Thiotepa-Induced Toxicity: A Clinical Mimic of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Featuring Severe Mucositis, Diffuse Dusky Discoloration, and Skin Sloughing.

Abstract

Background: Thiotepa, an alkylating agent commonly used in chemotherapy, is increasingly recognized to induce cutaneous reactions resembling toxic erythema of chemotherapy (TEC). This condition is characterized by erythema, hyperpigmentation, and mucositis, often affecting intertriginous areas, and can mimic the early stages of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

Case description: A 31-year-old woman with a history of systemic lupus erythematosus, antiphospholipid antibody syndrome, seizures, and chronic kidney disease was admitted for the management of central nervous system (CNS) lymphoma. Seven days after receiving thiotepa during an autologous stem cell transplant, she developed severe mucositis, requiring intubation for airway protection, followed by a dusky, gray, full-body rash with sloughing in the groin, axillae, and buttocks. A skin biopsy from the back revealed vacuolar interface changes, eccrine gland necrosis, and occasional necrotic keratinocytes at the dermal-epidermal junction, with no evidence of full-thickness necrosis or significant eosinophilic infiltration. The differential diagnosis included thiotepa-induced toxicity, SJS/TEN, and drug eruption. Based on the patient's clinical presentation and the biopsy findings, thiotepa-induced TEC was favored over SJS/TEN.

Discussion: Thiotepa is a potent lipophilic alkylating agent widely used in chemotherapy for pediatric and adult patients with various solid tumors and hematologic malignancies. Its anticancer mechanism involves DNA alkylation, leading to DNA strand cross-linking that disrupts replication and transcription, ultimately inhibiting cancer cell proliferation and survival. While thiotepa is primarily utilized in high-dose preparative regimens for stem cell transplantation in pediatric patients, its use in the adult population remains comparatively limited.This case emphasizes the importance of differentiating thiotepa-induced TEC from severe cutaneous adverse reactions such as SJS/TEN. While these conditions share clinical and histologic features, the absence of extensive epidermal necrosis, satellite cell necrosis, and systemic involvement, along with recent thiotepa exposure, supported a diagnosis of TEC.

Conclusions: This case highlights the diagnostic challenge of distinguishing thiotepa-induced TEC from SJS/TEN in post-transplant patients. Recognizing the characteristic involvement of intertriginous areas and eccrine gland necrosis in TEC is critical for accurate diagnosis and management. Awareness of this potential complication in patients receiving thiotepa is essential to avoid misdiagnosis and inappropriate treatment.