Nail clubbing

Clubbing
Synonyms	drumstick fingers, watch-glass nails[1]
Clubbing
Classification and external resources
Specialty	Pulmonology
ICD-10	R68.3
ICD-9-CM	781.5

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.^[2][3] Clubbing for no obvious reason can also occur, but is rare.^[4][5] Hippocrates was probably the first to document clubbing as a sign of disease, and the phenomenon is therefore occasionally called Hippocratic fingers.

Detection

Clubbing may be present in one of five stages:^[6]

1. No visible clubbing. Fluctuation (increased ballotability) and softening of the nail bed only. No visible changes of nails.
2. Mild clubbing. Loss of the normal <165° angle (Lovibond angle) between the nailbed and the fold (cuticula). Schamroth's window is obliterated. Clubbing is not obvious at a glance.
3. Moderate clubbing. Increased convexity of the nail fold. Clubbing is apparent at a glance.
4. Gross clubbing. Thickening of the whole distal (end part of the) finger (resembling a drumstick)
5. Hypertrophic osteoarthropathy. Shiny aspect and striation of the nail and skin

Schamroth's test or Schamroth's window test (originally demonstrated by South African cardiologist Leo Schamroth on himself)^[7] is a popular test for clubbing. When the distal phalanges (bones nearest the fingertips) of corresponding fingers of opposite hands are directly opposed (place fingernails of same finger on opposite hands against each other, nail to nail), a small diamond-shaped "window" is normally apparent between the nailbeds. If this window is obliterated, the test is positive and clubbing is present.

• 
  Severe clubbing
• 
  Front view
• 
  Side views

Causes

Although many diseases are associated with clubbing (particularly lung diseases), the reports are fairly anecdotal. Prospective studies of patients presenting with clubbing have not yet been performed, and hence there is no conclusive evidence of these associations.

Isolated clubbing

Clubbing is associated with:

• Lung disease:
  • Lung cancer, mainly non-small-cell (54% of all cases), not seen frequently in small-cell lung cancer (< 5% of cases)^[8]
  • Interstitial lung disease most commonly fibrosing alveolitis
  • Complicated tuberculosis
  • Suppurative lung disease: lung abscess, empyema, bronchiectasis, cystic fibrosis
  • Mesothelioma of the pleura
  • Arteriovenous fistula or malformation
• Heart disease:
  • Any disease featuring chronic hypoxia
  • Congenital cyanotic heart disease (most common cardiac cause)
  • Subacute bacterial endocarditis
  • Atrial myxoma (benign tumor)
  • Tetralogy of Fallot
• Gastrointestinal and hepatobiliary:
  • Malabsorption
  • Crohn's disease and ulcerative colitis
  • Cirrhosis, especially in primary biliary cirrhosis^[9]
  • Hepatopulmonary syndrome, a complication of cirrhosis^[10]
• Others:
  • Graves' disease (autoimmune hyperthyroidism) – in this case it is known as thyroid acropachy^[11]
  • 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 with significant degrees of clubbing, a search for signs of bronchogenic carcinoma (or other causes of clubbing) might be indicated.^[6]

A congenital form is also known.^[12] This may be inherited either in an autosomal recessive or dominant fashion. In these cases the thumbs are almost always affected: the other fingers may be affected.

HPOA

Bone scan of a patient with HPOA

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 HPOA

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.^[13]

Pathophysiology

The exact cause for sporadic clubbing is unknown, with numerous theories as to its cause. Vasodilation (distended blood vessels), secretion of growth factors (such as platelet-derived growth factor and hepatocyte growth factor) from the lungs, and other mechanisms have been proposed. The discovery of disorders in the prostaglandin metabolism in primary osteoarthropathy has led to suggestions that overproduction of PGE2 by other tissues may be the causative factor for clubbing.^[13] That is to say, up-regulation of PGE2 has been implicated as a possible etiology of nail clubbing.

Diagnosis

Clubbing of the fingernail: The red line shows the outline of a clubbed nail.

When clubbing is encountered in patients, doctors will seek to identify its cause. They usually accomplish this by obtaining a medical history—particular attention is paid to lung, heart, and gastrointestinal conditions—and conducting a clinical examination, which may disclose associated features relevant to a diagnosis. Additional studies such as a chest X-ray and a chest CT-scan may also be performed.^[6]

Epidemiology

The exact frequency of clubbing in the population is not known. A 2008 study found clubbing in 1%, or 15 patients, of 1511 patients admitted to a department of internal medicine in Belgium. Of these, 40%, or 6 patients, turned out to have significant underlying disease of various causes, while 60%, or 9 patients, had no medical problems on further investigations and remained well over the subsequent year.^[5]

See also

• Clubbed thumb (unrelated congenital deformity)

References

1. Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
2. Rutherford, JD (14 May 2013). "Digital clubbing.". Circulation. 127 (19): 1997–9. doi:10.1161/circulationaha.112.000163. PMID 23671180.
3. Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. ^:656
4. Schwatz, RA. "Clubbing of the Nails". Medscape. Medscape. Retrieved 14 August 2014.
5. Vandemergel X, Renneboog B (July 2008). "Prevalence, aetiologies and significance of clubbing in a department of general internal medicine". Eur. J. Intern. Med. 19 (5): 325–9. doi:10.1016/j.ejim.2007.05.015. PMID 18549933.
6. Myers KA, Farquhar DR (2001). "The rational clinical examination: does this patient have clubbing?". JAMA. 286 (3): 341–7. doi:10.1001/jama.286.3.341. PMID 11466101.
7. Schamroth L (February 1976). "Personal experience". S. Afr. Med. J. 50 (9): 297–300. PMID 1265563.
8. Sridhar KS, Lobo CF, Altman RD (1998). "Digital clubbing and lung cancer" (PDF). Chest. 114 (6): 1535–37. doi:10.1378/chest.114.6.1535. PMID 9872183.
9. Epstein O, Dick R, Sherlock S (1981). "Prospective study of periostitis and finger clubbing in primary biliary cirrhosis and other forms of chronic liver disease". Gut. 22 (3): 203–6. doi:10.1136/gut.22.3.203. PMC 1419499. PMID 7227854.
10. Naeije R (March 2003). "Hepatopulmonary syndrome and portopulmonary hypertension". Swiss Med Wkly. 133 (11–12): 163–9. PMID 12715285.
11. -724565997 at GPnotebook
12. Shah K, Ferrara TM, Jan A, Umair M, Irfanullah, Khan S, Ahmad W, Spritz RA (2016) Homozygous SLCO2A1 translation initiation codon mutation in a Pakistani family with recessive isolated congenital nail clubbing (ICNC). Br J Dermatol
13. Uppal S, Diggle CP, Carr IM, et al. (June 2008). "Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy". Nat. Genet. 40 (6): 789–93. doi:10.1038/ng.153. PMID 18500342.