Bedside to Bench: Clubbing Revisited

April 3, 2009

Commentary by Judith Brenner MD, Associate Editor, Clinical Correlations 

Faculty Peer Reviewed 

For an internist, discovering a patient with clubbing is so rewarding since it appeals to the core of our profession, a profession which can often be very similar to that of a detective. The physical finding of clubbing was first described by the ancient Greeks, who recognized it to be a clue to much more.

When a clinician discovers clubbing of the fingers, he must consider that hypoxemia may be present, whether secondary to a cardiac or pulmonary process. In fact, more than 90% of clubbing is pathologic, with the remainder being a benign familial condition.

How do we recognize clubbing on physical exam?

Let’s begin at the bedside. One can judge finger clubbing in many ways. The simplest way is to think of the clubbed finger is as a “drumstick digit”. There is an increase in the curvature of the nail and a general rounding at the tip. However, curvature is difficult to measure at the bedside. Most physicians look for the “Shamroth Sign”. This sign, named for the doctor who first described it in 1976, is performed by looking for loss of the diamond that is usually formed in non-clubbed fingers when the dorsal surfaces of the distal phalanx of the right and left fingers are apposed. Unfortunately, though commonly considered to be a “standard” in terms of diagnosis, this sign has never been rigorously studied.

Another way to determine if clubbing is present involves use of the “phalangeal depth ratio.” This ratio compares the “distal phalangeal depth” with the “interphalangeal depth”. In normal individuals, the DPD:IPD ratio is <1. However, in clubbed fingers, the distal portion is thicker and thus, the ratio of DPD:IPD is >1.

The last finding to consider is the hyponychial angle. The normal angle is 180 degrees. With clubbing the curvature of the nail increases and the angle thus increases. An angle greater than 190 degrees is considered consistent with clubbing.

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Unfortunately determining the evidence for these findings is difficult.  No sensitivities, specificities or likelihood ratios are available.  Why? Simply because there is no gold standard.   Here’s where experience counts.  A clinician can look at a finger, observe that its appearance is not “normal” and then start to ask the appropriate questions.

Is clubbing really a marker of hypoxic disease?

The answer is: yes.  In one study of 350 patients with clubbed fingers, 80% had underlying respiratory disorders, including tumors, abscesses, cystic fibrosis, and interstitial fibrosis.  An additional 10-15% had cyanotic heart disease, endocarditis, and even thyroid disease and inflammatory bowel disease.  Only 5% were found to be either idiopathic or hereditary.

What is the unifying pathology in all of these disorders?

On a molecular level, the pathophysiology has been studied by investigating rare individuals with familial hypertrophic osteoarthropathy.  In these patients, mutations of HPGD, a prostaglandin E2 catabolizing enzyme, has been identified.  This mutation results in elevated prostaglandin levels.  Although the familial form is rare, the secondary forms of hypertrophic osteoarthropathy (HO) are more common and clubbing is often the first clue.  The clinical commonality in many patients with secondary HO is right to left shunting.  Ordinarily, prostaglandin E2 (PGE2) is metabolized in the lung.  The hypotheseis is that, with shunting, the proper metabolism is prevented.  As a result, PGE2 levels are elevated and elevated prostaglandin levels result in platelet activation. 

Activated platelets are returned to the systemic circulation and are thought to lodge in the distal phalanges, releasing their growth factors.  While trapped, the platelets release growth factors, which leads to fibrovascular proliferation, ultimately manifesting in what we clinically call clubbing.

Though compelling, these explanations are all still just hypotheses.  While many diseases associated with clubbing have shunting in common, several do not, such as Graves’ Disease and inflammatory bowel disease.  The pathophysiology in these cases remains unclear.

The Bottom line:

Clubbing is indeed a clinical clue to an underlying disorder and thus must be taken seriously when recognized.  It is diagnosed at the bedside where simple observations are made.  When present, a search for diseases of the lungs or heart that cause right to left shunting is warranted.  If cardiac and pulmonary etiologies are ruled out, one can consider other diseases that are marked by platelet excess, such as inflammatory bowel disease.  Inheritance (<5%), since it is so rare, should be accepted as the etiology only as a diagnosis of exclusion.

Coggins, KG et al. The hippocratic finger points the blame at PGE.   Nature Genetics 2008;40:691-2.

Meyers, KA et al. Does this Patient Have Clubbing? JAMA 2001;286:341-347.

Uppal, S, et al.  Mutations in 15-hydroxyprostaglandin dehydrogenase cause
Primary Hypertrophic Osteoarthropathy.  Nature Genetics 2008;40:789-93.

McGee, S.  Evidence Based Physical Diagnosis (2nd edition).

Reviewed by Nishay Chitkara MD, NYU Division of Pulmonary and Critical Care Medicine

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