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Clubbing / HOA

posted Oct 7, 2013, 12:24 PM by Ewa Rakowski   [ updated Oct 7, 2013, 12:35 PM ]

Thanks to Nadia Ali for this weeks Monte Minute~

Last Friday in CRS we discussed a 43yoF who presented with symmetric joint pains in knees, shoulders and hands, new onset clubbing and low grade fevers.The physical exam was remarkable for normal cardiac and lung exam. There was joint warmth but no swelling or erythema. Both hands and feet had prominent clubbing bilaterally. Chest x-ray revealed a left upper lobe infiltrate that was confirmed to be a mass on chest CT. Pulmonary was consulted and bronchoscopic biopsy was positive for poorly differentiated adenocarcinoma. As it turned out the patient had hypertrophic osteoarthropathy secondary to lung cancer.

Here we explore clubbing and hypertropic osteoarthropathy:

Clubbing - What is it?

Clubbing is a physical exam finding (not a diagnosis) where there is enlargement of the distal segments of the fingers and toes due to proliferation of connective tissue.

How do we recognize it on physical exam?

The most useful clinical way to find clubbing is to look for Schamroth’s sign, which is the obliteration of the normal diamond-shaped window created by placing the back surfaces of opposite terminal phalanges together as shown in the picture.

What is hypertropic osteoparthropathy (HOA)?

HOA is the clinical syndrome of clubbing,  periostosis (new bone formation in the periosteum) of long bones, and synovial effusions. This can present as painful symmetric arthropathy in shoulders, knees, ankles, wrists and elbows and can be mistaken for an inflammatory arthropathy This can precede or occur simultaneously with clubbing as it did with our patient.

There are primary and secondary etiologies.

  • Primary - Primary primary or familial HOA, (also called pachydermoperiostosis and Touraine-Solente-Gole syndrome)is diagnosed through family history, exclusion of other possible diseases and then finally with genetic testing. The genetic abnormality in primary HOA involves a mutation in the HPGD gene that encodes 15-hydroxyprostaglandin dehydrogenase, which is the primary enzyme response for prostaglandin degradation.

  • Secondary: Due to numerous other causes. Often associated with primary and metastatic lung cancer as a paraneoplastic syndrome, mesothelioma, bronchiectasis, or hepatic cirrhosis.

    Interestingly in retrospective studies lung cancer (especially adenocarcinoma) is the most common cause of secondary HOA and this is more common in women than in men!

What are the underlying causes of Clubbing / HOA?

Mnemonic for the causes of CLUBBING (the L has an extension of ABCDEF)

Cyanotic heart disease

Lung disease



Cystic Fibrosis

Don’t say COPD (this is NOT a cause of clubbing!)


Fibrosis (Sarcoidosis/ Asbestosis/ Cystic fibrosis)

other - tuberculosis

Ulcerative Colitis + Inflammatory Bowel Disease(Crohn's Disease)

Biliary cirrhosis

Birth Defects (ie Familial HOA)

Infective Endocarditis

Neoplasm (ie. Lung cancer or mesothelioma)

Gastrointestinal malabsorption syndrome (Celiac disease)

What is the pathophysiology of clubbing?

    Still unclear but the known primary diseases are associated with intracardiac and pulmonary shunts; even GI and Liver diseases have been found to be associated with small pulmonary AVs.

    The most promising hypothesis is that clubbing is secondary to humeral substances that cause dilation of the vessels of the distal digits as well as growth factors released from unfragmented platelet precursors in the digital circulation.

    Megakaryocytes are normally fragmented into platelets in the lungs. Diseases that disrupt the normal pulmonary circulation allow whole megakaryocytes to enter the systemic circulation. When they become impacted in the fingertip circulation, they release platelet-derived growth factor (PDGF). There is also a release of VEGF and other cytokines. These factors promote growth, vascular permeability, and monocyte and neutrophil chemotaxis, and leads to an increased number of vascular smooth muscle cells and fibroblasts.

What work-up should be done?

The work up should be aimed at finding the underlying etiology from the long list above. This will include H and P on all patients. If there is a positive family history then consider referral for genetic testing. If there are no symptoms a screening chest x-ray should be performed. Further testing should be determined based on symptoms and exposures.

What is the treatment of HOA?

Treat the underlying cause!

Take Home Message

  • Clubbing is NEVER normal on physical exam (the only exception is familial HOA which is rare, and is still not normal)

  • Finding clubbing on physical exam is an indication that there is an underlying disease process ongoing and should prompt the clinician to do a thorough workup keeping in mind the known diseases associated with clubbing.
Ewa Rakowski,
Oct 7, 2013, 12:25 PM
Ewa Rakowski,
Oct 7, 2013, 12:26 PM