(D) Detailed view of a rash with red and raised patches. Although the symptoms of breathlessness improved after radiotherapy, a computed tomography scan showed progression of adrenal metastasis. programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1), provide dramatic survival benefits to patients with advanced non-small-cell lung cancer (NSCLC). Atezolizumab, a humanized, engineered immunoglobulin-G1 monoclonal antibody targeting PD-L1, has demonstrated improved survival rates over docetaxel in previously treated patients with NSCLC ABX-464 (1). However, immune checkpoint inhibitors like atezolizumab lead to various immune-related adverse events (irAEs) by increasing the activity of the immune system (2). Immune checkpoint inhibitor-induced skin toxicities are the most frequent irAE, and inflammatory dermatosis conditions, including erythema multiforme minor, lichenoid, and eczematous dermatitis, occasionally cause life-threatening events, such as Stevens-Johnson syndrome (3-5). Radiation recall dermatitis ABX-464 (RRD) is an acute inflammatory skin reaction in a previously irradiated area triggered by the administration of a systemic agent. RRD is a relatively rare phenomenon and develops within days to weeks after drug administration (6,7). Although most recall-triggering drugs are cytotoxic anticancer agents, information on RRD induced by immune checkpoint inhibitors is scanty. We herein report a patient with ABX-464 NSCLC who developed severe skin manifestations related to RRD after the administration of atezolizumab. To evaluate the immune microenvironment of RRD, we performed an immunohistochemistry analysis of a skin biopsy based on T lymphocytes and the PD-L1 expression. Case Report A 61-year-old man was diagnosed with clinical T3N2M0 stage IIIC lung squamous cell carcinoma with a PD-L1 expression of 1% in June 2018. Chemotherapy with carboplatin and nab-paclitaxel was administered as first-line treatment. After the initial treatment, however, he developed difficulty breathing with symptoms of superior vena cava syndrome caused by enlarged mediastinal lymph nodes and carcinomatous pericarditis. He received 1 mg of oral dexamethasone and palliative radiotherapy for lymph node metastases and pericardium with a total dose of 30 Gy in daily fractions of 3 Gy (Fig. 1A). Open in a separate window Figure 1. Clinical features of radiation recall dermatitis after atezolizumab treatment. (A) Portal radiographs of radiotherapy for enlarged lymph nodes and pericardium. (B) (C) Relatively well-circumscribed erythema at the site of previous irradiation over the chest and abdominal regions. (D) Detailed view of a rash with red and raised patches. Although the symptoms of breathlessness improved after radiotherapy, a computed tomography scan showed progression of adrenal metastasis. Subsequently, he was treated with intravenous infusion of 1 1,200 mg atezolizumab. Twenty-one days after the administration of atezolizumab, he was admitted with the occurrence of relatively well-circumscribed erythema at the previously ABX-464 irradiated skin field (Fig. 1B). An erythematous rash was mainly observed in the trunk, part of the upper extremities, and the face and not in the lower extremities, nails, and oral cavity. Signs of infection, autoimmune disorders, and suspected use of agents aside from anti-PD-L1 antibody were absent. A skin biopsy showed interface dermatitis with perivascular lymphocytic inflammatory cell infiltration (Fig. 2A). Based on these findings, we diagnosed him with severe skin disorder (CTCAE version 5.0, Grade 3) related to RRD induced by atezolizumab treatment. Open in a separate window Figure 2. Results of the histologic analysis of a skin biopsy sample. Hematoxylin and Eosin staining (A) (original magnification 400). Immunohistochemical staining for CD8 [Clone C8/144B (Nichirei Bioscience, Tokyo, Japan)] (B) (original magnification 400) and PD-L1 [Clone E1 L3N (Cell Signaling Technology, Danvers, USA)] (C) (original magnification 400). He discontinued atezolizumab treatment and received an intravenous 150-mg dose of methylprednisolone (2 mg/kg/day) for 3 days. Subsequently, he Rabbit Polyclonal to HDAC3 was treated with an intravenous 75 mg dose of methylprednisolone (1 mg/kg/day) for 4 days, and then oral prednisolone was reduced to 40 mg/day. Prednisolone was tapered ABX-464 by 10 mg per week and stopped 4 weeks after the occurrence of RRD. His skin disorders disappeared two weeks after steroid therapy initiation and did not relapse. Discussion To the best of our.