Clubbing

Overview
In medicine, clubbing, finger clubbing, or digital clubbing is a deformity of the fingers and fingernails that is associated with a number of diseases, mostly of the heart and lungs. Idiopathic clubbing can also occur. Hippocrates was probably the first to document clubbing as a sign of disease, and the phenomenon is therefore occasionally called Hippocratic fingers.

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

Pathophysiology
The exact cause for sporadic clubbing is unknown, and there are 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 osteo-arthropathy has led to suggestions that overproduction of PGE2 by other tissues may be the causative factor for clubbing.

Signs and symptoms
Clubbing develops in five steps:
 * 1) Fluctuation and softening of the nail bed (increased ballotability)
 * 2) Loss of the normal <165° angle ("Lovibond angle") between the nailbed and the fold (cuticula)
 * 3) Increased convexity of the nail fold
 * 4) Thickening of the whole distal (end part of the) finger (resembling a drumstick)
 * 5) Shiny aspect and striation of the nail and skin

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

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 may also be performed.

Disease associations
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 large-cell (35% of all cases), not seen frequently in small cell lung cancer
 * Interstitial lung disease
 * Tuberculosis
 * Bronchiectasis
 * Suppurative lung disease: lung abscess, empyema
 * Cystic fibrosis
 * Pulmonary hypertension
 * Mesothelioma
 * It is worth noting that clubbing is not associated with chronic obstructive pulmonary disease (COPD). Indeed, the presence of clubbing in a patient with COPD should prompt a search for an underlying (lung) cancer.
 * Heart disease:
 * Any disease featuring chronic hypoxia
 * Congenital cyanotic heart disease (most common cardiac cause)
 * Subacute bacterial endocarditis
 * Atrial myxoma (benign tumor)
 * Gastrointestinal and hepatobiliary:
 * Malabsorption
 * Crohn's disease and ulcerative colitis
 * Cirrhosis, especially in primary biliary cirrhosis
 * Other liver diseases (in the "hepatopulmonary syndrome", a complication of cirrhosis)


 * Others:
 * Hyperthyroidism (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)

HPOA
A special form of clubbing is hypertrophic pulmonary osteo-arthropathy, known in continental Europe as Pierre Marie-Bamberger syndrome. (In dogs the condition is known as hypertrophic osteopathy.) 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 HOA
Primary hypertrophic osteo-arthropathy is HPOA without signs of pulmonary disease. This form has a hereditary component, although subtle cardiac abnormalties can occasionally be found. It is known in continental Europe 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.

Secondary HOA
It is usually associated with lung cancer, pulmonary infections, cystic fibrosis, right-to-left cardiac shunts, and less often in Hodgkin lymphoma and cirrhosis. Among patients with lung cancer, HOA is most frequently associated with adenocarcinoma and least frequently with small cell carcinoma Rarely, arterial vascular prosthesis infections may be associated with HOA. Clinical features suggestive of vascular infection-related HOA include clubbing or periosteal new bone formation in a single limb.

Complete Differential Diagnosis of the Causes of Clubbing:
(In alphabetical order) Vascular anomalies
 * Achalasia
 * Arteriovenous malformations
 * Arterial vascular prosthesis infections
 * Atrial myxoma
 * Bronchial carcinomas
 * Bronchiectasis
 * Cannabis
 * Celiac Sprue
 * Cerebrovascular insult
 * Chronic obstructive jaundice
 * Cirrhosis
 * Cyanotic congenital heart disease
 * Tetralogy of Fallot
 * Total anomalous venous return
 * Transposition of the great vessels
 * Tricuspid atresia
 * Truncus arteriosus
 * Cystic Fibrosis
 * Endocarditis
 * Empyema
 * Hepatoma
 * Hodgkin's lymphoma
 * Interstitial lung disease
 * Liver tumors
 * Lung abscess
 * Metastatic melanoma
 * Mesothelioma
 * Myelofibrosis
 * Nasopharyngeal carcinoma
 * Pachydermoperiostosis
 * POEMS syndrome [polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes]: a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia in which clubbing may be seen. Other findings including peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes, sclerotic bone lesions, Castleman disease, thrombocytosis, papilledema, peripheral edema, pleural effusions, ascites, and white nails.
 * Primary biliary cirrhosis
 * Pulmonic stenosis
 * Pulmonary artery sarcoma
 * Pulmonary fibrosis
 * Pulmonary metastases
 * Right-to-left cardiac shunts
 * Sarcoidosis of the lungs
 * Silicosis
 * Thyroid cancer
 * Thyrotoxicosis
 * Tuberculosis
 * Ulcerative colitis

Complete Differential Diagnosis of the Causes of Clubbing:
(By organ system)