Case Presentation: A 52-year-old gentleman with past medical history of lupus nephritis, non-ST-elevation myocardial infarction, venous thromboembolism (on anticoagulation), and peripheral vascular disease requiring arterial bypass grafting presented to the hospital with left toe pain of two days’ duration and fever with chills. Physical examination demonstrated gangrenous changes of the left second toe as well as nontender, nonblanching erythematous macules and patches along the plantar surface of the left foot. Laboratory evaluation revealed prolonged partial thromboplastin time and elevated C-reactive protein without leukocytosis. Hepatitis serologies as well as human immunodeficiency virus and syphilis testing were negative, as were final blood cultures. Hypercoagulability panel studies, including antiphospholipid antibody titers and lupus anticoagulant, were within normal limits. On imaging, he was found to have a patent bypass graft but was noted to have a 2.5-cm vegetation on the tricuspid valve, which was confirmed on transesophageal echocardiogram. He had no atrial septal defect. Intravenous antibiotics were initiated for four weeks without resolution of the vegetation, and the patient subsequently underwent surgical tricuspid valve replacement and gangrenous toe amputation. Intraoperative pathology was notable for sterile tricuspid valve vegetation and toes with arterial thrombus but no organisms on Gram stain nor final culture.
Discussion: Antiphospholipid syndrome (APS) is a hypercoagulable state which often occurs secondary to systemic lupus erythematosus (SLE). The diagnostic criteria for APS require the presence of at least one clinical and one laboratory criterion. Clinical criteria include vascular thrombosis or pregnancy morbidity and laboratory criteria include the presence of lupus anticoagulant, anti-cardiolipin antibody, or anti-β2-glycoprotein antibody. APS also predisposes to the development of sterile thrombotic Libman-Sacks endocarditis, which most commonly affects the mitral valve. Seronegative APS (SN-APS) is diagnosed when clinical criteria are met but serologic testing is persistently negative. Testing must be performed outside the context of acute thrombosis and treatment with anticoagulation, as these conditions can cause a transient loss or consumption of antiphospholipid antibodies. This patient’s case was unusual for several reasons. The vegetation from his Libman-Sacks endocarditis was located on the tricuspid valve, a much rarer presentation than involvement of the mitral valve. Moreover, his toe ischemia was confirmed to be related to arterial thrombus rather than embolism from vegetation or ischemia from bypass graft stenosis. Given his extensive history of hypercoagulability in the setting of known SLE, thrombosis secondary to SN-APS was the unifying diagnosis for his clinical presentation.
Conclusions: APS is a hypercoagulable state associated with SLE. It confers an increased risk of developing Libman-Sacks endocarditis, most commonly affecting the mitral valve, as well as peripheral thrombotic events which may mimic other clinical entities such as limb ischemia or embolism. Seronegative APS is a clinically important diagnosis to consider in patients with clinical manifestations of the syndrome but persistently negative serology.