Lymphocytic thrombophilic arteritis: A distinct inflammatory type I interferon and C5b-9 mediated subcutaneous endovasculitis.

Abstract

Lymphocytic thrombophilic arteritis is a recently recognized subcuticular larger vessel vasculitis characterized by striking vascular luminal thrombosis. The clinical features, histopathology and phenotypic profile of ten patients with lymphocytic thrombophilic arteritis were explored in an attempt to better define the entity from a clinical and pathophysiologic perspective. The patients were all female (mean age of 43) presenting with generally asymptomatic lower and upper extremity hyperpigmented macules. A consistent picture diagnostic of a connective tissue disease syndrome was not seen. The disease was not progressive although it was typically persistent. The morphology was characterized by a temporally heterogeneous subcutaneous arteritis targeting the endothelium and intima with changes ranging from incipient intimal expansion by hyaluronic acid to concentric intimal fibrin deposition to one of an end stage acellular intraluminal obliterative fibrous arteriopathy. The infiltrate was predominated by lymphocytes and histiocytes. The intimal elastic lamina was intact in most cases. All tested cases showed intimal and endothelial C5b-9 deposition, an upregulated type I interferon microenvironment and marked upregulation of the inducible interferon gamma 16 protein. Lymphocytic thrombophilic arteritis is a unique form of C5b-9 mediated arteritic endotheliopathy where the brunt of the changes involves the endothelium and intima and that is morphologically distinct from the transmural arteritis of benign cutaneous polyarteritis nodosa.