|LETTER TO EDITOR
|Year : 2019 | Volume
| Issue : 1 | Page : 51-54
A first case of late-onset imatinib mesylate-induced lichenoid drug eruption
Farhana I Khan, Girishkumar R Ambade, A G. Krishna Greeshma, Anand J Asia
Department of Dermatology, Venereology and Leprosy, Government Medical College, Akola, Maharashtra, India
|Date of Web Publication||22-Jul-2019|
Dr. Farhana I Khan
Firdous Colony, Akola - 444 001, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Khan FI, Ambade GR, Greeshma A G, Asia AJ. A first case of late-onset imatinib mesylate-induced lichenoid drug eruption. Indian J Drugs Dermatol 2019;5:51-4
|How to cite this URL:|
Khan FI, Ambade GR, Greeshma A G, Asia AJ. A first case of late-onset imatinib mesylate-induced lichenoid drug eruption. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Nov 13];5:51-4. Available from: http://www.ijdd.in/text.asp?2019/5/1/51/263089
Imatinib mesylate (IM) is a 2-phenylaminopyrimidine derivative which selectively inhibits BCR-ABL, c-kit, and platelet-derived growth factor receptor (PDGFR). It has been approved for various conditions such as dermatofibrosarcoma protuberans, scleroderma, graft-versus-host disease, systemic sclerosis, systemic mastocytosis, melanoma, unresectable gastrointestinal stromal tumors (GIST), chronic myeloid leukemia (CML), myelodysplastic syndromes, hypereosinophilic syndromes, and chronic eosinophilic leukemia., IM-associated cutaneous adverse effects commonly include nonlichenoid reactions such as maculopapular eruptions, psoriasiform lesions, acute generalized exanthematous pustulosis, and Stevens–Johnson syndrome. Lichenoid drug eruption (LDE) due to IM is uncommon and has rarely been reported. In reported cases, LDE has been found to occur between 2 and 12 months after drug initiation. This case has been presented for unusually late occurrence of LDE secondary to IM, which, to best of our knowledge, has never been reported.
A 60-year-old female was a diagnosed case of Philadelphia chromosome-positive CML since April 2008. She was started on IM 800 mg/day by an oncologist, and she achieved hematological remission with IM 800 mg/day in 12 months. Then, she was maintained on IM 400 mg/day since May 2009. She presented to our hospital in June 2017 with multiple pruritic red lesions on the neck, back, dorsum of the hands and feet, and thighs. She did not give any history of fever, myalgias, fatigue, weight loss, similar episode, or recent intake of any new drug. There was no history of diabetes mellitus, tuberculosis, and hypertension. Cutaneous examination revealed well-defined erythematous lichenoid papules and plaques with minimal scaling on V-area of the neck, upper back, thighs, and dorsum of the hands and feet [Figure 1], [Figure 2], [Figure 3]. Mucosal surfaces, scalp, and nails were spared. Other general and systemic examination findings were within normal limits. She was admitted for further evaluation. Routine investigations, i.e. complete blood count, blood sugars, and renal and liver function tests, were within normal limits. HBsAg, anti-HCV, HIV, and autoimmune workup were negative. LDE due to IM, psoriasis, and leukemia cutis were our differential diagnoses. A skin biopsy from plaque was done. Histopathological examination on hematoxylin and eosin staining showed focal parakeratosis, focal absence of the granular layer, and inflammatory infiltrate consisting of lymphocytes, plasma cells, and eosinophils at dermoepidermal junction [Figure 4].
|Figure 1: Multiple erythematous and hyperkeratotic papules and plaques over dorsum of the hands|
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|Figure 2: Erythematous and hyperkeratotic papules and plaques over dorsum of the feet|
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|Figure 3: Multiple lichenoid papules and plaques with minimal scaling, in a photodistributed pattern on V-area of the neck and upper back|
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|Figure 4: Histopathology on hematoxylin and eosin staining: 1 – focal parakeratosis; 2 – focal absence of the granular layer; 3 – interface infiltrate is less dense and more pleomorphic, with abundant plasma cells and eosinophils|
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The absence of myeloid cells in the dermis and the presence of focal parakeratosis and eosinophilia on histopathological examination ruled out other differentials. These findings confirmed the diagnosis of LDE. Hence, IM was temporarily stopped, and topical corticosteroids (clobetasol propionate 0.05% cream) twice daily application with systemic antihistaminic drug (tablet cetirizine 10 mg once daily) were started. Within 2 weeks, there was complete healing of all the lesions with hyperpigmentation [Figure 5], [Figure 6], [Figure 7]. After oncologist consultation, IM was restarted in a reduced dose of 300 mg/day. Topical steroids were continued for 1 more week with once daily application and then stopped. Sustained complete remission achieved, and no recurrence in lesions was observed at 1 and 6 months of follow-ups.
|Figure 5: Posttreatment photograph of the dorsum of hands after 1 month; healing with hyperpigmentation is seen|
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|Figure 6: Posttreatment photograph of the dorsum of feet after 1 month; healing with hyperpigmentation is seen|
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|Figure 7: Posttreatment photograph of the upper back and nape of the neck|
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IM is a tyrosine kinase inhibitor. It inhibits the fusion product BCR-ABL which acts through the tyrosine kinase pathway to cause proliferation of leukemic cells in CML. IM also inhibits c-kit and PDGFR which acts through the tyrosine kinase pathway. Since the c-kit receptor is considered as the etiological factor in the pathogenesis of dermatofibrosarcoma protuberans, GIST, systemic sclerosis, and systemic mastocytosis, hence, IM is used at doses of 400–600 mg/day in CML, GIST, dermatofibrosarcoma protuberans, and systemic mastocytosis and at low dose of 200 mg/day in systemic sclerosis.,
Imatinib therapy carries potential for several side effects. The most common toxicities associated with this drug are mild nausea (70%) and diarrhea (56%). The other side effects include fluid retention, muscle cramps, skin rashes, and hematologic toxicity including hemolytic anemia and renal and hepatic failure. The most frequent imatinib-related cutaneous adverse events are maculopapular eruptions, erythematous eruptions, rashes, edema, and periorbital edema., Other cutaneous adverse effects are pigmentary disorders – hypopigmentation or depigmentation, hyperpigmentation, psoriasis and psoriasiform eruption, pityriasis rosea-like eruption, acute generalized exanthematous pustulosis, Stevens–Johnson syndrome, urticaria, neutrophilic dermatosis, photosensitivity, porphyria and pseudoporphyria, and uncommonly lichenoid reactions.,,
The term “lichenoid” refers to papular lesion of certain skin disorders which look like lichen planus (LP). Clinically, LDE simulates LP, but there are some differentiating features between the two. The lesional distribution of an LDE differs from that of LP, usually affecting the extensor aspects of the extremities and dorsal hands. Mucosal and nail involvement is rare. The eruption can occur months or years after administration of the offending drug. Healing with hyperpigmentation is seen in LDE as observed in our case. Histology of LDE, as well as LP, reveals a nonspecific lichenoid interface dermatitis, basal keratinocyte apoptosis, and pigmentary incontinence. Histopathological findings more specific of LDE include focal parakeratosis, focal absence of granular layer, presence of eosinophils and plasma cells, a deeper perivascular infiltrate, with a higher proportion of necrotic keratinocytes than seen in classic LP. In LP inflammatory infiltrate is more dense, mainly lymphocytic with saw-tooth appearance of rete ridge.
Lichenoid eruption to imatinib is also an adverse cutaneous reaction that is rarely seen in patients receiving imatinib therapy. There are occasional reports of lichenoid reaction due to imatinib. In the literature review, we found few reports of imatinib-associated cutaneous lichenoid eruption. Roux et al. reported a case of lichenoid cutaneous eruption requiring the suspension of drug and recurrence after reintroduction of imatinib, whereas Prabhash and Doval reported the occurrence of lichenoid skin eruption resolving without any treatment. In 2006, Dalmau et al. reported four cases of imatinib-induced lichenoid skin eruption consisting of three patients with CML and one with GIST. In their report, they stated that imatinib had necessarily been discontinued in one patient, whereas improvement achieved by concomitant administration of acitretin without need of imatinib dose alteration in remaining three patients. In 2018, Rajashekar et al. reported a case of imatinib-induced lichenoid skin eruption after 2 months of therapy with IM and conservative management by topical emollients and steroids without discontinuing IM. Kuraishi et al. reported a case of lichenoid eruptions on the extremities with palmoplantar hyperkeratosis that responded to temporary discontinuation of imatinib. Although pathophysiology of cutaneous reactions is unclear, altered tyrosine kinase signaling with the possible role of PDGFR and inhibition of c-kit which is normally expressed in several skin cells has been proposed as the underlying mechanism. Furthermore, Bhatia et al. in their report of LP with imatinib discussed that imatinib-related cutaneous reactions are mediated by changes in tyrosine kinase signal transduction mechanism rather than immunologic mechanism.
Naranjo scale score was 6 suggestive of probable drug reaction.
In all reported cases, the duration of appearance of LDE was between 2 and 6 months after starting IM therapy. In our case, LDE appeared after 9 years of starting IM therapy. From this, we conclude that LDE to IM may occur several years after starting the drug. We report this case because of delayed occurrence of LDE secondary to IM.
It is also concluded that low-dose or standard-dose imatinib reinduction following short-time discontinuation may be a reasonable therapeutic choice in case of severe and nontolerable LDE.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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