Indian Journal of Dermatology
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Year : 2022  |  Volume : 67  |  Issue : 6  |  Page : 838
Valproic acid monotherapy induced longitudinal melanonychia

Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Date of Web Publication23-Feb-2023

Correspondence Address:
Anil Budania
Department of Dermatology, Venereology and Leprology, All India Institute of Medical Sciences, Jodhpur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.370349

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How to cite this article:
Pathania YS, Mudugal R, Budania A. Valproic acid monotherapy induced longitudinal melanonychia. Indian J Dermatol 2022;67:838

How to cite this URL:
Pathania YS, Mudugal R, Budania A. Valproic acid monotherapy induced longitudinal melanonychia. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 23];67:838. Available from:


Drug-induced melanonychia encompasses nail bed pigmentation, transverse bands and longitudinal melanonychia.[1] Chemotherapeutic drugs are the most common agents. Phenytoin is the only anti-epileptic drug reported to cause melanonychia. We want to highlight and add a novel agent to the list of drug-induced melanonychia. Herein, we described sodium valproate-induced longitudinal melanonychia in a young male, which is a rare manifestation for which the literature is limited.

A 17-year-old male presented with asymptomatic progressive linear hyperpigmented bands over the finger and toenails since 2 years. There was no family history of a similar disease, any autoimmune disease, thyroid disease or trauma to nails. The patient is a known case of seizure disorder for the last 5 years and is on sodium valproate monotherapy for the past 2 years. General physical examination was unremarkable. Nail examination revealed multiple, well-demarcated, linearly arranged variable width, brownish-black hyperpigmented bands over the nail plates of both fingers [Figure 1]a and toenails with few nails having diffuse nail plate hyperpigmentation [Figure 1]b. Pseudo-Hutchinson's sign was absent [Figure 2]a. Hair, eyes and oral mucosa were normal. Fungal and bacterial elements were ruled out on culture and microscopy. Onychoscopic examination revealed sharply demarcated linear brown coloured bands with smooth edges with negative micro-Hutchinson's sign [Figure 2]b. Nail matrix biopsy ruled out the melanoma and also confirmed no nevus cells. The diagnosis of valproic acid-induced longitudinal melanonychia was established.
Figure 1: (a-b)Multiple linearly arranged variable width, brown-black bands over the finger nail plates (a). Toenails show linear hyperpigmented bands and diffuse nail plate hyperpigmentation (b)

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Figure 2: (a-b)Onychoscopy (Dermlite DL4 4th generation dermoscope) using non-polarized mode shows sharply demarcated linear brown coloured bands of variable width with smooth margins (a) with pseudo-Hutchinson's sign and micro-Hutchinson's sign negative (b)

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Valproic acid is a commonly used anti-seizure drug. Dermatology-associated adverse effects include alopecia, morbilliform rash, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, psoriasiform lesions, hyperpigmentation, onychomadesis and onycholysis. The index case had longitudinal melanonychia in multiple nails induced by valproic acid monotherapy. There is limited literature regarding this manifestation. Longitudinal melanonychia is a longitudinal brown-black/grey band extending proximally from the nail matrix or cuticle to the distal free edge of the nail plate. Drugs activate clusters of nail matrix melanocytes to produce melanin, giving rise to a band of melanonychia or multiple longitudinal or transverse bands.[2] Drug-induced melanonychia appears 3 to 8 weeks after drug intake. Pigmentation is usually reversible within 6 to 8 weeks but sometimes, persists for months after drug cessation. The pathogenesis of melanocyte activation is unclear and is independent of melanocyte-stimulating hormone and corticotropin activity and ultraviolet light.[3] Longitudinal melanonychia can be physiological, and drug-induced. It can occur after repetitive trauma, subungual haematoma, onychomycosis, pseudomonas infection or underlying systemic disease. Drugs like zidovudine, chemotherapeutic agents, hydroxyurea and psoralens induce melanonychia.[4] The index case started developing melanonychia after 3 months of valproic acid therapy and has been progressively increasing since then, which was bothering the patient. There were no other adverse effects noted in the case. The patient was counselled regarding the benign nature of the disease and advised to consult the treating neurologist for a suitable alternative drug.

The prognosis of melanonychia depends on its aetiology. Drug-induced melanonychia involves multiple nails that fade either partially or completely following drug withdrawal. Isolated longitudinal melanonychia after valproate monotherapy is observed very rarely. Our case would add this adverse effect induced by valproic acid in the literature.

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.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Andre J, Lateur N. Pigmented nail disorders. Dermatol Clin 2006;24:329-39.  Back to cited text no. 1
Baran R, Kechijian P. Longitudinal melanonychia: Diagnosis and management. J Am Acad Dermatol 1989;21:1165-75.  Back to cited text no. 2
Piraccini BM, Iorizzo M. Drug reactions affecting the nail unit: Diagnosis and management. Dermatol Clin 2007;25:215-21.  Back to cited text no. 3
Nguyen AL, Körver JE, Theunissen CCW. Longitudinal melanonychia on multiple nails induced by hydroxyurea. Case Rep 2017;2017:bcr2016218644. doi: 10.1136/bcr-2016-218644.  Back to cited text no. 4


  [Figure 1], [Figure 2]


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