Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature

Abstract: Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2–17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens–Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.