Concurrence of bullous pemphigoid and herpetiform pemphigus with IgG antibodies to desmogleins 1/3 and desmocollins 1–3

MADAM, Autoantibodies in pemphigus preferentially target desmoglein 1 (Dsg1) and Dsg3, and rarely desmocollins 1–3 (Dsc1–3). Pemphigus herpetiformis (PH) is a subtype of pemphigus and is characterized by pruritic annular erythemas with vesicles in the periphery, rarity of mucosal involvement and histopathologically determined eosinophilic spongiosis. Recently, it was suggested that immunoglobulin G (IgG) antiDsc3 autoantibodies caused skin lesion in a case of pemphigus vulgaris (PV). In this study, we report the first case of concurrent bullous pemphigoid (BP) and PH with IgG antibodies to both Dsgs and Dscs. An 83-year-old woman presented with a 3-month history of painful oral erosions and ulcers. The patient’s medical history was unremarkable. Physical examination revealed multiple blisters, erosions and ulcers on the tongue, soft palate and buccal mucosa (Fig. 1a). Ten days later, pruritic urticarial annular erythemas developed on the abdomen and lower extremities, some of which showed small vesicles at the periphery (Fig. 1b). Laboratory examination revealed slight hypereosinophilia. A biopsy specimen from the right lower extremity revealed eosinophilic spongiosis and many intraepidermal vesicles without apparent acantholysis in the epidermis (Fig. 1c), and also a few subepidermal vesicles with many eosinophilic infiltrates (Fig. 1d). Direct immunofluorescence showed IgG deposition on the cell surfaces of keratinocytes in the whole epidermis (Fig. 2a), and C3 deposition to the epidermal basement membrane zone (BMZ) and cell surfaces in the lower epidermis (Fig. 2b). Indirect immunofluorescence of normal human skin sections revealed IgG antikeratinocyte cell surface antibodies at a titre of 1:10. Indirect immunofluorescence of monkey oesophagus sections also revealed anticell surface antibodies (Fig. 2c). Indirect immunofluorescence of 1 mol L NaCl split skin sections showed negative results. Enzyme-linked immunosorbent assays (ELISAs) revealed elevated indices of anti-BP180 antibodies (97, normal < 20), anti-Dsg1 antibodies (47, normal < 20) and anti-Dsg3 antibodies (96, normal < 20). AntiBP230 antibodies were not detected by ELISA. The patient’s IgG reacted with Dsc1–3 expressed on the cell surfaces of COS-7 cells, which were transfected with cDNAs of human Dsc1–3 (Fig. 2d–f). By immunoblotting, IgG autoantibodies showed no positive reactivity in either normal human epidermal and dermal extracts, HaCaT cell culture supernatant or purified human laminin 332, while they reacted with a recombinant protein of BP180 NC16a domain (Fig. 2g), but not of BP180 C-terminal domain. Our new IgG ELISA using eukaryotic recombinant proteins of human Dsc1–3 (Ishii et al., manuscript in preparation) revealed a high titre of anti-Dsc2 antibodies and slightly elevated anti-Dsc3 antibodies, but the optical density value of anti-Dsc1 antibodies was lower than the cut-off value. Based on these findings, we diagnosed this case as concurrent BP with anti-BP180 antibodies and PH with IgG antibodies to Dsg1 ⁄3 and Dsc1–3. Systemic corticosteroids, 20 mg daily, improved all lesions, and the ELISA indices of BP180, Dsg1 and Dsg3 decreased to normal levels along with an improvement in the disease. In our case, a diagnosis of PH was suggested by all clinical, histopathological and immunofluorescence findings. While our previous studies using Dsg1 and Dsg3 ELISA showed that the target antigens of PH were mainly Dsg1 and occasionally Dsg3, anti-Dsc antibodies were also detected in some cases of