Methotrexate might become the sole treatment option for leukemia following the occurrence of Stevens–Johnson syndrome

Main Article Content

Carolina Sanchez Aranda
Katherine Maciel Costa Silvestre
Kamila da Silva Marques
Maria Lucia Lee
Dirceu Solé


allergy, drug allergy, children, Stevens–Johnson syndrome, leukemia


Introduction: Severe cutaneous adverse reactions (SCARs) arising from drug interactions can carry life-threatening implications and result in lasting effects. SCARs can be triggered by various factors, with trimethoprim/sulfamethoxazole identified as a primary culprit. Anticonvulsants and antineoplastic agents have been noted as secondary triggers. Notably, antineoplastics linked to SCARs include immunomodulatory agents. The higher mortality rates among cancer patients with SCARs underscore the significance of comprehending cancer--specific risk factors. Our objective is to present the case of a boy with acute lymphocytic leukemia (ALL) who developed Stevens-Johnson syndrome (SJS) following MTX treatment.

Case report: We present the case of a three-year-old male patient diagnosed with ALL who developed Stevens-Johnson syndrome (SJS) subsequent to the administration of MTX, following the “BFM 2009” protocol. He had undergone intrathecal MTX administration on six previous occasions. Our patient received IVIG at a dose of 2g/kg along with steroids, resulting in partial clinical improvement after 21 days. An innovative protocol was developed, involving IVIG before MTX infusion and dexamethasone before MTXi, with folinic acid rescue. Intravenous immunoglobulin (IVIG) mitigates SJS/TEN via type IV hypersensitivity down-regulation and apoptosis curbing.

Conclusion: As far as we know, the prophylactic use of IVIG to counteract SCARs in a pediatric leukemia patient represents uncharted territory. Moreover, research into the immune system dynamics within these patients and the preservation of indispensable treatments should involve allergist-immunologists as part of the multidisciplinary team attending to neoplastic conditions.

Abstract 179 | PDF Downloads 220 HTML Downloads 0 XML Downloads 7


1. Chung W-H, Wang C-W, Dao R-L. Severe cutaneous adverse drug reactions. J Dermatol. 2016;43(7):758–66. 10.1111/1346-8138.13430

2. Gillis NK, Hicks JK, Bell GC, Daly AJ, Kanetsky PA, McLeod HL. Incidence and triggers of Stevens-Johnson syndrome and toxic epidermal necrolysis in a large cancer patient cohort. J Invest Dermatol. 2017;137(9):2021–2023. 10.1016/j.jid.2017.05.010

3. Macedo FI, Faris J, Lum LG, Gabali A, Uberti JP, Ratanatharathorn V, et al. Extensive toxic epidermal necrolysis versus acute graft versus host disease after allogenic hematopoietic stem-cell transplantation: challenges in diagnosis and management. J Burn Care Res. 2014;35(6):e431–5.

4. Wu J, Lee YY, Su SC, Wu TS, Kao KC, Huang CC, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with malignancies. Br J Dermatol. 2015;173(5):1224–31.

5. Frey N, Jossi J, Bodmer M, Bircher A, Jick SS, Meier CR, et al. The Epidemiology of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the UK. J Invest Dermatol. 2017;137(6):1240–1247. 10.1016/j.jid.2017.01.031

6. Jacobsen A, Olabi B, Langley A, Beecker J, Mutter E, Shelley A, et al. Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome. Cochrane Database Syst Rev. 2022;3(3):CD013130. 10.1002/14651858.CD013130.pub2

7. Saeed HN, Chodosh J. Immunologic Mediators in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Semin Ophthalmol. 2016;31(1–2):85–90. 10.3109/08820538.2015.1115255

8. Ye LP, Zhang C, Zhu QX. The Effect of Intravenous Immunoglobulin Combined with Corticosteroid on the Progression of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis. PLoS ONE. 2016;11(11):e0167120. 10.1371/journal.pone.0167120

9. Saeed HN, Chodosh J. Immunologic Mediators in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Semin Ophthalmol. 2016;31(1–2):85–90. 10.3109/08820538.2015.1115255

10. Castells MC, Tennant NM, Sloane DE, Hsu FI, Barrett NA, Hong DI, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol. 2008;122(3):574–80. 10.1016/j.jaci.2008.02.044

11. Akıncı B, Siviş ZO, Şahin A, Karapınar DY, Balkan C, Kavaklı K, Aydınok Y. Stevens-Johnson Syndrome associated with methotrexate treatment for acute lymphoblastic leukemia: a case report. Arch Argent Pediatr. 2018;116(3):e459–e462.