Rapidly Progressive Nonuremic Calciphylaxis in the Setting of Warfarin

Abstract

PRESENTATIONA 63-year-old African American woman presented with multiple painful, violaceous nodules on her lower extremities for the preceding 3 weeks. Her past medical history was notable for mechanical aortic valve replacement 7 years prior, asthma, type 2 diabetes mellitus, congestive heart failure, hyperlipidemia, hypertension, and obesity. Her home medications included warfarin, longstanding low-dose prednisone for severe asthma, calcium, atorvastatin, glipizide, metformin, insulin, ipratropium-albuterol, montelukast, omalizumab, losartan, metoprolol, torsemide, and omeprazole.On physical examination, a 5 Â 6-mm firm, violaceous, tender papule was present on the left superior thigh. A 2 Â 2.5-cm hyperpigmented nodule was present on the left inferior thigh. A 5 Â 3.5-cm painful violaceous plaque with central retiform hypopigmentation was present on the left medial calf (Figure 1). Finally, a firm, tender plaque was present on the right posterior calf. ASSESSMENTA punch biopsy from the left calf showed predominantly concentric calcification of subcutaneous vessels approximately 200-250 mm in diameter ( Figure 2). There was no evidence of other entities in the clinical differential diagnosis including vasculitis, polyarteritis nodosa, warfarin necrosis, necrobiosis lipoidica, or a panniculitis such as erythema nodosum.Serum calcium (9.4 mg/dL), phosphorus (4.0 mg/dL), blood urea nitrogen (27 mg/dL), creatinine (1.3 mg/dL), albumin (3.8 g/dL), 25-hydroxyvitamin D (44 ng/mL), and parathyroid hormone (62 pg/mL) were all within normal limits. The international normalized ratio and prothrombin time were appropriately therapeutic. The patient also was up to date with malignancy screening.On follow-up, the biopsy site demonstrated a pathergic response with poor wound healing and evolution into a Figure 1 Two views of the 5 Â 3.5-cm painful violaceous plaque with central retiform hypopigmentation on the left medial calf.

A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the Thigh

“…Appropriate care aims to address the underlying process, metabolic derangements, risk factors, wound healing, and pain management, and, given the complexity of needs, is best served by multidisciplinary teams [ 1 ]. Nonuremic calciphylaxis treatment approaches are modeled after therapies for calciphylaxis in patients with renal disease [ 33 ] with intravenous sodium thiosulfate (STS) treatment as the most common first-line therapy for both types of calciphylaxis [ 1 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. STS was originally believed to reverse the disease via calcium-chelating properties [ 43 ], but its mechanism of action is still not precisely understood.…”

“…Case reports suggest a benefit from treating abnormalities of calcium and phosphorus [ 55 , 56 , 57 , 58 ] and elevated parathyroid hormone [ 49 , 59 , 60 ]. If possible, all medications that may contribute to calciphylaxis or decrease wound healing should be stopped, and known aggravating conditions should be addressed [ 33 , 61 ]. Aggressive wound care and pain control are critical.…”

Direct oral anticoagulant medications in calciphylaxis

“…In recent studies, warfarin was not effective in preventing calciphylaxis . Warfarin has been associated with calciphylaxis in a number of retrospective studies and is implicated in the pathogenesis of skin necrosis, mural calcification, and paradoxically, vessel occlusion . Warfarin therapy is thought to promote vascular intramural calcification through interruption of matrix Gla protein metabolism .…”

“…7,11 Warfarin has been associated with calciphylaxis in a number of retrospective studies and is implicated in the pathogenesis of skin necrosis, mural calcification, and paradoxically, vessel occlusion. [12][13][14][15] Warfarin therapy is thought to promote vascular intramural calcification through interruption of matrix Gla protein metabolism. 16 Matrix Gla protein, a potent inhibitor of vascular calcification, requires vitamin K-dependent carboxylation for activity.…”

Ecto-5' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients – Data from the German Calciphylaxis Registry

“…Although chronic kidney disease is the most important clinical risk factor, followed by malignancies, CUA does also occur in association with normal kidney function and liver cirrhosis. [ 7 ] Other risk factors are female sex[ 1 ], obesity[ 1 ], thrombophilia syndromes such as Protein S or C deficiency[ 8 ], treatment with vitamin K antagonists[ 9 ] and/or corticosteroids and low albumin levels. [ 1 ]…”