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KMID : 0363220140520090679
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Korean Journal of Dermatology
2014 Volume.52 No. 9 p.679 ~ p.680
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Acneiform Eruption Induced by Radotinib (IY5511 : HCL)
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Chae Woong-Suk
Jung Ha-Na
Seong Jun-Young
Suh Ho-Seok
Choi Yu-Sung
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Abstract
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In recent years, novel chemotherapeutic agents have been introduced to treat several cancers. Some of them are signal transduction inhibitors, which can be divided into epidermal growth factor receptor (EGFR) inhibitors and tyrosine kinase inhibitors (TKI). Imatinib (imatinib mesylate, STI571, GlivecTM) is one of the TKIs which has been used for chronic myeloid leukemia (CML)1. However, resistance to imatinib has developed with point mutations within the BCR-ABL kinase domain, leading to the development of second-generation TKIs2. Among these new TKIs in preclinical and clinical trials, radotinib (IY5511 : HCl) is the most advanced TKI which is currently being investigated in Phase III clinical trials for chronic myeloid leukemia patients who are resistant to imatinib. TKI-related mucocutaneous side effects have been described as non-specific rashes, pruritus, edema, pigmentary abnormalities, and Steven-Johnson syndrome3. While cutaneous side effects of early TKIs are well-known, cutaneous side effects of the newly developed agents are not yet well characterized. We report here a case of a cutaneous adverse reaction to radotinib manifesting as an acneiform rash in a young woman with chronic myeloid leukemia. A 34-year-old woman, diagnosed with chronic myeloid leukemia in the chronic phase for 2 years had been treated with imatinib. The patient showed no clinical response to imatinib in a one-year therapy protocol without skin rash, so treatment with radotinib 400 mg daily was attempted. After 3 weeks of treatment, follicular papules began to appear on both cheeks and the anterior chest area (Fig. 1). There were no further changes in the concomitant medication except the treatment with radotinib. Histopathologically, inflammatory cell infiltrates were observed around the follicles, which was consistent with the clinical impression of an acneiform eruption (Fig. 2). Skin lesions responded well to systemic treatment with 50 mg minocycline, applied twice a day for three weeks. However, similar lesions reappeared after continuous use of radotinib. The absence of both an apparent infectious etiology and another plausible drug suggest radotinib as the causative agent of this follicular eruption. Radotinib acts through competitive inhibition at the adenosine triphosphate binding site of the enzyme, leading to the inhibition of tyrosine phosphorylation of proteins involved in bcr-abl protein, c-kit, and platelet-derived growth factor receptors (PDGFR). The pathophysiology of follicular eruption in our case is unclear, but in recent studies, TKIs, like EGFR inhibitors, were able to induce alterations in follicular and epidermal cell homeostasis4. Moreover, several studies have reported a link between the antitumor efficacy of EGFR inhibitors and cutaneous side-effects5. Our patient, who was resistant to imatinib, is currently considered to be showing a partial response to the new drug with recurrent episodes of acneiform eruption. We can postulate the relationship between an acneiform eruption and the tumor response to TKIs in future.
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KEYWORD
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Acneiform eruption, Radotinib, Tyrosine kinase inhibitors
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