Nail Diagnosis

Hippocrates in the fifth century described clubbing as an important clue to myriad of systemic manifestations. (1) (Source). Since then many more nail findings have been found to be associated with systemic diseases. Therefore,examination of the nails should be an integral part of a complete dermatological and general health examination.

Clinicians must acquaint themselves with these nail findings as they can provide a clue in diagnosing certain systemic diseases. Moreover, at times, some nail changes can be a presenting feature before other signs of a systemic disease become clinically evident.

With the convenience with which all 20 nails can be examined, health practitioners and their patients would benefit from a finger and toe nail examination.  As a general rule, fingernails usually provide more accurate information than toenails, because clinical signs on toenails are often modified by trauma. But when the feet are in good shape, toenails can also provide relevant information on the patient’s health status.

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Anatomy of the basic parts of a human nail. A. Nail plate; B. lunula; C. root; D. sinus; E. matrix; F. nail bed; G. eponychium; H. free margin.

Fingernails have Four Parts

Along with skin and hair, nails are part of the body’s integumentary system,whose main function is to protect your body from damage and infection. Fingernails have four basic structures: the matrix, the nail plate, the nail bed, and the skin around the nail (including the cuticle).

Abnormalities of nail shape

Koilonychia

It is the presence of reverse curvature in the transverse and longitudinal axis, giving a concave dorsal aspect to the nail. These changes result in spooning of the nails capable of retaining a drop of water.It is appreciable more on fingernails then toenails (Exhibit A).

Exhibit A

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Koilonychia can be idiopathic or associated with a variety of conditions such as iron deficiency anemia(Plummer Vinson syndrome),malnutrition, hemochromatosis, coronary disease, thyroid disorders, Upper gastrointestinal malignancy or traumatic injury.(2,3)
Koilonychia is of common occurrence in young infants but tend to disappear in early years of life in majority. Subungual hyperkeratosis accompanying koilonychias is suggestive ofpsoriasis. A number of factors, such as old age, digital ischemia, and so on, leading to thinning of nails may cause koilonychia. Occupational softening and iron deficiency are probably the most common causes.[4,5] Mild nail-plate thickening and discoloration are also indicative of an occupational cause. The petaloid nail is an early stage of koilonychia and is characterized by flattening of the nail.[6]

In koilonychia (etymologically,  spoon nails),  these spoon nails bow in the opposite direction of normal nails, inward like a spoon, to the point where a few drops of water couldsit in the “spoon” shape without spilling out. Spoon nails is a sign of seriousmineral deficiency, specifically copper, zinc or iron. Protein deficiency could also be at issue. It’s as if the Body is trying to warn us of serious matters.

Fingernails with koilonychia and trachyonychia

Hereditary and congenital forms are rare and are sometimes associated with other nail signs such as leukonychia. The exact cause of koilonychia is elusive. An angulation of the nail matrix secondary to connective tissue changes or spooning of the nail resulting from a relatively low distal matrix as compared with the proximal matrix, are some of the proposed hypotheses.[7]

Clubbing

Clubbing is characterized by increased nail plate curvature longitudinally and transversely with soft tissue hypertrophy of the digital pulp usually involving all 20 digits. (pictures below)

Exhibit B

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Nail clubbing, also known as digital clubbing, is a deformity of the finger or toe nails associated with a number of diseases, mostly of the heart and lungs. Clubbing for no obvious reason can also occur, but is rare. Hippocrates was the first to formally document clubbing as a sign of disease, and the phenomenon is therefore occasionally called “Hippocratic fingers.” (See 7 bis for additional details)

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Clubbing has been studied extensively. Because of an exhaustive list of systemic associations, it is classified into three major categories: Idiopathic, hereditary–congenital, and acquired.[6,7] It may have connotations with systemic diseases, such as cyanotic congenital heart diseases, infective endocarditis, primary and metastatic lung cancer, bronchiectasis, lung abscess, cystic fibrosis, mesothelioma, inflammatory bowel disease, and hepatic cirrhosis.[8,9]

Clubbing may be an early sign of AIDS in pediatric HIV-positive patients. It may be associated with hypertrophic osteoarthropathy, in which subperiosteal new bone formation in the distal diaphysis of the long bones of the extremities causes pain and symmetric arthritis-like changes in the shoulders, knees, ankles, wrists, and elbows.

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Three forms of geometric assessment can be performed in clubbing. (1) Lovibond’s angle at the junction between nail plate and proximal nail fold and it is normally less than 160°. In clubbing, this is increased to over 180°. (2) Curth’s angle at distal interphalangeal (DIP) joint is normally approximately 180° and this diminishes to less than 160° in clubbing (Exhibit C). (3) Schamroth sign refers to the obliteration of normally diamond-shaped space formed when dorsal sides of the distal phalanges of corresponding right and left digits are opposed[10]

Exhibit C

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A diamond-shaped Schmaroth’s window present normally is obliterated in patients with clubbing

Pincer nail

When the transverse curvature of the nail is increased along the longitudinal axis of the nail reaching to its greatest proportion toward the tip, it is called pincer nails.

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Pincer nails (pin-sir): excessive curvature of the nail plate that causes the nail to pinch into the soft tissue of the surrounding skin

An association with a curved ingrown nail with bilateral penetration to the nail folds is not uncommon. Pincer nail may be hereditary or acquired. Although the mechanism of its development remains unknown, underlying systemic disease or medications are the common associations. The dorsal extension of bone caused by a subungual exostosismay also produce the pincer nail; hence the nail as well as the exostosis must be excised. The lateral borders of the nail exert a constant pressure, permanently constricting the deformed nail plate (unguis constringens). Moreover, a few reports suggest an onychomatricoma may present with a pincer nail. In addition, Kirkland and Sheth reported a case of acquired pincer nail deformity associated with end-stage renal disease secondary to diabetes mellitus.[4,11]

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Dolichonychia

It is defined as the length of nails greatly exceeding the width of nail and has been associated withMarfan’s syndrome and hypopituitarism.[12]

Dolichonychia refers to nails that are elongated and slender. This nail morphology has been described in single case reports of patients with Ehlers-Danlos syndrome, hypohidrotic ectodermal dysplasia, and Marfan syndrome.  The length and width of fingernails were measured in patients with Marfan syndrome and in individuals without the syndrome. A fingernail index was calculated for each person. A non-parametric sign test was used to compare the mean fingernail index of patients with Marfan syndrome and control subjects. RESULTS:The fingernail index ranged from 0.92 to 1.52 in patients with Marfan syndrome and from 0.77 to 1.30 in control individuals. The median fingernail index in women with Marfan syndrome (1.455) was significantly greater than the median fingernail index in women control subjects (1.080) (P = 0.035). Dolichonychia, defined as a fingernail index greater than or equal to 1.30, was present in six of eight (75%) of women with Marfan syndrome as compared with only one of 40 (2.5%) of women control subjects. CONCLUSIONS: Dolichonychia is a physical finding present in some patients with Marfan syndrome. The detection of long narrow fingernails in women should suggest the possibility of Marfan syndrome. (South Med J.2004 Apr;97(4):354-8.)

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Brachyonychia

In brachyonychia, the width of the nail plate is reduced as compared to the length. It may be a feature of hyperparathyroidism and psoriatic arthropathy as an early sign of bone resorption.[10,13] It could also suggest chronic kidney disease. (Source)

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Parrot beak nail

A symmetrical overcurvature of the free edge of finger nails mimics the beak of a parrot. It is typically seen in severe acrosclerosis with distal phalangeal resorption due to scleroderma. The nail plate may bend around the shortened fingertip.[4,14]

Macronychia and micronychia

These constitute nails that are too large or too small compared with other nails on nearby digits. Macronychia may be due to local gigantism, whereas micronychia may occur in association with plexiform neuromas.[10]

Abnormalities of nail attachment

Onycholysis

Onycholysis refers to the distal separation of the nail plate from the nail bed.

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Pterygium

Pterygium unguis results from a scarring involving the nail fold extending onto the matrix. It may be a “dorsal pterygium” where proximal nail fold fuses to matrix and later to nail bed or “ventral pterygium” where a distal extension of the hyponychium attaches to the undersurface of the nail plate thereby obliterating the distal nail groove.

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Pterygium in second and third fingernails in lichen planus

Dorsal pterygium is classically seen in lichen planus. It may also be seen in burns, cicatricial pemphigoid, dyskeratosis congenital, graft versus host disease, radiodermatitis, and lupus erythematosus. Also, ventral pterygium is seen in leprosy, neurofibromatosis, subungual exostosis, lupus erythematosus, and systemic sclerosis.[4,17]

Abnormalities of nail surface

Longitudinal brittle ridges (Onychorrhexis)

Longitudinal lines, or striations, may appear as indented grooves or projecting ridges and may represent long-lasting abnormalities

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Longitudinal ridging with beading and fissuring associated with severe anemia

Although a single nail fissure is most likely due to a minor trauma, systemic connotations have been found with systemic amyloidosis, nail-patella syndrome, collagen vascular diseases, graft versus host disease, and rheumatoid arthritis.[4,10]

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These Central ridges can also be causedby iron, folic acid, or protein deficiency. These lengthwise ridges are brittle. These are often seen in the nails of the elderly who tend to have malabsorption issues. But regardless of age, their presence is never normal, most especially in the non-elderly individual.

Beau’s lines

Described first in 1846, Beau’s lines are band-like depressions extending from one lateral edge of the nail to the other.

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It is the most common and least specific nail change in a systemic disease. Its exact cause is not known but there istemporary cessation of nail growth in the matrixby various factors, for example, trauma involving proximal nail fold, severe acute illness such as fever, heart attack, exposure to extreme cold, psychological stress, and poor nutritional status.

Idiopathic and inherited forms also occur. If there is complete inhibition of nail growth for around 2 weeks, Beau’s line will reach maximum depth resulting in onychomadesis  (See picture below)

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Multiple Beau’s lines in the middle finger and onychomadesis in the index finger

These are deep horizontal grooves that travel from one side of the nail to the other are deep enough to see with one’s own eyes and even feel. Beau’s nails  can indicate low calcium or zinc deficiency.

Recurrent bouts of illness may lead to the formation of series of transverse furrows/grooves . The width of the transverse groove relates to the duration of the disease that has affected the matrix. The distal limit of the furrow, if abrupt, indicates a sudden attack of disease; if sloping, a more protracted onset.[18] The presence of Beau’s lines on all 20 nails is usually the result of systemic disease such as mumps, pneumonia, coronary thrombosis, Kawasaki disease, syphilis, and hypoparathyroidism.[4,10]

Nail pitting/trachyonychia

Pits result from a defective keratinization of the proximal matrix with persistence of parakeratotic cells in the nail plate surface.[19]

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Trachyonychia in a patient with psoriatic arthritis without skin lesions

Its role and diagnostic utility is doubtful as a large number of local factors affect the matrix function. It may occasionally be useful in diseases such as psoriasis, psoriatic arthritis,SLE, dermatomyositis, syphilis, sarcoidosis, and pemphigus vulgaris.[2,19,20) If the nail surface is rippled or pitted, this may be an early sign of psoriasis or inflammatory arthritis. Discoloration of the nail is common; the skin under the nail can seem reddish-brown

Onychochizia

Horizontal splitting of nail toward its distal portion is also called lamellar splitting of nail. Although trauma is the most common cause, it has been reported with X-linked chondrodysplasia punctata, polycythemia vera, and systemic retinoid therapy.[4,21]

Abnormalities of nail color

Leukonychia

Leukonychia refers to the white discoloration of nail. It is traditionally classified into three subtypes.[22] True, when pathology originates in matrix and emerges in the nail plate. Apparent, when pathology is in the nail bed. Pseudo, when nail plate pathology is exogenous, for example, onychomycosis (See pic below)

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Superficial white onychomycosis

Leukonychia associated with systemic disease is usually true or apparent Mees lines: True leukonychia due to arsenic intoxication is characterized by a single or multiple, transverse, narrow whitish line running along the width of the nail and parallel to lunula, and may involve multiple nails. These lines do not disappear on blanching and move distally with time.[23,24] Histology shows fragmented nail plated with foci of parakeratotic cells. They have been reported with other conditions as well such as Hodgkin’s disease, leprosy, tuberculosis, malaria, herpes zoster, chemotherapeutic drugs, carbon monoxide (CO) and antimony poisoning, renal and cardiac failure, pneumonia, and childbirth.

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In Leukonychia, two white marks characterizations can be identified.  1) Punctata – these are white spots on the nails. 2) Striata – these are horizontal white lines across the nail bed. The spots are associated with a zinc deficiency. Lines are associated with a selenium deficiency. Both indicate serious issues, including for DNA transcription. (See links on zinc and selenium deficiencies),

Muehrcke’s lines

These are apparent leukonychia characterized by double white transverse line (See picture below), resulting possibly from a localized edematous state in the nail bed exerting pressure on the vascular bed. They are specific for hypoalbuminic state (occur in patients albumin <2 g/dL) and disappear when the protein level normalizes. Muehrcke’s lines are seen in nephrotic syndrome, glomerulonephritis, liver disease, chemotherapeutic drugs, and malnutrition.[22,25,26]

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Muehrcke’s lines in a patient withend-stage renal diseasewith hypoalbuminemia of <2 gm%

Half and half nail or Lindsay nail

Apparent leukonychia with a normal proximal half and abnormal brownish discolored distal half(See picture below). It is seen in patients of chronic kidney disease with uremic renal failure.[26,27]

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Half and half nails in a patient with chronic kidney disease

Terry nails

Apparent leukonychia with nail that is white proximally and normal distally(See picture below).  It is associated with congestive cardiac failure, adult-onset diabetes mellitus, peripheral vascular disease, hemodialysis, and HIV.[27,28]

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Terry’s nails in a patient with congestive heart failure

Melanonychia

A longitudinal or transversebrownish black pigmentation of nailhas been typically attributed to lichen planus commonly seen in our clinics. Melanonychia may be part of being racial pigmentation (constitutional). However, an underlying melanocytic nevus or malignant melanoma, drugs (antimalarials, minocycline, phenytoin, psoralens, sulfonamides, zidovudine, doxorubicin, methotrexate, azathioprine, and so on), hemochromatosis, malnutrition, thyroid disease, smoking, HIV infection (See pic below) and Addison’s diseasecan be causally related.[4,29]

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Diffuse melanonychia involving all nails in a HIV+ve patient

Cyanosis

Cyanosis may manifest as blue or purple discoloration of the nail bed and digits as a result of lower oxygen saturation causing accumulation of deoxyhemoglobin in the small blood vessels of the extremities.

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Central cyanosis is caused by congenital heart diseases and may manifest on mucosa and extremities, whereas peripheral cyanosis is usually diagnosed by examination of the nail and digits and is caused by vasoconstriction and diminished peripheral blood flowas occurs in cold exposure, shock, congestive cardiac failure, and peripheral vascular disease.[10]

But generally, when nails have a bluish tint, this means that it’s time for some exercises and ventilation type of breathing. However, if the blueish tint persists, this could indicate a serious lung problem, such as emphysema,copd, asthma or lung cancer.

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Dry, brittle nails that frequently crack or split have been linked to thyroid disease. Cracking or splitting combined with a yellowish hue is more likely due to a fungal infection

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If the skin around the nail appears red and puffy, this is known as inflammation of the nail fold. It may be the result of lupus or another connective tissue disorder.

Gnawed Nails

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Biting obsessively could be a sign of persistent anxiety or even obsessive-compulsive disorder.

Icterus

Yellowish discoloration of the mucosae as a result of deposition of bilirubin may extend to involve the nails in severe cases and may represent severe form of liver disease or hemolysis.[10]

Nicotine staining of nails

Heavy smokers may develop a yellow discoloration of nail due to nicotine deposition. The discoloration may be a tell tale sign of long-term chances of development of cigarette-associated diseases such as carcinoma lung, chronic obstructive airway disease, and coronary artery disease.[10,30]

Splinter hemorrhages

Splinter hemorrhages in nails are formed by theextravasation of blood from the longitudinally oriented vessels of the nail bed. They occur commonly in psoriasis but may be seen in the setting of infective endocarditis(See picture below)  rheumatic heart disease, valvular replacement, SLE, antiphospholipid syndrome, IV drug abusers, and congenital heart diseases.A simultaneous occurrence in multiple nails is indicative of a systemic cause.[2,22,31]

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Splinter hemorrhage with bacterial endocarditis

Yellow nail syndrome

It is characterized bythickening and yellow to yellow-green discolorationof the nails often associated with systemic disease, most commonlylymphedema and compromised respiration due to pleural effusion (See picture below) The condition usually occurs in adults but may occur in childhood. The lunula is obscuredand there is increased transverse and longitudinal curvature with loss of cuticle.[10,32]

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Yellow discoloration of all nail syndrome

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A light yellow nail like above can be indicative of a fungal infection. As the infection worsens, the nail bed may retract, and nails may thicken and crumble. In other cases, yellow nails can indicate a more serious condition such as severe thyroid disease, lung disease, diabetes or psoriasis(picture beyond).

Red lunula

Red lunulae are seen in collagen vascular disease, cardiac failure, chronic obstructive pulmonary disease (COPD), cirrhosis, chronic urticaria, psoriasis, and CO poisoning [33] It may merge with the nail bed in the distal part of the lunula or be demarcated by a pale line and can be obliterated by pressure on the nail plate.[10]

Nail bed telangiectasia

Periungual telangiectasia is an important clue to systemic involvement in systemic sclerosis, SLE  (See picture below) and dermatomyositis influencing the prognosis of the disease. Furthermore, they may also be seen in diabetes mellitus, COPD, and rheumatoid arthritis.[2,34]

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Nail bed telangiectasia in a patient with disseminated lupus erythematosus

Dark Ominous Line or Lines

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Dark lines beneath the nail, running vertically down the nail, could be a sign of melanoma,one of the most dangerous types of skin cancer.


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If the body of the nail is mostly white with darker rims, this can indicate liver problems, such as hepatitis. In this image, you can see the fingers are also jaundiced, another sign of liver trouble.

Pale finger nail

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This nail suggest a lack of strong “chi”, stamena, rich red blood cells and blood flow. Besides malnutrition, this type of nail could be related to congestive heart failure or liver disease. Many vegans can have nails like this one. It’s normal because they have less heme iron from animal foods. However, it may not be a strong enough sign to indicate weak health. Anemia standards in the US are based on over-consumption of meat and iron, that which leads to serious CVD and other chronic diseases. As long as the liver and heart work well, there should be no problem with nails like this one. However, if it gets too pinkish or whitish, an abundance of greens, pomegrenate and beets would be indicated as well as a visit to one’s doctor.

Nail Fungal Infection

Nail fungal infections are the most common diseases of the nails, making up about 50 percent of nail abnormalities. Fungus is normally present on the body, but if it overgrows, it can become a problem.

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They are also known as onychomycosis and tinea unguium. Both fingernails and toenails are susceptible to infection, which usually appears asdiscoloration and thickening of the nail, and crumbling edges.The condition most commonly occurs in toenails. Around 10 percentof the adult population suffers from nail fungus infection. Essential oils and hygiene will do wonders.

 Nail abnormalities in specific organ system

The following chart depicts nail involvement associated with certain specific organ systems. Although overlap in findings is common, subtle changes may predict an imbalanced internal involvement.[22]

 Nail manifestation specific to organ system involvement

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Nail involvement in genodermatosis

Genodermatosis may present with a constellation of signs and symptoms thereby clinching the diagnosis. However, many times subtle but characteristic findings in nails bring us very close to the diagnosis itself. The next chart depicts genodermatosis associated with nail involvement.[22,35]

 Nail manifestations in genodermatoses

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General  Nail-to-Disease Classifications

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It is also important to classify them according to the clinical presentation, that is, morphological changes in the nail unit.

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Discussion & Conclusion

In Traditional Chinese Medicine,bodily parts often indicate the general flow of Chi or Life, thereby helping the health practitioner to figure out how to rebalance the patient and get him or her back into homeostasis.

In this perspective, the Nail diagnosis is not only a window to a plethora of possible systemic diseases,  but it’s  also a window of opportunity to preventively reversean illness in gestation.

While nail changes accompany many conditions and can be only local, the result of an infection, many times they can indicate a serious imbalance, like erectile dysfunction being the canary that indicates a serious cardiovascular problem. Meanwhile, a few tips or hacks below.

Nail Health Restoration

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Top: this is what healthy finger and toenails look like, bright pinkish color, a decent cuticle and well defined hangnail and luna.

When the body lacks key nutrients, it’s innate intelligence manifests this problem via different bodily signs, including the nails. For example, a lack of vitamin A, vitamin D, or calcium can cause nail brittleness. Insufficient vitamin B12 can lead to excessive dryness, darkened nails, and rounded or curved nail ends and too many white spots can reflect a lack of zinc and while lines an deficiency of selenium. Insufficient intake of both vitamin A and B results in fragile nails with horizontal and vertical ridges. These and many other nutrients are needed for human DNA to be well read and its transcription and protein translation to function correctlly.

Healthcare and pre-hospital-care providers (EMTs or paramedics) often use the fingernail beds as a cursory indicator of distal tissue perfusion of individuals who may be dehydrated or in shock.(Source) This is known as the CRT or blanch test. The fingernail bed is briefly depressed to turn the nail-bed white. When the pressure is released, the normal pink colour should be restored within a second or two. Delayed return to pink color can be an indicator of certain shock states such as hypovolemia.(Source) While this is not a full-proof test, it can give some useful information as to the general state of the patient. In France, when a patient dies, traditional doctors will bite the little finger’s nail to make sure the person is dead. Since the heart meridian passes by the small finger, the biten patient can get a heart jolt and get out of his or her death process….More later.

Pr. Joubert

 To learn on a one to one basis how to optimize one’s nutritional status and nails and what the fingers’ lunula  mean,  consider scheduling a coaching session via this link.

References

1. Myers KA, Farquhar DR. The rational clinical examination. Does this patient have clubbing? JAMA. 2001;286:341–7.  [PubMed]
2. Lawry M, Daniel CR., 3rd . Nails in systemic disease. In: Scher RK, Daniel CR, editors. Nails: Diagnosis, Therapy, Surgery. 3rd ed. Philadelphia: Elsevier Science Limited; 2005. pp. 147–69.
3. Kumar V, Aggarwal S, Sharma A, Sharma V. Nailing the diagnosis: Koilonychia. Perm J. 2012;16:65.[PMC free article]  [PubMed]
4. Baran R, Dawber RP, Haneke E, Tosti A, Bristow I.  Martin Dunitz. 3rd ed. 2005. Nail configuration abnormalities. A Text Atlas of Nail Disorders: Techniques in Investigation and Diagnosis; pp. 18–24.
5. Bentley-Phillips B, Bayles MA. Occupational koilonychia of the toe nails. Br J Dermatol. 1971;85:140–4.  [PubMed]
6. Stone OJ. Spoon nails and clubbing. Cutis. 1975;16:235–41.
7. Stone OJ. Diseases of nail and their management. Cutis. 1975;16:235.
7 bis. The following has been associated with clubbed nails: Lung cancer, mainly non-small-cell (54% of all cases), not seen frequently in small-cell lung cancer (< 5% of cases) Interstitial lung disease most commonly idiopathic pulmonary fibrosis Complicated tuberculosis Suppurative lung disease: lung abscess, empyema, bronchiectasis, cystic fibrosisMesothelioma of the pleura Arteriovenous fistula or malformation  Sarcoidosis Heart disease: Any disease featuring chronic hypoxia Congenital cyanotic heart disease (most common cardiac cause) Subacute bacterial endocarditisAtrial myxoma (benign tumor) Tetralogy of Fallot Gastrointestinal and hepatobiliary: MalabsorptionCrohn’s disease and ulcerative colitisCirrhosis, especially in primary biliary cirrhosis[7] Hepatopulmonary syndrome, a complication of cirrhosis Graves’ disease (autoimmune hyperthyroidism) – in this case it is known as thyroid acropachy Familial and racial clubbing and “pseudoclubbing” (people of African descent often have what appears to be clubbing Vascular anomalies of the affected arm such as an axillary artery aneurysm (in unilateral clubbing) Nail clubbing is not specific to chronic obstructive pulmonary disease (COPD). Therefore, in patients with COPD and significant degrees of clubbing, a search for signs of bronchogenic carcinoma (or other causes of clubbing) might still be indicated. A congenital form has also been recognized. A special form of clubbing is hypertrophic pulmonary osteoarthropathy, known in continental Europe as Pierre Marie-Bamberger syndrome. This is the combination of clubbing and thickening of periosteum (connective tissue lining of the bones) and synovium (lining of joints), and is often initially diagnosed as arthritis. It is commonly associated with lung cancer. Primary hypertrophic osteoarthropathy is HPOA without signs of pulmonary disease. This form has a hereditary component, although subtle cardiac abnormalities can occasionally be found. It is known eponymously as the Touraine–Solente–Golé syndrome. This condition has been linked to mutations in the gene on the fourth chromosome (4q33-q34) coding for the enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD); this leads to decreased breakdown of prostaglandin E2 and elevated levels of this substance. For a deeper more detailed analysis of clubbing, with references, see the Diagnosis workshop.
8. Braunwald E. Hypoxia and cyanosis. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrison Principles of Internal Medicine. 16th ed. New York: McGraw-Hill; 2009. pp. 209–12.
9. Hansen-Flaschen J, Nordberg J. Clubbing and hypertrophic osteoarthropathy. Clin Chest Med. 1987;8:287–98.  [PubMed]
10. Motswaledi MH, Mayayise MC. Nail changes in systemic diseases. SA Fam Pract. 2010;52:409–13.
11. Kirkland CR, Sheth P. Acquired pincer nail deformity associated with end stage renal disease secondary to diabetes. Dermatol Online J. 2009;15:17.  [PubMed]
12. Cohen PR, Milewicz DM. Dolichonychia in women with Marfan syndrome. South Med J. 2004;97:354–8.  [PubMed]
13. Rasi A, Soltani-Arabshahi R, Naraghi ZS. Circumscribed juvenile-onset pityriasis rubra pilaris with hypoparathyroidism and brachyonychia. Cutis. 2006;77:218–22.  [PubMed]
14. Desai T, Magdum A, Patel T, Loghdey S. Parrot-beak nails. Clin Exp Dermatol. 2011;36:208–9.[PubMed]
15. Zaic MN, Daniel CR. Nails in systemic disease. Dermatologic Therapy. 2002;15:99–106.
16. Daniel CR., 3rd Onycholysis: An overview. Semi Dermatol. 1991;10:34–40.  [PubMed]
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