Nail clubbing, a dermatologic window into underlying systemic disease – an All of Us Study

Abstract

Introduction 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. Methods 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 Chi-Squared Test analyzed categorical variables. Independent Two-Sample t-Tests analyzed continuous variables. Odds ratios were analyzed with multivariate logistic regression adjusted for sociodemographic characteristics. Results In total, 85 participants had nail clubbing, of which 63.53% had a pulmonary disease vs. 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 vs. 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). Conclusion 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.