Longitudinal pigmentation of the nail is a common presenting problem in general podiatry. However, it is not something the patient always brings to your attention. You need to look for it.

   A 45-year-old African-American female presents to the office with a chief concern of incurvated dark nails with a history of failed treatment for fungal toenails. She recalled that her dermatologist prescribed terbinafine (Lamisil, Novartis) eight months ago but there is still discoloration over the entire nail plate on all of the nails. It turned out that she did not undergo a fungal nail culture prior to the initiation of treatment.

   I performed a workup of the patient with a history and physical examination. A nail culture found no evidence of fungal hyphae.

The physician should try and elicit a history as to whether the pigment has been present since birth or is acquired. Furthermore, the history of its duration, a history of what made the patient first become aware of it, and whether the patient has observed any change in the nail lesion may provide clues for the correct diagnosis. It is also important to look at the fingernails.

   Specific questions pertaining to athletic activities, recent trauma, physical exertion such as long hiking trips or the use of blood thinners such as aspirin and warfarin (Coumadin, Bristol-Myers Squibb) may help in differentiating subungual hemorrhage from other causes of nail pigment. Obtaining a thorough medication history may help identify drugs that may contribute to abnormal nail pigmentation.1

   Hutchinson’s sign is visible as an extension of the pigmentation to the proximal or lateral nail folds. It can also occur as periungual discoloration. It is an important indicator of nail melanoma.2 There are numerous conditions that produce a pseudo-Hutchinson’s sign, making the history together with the biopsy of utmost importance.1

1. What are the characteristic features of this condition?
2. What is the most likely diagnosis?
3. What is your differential diagnosis?
4. What does the patient workup entail?
5. When should you biopsy when faced with pigmented nails?

1. Characteristic features include nail pigmentation changes such as longitudinal bands, transverse bands and diffuse darkening.
2. Racial melanonychia
3. Fungal melanonychia, nutritional longitudinal melanonychia, traumatic longitudinal melanonychia, longitudinal melanonychia associated with inflammatory nail disorders or longitudinal melanonychia due to drugs
4. The workup entails taking a history, evaluating for Hutchinson’s sign and taking a biopsy.
5. Biopsy when the entire nail is involved, when variegated colors from light or dark brown to black are present, when the pigmented band has had recent color or width changes in Hispanic patients who have a new-onset acquired longitudinal melanonychia, even if more than one nail is affected, regardless of the age group.

The diagnosis was racial melanonychia, a type of nail pigmentation occurring in those with pigmented skin. Melanonychia frequently has a racial predilection. It occurs among more than 50 percent of African-Americans, approximately 10 percent of Japanese people and among people of Mediterranean origin.3

   Nail pigmentation changes include longitudinal bands, transverse bands and diffuse darkening. At times, there is overlap between the diffuse darkening and the longitudinal bands. The literature references longitudinal melanonychia more often because it occurs with nail melanoma, which can be deadly. The other causes of nail pigmentation are benign and are less known.

   Melanonychia is defined by the presence of melanin within the nail plate. It appears more often as a longitudinal brown-black band starting from the matrix and extending to the free edge of the nail plate. Less often, the pigmentation can involve the whole nail plate or present as a transverse band.2 There are many causes of discoloration of the nail plate.

   Melanonychia results from production of melanin by melanocytes of the nail matrix, where melanocytes are usually quiescent but may become active and start melanin synthesis. Melanonychia has four main causes: simple melanocytic activation; increased activation (with a normal number) of melanocytes; benign melanocyte proliferations (lentigo, nevus); and malignant melanocyte proliferation (melanoma). When matrix nevi present as melanonychia, the pigment producing nevus cells incorporate melanin into the nascent nail plate onychocytes, producing true brown nail plate discoloration.4

   Simple melanocyte activation can occur as melanotic macules. Melanotic macule of the nail unit, a benign condition resulting from an increase in production of melanin by melanocytes in the matrix, is the most common cause of a pigmented longitudinal band of the nail plate in adults.­5

   Less commonly, melanonychia due to melanocytic activation can result from inflammatory and traumatic nail disorders, fungus and drugs (chemotherapy, azidothymidine (AZT), anti-malarials, photochemotherapy).6 It may also be due to systemic diseases, such as Laugier-Hunziker and Peutz-Jeghers syndromes, HIV infection, acanthosis nigricans and even lupus and scleroderma, as well as cutaneous disorders such as psoriasis and lichen planus.7

   More commonly, melanonychia results from melanin produced by melanocytes in the matrix and may be a normal variant in darker-skinned people. Longitudinal melanonychia occurs with melanocytic macule, junctional or compound melanocytic nevus, or melanoma.5 Differentiating among these can be difficult.

   One way to view longitudinal melanonychia is that of a streak in the nail plate with normal nail surrounding it. Another way to view it is as a extra wide streak that is so wide that it comprises the entire nail plate.

In regard to racial melanonychia, clinicians should consider the color of pigment, band width, nail dystrophy and the number of nails affected.

   Color of pigment. Brown or black discoloration of the nail can represent a wide variety of disorders, the majority of which are benign.8 The color is normally light brown, dark brown, black or variegated. When it comes to racial melanoychia in the Hispanic population, the color is usually light or dark brown 97 percent of the time.8 Trauma, with underlying hematoma, remains the most common cause of melanonychia and is usually dark brown or black. Fungal melanonychia is either light brown, dark brown or variegated, and almost never black.

   Melanonychia width. Many studies use the following measurements: 1 to 3 mm wide, 4 to 6 mm wide and full width of the nail. One hundred percent of the nails diagnosed with racial melanoychia were 1 to 3 mm or 4 to 6 mm in width.8 Traumatic and fungal nails had a 1 to 3 mm melanonychia width. Squamous cell carcinoma, benign melanocytic hyperplasia and melanoma were always in the 4 to 6 mm range and full width measurement in terms of melanonychia width.8

   Nail dystrophy. Nail dystrophy is rare in racial melanonychia but common in traumatic and fungal melanonychia. Nail dystrophy occurs in squamous cell carcinoma and benign melanocytic hyperplasia, but does not occur with melanoma.

   Number of nails affected. Racial melanonychia usually occurs in two to five nails and to a lesser extent in one nail or all 10 toenails. Traumatic melanonychia usually affects one nail. Fungal melanonychia is usually present in two to five nails. In their study, Dominguez-Cherit and colleagues noted that squamous cell carcinoma, benign melanocytic hyperplasia and melanoma always occurred in one nail or two to five nails but never all 10 nails.8

Fungal melanonychia. Fungal melanonychia shares some characteristics with racial melanonychia, such as the different shades of brown color, width less than 4 mm and frequent involvement of more than one nail. Nail dystrophy seems to be the most important clinical sign to distinguish between these two types of melanonychia. It is common in fungal melanonychia and rare in racial longitudinal melanonychia.9

   Distal lateral subungual onychomycosis remains the most common form of fungal invasion of the nail plate, where the site of invasion is from the lateral or distal undersurface of the nail plate. The main features are onycholysis with hyperkeratosis and varying forms of dyspigmentation. Most commonly, this is white or yellowish but on occasion, other color changes can occur such as brown, black and orange discoloration.10

   Nutritional longitudinal melanonychia. Pigmentation of the nails and the skin can happen with vitamin B12 or folate deficiency.1 The pigmentation tends to have a bluish-black color. The pigmentation on the skin is accentuated over the knuckles and the distal phalanges. Usually, one diagnoses this based on laboratory examination. This type of nail pigmentation is completely reversible after vitamin B12 or folate administration.1

   Traumatic longitudinal melanonychia. In frictional melanonychia, repeated rubbing, trauma and friction stimulate matrix melanocytes to produce more pigment. Repeated trauma such as nail biting may induce nail pigmentation.11 We mainly see this as a result of shoes that are too small, hammertoes in a shoe with a shallow toebox, an excessively long second toe in which the nail is at a right angle to the ground, or an adductovarus fifth toe.

   It mainly arises on the toes and is often associated with foot deformities, inadequate footwear or both. This type of nail pigmentation may gradually fade once the repetitive trauma has subsided.11

   Longitudinal melanonychia associated with inflammatory nail disorders. This type of nail pigmentation occasionally develops in nails affected by lichen planus, onychomycosis, chronic radiodermatitis, pustular psoriasis or Hallopeau’s disease. The pigmentation can be subtle at the beginning and become clearly clinically evident as the inflammatory process progresses. It is usually associated with nail scarring and abnormalities of the surface of the nail plate.1

   Longitudinal melanonychia due to drugs. Several drugs may activate clusters of nail matrix melanocytes to produce melanin, giving rise to the appearance of a band of melanonychia or multiple longitudinal or transverse bands ranging in color from light brown to black.12 In drug-induced melanonychia, several nails are generally affected with multiple bands. In some cases, only one digit is involved.

   A diffuse activation of nail matrix melanocytes produces pigmentation of the whole nail plate. Drug-induced melanonychia most commonly appears three to eight weeks after drug intake.1Pigmentation is usually reversible within six to eight weeks but may persist for months after drug interruption.1

   Drugs that may cause melanonychia include zidovudine (Retrovir), chemotherapy agents, hydroxyurea (Hydrea) and psoralens. Radiation therapy for malignant disease far from the digit can also cause longitudinal melanonychia.3

Doctors are often unsure regarding their clinical diagnosis and lack confidence in managing this condition. Furthermore, many physicians are also reluctant to perform biopsies of the nail matrix because the procedure is painful and can result in permanent nail dystrophy. To complicate matters, when a physician finally decides to biopsy, it is not uncommon for one to submit inadequate biopsy specimens (e.g., biopsy specimen of the nail plate instead of the nail matrix) to the pathologist. This subsequently compromises the ability of the pathologist to render an accurate diagnosis.1

   I recommend a nail matrix biopsy of pigmented nail lesions in the following cases:
• when the entire nail is involved;
• when there are variegated colors from light or dark brown to black;
• when the pigmented band has had recent color; or
• when there are width changes in Hispanic patients who have a newly acquired longitudinal melanonychia, even if more than one nail is affected, regardless of the age group.9

Given the fact that the population of people with pigmented skin is increasing in the world, it is incumbent on us to understand nail pathology in those individuals. When it comes to the differential diagnosis, it is essential to be aware that there is much overlap between benign nail pigmentation and subungual malignant melanoma.

   Dr. Morse is the President of the American Society of Podiatric Dermatology. He is a Fellow of the American College of Foot and Ankle Surgeons, and the American College of Foot and Ankle Orthopedics and Medicine. Dr. Morse is board certified in foot surgery. He is on the Podiatric Residency Educational Committee at the Washington Hospital Center in Washington, D.C.

References
1. Skowron F, Combemale P, Faisant M, Baran R, Kanitakis J, Dupin M. Functional melanonychia due to involvement of the nail matrix in systemic lupus erythematosus. J Am Acad Dermatol. 2002; 47(2Suppl): S187-S188.
2. Tosti A. Diseases of hair and nails. In: Goldman L, Ausiello D (eds): Goldman’s Cecil Medicine, 24th ed. Ch. 450, Saunders Elsevier, Philadelphia, 2011.
3. Naylor EM, Ruben BS, Robinson-Bostom L, et al. Subungual blue nevus with combined phenotypic features. J Am Acad Dermatol. 2008; 58(6):1021-4.
4. Husain S, Scher RK, Silvers DN, Ackerman B. Melanotic macule of nail unit and its clinicopathologic spectrum. J Am Acad Dermatol. 2006; 54(4):664-667.
5. Grandinetti LM, Tomecki KJ. Dermatologic signs of systemic disease. In: Carey WD (ed): Cleveland Clinic: Current Clinical Medicine 2010, 2nd ed. Saunders Elsevier, Philadelphia, 2010.
6. Harwood M, Telang GH, Robinson-Bostom L, Jellinek N. Melanoma and squamous cell carcinoma on different nails of the same hand. J Am Acad Dermatol. 2008; 58(2):323-6.
7. Haneke E, Baran R. Longitudinal melanonychia. Dermatol Surg. 2001; 27(6):580-584.
8. Dominguez-Cherit J, Roldan-Marin L, Pichardo-Velazquez P, et al. Melanonychia, melanocytic hyperplasia, and nail melanoma in a Hispanic population. J Am Acad Dermatol. 2008; 59(5):785-91.
9. Hay RJ, Baran R. Onychomycosis: a proposed revision of the clinical classification. J Am Acad Dermatol. 2011; 65(6):1219-27
10. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007; 56(5):835-847.
11. Baran R. Frictional longitudinal melanonychia: a new entity. Dermatologica. 1987; 174(6):280-284.
12. Piraccini BM, Iorizzo M. Drug reactions affecting the nail unit: diagnosis and management. Dermatology Clinics. 2007; 25(2):215-21.