What Are These Hyperpigmented Bands on the Fingernails?

An 83-year-old woman was referred to our clinic with discoloration on her fingernails and toenails. The patient was diagnosed with invasive ductal carcinoma in the right breast 1 year ago. She underwent a right modified mastectomy and then received chemotherapy and localized radiotherapy. She reported that the nail pigmentation started 3 months after beginning a chemotherapy regimen of doxorubicin, dexamethasone, and cyclophosphamide. No prior nail abnormalities, history of recent trauma, or nail loss was reported. She also reported no accompanying pain or discomfort. During examination, multiple, brown-bluish, pigmented, horizontal nail bands ranging from poorly demarcated to well-demarcated were observed in all fingernails and toenails (Figure). No mucosal or skin involvement was detected. Further investigation showed no metabolic, endocrinologic, autoimmune, or infectious disorders. 

What’s Your Diagnosis?
Scroll below for the answer.

Chemotherapy-Induced Transverse Melanonychia

Chemotherapy-induced transverse melanonychia (also known as horizontal melanonychia or transverse hyperpigmented nail bands) is a rare, benign nail pigmentation disorder characterized by transverse hyperpigmented bands that can involve both fingernails and toenails. Activation of melanocytes by various causative factors leads to an increase in melanin production in the nail matrix.¹ Melanonychia refers to a darkening of the nail that may present with different morphologic patterns, including longitudinal, diffuse, and transverse patterns.¹

Hypo- and hyperpigmented nail changes can be seen after uses of various causative drugs, including some chemotherapeutics, antiretrovirals, antimalarials, and metals. Beau lines, true leukonychia, apparent leukonychia (such as Muehrcke lines), and melanonychia are the most common nail pigmentation anomalies reported after common medical therapies.²

Melanonychia, or dark brown-black hyperpigmentation on the nail plate, is described in three morphologic patterns: longitudinal melanonychia (also known as melanonychia striata) extending proximally from the nail matrix or cuticle to the distal free edge of the nail plate; diffuse melanonychia, which involves the entire nail plate; and transverse melanonychia, with bands lying across the width of the nail plate.¹ Although longitudinal melanonychia is more commonly reported, diffuse and transverse melanonychias are rarely reported. 

The etiology of melanonychia is discussed as melanocytic hyperplasia and melanocyte activation. Melanocyte hyperplasia can occur as inherited or acquired (sun induced) and presents with longitudinal streaking or total nail pigmentation, commonly as a nevus or melanoma. Melanocyte activation or stimulation of dormant melanocytes in the nail matrix can occur from trauma; inflammation; some nonmelanocytic tumors; and other systemic conditions, including autoimmune diseases, nutritional deficiencies, and HIV (eTable). Iatrogenic factors, such as chemotherapeutics, phototherapy, and radiation therapies, can also cause melanocyte activation.^3,4 Although trauma, inflammation, and tumors mostly present with a longitudinal pattern and single (or few) nail involvement,⁵ systemic conditions and iatrogenic causes present with entire fingernail and toenail involvement and multiple streaks in a longitudinal or transverse pattern on the nail plate. They can also be accompanied by mucosal or skin hyperpigmentation.⁶ Multiple or single nail involvement, morphologic pattern of pigmentation, and accompanying symptoms or lesions provide some clues to the etiology behind the melanocyte activation. Patients with darker skin types (Fitzpatrick types III–VI) are more susceptible to melanonychia when exposed to the discussed causative factors. In the evaluation of melanonychia, exogenous pigmentation and pregnancy should also be ruled out. 

Drug-induced melanonychia is a benign condition that should not require stopping the causative medication.⁷ It is commonly seen with chemotherapeutic agents (cyclophosphamide, doxorubicin, hydroxyurea, busulfan, taxanes, capecitabine, cisplatin, bleomycin, daunorubicin, dacarbazine, 5-fluorouracil, methotrexate, imatinib) and less commonly with antiretrovirals (zidovudine, lamivudine), antimalarials (amodiaquine, chloroquine, mepacrine, quinacrine) and metals (arsenic, thallium, mercury). The pattern of pigmentation varies with the causative drug and can be seen in 1 or more patterns.^8,9 Although most drugs present with longitudinal pigmentation, clofazimine, infliximab, psoralens, phenytoin, fluconazole, cyclins, ketoconazole, phenothiazines, and sulfonamides are reported with diffuse pigmentation. Limited cases have been reported of transverse melanonychia; causative drugs include hydroxyurea,^{6, 10-22} imatinib,^13,14 and etoposide.⁷ Transverse melanonychia has only been reported with drug use, whereas longitudinal and diffuse melanonychia have been reported with other causes. Drug-induced melanonychia outgrows partially or completely after cessation of the causative drug. Total resolution of pigmentation varies, from 6 to 8 weeks to several months and years. 

Dermoscopic findings for the longitudinal form of drug-induced melanonychia include a diffuse gray coloration of the nail plate and the presence of thin, longitudinal gray lines with regular thickness, spacing, coloration, and the absence of parallelism disruption.¹⁵ The gray color indicates melanocyte activation rather than melanocytic hyperplasia, which is characterized by a brown color.¹⁶

Histologically, melanocytes lie dormant or quiescent in both the nail matrix and nail bed. Stimulants cause melanocyte activation and the transferring of melanin-rich melanosomes to the differentiating matrix cells through dendrites. These matrix cells migrate distally and finally become nail plate onychocytes, resulting in visible pigmentation in the nail plate. An increase in the number of melanocytes or mitosis is not observed and the matrix cells have normal cytologic architecture.¹ Histopathologic examination does not provide a clue about the etiology of melanocyte activation in melanonychia but can distinguish melanocytic activation from melanocytic hyperplasia.¹⁷

Several conditions must be excluded for differential diagnosis, including hemosiderosis, hyperbilirubinemia, Addison disease, Cushing syndrome, vitamin B12 deficiency, HIV, hyperthyroidism, porphyria, and alkaptonuria. 

Drug-induced nail hyperpigmentation resolves shortly after discontinuation of the responsible drug. After ruling out nail malignancies and other causes of nail hyperpigmentation, observation and reassurance during and after chemotherapy are key in the management of drug-induced melanonychia. No additional examination or treatment is required. 

In this case, our patient received chemotherapy a year ago and lesions first started 3 months after initiation of chemotherapy. Other possible causes of transverse melanonychia, such as trauma, inflammation, and systemic conditions, were ruled out with further investigation. Our patient also had a history of local radiotherapy for breast cancer. Radiotherapy-related melanonychia has been reported in mycosis fungoides and arthritis cases,^3,4 but they were all whole-body radiotherapies involving hands. Our patient had a history of only localized radiotherapy for breast cancer. 

Drug-induced transverse melanonychia has been reported due to hydroxyurea, imatinib, and etoposide therapies before. In our case, the patient had a history of cyclophosphamide and doxorubicin therapies. Cyclophosphamide-induced melanonychia was reported as diffuse, black, longitudinal, or dark gray pigmentation of the proximal nail plate.¹⁸ Doxorubicin-induced tranverse melanonychia was reported as alternating bands of dark brown and white lines.¹⁸ In this case, our patient presented with transverse hyperpigmented bands in all fingernails and toenails. Drug-induced nail pigmentation can also be accompanied by mucosal hyperpigmentation,¹⁴ but in our case, there was no mucosal involvement. 

Transverse melanonychia has not been reported under dermoscopic examination before. Dermoscopic examination of the patient’s left middle fingernail showed gray-bluish discoloration of the distal two-thirds, with shiny white horizontal bands on a bluish background. No evidence of nail dystrophy was noted. Gray-blue discoloration is consistent with melanocytic activation and other drug-induced hyperpigmentation descriptions; however, the shiny white appearance of the bands was unique. 

Nail evaluation by dermatologists before and after chemotherapy can enrich current literature on the pathophysiology and patterns of drug-induced nail abnormalities. 

1. Singal A, Bisherwal K. Melanonychia: etiology, diagnosis, and treatment. Indian Dermatol Online J. 2020;11(1):1-11. doi:10.4103/idoj.IDOJ_167_19 

2. Bolognia JL, Schaffer JV, Duncan KO, Ko CJ. Dermatology Essentials. Elsevier Health Sciences; 2014. 

3. Quinlan KE, Janiga JJ, Baran R, Lim HW. Transverse melanonychia secondary to total skin electron beam therapy: a report of 3 cases. J Am Acad Dermatol. 2005;53(2 Suppl 1):112-114. doi:10.1016/j.jaad.2004.11.020 

4. Baumert BG, Wodarski C, Klein C, Wendt T. Transverse melanonychia (TM): induced by radiotherapy. Radiother Oncol. 2015;114(2):282-283. doi:10.1016/j. radonc.2014.12.014 

5. Andre J, Lateur N. Pigmented nail disorders. Dermatol Clin. 2006;24(3):329-339. doi:10.1016/j.det.2006.03.012 

6. Neculiseanu E, Harewood J, Sidhu G. Hydroxyurea-induced tongue hypermelanosis and transverse melanonychia. Cureus. 2019;11(12):e6311. doi:10.7759/cureus.6311 

7. Stephens M, Rubin AI, Castelo-Soccio L. Transverse melanonychia in a child receiving chemotherapy. Pediatr Dermatol. 2019;36(1):e60-e61. doi:10.1111/pde.13721 

8. Bianchi L., Iraci S, Tomassoli M, Carrozzo AM, Nini G. Coexistence of apparent transverse leukonychia (Muehrcke’s lines type) and longitudinal melanonychia after 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy. Dermatology. 1992;185(3): 216-217. doi:10.1159/000247451 

9. Dasanu CA, Vaillant JG, Alexandrescu DT. Distinct patterns of chromonychia, Beau’s lines, and melanoderma seen with vincristine, adriamycin, dexamethasone therapy for multiple myeloma. Dermatol Online J. 2006;12(6):10. 

10. Teo RYL, Tan E. A case of hydroxyurea-induced transverse melanonychia. Int J Dermatol. 2006;45(11):1329-1330. doi:10.1111/j.1365-4632.2006.02709.x 

11. Hernández-Martín A, Ros-Forteza S, de Unamuno P. Longitudinal, transverse, and diffuse nail hyperpigmentation induced by hydroxyurea. J Am Acad Dermatol. 1999;41(2 Pt 2):333-334. doi:10.1016/s0190-9622(99)70379-8 

12. Osemwota O, Uhlemann J, Rubin A. Twenty-nail transverse melanonychia induced by hydroxyurea: case report and review of the literature. J Drugs Dermatol. 2017;16(8):814-815. 

13. Das A, Podder I, Kumar D, Ghosh A, Shome K. Imatinib-Induced transverse melanonychia: an unusual presentation. Indian J Dermatol. 2015;60(4):412-413. doi:10.4103/0019-5154.160500 

14. Steele JC, Triantafyllou A, Rajlawat BP, Field EA. Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib. Clin Exp Dermatol. 2012;37(4):432-433. doi:10.1111/j.1365-2230.2011.04196.x 

15. Di Chiacchio ND, de Farias DC, Piraccini BM, et al. Consensus on melanonychia nail plate dermoscopy. An Bras Dermatol. 2013;88(2):309-313. doi:10.1590/S0365- 05962013000200029 

16. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007;56(5):835-847. doi:10.1016/j.jaad.2006.12.021 

17. Güneş P, Göktay F. Melanocytic lesions of the nail unit. Dermatopathology (Basel). 2018;5(3):98-107. doi:10.1159/000490557 

18. Ng CF, Tan HJ, Remli R. Chemotherapy-induced transverse melanonychia. BMJ Case Rep. 2021;14(8):e245878. doi:10.1136/bcr-2021-245878.