Anti–Laminin‐332 Subepidermal Autoimmune Blistering Disease With Extensive Cutaneous Involvement: A Case Report

Subepidermal autoimmune blistering diseases are heterogeneous disorders caused by autoantibodies targeting dermal–epidermal junction proteins 1. We report a case of anti-laminin-332-associated subepidermal autoimmune blistering disease with extensive cutaneous involvement. An 87-year-old woman had a seven-month history of progressive blisters and erosions on her trunk, extremities, and oral and nasal mucosa. Despite topical corticosteroids, doxycycline, nicotinamide, and prednisolone (PSL) 15 mg/day, her disease progressed, requiring admission. On admission, lesions involved > 30% of the body surface area (BSA). Oral mucosal erosions were present, with a bullous pemphigoid disease area index (BPDAI) score of 56 (blister/erosion 56, urticaria/erythema 6, mucosal 20) (Figure 1a–c). Mucosal lesions were limited to the oral and nasal mucosa, without ocular, laryngeal, esophageal, or vulvar lesions. It was therefore classified as low-risk, and no scarring or functional impairment occurred. Laboratory testing was negative for anti-BP180 (NC16A and C-terminal), anti-BP230, anti-type VII collagen, and anti-Dsg1/3 antibodies. Contrast-enhanced computed tomography and upper endoscopy showed no malignancy. A lower leg biopsy showed subepidermal blistering with superficial perivascular lymphocytic infiltration (Figure 1d). Direct immunofluorescence demonstrated linear IgG and C3 deposition along the basement membrane zone (BMZ) (Figure 1e). Indirect immunofluorescence using 1 mol/L NaCl-split skin revealed IgG reactivity on the dermal side, with a titer of 1:320 (Figure 1f). Immunoblotting detected antibodies to laminin-332 β3/γ2 (Figure 1g), but not to p200 or type VII collagen. These findings supported a diagnosis of anti–laminin 332 subepidermal autoimmune blistering disease. PSL 35 mg/day (1.0 mg/kg) with minocycline and nicotinamide led to rapid improvement. After tapering, she was discharged on day 63 on PSL 20 mg/day (BPDAI 4/0/0) (Figure 1h). One month after discharge, she achieved complete resolution (BPDAI 0), but died 2 months post-discharge from choking-induced asphyxiation. Subepidermal autoimmune blistering diseases include pemphigoid diseases, characterized by linear autoantibody deposition along BMZ. Bullous pemphigoid (BP) mainly affects skin and targets BP180 and BP230, whereas mucous membrane pemphigoid (MMP) primarily affects mucosa and targets BP180 or laminin-332 2 Although laminin-332 pemphigoid is generally classified as MMP, we used the broader term for the diagnosis because of the widespread nature of the skin lesions. A PubMed search (“laminin332 pemphigoid,” 51 results, 2008–2026) found no reports of skin involvement > 30% BSA. Laminin-332, an epidermis-specific extracellular matrix protein composed of α3, β3, and γ2 subunits, has poorly defined subunit-specific phenotypes 3 This case showed severe, extensive cutaneous involvement with isolated anti–laminin-332 autoantibodies. Although epitope spreading is associated with disease severity 4 reactivity was detected only to laminin-332. IgA autoantibodies and full-length BP180 reactivity were not assessed; therefore, epitope spreading cannot be excluded. Notably, β3 subunit dysfunction is common in severe generalized junctional epidermolysis bullosa 5 which shares features with this case and may influence disease severity. This case highlights extensive cutaneous involvement in anti-laminin-332 subepidermal autoimmune blistering disease and the need for thorough immunopathological assessment. Despite extensive skin disease, limited mucosal involvement and a favorable therapeutic response indicated a low-risk phenotype. The discordance warrants further case accumulation. Laminin β3 subunit dysfunction may contribute to extensive skin involvement and merits further investigation. The authors have nothing to report. We obtained written informed consent from the patient to publish his clinical details. Yasuhiro Fujisawa is an editorial board member of the Journal of Dermatology. The data that support the findings of this study are available from the corresponding author upon reasonable request.