Nail Clubbing: A Dermatologic Window into Underlying Systemic Disease - an All of Us Study

Nail clubbing is defined as distal phalanx thickening resulting in a bulbous appearance of the digit. We aimed to describe non-pulmonary medical conditions associated with nail clubbing using a cross-sectional approach.

We conducted a cross-sectional analysis of the All of Us Research Program, identifying nail clubbing patients by ICD-10-CM and/or SNOMED code. Nail clubbing patients with pulmonary disease (cases) were compared to nail clubbing patients without pulmonary disease (controls). Fisher's exact test/Pearson's χ² test analyzed categorical variables. Independent two-sample t tests analyzed continuous variables. Odds ratios (ORs) were analyzed with multivariate logistic regression adjusted for sociodemographic characteristics.

In total, 85 participants had nail clubbing, of which 63.53% had a pulmonary disease versus 36.47% of controls. Overall, across both cases and controls, 22% of patients had chronic liver disease, 17% hypothyroidism, 8% HIV infection, and 5% Graves' disease/hyperthyroidism. Male versus female patients with nail clubbing had decreased odds of having concurrent respiratory disease diagnosis (OR, 0.37; 95% CI, 0.14-0.92, p = 0.03).

Greater than one-third of patients had nail clubbing associated with a non-pulmonary systemic disease, and a significant proportion were male. Consideration of a broad differential of pathologies associated with nail clubbing is needed to initiate workup and make appropriate screening referrals.