What are the types of eosinophilic diseases involving the gastrointestinal (GI) system, including the peritoneum?

Types of Eosinophilic Diseases Involving the Gastrointestinal System Including Peritoneum

The gastrointestinal tract can be affected by multiple distinct eosinophilic diseases, which include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, eosinophilic colitis, and systemic conditions with gastrointestinal involvement such as hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis. 1

Primary Eosinophilic Gastrointestinal Diseases (EGIDs)

1. Eosinophilic Esophagitis (EoE)

• Defined as a primary clinicopathologic disorder characterized by esophageal symptoms and ≥15 intraepithelial eosinophils per high-power field in esophageal biopsies 1
• Distinguished from GERD by lack of response to proton pump inhibitor therapy
• Clinical presentation:
  • Children: feeding difficulties (infants/toddlers), vomiting or pain (school-aged)
  • Adolescents and adults: dysphagia, food impaction, chest pain 1
• Endoscopic findings: rings, furrows, white exudates, edema, strictures 1

2. Non-Esophageal EGIDs

Eosinophilic Gastritis (EoG)

• Characterized by pathologic eosinophilic infiltration limited to the stomach 2
• Symptoms: upper abdominal pain, nausea, vomiting, early satiety
• May present with anemia due to occult bleeding or malabsorption

Eosinophilic Enteritis (EoN)

• Eosinophilic infiltration of small bowel segments 2, 3
• Can be further specified by location (e.g., eosinophilic duodenitis)
• Symptoms: abdominal pain, diarrhea, malabsorption, protein-losing enteropathy

Eosinophilic Colitis (EoC)

• Eosinophilic infiltration limited to the colon 2, 3
• Symptoms: diarrhea (sometimes bloody), abdominal pain, weight loss

3. Multi-segment Involvement

• Multiple GI segments can be simultaneously affected 2
• Symptoms reflect the combination of involved segments
• Depth of infiltration often influences symptom presentation more than location 3

Systemic Conditions with GI Eosinophilic Involvement

1. Hypereosinophilic Syndrome (HES)

• Characterized by:
  • Persistent peripheral eosinophilia (>1500 cells/μL)
  • Eosinophil-mediated organ damage
  • Exclusion of secondary causes 1, 4
• Up to 38% have gastrointestinal symptoms 1
• Can affect any part of GI tract, including esophagus
• Distinguished from isolated EGIDs by marked peripheral eosinophilia and multi-organ involvement (skin, lung, heart, neurologic) 1

2. Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• Formerly known as Churg-Strauss syndrome
• Rare systemic eosinophilic vasculitis affecting small to medium-sized arteries
• Clinical presentation follows 3 stages:
  1. Prodromal (allergic rhinitis, nasal polyposis, asthma)
  2. Eosinophilic (peripheral blood eosinophilia and tissue infiltration)
  3. Vasculitic (necrotizing vasculitis affecting multiple organ systems) 1
• GI involvement can cause eosinophilic infiltration or neuropathy due to vasculitis
• ANCA-positive in only 30-40% of cases 1

Secondary Causes of Gastrointestinal Eosinophilia

1. Inflammatory Bowel Disease

• Crohn's disease can present with esophageal involvement (more common in children)
• Characterized by superficial or deep esophageal mucosal ulcerations 1

2. Connective Tissue Diseases

• Systemic sclerosis: esophageal hypomotility and incompetent lower esophageal sphincter
• Other connective tissue diseases may have GI eosinophilic manifestations 1

3. Parasitic Infections

• Various parasitic infections can cause eosinophilic infiltration of GI tissues
• Examples include strongyloidiasis, toxocariasis, schistosomiasis 4

4. Drug-Induced Eosinophilic Gastroenteritis

• Medications can trigger eosinophilic infiltration of GI tissues 1
• Requires medication history and improvement after discontinuation

5. Peritoneal Eosinophilia

• Can occur as part of eosinophilic gastroenteritis when the serosal layer is involved
• May present with ascites and peritoneal symptoms
• Can mimic acute abdomen, including appendicitis or peritonitis 5

Pathophysiologic Classification

1. Based on Depth of Infiltration

• Mucosal: most common, presents with malabsorption, protein loss, diarrhea
• Muscular: presents with obstructive symptoms due to thickening of bowel wall
• Serosal: presents with ascites, peritoneal symptoms 5

2. Based on Immunologic Mechanism

• Type 2 inflammation-driven (most common)
• IgE-mediated food allergic reactions (especially in EoE)
• Non-IgE-mediated immune reactions 6, 7

Diagnostic Approach

• Complete blood count with differential to confirm eosinophilia (>0.5 × 10^9/L) 4
• Endoscopy with multiple biopsies from affected and unaffected areas
• Diagnostic criteria:
  • EoE: ≥15 eosinophils/HPF in esophageal biopsies
  • Non-EoE EGIDs: consensus on diagnostic thresholds is still lacking 3
• Rule out secondary causes of eosinophilia (parasites, medications, other systemic diseases)

Clinical Pitfalls and Caveats

• EGIDs are often underdiagnosed due to nonspecific symptoms and normal endoscopic appearance 2, 3
• Multiple biopsies are essential as eosinophilic infiltration can be patchy
• PPI-responsive esophageal eosinophilia should be distinguished from true EoE 1
• Peripheral eosinophilia is not always present, especially in isolated EoE
• Symptoms may not correlate with the degree of eosinophilic infiltration
• Overlapping features with functional GI disorders can lead to misdiagnosis

Understanding the spectrum of eosinophilic diseases involving the GI tract is crucial for proper diagnosis and management, as treatment approaches differ based on the specific condition and its extent.