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 Table of Contents  
Year : 2017  |  Volume : 5  |  Issue : 2  |  Page : 269-274

Nail evaluation in internal diseases: An indispensable exercise

1 Consultant Dermatologist, Kaya Clinic, Chennai, Tamil Nadu, India
2 Department of Dermatology, Yenepoya Medical College, Yenepoya University, Mangalore, Karnataka, India

Date of Web Publication15-Dec-2017

Correspondence Address:
Manjunath M Shenoy
Department of Dermatology, Yenepoya Medical College, Yenepoya University, Mangalore - 575 018, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/amhs.amhs_124_17

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Nails are the structures without any vital functions, but their diagnostic significance cannot be undermined. Nail unit constitutes the nail plate, nail bed, and nail folds which exhibit signs of the nail unit and internal disorders. Most nail changes are nonspecific, but some of them have high diagnostic significance. Many such changes have been described since the historic times, and many have been discussed in the recent literature. Diseases of the nail units such as infections may also indicate the presence of immunosuppression or diabetes. Interpretation of the nail changes requires an amount of expertise which any physician can obtain by careful observation. This article emphasizes the important nail signs in internal disorders.

Keywords: Beau's line, internal diseases, melanonychia, nail changes

How to cite this article:
Gopal V, Shenoy MM. Nail evaluation in internal diseases: An indispensable exercise. Arch Med Health Sci 2017;5:269-74

How to cite this URL:
Gopal V, Shenoy MM. Nail evaluation in internal diseases: An indispensable exercise. Arch Med Health Sci [serial online] 2017 [cited 2023 Feb 2];5:269-74. Available from: https://www.amhsjournal.org/text.asp?2017/5/2/269/220820

  Introduction Top

The nail has often been overlooked in routine clinical examinations as it is a seemingly unimportant structure with limited functions. Time and again, nail changes have proven to be an important indicator of underlying disease processes and at times appear as an impending sign, before the full-blown manifestation of systemic illness.[1] Nail is a mirror of internal disorders, and a clinician familiar with the nail changes can develop himself/herself into an astute diagnostician. One of the first such associations was historically described by Hippocrates in the 5th century BD later termed as clubbing by trousseau.[2],[3] Since then, numerous nail and systemic associations have been described that include splinter hemorrhages, Beau's lines, koilonychia, and Terry's nails. Nail examination is an integral part of routine examinations as it provides diagnostic clues to systemic illness and makes way for early intervention.

The nail is a fully keratinized structure that develops from the nail matrix germinative epithelium between the 9th and 20th weeks of intrauterine life.[4] The nail plate consists of epithelium that keratinizes without the formation of a granular layer. There is also an intimate anatomic relationship between the nail and the bone; hence, there can be bone alterations in nail disorders and vice versa. The nail functions as an important appendage, and it not only contributes to the pleasing appearance of the hands but protects the distal phalanges, enhances tactile discrimination, aids in scratching, grooming, picking up small objects, and also is an efficient natural weapon.[5]

Most nail changes are conspicuous and can be observed without any difficulty. Certain signs can be observed with the aid of special instruments such as nail fold capillaroscope [Figure 1] or dermatoscope. Such changes not only aid in the diagnosis but also prognosticate an underlying condition.[6]
Figure 1: (a) Nail fold capillariscopy, (b) Onychorrhexis, (c) Longitudinal melanonychia, (d) Nails in paraneoplastic pemphigus, (e) Muehrcke's line, (f) Pterygium unguis , (g) Psoriatic arthropathy with nail changes, (h) Pemphigus showing paronychia, (i) Dystrophic epidermolysis bullosa, (j) Onychomadesis, (k) Beau's lines, (l) Photo-onycholysis

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  Nail Structure Top

The nail apparatus consists of a horny “dead” product, the nail plate, and four specialized epithelia: (1) the proximal and the two lateral nail folds, (2) the nail matrix, (3) the nail bed, and (4) the hyponychium. It is surrounded by soft tissue and has vascular and neural innervation.

The nail plate is a laminated keratinized structure plate that lies on the nail matrix at the proximal end, nail bed, and then hyponychium in the distal-free edge. It is flanked by the proximal and lateral nail folds which cover the proximal third and lateral margins. The proximal part of visible nail plate is marked by a half moon crescent shape on the nail plate known as lunula. There is a thin distal transverse white band known as the onychodermal band and marks the most distal portion of attachment of the nail plate to the nail bed.[7],[8] On transverse section, the nail plate has three portions: dorsal nail plate, intermediate nail plate, and ventral nail plate.[9]

  Pathogenesis of Nail Changes Top

Nail plate is surrounded by highly vascular and innervated structures that contribute to its formation and growth. The interrelationship between these tissues is responsible for the way nails present with changes. Changes that contribute to the diagnosis can be the changes of nail plate, nail bed, or nail folds. Most conspicuous changes occur over the nail plate where there could be discoloration, lines, bands, grooves, altered shape, and attachment to the nail bed. Each change represents damage to the matrix such as hypoxia. Some of the changes could have similar underlying mechanism; for example, onychomadesis and Beau's line.[10] Systemic diseases can affect the nail matrix growth and thus bring about the nail changes. Pathologies caused by diabetes mellitus, bacterial endocarditis, drugs, and sepsis can affect the nail folds.[11] Nail development may be affected in many genetic disorders such as nail–patella syndrome and dyskeratosis congenita, where there can be other organ system diseases.[12],[13] However, it is difficult to understand the pathogenesis of most nail dystrophies associated with internal disorders, and often, it is due to more than one factors. Many of these patients are on polypharmacy and that may contribute to the nail changes due to their toxicity.

  Nail Signs Top

  1. In primary internal disorders
  2. In primary dermatological disorders
  3. In drug toxicity
  4. In immunosuppression.

  Nail Signs in Primary Internal Disorders Top

Renal disease

Mucocutaneous manifestations are well described in chronic kidney disease, which include pruritus, xerosis, folliculitis, to name a few. Various nail changes have also been observed which include clubbing, koilonychia, leukonychia, half-and-half nails, pitting, nail plate thinning, subungual hyperkeratosis, Muehrcke's line, Terry's nail, splinter hemorrhages, onychomycosis, and Mees lines. Of these, leukonychia, nail bed thinning, half-and-half nails, onycholysis, and absence of lunula were found to have a high prevalence in multiple studies.[14],[15],[16],[17],[18],[19] In a study by Tajbakhsh et al., they found a significant association between duration of dialysis and leukonychia as well as a significant association of clubbing with a high calcium-phosphorus product. The factors responsible for mucocutaneous changes are uremia, metabolic disorders, dialysis, and adverse effects of immunosuppressive drugs.[20]

Hepatic disease

The various changes observed are onychomycosis, onychorrhexis, brittle nails, clubbing, nail dystrophy, leukonychia, and longitudinal melanonychia in the descending order of frequency described in the study by Salem et al. These changes are not only observed in liver cirrhosis but also in hepatitis B and hepatitis C infection.

Terry's nails are an apparent leukonychia where the nail bed appears white with a ground-glass opacity. There are multiple reports on its appearance in relation to chronic alcoholic liver disease.[21],[22],[23],[24] A blue discoloration of lunula has been observed in Wilson's disease and in hemochromatosis.[25]


Sudden and obvious changes in nails have often been clues to systemic malignancies. Hypertrophic osteoarthropathy is one such entity characterized by digital, periosteal reaction, polyarthralgia, arthritis, and synovitis. It appears secondary to pulmonary malignancies with or without metastases. There are reports of its occurrence in other malignancies such as sarcomas and nasopharyngeal carcinomas.[26] Nail dystrophy can be seen in paraneoplastic pemphigus, which clinically manifests as recalcitrant painful oral erosions and cutaneous eruption.[27] It occurs secondary to non-Hodgkin's lymphoma, chronic lymphoid leukemia, and Castleman disease and must be investigated further if such clinical manifestations appear.[28] The coral bead sign in multicenter reticulohistiocytoses is characterized by multiple pink-brown papules measuring few millimeters to 2 cm located on the nail folds on the dorsum of fingers. This condition is also associated with hematological malignancies and solid organ tumors of breast, stomach, and ovaries.[29],[30] Yellow nail syndrome is a triad of lymphedema, respiratory disease, and yellow nails. It can be seen in systemic malignancies such as mycosis, fungoides, and lymphomas. In this syndrome, the nails are thick, over-curved greenish nails with loss of cuticle and on occasion undergo onycholysis. Resolution of nail changes with clearance of systemic diseases has been well documented.[31],[32]

Endocrine disorders

Onycholysis, longitudinal ridging, and brown discoloration of nail plate are known to occur in hypopituitarism.[33] Nail changes occurring in hypoparathyroidism are dyschromias, distal onycholysis, transverse ridging, opaque appearance, and ungual dystrophy.[34] Longitudinal melanonychia appearing as pigmented bands on the nails occurs in patients with Addison's disease.[35] In acromegaly, the changes on the extremities are wide-thickened stubby fingers along with short, wide, and brittle nails.[36]

In diabetes mellitus, certain nail changes such as periungual erythema and telangiectasia appear early on. Chronic changes include thickened nails, yellow discoloration, onychorrhexis, and nail fragility. Rosenau's spots are pit-like depressions seen in nails of diabetic patients.[37] Paronychias and onychomycosis may be more frequent in diabetics and may contribute to the development of foot ulcer and cellulitis.[38]

Specific nail changes are seen in thyroid disorders. Thyroid acropachy associated with Grave's syndrome is characterized by clubbing of fingers and toes, fibrosis, and thickening of subcutaneous tissues and diaphyseal periosteal proliferation. Other nail changes in hyperthyroidism are onycholysis in the 4th and 5th nails known as Plummer's nails.[35],[39],[40],[41]

Specific changes

Lindsay's nails or half-and-half nails appear as red, pink, or brown bands occupying the distal portion of nail bed in patients with chronic kidney disease. The proximal portion is white and is thought to result from chronic anemia. The brown band is a result of increased melanin deposition distally.[42] It is observed to be found in as much as 21% of patients on dialysis and has no relation with azotemia levels.[43],[44]

Splinter hemorrhage is a frequent finding in dialysis patients, described as dark reddish filiform longitudinal lines growing in the distal portion of the nail plate. It is seen in patients with subacute bacterial endocarditis and arterial emboli. Trauma which is the most common cause must be ruled, and involvement of multiple nails points to systemic involvement. It can be seen in rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and malignancies.[45],[46]

Terry's nails are seen as an entire nail bed leukonychia sparing the 2 mm distal margin. It is an apparent leukonychia first described by Dr. Richard Terry in 1954. It is seen bilaterally and is more marked on the thumb and forefinger. Holzberg and Walker in 1984 formulated a criterion for Terry's nail as follows – distal thin pink-to-brown transverse band, 0.5–3.0 mm in width, decreased venous return not obscuring the distal band, white or light pink proximal nail, absent lunula, and at least 4 of 10 nails with the above criteria.[23]

Mees lines appear as a single, transverse, narrow whitish band on multiple nail plates. A classical cause of this is arsenic poisoning. They do not disappear when blanched. These lines can appear in the setting of congestive heart failure, Hodgkin's lymphoma, and carbon monoxide poisoning.[47] Muehrcke's lines are white horizontal lines running parallel to lunula that represents an abnormality of the vascular nail bed. When blanched, they disappear temporarily. They were usually seen on the middle three fingernails. Conditions causing chronic hypoalbuminemia are implicated including nephrotic syndrome, glomerulonephritis, chronic liver disease, chemotherapeutic drugs, and malnutrition. They differ from Mees lines, in that they disappear on blanching, resolve with normalization of serum albumin levels (2.2 g/100 ml), and do not grow out distally.[37],[48]

Koilonychia also known as spoon-shaped nails is a reverse curvature in the transverse and longitudinal axes of nail plate giving a concave appearance. It is most prominent on the thumb and great toe. It is seen in iron deficiency anemia and hemochromatosis.[49] Pterygium formation (proximal nail fold fusing with nail bed) is classically described in lichen planus but also in graft versus host diseases, sarcoidosis, and lupus. Some of the named nails are summarized in [Table 1].
Table 1: Named nail signs of importance in internal medicine

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  Nail Signs in Primary Dermatological Diseases Top

Papulosquamous diseases

Papulosquamous disorders include inflammatory skin disorders that morphologically monies as clay papule or plaques. They include conditions such as psoriasis and lichen planus. Many of these conditions are associated with systemic inflammation leading to internal manifestations such as arthritis, nonalcoholic fatty liver disease, gastrointestinal disease, and ocular diseases.[50] There can be dyslipidemia and metabolic syndrome with associated cardiovascular morbidities.[51] Fifty percent of psoriasis patients present with nail changes such as pitting of nail plate separations of nail plate from nail bed known as onycholysis, and such changes are more frequent and more pronounced in patients with arthritis.[52]

Bullous disorders

Mechanobullous disorders such as epidermolysis bullosa (EB) and immunobullous disorders such as pemphigus frequently produce nail dystrophies. EB are hereditary disorders characterized by easy blistering of skin and mucosa and can often be associated with internal manifestations such as esophageal disease, pyloric atresia, and cardiac disease. Nail involvement can be the only sign of EB, and it has been included in the criteria for the EB severity.[53] Pemphigus can manifest with paronychia, Beau's lines, and onychomadesis.


Genetic diseases that affect the skin have high frequency of nail involvement and many of them have internal manifestations too. Thus, nail examination is an integral part of genetic diseases. Many of these signs are pathognomonic such as triangular lunula in nail–patella syndrome.[54] Nail–patella syndrome manifests with iliac horns, absent patellae, nail hypoplasia, and renal disease. Dyskeratosis congenita can have pigmentation, nail dystrophy, and oral leukokeratosis that can have potential for malignant transformation. Nail dystrophies are often common findings in ectodermal dysplasia.

  Nail Signs in Drug Toxicity Top

Drug-induced nail changes usually involve multiple or all of the nails. A large number of drugs can be responsible for the development of nail changes. Most commonly incriminated drugs are cancer chemotherapeutic agents and retinoids. These changes occur as a result of toxicity to the matrix, nail bed, periungual tissues, or digit blood vessels.[55]

Patients treated with systemic anticancer drugs often nail changes which are usually well tolerated and resolve on cessation of treatment. These nail changes are melanonychia, leukonychia, onycholysis, onychomadesis, Beau's lines, or onychorrhexis. However, there are certain nail toxicities that cause pain and functional impairment. These are especially seen with taxanes and epidermal growth factor receptor inhibitors, which may cause painful paronychia or pyogenic granuloma.[56]

Retinoids can cause brittle nails, Beau's lines, medial nail dystrophy, and paronychia. Certain antiretroviral drugs are known to produce nail changes. Zidovudine can cause blue or azure nails and diffuse nail plate melanonychia and paronychia. Lamivudine causes paronychia, longitudinal melanonychia, and pseudopyogenic granuloma. Photo-onycholysis (tender, painful nails with photosensitivity and onycholysis) can be caused by tetracyclines and psoralens. Nail pigmentation can be caused by minocycline. Other drugs causing photo onycholysis are captopril, fluoroquinolones, oral contraceptives, psoralens, chloramphenicol, and 5-flurouracil.[57],[58] However, retinoids are known to produce nonphoto-dependant onycholysis.[59]

  Nail Signs in Immunosuppression Top

In the recent past, HIV epidemic, malignancies, and iatrogenic immunosuppression has caused a large number of people living with immunosuppressed. Skin is the organ that exhibits the initial and conspicuous signs of immunosuppression; nail and hair are the appendage that also reciprocates. Nail as an organ that signifies immunosuppression has been recognized increasingly. Proximal-subungual onychomycosis has been associated with HIV-associated immunosuppression.[60] Immunosuppression is important in the clinical behavior of many diseases such as nail unit squamous cell carcinoma.[61] Nail changes are common with many anti-cancer chemotherapy. Hence, nail examination is indispensable in immunosuppressed patients throughout the course of illness and therapy.

  Conclusion Top

Many nail changes are trivial, but many others are suggestive of a nail pathology or internal disorder. Distinction between them is crucial, and a detailed clinical examination often supported by an office tools such as capillaroscopy or dermoscopy can help. Laboratory diagnosis especially bacteriological and mycological workup can be of benefit; for direct microscopy, fungal culture nail histopathology is useful.[62] Most nail changes of the internal disorders are either permanent or self-limiting. There are few therapeutic options, thus limiting them to a clinical sign than a disorder.

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  [Table 1]


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