Nonesophageal eosinophilic gastrointestinal disorders

Nonesophageal eosinophilic gastrointestinal disorders (nonEoE EGIDs) are chronic, immune-mediated conditions characterized by eosinophil-predominant inflammation of the stomach, i.e., eosinophilic gastritis (EoG), small intestine, i.e., eosinophilic enteritis (EoN), or colon, i.e., eosinophilic colitis (EoC) in the absence of other causes of GI eosinophilia. The etiology of EoG and EoN is not fully understood but is believed to involve a Th2 inflammatory response to allergens and is associated with a personal or family history of atopic disease. The cause of EoC is unknown, but contributing factors may include food allergies, intestinal dysbiosis, and genetic predisposition. Clinical features depend on the depth of infiltration (mucosal, muscularis, or serosal/subserosal) and commonly include abdominal pain, nausea, vomiting, and diarrhea. Muscularis or serosal/subserosal involvement may manifest with obstruction or ascites. Diagnosis requires endoscopic biopsy of the affected segments that reveals eosinophilic infiltration. Other causes of gastrointestinal eosinophilia, such as parasitic infections and inflammatory bowel disease, must be excluded. Management involves dietary therapy (e.g., empiric elimination of common food antigens) in consultation with a dietician. First-line pharmacological treatment for inducing remission consists of glucocorticoids (e.g., oral prednisone or enteric-release budesonide).

Eosiniphilic esophagitis is described in "Esophagitis."

Nonesophageal eosinophilic gastrointestinal disorders (nonEoE EGIDs) are chronic, immune-mediated conditions characterized by eosinophil-predominant inflammation of the stomach, i.e., eosinophilic gastritis (EoG), small intestine, i.e., eosinophilic enteritis (EoN), or colon, i.e., eosinophilic colitis (EoC) in the absence of other causes of GI eosinophilia. ^[1][2]

• EoG and EoN ^[2][3]
  • The exact pathogenesis is not fully understood but is thought to be driven by a Th2 inflammatory response to food or environmental antigens.
  • Associated with a personal or family history of atopic disease (e.g., asthma, eczema, food allergies, allergic rhinitis)
• EoC ^[2][3]
  • The underlying cause is unknown.
  • Potential contributing factors include:
    • Food allergies
    • Intestinal dysbiosis
    • Genetic predisposition

NonEoE EGIDs are classified based on the depth of eosinophilic infiltration in the GI tract. ^[1][2]

• Mucosal involvement (most common)
• Muscularis involvement
• Serosal and/or subserosal involvement

Symptoms depend on the depth of inflammation.

Common features ^[1][3]

• Mucosal involvement
  • Abdominal pain
  • Nausea, vomiting
  • Diarrhea or constipation
  • Early satiety, anorexia
  • Hematochezia or occult bleeding (less common in EoG and EoN, more common in EoC)
• Muscularis involvement: obstructive symptoms
• Serosal and/or subserosal involvement
  • Abdominal distention
  • Ascites

Features specific to EoG ^[1][3]

• Dyspepsia
• Clinical features of gastric outlet obstruction

Features specific to EoN ^[1][3]

• Malabsorption syndromes
• Protein-losing enteropathy
• Clinical features of small bowel obstruction

Features specific to EoC ^[1][3]

• Tenesmus
• Fecal urgency
• Clinical features of colonic obstruction

General principles

Diagnostic criteria ^[1][2]

Confirmation of nonEoE EGID requires:

• The presence of typical GI features
• Dense eosinophilic infiltrates (above organ-specific thresholds) on biopsy
• Exclusion of other causes of GI eosinophilia

Endoscopy with biopsy ^[1][2]

• Confirmatory test for eosinophilic gastrointestinal disorders
• Multiple biopsies are obtained from both normal and abnormal-appearing areas of involved segments.
• Upper GI tract (for suspected EoG or EoN): biopsies from the gastric antrum, gastric body, and duodenum
• Lower GI tract (for suspected EoC): biopsies from the terminal ileum and at least three colonic sites

Laboratory studies ^[1][2]

Laboratory studies are nonspecific.

• CBC may show eosinophilia and/or anemia.
• Hypoalbuminemia may be present.
• Total IgE levels may be increased.
• Stool studies should be obtained to rule out parasitic and other infections.
• Paracentesis is indicated if ascites is present.

Imaging

• Not used for primary diagnosis
• May be used to assess the depth of inflammation, extent of disease, and/or presence of complications
• Modalities: abdominal ultrasound, CT, or MRI

Diagnosis of EoG

Upper endoscopy with biopsy

• Endoscopic findings ^[1][3]
  • The gastric mucosa may appear normal.
  • Abnormal findings include:
    • Erythema
    • Nodularity and/or granularity
    • Erosions or ulcers
    • Mucosal friability
    • Polyps
    • Thickened folds
• Histological findings ^[1][2][3]
  • Tissue eosinophilia above site-specific diagnostic thresholds
  • Supportive features include:
    • Eosinophilic glandulitis
    • Eosinophils in the muscularis mucosa or submucosa
    • Lamina propria fibrosis or fibroplasia
    • Eosinophil degranulation
    • Eosinophil sheets or clusters

Cross-sectional imaging ^[1][2]

Findings may include:

• Polyps
• Ulcers
• Thickening of the intestinal wall or gastric folds

Diagnosis of EoN

Upper endoscopy and biopsy

• Endoscopic findings ^[1][2]
  • May appear normal
  • Abnormal findings include:
    • Mucosal edema, nodularity, and/or friability
    • Punctate erythema
• Histological findings ^[1][2][3]
  • Tissue eosinophilia above site-specific diagnostic thresholds
  • Supportive features
    • Eosinophilic glandulitis or cryptitis
    • Lymphoid aggregates
    • Eosinophil degranulation
    • Eosinophils in the muscularis mucosa or submucosa

Cross-sectional imaging ^[1][2]

Findings may include:

• Thickening of the intestinal wall
• Bowel narrowing
• Ascites
• Lymphadenopathy

Diagnosis of EoC

Colonoscopy

• Endoscopic findings ^[1][2]
  • May appear normal
  • Abnormal findings include:
    • Mucosal edema, nodularity, and/or friability
    • Punctate erythema
• Histological findings ^[1][3]
  • Tissue eosinophilia above site-specific diagnostic thresholds ^[2]
  • Supportive features
    • Eosinophilic cryptitis or crypt abscesses
    • Lymphoid aggregates
    • Eosinophil degranulation
    • Eosinophils in the muscularis mucosa or submucosa

Cross-sectional imaging ^[1][2]

Findings may include:

• Concentric thickening of the colon wall
• Ascites
• Prominent contrast enhancement within the mucosal sinuses in the longitudinal section of the bowel on CT

• Infections (e.g., parasitic, helminthic)
• Inflammatory bowel disease
• Hypersensitivity reactions (e.g., food allergy, drug hypersensitivity reaction)
• Hypereosinophilic syndrome
• Connective tissue disorders
• Vasculitis (e.g., eosinophilic granulomatosis with polyangiitis)
• Celiac disease
• Malignancy (e.g., leukemia)
• Systemic mastocytosis
• Adrenal insufficiency
• Graft-versus-host disease

The differential diagnoses listed here are not exhaustive.

• NonEoE EGIDs should be managed by a gastroenterologist in consultation with a dietician.
• First-line pharmacological therapy: glucocorticoids (e.g., systemic prednisone or enteric-release budesonide) for induction of remission
• Consider empiric elimination of commonly implicated food antigens (i.e., six-food elimination diet).
• IgE-based food allergy testing to guide dietary restrictions is not recommended.

• Complications of EoG ^[1]
  • Gastric outlet obstruction
  • Ulceration with or without perforation
  • Iron-deficiency anemia
• Complications of EoN ^[1][2]
  • Intestinal obstruction
  • Malabsorption and nutrient deficiencies
  • Protein-losing enteropathy
• Complications of EoC ^[2]
  • Volvulus
  • Intussusception
  • Colon perforation

We list the most important complications. The selection is not exhaustive.

The prognosis of nonEoE EGIDs is variable, resulting in one of the following: ^[1][2]

• A single episode without relapse
• A relapsing and remitting course
• Chronic disease without remission