Imatinib Mesylate–Induced Lichenoid Drug Eruption
Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor initially approved by the US Food and Drug Administration in 2001 for chronic myeloid leukemia (CML). Since then, the number of indicated uses for imatinib has substantially increased. It is increasingly important that dermatologists recognize adverse cutaneous manifestations of imatinib and are aware of their management and outcomes to avoid unnecessarily discontinuing a potentially lifesaving medication. Adverse cutaneous manifestations in response to imat-inib are not infrequent and can include dry skin, alopecia, facial edema, and photosensitivity rash. Other less common manifestations include exfoliative dermatitis, nail disorders, psoriasis, folliculitis, hypotrichosis, urticaria, petechiae, Stevens-Johnson syndrome, erythema multiforme, Sweet syndrome, and leukocytoclastic vasculitis. We report a case of imatinib-induced lichenoid drug eruption (LDE), a rare cutaneous manifestation, along with a review of the literature.
Practice Points
- Imatinib mesylate can cause cutaneous adverse reactions including dry skin, alopecia, facial edema, photosensitivity rash, and lichenoid drug eruption (LDE).
- Topical corticosteroids, oral acitretin, and oral steroids may be reasonable treatment options for imatinib-induced LDE if discontinuing imatinib is not possible in a symptomatic patient.
Comment
In addition to CML, imatinib has been approved for acute lymphoblastic leukemia, myelodysplastic syndromes, aggressive systemic mastocytosis, hypereosinophilic syndrome, chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and GIST. Moreover, off-label use of imatinib for various other tyrosine kinase–positive cancers and rheumatologic conditions have been documented.2,3 With the expanding use of imatinib, there will be more occasions for dermatologists to encounter cutaneous manifestations associated with its use.
According to a PubMed search of articles indexed for MEDLINE using the terms imatinib mesylate lichenoid drug, there have been few case reports of LDE associated with imatinib in the literature (eTable).4-24 Compared to classic LDE, imatinib-induced LDE has a few characteristic findings. Classic LDE frequently spares the oral mucosa and genitalia, but imatinib-induced LDE with manifestations on the oral mucosa and genitalia as well as cutaneous eruptions have been reported.4-9 In fact, the first known case of imatinib-induced LDE was an oral eruption in a patient with CML.4 In patients with oral involvement, lesions have been described as lacy reticular macules and violaceous papules, erosions, and ulcers.4,5,12 Interestingly, of those cases manifesting as concomitant oral and cutaneous LDE, the oral eruptions recurred more frequently, with 3 of 12 patients having recurrence of oral lesions after the cutaneous manifestations resolved.8,16 Genital manifestations of imatinib-induced LDE were much less common.9,11
To date, subsequent reports of imatinib-induced LDE have documented skin manifestations consistent with classic LDE occurring in a diffuse, bilateral, photodistributed pattern.10,15,16 One case presented with diffuse hyperpigmentation associated with LDE in a Japanese patient.20 The authors suggested this finding may be more prominent in patients with skin of color,20 which is consistent with the current case. Nail findings such as subungual hyperkeratosis and longitudinal ridging also have been reported.9,11
,The latency period between initiation of imat-inib and onset of LDE generally ranges from 1 to 12 months, with onset most commonly occurring between 2 to 5 months or with dosage increase (eTable). Imatinib-induced LDE primarily has been documented with a 400-mg dose, with 1 case of a 600-mg dose and 1 case of an 800-mg dose, which suggests dose dependency. Furthermore, reports exist of several patients responding well to dose reduction with subsequent recurrence on dose reescalation.13,15
Historically, LDE resolves with discontinuation of the drug after a few weeks to months. When discontinuation of imatinib is unfavorable or patients report symptoms including severe pruritus or pain, treatment should be considered. Topical or oral corticosteroids can be used to treat imatinib-induced LDE, similar to lichen planus. When oral corticosteroids are contraindicated (eg, due to poor patient tolerance), oral acitretin at 25 to 35 mg once daily for 6 to 12 weeks has been reported as an alternative treatment.25
In the majority of cases of imatinib-induced LDE, it was undesirable to stop imatinib (eTable). Notably, in half the reported cases, imatinib was able to be continued and patients were treated symptomatically with either oral and/or topical steroids and/or acitretin with complete remission or tolerable recurrences. Dalmau et al9 reported 3 patients who responded poorly to topical and oral steroids and were subsequently treated with acitretin 25 mg once daily; 2 of 3 patients responded favorably to treatment and imatinib was able to be continued. In the current case imatinib initially helped, but because his rash was relatively asymptomatic, imatinib was restarted with control of rash with topical steroids. He developed some pancytopenia, which required intermittent stoppage of the imatinib.
Conclusion
We present a case of imatinib-induced cutaneous and oral LDE in a patient with GIST. Topical corticosteroids, oral acitretin, and oral steroids all may be reasonable treatment options if discontinuing imatinib is not possible in a symptomatic patient. If these therapies fail and the eruption is extensive or intolerable, dosage adjustment is another option to consider before discontinuation of imatinib.
