From esophagus to colon: A narrative review of eosinophilic gastrointestinal disorders

Table 1 Differential diagnoses of esophageal eosinophilia

Diagnoses of esophageal eosinophilia
Gastroesophageal reflux disease
Achalasia
Crohn's disease
Parasitic infection
Drug hypersensitivity
Connective tissue diseases (e.g., scleroderma)
Celiac disease
Hypereosinophilic syndrome
Proton pump inhibitor-responsive esophageal eosinophilia

Table 2 Clinico-pathological comparison of eosinophilic esophagitis and gastroesophageal reflux disease

	Eosinophilic esophagitis	Gastroesophageal reflux disease
Pathophysiology	Chronic immune mediated (Th2) disease of the esophagus	Acid-mediated mucosal injury from reflux of gastric contents
Age/gender	Children and young adults. Male predilection	All age groups, more common in adults. No sex predilection
Associations	Atopy, allergies	Obesity, pregnancy, hiatal hernia
Clinical symptoms	Dysphagia, food impaction	Heartburn, regurgitation
Endoscopic findings	Rings, linear furrows. White exudates, strictures	Erosions, erythema, ulceration, hiatal hernia
Distribution	Patchy; proximal, distal esophagus	Predominantly distal esophagus
Histologic criteria	≥ 15 eosinophils/hpf	< 15 eosinophils/hpf
Esophageal pH	Usually normal	Acid exposure
Treatment	PPI, swallowed corticosteroids, diet	PPI, H2RB, lifestyle modifications
Response to PPI	Variable: Partial or absent	Robust response
Response to dietary intervention	Good	Minimal
Complications	Fibrosis, strictures. Recurrent food impaction	Barrett’s esophagus. Adenocarcinoma

hpf: High power field; PPI: Proton pump inhibitors; H2RB: Histamine-2 receptor blockers.

Table 3 Differential diagnoses of colonic eosinophilia

Parasitic infections	Strongyloides stercoralis, Enterobius vermicularis, Trichuris trichiura
Drugs	Clozapine, carbamazepine, rifampicin, gold, NSAIDs, tacrolimus
Transplant-related	Prolonged immunosuppression (e.g., tacrolimus in liver transplant recipients)
Systemic disorders	Hypereosinophilic syndrome, Churg-Strauss, autoimmune diseases
IBD overlap	Eosinophilic infiltration may mimic or precede ulcerative colitis
Others	Radiation colitis, Tolosa-hunt syndrome

IBD: Inflammatory bowel diseases; NSAIDs: Nonsteroidal anti-inflammatory drugs.

Table 4 The emerging molecules in management of eosinophilic gastrointestinal disorders

Molecule	Mechanism	Development phase
Cendakimab	Anti IL-13. Reduce eotaxin-3 mediated eosinophil recruitment	Phase 2
Mepolizumab	Anti IL-5. Reduces eosinophil survival/activation	Phase 2
Benralizumab	Anti IL-5Rα. Induces near-complete eosinophil depletion	Phase 3
Tezepelumab	Anti-TSLP. Blocks epithelial “alarmin” TSLP upstream of Th2 cascade	Phase 3
Lirentelimab	Anti-Siglec-8. Depletes eosinophils and inhibits mast cells	Phase 2/3

IL: Interleukin; TSLP: Thymic stromal lymphopoietin; Th2: T helper type 2.