Epitope spreading in pemphigus patients from Sao Paulo, Brazil: A 10-year follow-up

Abstract

Background: Pemphigus is a rare autoimmune blistering dermatosis. The shift from a disease to another is known as ‘‘epitope spreading’’ (ES). A primary inflammatory/autoimmune process releases ‘‘hidden’’ epitopes, and evokes a secondary reaction to antigens, distinct from and none cross-reactive with the target epitope. ES may be intra- or intermolecular. Objectives: The aim of the present study is to analyze the occurrence of ES within a 10-year interval in pemphigus patients followed-up at the Department of Dermatology, University of São Paulo, Brazil. Methods: Thestudy wascarried out in 351 pemphigus patients from January 2002 to January 2012. A careful search for clinical and laboratory changes suggestive of transition to a secondary bullous disease was performed, including clinical evaluation by at least 2 dermatologists. Laboratory profile (histopathology, direct-DIF and indirect-IIF immunofluorescence, and ELISA) was requested when suspicious skin lesions were detected. Results: Eight out of 351 pemphigus patients (153 pemphigus foliaceus-PF and 198 pemphigus vulgaris-PV) presented clinical transition: 7 from PV to PF (group 1) and 1 from PF to epidermolysis bullosa acquisita (EBA) (group 2). In group 1, median age at PVonset was 54 years and median interval of the disease shift was 3 years. Of the 7 patients with clinical PF, 4 showed change of pattern from suprabasilar cleavage to subcorneal acantholysis, 2 had cleavage within the middle epidermal layer, and 1 sustained the suprabasilar acantholysis. All patients showed intercellular IgG and C3 deposits during PVand PF diagnosis by DIF. IIF titers varied from 1:160 to 1:5120, and were positive during ES. ELISA index for Dsg1 varied from 1 to 319, and for Dsg3 from 0 to 290. Dsg1/Dsg3 indexes corresponded to the clinical PV-PF changes. In group 2, one patient switched from PF to EBA; onset of PF occurred at the age of 7, and ES to EBA 25 years later. Laboratory evaluation showed subepidermal cleavage with neutrophils, IgG intercellular staining in the epidermis and IgM, IgA, IgG and C3 deposits at BMZ by DIF, IgG deposits by indirect salt-split, recognition of collagen VII by immunoblotting, and positive ELISA for Dsg1. Conclusions: Intermolecular ES occurred in 2.2% of pemphigus patients. Futures studies will be necessary to elucidate the pathogenesis of this event and its significance in pemphigus progression.