Calciphylaxis

Abstract

Stratified squamous epithelium Calcification in the subcutis Calcification in the blood vessels Calcification of the walls along with calcific obliteration of the lumen A 55-year old gentleman with diabetic chronic kidney disease on regular haemodialysis for the past three years, sought advice for painful skin lesions on the left leg. There was no history of fever, trauma or insect bite. His other comorbidities were obesity, ischemic heart disease, hypertension, HCV seropositive status and left subclavian vein stenosis with severe venous hypertension. His medications included nifedipine, clonidine, sodium bicarbonate, periodic erythropoietin and iron sucrose injections. On evaluation, he had a 2×4 cm necrotic ulcer covered with eschar over the left leg two inches above the lateral malleolus and two smaller necrotic areas 0.5×0.5 cm above the medial malleolus (Figure 1). Dorsalis pedis and posterior tibial arterial pulsations were not felt in both legs. His lab results were as follows: Haemoglobin-7.4 g/dl, serum creatinine-10.5mg/ dl, calcium-10.5 mg/dl, phosphorus - 4.1 mg/ dl (Ca*P product 41.1mg2 / dl2), albumin - 4.1 g/ dl, alkaline phosphatase-163 IU/l, parathyroid hormone -276.8 pg/ml(normal-10-65 pg/ml). X-ray of the left foot showed extensive calcification of the blood vessels. Histopathologic examination of skin biopsy revealed extensive calcification in the subcutaneous tissue with calcific plugs in the dermal vessels confirming calciphylaxis (Figure 2). He was treated with intensification of dialysis against low calcium concentrates, cinacalcet and antibiotics. Sodium thiosulfate was not available and not given. The lesions worsened despite these measures. He succumbed to intractable sepsis ten weeks later.Figure 1: Clinical photograph of the Skin lesionsFigure 2: Skin biopsy of the lesion demonstrating calciphylaxis(HE, 40×)Calciphylaxis or calcific uraemic arteriolopathy(CUA) is a chronic progressive syndrome of arteriolar media calcification, thrombotic ischemia, and necrotic ulceration.[1] It is mostly seen in patients with advanced chronic kidney disease on haemodialysis. It may rarely be seen in renal transplant recipients with functioning kidneys.[2,3] Few cases are reported even in non-uraemic settings such as alcoholic liver disease, connective tissue disease and malignancies.[3] The pathogenesis is unclear. Disturbances in calcium-phosphorus metabolism are mostly implicated. Hyperparathyroidism, increased serum phosphorus, increased calcium x phosphorus product>70 mg2/dl2, female sex, obesity, diabetes, vitamin D therapy and warfarin use are some of the factors associated with calciphylaxis.[1,4] Lesions start with tender red areas developing into indurated plaques or nodules. Patients may subsequently develop an eschar followed by frank ulceration, gangrene or sepsis. Proximal pattern of involvement with lesions abdomen, thigh and buttocks carries a worse prognosis.[5] Rarely, penis, breasts and ear lobules may become necrotic. The treatment is not well-defined. Parathyroidectomy, oral calcimimetics, sodium thiosulfate are some of the measures that have been employed with variable success. Aggressive wound debridement has been advocated and hyperbaric oxygen may be useful in healing of ulcers.[5,6] The condition is associated with significant morbidity and mortality. 80% of the affected patients die of sepsis or organ failure, usually within a year.[1] Our patient was obese and diabetic, but parathyroid hormone levels were within acceptable range for the level of kidney function. His calcium phosphorus product was also within the recommended range for dialysis patients. The cause for the lesions was not clear. High index of suspicion in patients with CKD is necessary for early diagnosis and limitation of morbidity.