is critical to prevent progression of the disease process.     

Cutaneous necrotic lesion: A wonderful delay adverse effect of interferon beta‐1b injection for multiple sclerosis treatment

Multiple sclerosis (MS) is a chronic and inflammatory autoimmune disease. These patients may manifest severe inflammatory cutaneous reactions after using interferon beta‐1b. This article describes a 55‐year‐old man with severe injection site reactions after 10 years administration of interferon beta‐1b. The biopsy specimens revealed skin and subcutaneous tissue necrosis. Histologic evaluation revealed nonspecific inflammatory reactions with no evidence of vasculitis or granulomatous reactions. Based on clinical and pathological findings, the diagnosis of skin and soft tissue necrosis due to interferon injection was given. The injection of interferon beta‐1b in the affected areas was stopped, and the patient's clinical condition improved by wound care. This report is aimed to increase awareness about severe adverse skin reactions, which may infrequently occur with subcutaneous interferon beta‐1b injection after several years. Early diagnosis of this reaction can help to prevent associated complications.     

An Unusual Case of Calciphylaxis

Background: Cutaneous calciphylaxis is a rare disorder that occurs most frequently in patients with end-stage renal disease (ESRD), those on hemodialysis, and renal transplant recipients. It is frequently associated with hyperparathyroidism and a markedly elevated calcium–phosphate product, and it carries a high mortality rate. The usual clinical presentation is of painful, stellate necrosis of the thighs or buttocks, often in the setting of livedo reticularis. Death usually results from septicemia. Objective: This report documents an unusual case of recurrent, self-limiting calciphylaxis in the setting of a patient with ESRD and discusses the clinical and pathologic features of this potentially very fatal disorder. Methods and Results: A 52-year-old woman presented with a greater than one-year history of relapsing and remitting, exquisitely painful, necrotic, numular plaques on the abdomen, breast, and arm. This patient had a markedly elevated calcium–phosphate product and parathyroid hormone level. The diagnosis of calciphylaxis was made by wedge biopsy of the most recent plaque, revealing calcification of medium-sized subcutaneous vessels and lobular capillaries with associated epidermal necrosis. Conclusions: This case demonstrates an unusual clinical variant of calciphylaxis that presented without the characteristic stellate necrosis or livedo reticularis that normally marks this condition and spontaneous resolution without incurring septicemia. Regardless of morphology, calciphylaxis should be considered in the differential diagnosis of painful, necrotic lesions occurring in the setting of ESRD.     

Fatal childhood calciphylaxis in a 10-year-old and literature review

Calciphylaxis is a rare but highly morbid disorder of vascular calcification and skin necrosis, affecting 1% to 4% of adults with end-stage renal disease. Only three affected children have previously been described. We report an unusual instance of fatal calciphylaxis involving a 10-year-old boy, in the setting of sarcoidosis-induced end-stage renal disease. A review of pediatric calciphylaxis cases suggests: (a) increased risk in boys with end-stage renal disease and secondary hyperparathyroidism; (b) frequent distal extremity and visceral organ involvement, (c) worse prognosis with acral necrosis, and (d) possible increased resistance to medical treatment compared to adult patients. Hyperesthetic pain is a common sentinel symptom, and soft tissue x-rays or xeroradiography or both may aid in the diagnosis of pediatric calciphylaxis. Parathyroidectomy in combination with supportive medical management may be the best treatment option in stopping the progression of disease in the pediatric population.