How is non-reflux induced esophagitis classified and treated?

Classification of Non-Reflux Induced Esophagitis

Non-reflux induced esophagitis should be classified into several distinct categories: eosinophilic esophagitis, infectious esophagitis, drug-induced esophagitis, caustic esophagitis, and other immune-mediated esophagitis. 1

Eosinophilic Esophagitis (EoE)

Eosinophilic esophagitis is the most well-characterized form of non-reflux esophagitis and has specific diagnostic criteria:

• Diagnostic criteria: Symptoms of esophageal dysfunction AND ≥15 eosinophils per high-power field (or ~60 eosinophils per mm²) on esophageal biopsy 2
• Key symptoms: Dysphagia, food impaction, food refusal, heartburn, regurgitation, chest pain 2
• Endoscopic findings: Esophageal rings, longitudinal furrows, exudates, edema, strictures, narrow caliber esophagus (quantified using the EoE Endoscopic Reference Score [EREFS]) 2
• Histology: ≥15 eosinophils/HPF, basal cell hyperplasia, eosinophil microabscesses, eosinophil layering, eosinophil degranulation, subepithelial sclerosis 2

Important Update on PPI-Responsive Esophageal Eosinophilia

Previously, PPI-responsive esophageal eosinophilia (PPI-REE) was considered a separate entity from EoE. However, current evidence shows that:

• PPI-REE and EoE are clinically, endoscopically, and histologically indistinguishable at baseline 2
• They share features of Th2 immune-mediated inflammation and gene expression 2
• PPIs are now considered a first-line treatment for EoE rather than a diagnostic criterion 2

Infectious Esophagitis

• Common pathogens: Candida albicans, Herpes simplex virus (HSV), Cytomegalovirus (CMV) 1
• Risk factors: Immunocompromised status (HIV, transplant recipients, chemotherapy) 1
• Symptoms: Odynophagia (painful swallowing), chest pain 1
• Diagnosis: Endoscopy with biopsy showing characteristic findings (e.g., pseudohyphae for Candida, viral inclusions for CMV/HSV)

Drug-Induced Esophagitis

• Common culprits: Bisphosphonates, NSAIDs, antibiotics (doxycycline, tetracycline), potassium chloride, iron supplements 1
• Mechanism: Direct mucosal injury from pill contact with esophageal mucosa
• Symptoms: Acute onset chest pain, odynophagia
• Endoscopic findings: Discrete ulcers, often in mid-esophagus

Caustic Esophagitis

• Etiology: Ingestion of alkaline or acidic substances
• Mechanism: Alkaline substances cause colliquative necrosis; acidic substances cause coagulative necrosis 1
• Symptoms: Severe chest pain, odynophagia, drooling
• Complications: Stricture formation, perforation

Other Immune-Mediated Esophagitis

• Lymphocytic esophagitis: Characterized by increased intraepithelial lymphocytes 3
• Crohn's disease of the esophagus: Rare manifestation of inflammatory bowel disease 1
• Esophagitis dissecans superficialis: Sloughing of esophageal mucosa 3
• Bullous disorders: Pemphigus vulgaris, bullous pemphigoid, epidermolysis bullosa 3

Diagnostic Approach

1. Endoscopy with biopsy: Multiple biopsies from at least two esophageal levels, targeting areas of inflammation 2

   • For suspected EoE: At least 6 biopsies from different anatomical sites 2
   • For suspected infectious esophagitis: Biopsies for histology and culture

2. Histological assessment:

   • Quantification of eosinophils per HPF
   • Assessment of other inflammatory cells
   • Special stains for infectious agents when indicated

3. Additional testing:

   • For suspected EoE: Consider allergy testing (though not recommended for choosing dietary therapy) 2
   • For refractory symptoms: Esophageal physiological testing (pH monitoring, manometry) 2

Treatment Approach

Eosinophilic Esophagitis

• First-line: Proton pump inhibitors (PPI) due to safety profile and high response rates (up to 50%) 2, 4
• Second-line options:
  • Topical corticosteroids (fluticasone, budesonide) with histologic remission in 64.9% vs 13.3% for placebo 4
  • Elimination diets (six-food, four-food, or two-food elimination) 2
  • Support from experienced dietitian for dietary therapy 2
• For strictures: Endoscopic dilation 4

Infectious Esophagitis

• Pathogen-specific antimicrobial therapy
• Treatment of underlying immunodeficiency when possible

Drug-Induced Esophagitis

• Discontinuation of offending medication
• PPI therapy for symptom relief
• Proper medication administration (with sufficient water, upright position)

Caustic Esophagitis

• Acute management: NPO status, IV fluids, pain control
• Endoscopic assessment of injury severity
• Prevention of stricture formation

Monitoring and Follow-up

For EoE:

• Endoscopy with biopsy while on treatment to assess response, as symptoms may not correlate with histological activity 2
• Remission defined as maximum eosinophil count <15 eosinophils/0.3 mm² 2

Pitfalls and Caveats

1. Overlap with GERD: EoE and GERD are not mutually exclusive and can coexist in the same patient 2

2. Diagnostic challenges:

   • Normal-appearing mucosa does not exclude EoE 2
   • PPI use prior to endoscopy may mask findings of EoE 2

3. Treatment considerations:

   • Patients with Barrett's esophagus, severe erosive esophagitis, or EoE should generally not discontinue PPI therapy 2
   • Combining elimination diets with pharmacological treatment is not routinely recommended for EoE 2

4. Monitoring challenges:

   • Symptoms may not correlate with histological activity in EoE 2
   • Endoscopic findings alone are insufficient for diagnosis of EoE 2

By systematically approaching non-reflux esophagitis with appropriate diagnostic testing and targeted therapy based on the specific etiology, clinicians can effectively manage these conditions and prevent long-term complications.