Digital Clubbing: A sign of underlying disease

The term digital clubbing is used to describe an enlargement of the distal segments of the fingers. The toes also may be affected by clubbing. Clubbing may be hereditary, but more often it is a sign of underlying disease. Clubbing is associated with a variety of pulmonary diseases, including idiopathic pulmonary fibrosis, lung cancer, bronchiectasis,lung abscess, and cystic fibrosis. Nonpulmonary conditions that may be accompanied by clubbing include cyanotic congenital heart disease, infective endocarditis, inflammatory bowel disease, and cirrhosis. Clubbing also may be idiopathic.

DETECTING THE PRESENCE OF CLUBBING:
Digital clubbing is defined by structural changes at the base of the nails that results in a convex distal phalanx (Figure 1). The Schamroth sign can be used in the detection of clubbing. This sign is elicited by placing the dorsal surfaces of the terminal phalanges on opposing fingers together (Figure 2). Normally, a diamond shaped window appears in a patient without clubbing, whereas in a patient with clubbing (Figure 1B) this window is obliterated. Identification of advanced clubbing poses little challenge when the so-called "drumstick fingers” are obvious; however, identification of the early stages of clubbing can prove difficult. Two objective measures for determining the presence of clubbing have been proposed. The first, known as the digital index, measures 2 separate circumferences on each of the 10 fingers at the nail bed (NB) and the distal interphalangeal joint (DIP) (Figure 3).4 The sum of the 10 ratios (NB:DIP) determines the digital index. A digital index of 10.2 or higher signifies the presence of clubbing. Although a NB:DIP ratio of 1.0 or greater at any single digit is suggestive of clubbing, the sum of the 10 ratios is more specific for clubbing.
The second objective method for the detection of clubbing is calculation of the phalangeal depth ratio. In the normal finger, the distal phalangeal depth (DPD) is smaller than the depth of the interphalangeal joint (IPD). To perform this test, calipers should be used. The calipers should touch but not compress the skin. For clubbing to be present, the DPD:IPD ratio should exceed 1.0 (Figure 4). The index finger is the suggested digit used for measurement.



SUMMARY OF ASSESSMENT OF DIGITAL CLUBBING :

Schamroth sign—Diamond-shaped window is absent
when dorsal surfaces of terminal phalanges on oppo-
site fingers are apposed. 
Digital index—Sum of NB:DIP ratios for all 10 fingers
(ratio of circumference at nail bed to circumference
at distal interphalangeal joint). Index ≥10.2 indi-
cates clubbing.
Phalangeal depth ratio—ratio of distal phalangeal
depth to interphalangeal joint depth of index finger.
Ratio > 1.0 indicates clubbing

Figure 1

 

Figure 2

Figure 3

 

Figure 4

CLINICAL CORRELATIONS/PATHOGENESIS:
Digital clubbing is a clinical syndrome with an unknown pathogenesis. Possible mechanisms include
dilation of peripheral vessels and stimulation of connective tissue growth by platelet-derived growth factor (PDGF) or hepatocyte growth factor (HGF). Digital clubbing typically is a sign of underlying disease, usually of pulmonary or cardiovascular origin .Pulmonary conditions often accompanied by clubbing include chronic lung infections, malignancy, and chronic interstitial lung diseases. Idiopathic pulmonary fibrosis is one of the most common underlying causes of digital clubbing. Digital clubbing does not usually occur in chronic obstructive pulmonary disease or asthma. If clubbing is seen in a patient with chronic obstructive pulmonary disease, a work-up for underlying malignancy should be undertaken. Clubbing in patients with pulmonary diseases is usually accompanied by cyanosis. Clubbing is not specific to pulmonary disorders and
also can be seen in cyanotic congenital heart disease,infective endocarditis, cirrhosis of the liver, and inflammatory bowel disease. In fact, one study found that the highest incidence of clubbing occurred in patients with chronic liver disease.  Clubbing without cyanosis is common in patients with infective endocarditis, inflammatory bowel disease, and cirrhosis. Clubbing can be associated with hypertrophic osteoarthropathy. Unlike other forms of clubbing, clubbing associated with hypertrophic osteoarthropathy is a painful process. Hypertrophic osteoarthropathy results from subperiosteal formation of new bone in the distal long bones, and it occurs in patients with lung cancer, bronchiectasis, and cirrhosis. Clubbing in patients with hypertrophic osteoarthropathy is believed to be stimulated by PDGF leading to proliferation of connective tissue and periosteum. 6 Several mechanisms have been proposed by which platelet clumps accumulate in the finger tips and release PDGF. HGF is another potential stimulator of clubbing. One study found higher levels of HGF in lung cancer patients with clubbing than in those without clubbing, suggesting that HGF may play a role in the formation of digital clubbing. Clubbing has been reported in 29% of patients with lung cancer and is more common in patients with non–small-cell lung cancer than those with small-cell lung cancer. 9 Another study found higher levels of HGF in patients with idiopathic pulmonary fibrosis as compared to normal age-matched controls, suggesting that HGF may play a role in the pathogenesis of idiopathic pulmonary fibrosis in addition to the development of clubbing.

Pathophysiology Explained in detail:
The specific pathophysiologic mechanism of digital clubbing remains unknown. Many theories have been proposed, yet none have received widespread acceptance as a comprehensive explanation for the phenomenon of digital clubbing. As stated best by Samuel West in 1897, "Clubbing is one of those phenomena with which we are all so familiar that we appear to know more about it than we really do."
Alterations in size and configuration of the clubbed digit result from changes in the nail bed, beginning with increased interstitial edema early in the process. As clubbing progresses, the volume of the terminal portion of the digit may increase because of an increase in the vascular connective tissue and change in quality of the vascular connective tissue, although some cases have been associated with spurs of bone on the terminal phalanx.
Although clubbing is a common physical finding in many underlying pathological processes, surprisingly, the mechanism of clubbing remains unclear. Different pathological processes may follow different pathways to a common end. Many studies have shown increased blood flow in the clubbed portion of the finger.
High-resolution magnetic resonance imaging uisng a contrast agent in 4 patients with finger clubbing and 4 healthy volunteers documented nail bed hypervascularization as linked with clubbed nails.^[5] Most researchers agree that this results from an increase in distal digital vasodilation, the cause of which is unknown. Also unknown is the exact mechanism by which increased blood flow results in changes in the vascular connective tissue under the nail bed.
Many researchers agree that the common factor in most types of clubbing is distal digital vasodilation, which results in increased blood flow to the distal portion of the digits. Whether the vasodilation results from a circulating or local vasodilator, neural mechanism, response to hypoxemia, genetic predisposition, or a combination of these or other mediators is not agreed on currently.
Evidence that favors the presence of a circulating vasodilator derives from the association of clubbing with cyanotic congenital heart disease. Many potential vasodilators, which usually are inactivated as blood passes through the lungs, bypass the inactivation process in patients with right-to-left shunts. Patients with tetralogy of Fallot with substantial shunting have a high incidence of clubbing. After surgical correction diminishes the shunt, the clubbing improves. Also previously observed is clubbing confined to the feet in patients with late untreated patent ductus arteriosus in whom blood from the pulmonary artery bypasses the lungs and is shunted into the descending aorta. In the absence of a shunt, the circulating vasodilator may be produced by the lung tissue, or, possibly, it passes through the pulmonary circulation without becoming inactivated. Proposed vasodilatory factors include ferritin, prostaglandins, bradykinin, adenine nucleotides, and 5-hydroxytryptamine.
A neural mechanism has been proposed with particular consideration of the vagal system. An increased incidence of digital clubbing has been associated with the pathology and disease of vagally innervated organs. Furthermore, regression of clubbing after vagotomy has been reported. Although some factor related to the vagal system is a possible contributor to the development of clubbing, especially clubbing occurring with hypertrophic osteoarthropathy, the hypothesis of a neural mechanism has decreased in popularity because of the lack of evidence of clubbing in neurologic disorders and the presence of clubbing in diseases of organs not innervated by the vagal system.
Hypoxia has been proposed as an alternative explanation for clubbing in cyanotic heart disease and pulmonary diseases. An increase in hypoxia may activate local vasodilators, consequently increasing blood flow to the distal portion of the digits; however, in most cases, hypoxia is absent in the presence of clubbing, and many diseases with noted hypoxia are not associated with clubbing.
Genetic inheritance and predisposition also may play a role in digital clubbing. Hereditary clubbing is observed in 2 forms, including idiopathic hereditary clubbing and clubbing associated with pachydermoperiostosis. The 2 forms are believed to be separate entities. Both demonstrate autosomal dominant inheritance with incomplete penetrance.
More recently, platelet-derived growth factor released from fragments of platelet clumps or megakaryocytes has been proposed as the mechanism by which digital clubbing occurs.^[6] The fragments are large enough to lodge in the vascular beds of the fingertips, and, subsequently, they release platelet-derived growth factor. This factor has been shown to have general growth-promoting activity and causes increased capillary permeability and connective tissue hypertrophy.

Diseases Commonly Associated with Digital Clubbing :

Pulmonary
Bronchiectasis
Chronic interstitial lung diseases
Chronic lung infection
Cystic fibrosis
Lung abscess
Lung cancer
Cardiovascular
Cyanotic congenital heart disease
Infective endocarditis
Other causes
Cirrhosis of liver
Inflammatory bowel disease


Mnemonic:
the mnemonic is C.L.U.B.B.I.N.G, while the L has an extension of A.B.C.D.E.F

Cyanotic heart disease
Lung disease
Abscess
Bronchiectasis
Cystic Fibrosis
Dont say COPD or Asthma
Empyema
Fibrosis
Ulcerative Collitis + Inflammatory Bowel Disease(Crohn's Disease)
Biliary cirrhosis
Birth Defects
Infective Endocarditis
Neoplasm(eg. Lung cancer or mesothelioma)
Gastrointestinal malabsorption syndrome(Coeliac disease)



Good Luck ;-)