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