What is the differential diagnosis (ddx) of esophagitis?

Differential Diagnosis of Oesophagitis

The differential diagnosis of oesophagitis includes gastroesophageal reflux disease (GERD), eosinophilic esophagitis, infectious esophagitis (Candida, herpes), drug-induced esophagitis, eosinophilic gastroenteritis, Crohn's disease, connective tissue diseases, hypereosinophilic syndrome, and drug hypersensitivity reactions. 1

Primary Differential Diagnoses

Most Common Causes

• Gastroesophageal Reflux Disease (GERD): The most common cause of esophagitis, presenting with heartburn, regurgitation, and erosive changes typically in the distal esophagus 1. GERD affects 10-20% of the population and can coexist with other forms of esophagitis 1.

• Eosinophilic Esophagitis (EoE): Characterized by ≥15 eosinophils per high-power field on biopsy, presenting with dysphagia and food impaction in adults, or feeding intolerance and vague abdominal complaints in children 1. Endoscopic features include rings, furrows, edema, white plaques, and a fragile "crêpe paper" appearance 2.

• Infectious Esophagitis:

  • Candida esophagitis: White plaques on endoscopy, common in immunocompromised patients 1
  • Herpes esophagitis: Presents with odynophagia and discrete ulcerations 1

• Drug-Induced Esophagitis: Associated with medications such as NSAIDs, bisphosphonates, tetracyclines, and potassium chloride 1. Presents with acute odynophagia and discrete ulcerations.

Less Common but Important Causes

• Eosinophilic Gastroenteritis: Eosinophilic infiltration extending beyond the esophagus to involve stomach and/or intestines 1

• Crohn's Disease: Can cause esophageal eosinophilia with characteristic granulomatous inflammation 1, 3

• Connective Tissue Diseases: Including scleroderma and other collagen vascular diseases that can cause esophageal inflammation with eosinophilia 1, 3

• Hypereosinophilic Syndrome: Systemic condition with marked peripheral eosinophilia (>1,500 eosinophils/μL) and multi-organ involvement 1

• Drug Hypersensitivity Reactions: Allergic responses to medications causing esophageal eosinophilia 1

Rare Causes

• Achalasia: Can present with esophageal eosinophilia due to food stasis 1

• Lymphocytic Esophagitis: Characterized by lymphocytic infiltration rather than eosinophilic 4

• Esophagitis Dissecans Superficialis: Rare condition with sloughing of esophageal mucosa 4

• Bullous Disorders: Including pemphigus and pemphigoid affecting the esophagus 4

Critical Diagnostic Distinctions

GERD vs. Eosinophilic Esophagitis

This is the most challenging differential diagnosis clinically. 1 Key distinguishing features:

• Location: EoE often involves long segments and frequently affects the proximal esophagus, while GERD typically involves the distal esophagus 5
• Endoscopic appearance: EoE shows rings, furrows, and white exudates; GERD shows erosions and ulcerations in the distal esophagus 2
• Response to PPI: GERD responds to acid suppression; classic EoE does not (though PPI-responsive esophageal eosinophilia exists as a separate entity) 1
• Distribution: EoE can be patchy or focal; GERD is typically continuous in the distal esophagus 5

Important Caveats

No single test reliably distinguishes EoE from GERD, and clinicians must integrate clinical features, endoscopic findings, histology, and response to therapy 1. The high background prevalence of GERD (10-20%) means these conditions frequently coexist 1.

Esophageal eosinophilia alone cannot be equated with a definitive diagnosis of EoE 1. All other causes must be systematically excluded before confirming EoE 1.

PPI-responsive esophageal eosinophilia (PPI-REE) represents a distinct entity that shares features with both GERD and EoE, showing increased GERD signatures on pH testing but eosinophilia on biopsy 1.