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. 4, 5 Type III achalasia with spastic contractions responds best to POEM with extended myotomy. 4

• Critical caveat: Achalasia and obstructive motor disorders occur in approximately 15% of patients with EoE 6, and up to 34% of EoE patients have abnormal manometry findings. 6 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. 4, 5

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, 7

• 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. 7 This suggests shared pathophysiology in some cases.

• Female sex, longer diagnostic delay, and abnormal esophagogram are more common in EoE patients with concurrent achalasia. 6

Histologic Patterns

• In primary achalasia, esophageal biopsies may show some eosinophils (median 3 eos/hpf) in 34% of patients 8, 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). 8

• 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. 6 These patients require invasive treatment.

• Offer pneumatic dilation or Heller myotomy/POEM for achalasia, but combine with topical steroids for optimal outcomes. 9, 10 In one series, 50% of EoE patients with achalasia required invasive achalasia management for symptom relief. 6

• For type III achalasia with EoE, POEM is preferred because it allows extended proximal myotomy to address spastic contractions. 4

• 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. 6

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. 9, 10 However, dilation must be combined with anti-inflammatory therapy (topical steroids or PPIs) to prevent recurrence. 1, 9

• Chest pain occurs in 74% of patients after dilation but is usually self-limited. 10

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, 6

• 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. 6

• Do not perform myotomy or dilation without first obtaining esophageal biopsies, as treating achalasia-like symptoms without addressing underlying EoE leads to poor outcomes. 6

• 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. 11, 12 In rare cases, high-dose corticosteroids can reverse both the eosinophilia and motility abnormalities. 12