What diagnostic tests should be done after discovering clubbing in a patient without cardiopulmonary symptoms?

DETECTING CLUBBING ON EXAMINATION

Most clinicians can detect advanced clubbing. However, older studies suggest that the precision and interrater reliability of the physical examination for clubbing is fair to moderate at best.² Clubbing, unlike other examination findings such as ascites or splenomegaly, does not have a gold standard radiographic correlate to validate against. Instead, it depends on careful observation of changes to the depth of the distal phalanx and altered nail-fold angles. In the past, plaster casts, shadowgraphs, and calipers were used to obtain the quantitative measurements that define clubbing.²

Different views of our patient’s fingernails are presented in Figure 1. Early clubbing can be difficult to identify from a superior view (Figure 1A). The changes that define clubbing are easier to discern on profile view (Figure 1B). In our clinical experience, measurement of the distal phalanx depths has higher reproducibility and interrater reliability than an estimation of nail-fold angles (Figure 1C).

THE RELATIONSHIP OF CLUBBING TO HYPERTROPHIC OSTEOARTHROPATHY

Clubbing can sometimes occur as part of a triad of symptoms that comprise hypertrophic osteoarthropathy, a systemic syndrome. Hypertrophic osteoarthropathy has 3 manifestations: clubbing, synovial effusions, and periosteal bone formation in tubular bones including the radius, ulna, tibia, and fibula.³ Formal diagnostic criteria require the presence of clubbing combined with radiographic evidence of periosteal bone formation in tubular bones. In other words, all patients with hypertrophic osteoarthropathy have clubbing, but only a small percentage of patients with clubbing have hypertrophic osteoarthropathy. Some patients with hypertrophic osteoarthropathy may report deep-seated, severe bone pain most prominently in the lower extremities along with joint swelling, while others do not experience pain and may not even be aware of the clubbing changes in their fingernails.³

DISEASES ASSOCIATED WITH CLUBBING

Hypertrophic osteoarthropathy can occur as a primary disease or secondary to other disease processes.⁵ Primary hypertrophic osteoarthropathy is a rare inherited condition that manifests with clubbing, skin changes such as progressive thickening and furrowing wrinkling of skin on the forehead and hyperhidrosis, and periosteal bone formation. Secondary hypertrophic osteoarthropathy is much more common, comprising 95% to 97% of cases.

Clubbing observed on only 1 hand is commonly associated with hemiplegia or a local vascular disease, such as dialysis fistulas or arterial aneurysms.¹ Bilateral clubbing is associated with an extensive list of diseases, with intrathoracic disease, including lung cancer as a paraneoplastic phenomenon, being the most common.⁵ It should be noted that, although paraneoplastic syndromes are more common in small cell lung carcinoma than in non–small cell lung carcinoma, non–small cell lung carcinoma is more commonly linked with clubbing. Specifically, clubbing is observed in approximately 35% of patients with non–small cell lung carcinoma vs 4% of patients with small cell lung carcinoma.¹

Other intrathoracic causes include the following^1,2,5:

• Metastatic lung nodules

• Interstitial lung disease

• Bronchiectasis

• Chronic mycobacterial or fungal infection

• Cyanotic congenital heart disease

• Infective endocarditis

• Esophageal carcinoma.

Extrathoracic diseases associated with bilateral clubbing include cirrhosis, inflammatory bowel disease, celiac disease, and thyroid acropachy.

Notably, chronic obstructive pulmonary disease is not associated with clubbing, but it is itself an independent risk factor for primary lung cancer, which is strongly associated with clubbing. More than 90% of cases of secondary hypertrophic osteoarthropathy are associated with malignancies or other chronic pulmonary diseases.⁶

SEARCHING FOR THE CAUSE OF CLUBBING

If the clubbing, within or outside the context of hypertrophic osteoarthropathy, is new, bilateral, and asymptomatic, we recommend chest computed tomography because of the strong association between clubbing and lung malignancy or chronic lung disease.⁶ If access to chest computed tomography is delayed, chest radiography can be done, bearing in mind that chest computed tomography has higher sensitivity (93.8% vs 73.5%) in detecting nodules and malignancy at earlier stages.^7,8 Otherwise, efforts to identify the cause of clubbing should be driven by symptoms and signs. For example, a patient found to have clubbing with symptoms of intermittent bloody diarrhea will require an evaluation for inflammatory bowel disease. If a patient already has a condition known to be associated with clubbing but newly develops clubbing, we still suggest computed tomography of the chest to exclude an emerging intrathoracic malignancy. Figure 2 presents our suggested approach to the evaluation of clubbing.

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Figure 2

Suggested approach to evaluation of bilateral clubbing.

Computed tomography of our patient’s chest showed a necrotic mass in the apical right lung. Pathology revealed lung adenocarcinoma. Plain radiographs of the tibia and fibula showed bilateral periosteal new bone with cortical thickening. Nuclear bone scan showed radiotracer uptake involving the tibial and fibular cortices, corresponding to periosteal bone formation. Both the plain radiographs and the nuclear bone scan confirmed the presence of hypertrophic osteoarthropathy.

THE BOTTOM LINE

If the presence of clubbing is uncertain, a profile view of the distal phalanx with a focus on the change in depth is more practical than estimation of nail-fold angles. If the depth increases from the distal interphalangeal joint to the nail fold, clubbing is present. If leg or wrist pain with swelling is present, plain radiographs with or without bone scintigraphy are indicated to diagnose hypertrophic osteoarthropathy. All 3 features of hypertrophic osteoarthropathy (clubbing, periosteal bone formation, synovitis) are not always present. Aggressive evaluation of new, asymptomatic bilateral clubbing with or without hypertrophic osteoarthropathy presents an opportunity to diagnose malignancy earlier. We suggest chest computed tomography as the first step in searching for the cause, even in patients without cardiopulmonary symptoms.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.