Oral lichenoid eruption associated with imatinib treatment

ARTICLE

Auteur(s) : Cristina Gómez Fernández¹, Elena Sendagorta Cudós¹, Beatriz Casado Verrier¹, Marta Feito Rodríguez¹, Judith Suárez Aguado², Carmen Vidaurrázaga Díaz de Arcaya¹

¹Universitary Hospital La Paz. Department of Dermatology, Paseo de la Castellana, 261, 28046 Madrid, Spain
²Universitary Hospital La Paz. Department of Pathology, Paseo de la Castellana, 261, 28046 Madrid, Spain

Imatinib mesylate (Glivec^®, formally known as STI₅₇₁), which was approved in 2001, is a potent and specific inhibitor of several protein-tyrosine kinases that are frequently mutated or otherwise deregulated in human malignancies. This drug targets BCR-ABL which is responsible for the pathogenesis of chronic myeloid leukemia (CML), c-KIT, which is expressed in gastrointestinal stromal tumor and platelet-derived growth factor receptor, activated in dermatofibrosarcoma protuberans. Adverse cutaneous reactions seem frequent. We report a new case of an oral lichenoid eruption during imatinib therapy.

A 75-year-old man presented with a 4-month history of asymptomatic lesions affecting his tongue. He had been diagnosed as having CML and had started imatinib treatment at an oral dose of 400 mg daily. He was not taking any other drugs. The patient denied exposure to dental restorative materials (amalgam, gold or composite).Two months later, he developed whitish reticulate plaques on the dorsal and lateral aspects of the tongue (figure 1A). An examination excluded skin or mucosal lesions elsewhere. A skin biopsy specimen from the patient’s tongue was taken. Histopathological examination showed a dense lichenoid inflammatory infiltrate with necrotic epithelial cells in the lower epithelium, along with parakeratosis. The infiltrate was mainly composed of lymphocytes, located also within the epithelium, and no eosinophils were identified. No deep inflammation was found (figure 1B). On the basis of clinical and histopathological findings, the diagnosis was a lichenoid drug eruption associated with imatinib. Imatinib was withdrawn, and he was treated with oral prednisone at a dose of 30 mg daily. The lesions improved progressively but, when the treatment was reinitiated three weeks later at a dose of 400 mg daily, the lichenoid eruption recurred.

The success of imatinib in improving prognosis in CML, producing considerably higher response rates than seen with previous drug therapies, has led to its wide use as first-line therapy at a standard dose of 400 mg daily. The most common toxicities associated with this drug include nausea, diarrhoea, muscle cramps and oedema (frequently involving the periorbital region). A variety of adverse cutaneous reactions have been reported, including urticaria, maculopapular exanthem, pityriasis rosea-like eruption, skin hypopigmentation, Sweet syndrome, acute generalized exanthematous pustulosis, exacerbation of psoriasis, pseudoporphyria, mycosis fungoides-like reaction, Stevens-Johnson syndrome and toxic epidermal necrolysis. The skin eruptions appear to be dose-dependent, with mild reactivity to doses of imatinib of 200-600 mg daily, but severe reactions to high doses of 600-1000 mg daily.

To our knowledge, since 2002, there have been fourteen case reports of lichenoid drug eruptions associated with imatinib, ten of them in the context of CML treatment. Two cases had oral involvement as the only manifestation [1, 2] and six had mucocutaneous lesions [3-6]. The appeareance of the majority of the lichenoid eruptions was within 2-3 months. In some reported cases, withdrawal of imatinib treatment was necessary [1, 5]. In others, dose adjustment and topical or systemic corticosteroid treatments allowed continuation of imatinib therapy [2, 4, 6]. Treatment with oral acitetrin has also been reported as a successful treatment in refractory cases [3].

As imatinib has become an essential tool for the treatment of CML, and as new indications appear, an increasing incidence of this unusual drug eruption is expected. Therefore dermatologists need to be aware that new cutaneous reactions may develop, and be able to recognize and treat them appropriately.

Acknowledgements

References

2 Ena P, Chiarolini F, Siddi GM, et al. Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat 2004; 15: 253-5.

3 Dalmau J, Peramiquel L, Puig L, et al. Imatinib-associated lichenoid eruption: acitetrin treatment allows maintained antineoplastic effect. Br J Dermatol 2006; 154: 1213-6.

4 Pascual JC, Matarredona J, Miralles J, et al. Oral and cutaneous lichenoid reaction secondary to imatinib: report of two cases. Int J Dermatol 2006; 45: 1471-3.

5 Sendagorta E, Herranz P, Feito M, et al. Lichenoid drug eruption related to imatinib: report of a new case and review of the literature. Clin Exp Dermatol 2009: 18.

6 Wahiduzzaman M, Pubalan M. Oral and cutaneous lichenoid reaction with nail changes secondary to imatinib: report of a case and literature review. Dermatol Online J 2008; 15: 14.