Severe digital necrosis as the clinical onset of antiphospholipid syndrome

A 70-year-old man, non-smoker, presented with bilateral digital necrosis, which had developed over the prior month, related to an aggressive Raynaud’s phenomenon of 2 months of evolution (Fig. 1a). The patient had no familial or personal history of previous thrombosis events, heart valve disease, livedo reticularis, nephropathy, thrombocytopenia or neurological manifestations. Upon examination, pulses were present, capillaroscopy was normal, and there was no sclerodactyly or skin sclerosis. Treatment with nifedipine, endovenous alprostidil, bosentan and analgesics was initiated with poor results. A complete blood count and biochemical tests, urinalysis, immunoglobulin, serum protein electrophoresis, cryoglobulin, serology for hepatitis B and C, antinuclear and antineutrophil cytoplasmic antibodies were either normal (the platelet count was 160,000 per mm³) or negative. 18F-FDG PET-CT did not show tumours or large vessel vasculitis. A biopsy of the ischemic areas of the hands only indicated epidermic necrosis. A thrombophilia workup showed the patient to be heterozygous for the C677T polymorphism of the MTHFR gene and for factor XII and test positively for IgG anti-β2-glycoprotein-1 antibodies in two separate determinations made 12 weeks apart (93.80 and 205 U/mL, respectively). Even though the genetic thrombophilia may have contributed to a procoagulant state, the severity of the lesions led us to consider the diagnosis of antiphospholipid syndrome (APS). Treatment with enoxaparin (60 mg/12 h) was started, and progressive improvements in the pain and reperfusion of the base of the fingers were observed (Fig. 1b). The APS is a prothrombotic disorder characterized by the predisposition to venous or arterial thrombosis, and with an increased morbidity of pregnancy due to the presence of autoantibodies directed against certain types of phospholipids. Less frequently, APS should also be suspected when a patient presents with refractory headaches, unexplained nephropathy or heart valve disease, dementia or cognitive disorders, seizures, livedo reticularis or thrombocytopenia. Currently, to establish the diagnosis of APS, both a characteristic clinical presentation and detection of APS autoantibodies are necessary [1]. Concomitant thrombosis and necrosis of multiple fingers are unusual but previously reported manifestations of APS [2] that should be included in the differential diagnosis of digital necrosis along with systemic sclerosis, gammopathies, paraneoplastic syndromes, Buerger’s disease, cryoglobulinemia, systemic vasculitis, cholesterol crystal embolism and thrombophilias (normally associated with other procoagulant conditions) [3].

Fig. 1

a Bilateral digital necrosis at the time of presentation. b Improvement of the lesions after treatment with anticoagulants during 9 months