Activation of coagulation in bullous pemphigoid and other eosinophil-related inflammatory skin diseases

Abstract

Summary Bullous pemphigoid (BP) is a skin disease caused by autoantibodies to hemidesmosomal proteins BP180 and BP230, with eosinophils participating in blister formation. Tissue factor (TF), the initiator of coagulation, is embodied within the eosinophil granules and exposed upon activation. We evaluated the coagulation activation in patients with BP (63), chronic urticaria (CU; 20), atopic dermatitis (AD; 14), cutaneous drug reactions (CDRs; six), psoriasis (20), dermatitis herpetiformis (DH; four) and primary cutaneous T cell lymphoma (CTCL; five), and in 40 healthy controls. Prothrombin fragment F1+2 and d-dimer (coagulation markers) were measured by enzyme-linked immunosorbent assay (ELISA) in all plasma samples and BP blister fluid. Skin TF expression was evaluated immunohistochemically in the patients and 20 controls. F1+2 and d-dimer levels were higher in BP plasma than in control plasma (P = 0·0001 for both), and dramatically high in blister fluid; both correlated positively with disease severity, esinophil counts and anti-BP180 antibodies (P = 0·006–0·0001). Plasma F1+2 and d-dimer levels were higher in the CU, AD and CDR patients than in controls (P = 0·0001 for all), but normal in the psoriasis, DH and CTCL patients. Skin TF was expressed in the BP (P = 0·0001), CU (P = 0·0001), AD (P = 0·001) and CDR patients (P = 0·01), but not in the psoriasis, DH or CTCL patients. Co-localization confocal microscopy studies confirmed eosinophils as the source of TF in 10 BP patients. The coagulation cascade is activated in BP and other eosinophil-mediated skin disorders, but not in non-eosinophil driven conditions. This hypercoagulability may contribute to inflammation, tissue damage and, possibly, thrombotic risk.