In Patients With Uveitis, Tuberculosis is a Risk Factor for Behçet Disease

Fundoscopy of the left eye showing Behcet’s disease (Behcet’s syndrome), a rare chronic inflammatory disorder, in a young adult patient. (c) Sovereign
In paired genetics and observational study, tuberculosis is linked to an increased likelihood for noninfectious inflammation.

Clinicians may suspect that a presenting noninfectious eye inflammation is secondary to the patient’s unique immune response after a primary infection, and a JAMA Ophthalmology study is one of the first to demonstrate this type of association with a specific pathogen. Participants exhibiting a genetic susceptibility to Mycobacterium tuberculosis also displayed increased risk for Behçet disease, according to the research. 

Investigators paired Mendelian randomization of 8349 individuals in 2 populations — 7001 in China and 1348 in Japan — with a prospective observational cohort analysis in Japan, including 237 participants with a history of uveitis. In the genetic study arm, 5 single nucleotide variants (SNV) in the Chinese genome connected to tuberculosis vulnerability were used as the main variable for tuberculosis exposure, and all 5 correlated with a higher risk of Behçet disease.

“The genetically determined tuberculosis susceptibility was associated with an increased risk of Behçet disease; in the Chinese cohort, the odds ratio of Behçet disease per 2-fold increase in tuberculosis incidence was 1.26 (95% CI, 1.12-1.43; P = 1.47×10−4),” according to the study. Investigators found no associations for other noninfectious conditions such as Fuchs’ uveitis syndrome, Vogt-Koyanagi-Harada disease, or ankylosing spondylitis-related inflammation.

In the observational study arm, 116 participants with Behçet disease and 121 in a control group underwent a tuberculosis test that demonstrates past or present tuberculosis infection. Positive tests occurred in 32.8% of patients who had Behçet disease and 15.7% of those in the control group. After researchers adjusted for covariables such as age and sex, they found that for participants with uveitis, a positive TB test was an independent risk factor for Behçet disease (P =.03).

Investigators noted that estimates based on a genetic association of tuberculosis susceptibility with a higher risk of Behçet disease are only suggested. Another limitation was that individual-level Mendelian randomization was not performed in the observational cohort. Conversely, the study’s strength “was the use of naturally randomly inherited variants to indicate the tuberculosis exposure from the perspective of the time of birth, which might minimize the possibility of reverse causality and provide nearly randomized evidence in this population,” the research explains.

Genetic analysis was conducted in July 2019 and January 2020, and the prospective observation from July 2019 to November 2019. The first data set originated from a genome-wide genotyping and association study (GWAS) including participants with and without uveitis enrolled at 5 centers in China between April 2008 and January 2018. The Japanese GWAS comprised data from patients with and without Behçet disease visiting 8 centers from January 2002 to June 2009. The larger Chinese GWAS served as the primary analysis, and the second GWAS set was used for replication.

This study points to some potential new practices for clinics, including screening patients with Behçet disease for tuberculosis. Also, glucocorticoids and immunosuppressive drugs that treat Behçet may raise the risk for recurrence of tuberculosis. Overall, this new data may help in preventing or treating uveitis, a potentially vision-threatening condition, the study says.


Zhong Z, Su G, Zhou Q, et al. Tuberculosis exposure with risk of behçet disease among patients with uveitisJAMA Ophthalmol. Published online February 18, 2021. doi:10.1001/jamaophthalmol.2020.6985