The risk for developing eosinophilic esophagitis (EoE) was higher among patients with a history of infection compared with a matched general patient population, according to new case-control study findings published in United European Gastroenterology Journal.

The authors’ analysis encompassed 1587 patients with biopsy-verified EoE who were matched 1:5 to a control group comprising general population individuals. This study took place in Sweden from 2000 and 2017, and it utilized histopathology codes from the Epidemiology Strengthened by histopathology Reports in Sweden study, “a validated cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden,” the authors noted, to identify patients for inclusion in the study group. The control group was identified via the Swedish Total Population Register and matched based on age, sex, county of residence, and birth year; this group had to be free of EoE at study inclusion.

“In secondary analyses, we compared EoE patients with their full siblings to further reduce residual confounding,” they added. These persons were identified using the Swedish Multigeneration Register, which is part of the Swedish Total Population Register.

More patients with confirmed EoE had a history of infection—handled on an inpatient or outpatient basis—compared with the matched control population: 35.7% vs 23.4%. This equates to a prevalence difference of 34.4%, or 12.3 percentage points separating the groups and an elevated risk of infection in individuals who have EoE (odds ratio [OR], 2.01; 95% CI, 1.78-2.27).

The risks of developing EoE in connection with more specific previous infection were even higher:

• Previous gastrointestinal (GI) infection had an odds ratio of 2.73 (95% CI, 2.17-3.471) for persons with EoE compared with healthy controls; such an infection was seen in 8.0% of the EoE cohort and 3.5% of the control group
• Previous respiratory infection had an OR of 1.89 (95% CI, 1.63-2.20); this type of infection was seen in 19.2% and 12.5%, respectively

In addition, individuals with EoE had an elevated risk of sepsis vs both the control population (OR, 3.39; 95% CI, 1.68-6.65) and compared with full siblings (OR, 1.57; 95% CI, 1.30-1.89), and female and male patients had higher risks of developing EoE when considering history of prior infection (female patients, ORs, 2.25; 95% CI, 1.78-2.83; male patients, OR, 1.94; 95% CI, 1.67-2.24).

Additional findings from the authors’ analysis include the following:

• The patients with diagnosed EoE were more likely born in a Nordic country (Denmark, Norway, Sweden, Finland, Iceland, Faroe Islands, Greenland, Åland)
• Children (younger than 18 years) with history of prior infection had a higher risk of EoE (OR, 2.76; 95% CI, 2.16-3.54) compared with adults (18 years or older) (OR, 1.78; 95% CI, 1.51-2.02)

• Infection exposure in the year leading up to an EoE diagnosis was associated with higher risk compared with infection exposure 5 or more years prior (OR, 2.28 vs 2.25)
• Autoimmunity was linked to a lower risk of developing EoE vs individuals lacking autoimmunity (OR, 1.68 vs 2.03)
• Compared with healthy sibling controls, their sibling who were patients living with EoE had greater odds of any type of prior infection (OR, 1.51; 95% CI, 1.30-1.89), with GI infection having the highest overall odds (OR, 2.37; 95% CI, 1.64-3.42); in contrast, opportunistic infection had the lowest risk (OR, 1.10; 95% CI, 0.41-2.97)
• Looking specifically at inpatient infection, GI infection had the highest associated odds of developing EoE, both in the overall study population (OR, 3.95; 95% CI, 2.90-5.36) and according to the sibling analysis (OR, 2.78; 95% CI, 1.76-4.39)

The authors noted both strengths and limitations to their findings. Strengths include the use of a nationwide population that had validated histological data and the incorporation of a sibling analysis, “which allows us to address difficult-to-control factors such as genetics, environmental, and social aspects that could confound risk calculations.” Wider generalizability limits included using diagnostic codes for patients who sought hospital-based care and the potential for undiagnosed EoE in the study group or healthy controls.

“Future investigations should be directed at specific types of gastrointestinal infections,” the study authors concluded, “such as luminal versus nonluminal infections, which may have differing effects.”

Reference

Uchida AM, Ro G, Garber JJ, Roelstrade B, Ludvigsson JF. Prior hospital-based infection and risk of eosinophilic esophagitis in a Swedish nationwide case-control study. United European Gastroenterol J. 2022;10(9):999-1007. doi:10.1002/ueg2.12324