Imatinib mesylate-induced cutaneous rash masquerading as pityriasis rosea of gilbert.

Sir,

A pityriasis rosea-like rash can, on occasion, be triggered by a number of drugs: Metronidazole, bismuth, barbiturates, captopril, gold, organic mercurials, methoxypromazine, metronidazole, D-penicillamine, isotretinoin, tripelennamine hydrochloride, ketotifen, and salvarsan, among others. Imatinib mesylate, a tyrosine kinase inhibitor, is being widely used in the treatment of chronic myeloid leukemia. We describe a case of an imatinib mesylate-induced pityriasis rosea-like rash.

A 24-year-old man, diagnosed with chronic myeloid leukemia, was seen in our dermatology clinic with a generalized erythematous papulosquamous eruption for the past 7 days. He was started on imatinib mesylate, 400 mg daily for the previous 4 weeks. Three weeks into his treatment he developed a progressive, slightly pruritic rash. The rash was neither accompanied by fever nor any cough, cold or coryza. Examination revealed multiple erythematous, 1-3-cm-sized, well-defined, oval to round papules and plaques [Figure 1], symmetrically distributed over his chest, back, arms, legs and abdomen. The surface of the plaques depicted semi-adherent, greyish white scaling, accentuated toward the periphery of the lesions [Figure 2]. Auspitz sign was negative. Venereal disease research laboratory (VDRL) and enzyme linked immunoabsorbent assay (ELISA) testing for HIV were negative. A differential diagnosis of pityriasis rosea of Gilbert, secondary syphilis, drug rash, and psoriasis were considered. Histopathological examination [Figure 3] of the section from a representative lesion revealed parakeratosis, moderate acanthosis and spongiosis in the epidermis accompanied by some focal keratinocyte necrosis. Dermis showed lymphocytic and erythrocyte extravasation, neutrophils and eosinophils. Imatinib was then discontinued. Over a period of 2 weeks, the rash regressed completely. Three weeks after resolution of the rash, imatinib mesylate was reintroduced in a dose of 100 mg following which, a flare up of the rash was noticed. Accordingly, a ‘certain’ diagnosis of imatinib mesylate-induced pityriasis rosea-like rash was made according to the World Health Organisation drug reaction causality definition. The patient was then prescribed levocetirizine 5 mg once daily and topical betamethasone valerate 0.1% once daily, and the dose of imatinib was gradually escalated to 400 mg over a period of 2 weeks. The rash was well under control. In view of the mildness of the rash and the fact it was under control with conservative management, imatinib was continued in regular dosage. The patient, however, has not been followed up since then.

Figure 1

Multiple erythematous, 1-3-cm-sized, well-defined, oval to round papules and plaques over back

Figure 2

Closeup view depicting collarette-like scale

Figure 3

Histopathology illustrating parakeratosis, moderate acanthosis and spongiosis in the epidermis accompanied by some focal keratinocyte necrosis. Dermis showed lymphocytic and erythrocyte extravasation, neutrophils and eosinophils (H and E, × 400)

Imatinib mesylate is a potent, competitive inhibitor of the BCR-ABL protein tyrosine kinase, frequently administered for chronic myeloid leukemia. Imatinib mesylate is being frequently prescribed in the management of chronic myelogenous leukemia and gastrointestinal stromal tumors, as a targeted therapy.[1] It has been used effectively in metastatic dermatofibrosarcoma protuberans.[2] Besides, it may prove beneficial in systemic sclerosis[3] and pulmonary arterial hypertension.[4] Although largely innocuous, nausea, fatigue and myalgias, which are mostly mild or moderate, are the common nondermatological side effects of imatinib. Cutaneous reactions to imatinib are common and occur in 9.5-69% of patients.[5] Maculopapular eruptions, erythematous eruptions, edema, and periorbital edema are the most common adverse events observed. Imatinib can also induce severe skin eruptions and generalized skin eruptions. Toxic epidermal necrolysis, Stevens Johnson syndrome, acute generalized exanthematous pustulosis, purpuric vasculitis and mycosis fungoides-like reactions have been linked to imatinib use. Hypopigmentation, hyperpigmentation, lichenoid reactions, pityriasiform eruptions, pityriasis rosea, psoriasis, reactivation or induction of porphyria cutanea tarda, neutrophilic eccrine hidradenitis, Sweet's syndrome, erythema nodosum, EBV-positive cutaneous B-cell lymphoproliferative disease, possible induction of squamous cell carcinoma, hyaline cell syringomas, follicular mucinosis, pseudolymphoma-type drug eruptions, and Malpighian epitheliomas are other rare side effects.[56] To our knowledge there is only a single report of a ‘certain’ imatinib-induced pityriasis rosea like cutaneous rash.[7] However, in that report there was no typical collarette scale. In the present report, the lesions morphologically masqueraded as ‘pityriasis rosea of Gilbert’ with peripherally accentuated scaling. A complete regression following dechallenge and flare-up following a rechallenge established the causality of the rash with certainty. Histopathologically, a prominent keratinocyte necrosis and eosinophils is compatible with the diagnosis of drug rash, yet not diagnostic. In the present case, there was some keratinocyte necrosis and eosinophils. The mechanism of such a rash has been postulated to be through the modulation of cutaneous growth factor receptors. If correctly recognized, management of this type of rash should not warrant a discontinuation of therapy as it is largely benign and can be managed with topical corticosteroids, emollients, and antihistamines as described in the present illustration.