CPC11 Immunobullous crossroads: navigating serological overlap between pemphigus and pemphigoid without paraneoplastic autoimmune multiorgan syndrome

Abstract

We present a rare case of immunobullous disease with serological features of pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP), in the absence of paraneoplastic autoimmune multiorgan syndrome (PAMS). A 50-year-old man presented with significant widespread oral erosions, lip ulceration and erosions of the scalp and skin. Clinically, the distribution and morphology were consistent with PV. Histological features from a cutaneous biopsy confirmed PV, and direct immunofluorescence (DIF) demonstrated intercellular deposition of IgG and C3 within the epidermis. Indirect immunofluorescence (IIF) revealed high-titre intercellular IgG antibodies on monkey oesophagus (> 1 : 1600) and normal human skin (1 : 400). Enzyme-linked immunosorbent assay (ELISA) detected anti-desmoglein (Dsg)1 antibodies (165 U mL−1) and anti-Dsg3 antibodies (157 U mL−1), consistent with PV. However, it also revealed anti-BP180 (56 U mL−1) and anti-BP230 antibodies (39 U mL−1), which are more typical of MMP. IIF for IgG on rat bladder (transitional epithelium) and ELISA for anti-collagen VII were both negative. Given the dual serological profile, PAMS was considered. Expert review from the St John’s Institute of Dermatology concluded this was unlikely, as IIF on transitional epithelium was negative and DIF showed pemphigus pattern only. Additionally, the patient was clinically well and a systems review was unremarkable. Computed tomography of the neck with contrast demonstrated reactive cervical lymph nodes. Two courses of rituximab were given under dermatology, 6 months apart (1000 mg × two doses per course, 2 weeks apart). The oral lesions completely resolved, while the skin and scalp improved significantly. Follow-up serology showed that the anti-Dsg1 antibodies had become negative (5 U mL−1), anti-Dsg3 reduced to 42 U mL−1 and there were significant reductions in anti-BP180 (24 U mL−1) and BP230 (20 U mL−1). This dual antibody profile without PAMS may be explained by epitope spreading, whereby the primary autoimmune response leads to tissue damage revealing new antigenic sites (epitopes), triggering a secondary autoimmune response. This case highlights the diagnostic complexity of immunobullous diseases and the need for integrated clinical, histological, immunological and multidisciplinary assessment.