A Systematic Review and Meta-Analysis of Human Leukocyte Antigen-DR (HLA-DR) in Onychomycosis: HLA-DR8 Confers Susceptibility

Onychomycosis (OM) is a nail infection from various fungal species, representing a worldwide dermatologic health concern. The toenails are most often affected. Comorbid chronic health conditions and environmental and genetic factors play a role in the development of OM. It has been observed that certain populations have an increased risk of developing OM, suggesting an inherited component to its etiology. Recent studies have observed the impact of the human leukocyte antigen-DR (HLA-DR) profile on the likelihood of developing OM; however, none have aggregated these studies for a meta-analysis to determine a statistical effect. The literature was systematically reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to determine the effect of the HLA-DR profile on OM susceptibility. Studies that contained HLA-DR allele frequency data on patients with OM were included. Studies that contained too much allele frequency data, did not contain HLA-DR allele frequency data, or were written in a non-English language were excluded. Google Scholar, PubMed, and Scientific Direct databases were searched. The risk of bias was assessed by using the National Institutes of Health (NIH) quality assessment case-control study tool. The results were generated using Review Manager version 5.4 by extracting and inputting HLA-DR allele frequency data into the program. The program created aggregated odds ratios that were visually represented in forest plots. A total of five articles were included in the analysis. One hundred fifty-six patients with OM were used in this analysis. Mexican mestizos and United States Caucasian populations were represented in this study. Overall, the NIH risk of bias tool revealed that most studies included did not justify their sample size, or the assessors were not blinded. Of all the HLA-DR alleles analyzed, only HLA-DR8 revealed a statistically significant result with an odds ratio of 1.70 with a 95% CI (1.05-2.76). This suggests that HLA-DR8 confers a 70% higher risk of susceptibility to OM. This finding can help identify these target populations and serve as the basis for personalized treatment solutions.