Widespread Cutaneous Necrosis and Antiphospholipid Antibody Syndrome

Abstract

Sir: Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of arterial/venous thrombosis and thrombocytopenia. Specific hematologic indicators of antiphospholipid antibody syndrome include elevated titers of lupus anticoagulant and/or anticardiolipin antibodies. Elevated levels of these enzymes detected on two separate occasions at least 12 weeks apart are necessary for the diagnosis.1–3 Widespread cutaneous necrosis secondary to thrombosis of dermal microvasculature is an exceedingly rare manifestation of antiphospholipid antibody syndrome and has been reported in only 23 cases worldwide to date.3 We present a patient with recurrent widespread cutaneous necrosis secondary to antiphospholipid antibody syndrome. A 40-year-old woman presented with a painful, swollen, discolored left breast with the absence of trauma or other inciting events. The patient had a significant history of coronary artery disease, myocardial infarction, deep vein thrombosis, pulmonary embolism, and arterial thrombosis resulting in a below-knee amputation. She had been taking warfarin for 8 years with variable compliance. She was started on intravenous heparin. Demarcation of the breast was complete by hospital day 3 (Fig. 1).Fig. 1: Cutaneous necrosis and dense eschar of the left breast.A left mastectomy was performed, and the breast reconstructed with a split-thickness skin graft. The patient did well and was discharged on therapeutic dabigatran (Pradaxa). A diagnosis of warfarin-induced cutaneous necrosis was made based on wound appearance, wound location, warfarin noncompliance, histological analysis, and timing of presentation. Three weeks after discharge she presented with a painful discolored upper back. She was started on systemic lepirudin therapy and repletion of protein C (Fig. 2).Fig. 2: Cutaneous manifestation of widespread cutaneous necrosis caused by antiphospholipid antibody syndrome.Hypercoagulation panels revealed a positive result for heparin-induced thrombocytopenia (anti-heparin-PF4 enzyme-linked immunosorbent assay, immunoglobulin G 0.809 O.D.). Additional serum testing was consistent with antiphospholipid antibody syndrome (diluted viper venom screening test confirmed with elevated anticardiolipin immunoglobulins G, M, and A). Serial operative débridement of the full-thickness necrosis was performed with wound vacuum-assisted closure stabilization. The patient remained fully anticoagulated on lepirudin but sustained a cardiorespiratory arrest and passed away. Full-thickness cutaneous necrosis secondary to microvascular thrombosis is a rare clinical manifestation of antiphospholipid antibody syndrome, with only 23 cases reported worldwide. This manifestation is more commonly associated with warfarin-induced skin necrosis, but antiphospholipid antibody syndrome should be suspected in patients with recurrent skin necrosis despite warfarin cessation and alternative anticoagulation. The presence of elevated titers of lupus anticoagulant and/or systemic lupus erythematosus is diagnostic. No specific mechanism of thrombosis caused by antiphospholipid antibody syndrome has been determined; however, it is hypothesized that the antibodies have a direct effect on coagulation. Antiphospholipid antibodies have been shown to directly cause endothelial injury and activation, modulation of protein C and S pathways, activation of platelets, inhibition of the phospholipid placental anticoagulant protein-1, interference with antithrombin III, and/or fibrinolytic impairment.1,3,4 Management of patients with widespread cutaneous necrosis and antiphospholipid antibody syndrome involves local treatment of cutaneous infarction and systemic anticoagulation for long-term minimization of thrombotic recurrence. Initial administration of high-dose systemic steroids may be considered to reduce concurrent vasculitis. Plasmaphoresis has also been reported to successfully remove present aPL.1–3 Treatment for widespread cutaneous necrosis is conservative and involves local antiseptic therapy, including serial débridement of the necrotic eschar. The resulting ulceration is then either healed by secondary intention or corrected surgically by skin flap or grafting techniques.1 DISCLOSURE The authors have no financial interest to declare in relation to the content of this article. J. Walter Dutton, M.D. West Virginia University School of Medicine Morgantown, W.Va. R. Wesley Vosburg, M.D. West Penn Allegheny Health System Pittsburgh, Pa. W. Thomas McClellan, M.D. Plastic and Reconstructive Surgery West Virginia University Morgantown, W.Va.