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CORRESPONDENCE
Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 412-413
Imatinib-induced transverse melanonychia: An unusual presentation


Department of Dermatology, Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication10-Jul-2015

Correspondence Address:
Anupam Das
Department of Dermatology, Medical College and Hospital, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.160500

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How to cite this article:
Das A, Podder I, Kumar D, Ghosh A, Shome K. Imatinib-induced transverse melanonychia: An unusual presentation. Indian J Dermatol 2015;60:412-3

How to cite this URL:
Das A, Podder I, Kumar D, Ghosh A, Shome K. Imatinib-induced transverse melanonychia: An unusual presentation. Indian J Dermatol [serial online] 2015 [cited 2019 Sep 18];60:412-3. Available from: http://www.e-ijd.org/text.asp?2015/60/4/412/160500


Sir,

Cutaneous adverse effects are very commonly seen with a wide plethora of drugs, imatinib mesylate being one of the more common offending agents. About 9.5% to 69% of patients receiving this drug reported with at least one cutaneous adverse reaction. [1]

Imatinib is a tyrosine-kinase inhibitor which has revolutionized the treatment of many cancers like Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST) and many other malignancies. Currently, it is considered to be the drug of choice for the treatment of CML. Most of the patients receiving imatinib experience hematological or non-hematological side effects. Skin changes are the most common non-hematological toxicities. There are very few reports of nail pigmentation alone. Prabhas et al. reported localized nail hyperpigmentation, mainly in the central part, in a patient receiving imatinib. [2] Another case of mucocutaneous lichenoid eruptions with single nail involvement in the form of longitudinal ridging has been described. [3] Subungual hyperkeratosis of finger and toe nails accompanying lichenoid eruptions on chest and upper limbs, sparing mucosa, has also been described, that required substitution of imatinib with hydroxyurea. [4] Here, we report a patient with CML who developed transverse bands of hyperpigmentation involving the nails (transverse melanonychia) while receiving imatinib.

A 50-year-old lady presented to us with the complaint of blackish discoloration of all the fingernails and toenails. She had been diagnosed with CML with a leukocyte alkaline phosphatase score of 5. A cytogenetic study showed that she was Philadelphia-chromosome-positive. On September 2013, she was started on 400 mg/day imatinib. Serial routine blood investigations showed that there was complete hematological response after 5 weeks of therapy. Around October 2013, she noted pigmentation of the fingernails whereas pigmentation of the toenails was noted by her in November 2013. The bands of hyperpigmentation progressed outwards, in due course of time. At the outset, the pigmentation was brownish but it gradually darkened with time. When she presented to us, the hyperpigmentation was darker in the middle of the nails than in the nail-bed area and tip. All fingernails were affected [Figure 1] and [Figure 2]. Similar pigmentation was also present on the toenails but they were relatively less dark. There was no change in the color of the skin. All relevant investigations were done to rule out HIV, hyperthyroidism, hemosiderosis, hyperbilirubinemia, Addison's disease, Cushing's syndrome, Vitamin B-12 deficiency and scleroderma. Besides this, the patient was not on drugs known to produce this phenomenon like cyclophosphamide, adriamycin, hydroxyurea, antimalarials, amodiaquine, quinacrine, chloroquine, antivirals (zidovudine, lamivudine). She was on imatinib, rabeprazole, cefadroxyl, domperidone, levocetirizine and fluconazole. Since she was not taking any other drug that could have caused the nail hyperpigmentation, a diagnosis of "imatinib-induced transverse melanonychia" was done for our patient.
Figure 1: Close-up clinical photograph of the fingernails

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Figure 2: Hyperpigmentation involving all the nails of fingers and toes, the pigmentation of toenails being less in comparison to fingernails

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   Discussion Top


Melanonychia is a darkening of the nail caused by deposition of melanin or other pigments occurring in two patterns-the more commonly reported longitudinal melanonychia and transverse melanonychia, which has been rarely reported. Some of the common etiologies of longitudinal melanonychia include acanthosis nigricans, Addison's disease, Vitamin B12 deficiency, PUVA etc. However, transverse melanonychia is uncommon. Medications such as cyclophosphamide, adriamycin, hydroxyurea, antimalarials notably amodiaquine, quinacrine, chloroquine. Antivirals (zidovudine, lamivudine) may cause both transverse and longitudinal bands, with multidrug chemotherapy causing the majority of the former. The mechanism of melanonychia is unknown. Potential causes include toxicity affecting the nail bed or nail matrix, focal stimulation of nail-matrix melanocytes, and photosensitization. Other rarely reported causes of transverse melanonychia include conventional radiographic therapy, total skin electron beam therapy (TSEBT), infliximab etc. [5] The difference between longitudinal and horizontal pigmented bands lies in their focus of origin. Longitudinal melanonychia occurs as a consequence of two mechanisms, one being melanocyte activation due to inflammation, infections, non-melanocytic neoplasms genetic factors and drugs. The other mechanism is melanocyte hyperplasia caused by benign melanocytic nevi or malignant melanoma. [6] Transverse pigmentation of nail probably develops due to intermittent courses of chemotherapeutic drugs like hydroxurea, imatinib (consistent with our case) due to a direct toxic effect on the nail matrix. [7]

Our patient, who was on imatinib, presented with transverse melanonychia. The patient did not take any of the aforementioned offending drugs. No history of trauma or radiation could be elicited. Systemic examination and laboratory investigations also ruled out any systemic disorder that could result in melanonychia. So, imatinib appears to be the offending agent in this case, thus including itself in the list of drugs causing transverse melanonychia.

The most common side-effects of imatinib include maculopapular rashes, erythematous eruptions and periorbital edema which are usually self-limited. Severe adverse events like Stevens Johnson syndrome, toxic epidermal necrosis, erythroderma and acute generalized exanthematous pustulosis are less common in occurrence. Lichenoid reactions, [8] lichen planus, pityriasiform eruptions, pityriasis rosea, psoriasis etc. are even rarer in occurrence. A single study has shown it to cause painful rash of the feet or palmoplantar dysaesthesia (PPD). [9]

In nearly all cases, the mechanism of hyperpigmentation remains obscure. However, a molecular mechanism has been hypothesized for the pigmentary disturbances. Imatinib targets tyrosine kinases of BCR-ABL, c -kit, and platelet-derived growth factor receptor-a. C-kit is normally expressed in skin basal cells, melanocytes, epithelial cells of breast tissue and mast cells. It has a regulatory role in melanogenesis, melanocyte homeostasis, and pigmentation. Imatinib interferes in the function of c-kit, and thus may lead to stimulation of melanocytes in the visible portion of distal nail matrix.

In conclusion, imatinib can rarely cause transverse melanonychia of both finger and toe nails. The occurrence of such a rare adverse effect with a common drug has prompted this report.

 
   References Top

1.
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. 1
    
2.
Prabhash K, Biswas G, Prasad N, Karant N, Sastry PS, Parikh PM. Imatinib-induced nail hyperpigmentation in chronic myeloid leukemia. Indian J Dermatol Venereol Leprol 2006;72:63-4.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
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. 3
    
4.
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. 4
    
5.
Quinlan KE, Janiga JJ, Baran R, Lim HW. Tranverse melanonychia secondary to total skin electron beam therapy: A report of 3 cases. J Am Acad Dermatol 2005;53(Suppl 1): S112-4.  Back to cited text no. 5
    
6.
Giraldo WA, de la Puente Bujidos C. Longitudinal melanonychia associated with limited cutaneous systemic sclerosis. J Clin Rheumatol 2014;20:118-9.  Back to cited text no. 6
    
7.
Hernández-Martín A, Ros-Forteza S, de Unamuno P. Longitudinal, transverse, and diffuse nail hyperpigmentation induced by hydroxyurea. J Am Acad Dermatol 1999;41:333-4.  Back to cited text no. 7
    
8.
Arshdeep, De D, Malhotra P, Saikia UN. Imatinib mesylate-induced severe lichenoid rash. Indian J Dermatol Venereol Leprol 2014;80:93-5.  Back to cited text no. 8
    
9.
Kumar P, Das NK, Sil A, Chakrabarti P. A patient of chronic myelogenous leukemia developing painful rash on feet. J Postgrad Med 2012;58:331-4.  Back to cited text no. 9
[PUBMED]  Medknow Journal  


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