Acta Dermato-Venereologica 99-12CompleteContent | Page 27

1172 SHORT COMMUNICATION Refractory Pemphigoid with Autoantibodies to Both BP230 and Laminin gamma1 Himino ASHIDA 1 , Toshihisa HAMADA 1 *, Yoichiro HOSOKAWA 1 , Takashi HASHIMOTO 2 , Wataru NISHIE 3 , Norito ISHII 4 , Takekuni NAKAMA 4 , Taisuke KANNO 5 and Masami IKEDA 1 1 Department of Dermatology, Takamatsu Red Cross Hospital, 4-1-3 Ban-cho, Takamatsu, Kagawa 760-0017, 2 Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, 3 Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, 4 Department of Dermatology, Kurume University School of Medicine, Kurume, 5 Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. E-mail: [email protected] Accepted Aug 22, 2019; E-published Aug 22, 2019 Bullous pemphigoid (BP) is characterized by autoantibody production against BP180, one of the structural proteins in the dermal–epidermal junction of the skin (1). Patients with BP can also have circulating autoantibodies against BP230, one of the plakin family proteins localized in the inner plaque of the hemidesmosomes (2). Several molecules other than BP180 constituting the dermal–epidermal junction have been identified as auto­ antigens in BP and other types of pemphigoid (1). For instance, anti-p200 (or anti-laminin γ1) pemphigoid is a distinct autoimmune subepidermal blistering disorder characterized by circulating autoantibodies against lami- nin γ1, a 200-kDa glycoprotein localized to the basement membrane zone (BMZ) of the skin (3). We hereby report a rare case of a Japanese patient with pemphigoid resistant to high-dose corticosteroid and oral colchicine, who had circulating autoantibodies against both BP230 and laminin γ1 but not BP180. CASE REPORT A 50-year-old Japanese man first noticed itchy erythematous pa- pules on his trunk and extremities. He was referred to us because of his recalcitrant clinical course, which was suggestive of prurigo chronica multiformis. He had been treated with a potent topical corticosteroid and oral antihistamines with a favorable clinical course. However, 4 years later, his eruption intensified rapidly with the development of multiple itchy erythematous patches and vesicles, and severe itching began to interfere with his sleep. He had tattoos on almost his entire trunk and extremities dating back to his late 20s. He had no history of psoriasis. A physical examination revealed widespread, coalescent in- filtrating erythematous patches and multiple vesicles that were distributed independently of the sites of his tattoos (Fig. 1a, b). No mucosal lesions were observed. Routine laboratory tests revealed a white blood cell count of 13,330/µl with 4.7% eosinophils, increased serum levels of IgE at 23,314 IU/ml (3–311) and CC chemokine ligand 17 at 584 pg/ml (0–449). A biopsy specimen from a vesicle showed subepidermal blister formation with many eosinophils and neutrophils bound to the dermal side of the blisters (Fig. 1c,d). Direct immunofluorescence showed a linear deposit of IgG on the BMZ (Fig. 1e). Indirect immunofluorescence detected circulating IgG class autoantibodies reacting to both the epidermal and dermal sides of 1M NaCl split skin (Fig. 1f). Enzyme-linked immunosorbent assays (ELISAs) were positive for N-terminal and C-terminal domains of BP230 (index 23.53, cut-off < 9), but negative for the BP180 NC16A domain, and the NC1 and NC2 domains of type VII collagen (MBL, Nagoya, Japan). ELISA for full-length BP180 showed a negative result (4). Immunoblotting (IB) using normal human epidermal extract as a substrate showed that the patient’s IgG autoantibodies reacted weakly but clearly with BP230, but not with BP180 (Fig. S1a 1 ), compatible with the results of the ELISAs. No positive reactivity was detected by IB using either BP180 NC16A domain recombinant protein (Fig. S1b 1 ). IB using normal human dermal extract demonstrated that the patient’s IgG autoantibodies reacted with the 200-kDa laminin γ1, but not with the 290-kDa type VII collagen, thereby ruling out the possibility of epidermolysis bullosa acquisita (Fig. S1c 1 ). Based on the above findings, a diagnosis of pemphigoid with IgG autoantibodies to both laminin γ1 and BP230 with a bullous pemphigoid disease area index (BPDAI) score of 33 was made. The patient was initially treated with intravenous methylpred- nisolone pulse therapy (1,000 mg daily, for 3 consecutive days) followed by oral prednisolone 40 mg daily (Fig. S2 1 ). Because of the refractory clinical course with corticosteroid therapies alone, we added diaminodiphenyl sulfone 50 mg daily and colchicine 1.5 mg daily, with only slight beneficial effect. Frequent recurrences of erythema with severe itching continuously interfered with his sleep. Eventually, combination therapy of oral cyclosporine and https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3294 1 Fig. 1. Clinical, histopatho­ logical and immunofluore­ scence findings. (a,b) Multiple erythematous papules and vesicles on the trunk and extremities. (c,d) Subepidermal blister formation with many eosinophils and neutrophils [hematoxylin and eosin stain; original magnification (c) x40, (d) x200]. (e) Direct immuno­ fluorescence shows a linear deposit of IgG on the basement membrane zone (x100). (f) Indirect immunofluorescence using 1M NaCl split skin detects circulating IgG class autoantibodies reacting to both the epidermal and dermal sides (×100). doi: 10.2340/00015555-3294 Acta Derm Venereol 2019; 99: 1172–1173 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.