Diagnosis: Calciphylaxis
Calciphylaxis is an uncommon disorder of vascular calcification and thrombosis resulting in skin necrosis.1 It most commonly occurs in people with end-stage renal disease (ESRD) on hemodialysis, but in nonuremic patients the most frequent cause is primary hyperparathyroidism.2,3 Similar vascular calcifications may be observed in milk alkali syndrome, rickets, collagen diseases, and hypervitaminosis D. Progression to necrosis in these cases is extremely rare.1 There are only a few documented cases of calciphylaxis associated with sarcoidosis, hypercalcemia, and non-ESRD.4
Female sex and diabetes appear to be risk factors.2 The presence of autoimmune disorders is a major feature in patients without ESRD.2,5 Although this patient did not have a previously diagnosed autoimmune disorder, an antinuclear antibody (ANA) test and lupus anticoagulant values were later found to be positive. In patients with autoimmune disorders, prednisone administration is associated with an increased risk of calciphylaxis.5 A hypercoagulable state can also underlie development of calciphylaxis. Our patient did have a mild protein C and S deficiency.
The prognosis of patients diagnosed with calciphylaxis is very poor. The mortality rate is reported to be as high as 60% to 80%.6
4 other possibilities comprise the differential diagnosis
Several conditions may present with erythema or necrosis similar to that of calciphylaxis (TABLE).
Warfarin-induced skin necrosis may produce hemorrhagic bullae and necrotic eschar, but generally presents within 3 to 10 days of initiating warfarin therapy.7 Severe dermatologic manifestations tend to affect the breasts, buttocks, and thighs.
Cutaneous anthrax causes painless necrotic lesions with black eschar, but is linked to bioterrorism or contact with infected animals. Constitutional symptoms such as fever, chills, and malaise are often present. Skin lesions are located primarily on the face, neck, and upper extremities.
Cholesterol embolization results from cholesterol crystals detaching and obstructing smaller arteries. Skin involvement includes livedo reticularis, petechiae, purpura, and ulcerations.
Vasculitis can affect all sizes of blood vessels. It can occur as a complication of connective tissue disorders, viral infections such as hepatitis B and C, or hypersensitivity reactions to medications such as penicillins and cephalosporins. Systemic symptoms are common, as is palpable purpura. Tissue biopsy is important for diagnosis and reveals blood vessel inflammation, not vessel wall calcification.
TABLE
Is it calciphylaxis or something else?1,3,7-9
| Condition | Characteristics |
|---|---|
| Warfarin-induced skin necrosis | Painful, erythematous, edematous lesions; rapidly progressive; petechiae, hemorrhagic bullae, then necrotic eschar |
| Cutaneous anthrax | Small painless, pruritic papules; advances to bullae; finally erodes to painless necrotic lesions with black eschar |
| Cholesterol embolization | Majority with livedo reticularis, cyanosis, or gangrene; smaller percentage with cutaneous ulceration, purpura, petechiae, or painful, firm erythematous nodules |
| Vasculitis | Palpable purpura; biopsy of most affected area is necessary for diagnosis |
| Calciphylaxis | Painful erythematous papules, plaques, nodules, or ulcerations in areas with high adiposity; may progress to necrosis |