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See also in: Cellulitis DDx
Other Resources UpToDate PubMed


See also in: Cellulitis DDx
Contributors: Erin X. Wei MD, Amy E. Blum MD, Philip I. Song MD, Belinda Tan MD, PhD, Susan Burgin MD
Other Resources UpToDate PubMed


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.

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

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • 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 antibody syndrome
  • 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 panniculitis 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.
  • Primary 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 hypertensive leg ulcer
  • Ecthyma gangrenosum – Begins as a painless macule or papule and is associated with gram-negative sepsis.
  • Arterial calcification due to deficiency of CD73 (ACDC)

Best Tests

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Management Pearls

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Reviewed:06/06/2022
Last Updated:04/25/2023
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See also in: Cellulitis DDx
A medical illustration showing key findings of Calciphylaxis : Buttocks, Painful skin lesions, Eschars, Arms, Legs, Skin ulcers, Retiform purpura, warfarin
Clinical image of Calciphylaxis - imageId=153991. Click to open in gallery.  caption: 'Circumferential, erythematous plaque on the lower leg.'
Circumferential, erythematous plaque on the lower leg.
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