What is the best treatment approach for an allergic patient with elevated eosinophils (high eosinophil count)?

Management of Allergic Patients with High Eosinophils

For an allergic patient with elevated eosinophils, the primary treatment depends on whether eosinophilic esophagitis (EoE) is present: if EoE is confirmed, topical corticosteroids are first-line therapy; if the eosinophilia is related to other atopic conditions (asthma, allergic rhinitis, eczema), treat the underlying allergic disease with standard therapies, as supplements and antihistamines are not effective for reducing eosinophil counts. 1, 2

Initial Diagnostic Approach

Determine the cause of eosinophilia:

• Peripheral blood eosinophil counts alone are not diagnostic and provide only supportive evidence for eosinophilic disorders, with 10-50% of adults and 20-100% of children with EoE showing elevated counts (typically only 2-fold elevation). 1

• Evaluate for eosinophilic esophagitis if the patient has dysphagia, food impaction, or reflux-like symptoms by performing upper endoscopy with esophageal biopsies (≥15 eosinophils per high-power field confirms EoE). 2, 3

• Screen for concomitant atopic diseases including allergic rhinitis, asthma, and eczema, which are highly prevalent in patients with eosinophilia—allergic rhinitis is the most common comorbidity. 1

• Rule out other causes of hypereosinophilia including parasitic infections, drug reactions, myeloid neoplasms, and autoimmune conditions through appropriate serologic testing, imaging, and potentially bone marrow evaluation if counts are markedly elevated. 4, 5

Treatment for Eosinophilic Esophagitis (If Present)

First-Line Pharmacotherapy

Topical corticosteroids are the preferred initial treatment:

• Efficacy: Approximately 65% of patients achieve histological remission (<15 eosinophils/hpf) with moderate certainty of evidence. 2, 3

• Duration: Treat for 8-12 weeks before evaluating histological response with repeat endoscopy and biopsies. 2, 3

• Safety: Systemic side effects have not been documented during long-term treatment, though monitoring bone mineral density and adrenal suppression is recommended in children and adolescents. 2

• Common adverse effect: Candida infection occurs in a small proportion and should be managed with topical antifungals while continuing topical steroids. 2

Proton pump inhibitors (PPIs) are an acceptable alternative:

• Efficacy: Overall histological response rate is approximately 42% with very low certainty of evidence. 3

• Regimen: Use double-dose therapy (e.g., esomeprazole 40 mg twice daily) for 8 weeks. 3

Dietary Therapy Options

If pharmacotherapy fails or patient prefers dietary management:

• Empiric 6-food elimination diet (removing milk, egg, wheat, soy, nuts, fish/shellfish) has a 68% histologic response rate with low certainty evidence. 1, 2

• Empiric 2- or 4-food elimination diets are more practical step-up approaches with low certainty evidence. 2

• Elemental diets have moderate certainty evidence and are highly effective but impractical in most patients due to taste, cost, and need for potential gastrostomy tube. 1, 2

• Critical caveat: Dietary elimination should only be conducted under supervision of an experienced dietitian due to risk of nutritional deficiencies and potential development of de novo IgE-mediated food allergy upon reintroduction. 1, 2

• Allergy testing-directed elimination has very low certainty evidence with higher failure rates compared to empiric elimination and is not recommended. 1, 2

Maintenance Therapy

For patients achieving remission:

• Continue maintenance therapy rather than discontinuation to prevent recurrent dysphagia, food impaction, and esophageal stricture formation. 2

• Medical treatment with topical steroids likely reduces stricture development with moderate evidence and strong recommendation. 2

Treatment for Eosinophilia Related to Other Atopic Conditions

What NOT to Use

Supplements, antihistamines, montelukast, and sodium cromoglycate are not recommended for managing eosinophilia:

• Montelukast showed no benefit in maintaining EoE remission (40% treatment group vs 23.8% control group in remission after 26 weeks, OR 0.48, p=0.33). 1

• Montelukast does reduce peripheral blood eosinophil counts by 9-15% in asthma patients, but this effect is unrelated to clinical benefit in eosinophilic disorders. 6

• Sodium cromoglycate showed no improvement in symptom or histological profiles in clinical studies despite laboratory evidence of reduced immunological response. 1

• Antihistamines have no convincing evidence for managing eosinophilia but are useful for co-existing allergic disease. 1

What TO Use

Treat the underlying atopic condition with standard therapies:

• For asthma with eosinophilia: Use inhaled corticosteroids as first-line; consider biologics targeting IL-5 pathway (mepolizumab, benralizumab) for severe eosinophilic asthma. 1

• For allergic rhinitis: Use intranasal corticosteroids and oral antihistamines for symptom control (not for eosinophil reduction). 1

• For eczema: Use topical corticosteroids and emollients; consider dupilumab for severe cases. 1

Novel Biologics for Refractory Cases

For patients with EoE refractory to standard treatment and/or significant concomitant atopic disease:

• Dupilumab (anti-IL-4 receptor) showed significant reduction in dysphagia scores and 86.8 eosinophil reduction per hpf (107.1% decrease) compared to placebo in phase 2 trials. 1

• Benralizumab (anti-IL-5 receptor) demonstrated efficacy in eosinophilic asthma and resulted in complete resolution of dysphagia in case reports of EoE patients. 1

• Mepolizumab (anti-IL-5) showed 54% reduction in esophageal eosinophil count but no symptom improvement. 1

• Current recommendation: These biologics cannot be routinely recommended for EoE alone pending phase 3 trial results, but may be treatment options in patients with coexisting allergic diseases. 1

Monitoring and Follow-Up

Endoscopy with biopsy is required while on treatment:

• Symptoms do not always correlate with histological activity, making objective assessment essential. 2

• Repeat endoscopy after 8-12 weeks of treatment to confirm histological remission. 2, 3

• If symptoms recur while on treatment, repeat endoscopy to assess for refractory inflammatory disease, fibrostenotic disease, or treatment complications like esophageal candidiasis. 1

Key Clinical Pitfalls

Avoid these common errors:

• Do not use allergy testing (skin prick, specific IgE, patch testing) to guide dietary elimination in EoE—it is no more effective than empirical elimination and has 100% agreement on strong recommendation against this approach. 1

• Do not combine elimination diets with pharmacological treatment routinely—reserve combination therapy only for selected patients who fail monotherapy. 1

• Do not rely on peripheral eosinophil counts alone to diagnose or monitor eosinophilic disorders—tissue diagnosis is essential. 1

• Do not discontinue systemic corticosteroids immediately before checking eosinophil counts—blood eosinophil counts remain suppressed for several weeks after SCS discontinuation (only 21-26% normalized within 1 month). 7