Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2025;15(1):4713 1 Significance of Clinical-Pathological Correlation in Ponatinib Reactions Judith Monserrat Corona-Herrera1, Fanny Carolina Lopez-Jimenez1, Verónica Monserrat Díaz Sánchez1, Betzabé Quiles-Martínez1, Marcela Saeb-Lima2, Silvia Méndez-Flores1 1 Dermatology Department, National Institute of Nutrition Salvador Zubirán, Mexico City, Mexico 2 Pathology Department, National Institute of Health Sciences and Nutrition Salvador Zubirán, Mexico City, México Key words: Ponatinib, Adverse Drug Reactions, Stevens-Johnson Syndrome Citation: Corona-Herrera JM, Lopez-Jimenez FC, Díaz Sánchez VM, Quiles-Martínez B, Saeb-Lima M, Méndez-Flores S. Significance of Clinical-Pathological Correlation in Ponatinib Reactions. Dermatol Pract Concept. 2025;15(1):4713. DOI: https://doi.org/10.5826 /dpc.1501a4713 Accepted: August 1, 2024; Published: January 2025 Copyright: ©2024 Corona-Herrera et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Silvia Méndez-Flores MD, PhD, Dermatology Department, National Institute of Nutrition Salvador Zubirán. Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. E-mail: silvia.mendezf@incmnsz.mx Introduction The advent of molecular therapies targeting specific cellular pathways has significantly enhanced the prognosis for nu- merous cancer patients. However, these advancements often come with diverse cutaneous adverse drug reactions (CADR). These reactions can be serious, such as in Stevens-Johnson Syndrome (SJS), which has been reported as an adverse reac- tion induced by tyrosine kinase inhibitors (TKIs) like imati- nib and masitinib. There have been no reports of SJS induced by ponatinib [1]. Ponatinib is a third-generation TKI specifically devel- oped to target the gatekeeper T315I mutation. It is currently approved for the treatment of chronic myeloid leukemia in all phases of the disease, particularly for patients who have developed resistance to or cannot tolerate dasatinib or ni- lotinib, and for those with the T315I mutation for whom imatinib is no longer effective. Ponatinib is also indicated for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) [2]. With over 10 years on the market, some CADR have been reported, including pityriasis rubra pilaris-like eruptions, ichthyosiform eruptions, and erythem- atous rash [3,4]. Recently, the term “ponatinib-induced des- quamation” described sheet-like desquamation, symmetrical dermatitis, and lamellar ichthyosis-like. It was proposed because, regardless of its extensive total body surface area involvement, it is a benign, temporary condition that does not require discontinuing the medication [5]. Case Presentation A 59-year-old woman was diagnosed with Ph+ ALL in 2022 and began treatment with imatinib. Upon detecting T315I mutation, the treatment was switched to ponatinib with a daily dosage of 45 mg. Twenty-seven days after initiating ponatinib, she developed a CADR that affected all body 2 Research Letter | Dermatol Pract Concept. 2025;15(1):4713 segments. The lesions were characterized by the presence of plaques with erythematous-purpuric and ochre hues, arranged in a reticular pattern with fine adherent scaling at the center, and surrounded by a halo of increased ery- thema. Over time, the lesions evolved with blood-tinged scaling. No involvement of mucous membranes was ob- served (Figure 1, A-C). Histopathologic examination showed pauci- inflammatory subepidermal blistering dermatosis with multiple necrotic keratinocytes and lymphocytic and neutro- philic infiltration (Figure 2, A-D). Although these histological features were consistent with findings described in SJS and other CADR, the clinical presentation of our patient, includ- ing the absence of other clinical features such as mucosal involvement, conjunctival inflammation, and absence of blisters, or the Nikolsky sign, led us to conclude that SJS was an unlikely diagnosis. Due to discrepancy between clinical Figure 1. (A-C) Plaques with erythematous purpuric and ochre hues, arranged in a reticular pattern and surrounded by a halo of increased erythema. In some central areas of the lesions, there is evidence of fine adherent scaling. (D) Hypopigmented post-inflammatory patches with a reticulated appearance. Figure 2. (A,B) Skin biopsy of the back show pauci-inflammatory subepidermal blistering derma- tosis with multiple necrotic keratinocytes and lymphocytic and neutrophilic infiltration (H&E, x4). (C,D) Higher magnification (x40). Research Letter | Dermatol Pract Concept. 2025;15(1):4713 3 References 1. Ikeda M, Fujita T, Amoh Y, Mii S, Matsumoto K, Iwamura M. Stevens-Johnson syndrome induced by sorafenib for metastatic renal cell carcinoma. Urol Int. 2013;91(4):482-3. DOI: 10.1159 /000351918. PMID: 23969404. 2. Massaro F, Molica M, Breccia M. Ponatinib: A Review of Efficacy and Safety. Curr Cancer Drug Targets. 2018;18(9): 847-56. DOI: 10.2174/1568009617666171002142659. PMID: 28969556. 3. Hsiao LT, Chung HM, Lin JT, et al. Stevens-Johnson syndrome after treatment with STI571: a case report. Br J Haematol. 2002;117(3):620-22. DOI:10.1046/j.1365-2141.2002.03499.x. PMID: 12028031. 4. Chaigne B, Lagier L, Aubourg A, et al. Stevens-Johnson Syndrome induced by masitinib. Acta Derm Venereol. 2012;92(2):210-2. DOI: 10.2340/00015555-1196. PMID: 21953477. 5. Danish M, Patel V, Arava S, Ahuja R. Ponatinib-induced desquamation-Unifying eponymous terminology for a rare adverse event. J Eur Acad Dermatol Venereol. 2024;38(3): e247-e249. DOI:10.1111/jdv.19553. PMID: 37795667. and pathological findings and the persistent cytopenias, it was decided to discontinue ponatinib treatment. Resolution of the initial lesions resulted in post-inflammatory hypopig- mentation (Figure 1D). Conclusions We report a cutaneous reaction with an uncommon mor- phology currently known as Ponatinib-induced desqua- mation. Our patient exhibited skin lesions with a reticular pattern and peripheral erythema, even though the histo- pathological findings were consistent with SJS. We reported this case to highlight the significance of recording emerging cutaneous reactions linked to molecular therapies, emphasiz- ing the importance of acting according to evolution in a pa- tient instead of guiding our treatment based on only clinical or histopathological findings, especially when considering the implications for the patient’s prognosis.