Acta Dermato-Venereologica 99-7CompleteContent

SHORT COMMUNICATION 687 Mucosal Lichen Planus Mimicking Mucosal Lesions in Stevens-Johnson Syndrome after Nivolumab Therapy Fumi MIYAGAWA 1 , Anna NAKAJIMA 1 , Shin-ichiro OHYAMA 1 , Yuki AOKI 1 , Mitsuko NISHIKAWA 1 , Yuki NAKAMURA 1 , Takashi HASHIMOTO 2 and Hideo ASADA 1 1 Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo, Kashihara, Nara 634-8522, Japan, and 2 Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan. E-mail: fumim@ naramed-u.ac.jp Accepted Apr 2, 2019; E-published Apr 2, 2019 Nivolumab is a fully human monoclonal antibody against the programmed cell death (PD)-1 receptor, an immune checkpoint receptor, which is expressed on activated T cells. PD-1 acts as a negative regulator of the anti-tumour T-cell effector functions when bound to its programmed death ligand 1 (PD-L1) (1). The expression of PD-L1 on tumour cells can help tumours escape from host immune responses, and thus, blocking PD-1/PD-L1 interactions, with therapeutic antibodies, results in the stimulation of antitumor T cells (1, 2). Treatment with nivolumab or a PD-1 inhibitor can induce immune-related adverse events (irAE), such as lichen planus (LP), as it results of T-cell activation (3). Typically, the lichenoid reactions, caused by nivolumab, demonstrate similar cutaneous manifestations to the well characterized lichenoid drug reactions, caused by a variety of other medications, such as anti-hypertensive and β-adrenergic blockers; i.e., violaceous, flat-topped papules (4). However, the mucous membranes are usually spared (5). We report an unusual case of a lichenoid drug reaction caused by nivolumab, which was restricted to the oral cavity and anal region. In this case, painful hemorrhagic erosions arose on the lips and oral mucosa, which looked similar to the mucosal lesions seen in Stevens-Johnson syndrome (SJS). CASE REPORT A 75-year-old Japanese man presented with painful oral and anal erosions after 19 cycles of nivolumab treatment. The lesions first appeared after the 13 th cycle of therapy. The patient was started on 3 mg/kg nivolumab every 2 weeks for stage IV gastric cancer (T4bN3aM1), which was refractory to multiple lines of chemotherapy, 9 months before his presentation. A physical examination showed erosions limited to the mucous membranes; the buccal, gingival and glossal mucosae; the lips (Fig. 1a, b); and the perianal region (Fig. 1c). Massive hemorrhagic erosions covered by crusts were seen on the lip (Fig. 1a, b). The skin was not affected. He had also developed erosions on his glans penis, but they had spontaneously healed a few weeks ago. His medical history included hypertension and alcoholic liver disease. Laboratory tests showed the following abnormalities: red blood cells: 368 × 10 4 /µ (normal range: 435–555), hemoglobin: 11.9 g/dl (13.7–16.8), hematocrit: 35.1% (40.7–50.1), C-reactive protein: 2.42 mg/dl (< 0.14), al- bumin: 3.8 g/dl (4.1–5.1), alkaline phosphatase: 1,221 U/l (106–322), γ-glutamyltranspeptidase: 249 U/l (13–64), and cholinesterase: 182 U/l (240–486). Enzyme-linked immunosorbent assays for anti-desmoglein 1, anti- desmoglein 3, anti-BP180, and anti-BP230 antibodies Fig. 1. (a) Painful hemorrhagic erosions, coated by crusts on the lip. (b) Extensive erosions on the oral mucosae. (c) Perianal erosions. (d) Histopathology of the anal lesions (x40). Lichenoid inflammation and scattered necrotic keratinocytes in the epidermis were detected. (e) Higher magnification of (d) (x100). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3185 Acta Derm Venereol 2019; 99: 687–688

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