Nail clubbing

Nail clubbing, also known as digital clubbing or clubbing, is a deformity of the finger or toe nails associated with several diseases, anomalies and defects, some congenital, mostly of the heart and lungs. When it occurs together with joint effusions, joint pains, and abnormal skin and bone growth it is known as hypertrophic osteoarthropathy.
Clubbing is associated with lung cancer, lung infections, interstitial lung disease, cystic fibrosis, or cardiovascular disease. Clubbing may also run in families, and occur unassociated with other medical problems.
Clubbing has been recognized as a sign of disease since the time of Hippocrates.

Causes

Clubbing is associated with

Lung disease:
* Lung cancer
* Interstitial lung disease most commonly idiopathic pulmonary fibrosis
* Complicated tuberculosis
* Suppurative lung disease: lung abscess, empyema, bronchiectasis, cystic fibrosis
* Mesothelioma of the pleura
* Sarcoidosis
Heart disease:
* Any disease featuring chronic hypoxia
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* Infective endocarditis
* Atrial myxoma
* Arteriovenous fistula or malformation
Gastrointestinal and hepatobiliary:
* Malabsorption
* Crohn's disease and ulcerative colitis
* Cirrhosis, especially in primary biliary cholangitis
* Hepatopulmonary syndrome, a complication of cirrhosis
Others:
* Graves' disease – in this case, it is known as thyroid acropachy
* Familial and hereditary clubbing and "pseudoclubbing"
* Vascular anomalies of the affected arm such as an axillary artery aneurysm
* Primary hypertrophic osteoarthropathy

Nail clubbing is not specific to chronic obstructive pulmonary disease. Therefore, in patients with COPD and significant degrees of clubbing, a search for signs of bronchogenic carcinoma might still be indicated. A congenital form has also been recognized.

Hypertrophic pulmonary osteoarthropathy

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 and synovium, and is often initially diagnosed as arthritis. It is commonly associated with lung cancer.

Primary hypertrophic osteoarthropathy

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 coding for the enzyme 15-hydroxyprostaglandin dehydrogenase ; this leads to decreased breakdown of prostaglandin E2 and elevated levels of this substance.

Pathogenesis

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

Vasodilation.
Secretion of growth factors from the lungs.
Overproduction of prostaglandin E2 by other tissues.
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 entering 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 and vascular endothelial growth factor. PDGF and VEGF have growth-promoting properties and cause connective tissue hypertrophy and capillary permeability.
Diagnosis

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.

Stages

Clubbing is present in one of five stages:

No visible clubbing – Fluctuation and softening of the nail bed only. No visible changes in nails.
Mild clubbing – Loss of the normal <165° angle between the nailbed and the fold. Schamroth's window is obliterated. Clubbing is not obvious at a glance.
Moderate clubbing – Increased convexity of the nail fold. Clubbing is apparent at a glance.
Gross clubbing – Thickening of the whole distal finger
Hypertrophic osteoarthropathy – Shiny aspect and striation of the nail and skin

Schamroth's sign or Schamroth's window test is a popular test for clubbing. When the distal phalanges of corresponding fingers of opposite hands are directly opposed, a small diamond-shaped "window" is normally apparent between the nailbeds. If this window is obliterated, the test is positive, and clubbing is present.

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, had significant underlying disease of various causes, while 60%, or nine patients, had no medical problems after further investigation and remained well over the subsequent year.

History

At least since the time of Hippocrates, clubbing has been recognized as a sign of disease. The phenomenon has been called "Hippocratic fingers".
The Dutch painter Dick Ket had nail clubbing, as is seen from his paintings. He had an underlying disease, probably dextrocardia.