Nail 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 idiopathic pulmonary fibrosis
  • Complicated tuberculosis
  • Suppurative lung disease: lung abscess, empyema, bronchiectasis, cystic fibrosis
  • Mesothelioma 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 endocarditis
  • Atrial myxoma (benign tumor)
  • Tetralogy of Fallot
• Gastrointestinal and hepatobiliary:
  • Malabsorption
  • Crohn's disease and ulcerative colitis
  • Cirrhosis, especially in primary biliary cholangitis[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 hereditary 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.[12]

A congenital form has also been recognized.[13]

Hypertrophic pulmonary osteoarthropathy

Main article: Periosteal reaction

Bone scan of a patient with HPOA

A special form of clubbing is hypertrophic pulmonary osteoarthropathy (HPOA), 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.

The exact cause for sporadic clubbing is unknown. Theories as to its cause include:

• Vasodilation (i.e., distended blood vessels).
• Secretion of growth factors (e.g., platelet-derived growth factor and hepatocyte growth factor) from the lungs.

• Overproduction of prostaglandin E2 by other tissues.[14]
• Increased entry of megakaryocytes into the systemic circulation. Under normal circumstances in healthy individuals, megakaryocytes that arise from the bone marrow are trapped in the pulmonary capillary bed and broken down before they enter the systemic circulation. It is thought that in disorders where there is right-to-left shunting or lung malignancy, the megakaryocytes can bypass the breakdown within the pulmonary circulation and enter the systemic circulation. They are then trapped within the capillary beds within the extremities, such as the digits, and release platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). PDGF and VEGF have growth promoting properties and cause connective tissue hypertrophy and capillary permeability.[15]

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

When clubbing is observed, pseudoclubbing should be excluded before making the diagnosis. Associated conditions may be identified by taking a detailed medical history—particular attention is paid to lung, heart, and gastrointestinal conditions—and conducting a thorough clinical examination, which may disclose associated features relevant to the underlying diagnosis. Additional studies such as a chest X-ray and a chest CT-scan may reveal otherwise asymptomatic cardiopulmonary disease.[12]

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.[7]

At least since the time of Hippocrates, clubbing has been recognized as a sign of disease.[5] The phenomenon has been called "Hippocratic fingers".

• Clubbed thumb (unrelated congenital deformity)