James Q. del Rosso DO1
Clinical Assistant Professor
Clinical Professor of Medicine (Dermatology)
1Department of Dermatology, University of Nevada School of Medicine
2University of Mississippi School of Medicine
James Q. Del Rosso, D.O., participates in the speakers' bureaus and is a consultant for Bradley (Doak) Pharmaceuticals; Galderma Laboratories, Medicis, Novartis Pharmaceuticals, Ortho Neutrogena, and Stiefel Laboratories
The human nail is a complex unit composed of five major modified cutaneous structures: the nail matrix, nail bed, nail plate, nail folds, and cuticle (eponychium).1 These components are structurally supported by specialized mesenchyme, which serves a ligamentlike function, anchoring the soft tissue structures of the nail to the underlying phalangeal bone. The primary function of the human nail is to provide protection for the distal digits. Nails also facilitate fine touch and digital dexterity. For many individuals, nails serve as an important aesthetic symbol of optimal appearance, enhanced self-image, or individuality; several cosmetic techniques are available to modify the appearance of the nail plate. The basic anatomic components of the nail unit are diagrammed [see Figure 1].
Figure 1. Longitudinal section of the fingernail. Major components of the nail include the nail matrix, nail plate, eponychium, hyponychium, nail bed, and the proximal and lateral nail folds.
Nail Structure, Function, and Pathophysiology
The nail matrix is the dynamic, germinative portion of the nail unit that produces the nail plate.2,3,4 The lunula is the visible portion of the nail matrix, appearing under the proximal nail plate as a gray-white half moon projecting just distal to the proximal nail-fold cuticle. The lunula decreases with age in approximately 20 % of persons.5
Nails are usually devoid of pigmentation because of the relatively sparse number of melanocytes present in matrix epithelium.1,2 Because nail-matrix or nail-bed melanocytes tend to be more numerous in blacks, Asians, and Hispanics, persons of these racial backgrounds may present more commonly with diffuse or banded nail-plate or nail-bed hyperpigmentation.
Pathophysiology Affecting the Nail Matrix
Because of the diagonal orientation of the ventral nail matrix, the proximal portion of the nail matrix produces the superior portion of the nail plate.6 As a result, disorders of the proximal matrix produce surface abnormalities of the nail plate. A characteristic example is nail-plate pitting secondary to psoriasis. Diseases of the distal nail matrix result in abnormalities of the undersurface of the nail plate, changes that are visible at the free edge of the nail, or both. Permanent damage to the matrix as the result of trauma, surgical intervention, or disease may result in permanent nail-plate dystrophy.
The nail bed is a layer of epithelium lying between the lunula and the hyponychium (the distal epithelium at the free edge of the nail). The surface epithelium of the nail bed is longitudinally ridged, with small superficially oriented vessels coursing along the same axis, interdigitating with a complementary array of ridges on the undersurface of the nail plate.3 This anatomic feature explains the longitudinal linearity of splinter hemorrhages, which are foci of extravasation wedged between the bed and the plate. As outgrowth of the nail plate occurs, splinter hemorrhages progress distally.
Pathophysiology Affecting the Nail Bed
The epidermis of the nail bed is thin and minimally keratinized, without a granular layer. If there is prolonged loss of nail plate as a result of disease or surgical intervention, increased nail-bed keratinization with development of a granular layer prevents the firm attachment of the ingrowing nail plate to the underlying nail bed. Melanocytes are more sparsely distributed in nail-bed epithelium than in the nail matrix [seeNail Matrix, above]. The dermal layer of the nail bed is very thin and is supported by very sparse subcutaneous tissue; it is firmly attached to the underlying bony phalanx.
The nail plate, which is composed of densely compacted keratinized epithelial cells, is produced by the matrix and progresses distally toward the free edge of the nail as newly formed plate slowly pushes forward in a distal direction. Formation and outgrowth of the nail plate is a continual process. A fully formed nail plate extends from below the proximal nail-fold cuticle to beyond the hyponychium and extends laterally below the cuticle of the lateral nail folds. Nail-plate abnormalities frequently occur secondary to changes or disorders affecting function of the nail matrix, infections such as onychomycosis, or trauma.
Age-Related Nail-Plate Findings
The growth rate of an adult fingernail plate is approximately 3 mm/mo, with marked variability among individuals.2 Toenail plate growth occurs at one third to one half the rate of fingernail growth. A general rule is that adult fingernails take approximately 6 months to grow out fully; adult toenails, 12 to 18 months. Nail-plate growth is faster in children, peaking between 10 and 14 years of age; there is a slowly progressive decline after the second decade of life.2 Linear nail-plate growth decreases by 50% over a lifetime, with periods of slow decline alternating with periods of rapid decline in approximate 7-year increments.7 Nail-plate growth increases during pregnancy and decreases during lactation, after use of chemotherapeutic agents, and in conditions characterized by limb paralysis, persistently diminished circulation, or malnutrition.2,3,8 Yellow nail syndrome is characterized by very slow or absent growth of nail plate; it usually affects both fingernails and toenails and is seen in association with several underlying conditions, such as lymphedema, respiratory disorders (e.g., bronchiectasis and pleural effusions), and nephrotic syndrome.9
Constitutional age-related findings in the nail plate include changes in nail color and luster, longitudinal ridging, changes in convexity, and brittle nails.8,10 Nail plates, especially of toenails, often develop a yellow or gray color with a dull, opaque appearance. Longitudinal ridging may affect some or all nails and may present as slightly indented grooves or projection ridges or as beading. Over time, the surface of the nail plate may become flattened (platyonychia) or spooned (koilonychia). Temporary koilonychia, especially of the toenails, is also seen in infants.6
Pathophysiology Affecting the Nail Plate
Brittle nails is a common complaint; its incidence is 20% in the overall population (27% in female patients) and increases with advancing age.10 When nail water content falls below 16%, nail plates become brittle; when the water content rises above 25%, nail plates become soft. The most common cause of brittle nails is dehydration, which can be caused or exacerbated by external factors such as use of nail-polish remover or exposure to dry climate. Onychoschizia, which presents as a layered, superficial splitting of the nail plate, may increase in incidence with age. This condition is seen much more frequently in female patients. It is likely related to recurrent exposures to water or irritants, such as during nail-care procedures.
Fingernails demonstrate a tendency to become thinner and more fragile over time. Toenails usually become thicker and harder. Onychogryphosis is a marked thickening, usually of the large toenail, resulting in a compacted mass of heaped-up dystrophic nail plate.8Contributing factors appear to be advanced age, poor nail care, chronic trauma, decreased peripheral circulation, and neuropathy. Poor-fitting shoewear causes long-term exposure to lateral pressure and friction, resulting in gryphotic changes (marked thickening or heaping of nail plate), usually of the first and fifth toenails.
The nail folds are the cutaneous soft tissue that houses the nail unit, invaginating proximally and laterally to encompass the emerging nail plate. The proximal nail fold, with the exception of the lunula, covers the underlying matrix and is devoid of sebaceous glands and dermatoglyphic skin markings.11 The term paronychia describes inflammation of the nail folds. Paronychia may be acute or chronic and may occur secondary to a variety of conditions, including contact dermatitis, psoriasis, bacterial infection, and fungal infection.12,13 The cuticle (eponychium) is a thin, keratinized membrane of modified stratum corneum that extends from the distal portion of the nail fold, reflecting onto the nail-plate surface. Intact cuticle serves as a seal that protects the space between the nail folds and the nail plate from exposure to external irritants, allergens, and pathogens. Loss of cuticle allows for exposure and trapping of these deleterious external agents, providing an environment in which either inflammatory or infectious paronychia can develop.
Nail Findings Associated with Disease States
Several nail findings have been associated with both underlying systemic and dermatologic conditions. The following is a review of selected, recognized associations. Diagnosis is based on proper evaluation of clinical findings; treatment is based on a confirmed etiology or the recognition of an underlying systemic association.
Special care must be taken when performing biopsy of the nail bed or matrix to avoid trauma to the tissue specimen and surrounding structures upon specimen removal. The most appropriate plane of dissection during nail-bed or nail-matrix biopsy is subdermal. The sampled tissue should be manipulated very gently throughout the biopsy procedure to avoid crush artifact, which may interfere significantly with histopathologic evaluation. It is also important to carefully dissect along the undersurface of the specimen, ensuring nontraumatic separation of the biopsy tissue from its underlying firm attachment to bone.
Splinter hemorrhages may be secondary to trauma, high altitude, primary dermatoses (i.e., psoriasis), or several underlying conditions (e.g., arterial emboli, collagen vascular disease, or thromboangiitis obliterans). The simultaneous appearance of splinter hemorrhages in several nails should raise suspicion of a possible underlying systemic disorder, especially in female patients.14
Koilonychia may be found in association with other conditions, including congenital conditions, iron deficiency anemia, cardiac disease, endocrinopathy, occupational exposures, and trauma.3,15
Transverse Nail-Plate Depressions (Beau Lines)
Beau lines present as well-delineated, transverse depressions in the nail plate. They are believed to occur secondary to temporary growth arrest of the nail matrix. The grooves become evident weeks after the occurrence of an abrupt, stressful event, such as an acute febrile illness. The width of the groove reflects the duration of interrupted nail-matrix function. When limited to one or a few digits, Beau lines may be associated with trauma, carpal tunnel syndrome, or Raynaud disease, or they may occur subsequent to tourniquet application during hand surgery.15 Approximately 1 to 2 months after birth, infants may demonstrate physiologic Beau lines, which mark the transition from intrauterine to extrauterine life.16 Multiple transverse grooves (stepladder appearance) may be seen in association with repeated cycles of chemotherapy, or they may be related to zinc deficiency. Multiple Beau lines should not be confused with habit-tic deformity, which consists of multiple transverse depressions, stacked longitudinally along the central nail plate (washboard nails), resulting from the obsessive habit of repeatedly pushing back the cuticle or picking at the proximal nailfold margin [see Figure 2].15,17 There is no specific treatment for Beau lines. They grow out over time after resolution of the growth-arrest period.
Figure 2. Stacking of transverse linear grooves traversing the entire length of the central nail plate, resulting from the repeated picking of the proximal nail fold margin (habit-tic deformity). Note the marked hypertrophy of the lunula, which is typical of this disorder.
Onycholysis is defined as the separation of the nail plate from the nail bed. In most cases, onycholysis begins distally; it is often related to acute or chronic trauma that produces a lever effect, lifting the nail plate upward and away from its bed. Other causes of onycholysis are chemical exposure (allergic or irritant dermatitis), onychomycosis, and primary dermatoses (e.g., psoriasis or lichen planus).13 Associations with underlying systemic disease (e.g., thyroid disease) have been sporadically reported but are less commonly encountered in clinical practice. When moisture accumulates under onycholytic nail plate, bacterial proliferation may occur. This can cause a green discoloration of the nail plate as a result of a pigment produced by certain organisms (e.g., Pseudomonas aeruginosa) [see Figure 3].
Figure 3. Colonization of the closed space between the nail bed and nail plate with Pseudomonas aeruginosa, causing a green nail. Moisture trapped in the onycholytic space provides an optimal environment for proliferation of this bacterium.
Treatment requires avoidance of precipitating factors for onycholysis, debridement of separated nail plate, and the twice-daily topical application of diluted acetic acid solution (consisting of equal parts white vinegar and water), gentamicin, or the combination of polymyxin B and bacitracin.18
Leukonychia, a white discoloration of the nail plate or subungual tissue, has multiple presentations. Small 1 to 3 mm white spots (punctate leukonychia) or irregular transverse streaks (leukonychia variegata) of the nail plate are the most common varieties.15 These two presentations are generally secondary to repeated microtrauma to the matrix, growing out distally with outgrowth of the nail plate. Mee lines specifically refer to transverse 1 to 2 mm white bands, which usually are demonstrated at the same site in multiple nails and occur in association with arsenic intoxication, Hodgkin disease, sickle cell anemia, renal failure, and cardiac insufficiency. Leukonychia is also associated with systemic infection and chemotherapy.19,20,21
Half-and-half nails (Lindsay nails) present as a diffuse, dull whitening of the proximal nail bed that obscures the lunula and as a distal region of pink or reddish-brown discoloration that occupies from 20% to 60% of the nail length.15,22 The most commonly reported association with half-and-half nails is chronic renal failure. When the distal brown band of discoloration constitutes less than 20% of the total nail length, the anomaly is known as Terry nails, which occurs in association with chronic congestive heart failure, hepatic cirrhosis, type 2 diabetes mellitus, and advanced age. In both half-and-half nails and Terry nails, the proximal portion of the nail bed may be light pink, exhibiting a more normal appearance, rather than white.
Muehrcke nails present as paired, white, narrow transverse bands of the nail bed, separated by normal-appearing thin pink bands.15,22Muehrcke nails have been associated with chronic hypoalbuminemia. Resolution of this nail finding correlates with normalization of serum albumin levels.15
When the normal angle between the proximal nail fold and the nail plate exceeds 180B0, digital clubbing is present. The morphologic changes of clubbing typically include hypertrophy of the surrounding soft tissue of the nail folds as a result of hyperplasia of dermal fibrovasculature and edematous infiltration of the pulp tip.21 Radiologic changes are identified in fewer than 20% of cases.15
Clubbing may be hereditary, or it may be seen in association with several underlying disease states, such as hypertrophic pulmonary osteoarthropathy, chronic congestive heart failure, congenital heart disease associated with cyanosis, polycythemias associated with hypoxia, Graves disease, chronic hepatic cirrhosis, lung cancer, Crohn disease, and irritable bowel disease.15,22,23 When clubbing is unilateral, consideration should be given to underlying causes of obstructed circulation, such as aneurysm, arteriovenous fistula, and a pulmonary sulcus tumor (Pancoast tumor); disorders producing soft tissue edema; and diseases causing localized changes in underlying digital bone (e.g., sarcoidosis). Unilateral clubbing can also be found in cases of hemiplegia,24 and a case of subungual perineurioma caused by unilateral clubbing has been reported.25 Paronychia and distal phalangeal resorption may cause changes that simulate true clubbing (pseudoclubbing).
Nail-plate pitting (onychia punctata) develops as a result of focal defects in nail-plate formation from the proximal nail matrix. The number, size, and shape of the superficial depressions may vary.15 The extent and duration of involvement with nail pitting correlates with the duration of nail-matrix abnormality. Psoriasis, the most common condition associated with nail pitting, may produce a random array of shallow or deep pitted indentations, usually affecting one or more fingernails.26,27
Psoriasis of the nails often responds poorly to treatment, and it tends to recur. Topical corticosteroids, topical tazarotene, and intralesional corticosteroid injection may help in some cases.28,29 It is a common misconception that nail pitting is pathognomonic for psoriasis.27 Nail pitting may also be seen in association with alopecia areata, punctate keratoderma, idiopathic trachyonychia, occasionally in normal nails, and rarely in association with collagen vascular disease or syphilis. Fingernail pitting occurs in one third of children with alopecia areata; mild disease involving only a few nails is observed in approximately 20% of cases.27 Compared to psoriasis, nail pitting seen in alopecia areata is typically more uniform and patterned, often presenting as orderly rows of shallow pitted depressions. Currently, there is no available treatment for this type of nail pitting.
Longitudinal Pigmented Bands
Longitudinal pigmented bands (melanonychia striata), also referred to as longitudinal melanonychia, is the presence of single or multiple longitudinally oriented brown or black bands [see Figure 4]. Homogeneous longitudinal bands occur in approximately 75% of African Americans older than 20 years. It usually affects the thumb and index finger.30,31 Melanonychia striata is also commonly seen in Hispanics and may be found in up to 20% of Japanese, but is rare in whites.30
Figure 4. Melanonychia striata (longitudinal pigmented band) produced by a melanocytic nevus of the nail matrix. A high index of suspicion for subungual melanoma is very important when a longitudinal pigmented band of the nail is identified.
The deposition of melanin in the nail plate may result from increased melanin synthesis by matrix melanocytes that are usually nonfunctional; it may also occur as a result of a proliferation of matrix melanocytes.30 Melanonychia striata affecting a single nail may result from a benign melanocytic nevus or a subungual melanoma. Thus, it is important to distinguish between a benign cause and a malignant cause of a longitudinal pigmented band. Factors suggesting the presence of melanoma or an atypical melanocytic proliferation are (1) single digit involvement; (2) periungual spread of pigment onto the nail-fold region (Hutchinson sign); (3) border irregularity or variegated color within the linear streak; and (4) changes in appearance (e.g., color or borders) involving an established longitudinal band.32 Because of the severity of subungual melanoma and the importance of making a prompt diagnosis, the index of suspicion must be high. A simple biopsy of the nail plate is not satisfactory in establishing the diagnosis, because it will only demonstrate the presence of melanin. An appropriate biopsy inclusive of the nail matrix, as well as the nail bed if clinically indicated, should be performed by a surgeon who is familiar with the intricacies of performing a nail biopsy.33 Because of limited experience and the difficulties that are commonly confronted in the histologic interpretation of nail specimens, biopsies of melanonychia striata are best interpreted by a dermatopathologist.34
When nail-bed pigmentation is noted, other causes such as systemic drugs (e.g., antimalarials, zidovudine, bleomycin, doxorubicin, minocycline, and hydroxyuria) or systemic disease (e.g., Addison disease and HIV infection) must be considered; however, these causes usually result in a broader, more diffuse pigmentation, often involving multiple nails.35 Another reported association with melanonychia striata is systemic lupus erythematosus.36 Frictional melanonychia resulting from trauma from athletic activities or poorly fitting shoewear may cause nail pigmentation, including pigmentation of the nail fold (pseudo-Hutchinson sign); such pigmentation is more common in dark-skinned persons.32
Bacterial and Fungal Nail Infections
Bacterial infection of the nail folds (bacterial paronychia) is usually acute in nature. It is characterized by swelling, erythema, discomfort, and sometimes purulence. The most common etiologic pathogen is Staphylococcus aureus. Treatment requires drainage of a focal abscess, if present, and oral antibiotic therapy.37
Chronic paronychia results from persistent or frequently recurrent nail-fold inflammation, which is usually the result of chronic irritant dermatitis and loss of cuticle from trauma or nail-care practices. Secondary candidal infection may occur.29,38
Onychomycosis, the most common infection of the nail, is a fungal infection characterized by nail-bed and plate involvement. Dermatophyte onychomycosis (tinea unguium) is the most common type of fungal nail infection.39 It is seen far more commonly in adults than in children and most frequently affects one or more toenails. The mode of fungal invasion usually presents as distal-lateral subungual onychomycosis, occurring as dermatophyte organisms migrate from pedal skin to below the nail plate and invade nail-bed tissue.40 Tinea pedis and onychomycosis frequently coexist in a patient.41,42
The dermatophytes that most commonly cause onychomycosis are Trichophyton rubrum and T. mentagrophytes.43 The tendency to harbor dermatophytes (especially T. rubrum), predominantly on pedal skin, has been noted in some kindreds. As a result, patients with such a tendency are prone to tinea pedis, tinea unguium, tinea cruris, and diffuse tinea corporis. They may present with dermatophyte infections earlier in life than usually seen and often experience recurrence of dermatophyte infection after completion of initially effective therapy.
The most characteristic clinical features of dermatophyte onychomycosis are distal onycholysis, subungual hyperkeratosis, and a dystrophic, discolored nail plate.42 Because this combination of features is also seen in persons with nail psoriasis, accurate diagnosis may require performance of a potassium hydroxide (KOH) preparation and fungal culture [see Figure 5]. It is important that specimens be obtained from the nail bed [see Figures 6a and 6b] and that culture specimens be transported and plated appropriately, because different culture media are required for identification of dermatophyte and nondermatophyte fungal nail pathogens.42 Dermatophyte test medium (DTM) may be used as an in-office culture technique that has no special incubation requirements. DTM is inexpensive and accurate in the diagnosis of dermatophyte onychomycosis.44
Figure 5. Psoriasis of the nail, characterized by subungual hyperkeratosis and loss of distal onycholytic nail plate. This patient was unsuccessfully treated with oral antifungal therapy after an erroneous diagnosis of onychomycosis was made on the basis of clinical diagnosis alone. Careful examination of the proximal intact nail plate reveals pitting, a feature characteristic for psoriasis and not onychomycosis.
Figure 6. (a) When obtaining a nail specimen for potassium hydroxide (KOH) preparation, it is important to expose the affected nail bed by first trimming away and discarding the distal, separated (onycholytic) nail plate. (b) Small specimen fragments of subungual hyperkeratosis of the nail bed and exposed undersurface of the nail plate are effectively obtained using a small curette. The smaller fragments are more easily dissolved by KOH, allowing for more accurate microscopic visualization, and can be easily plated on fungal culture medium.
Another method used to diagnose onychomycosis involves histologic examination of a nail plate specimen obtained from the distal free edge of the plate at its attachment to the nail bed.45 The nail-plate sample is sent to the histology laboratory, where it is thinly sectioned and stained with periodic acid-Schiff (PAS) stain. Under microscopic examination, fungi appear red, because the PAS stain highlights glycogen and mucoprotein in the cell walls of hyphae.45
Proximal white subungual onychomycosis is another presentation of dermatophyte onychomycosis. It has been reported in association with systemic immunosuppression, including HIV disease.46
The majority of patients presenting with dermatophyte toenail onycomycosis are affected by concomitant plantar (dry-type, moccasin) tinea pedis.45,46,47,48 Tinea pedis is believed to be the source of both primary and recurrent dermatophyte nail infections. The clinical presentation of tinea pedis in patients with onychomycosis may be visibly obvious or may be subtle, sometimes simulating mild xerosis (“dry skin”). Chronic dermatophytoses of the feet and toenails have been shown to be important risk factors for acute bacterial cellulitis of the leg, apparently providing a portal of entry for pathogenic bacteria.47
Candida onychomycosis is far less common than dermatophyte onychomycosis. Candida onychomycosis is often associated with immunosuppression (e.g., HIV disease and chronic mucocutaneous candidiasis). The Candida organisms may invade the nail as a secondary pathogen, and they more frequently affect the fingernails.42 Nondermatophyte molds, including Aspergillus species, Scopulariopsis brevicaulis, Fusarium species, Scytalidium hyalinum, and Scytalidium dimidiatum, have been reported to cause fingernail or toenail infection; however, such infections are relatively uncommon.42,48 Associated paronychia may be seen when nondermatophytic fungi cause onychomycosis. Effective therapy for onychomycosis includes the use of an oral antifungal agent [see Table 1]; topical therapy offers limited efficacy except in some cases of superficial white onychomycosis.48,49 Because nails grow slowly, clinical response is delayed.48 Infections with Scytalidium species are rare in the United States, and such infections respond poorly to currently available antifungal agents.
Table 1 Oral Antifungal for Toenail Onychomycosis*48
Pharmacologic therapy alone may be inadequate in some cases of onychomycosis. A very thick mycotic nail plate, marked onycholysis, and cases presenting as lateral infection may warrant adjunctive debridement.50 In addition, the presence of a dermatophytoma has been shown to reduce the response to medical therapy, including oral antifungal agents. A dermatophyoma presents as a visible, walled-off column or spike that contains multiple, thick-walled hyphae. When a dermatophytoma is present, response to oral antifungal therapy is maximized by physical removal of the loculated mass through either surgical or chemical debridement.50 In some cases, the use of more prolonged oral antifungal therapy (beyond standard recommendations) may be needed to clear the infection, especially in immunocompromised patients, elderly patients with slow-growing nails, and in more severe cases of onychomycosis.
Dermatologic Disorders Affecting the Nail
Complete reviews of dermatologic, systemic, neoplastic, and exogenous disorders affecting the nail are beyond the scope of this chapter. An overview of selected dermatologic disorders affecting the nail unit and their associated clinical findings is provided [see Table 2].
Table 2 Selected Dermatologic Disorders Affecting the Nail Unit
Figure 1 Tom Moore.
Editors: Dale, David C.; Federman, Daniel D.