In a patient with suspected eosinophilic esophagitis, is measuring serum interleukin‑6 useful for diagnosis or management?

Blood Interleukin-6 Testing Has No Role in Eosinophilic Esophagitis

Serum interleukin-6 (IL-6) measurement is not useful for the diagnosis or management of eosinophilic esophagitis and should not be ordered. The diagnosis of EoE requires endoscopy with esophageal biopsies demonstrating ≥15 eosinophils per high-power field, combined with symptoms of esophageal dysfunction; blood tests do not contribute to diagnosis or monitoring. 1, 2

Why Blood Tests Are Not Helpful in EoE

Eosinophilic esophagitis is a tissue-based diagnosis that cannot be made or monitored with blood markers. The disease is characterized by localized eosinophilic infiltration confined to the esophageal mucosa, making systemic blood markers unreliable diagnostic tools. 1, 2

• Endoscopy with multiple biopsies (minimum 6 samples: 2–3 from proximal and 2–3 from distal esophagus) is the only reliable diagnostic test for EoE. 1, 2
• Even when the esophageal mucosa appears endoscopically normal, biopsies are mandatory because histologic EoE is present in approximately 9–10% of patients with normal-appearing mucosa. 1, 2
• Peripheral blood eosinophil counts are present in only 10–50% of adults with EoE, so normal blood eosinophil levels do not exclude the disease. 3, 2

The Evidence on Biomarkers in EoE

While research has explored various blood biomarkers in EoE, none are validated for clinical use, and IL-6 specifically has not been shown to have diagnostic or monitoring value. 4, 5

• Research studies have investigated blood levels of absolute eosinophil count (AEC), eosinophil-derived neurotoxin (EDN), and eotaxin-3, which showed correlation with esophageal eosinophil density in pediatric cohorts, but these remain investigational tools not recommended for routine clinical practice. 5
• Emerging biomarkers such as major basic protein (MBP), transforming growth factor β1 (TGF-β1), IL-5, and IL-13 have been studied in research settings, but none are ready for clinical application. 6
• IL-6 is not among the biomarkers that have demonstrated any correlation with EoE disease activity or severity in published research. 5, 6

The Correct Diagnostic Approach

The diagnostic algorithm for EoE requires three elements: clinical symptoms of esophageal dysfunction, histologic evidence of ≥15 eosinophils per high-power field on esophageal biopsy, and evaluation to exclude other causes of esophageal eosinophilia. 1, 4

• Suspect EoE clinically in patients with dysphagia, food impaction, heartburn, regurgitation, chest pain, or feeding difficulties, particularly when atopic comorbidities (asthma, atopic dermatitis, food allergies) are present. 1
• Perform upper endoscopy evaluating for characteristic findings including esophageal rings, longitudinal furrows, white exudates, edema, strictures, or narrow-caliber esophagus, ideally quantified using the EoE Endoscopic Reference Score (EREFS). 1
• Obtain multiple biopsies from at least two esophageal levels targeting areas of apparent inflammation to increase diagnostic yield. 1

Monitoring Disease Activity

Blood tests are equally unhelpful for assessing treatment response or disease activity; repeat endoscopy with biopsies is required when symptoms recur during treatment. 1, 2

• Histological remission is defined as <15 eosinophils per 0.3 mm², and deep remission as <5 eosinophils per 0.3 mm². 3
• Symptom improvement alone may not reflect ongoing inflammation, so histologic assessment remains the gold standard for monitoring. 1

Common Pitfalls to Avoid

• Do not rely on peripheral eosinophil counts to diagnose or exclude EoE; tissue biopsy is the gold standard. 3, 2
• Do not order IL-6 or other investigational biomarkers as they have no established clinical utility in EoE management. 2, 4, 5
• Do not assume normal-appearing esophageal mucosa excludes EoE; biopsies must still be obtained when clinical suspicion exists. 1, 2
• Do not use allergy testing (IgE, IgG, or patch testing) to guide dietary therapy in EoE, as IgE-guided elimination diets are no more effective than empirical elimination. 2