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 Table of Contents  
LETTER TO EDITOR
Year : 2021  |  Volume : 7  |  Issue : 1  |  Page : 46-48

Imatinib mesylate-induced psoriasiform drug reaction: A case of dose-dependent cutaneous toxicity


Department of Dermatology, SKNMC, Pune, Maharashtra, India

Date of Submission27-Apr-2020
Date of Decision20-Nov-2020
Date of Acceptance22-Feb-2021
Date of Web Publication25-Jun-2021

Correspondence Address:
Aditya Holani
Department of Dermatology, SKNMC, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_25_20

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How to cite this article:
Holani A, Khatu S, Bagane R, Bedi A. Imatinib mesylate-induced psoriasiform drug reaction: A case of dose-dependent cutaneous toxicity. Indian J Drugs Dermatol 2021;7:46-8

How to cite this URL:
Holani A, Khatu S, Bagane R, Bedi A. Imatinib mesylate-induced psoriasiform drug reaction: A case of dose-dependent cutaneous toxicity. Indian J Drugs Dermatol [serial online] 2021 [cited 2021 Dec 2];7:46-8. Available from: https://www.ijdd.in/text.asp?2021/7/1/46/319352



Sir,

Imatinib, being a tyrosine kinase inhibitor, is approved as a first-line treatment for gastrointestinal stromal tumors (GIST) as well as chronic myeloid leukemia (CML).[1] GIST is the most common sarcoma, accounting for 18% of all sarcomas and 1% of all intestinal neoplasms. GISTs arise due to oncogenic mutations in the KIT tyrosine kinase, and subsequently, it was found that mutations in platelet-derived growth factor receptor α can also occur.[2] The drug is mostly well-tolerated. Few side effects reported with imatinib are mainly hematological such as neutropenia and thrombocytopenia. The incidence of dermatological adverse effects varies between 9.5% and 69%.

A 53-year-old female patient, a diagnosed and operated case of duodenal GIST presented to the dermatology outpatient department with generalized erythematous pruritic scaly lesions over the face, trunk, and both upper limbs for the past 35–40 days. The rash first started on the face and then gradually increased to involve the upper limbs and the trunk. She was started on Imatinibmesylate 400 mg once daily for the management of GIST for the past 4 months. After about 3 months of treatment, she started developing this progressive pruritic rash and periorbital edema. There was no history of fever, cough, and coryza with rash, photosensitivity, or working in fields. Similarly, there was no history of oral or genital lesions.

On examination, dusky diffuse erythema with overlying semi-adherent scaling was present over the face [Figure 1], neck, flexor, and extensor aspect of bilateral upper limbs with a relative sparing of flexural areas [Figure 2]. Multiple hyperpigmented scaly papules over the abdomen and periumbilical area were also present [Figure 3]. Oral and genital mucosa appeared to be normal. Examination of the scalp revealed diffuse scaling.
Figure 1: Diffuse erythematous rash with scaling present over the face and upper limbs.

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Figure 2: Scaling and erythema involving flexor aspect of upper limbs with sparing of cubital fossa.

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Figure 3: Multiple hyperpigmented scaly papules over the abdomen and periumbilical area.

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There was no evidence of significant lymphadenopathy or hepatosplenomegaly. Based on the history and clinical examination, differential diagnosis of Imatinib mesylate-induced exfoliative dermatitis, adult onset atopic dermatitis, psoriasiform dermatitis, and seborrheic dermatitis were considered.

Complete blood count, liver function test with enzymes, and renal function test with electrolytes revealed no significant abnormalities. Enzyme-linked immunosorbent assay for human immunodeficiency virus and Hepatitis B-surface antigen was nonreactive. Histopathology of skin punch biopsy showed hyperkeratosis, focal parakeratosis, and irregular acanthosis with few necrotic keratinocytes. There was moderate perivascular inflammatory cell infiltrate comprising of predominantly lymphocytes, histiocytes, and eosinophils. Mild edema in papillary dermis was also noted. Based on the history and histopathology, the diagnosis of exfoliative dermatitis or psoriasiform drug rash secondary to imatinibmesylate was made. The patient was advised to stop Imatinib and consult the oncologist for alternative management options. She was started on antihistaminines, mild topical fluorinated steroid preparation and emollients. She responded well to the supportive treatment with complete resolution of rash within 2 weeks. The papular lesions over the abdomen healed with hyperpigmentation [Figure 4]. She did not need oral steroids.
Figure 4: Near complete resolution of lesions with stoppage of imatinib and other supportive treatment.

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As IM was needed for the treatment of malignancy, after consulting with the oncologist, IM was reintroduced after 6 weeks at half the initial dosage, i.e., 200 mg once daily. The patient tolerated the dose well without any cutaneous reaction as observed regularly at an interval of 2 weeks for a period of 3 months. Furthermore, she remained in remission for GIST with the same dosage.

Imatinibmesylate is a 2-phenylaminopyrimidine derivative and a tyrosine kinase inhibitor. It inhibits several tyrosine kinases, including BCR-ABL, c-kit, and platelet-derived growth factor receptor, which are central to the pathogenesis of human cancers.[3] It is mainly used for CML and GIST. Milder skin reactions are more common (30%–40%) with Imatinib 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.[4] Rare cutaneous eruptions are exfoliative dermatitis, lichenoid reactions, pityriasiform eruptions, psoriasis, reactivation or induction of porphyria cutaneatarda, and hair depigmentation.[3],[5]

The pathophysiology of imatinib-associated skin reactions is unclear. The majority of these reactions seem to directly depend on its mechanism of action, namely the inhibition of the physiologic function of cutaneous protein kinases and appear to be dose dependent.[6] Other cutaneous reactions observed with Imatinib are caused by immune-mediated hypersensitivity and generally consist of urticaria, angioedema, maculopapular rash up to more severe cases of acute generalized exanthematous pustulosis, Stevens–Johnson syndrome, neutrophilic dermatitis, and mucositis[7] [Table 1]. In case of adverse reactions, treatment discontinuation and symptomatic therapy are generally indicated.
Table 1: Skin reaction association to Imatinib according to the presumed pathogenetic mechanism

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The evaluation of the type and severity of the adverse reaction is crucial. If the reaction is predictable, dose dependent, and milder, it is often possible to avoid treatment discontinuation. In such cases, combining a topical steroid treatment with emollient or even adding a few weeks-course of systemic steroid and eventual tapering of the therapeutic dose helps in majority of the cases.[8] On the other hand, when the clinical presentation suggests an IgE-mediated hypersensitivity reaction or if the cutaneous lesions are particularly severe, and there are no equally effective therapeutic options available, oral desensitization may be indicated.[9] For imatinib-intolerant patients, dasatinib and nilotinib (second-generation tyrosine kinase inhibitors) are the alternatives.[10]

Our case presented with milder form of psoriasiform rash, and it responded well to oral antihistaminies, topical steroids and topical emollients along with temporary discontinuation of therapy, indicating that it is most likely a dose dependent reaction in our patient. Therefore, being a dose-dependent reaction, reintroduction of Imatinib with a low dose protocol helped in achieving clinical remission as well as avoiding cutaneous reactions.

In conclusion, skin rashes are well-recognizable side effect of Imatinib treatment. The dermatologists should be aware of pathophysiology of such reactions for their proper management and predicting prognosis. It is also concluded that low-dose or standard-dose Imatinib reinduction following short-term discontinuation may be a reasonable therapeutic choice in case of mild-to-moderate drug reactions.


  Declaration of patient consent Top


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Guilhot F. Indications for imatinibmesylate therapy and clinical management. Oncologist 2004;9:271-81.  Back to cited text no. 1
    
2.
Balachandran VP, DeMatteo RP. Gastrointestinal stromal tumors: Who should get imatinib and for how long? Adv Surg 2014;48:165-83.  Back to cited text no. 2
    
3.
Kumar M, Mandal PK, Dolai TK, Bhattacharrya M. Imatinib causing drug rash with eosinophilia and systemic symptoms: A rare cutaneous reaction. Indian Dermatol Online J 2014;5:S120-2.  Back to cited text no. 3
    
4.
Khan FI, Ambade GR, Greeshma A G, Asia AJ. A first case of late-onset imatinibmesylate-induced lichenoid drug eruption. Indian J Drugs Dermatol 2019;5:51-4.  Back to cited text no. 4
  [Full text]  
5.
Hartmann JT, Haap M, Kopp HG, Lipp HP. Tyrosine kinase inhibitors-A review on pharmacology, metabolism and side effects. Curr Drug Metab 2009;10:470-81.  Back to cited text no. 5
    
6.
Sanghavi SA, Dongre AM, Khopkar US. Imatinibmesylate induced erythroderma. Indian J Dermatol Venereol Leprol 2012;78:408.  Back to cited text no. 6
  [Full text]  
7.
Paolo CD, Minetti S, Mineni M, Inverardi S, Rizzini FL, Cinquini M, et al. Cutaneous adverse reactions to imatinib: A case report of a successful slow protocol for induction of drug tolerance. J Allergy Ther 2015;5:203. doi:10.4172/2155- 6121.1000203.  Back to cited text no. 7
    
8.
Tanvetyanon T, Nand S. Overcoming recurrent cutaneous reactions from imatinib using once-weekly dosing. Ann Pharmacother 2003;37:1818-20.  Back to cited text no. 8
    
9.
Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, et al. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: An open-label multicentre randomised phase 3 trial. Lancet Oncol 2010;11:942-9.  Back to cited text no. 9
    
10.
Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial. Lancet 2006;368:1329-38.  Back to cited text no. 10
    


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