DP14 Clinicopathological correlation in seronegative antiphospholipid syndrome presenting with cutaneous thrombotic microangiopathy

Abstract

A 33-year-old man presented acutely with a 4-year history of Raynaud symptoms and intermittent purple discoloration extending proximally from the feet to the lower torso. He reported worsening painful nodules on his legs evolving into blisters and necrotic ulcers. He took no medications or recreational drugs. He had no personal or family history of thrombosis. He smoked 15 cigarettes a day. Clinical examination showed multiple necrotic ulcers on his lower legs with a livedoid rash over his extremities, back and flanks. Histology demonstrated focal epidermal and underlying dermal necrosis. Superficial and deep dermal vessels showed reactive angioendotheliomatosis with erythrocyte extravasation and occasional homogeneous intraluminal pink thrombi. An active chronic inflammatory infiltrate with panniculitis and fat necrosis was present, consistent with cutaneous thrombotic microangiopathy within an antiphospholipid syndrome (APS) spectrum disorder. Thrombophilia, autoimmune and infective screenings were unremarkable, apart from a single transient lupus anticoagulant positivity on dilute Russell’s viper venom time testing using the DOAC-Stop method, reducing anticoagulant interference. Despite absent persistent antiphospholipid antibody positivity, clinicopathological findings supported an APS spectrum disorder. Over time, he was treated with high-dose oral prednisolone, pentoxifylline, nifedipine, mycophenolate mofetil, intravenous methylprednisolone, iloprost, morphine, pregabalin, enoxaparin, aspirin and low-dose apixaban, with fluctuating clinical improvement. He deteriorated when off enoxaparin and improved each time anticoagulation was increased. New ulcers, increasing pain and toe infarction prompted an increase in dose of apixaban, with subsequent stabilization on warfarin. There was sustained clinical improvement, accompanied by eventual complete resolution of the ulceration and pain, allowing discontinuation of all other treatments. Seronegative APS is a diagnosis of exclusion, reliant on clinicopathological correlation. Cutaneous thrombotic microangiopathy, clinical deterioration on anticoagulant withdrawal, and exclusion of alternative prothrombotic causes supported the diagnosis and guided management. APS spectrum disease should be considered in patients with ulceration and thrombotic vasculopathy despite negative serology.