European Journal of Cardiovascular Medicine

Eosinophilic gastrointestinal disorders (EGIDs) are a group of chronic, immune-mediated conditions characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of known secondary causes such as parasitic infection, inflammatory bowel disease, or drug reactions【1】. Among these, eosinophilic esophagitis (EoE) is now recognized as a distinct clinicopathological entity, previously misclassified as a variant of gastroesophageal reflux disease (GERD)【2】. EoE is a Th2-predominant, antigen-driven disorder, in which chronic eosinophil-rich inflammation leads to esophageal dysfunction, including dysphagia and food impaction【3】. Notably, the esophagus is physiologically devoid of eosinophils; hence, their presence is inherently pathological【4】. While most patients with EoE and eosinophilic duodenitis exhibit atopic tendencies such as asthma, eczema, or allergic rhinitis, cases in non-atopic individuals are uncommon and diagnostically challenging【5】. This report discusses an unusual presentation of duodenal eosinophilia with suspected EoE in a non-atopic adult male, emphasizing the expanding spectrum of EGIDs and the need for thorough clinical evaluation.               

The patient is a 36-year-old male presenting with a one-year history of persistent upper gastrointestinal and systemic symptoms. Chief complaints include chronic sore throat, a constant sensation of pressure in the throat, especially during meals and a feeling of food being stuck that often recurs postprandially. These are accompanied by a persistent sour sensation in the throat and frequent episodes of pressure-like headaches that intensify while eating, along with a sensation of fuzziness in the head and light-induced blurry vision. Over the past 3–4 months, the patient has experienced significant unintentional weight loss of 12 kg, despite maintaining a healthy routine that includes regular exercise and home-cooked meals.

Gastrointestinal symptoms are prominent, with marked bloating, trapped gas, and alternating bowel habits ranging from constipation to diarrhea, with a sense of incomplete evacuation. He reports three bowel movements daily on average, often associated with a feeling of abdominal discomfort and heaviness in the left lower back and thigh. The patient also complains of general body weakness and a persistent sore throat that has not responded to standard antacid therapy. His blood pressure has been managed with Amlodipine 5 mg since September 2024 for non-compliant hypertension. A Holter study was within normal limits, and the patient denies any history of asthma, diabetes, or thyroid disorders.

An upper GI endoscopy (OGD) was performed, revealing multiple concentric rings and longitudinal furrows throughout the esophagus, raising suspicion for eosinophilic esophagitis. The GE junction was at 39 cm with the Z-line at 36 cm. The gastric mucosa (fundus, body, and antrum) appeared erythematous, and the pyloric opening was noted to be tight and spastic. In the duodenum, D1 appeared normal, whereas D2–D3 showed congested and edematous mucosa. Multiple biopsies were taken from both the esophagus and the duodenum. A rapid urease test for H. pylori was negative.

Histopathological examination of the duodenal biopsy revealed mildly blunted villi with focal epithelial desquamation. There was infiltration of the lamina propria by lymphocytes, plasma cells, and a significant number of eosinophils (30–32 per high-power field). No degranulated eosinophils or eosinophilic infiltration of the glands or epithelial lining was observed. The findings suggest eosinophilic duodenitis, though differential diagnoses such as drug-induced inflammation, parasitic infections, hypereosinophilic syndrome, Crohn’s disease, milk protein enteropathy, and other systemic conditions must also be considered. The esophageal biopsy revealed mild spongiosis, basal cell hyperplasia, and rare eosinophils, with no significant eosinophilic infiltration or fungal elements.

The overall clinical, endoscopic, and histological findings point towards a diagnosis of duodenal eosinophilia with suspected eosinophilic esophagitis, forming a part of the eosinophilic gastrointestinal disorders (EGIDs) spectrum. Further multidisciplinary evaluation is warranted to confirm the diagnosis, rule out secondary causes, and formulate a long-term management plan involving dietary therapy, pharmacologic intervention, and follow-up endoscopic surveillance.

 Table 1: Investigations

Table 2: Investigations

Table 3: Positive Findings

Table 4: Positive Findings

Differential Diagnosis:

• GERD
• Functional GI disorder
• Food allergy
• Celiac disease
• IBD
• Eosinophilic gastroenteritis

Diagnosis

Confirmed diagnosis based on clinical features, endoscopic findings, and histopathology Eosinophilic esophagitis with coexisting mild gastroduodenitis.

Management and Outcome

The patient was advised the following dietary and pharmacological regimen:

Dietary Modifications: Avoid spicy and oily foods, Refrain from large, heavy meals

Medications (for 3 weeks):

1. Nexpro-IT – Once daily before food
2. Famocid 40 mg – Once daily before food
3. Allegra-M – Once daily after food
4. Raniraft / Gaviraft – 10 mL after food, three times a day
5. Rejunex CD3 – Once daily after food

Note: Patient was strictly advised not to discontinue medications without medical consultation.

Follow-up: A review visit was scheduled after 3 weeks to reassess clinical response and determine the need for further evaluation or continuation of therapy.

Eosinophilic gastrointestinal disorders (EGIDs) comprise a spectrum of chronic, immune-mediated conditions marked by selective eosinophilic infiltration of the gastrointestinal (GI) tract in the absence of identifiable secondary causes such as parasitic infections, drug reactions, or systemic eosinophilic syndromes【6】. These disorders are generally driven by type 2 (Th2) immune responses, often triggered by food or environmental allergens【7】.

Among EGIDs, eosinophilic esophagitis (EoE) is the most studied and well-defined subtype, with established diagnostic criteria and two FDA-approved therapies. In contrast, non-EoE EGIDs—including eosinophilic gastritis (EG), duodenitis (EoD), and gastroenteritis (EGE)—remain less understood, with no approved pharmacologic treatments to date【8】. Clinical manifestations vary based on the site of involvement, and although a history of atopic disease is frequently observed, non-atopic presentations such as in our patient are increasingly being recognized【9】.

Emerging research suggests that mast cells, alongside eosinophils, may play a contributory role in symptom generation in EGIDs. Lirentelimab (AK002), an anti-Siglec-8 monoclonal antibody, has shown promise in early studies by depleting eosinophils and inhibiting mast cell activity, providing a potential novel treatment avenue for patients with eosinophilic gastritis and duodenitis【10】.

Although large-scale epidemiologic data remain scarce, U.S. health insurance datasets estimate prevalence rates of 6.3 per 100,000 for eosinophilic gastritis and 8.4 per 100,000 for eosinophilic gastroenteritis【11】. However, the actual prevalence is likely underestimated due to diagnostic challenges, heterogeneity of symptoms, and limited clinical awareness【12】.

The diagnosis of eosinophilic gastroenteritis (EGE) is based on three key criteria: the presence of GI symptoms, histologic evidence of eosinophilic infiltration in one or more regions of the GI tract, and the exclusion of other potential causes of tissue eosinophilia【13】. Most patients respond well to conservative approaches, including dietary elimination (such as a six-food elimination or elemental diet) and corticosteroids【14】. Biologic therapies targeting IL-5 or IgE pathways (e.g., mepolizumab, omalizumab) have demonstrated reductions in eosinophil counts but limited clinical benefit in symptom resolution【15】.

Clinicians should maintain a high index of suspicion for food allergies as a potential underlying cause of gastrointestinal symptoms, even in the adult population. When evaluating persistent or atypical cases of dyspepsia or suspected GERD, eosinophilic gastrointestinal disorders should be included in the differential diagnosis. Early upper GI endoscopy, coupled with targeted tissue biopsies, plays a crucial role in confirming the diagnosis and initiating timely management. Prompt identification and intervention can significantly reduce morbidity and prevent long-term gastrointestinal complications.

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