How should I evaluate and manage a patient with dysphagia to differentiate primary achalasia from eosinophilic esophagitis‑related pseudo‑achalasia and treat accordingly?

Differentiating Achalasia from Eosinophilic Esophagitis-Related Pseudo-Achalasia

In patients with dysphagia, perform esophageal biopsies during initial endoscopy regardless of endoscopic appearance, as eosinophilic esophagitis (EoE) can mimic achalasia and requires fundamentally different treatment. 1

Initial Diagnostic Evaluation

Endoscopy with Systematic Biopsy

• Obtain at least 6 esophageal biopsies (2-3 from proximal and 2-3 from distal esophagus) in all adults with dysphagia or food bolus obstruction, even with normal-appearing mucosa. 1 This is critical because EoE can present with achalasia-like symptoms but requires tissue diagnosis.

• Withdraw proton pump inhibitors for at least 3 weeks before biopsy to ensure accurate diagnosis of EoE, as PPIs can reduce esophageal eosinophilia and mask the diagnosis. 1

• Diagnostic threshold: ≥15 eosinophils per 0.3 mm² (high-power field) confirms EoE. 1, 2 Note that peripheral blood eosinophilia occurs in only 10-50% of adults with EoE, so normal blood counts do not exclude the disease. 2, 3

High-Resolution Manometry (HRM)

• Perform HRM to define achalasia subtype according to Chicago Classification (types I, II, or III), as this guides treatment selection. 1, 4 Type III achalasia with spastic contractions responds best to POEM with extended myotomy. 1

• Critical caveat: Achalasia and obstructive motor disorders occur in approximately 15% of patients with EoE 5, and up to 34% of EoE patients have abnormal manometry findings. 5 Therefore, finding achalasia on manometry does not exclude concurrent EoE.

Timed Barium Esophagram

• Obtain barium swallow to assess esophageal emptying and structural changes, including the classic "bird's beak" appearance of achalasia or the ringed/corrugated appearance sometimes seen in EoE. 1, 4

Distinguishing Features

Clinical Clues Favoring EoE Over Primary Achalasia

• History of atopy (asthma, allergic rhinitis, atopic dermatitis, food allergies) strongly suggests EoE, as 50-80% of EoE patients have concurrent atopic conditions. 2, 6

• Recent epidemiologic data show achalasia patients have a 33-fold increased risk of having EoE (RR 32.9), with even higher risk (RR 69.6) in patients ≤40 years old. 6 This suggests shared pathophysiology in some cases.

• Female sex, longer diagnostic delay, and abnormal esophagogram are more common in EoE patients with concurrent achalasia. 5

Histologic Patterns

• In primary achalasia, esophageal biopsies may show some eosinophils (median 3 eos/hpf) in 34% of patients 7, but this is typically due to stasis and reflux rather than primary EoE. However, 8% of achalasia patients meet full pathologic criteria for EoE (≥15 eos/hpf). 7

• If eosinophil counts are ≥15 eos/hpf with accompanying features (basal cell hyperplasia, eosinophil microabscesses, eosinophil layering, subepithelial sclerosis), diagnose EoE even if manometry shows achalasia. 1

Treatment Algorithm

For EoE Without Achalasia or With Reversible Motility Abnormalities

1. First-line: Topical swallowed corticosteroids (fluticasone or budesonide) twice daily for 8-12 weeks, which achieve histologic remission in the majority and can normalize motility abnormalities in some cases. 1, 3

2. Alternative first-line: Proton pump inhibitor therapy twice daily for 8-12 weeks, which is effective in inducing histologic and clinical remission. 1, 3

3. Elimination diets (six-food or empiric elimination) are effective but require dietitian support and have lower compliance. 1

4. Maintenance therapy is mandatory after achieving remission, as relapse rates are high (>50%) after treatment withdrawal. 1, 2

For EoE With Concurrent True Achalasia (Irreversible Motility Disorder)

• A subset of EoE patients (15%) have true achalasia or obstructive motor disorders that do not respond to anti-inflammatory therapy alone. 5 These patients require invasive treatment.

• Offer pneumatic dilation or Heller myotomy/POEM for achalasia, but combine with topical steroids for optimal outcomes. 1 In one series, 50% of EoE patients with achalasia required invasive achalasia management for symptom relief. 5

• For type III achalasia with EoE, POEM is preferred because it allows extended proximal myotomy to address spastic contractions. 1

• Important: Patients with EoE and achalasia respond less well to topical steroids alone (lower response rate compared to EoE without motility disorders), necessitating combined medical and mechanical treatment. 5

For Fibrostenotic EoE

• Endoscopic dilation is safe and effective for strictures, with perforation rates (0.4%) similar to non-EoE strictures when using conservative technique. 1 However, dilation must be combined with anti-inflammatory therapy (topical steroids or PPIs) to prevent recurrence. 1

• Chest pain occurs in 74% of patients after dilation but is usually self-limited. 1

Monitoring and Reassessment

• Repeat endoscopy with biopsies 8-12 weeks after initiating therapy to assess histologic response, as symptoms do not always correlate with histologic activity. 1, 2, 3

• If symptoms persist despite histologic remission (<15 eos/hpf), consider repeat HRM to evaluate for persistent motility disorders that may require mechanical intervention. 1, 5

• If initial histology is not diagnostic but clinical suspicion remains high, repeat endoscopy with adequate biopsies. 1

Critical Pitfalls to Avoid

• Do not assume normal peripheral eosinophil counts exclude EoE—tissue diagnosis is mandatory. 2, 3

• Do not rely on manometry alone to exclude EoE—up to 15% of EoE patients have achalasia or obstructive patterns. 5

• Do not perform myotomy or dilation without first obtaining esophageal biopsies, as treating achalasia-like symptoms without addressing underlying EoE leads to poor outcomes. 5

• Do not discontinue maintenance therapy after achieving remission, as this leads to high relapse rates and potential progression to fibrosis. 1, 2

• Consider that some cases represent a muscle-predominant form of EoE with eosinophilic infiltration of the muscularis propria (not visible on mucosal biopsy), which may cause irreversible neuronal damage mimicking primary achalasia. 8, 9 In rare cases, high-dose corticosteroids can reverse both the eosinophilia and motility abnormalities. 9