Calciphylaxis is increasing in incidence and is most commonly associated with chronic renal failure, hemodialysis, and secondary hyperparathyroidism. There are also many cases of "nonuremic" or "nontraditional" calciphylaxis, which can occur in the setting of liver disease, diabetes, warfarin use, use of calcium-based phosphate binders, systemic corticosteroid use, solid organ malignancies, systemic lupus erythematosus, and Crohn disease. Other risk factors include female sex, obesity, Northern European descent, and hypoalbuminemia.
Notably, warfarin-associated nonuremic calciphylaxis tends to occur about 2.5 years after warfarin initiation on the lower extremities, does not have associated calcium abnormalities, and appears to have a more favorable prognosis than calciphylaxis associated with renal failure states.
Early lesions are extremely painful, violaceous, retiform patches and plaques, classically on fat-bearing areas such as the thighs, buttocks, and abdomen. This is followed by necrosis, ulcers, eschar formation, and possibly gangrene. Induration of the surrounding tissues may be present. Lesions have been reported to be triggered by local trauma, including from insulin or heparin injections, or a skin biopsy. Most lesions develop over the course of weeks to months, while some may progress more rapidly.
Mortality from calciphylaxis is high (60%-87%) and is largely secondary to sepsis from large, nonhealing ulcers.
E83.59 – Other disorders of calcium metabolism
237900002 – Calciphylaxis
- Cholesterol emboli
- Cryoglobulinemia – Favors extremities and acral areas where body temperatures are lower.
- Cellulitis – No association with chronic renal failure and does not have the presence of tissue necrosis and ulceration.
- Antiphospholipid syndrome
- Coumadin (warfarin) necrosis – Typically occurs 3-10 days after warfarin initiation and is characterized by hemorrhagic bullae with retiform purpura, typically on the breasts, thighs, and buttocks, which is distinct from warfarin-associated calciphylaxis, which occurs months to years after warfarin initiation.
- Heparin-induced thrombocytopenia
- Vasculitis – Favors the lower extremities.
- Disseminated intravascular coagulation
- Nephrogenic systemic fibrosis
- Lupus profundus lesions may have calcification on x-ray.
- Dermatomyositis and CREST syndrome may have associated calcification.
- Myxoma emboli (atrial myxoma)
- Pancreatic panniculitis
- Ischemic atherosclerotic vascular disease (ischemic ulcer) – Look for decreased pulses and cold extremities.
- Pyoderma gangrenosum
- Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
- Cocaine levamisole toxicity – Look for purpura on the helix of the ear.
- Hyperoxaluria – Oxalate deposition may cause similar deposition in vessels and is also associated with renal failure.
- Stasis ulcer
- Calcinosis cutis
- Livedoid vasculopathy
- Purpura fulminans
- Martorell ulcer
- Ecthyma gangrenosum – Begins as a painless macule or papule and is associated with gram-negative sepsis.