The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease

An appraisal of routine direct immunofluorescence in vulvar disorders

Sixty-four biopsies were obtained from patients with a variety of vulvar disorders for direct immunofluorescence study. Twelve of 24 vulvar biopsies from patients with lichen sclerosus demonstrated deposition of fibrin in the upper dermis, while 7 vulvar biopsies showed fibrin deposition at the dermal-epidermal junction. Blood vessel immunofluorescence was observed in several patients but was not a disease-specific finding. Patients with pemphigus and pemphigoid yielded characteristic reactions and served as positive controls. Direct immunofluorescence may be of value in assessing patients with vulvar disorders, and in particular lichen sclerosus.</jats:p

Erythema Multiforme: Direct Immunofluorescence Studies and Detection of Circulating Immune Complexes

The immunologic parameters of 23 patients with erythema multiforme who were seen by us (17 patients) or who had biopsies sent for immunofluorescence testing (6 cases) are reviewed. Biopsy specimens were sectioned and tested with labeled antisera to human IgG, IgA, 1gM, C3 and fibrin. Fourteen biopsies showed 1gM deposits in the superficial blood vessels, 13 demonstrated C3, 15 showed fibrin deposition, and 1 biopsy showed IgA deposition. All biopsies were negative for IgG. Eight serum samples tested by indirect IF were negative for skin-reactive antibodies. In addition to IF testing, serum samples from 20 patients were tested for circulating immune complexes with a Clq binding radioassay and a monoclonal rheumatoid factor (mRF) inhibition assay. Immune complexes were not detected by the Clq binding assay, but 6 of 20 serum samples demonstrated low to moderate levels of immune complexes by the mRF inhibition assay. By sucrose density gradient ultracentrifugation the mRF-reactive material in one serum sample sedimented in high molecular weight fractions and also demonstrated anticomplementary activity. These findings suggest that immune complex formation and subsequent deposition in the cutaneous microvasculature may play a role in the pathogenesis of erythema multiforme