tients with malignancies, both in the isolated form and in combination with diverse anticancer drugs. However, RT is reported to cause various cutaneous adverse reactions, including acute and chronic radiation dermatitis and radiation recall reaction, which tend to be limited to the irradiated skin areas. 1 In addition, widespread mucocutaneous reactions resembling erythema multiforme (EM) can occur in association with RT, including its more severe forms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). 2 Over 100 cases have been previously reported; however, most studies had a limited number of cases. [3][4][5][6][7][8][9][10] In addition, the definite association between RT and EM-like rash is not always clear, especially in cases with concurrent drug administration. 3 To evaluate the potential association in a larger sample, we examined the records of patients who received RT and developed EM-like mucocutaneous eruptions and were referred to a dermatologist at our institute (a tertiary cancer center) within a 10-year period. Herein we report the details of the included cases. | ME THODS | Patients and inclusion criteriaWe identified patients who developed skin rash clinically resembling EM, SJS, and TEN while receiving RT for various malignancies from 2010 to 2021.
In recent years, the development of combination therapies with immune checkpoint inhibitors (ICIs) and cytotoxic anticancer drugs has radically changed the management of diverse malignancies and significantly improved patient outcomes. Several clinical trials have shown that skin rash caused by combination therapy with ICIs and cytotoxic drugs may be more frequent and severe than that developing after administration of ICIs alone or cytotoxic drug monotherapy. However, most reports provide little information on severity, treatment, post‐diagnosis course, and recurrence of rashes on drug rechallenges. We aimed to describe the experience of skin rashes developing within 2 weeks from the first administration of combination therapy with ICIs and cytotoxic drugs in 11 patients visiting our dermatology department. This study included seven men and four women, and the patients' median age was 52 years. The primary disease was non‐small‐cell lung cancer in eight patients, cervical cancer in two patients, and esophageal cancer in one patient. Nine patients had a maculopapular rash and two patients developed erythema multiforme‐like eruptions. The skin rash was often accompanied by extracutaneous symptoms, such as fever (n = 9), mucositis (n = 4), and liver dysfunction (n = 2). In all cases, the symptoms improved with topical steroid therapy alone, with no patients exhibiting severe symptoms requiring systemic steroids or immunosuppressive agents. In addition, when the causative drugs were re‐administered after recovery from the rash, only two patients relapsed with accompanying systemic symptoms, and all patients except one were able to continue treatment using the same drug regimen. Although it was suggested that the rash caused by the combination therapy of ICIs and cytotoxic drugs may be more prominent than that caused by each agent alone, comprehensive judgment, including histopathological examination, may indicate the feasibility of continuing the treatment regimen for cancer.
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