Epidemiology of digital clubbing and hypertrophic osteoarthropathy: A systematic review

In reporting this systematic review, we were guided by PRISMA statements. Studies reporting the prevalence of HOA/clubbing that had been released up to 23 March 2021, were searched for in electronic databases (PubMed, EMBASE, Web of Sciences) and manually. Studies not involving humans, those with fewer than 10 participants, those whose full-texts were not available after a request to the corresponding author, and qualitative studies were excluded. The risk of bias of each included study was assessed using Hoy et al’s criteria. Data were analysed through random-effects meta-analysis using the ‘meta’ packages of the R statistical software. Between-study heterogeneity was assessed through Cochran’s Q statistics, with I² values of < 25%, 25%-75% and > 75% corresponding to low, moderate and high heterogeneity, respectively. Publication bias was assessed through Egger’s test of funnel plot asymmetry. P-values less than 0.05 were considered statistically significant for heterogeneity assessment, whereas p-values less than 0.01 were considered statistically significant for publication of bias assessment.

Of the total 3973 records identified through database and hand searches, 142 articles were included. These studies were conducted in 43 countries between1966-2020, and mostly came from 4 United Nations Statistics Division regions (Asia, America, Europe and Africa). 106 studies involved adults, and 36 studies involved children and adolescents, giving a total population of 45158 individuals. The mean age of the population ranged from 2.8 to 77 years. The risk of bias of studies was low (n = 74) and moderate. (n = 68).

In adults, the pooled prevalence of digital clubbing was 33.4% (95% confidence interval [CI] 16.6-52.8), 31.3% (95% CI 22.4-41.1), 27% (95% CI 9.4-49.5) and 22.8% (95% CI 10.8-37.6) in subjects with intestinal diseases, interstitial lung diseases, infective endocarditis and hepatic diseases, respectively. In children and adolescents, the pooled prevalence of digital clubbing was 29.1% (95% CI 19.4-39.9), 23% (95% CI 9.0-41.1), 19.5% (95% CI 4.1-42.4) and 17.1% (95% CI 9.5-26.5) in subjects with HIV infection, hemoglobinopathies, cystic fibrosis and tuberculosis. The pooled prevalence of HOA was 10.1% (95% CI 2.0-23.1) in adults with cancers, and 5% (95% CI 2.5-8.2) in children and adolescents with cystic fibrosis.

In conclusion, this review suggests that clubbing mostly manifests in adults affected by pleuropulmonary, intestinal, cardiac and hepatic diseases; and in children and adolescents affected by HIV infection , hemoglobinopathies, cystic fibrosis and tuberculosis. As regards full spectrum HOA, it appears to mostly manifest in adult patients with cancers and liver diseases, and in children and adolescents with  cystic fibrosis.