A 62-year-old man complains of a black lesion and severe pain in his left leg. Initially the lesion was red, but over the past 3 days it has become black. He has end-stage renal disease due to diabetic nephropathy and has been on hemodialysis for the last 10 years. The patient's past medical history is also significant for hypertension, gout, and previous episodes of deep venous thrombosis requiring lifelong anticoagulation with warfarin.
His vitals signs are within normal limits. The leg lesion is shown in the picture below.

The lesion is exquisitely tender, but the area is not warm to palpation. Femoral and other peripheral pulses are 2+ bilaterally. There is no lymphadenopathy and no other skin lesions are noted. The remainder of the physical examination is within normal limits.
Laboratory results are as follows:

Which of the following is the most likely diagnosis?

Question

A 62-year-old man complains of a black lesion and severe pain in his left leg.  Initially the lesion was red, but over the past 3 days it has become black.  He has end-stage renal disease due to diabetic nephropathy and has been on hemodialysis for the last 10 years.  The patient's past medical history is also significant for hypertension, gout, and previous episodes of deep venous thrombosis requiring lifelong anticoagulation with warfarin.
His vitals signs are within normal limits.  The leg lesion is shown in the picture below.

The lesion is exquisitely tender, but the area is not warm to palpation.  Femoral and other peripheral pulses are 2+ bilaterally.  There is no lymphadenopathy and no other skin lesions are noted.  The remainder of the physical examination is within normal limits.
Laboratory results are as follows:

Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This patient with end-stage renal disease (ESRD) likely has calciphylaxis (also known as calcific uremic arteriolopathy). Calciphylaxis is due to systemic arteriolar calcification leading to soft-tissue calcium deposition, ischemia, and necrosis. Although previously thought to be rare, calciphylaxis occurs most commonly in ESRD patients on hemodialysis or kidney transplant recipients. ESRD patients taking warfarin are at increased risk due to the drug inhibiting matrix proteins that prevent vascular calcification. Patients usually present with extremely painful subcutaneous nodules that can be violaceous (purpuric) and plaquelike. The nodules can progress to ischemic or necrotic ulcers, become infected, or lead to possible sepsis. In contrast to atherosclerosis, calciphylaxis usually presents with intact peripheral pulses. There should also be a high index of suspicion in ESRD patients with nonhealing ulcers. Laboratory studies may show high serum parathyroid hormone, phosphorus, calcium, and calcium-phosphorus product. Imaging may show soft-tissue calcium deposition but is not required for diagnosis. Skin biopsy usually shows arterial calcification/occlusion with subintimal fibrosis and can differentiate calciphylaxis from other disorders (eg, vasculitis, cryoglobulinemia, nephrogenic systemic fibrosis, warfarin necrosis). Calciphylaxis treatment and prevention options include local wound care, avoiding trauma, maintaining calcium-phosphorus product < 55 mg²/dL², increasing dialysis sessions, parathyroidectomy, intravenous sodium thiosulfate, decreasing immunosuppression in renal transplant patients, and possibly discontinuing warfarin. Because infection is the most common cause of the high mortality in calciphylaxis, surgical debridement is controversial as debridement exposes necrotic subcutaneous tissue to bacteria and increases sepsis risk. (Choice B) Dermatologic findings of cholesterol atheroembolism include livedo reticularis, gangrene, cyanosis, or skin ulcers, all of which are usually prominent peripherally. Embolization may be spontaneous or iatrogenic due to instrumentation. livedo reticularis (Choice C) Necrobiosis lipoidica presents with asymptomatic skin lesions that appear as indurated, yellowish plaques with central atrophy most often located on the shins. It is an inflammatory skin disorder that is most common in diabetics. (Choice D) Pyoderma gangrenosum is a rapidly progressing, painful, purulent ulcer with a violaceous and undermined border. More than 50% of patients have associated systemic disease (eg, inflammatory bowel disease, hematologic malignancies, arthritis). Given this patient's ESRD, calciphylaxis is more likely than pyoderma gangrenosum. Pyoderma gangrenosum (Choice E) Warfarin-induced skin necrosis usually occurs in the first few days of warfarin therapy (typically with large loading doses) and is due to the transient hypercoagulable state induced by reduced levels of protein C. This patient has been on warfarin for some time and thus is not at risk for warfarin-induced skin necrosis. Educational objective: Calciphylaxis is due to systemic arteriolar calcification leading to soft-tissue calcium deposition, ischemia, and necrosis. It occurs more commonly in end-stage renal disease patients on long-term hemodialysis with elevated calcium-phosphorus product. __________ References: Calcified subcutaneous arterioles with infarcts of the subcutis and skin ("calciphylaxis") in chronic renal failure. (http://www.ncbi.nlm.nih.gov/pubmed/10739777) Diagnosis and treatment of calciphylaxis. (http://www.ncbi.nlm.nih.gov/pubmed/22779099)

A 62-Year-Old Man Complains of a Black Lesion and Severe