A 66-year-old man is brought to the office by his daughter for medical evaluation. The patient reports no chronic medical conditions but has not seen a physician for many years. He takes no medications. The patient is a retired veteran and recently relocated to live closer to his daughter. He is an ex-smoker and does not use alcohol or recreational drugs. Oxygen saturation on room air is 98%. On physical examination, normal breath sounds are heard throughout both lungs. Hand examination findings are shown in the exhibit. The patient's hand findings are most suggestive of which of the following underlying conditions?
Conditions associated with digital clubbing | |
Pulmonary |
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Cardiopulmonary disease with hypoxemia |
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Chronic cardiopulmonary infections |
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The patient is a former smoker and presents with digital clubbing, a thickening and widening of the nail bed and distal phalanges that give the fingers a bulbous drumstick appearance. Normally, when two opposing fingers are held nail to nail, a diamond-shaped space is formed between proximal nail folds; obliteration of this space is consistent with clubbing.
Clubbing is observed in cardiopulmonary disease states where hypoxic-inflammatory pathways are activated, releasing platelet and fibroblast-derived growth factors (especially vascular endothelial growth factor [VEGF]) that promote platelet clumping/embedment in the distal capillary beds (fingers, toes), which then leads to local fibrovascular proliferation.
Lung adenocarcinoma (ie, tumor-secreted VEGF) is the most common cause of clubbing in adults. Other common causes of clubbing include chronic chest infections (eg, bronchiectasis) and cardiopulmonary diseases with hypoxemia (eg, cyanotic heart defects). Occasionally, clubbing is associated with a painful periosteal reaction and synovitis, known as hypertrophic pulmonary osteoarthropathy, a paraneoplastic syndrome strongly linked to lung adenocarcinoma.
Examination for clubbing is clinically valuable because it may be the only visible physical sign of lung cancer, including small and surgically resectable (curable) tumors that would be otherwise asymptomatic. Therefore, the presence of clubbing should prompt further imaging of the chest for malignancy.
(Choice A) Uncomplicated chronic obstructive pulmonary disease (COPD without hypoxemia) alone is not associated with clubbing; clubbing in a patient with COPD should trigger further investigation for underlying complications (eg, malignancy, bronchiectasis, pulmonary hypertension). In addition, this patient has normal breath sounds, making COPD (eg, emphysema, chronic bronchitis) unlikely.
(Choice B) Chronic renal failure is associated with "half-and-half" nails (Lindsay nails), a sharply demarcated transverse leukonychia. The mechanism remains unknown but is unlikely to be related to azotemia because the transition line disappears after renal transplantation but not with hemodialysis.
(Choice C) Iron deficiency anemia is associated with koilonychia, or scooped concavity of the nail bed ("spoon nails"), possibly due to chronic nutrient deficiency leading to regression of the nail matrix.
(Choice E) Psoriatic nail dystrophy is due to primary involvement of the nail by psoriasis itself. It manifests as nail pitting, thickening, brittleness, and onycholysis (separation from the underlying nail bed).
Educational objective:
The most common cause of digital clubbing in adults is pulmonary malignancy (especially lung adenocarcinoma). More generally, clubbing is a sign of chronic cardiopulmonary disease associated with activation of hypoxic-inflammatory signaling (eg, chronic chest infections, right-to-left shunting).