LAUSR

Anti-laminin-c1 pemphigoid in an epitope spreading phenomenon, successfully treated with rituximab Dear Editor, Anti-laminin-c1 pemphigoid, also known as anti-p200 pemphigoid, is a rare subepidermal autoimmune blistering disorder with binding of autoantibodies (AAbs) to the dermal side on indirect immunofluorescence (IIF) microscopy. Other blistering disorder with binding of AAbs to the dermal side of salt-split skin includes epidermolysis bullosa acquisita (EBA), mucous membrane pemphigoid (MMP), cicatricial pemphigoid, and linear IgA bullous dermatosis (LABD). Dermal binders comprise about 15% of pemphigoid sera. Anti-p200/laminin-c1 pemphigoid was recently shown to be the most frequent pemphigoid disease with dermal binding AAbs, comprising 78.7% of 141 patients, and occurs more frequently in males and Asians. We report a 71-year-old Chinese man who was diagnosed with LABD in 2003 at the age 55. Histology was consistent on two skin biopsies which showed a subepidermal blister with neutrophils and occasional eosinophils, with linear IgA deposition at the dermo-epidermal junction (DEJ) on direct immunofluorescence (DIF). He was initially treated with dapsone but was switched to colchicine and prednisolone after he developed erythema multiforme. He had required prednisolone of up to 40 mg/day before he was lost to follow-up. Sixteen years later in 2019, he presented with urticarial plaques and blisters on his trunk (Fig. 1). Reassessment of disease with skin biopsy showed subepidermal vesicle containing neutrophils and rare eosinophils (Fig. 2). DIF showed positive reaction at the DEJ for IgG(2+) and C3(1+). IIF, BP180, BP230, and collagen VIIspecific ELISA were negative. Immunoblot testing detected circulating IgG4 autoantibodies against p200 antigen and immunodominant domain of laminin-c1. Autoimmune and malignancy screen were unyielding. As the condition was not controlled with prednisolone 30 mg/day along with doxycycline and nicotinamide, the patient was given two doses of IV rituximab 500 mg (day 1 and day 15) and had remained in clinical remission off therapy for 15 months (Fig. 3). The transition from LABD to anti-laminin-c1 pemphigoid in this case suggests epitope spreading (ES) phenomenon, which has been increasingly described. ES involves two major mechanisms; an “independent” mechanism where tissue inflammation induces T cells to recognize cryptic epitopes and activate B cells, and a “dependent” mechanism that relies on activation of T and B cells. Although ES preferentially occurs at an early stage of the disease, it is possible to occur in longstanding disease which has not achieved remission, hypothesized to be due to insufficient immunosuppressive treatment with ongoing serological activity. To date, there is no gold standard therapeutic approach for anti-laminin-c1 pemphigoid. In a recent systematic review,