Differentials

Gastro-oesophageal reflux disease (GORD)

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SIGNS / SYMPTOMS

Clinical presentation can overlap with eosinophilic oesophagitis (EoO) and both conditions can be present in the same patient.

No single sign or symptom distinguishes the conditions; however, erosive oesophagitis and a hiatal hernia are less common in EoO than in GORD. EoO can cause secondary reflux due to strictures or oesophageal dysmotility.

GORD may impact EoO by worsening oesophageal mucosal barrier function and potentially providing a route for antigen presentation.

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Oesophagogastroduodenoscopy: may show oesophagitis, erosions, ulcerations, strictures.

pH or pH/impedance testing: pH <4 more than 4% of the time with acid or non-acid reflux events.

Eosinophilic gastroenteritis

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Patients often have gastrointestinal symptoms not directly attributed to the oesophagus such as abdominal pain, nausea, weight loss, gastrointestinal bleeding, diarrhoea, malabsorption, or protein-losing enteropathy.

Oesophageal involvement may be present.

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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 EoO.

Achalasia

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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 oesophageal contents.

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Oesophagogastroduodenoscopy: dilated oesophagus with retained secretions and a hypertonic lower oesophageal sphincter.

Barium swallow: classic bird beak-like appearance.

Oesophageal manometry: incomplete relaxation of the lower oesophageal sphincter and oesophageal aperistalsis.

Crohn's disease

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Oesophageal involvement is rare. Gastric, small bowel, and/or colonic involvement is likely to be present.

Patients with Crohn's disease often have prolonged diarrhoea, perianal lesions, blood in stools, and fever.

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Oesophagogastroduodenoscopy and biopsy: oesophageal ulcerations, intramural oesophageal tracts, oesophagobronchial fistulae, non-caseating granuloma.

Colonoscopy or wireless capsule endoscopy: aphthous ulcers, hyperaemia, oedema, cobblestoning, skip lesions.

Connective tissue disorders

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Inflammatory arthritis, psoriasis or psoriatic arthritis, or skin changes suggestive of lupus or scleroderma may be seen, depending on the underlying condition.

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Auto-antibody tests: positive (corresponding to the specific connective tissue disorder).

Hypereosinophilic syndrome

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Symptoms reflective of end-organ tissue infiltration by eosinophils.

Constitutional symptoms are common.

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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

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Acute onset after drug exposure, or as an idiosyncratic reaction to an established medication.

Common causative medications include antimalarials, antibiotics, ACE inhibitors, anticonvulsants, non-steroidal anti-inflammatory drugs, gold, proton-pump inhibitors, H2 receptor antagonists, tryptophan, aminosalicylates, and chlorpropamide.

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Removal of the medication: resolution of eosinophilia.

Pill oesophagitis

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Acute onset after a history of having a pill stick in the oesophagus after swallowing.

Frequently reported with doxycycline and other antibiotics, non-steroidal anti-inflammatory drugs, and bisphosphonates.

Chest discomfort and odynophagia are typical. Resolves within several weeks with supportive therapy.

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Oesophagogastroduodenoscopy: focal findings or reveals impacted pill.

Graft-versus-host disease

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History of bone marrow or stem cell transplant.

Can involve the entire gastrointestinal tract, including the liver, as well as the skin.

INVESTIGATIONS

Oesophagogastroduodenoscopy: may show gastric, duodenal, or colonic erythema, congestion, or ulceration.

Parasitic infections

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May be a history of travel, pet exposure, or unsafe drinking water (depending on the parasite).

Often associated with diarrhoea, abdominal pain, anaemia, or fever.

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Peripheral eosinophil count: typically elevated.

Stool or serology testing: confirms diagnosis of suspected pathogen.

Adrenal insufficiency

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Rare cause of systemic eosinophilia.

Symptoms are non-specific and can include dizziness, nausea, weight loss, and even abdominal pain.

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Peripheral eosinophil count: may be elevated.

Adrenocorticotropic hormone stimulation test: serum cortisol <497 nanomols/L (<18 micrograms/dL) confirms diagnosis.

Infectious oesophagitis

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Presentation tends to be more acute.

Associated with fever, odynophagia, and oral lesions.

INVESTIGATIONS

Oesophagogastroduodenoscopy: with tissue sampling: confirms presence of Candida, herpes simplex virus, or cytomegalovirus.

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