Calciphylaxis, also known as calcific uremic arteriolopathy, is a microvascular occlusion syndrome thought to be due to diffuse deposition of insoluble calcium salts in cutaneous blood vessels with associated thrombosis. While the exact pathogenesis is unclear, characteristic pathologic findings include progressive medial calcification of cutaneous blood vessels and subsequent ischemic necrosis of the skin. The process may be triggered by chronic hypocalcemia from decreased intestinal absorption of calcium, leading to increased levels of parathyroid hormone (PTH) and subsequent recruitment of calcium and phosphate from bone. Hypercoagulable states are also thought to play a possible role. Penile calciphylaxis is estimated to occur in approximately 6% of patients with calciphylaxis.

Calciphylaxis is increasing in incidence and is most commonly associated with chronic renal failure, hemodialysis, and secondary hyperparathyroidism. According to one study, patients with penile calciphylaxis are more likely to have end-stage renal disease, hyperparathyroidism, and normal body mass index compared to nonpenile calciphylaxis patients. 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. Mortality from penile calciphylaxis is estimated to be 64%, with average survival of 2.5 months, with 50% of mortality occurring at 3 months and 62.5% at 6 months, according to one study.