A case of antilaminin 332 mucous membrane pemphigoid showing a blister on the bulbar conjunctiva and a unique epitope on the α3 subunit

MADAM, A 57-year-old Japanese woman developed severe erosive lesions on the oral mucosae including buccal mucosae, gingivae, hard palate and soft palate, as well as bleeding and crust formation on the nasal mucosae in August 2007. She also showed bloody blisters and crusted erosions 2–4 cm in size scattered on the trunk and extremities. Oral minocycline 200 mg daily was given. However, the erosive lesions on the oral and nasal mucosae continued to develop and a clear blister 5 · 8 mm in size appeared on the left bulbar conjunctiva (Fig. 1). Therefore, minocycline was replaced by oral prednisolone 40 mg daily, but the mucosal and skin lesions still continued. Then, a combination therapy of oral prednisolone 40 mg daily and dapsone 75 mg daily was initiated. The oral and nasal mucosal lesions healed without any scarring. The blister on the bulbar conjunctiva disappeared without any scarring or sight disturbance. The skin lesions also healed leaving slight scarring. Then, the dose of prednisolone was tapered gradually without lowering the dose of dapsone, but no mucosal or skin lesions recurred. In March 2008, the patient was free from any mucosal or skin lesions on a combination therapy of prednisolone 5 mg daily and dapsone 75 mg daily. Histopathology of a skin biopsy specimen from the back showed a subepidermal bulla with massive neutrophil infiltration and scattered eosinophils. Direct immunofluorescence did not show positive results, probably because of damage to the basement membrane zone of the biopsy specimen. Indirect immunofluorescence using normal human skin detected IgG, but not IgA, antibasement membrane zone antibodies at a titre of 1 : 40, which reacted exclusively with the dermal side of 1 mol L NaCl-split skin. Immunoblot analysis using purified human laminin 332 as a substrate was performed as described previously. In this study, IgG antibodies of a representative control patient with antilaminin 332 mucous membrane pemphigoid (MMP) reacted with both the 165-kDa form and the 145-kDa form of the a3 subunit, the 140-kDa b3 subunit and the 105-kDa c2 subunit of laminin 332 (Fig. 2, lane 1). IgG antibodies of the present case reacted clearly and exclusively with the 165-kDa form of the a3 subunit (Fig. 2, lane 2). From these results, the diagnosis of antilaminin 332 MMP was confirmed in this patient. Cicatricial pemphigoid shows blisters and erosive lesions mainly on the mucous membranes, such as the oral, ocular, nasal, laryngeal, pharyngeal and genital mucosae, and skin lesions appear occasionally. These lesions heal with scar formation. However, because this subset of autoimmune bullous disease mainly shows mucosal lesions, and oral mucosal lesions usually heal without scarring, the term ‘MMP’ is now commonly used, following a consensus meeting. The members of the consensus meeting agreed that dapsone or tetracycline (or minocycline) may be effective when the lesions are localized to the oral mucosae. However, stronger therapies have to be selected when progressive lesions are seen on the ocular or laryngeal mucosae, which may lead to blindness or dyspnoea, respectively. MMP is highly heterogeneous, but there are at least three major subtypes: anti-BP180 MMP, antilaminin 332 MMP and ocular MMP. About 80% of cases of MMP are anti-BP180