These findings on their own are nonspecific and present a diagnostic challenge, considering the vast differential diagnosis. Evaluation is required for potential macrovascular and microvascular disease, including non-inflammatory conditions, such as thromboembolic disease, hypercoagulable states, TAO, toxin exposure and freeze injury, as well as inflammatory causes, such as infection and vasculitis.
Our patient met the classification criteria for APS as defined by Miyakis et al., including clinical episodes of thrombosis in conjunction with lupus anticoagulant on two occasions 12 weeks apart, and histopathology to exclude vasculitis.2 Imaging findings could not unequivocally confirm thrombosis because CT angiogram (CTA) with runoff did not reach beyond the patient’s ankles.
Differential Diagnosis
In our patient, who had an active smoking history and in whom macrovascular disease had been ruled out by appropriate imaging studies, TAO was a strong possibility. TAO is a diagnosis of exclusion, determined after elimination of other vascular occlusive diseases. Because cessation of smoking is the only way to prevent its progression, the improvement seen in our patient following treatment while continuing to smoke argued against this diagnosis. In addition, he had none of the classic signs of TAO in the CTA, such as a corkscrew collateral appearance of the small and medium vessels.
The hematologic evaluation includes assessment for primary (i.e., inherited) and secondary (i.e., acquired) causes of hypercoagulable states, such as Factor V Leiden and APS. In this case, the hypercoagulation panel revealed a positive lupus anticoagulant, as well as IgM cardiolipin and beta2-glycoprotein1 ABS. Twelve weeks later, the lupus anticoagulant remained positive, but the other ABS results were negative, perhaps due to treatment with glucocorticoids and hydroxychloroquine.
aPL ABS can be identified in as many as 50% of patients with systemic lupus erythematosus (SLE) and are present in 5–20% of patients with other connective tissue diseases, such as rheumatoid arthritis, dermatomyositis, Sjögren’s disease and systemic sclerosis.3 Our patient had transient joint symptoms and fever at the start of his illness, acute phase reactants were elevated, and his ANA was weakly positive. In the context of positive antiphospholipid ABS, this raised the possibility of SLE. Although SLE could not be entirely ruled out, he had no additional clinical or laboratory criteria for this condition.
Small to medium vessel vasculitis was a concern due to the prodromal fever and polyarthralgias prior to digital gangrene. However, he lacked other features of systemic vasculitis, his ANCA was negative, and vasculitis was not seen on pathology. Nevertheless, because vasculitis and lupus could not be fully ruled out, he was treated with glucocorticoids for several weeks.
