|Year : 2015 | Volume
| Issue : 4 | Page : 993-996
Imatinib mesylate induced erythroderma: A rare case series
Sumir Kumar, Bharat Bhushan Mahajan, Sandeep Kaur, Raja Paramjeet Singh Banipal, Amarbir Singh
Department of Dermatology, Venereology and Leprology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
|Date of Web Publication||15-Feb-2016|
Skin OPD, 1st Floor, Guru Gobind Singh Medical Hospital, Sadiq Road, Faridkot, Punjab - 151 203
Source of Support: None, Conflict of Interest: None
Imatinib is a tyrosine kinase inhibitor approved as a first line treatment for chronic myeloid leukemia and gastrointestinal stromal tumors. Usually the drug is well-tolerated with hematological adverse effects being most commonly seen. Dermatological side effects are seen in 9.5-69% of patients on imatinib; majority of which are minor and self-limiting. We, hereby, report a case series of erythroderma occurring secondary to imatinib in two patients with chronic myeloid leukemia. Both the patients improved upon the discontinuation of the drug. The literature review revealed only six probable cases of erythroderma due to imatinib. So, this case series is being reported for the rarity of this adverse effect of imatinib.
Keywords: Adverse cutaneous drug reaction, erythroderma, imatinib
|How to cite this article:|
Kumar S, Mahajan BB, Kaur S, Banipal RP, Singh A. Imatinib mesylate induced erythroderma: A rare case series. J Can Res Ther 2015;11:993-6
| > Introduction|| |
Imatinib mesylate is the first of a novel group of drugs targeting protein tyrosine kinases and has been approved as a first-line therapy for chronic myeloid leukemia (CML). The drug is mostly well-tolerated. Few side effects are reported with imatinib, consisting mainly of hematological side effects such as neutropenia and thrombocytopenia. Incidence of dermatological adverse effects varies between 9.5 and 69%. There are only six probable cases of exfoliative dermatitis due to imatinib reported in literature. ,,,,
So, this case series is being reported for the rarity of this adverse effect of imatinib mesylate and to sensitize dermatologists and oncologists regarding this potentially severe cutaneous adverse effect to aid in timely intervention and decrease patient suffering.
| > Case Reports|| |
A 45-year-old male presented in dermatology department with generalized body rash and scaling of 4 months' duration. The rash initially started on trunk and rapidly became generalized and was associated with intense itching. He complained of air intolerability in the form of burning and needle prick sensation upon contact with air. So, he was keeping his whole body wrapped in clothes, even his scalp and face, in order to avoid room air. He also complained of swelling on his face, hands, and feet. He developed ulcerative lesions on his lower lip and scalp about 15 days after the onset of body rash. For the past 4 months, he was being treated symptomatically without much relief.
Past medical history revealed that he was diagnosed with CML about 6 months back. So, he was started on imatinib mesylate 400 mg/day monotherapy, which led to the improvement of his hematological malignancy.
On further probing, he mentioned worsening of his cutaneous complaints about 1.5 month back when dose of imatinib mesylate was increased to 800 mg/day (attained hematological remission with 800 mg/day dose).
On examination [Figure 1], dusky blanchable erythema and fine scaling was evident on the whole body including palms, soles, and face [Figure 1]d]. There was sparing of depths of folds on neck and abdomen (deck chair sign) [Figure 1]e]. Scalp inspection showed multiple, confluent, well-defined, irregularly shaped, erythematous ulcers of size ranging from 3 to 7 cm in diameter and about 0.2 cm deep with floor covered with pus [Figure 1]a]. Diffuse noncicatricial alopecia was evident on the whole scalp. There was seen periorbital edema and loss of eyebrows as well as eyelashes [Figure 1]b and c]. An ill-defined erosion of size 1.5 × 1.5 cm in diameter was present over the lower lip [Figure 1]b]. Crusting and fissuring was seen along lip margins. Profound, pitting edema was seen on both hands and feet with fissures present around wrist and interphalangeal joints [Figure 1]d]. Nail examination revealed yellowish, thickened nail plates with subungual hyperkeratosis, onychomadesis and absent cuticle [Figure 1]f]. Routine investigations including complete blood count and liver and renal function tests were within normal limits. Skin biopsy showed features of spongiotic dermatitis [Figure 2]. The drug was immediately stopped and he was managed with oral steroids (prednisolone 1 mg/kg/day); antibiotics; antihistaminics; and topical steroids along with general measure for erythroderma including nutritional, fluid, electrolyte, and temperature maintenance. The rash subsided completely in about 2 weeks [Figure 3]. As erythroderma is considered as severe cutaneous adverse drug reaction, so rechallenge was not attempted. In this case, causality assessment using Naranjo scale showed that imatinib was the probable cause for the adverse drug reactions (ADRs; score 7). Imatinib was replaced with hydroxyurea 500 mg twice a day without recurrence of erythroderma and the patient has been in hematological remission with hydroxyurea since then.
|Figure 1: (a) Ulcers and alopecia on the scalp. (b) Periorbital edema. (c) Alopecia affecting eyebrows and eyelashes. (d) Diffuse erythema and scaling on trunk and upper limbs, edema on both hands. (e) Scaling and erythema on neck with deck-chair sign. (f) Nail changes|
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|Figure 2: Histopathology (H and E, ×10): Focal parakeratosis, spongiosis, and edema of dermis with mild perivascular infiltration by lymphomononuclear cells and eosinophils. H and E = Hematoxylin and eosin|
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|Figure 3: (a) Clearance of scaling and edema of face. (b) Healed ulcers on scalp with post-inflammatory hypopigmentation. Regrowth of scalp hair seen. (c) Normalization of skin on trunk. (d) Clearance of edema from hands with few areas of hypopigmentation seen on dorsum of fingers. Nail changes still persistent|
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A 45-year-old female, known case of CML on treatment with imatinib 400 mg/day (in hematological remission) since 3 months prior to presentation, presented with generalized pruritus, erythema, and scaling of 20 days' duration. She also complained of pain and burning sensation on exposure to air. She also used to have nausea and vomiting with drug intake. Past medical history did not reveal any chronic illness like hypertension, diabetes, bronchial asthma, tuberculosis, or epilepsy. On examination, diffuse dusky erythema and scaling was evident. There was bilateral conjunctivitis. Abdominal palpation showed splenomegaly 3 cm below left costal margin. Routine investigations revealed normal complete blood counts were within normal limits without any evidence of cytopenias.
Diagnosis of erythroderma due to imatinib was made. The drug was stopped and patient was managed with oral and topical steroids, emollients, antihistamines. She improved markedly both symptomatically as well as objectively on subsequent follow-ups. In this case, causality assessment using Naranjo scale showed that imatinib was the probable cause for the ADRs (score 7). She was subsequently shifted to hydroxyurea 500 mg twice a day which helped to attain hematological remission. After about 6 months of hydroxyurea, she developed pancytopenia which improved with temporary discontinuation of hydroxyurea and supportive management.
| > Discussion|| |
Imatinib inhibits several tyrosine kinases including BCR-ABL, c-kit, and platelet-derived growth factor receptor, which are central to the pathogenesis of human cancers. 
Various cutaneous adverse effects of imatinib are given in [Table 1].
|Table 1: Cutaneous adverse effects of imatinib mesylate with possible underlying pathophysiology |
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Milder skin reactions are commoner (30-40%) than the severe ones (2-5%). The common side effects include maculopapular eruptions, periorbital edema; and are usually self-limited. Severe but uncommon skin reactions include Stevens Johnson's syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. Rare cutaneous eruptions are exfoliative dermatitis, lichenoid reactions, pityriasiform eruptions, psoriasis, and reactivation or induction of porphyria cutanea tarda. 
Exfoliative dermatitis generally occurs 1-3 weeks after starting therapy on initial exposure and within hours to days on rechallenge. Hypersensitivity reaction as a mechanism has been postulated.  Both of our patients complained of discomfort in the form of pain, burning or needle pricking sensation upon exposure to air. One patient had severe ulcerations covering most of the scalp. These features have not been previously mentioned in the literature, so may represent additional cutaneous side effects of imatinib therapy. Moreover, these patients had exfoliative dermatitis persisting for months before reporting to our department, which highlights the lack of awareness regarding this potential side effect of imatinib among the practicing physicians, oncologists, and dermatologists adding to the suffering of the subjects already facing a life-threatening malignancy.
As the milder side effects of imatinib are usually self-limiting, it can be continued under the cover of oral antihistaminics and topical steroids. In contrast, severe reactions require discontinuation of drug. Oral desensitization has been found to be successful in some patients with leukemia.  For imatinib-intolerant patients, dasatinib and nilotinib (second generation tyrosine kinase inhibitors) are the alternatives.  However, both of our patients were treated with hydroxyurea (choice based on availability and affordability) without recurrence of erythroderma and hydroxyurea was associated with good clinical and hematological response in both the patients.
Thus, we report two cases of this rare adverse effect of imatinib which required discontinuation of the drug. The physicians should be aware of this being a cause of erythroderma to aid in the timely management.
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[Figure 1], [Figure 2], [Figure 3]