Eosinophilic Duodenitis: A Pediatric Case Misinterpreted as Acute Pancreatitis

A 13-year-old girl presented with epigastric pain, vomiting, and abdominal discomfort accompanied by raised levels of amylase and lipase. Despite acute pancreatitis suspicion, worsening eosinophilia without a known cause led to further examination, revealing eosinophilic duodenitis via histopathology. Treatment with oral prednisone tapering resulted in symptom resolution. At 1-year follow-up, the patient remained symptom-free. This case highlights the need to consider non-EoE EGIDs in children with peripheral blood eosinophilia and duodenal wall thickening to avoid misdiagnosis and ensure proper treatment. 

The patient, a 13-year-old girl, presented with a week-long history of abdominal distension (bloating and swelling in the belly area), vomiting, and epigastric pain, which had progressively worsened. Pain in the abdominal area was described as continuous, with a severity rating of 3–4 on the Abdominal Pain Severity - Numeric Rating Scale (APS-NRS). She had a history of persistent epigastric aches over the past 10 years, unresponsive to acid-reducing agents.

Eosinophilic gastrointestinal disorders (EGIDs) beyond eosinophilic esophagitis (non-EoE EGIDs) are a poorly understood group of chronic inflammatory conditions that can markedly impact the gastrointestinal (GI) tract. These disorders often present diagnostic challenges due to their nonspecific symptoms and overlap with other GI conditions. Marked by eosinophil-rich inflammation in the mucosa, these disorders disrupt organ function in ways that are still shrouded in mystery. The spectrum of non-EoE EGIDs encompasses eosinophilic gastritis (EoG), eosinophilic colitis (EoC), and eosinophilic enteritis (EoN)—which branches into eosinophilic duodenitis (EoD), jejunitis (EoJ), and ileitis (EoI).

While their exact cause remains elusive, allergic responses to dietary antigens are suspected in a few cases. Symptoms can vary dramatically depending on which part of the GI tract is impacted, the intensity of eosinophilic infiltration, and how deeply the inflammation penetrates the bowel wall. Without definitive biological markers, diagnosis relies heavily on clinical assessment and histological findings, posing a unique challenge for clinicians.

Although non-EoE EGIDs are rare in children and rarely life-threatening, they demand attention for their potential to masquerade as other conditions. As pediatricians delve deeper into the complexities of these disorders, there’s growing interest in refining diagnostic strategies for timely intervention. This case report presents the first case of EoD associated with a concurrent pancreatic reaction, which was initially misdiagnosed as acute pancreatitis, leading to a delay in diagnosis and intervention.

(a) Preliminary investigation:

• The patient presented with:

(i) 1-week history of abdominal distension, vomiting, and epigastric pain.

(ii) Continuous abdominal pain (APS-NRS score 3-4), no diarrhea or fever.

(iii) Recurrent epigastric pain for 10 years, unrelieved by acid-reducing agents.

• Growth and development were normal, with no signs of growth retardation or delayed puberty (stature, weight, body mass index [BMI] within normal range for age).

(b) Medical history:

• No allergic diseases (e.g., asthma, atopic dermatitis, allergic rhinitis).
• She had no exposure to any pets.

(c) Physical assessment:

• All findings were normal, except for tenderness in the epigastric area.
• No abdominal masses were palpated.

(d) Investigations:

• Abdominal ultrasound: Mild pancreatic duct dilatation and mild ascites (74 × 40 mm).
• Vital signs upon hospitalization: Stable with blood pressure 122/75 mmHg, pulse rate 78 beats/minute, body temperature 36.9 °C, and respiratory rate 20 breaths/minute.
• Laboratory findings:

(i) Elevated white blood cell (WBC) count: 1.385 × 10^4/mm³ (normal: 0.4-1.0 × 10^4/mm³).
(ii) High eosinophil percentage: 16.5% (normal: 0.5-5%).
(iii) Mildly elevated serum amylase: 256.6 U/L (normal: 40-132 U/L).
(iv) Mildly elevated serum lipase: 134.4 U/L (normal: 0-67 U/L).
(v) Normal levels of alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), alkaline phosphatase, cholesterol, bilirubin, and triglycerides.
(vi) Urine test: Elevated amylase levels at 1921.7 U/L (normal: 0-490 U/L).
(vii) Fecal examination: Negative for ova and parasites on two separate tests.
 

(e) Imaging findings:

• Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) illustrated diffuse wall thickening of the antrum and duodenum (signifying inflammation).
• Mild dilatation of common bile duct and pancreatic duct.
• Few ascites.
• No intestinal obstruction, gallstones, or pancreatic swelling.

(a) Initial management:

• The girl was hospitalized for acute pancreatitis and supportive care was commenced.
• This included goal-directed intravenous fluids and restoration of electrolyte and metabolic abnormalities.
• Due to the mild severity of her pancreatitis, supplemental nutrition was not considered necessary.
• Instead, a low-residue, low-fat, and soft diet was introduced within 24 hours as tolerated, given the reduction in pain and the absence of ileus, significant nausea, or vomiting.

(b) Follow-up after 2 weeks:

• Over the course of 2 weeks, the patient’s abdominal symptoms gradually improved, and her serum amylase levels normalized, indicating resolution of acute pancreatitis.
• Nonetheless, mild epigastric tenderness remained despite improvement in other symptoms.
• Laboratory data revealed an unexpected increase in blood eosinophil levels after 2 weeks:

(i) Eosinophil percentage rose to 31.5% (normal range: 0.5–5%).

(ii) Eosinophil count increased to 2.55 × 10³/µL (normal range: 0.05–0.5 × 10³/µL).

• The increase in eosinophilia was unexplained, as there was no obvious cause identified for the elevation during her hospitalization.
   

(c) Suspected EoD:

• Persistent peripheral eosinophilia prompted investigation for EoD, leading to esophagogastroduodenoscopy (EGD). 
• EGD findings:

(i) Mucosal edema observed on the gastric antrum and ampulla.

(ii) Diffuse mucosal erythema present in the duodenum's second portion.

(iii) Pylorus appeared normal with no signs of pyloric stenosis.

• Biopsy samples from the gastric antrum and duodenum were sent for histopathological investigation. The analysis revealed:

(i) Peak eosinophil count of 10 per high-power field (HPF) in the mucosal lining of the gastric antrum.

(ii) Peak eosinophil count of 120 per HPF in the duodenal mucosa, exceeding the cutoff of ≥50 eosinophils/HPF for diagnosis of EoD.

• Histopathological analysis findings:

(i) Chronic inflammatory changes in the mucosa accompanied by prominent eosinophils.

(ii) Eosinophilia extended into the muscularis mucosa and submucosa, particularly from the erythematous duodenal lesion.

(iii) No eosinophil crypt abscesses were detected.

• Helicobacter pylori (H. pylori) testing on the gastric mucosa biopsy was negative.
• Allergy examinations showed:

(i) Normal serum immunoglobulin E (IgE) level of 19.7 kIU/L.

(ii) No elevated IgE titers specific to food allergens or aeroallergens.

• The final diagnosis was EoD based on the clinical, endoscopic, histopathological, and allergy test findings.
   

(d) Treatment for EoD:

• Initiated oral prednisone therapy (40 mg/day for 2 weeks, tapered by 5 mg weekly).
• Achieved rapid symptom resolution and prominent reduction in eosinophil counts (from 2.55 × 10³/µL to 0.3 × 10³/µL).

(e) Follow-up:

• 1-week follow-up: Normal lab results, abdominal ultrasound showed resolution of ascites, no symptom relapse.
• 1-year follow-up: Patient remained symptom-free without recurrence.
• Patient declined repeat endoscopy; regular serum eosinophil testing continued.

Non-EoE EGIDs are rare immune-mediated GI disorders in children, characterized by upper and lower GI symptoms. Diagnosis is based on clinical signs and histologic evidence of eosinophilic inflammation after excluding secondary causes or systemic illnesses. Importantly, GI segment-specific eosinophil thresholds play a fundamental role in confirming a non-EoE EGIDs diagnosis, ensuring accuracy in differentiating these ailments from other inflammatory or immune-linked conditions.

In this case report, the 13-year-old girl presented with a puzzling combination of symptoms. Imaging offered some clues—mild dilation of the common bile and pancreatic ducts—but no striking signs of pancreatic swelling or peripancreatic fluid that would confirm acute pancreatitis. The plot thickened with a 7-day history of abdominal discomfort and enzyme levels that, while elevated, fell short of the diagnostic threshold for acute pancreatitis (≥3 times the upper limit of normal). Despite imaging not supporting acute pancreatitis, the possibility of resolving pancreatic inflammation remained, presenting a diagnostic challenge.

Elevated amylase and lipase levels are rare in non-EoE EGIDs in children, increasing the risk of diagnostic errors. Few adult cases of non-EoE EGIDs with acute pancreatitis have been reported, with similar findings of elevated enzymes without gallstones. In this case study, abdominal CT and MRCP exhibited no evidence of pancreatic or biliary duct obstructions. However, the elevated pancreatic enzyme levels during symptomatic episodes, combined with normal alkaline phosphatase and bilirubin levels, pointed to eosinophilic infiltration of the GI tract causing subtle pancreatic duct injury.

The authors hypothesized that pancreatic inflammation resulted from obstruction of the pancreatic duct at the site where it enters the thickened and inflamed duodenal wall, rather than direct extension of inflammation to the pancreas. Imaging-supported dilation of the pancreatic duct corroborated this hypothesis. Initially, peripheral eosinophilia was overlooked, delaying diagnosis and intervention. Indicators like duodenal wall thickening on imaging and elevated eosinophils in blood can guide healthcare professionals toward this diagnosis. Parasitic infection was also explored but ruled out.

Notably, 2 separate stool examinations illustrated no ova or parasites. Moreover, the patient reported no exposure to potential sources such as meat, raw or undercooked fish, shellfish, or contaminated vegetables. The rapid resolution of symptoms and normalization of eosinophil counts after prednisone use further diminished the likelihood of parasitic etiology, though appropriate serological tests would have yielded better diagnostic certainty. Rarely, inflammatory bowel diseases (IBD) like Crohn's disease or ulcerative colitis may present with peripheral eosinophilia and eosinophil-rich tissue infiltrates.

However, these ailments are typically distinguished from EGIDs by findings such as crypt abscesses, architectural distortion, and granulomas in tissue biopsies. For detecting non-EoE EGIDs in patients, peak eosinophil counts are employed as GI segment-specific threshold levels. Interestingly, the GI mucosa can appear non-specific, or even normal, in many instances of non-EoE EGIDs during endoscopy. For this reason, it is strongly advocated to procure multiple biopsies from the affected GI segments, including the gastric antrum, gastric body, and duodenum, and to sample both normal-appearing and abnormal-appearing mucosal areas.

For diagnosis, peak eosinophil counts are typically ≥30 per HPF for EoG and ≥50 per HPF for EoD.  In this case study, the girl was diagnosed with EoD based on the combination of clinical signs, histological findings, and the exclusion of other GI conditions that could arouse eosinophilic inflammation. Imaging studies, though not directly diagnosing EoD, provide crucial insights for identifying affected areas and guiding biopsy. In this case, increased thickness of the duodenal wall on CT, stimulated by eosinophilic infiltration, was a key diagnostic clue initially overlooked.

Mild acute pancreatitis typically doesn't affect the GI wall, with wall swelling seen only in severe cases. This case highlights the rarity of conditions like EoG/EoN and the importance of including them in the differential diagnosis when GI symptoms and eosinophilic inflammation are present. On the basis of predominantly affected intestinal layers, Klein et al. classified EoN into 3 subtypes: mucosal, muscular, and subserosal. In situations where the inflammatory process is confined to the mucosal layer, the most common symptoms encompass abdominal pain, diarrhea, nausea,  vomiting, with potential complications like protein loss and iron deficiency anemia.

When the muscular layer is involved, patients may present with obstructive symptoms like abdominal distension and severe constipation. Additionally, more severe manifestations like intussusception or bowel perforation may occur. Subserosal involvement is typically connected with ascites. This case likely represents the mucosal type, given the predominant symptoms of recurrent epigastric pain and vomiting. Although the girl had obstructive symptoms like abdominal distension, she lacked signs of muscular disease, such as perforation or intussusception.

Additionally, there was no evidence of subserosal eosinophilic infiltration or hypereosinophilia in ascitic fluid. Therefore, the girl does not fit the muscular or subserosal classifications. Systemic oral steroids are crucial for both clinical and histological remission in kids battling non-EoE EGIDs, as shown in several studies. Oral prednisone is commonly advocated at a dose of 0.5–1 mg/kg (up to 40 mg) for 2 weeks to induce remission, followed by a gradual dose reduction over 2–8 weeks. Few patients may relapse after stopping therapy, requiring maintenance treatment at a lower dose for long-term care.

Topical steroids like budesonide are useful in tackling non-EoE EGIDs, particularly in EoE and EoG, due to their local anti-inflammatory effects on the mucosal surface. They are now advocated for maintenance therapy to prevent relapses, as they have a low risk of long-term side effects. Food allergen elimination diets might benefit children affected with EoN or EoC, though data on histologic response and long-term outcomes is lacking. Additionally, ensuring diet adherence and preventing nutritional deficiencies can be challenging during prolonged treatment.

Learning

Non-EoE EGIDs should be considered in children with duodenal wall thickening and peripheral blood eosinophilia on imaging. Accurate diagnosis requires careful examination of pathologic specimens and regular monitoring of eosinophil counts, as the condition is rare. Management includes initiating oral prednisone for remission, followed by long-term maintenance therapy, ongoing symptom monitoring, and histological evaluation to prevent recurrences and complications.