ID #1177 Temozolomide induced urticarial reaction: Case series and approach to management of a unique drug side effect

Background

Temozolomide (TMZ) is an oral alkylating agent used in the treatment of high-grade gliomas and other central nervous system tumors. TMZ is generally welltolerated, and cutaneous adverse drug reactions are uncommon with limited case reports in the pediatric literature[1-3].

Case/methods

Three pediatric patients developed delayed urticarial hypersensitivity reactions temporally associated with TMZ therapy.

Case 1 

A 12-year-old female with relapsed anaplastic ependymoma status post resection and radiation developed a diffuse maculopapular and urticarial eruption three days after completing her first cycle of TMZ.  Symptoms progressed despite antihistamines and included nausea and vomiting. She required treatment with intravenous corticosteroids and epinephrine, resulting in complete resolution of her symptoms. Due to drug-related side effects, she did not undergo further chemotherapy. 

Case 2 

A 6-year-old  female with relapsed astroblastoma received TMZ with radiation followed by standard dose (200mg/m2/dose x 5 days) maintenance therapy. Three days after completing cycle 5 of maintenance TMZ, she developed an urticarial eruption that resolved with cetirizine, hydroxyzine and diphenhydramine. With subsequent cycles, antihistamine premedication reduced severity, though mild recurrent urticaria persisted. 

Case 3 

A 15-year-old  patient with high grade glioma tolerated concurrent chemoradiation with TMZ without adverse effects but developed an urticarial eruption with angioedema 3 days after completing cycle 7 of maintenance therapy with standard dosing. Symptoms partially improved with antihistamines. Premedication with cetirizine prior to subsequent doses of TMZ led to improvement in severity. However, the patient continued to experience mild, recurrent urticarial lesions following later cycles. 

Conclusions

All cases demonstrated onset of urticaria occurring approximately three days after TMZ exposure, with two of them having delayed presentation after tolerating drug for multiple cycles.  While antihistamine premedication mitigated symptoms, hypersensitivity reactions recurred in patients who continued therapy, highlighting the importance of recognition and management of delayed TMZ hypersensitivity.  

1. Pothiawala S, Hsu MY, Yang C, Kesari S, Ibrahimi OA. Urticarial hypersensitivity reaction caused by temozolomide. J Drugs Dermatol. 2010 Sep;9(9):1142-4. PMID: 20865848

2. Deluche E, Leobon S, Touraine F, Clavère P. Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma Curr Oncol Tor Ont. 2014;21:e779–781

3. Virmani P, Chung E, Thomas AA, Mellinghoff IK, Marchetti MA. Cutaneous adverse drug reaction associated with oral temozolomide presenting as dermal and subcutaneous plaques and nodules. JAAD Case Rep. 2015 Jul 29;1(5):286-8. doi: 10.1016/j.jdcr.2015.06.012. PMID: 27051755; PMCID: PMC4809268.