Myriads of cutaneous manifestations with Nilotinib, treated by acitretin – a case report

Amrita A Hongal; TN Revathi; Seetharampura Ramamurthy Radhika; Kanathur Shilpa

doi:10.4103/ijdd.ijdd_13_20

CASE REPORT

Year : 2020 | Volume : 6 | Issue : 2 | Page : 85-87

Myriads of cutaneous manifestations with Nilotinib, treated by acitretin – a case report

Amrita A Hongal, TN Revathi, Seetharampura Ramamurthy Radhika, Kanathur Shilpa
Department of Dermatology, Venereology, Leprosy, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission	20-Mar-2020
Date of Decision	06-Jun-2020
Date of Acceptance	19-Nov-2020
Date of Web Publication	28-Dec-2020

Correspondence Address:
Seetharampura Ramamurthy Radhika
#12, Raghav Kuteera, 1^st Cross, Sri Krupa Layout, Abbigere, Chikkabanavara Post, Bengaluru - 560 090, Karnataka
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/ijdd.ijdd_13_20

Abstract

A remarkable advancement is been made in the treatment of cancer, through chemotherapeutic drugs like tyrosine kinase inhibitors (TKI), etc. Chemotherapy induced cutaneous side effects are multiple and usually they are underreported. Nilotinib is a second generation TKI, which is approved for imatinib resistant CML. Various cutaneous and its appendageal changes have been noticed with the use of nilotinib usage. Here, we report such case of a 34 year old male, who is a case of CML being treated with Nilotinib for 2.5 years, presented to us with perforating folliculitis, psoriasiform dermatosis, KP like lesions, madarosis and textural changes of scalp hair.

Keywords: Acitretin, chronic myelogenous leukemia, cutaneous side effects, defective keratinization, nilotinib

How to cite this article:
Hongal AA, Revathi T N, Radhika SR, Shilpa K. Myriads of cutaneous manifestations with Nilotinib, treated by acitretin – a case report. Indian J Drugs Dermatol 2020;6:85-7

How to cite this URL:
Hongal AA, Revathi T N, Radhika SR, Shilpa K. Myriads of cutaneous manifestations with Nilotinib, treated by acitretin – a case report. Indian J Drugs Dermatol [serial online] 2020 [cited 2023 Dec 7];6:85-7. Available from: https://www.ijdd.in/text.asp?2020/6/2/85/305122

Introduction

In the past few decades, cancer chemotherapy has attained major medical advances with the invention of newer drugs directed against cancer-specific molecules and signaling pathways, thus increasing the selectivity of drug action and decreasing its side effects.^[1]

Nilotinib is a new oral tyrosine kinase inhibitor, designed to overcome imatinib resistance in chronic myelogenous leukemia (CML). Nilotinib has demonstrated potent antiproliferative activity against cell lines harboring KIT mutations that are associated with imatinib resistance.^[2] With the use of nilotinib, cutaneous reactions that are commonly reported include morbilliform rash, keratosis pilaris-like lesions, dry skin, pruritus, alopecia, eczema, urticaria, erythema nodosum, and Sweet's syndrome.

Case Report

A 34-year-old male patient of chronic myeloid leukemia on treatment with nilotinib for 2.5 years came with complaints of blackish-colored itchy skin lesions over the legs and hands for 1 year. On examination, multiple well defined hyperpigmented hyperkeratotic plaques of varying sizes and shapes present over the dorsum of foot, knees and hands; few hyperkeratotic papules with central crusting present over the bilateral lower limbs; also few follicular oriented papules with keratotic plugging seen over outer aspects of arms. On close examination he had lateral thinning of eyebrows, scalp hair showed textural changes; [Figure 1] –a- showing madarosis (black rectangle), b - proriasiform lesions of legs, c- perforating folliculitis (black circle) with psoriasiform lesions, d - proriasiform lesions of hands). Upon retrospective questioning, the patient gave a history of the textural changes of scalp hair after he was started on nilotinib. The patient was advised biopsy from two sites. Hyperkeratotic crusted papule showed psoriasiform epidermal hyperplasia with hyperkeratosis, parakeratosis, and focal loss of the granular layer. Biopsy from follicular keratotic papule showed dilated infundibulum filled with orthokeratotic material and degenerated basophilic debris consisting of neutrophils and vertical perforation. Hepatitis B and C serology was negative. Light microscopy of scalp hair did not reveal any structural abnormality of hair. Considering temporal correlation of nilotinib with occurrence of skin lesions, a possibility of nilotinib-induced perforating folliculitis and psoriasiform dermatitis was thought of. Since the patient had multiple manifestations of altered keratinization, the patient was worked up for acitretin and was started on acitretin 25 mg OD, which was given for 3 months and then tapered over the next 3 months with acitretin 25 mg on alternate days, and nilotinib was continued. His blood picture was routinely monitored. He showed a progressive improvement in his psoriasiform lesions, perforating folliculitis, and KP-like lesions allowing the oncologist to continue nilotinib as his CML status was maintained. However, there was no improvement with frizzy textural changes of scalp hair and madarosis [Figure 2].

Figure 1: Pretreatment photographs of the patient (a-madarosis [black rectangle], b-psoriasiform lesions of legs, c-perforating folliculitis [black circle] with psoriasiform lesions, d-psoriasiform lesions of hands)

Click here to view

Figure 2: Posttreatment with acitretin showing near-to-complete clearance of psoriasiform lesions, perforating folliculitis (which can be seen in b, c, and d) but no improvement in madarosis (a)

Click here to view

Discussion

Nilotinib is a second-generation tyrosine kinase inhibitor approved for use in CML. Even though it is structurally similar to imatinib, it shows 10–30 times more potency than imatinib at inhibiting BCR-ABL tyrosine kinase activity. It is usually well tolerated. However, adverse cutaneous reactions are one of the most common side effects, with incidence varying from 20% to 60% in clinical trials. The possible mechanism of these cutaneous side effects could be inhibition of tyrosine kinases in skin and hair follicles as well as the decreased extracellular matrix protein synthesis in fibroblasts by nilotinib.^[3] Keratosis pilaris-like or folliculitis-like lesions are known to be induced by vemurafenib through the same ERK/MAPK pathway,^[4],[5] and multikinase inhibitor, the sorafenib, acts through PDGFR and c-Kit pathway.^[6] Common cutaneous reactions caused by these groups of drugs are morbilliform rash, keratosis pilaris-like lesions, psoriasiform lesions, dry skin, pruritus, alopecia, eczema, urticaria, erythema nodosum, Sweet's syndrome, and alopecia areata. Diffuse follicular papules were reported with nilotinib after 2 weeks of therapy in a patient of CML by Yassin et al., but lesions disappeared in 7 days after nilotinib discontinuation unlike in our case where lesions were KP like and perforating folliculitis like and they appeared after the long-term use of nilotinib.^[7] However, management of these cutaneous reactions is symptomatic treatment with topical emollients, topical steroids, and systemic antihistamines and a few cases requiring a short course of oral steroids. Interruption or discontinuation of nilotinib is not indicated or advisable due to nonthreatening nature of cutaneous lesions and excellent antineoplastic effect of nilotinib.

The mode of action of acitretin in hyperkeratotic disorders is by acting on the target receptor sites such as cellular retinoic acid-binding protein, the epidermal growth factor (EGF) receptor, and retinoic acid nuclear receptors. In addition, the EGF receptor may be involved, as acitretin has been found to influence normal modulation of cell growth in both normal fibroblasts and abnormal cell lines. Cyclic adenosine monophosphate-dependent protein kinases and ornithine decarboxylase are considered to be the probable mediators of clinical response.^[8] There are no significant interactions of nilotinib with acitretin as per the published literature. According to the case series by Dalmau et al., acitretin not only maintained the antineoplastic effect of imatinib but also improved its cutaneous side effects caused due to imatinib-induced defective keratinization.^[9] Our patient was started on acitretin considering the nilotinib-induced abnormal keratinization. As the patient showed near-total resolution, he was started on topical tazarotene and was maintaining the remission after 5 months of its use. We planned to restart acitretin in this patient in case of recurrence.

Conclusion

To the best of our knowledge, this is the first case of nilotinib-induced cutaneous changes of varied morphological presentations such as perforating folliculitis, psoriasiform dermatitis, KP-like lesions, madarosis, and frizzy textural changes of scalp hair that were seen in a single patient. This case report also emphasizes the use of acitretin for treating various cutaneous side effects of nilotinib-related disorders of keratinization of follicular and nonfollicular skin.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Brazzelli V, Grasso V, Borroni G. Imatinib, dasatinib and nilotinib: A review of adverse cutaneous reactions with emphasis on our clinical experience. J Eur Acad Dermatol Venereol 2013;27:1471-80.
2.	Blay JY, von Mehren M. Nilotinib: A novel, selective tyrosine kinase inhibitor. Semin Oncol 2011;38 Suppl 1:S3-9.
3.	Tawil MH, El Khoury R, Tomb R, Ghosn M. Nilotinib-induced keratosis pilaris associated with alopecia areata and eyebrow thinning. Int J Trichology 2017;9:87-9.
4.	Shimizu A, Hattori M, Takeuchi Y, Ishikawa O. Generalized keratosis pilaris-like eruptions in a chronic myelogenous leukemia patient treated with Nilotinib. J Dermatol 2016;43:1100-1.
5.	Leong WM, Aw CW. Nilotinib-induced keratosis pilaris. Case Rep Dermatol 2016;8:91-6.
6.	Patel AB, Solomon AR, Mauro MJ, Ehst BD. Unique cutaneous reaction to second- and third-generation tyrosine kinase inhibitors for chronic myeloid leukemia. Dermatology 2016;232:122-5.
7.	Yassin MA, Mudawi D, Abdulqadir N, Kassem N. Cutaneous manifestations of Nilotinib. Int J Hematol Blo Dis 2018;3:1-3.
8.	Pilkington T, Brogden RN. Acitretin. Drugs 1992;43:597-627.
9.	Dalmau J, Peramiquel L, Puig L, Fernandez-Figueras MT, Roe E, Alomar A. Imatinib-associated lichenoid eruption: Acitretin treatment allows maintained antineoplastic effect. Br J Dermatol 2006;154:1213-6.