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CASE REPORT
Year : 2013  |  Volume : 58  |  Issue : 5  |  Page : 388-392
Generalized lichenoid drug eruption associated with imatinib mesylate therapy


Department of Dermatology, Venereology, and Leprosy, R.G. Kar Medical College, 1, Khudiram Bose Sarani, Kolkata, India

Date of Web Publication30-Aug-2013

Correspondence Address:
Sudip Kumar Ghosh
Department of Dermatology, Venereology, and Leprosy, R. G. Kar Medical College, 1, Khudiram Bose Sarani, Kolkata - 700 004
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.117315

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   Abstract 

Imatinib mesylate (IM), an anticancer drug, has been widely used to treat chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST), and dermato-fibrosarcoma protuberans. Cutaneous reactions to IM have been reported to occur in varying number of patients in different case series. Non-lichenoid cutaneous reactions secondary to IM have been well-documented in the literature and are the commonest non-hematologic adverse reactions associated with its use. Lichenoid drug eruption (LDE) associated with IM therapy has rarely been reported in the literature. A case of a generalized LDE associated with IM therapy has been described here for its rarity and interesting clinical presentation. As the clinical usage of IM is increasing, one might expect an increasing number of similar patients in the future. It is thus important to realize the potential of IM to produce LDE and to differentiate this entity from idiopathic lichen planus. In the present article, the reports of IM-associated LDE, described in the PubMed and Medline database (in English language literature), have also been reviewed.


Keywords: Imatinib mesylate, lichen planus, lichenoid drug eruption


How to cite this article:
Ghosh SK. Generalized lichenoid drug eruption associated with imatinib mesylate therapy. Indian J Dermatol 2013;58:388-92

How to cite this URL:
Ghosh SK. Generalized lichenoid drug eruption associated with imatinib mesylate therapy. Indian J Dermatol [serial online] 2013 [cited 2020 Jul 14];58:388-92. Available from: http://www.e-ijd.org/text.asp?2013/58/5/388/117315

What was known?
1. Non.lichenoid cutaneous reactions secondary to imatinib mesylate are the most common non.hematologic adverse reactions associated with its use.
2. Lichenoid drug eruption usually occurs on the photo.exposed parts of the skin.



   Introduction Top


Imatinib mesylate (IM) is an anticancer drug judiciously designed to selectively inhibit certain protein tyrosinase kinase implicated in oncogenesis. [1] IM has been used to treat chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans. [1],[2],[3] Cutaneous reactions to IM have been reported to occur in 9.5-69% of patients in different series. [3] Non-lichenoid cutaneous reactions due to IM have been well-documented in the literature and are the commonest non-hematologic adverse reactions associated with its use. [4]

A case of a generalized lichenoid drug eruption (LDE) associated with imatinib mesylate therapy has been described here for its rarity and unusual clinical presentation. In view of the fact that the clinical usage of IM is growing, one might expect an increasing number of similar patients in the future. It is thus important to realize the potential of IM to produce lichenoid drug reaction and to differentiate this entity from idiopathic lichen planus. These issues have been elaborated in the present article. Reports of IM-associated lichenoid drug eruption in the English language literature, described in the PubMed and Medline database, have also been reviewed.


   Case Report Top


A 63-year-old man was referred to the dermatology department with a 3-week history of acute onset, raised, itchy, purple-colored fairly generalized skin lesions over his body. There was no history of blistering or ulceration over the lesions. Two months before the onset of the skin lesions the patient was put on monotherapy with imatinib mesylate (IM) (400 mg/day) for the treatment of CML. There was no history of allogenic bone marrow transplantation. Considering the skin eruption, IM had been discontinued ten days prior to his first dermatological consultation. According to the patient, stoppage of the drug led to mild improvement of the skin lesions. Cutaneous examination revealed numerous, well-defined, violaceous, discrete and coalescing papules and plaques over the limbs, abdomen, chest, and the back. A few scattered hyperkeratotic papules were present on his palms. The lesions exhibited koebnerisation on the chest wall. There was fine scaling but no evident vesiculation, oozing or crusting [Figure 1] and [Figure 2]. The mucosae as well as the nails and hair were uninvolved.
Figure 1: (a and b) Numerous violaceous, coalescing papules and plaques exhibiting koebnerisation and fine scaling

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Figure 2: (a and b) Close-up showing purple-colored coalescing papules and plaques with fine scaling

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Lesional punch biopsy specimens were obtained from two different sites. Histopathological examination [Figure 3] and [Figure 4] of both the specimens showed similar features. Epidermis showed hyperkeratosis with focal parakeratosis, irregular acanthosis and focal wedge-shaped hypergranulosis. Focal basal cell degeneration and pigment incontinence were found. An upper dermal band-like infiltrate comprising mononuclear cells and eosinophils was present at the dermoepidermal junction. Multiple colloid bodies were noticed. Sparse perivascular infiltrates were also seen in the dermis. Serological tests for human immunodeficiency virus (HIV) and hepatitis B and C were negative.
Figure 3: (a) Hyperkeratosis, irregular acanthosis, and focal wedge-shaped hypergranulosis, upper dermal band-like cellular infiltrate at the dermoepidermal junction and a few colloid bodies. (H and E, ×100). (b) Focal basal cell degeneration and melanin incontinence (H and E, ×400). (c) Eosinophil in the dermis (marked by arrow) (H and E, ×1000)

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Figure 4: (a) Focal parakeratosis, (marked by arrows) irregular acanthosis, wedge-shaped hypergranulosis, focal basal cell degeneration, pigment incontinence, and upper dermal band-like infiltrate (H and E, ×100). (b and c) Prominent parakeratosis (marked by arrows) (H and E, ×400)

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Based on the clinical presentation and histopathological examination, a diagnosis of generalized LDE associated with IM was made. According to the Naranjo probability scale for adverse drug reaction, this diagnosis was "highly probable". [5]

The patient was treated with topical clobetasol propionate (0.1%) cream application over the active skin lesions as well as oral antihistamines. Within a couple of weeks, almost all the lesions healed with residual post-inflammatory hyperpigmentation [Figure 5] and new lesions stopped appearing. Since the type of the adverse cutaneous drug reaction was not life- threatening, IM was gradually re-introduced to achieve a dose of 400 mg/day by hemato-oncologists. The patient was advised regular dermatological follow-up. After re-introduction of imatinib, he had a few new lesions of LP over the next couple of months. However, he was being maintained on intermittent topical steroid application over the active lesions with excellent control of the skin condition.
Figure 5: Post inflammatory hyperpigentation following resolution of skin lesions

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   Discussion Top


Non-lichenoid dermatoses associated with IM therapy may include: Maculopapular eruption, edema,  Stevens-Johnson syndrome More Details, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, vasculitis and mycosis fungoides-like eruption. [2],[3],[4],[6] Other less commonly described side effects of IM include, hypopigmentation, pityriasis rosea, psoriasis, neutrophilic eccrine hidradenitis, Sweet's syndrome, erythema nodosum, Epstein-Barr Virus-positive cutaneous B-cell lymphoproliferative disease, follicular mucinosis and pseudolymphoma-like drug eruptions amongst others. [2],[4],[6]

On the other hand, only a few reports of IM-associated lichenoid drug eruption have been described over the last decade. Lichenoid drug eruption is an interface dermatitis induced by ingestion, contact or inhalation of a variety of drugs and has a latent period that ranges from a few weeks to several months. [7] This reaction may rarely involve the oral mucosa. The latent period between the start of treatment and the appearance of LDE may be shortened if the individual has had earlier exposure to the agent. LDE have been described with a wide gamut of medications. As newer agents continue to be introduced and prescribed, the list of the offending drugs for LDE is ever expanding. These may commonly include, angiotensin converting enzyme inhibitors, thiazide diuretics, gold, antimalarials, penicillamine, nonsteroidal anti-inflammatory agents, dental amalgams, sulfasalazine, β-blockers, and proton-pump inhibitors, to name afew. [8] Clinically, these eruptions are often look like those of lichen planus (LP). LDE commonly presents as skin lesions comprising papules or plaques, usually on the photo exposed parts of the skin. Lesions of LDE are often larger in size, less monomorphic and more prone to be eczematous and associated with desquamation in contrast to that of LP. LDE often spare the oral mucosa, genitalia and typically lack Wickham's striae. [8] Unilaterality and erosions are seen more often in oral LDE compared to idiopathic LP. [9]

Patients with LDE are often taking more than one medication, which may make the recognition of the causative agent tricky. [9] Resolution of lesions on discontinuation of the offending drug favors the diagnosis of LDE. [9]

Histopathologically, a number of findings are more typical of LDE and comprise focal parakeratosis, presence of eosinophils and plasma cells, and a deeper perivascular and periadnexal infiltrate. [8] The present patient had most of these clinical and histopathological features suggestive of LDE. However, one interesting and unusual finding in the present case was the presence of LDE in both photo exposed and covered parts of the body. It is worth mentioning that, in the setting of CML, IM-associated oral LDE must be differentiated from idiopathic lichen planus, paraneoplastic pemphigus, and graft-versus-host disease. [9]

Specific causes of imatinib induced skin lesions remain elusive. Due to its fairly low molecular weight, IM is not likely to be immunogenic. The dose dependence of adverse reactions favors the assumption that imatinib related cutaneous reactions are mediated by changes in tyrosinase kinase signaling rather than immunologic mechanism. [1] It has been also proposed that the lesions in oral LDE may be closely correlated with the altered expression of epidermal markers caused by imatinib. [7]

PubMed and Medline database have been searched with the search terms 'imatinib', 'lichenoid drug eruption', 'lichenoid eruption' and 'cutaneous lichenoid eruption'. [Table 1] summarizes reported cases of IM-associated LDE in the English language literature as found in these databases. [2],[3],[4],[7],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] Patients of both sexes were affected. The severity of LDE due to IM varied from mild to severe and the extent of involvement varied from localized to extensive.
Table 1: Profile of patients of lichenoid drug eruption associated with imatinib mesylate therapy


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Some of the reported patients had only mucosal lesions [7],[9],[10],[13],[16] some had only cutaneous lesions [2],[4],[11],[14],[15],[18],[19] and the remainder had both [2],[3],[12],[17],[18] lesions. All the patients took imatinib mesylate in the dose of 400 mg/day or above. This observation probably supports the view that the IM-associated LDE are dose dependent rather than immunogenic in nature. Most common indication of IM usage was CML. [2],[4],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] In a few cases IM was used to treat GIST. [2],[3],[7]

The time interval between the adverse effects appeared and the initiation of IM ranged from one month, [2] to 15 months. [10] In some cases such drug eruptions have led to temporary or permanent discontinuation of IM. [2],[3],[4],[9],[11],[12],[13],[14],[18] The use of a systemic or topical corticosteroid and a gradual increase in the IM dose may be a useful and practical approach to permit the continuation of treatment with IM. [12] Dalmau et al. has shown that acitretin may be successfully used to treat IM-associated LDE, enabling the continuation of the effective IM dosage. [2] In the present patient, temporary discontinuation of IM improved the condition. On restarting and gradually increasing the dose of IM to 400 mg/day, only a few lesions of LP reappeared.

It is important to understand the potential of IM to produce LDE and to differentiate this entity from its idiopathic counterpart. Moreover, early recognition of the morphological pattern of such drug eruption is crucial to prevent the subsequent discontinuation of IM, which has radically changed the treatment and prognosis of CML and GIST.

 
   References Top

1.Guilhot F. Indications for imatinib mesylate therapy and clinical management. Oncologist 2004;9:271-81.  Back to cited text no. 1
[PUBMED]    
2.Dalmau J, Peramiquel L, Puig L, Fernández-Figueras MT, Roé E, Alomar A. Imatinib-associated lichenoid eruption: Acitretin treatment allows maintained antineoplastic effect. Br J Dermatol 2006;154:1213-6.  Back to cited text no. 2
    
3.Sendagorta E, Herranz P, Feito M, Ramírez P, Feltes R, Floristán U, et al. Lichenoid drug eruption related to imatinib: Report of a new case and review of the literature. Clin Exp Dermatol 2009;34:315-6.  Back to cited text no. 3
    
4.Chan CY, Browning J, Smith-Zagone MJ, Martinelli PT, Hsu S. Cutaneous Lichenoid dermatitis associated with imatinib mesylate. Dermatol Online J 2007;13:29.  Back to cited text no. 4
[PUBMED]    
5.Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 5
[PUBMED]    
6.Scheinfeld N. Imatinib mesylate and dermatology part 2: A review of the cutaneous side effects of imatinib mesylate. J Drugs Dermatol 2006;5:228-31.  Back to cited text no. 6
[PUBMED]    
7.Ena P, Chiarolini F, Siddi GM, Cossu A. Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat 2004; 15:253-5.  Back to cited text no. 7
[PUBMED]    
8.Brauer J, Votava HJ, Meehan S, Soter NA. Lichenoid drug eruption. Dermatol Online J 2009;15:13.  Back to cited text no. 8
    
9.Lim DS, Muir J. Oral lichenoid reaction to imatinib (STI 571, Gleevec). Dermatology 2002;205:169-71.  Back to cited text no. 9
[PUBMED]    
10.Brazzelli V, Muzio F, Manna G, Moggio E, Vassallo C, Orlandi E, et al. Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate. Photodermatol Photoimmunol Photomed 2012;28:2-5.  Back to cited text no. 10
[PUBMED]    
11.Sudha R, Vetrichevvel TP, Krishnarathnam K, Anandan S. Imatinib induced lichen planus. Indian J Dermatol 2011;56:351-2.  Back to cited text no. 11
[PUBMED]  Medknow Journal  
12.Kuraishi N, Nagai Y, Hasegawa M, Ishikawa O. Lichenoid drug eruption with palmoplantar hyperkeratosis due to imatinib mesylate: A case report and a review of the literature. Acta Derm Venereol 2010;90:73-6.  Back to cited text no. 12
[PUBMED]    
13.Gómez Fernández C, Sendagorta Cudós E, Casado Verrier B, Feito Rodríguez M, Suárez Aguado J, Vidaurrázaga Díaz de Arcaya C. Oral lichenoid eruption associated with imatinib treatment. Eur J Dermatol 2010;20:127-8.  Back to cited text no. 13
    
14.Kaliyadan F, Ganesan TS. Lichen planus associated with imatinib mesylate. Indian J Dermatol Venereol Leprol 2009;75:527-8.  Back to cited text no. 14
[PUBMED]  Medknow Journal  
15.Kawakami T, Kawanabe T, Soma Y. Cutaneous lichenoid eruption caused by imatinib mesylate in a Japanese patient with chronic myeloid leukaemia. Acta Derm Venereol 2009;89:325-6.  Back to cited text no. 15
[PUBMED]    
16.Basso FG, Boer CC, Corrêa ME, Torrezan M, Cintra ML, de Magalhães MH, et al. Skin and oral lesions associated to imatinib mesylate therapy. Support Care Cancer 2009;17:465-8.  Back to cited text no. 16
    
17.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;14:14.  Back to cited text no. 17
    
18.Pascual JC, Matarredona J, Miralles J, Conesa V, Borras-Blasco J. Oral and cutaneous lichenoid reaction secondary to imatinib: Report of two cases. Int J Dermatol 2006;45:1471-3.  Back to cited text no. 18
[PUBMED]    
19.Prabhash K, Doval DC. Lichenoid eruption due to imatinib. Indian J Dermatol Venereol Leprol 2005;71:287-8.  Back to cited text no. 19
[PUBMED]  Medknow Journal  

What is new?
1. Generalized lichenoid drug eruption may rarely be associated with imatinib mesylate therapy.
2. Imatinib mesylate induced lichenoid drug eruption may involve both the photo exposed and covered parts of the body.


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1]

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