• AHW Lim, et al. Am J Gastroenterol 2024; 119: 1066-1073. Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis Thanks to Dr. Benjamin Gold for these references.
• G Hiermath. Am J Gastroenterol 2024; 119: 1021-1022. Navigating the Complex Landscape of Dietary Elimination Therapy in Eosinophilic Esophagitis: Can We Personalize It?

On first glance at this article, it looks like the authors have found that testing for food-specific IgG4 (FS-IgG4) could be useful in guiding dietary treatment for eosinophilic esophagitis (EoE). However, the data don’t support this conclusion.

Methods: Prospective observational cohort in adult patients with EoE (n=22 along with 13 controls) placed on elimination diet based on FS-IgG4 levels (ImmunoCAP, cutoff of 10 mgA/L).

Key findings:

• Elevated serum FS-IgG₄ to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination
• Nine (45%) patients had histological remission (<15 eosinophils per high-power field)
• Serum FS-IgG₄ did not decline by 6-week follow-up. In addition, there was no difference in the FS-IgG4 levels between active and inactive EoE
• 19 of 22 (86.4%) patients had high FS-IgG4 to milk and 13 of 22 (59.1%) had high FS-IgG4 to wheat. No patients required seafood elimination

The authors note in their introduction that total IgG4 levels in the esophagus are 45-fold those of healthy controls. In addition, “a preliminary study assessing trigger foods in patients undergoing 6FEDs has demonstrated elevated FS-IgG4 was associated with trigger foods in esophageal secretions but not foods that did not trigger esophageal eosinophilia” (K Peterson et al. Aliment Pharmacol Ther 2020; 52: 997-1007).

Despite the lack of any proven efficacy of this FS-IgG4-directed diet (over empiric elimination), the editorial suggests that FS-IgG4 levels may be beneficial, noting that the histologic remission rate increased to 64.3% after excluding ~30% patients with concerns of non-adherence. Removing 30% of patients to get better results would often be called “cherry-picking.”

In addition, neither the editorial (nor the study) delves into the fairly high rates of FS-IgG4 to milk and wheat. This suggests that FS-IgG4 testing will be unreliable with numerous false-positives (though there is wide range of reported reactions to milk and wheat in the literature). Even the control group had high FS-IgG4 to milk in half of the patients. Both the editorial and the study review the limitations which include small sample size, need for control group with atopy, and a lack of established cutoff values for FS-IgG4.

My take: This is a NEGATIVE study. Using FS-IgG4 levels to guide elimination diet was NOT better than empiric elimination of either 1 or 2-food groups. This finding should be more clearly stated in both the study and the editorial. It would be very useful to provide specific dietary advice to our patients with EoE. It is possible that a larger study with higher cutoff levels could find some utility for FS-IgG4. However, this study does not make this approach look terribly promising.

Related blog posts.

• Practical Guide to Dietary Therapy for Eosinophilic Esophagitis This link to an open access article provides extensive useful advice of dietary therapy for EoE
• “Tug” Sign For Eosinophilic Esophagitis and EoE Bowel Sounds Tips
• Best Approach for Identifying Eosinophilic Esophagitis
• What is EoE?
• How Useful Are 3-site Esophageal Biopsies for Eosinophilic Esophagitis
• Long-Term Treatment of Eosinophilic Esophagitis with Budesonide
• Dupilumab: FDA Approval for Eosinophilic Esophagitis
• 2020 Eosinophilic Guidelines (AGA)