Differentials
Gastroesophageal reflux disease (GERD)
SIGNS / SYMPTOMS
Clinical presentation can overlap with eosinophilic esophagitis (EoE) and both conditions can be present in the same patient.
No single sign or symptom distinguishes the conditions; however, erosive esophagitis and a hiatal hernia are less common in EoE than in GERD. EoE can cause secondary reflux due to strictures or esophageal dysmotility.
GERD may impact EoE by worsening esophageal mucosal barrier function and potentially providing a route for antigen presentation.
INVESTIGATIONS
Esophagogastroduodenoscopy: may show esophagitis, erosions, ulcerations, strictures.
pH or pH/impedance testing: pH <4 more than 4% of the time with acid or nonacid reflux events.
Eosinophilic gastroenteritis
SIGNS / SYMPTOMS
Patients often have gastrointestinal symptoms not directly attributed to the esophagus such as abdominal pain, nausea, weight loss, gastrointestinal bleeding, diarrhea, malabsorption, or protein-losing enteropathy.
Esophageal involvement may be present.
INVESTIGATIONS
Gastric, duodenal, ileal, and/or colonic biopsies: increased levels of eosinophils (threshold varies by location). Eosinophilic infiltration of other areas of the gastrointestinal tract is not present in EoE.
Achalasia
SIGNS / SYMPTOMS
Chronic liquid and solid food dysphagia.
Can be associated with weight loss, heartburn, regurgitation (especially with lying flat), and aspiration pneumonias.
Eosinophilia is thought to be due to a reactive process from stasis of esophageal contents.
INVESTIGATIONS
Esophagogastroduodenoscopy: dilated esophagus with retained secretions and a hypertonic lower esophageal sphincter.
Barium swallow: classic bird beak-like appearance.
Esophageal manometry: incomplete relaxation of the lower esophageal sphincter and esophageal aperistalsis.
Crohn disease
SIGNS / SYMPTOMS
Esophageal involvement is rare. Gastric, small bowel, and/or colonic involvement is likely to be present.
Patients with Crohn disease often have prolonged diarrhea, perianal lesions, blood in stools, and fever.
INVESTIGATIONS
Esophagogastroduodenoscopy and biopsy: esophageal ulcerations, intramural esophageal tracts, esophagobronchial fistulae, noncaseating granuloma.
Colonoscopy or wireless capsule endoscopy: aphthous ulcers, hyperemia, edema, cobblestoning, skip lesions.
Connective tissue disorders
SIGNS / SYMPTOMS
Inflammatory arthritis, psoriasis or psoriatic arthritis, or skin changes suggestive of lupus or scleroderma may be seen, depending on the underlying condition.
INVESTIGATIONS
Autoantibody tests: positive (corresponding to the specific connective tissue disorder).
Hypereosinophilic syndrome
SIGNS / SYMPTOMS
Symptoms reflective of end-organ tissue infiltration by eosinophils.
Constitutional symptoms are common.
INVESTIGATIONS
Peripheral eosinophil count: ≥1.5 x 10⁹ cells/L (1500/mm³).
Bone marrow aspirate: positive. PDGFR-alpha/FIP1L1 gene mutation: positive.
Evidence of eosinophil infiltration of other organs and exclusion of other causes of systemic eosinophilia.
Drug hypersensitivity
SIGNS / SYMPTOMS
Acute onset after drug exposure, or as an idiosyncratic reaction to an established medication.
Common causative medications include antimalarials, antibiotics, ACE inhibitors, anticonvulsants, nonsteroidal anti-inflammatory drugs, gold, proton-pump inhibitors, H2 receptor antagonists, tryptophan, aminosalicylates, and chlorpropamide.
INVESTIGATIONS
Removal of the medication: resolution of eosinophilia.
Pill esophagitis
SIGNS / SYMPTOMS
Acute onset after a history of having a pill stick in the esophagus after swallowing.
Frequently reported with doxycycline and other antibiotics, nonsteroidal anti-inflammatory drugs, and bisphosphonates.
Chest discomfort and odynophagia are typical. Resolves within several weeks with supportive therapy.
INVESTIGATIONS
Esophagogastroduodenoscopy: focal findings or reveals impacted pill.
Graft versus host disease
SIGNS / SYMPTOMS
History of bone marrow or stem cell transplant.
Can involve the entire gastrointestinal tract, including the liver, as well as the skin.
INVESTIGATIONS
Esophagogastroduodenoscopy: may show gastric, duodenal, or colonic erythema, congestion, or ulceration.
Parasitic infections
SIGNS / SYMPTOMS
May be a history of travel, pet exposure, or unsafe drinking water (depending on the parasite).
Often associated with diarrhea, abdominal pain, anemia, or fever.
INVESTIGATIONS
Peripheral eosinophil count: typically elevated.
Stool or serology testing: confirms diagnosis of suspected pathogen.
Adrenal insufficiency
SIGNS / SYMPTOMS
Rare cause of systemic eosinophilia.
Symptoms are nonspecific and can include dizziness, nausea, weight loss, and even abdominal pain.
INVESTIGATIONS
Peripheral eosinophil count: may be elevated.
Adrenocorticotropic hormone stimulation test: serum cortisol <18 micrograms/dL confirms diagnosis.
Infectious esophagitis
SIGNS / SYMPTOMS
Presentation tends to be more acute.
Associated with fever, odynophagia, and oral lesions.
INVESTIGATIONS
Esophagogastroduodenoscopy: with tissue sampling: confirms presence of Candida, herpes simplex virus, or cytomegalovirus.
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