Materials and Methods
We conducted this retrospective study in accordance with the concepts enshrined in the Declaration of Helsinki. This study was approved by the Kyushu University Institutional Ethics Committee (30-363; November 27, 2018).
We identified 42 patients who underwent skin biopsy and received a diagnosis of cutaneous irAE at the Department of Dermatology of Kyushu University Hospital between November 2014 and August 2020. The patients were referred to us for the evaluation of eruptions that developed during treatment with ICIs (nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, and durvalumab). Excluded patients were [1] those with inflammatory eruption attributed to another drug type other than ICIs (e.g. nonsteroidal anti-inflammatory drugs, antibiotics) and [2] those with an irAE of vitiligo alone or pruritus without inflammatory eruption. All skin biopsy samples were subjected to hematoxylin-eosin staining, and the diagnosis was confirmed by at least three experienced dermatopathologists.
The medical records were reviewed and analyzed for patient demographics, underlying malignancies, and medications. The grade of rash, the duration from the start of treatment to reaction, the presence or absence of pruritus and mucosal lesions, blood eosinophil counts, and the presence or absence of other irAEs were also analyzed according to the rash type, and the treatment of rash, response of rash, and impact of the rash on immunotherapy (none, temporarily interrupted, or discontinued) were analyzed according to the grade of rash. The rash grade was determined using Common Terminology Criteria for Adverse Events, version 5.0 as follows: a grade 1 rash covered <10% of the body surface area (BSA) with or without symptoms; a grade 2 rash covered 10–30% of the BSA with or without symptoms affecting instrumental activities of daily living (ADLs) or covered >30% of the BSA with or without mild symptoms without limiting self-care ADLs; a grade 3 rash covered >30% of the BSA with moderate or severe symptoms limiting self-care ADLs; and a grade 4 rash represented life-threatening consequences requiring urgent intervention including intensive care.
Results