Muscular and serosal eosinophilic gastritis and enteritis with eosinophilic ascites successfully treated with dupilumab

Abstract

Primary eosinophilic gastrointestinal disorders beyond the esophagus (EGIDs) are rare, predominantly Th2‐mediated inflammatory conditions, affecting various segments of the gastrointestinal tract. We report the case of a 12‐year‐old boy with recurrent abdominal pain, peripheral eosinophilia, and progressive gastritis, duodenitis, and enteritis with eosinophilic ascites. He was diagnosed with extensive EGID with muscular and serosal involvement. He was treated with oral corticosteroids and milk elimination diet, which provided temporary relief, but relapses prompted the addition of dupilumab, which achieved durable remission. To our knowledge, this is the first reported case demonstrating the effectiveness of this monoclonal antibody in EGIDs with serosal involvement and eosinophilic ascites. This case highlights the therapeutic potential of dupilumab in refractory EGID cases involving deeper gastrointestinal layers.

1. INTRODUCTION

Primary eosinophilic gastrointestinal disorders beyond the esophagus (EGIDs) are rare chronic inflammatory diseases characterized by eosinophilic infiltration of the gastrointestinal tract. While often considered Th2‐mediated, some non‐esophageal variants may involve dominant Th1‐mediated responses. ¹

EGIDs are classified by location: eosinophilic gastritis (EoG), enteritis (EoN—duodenitis [EoD], jejunitis [EoJ], and ileitis [EoI]), and colitis (EoC). ² Symptoms depend on the gastrointestinal segment involved, the extent of inflammation, and the depth of eosinophilic infiltration. ³

Recent consensus guidelines for EGIDs exist, but therapeutic evidence remains limited. ³ Systemic corticosteroids are effective in the short term, but relapses are common. Elimination diets or topical corticosteroids have shown limited efficacy as maintenance therapy. Dupilumab, a monoclonal antibody blocking the common receptor component for interleukin‐4 (IL4) and interleukin‐13 (IL13), has emerged as a promising alternative for refractory patients, promoting clinical and histological remission. ¹

2. CASE REPORT

A 12‐year‐old adolescent with a history of atopy presented with 1 month of periumbilical pain and nausea. Blood tests showed peripheral eosinophilia (800 eosinophils/µL), abdominal ultrasound showed thickening of the first and second duodenal segments with minimal adjacent free fluid, and upper endoscopy was macroscopically normal but revealed esophageal eosinophilia (20 eosinophils/high power field). He was treated with omeprazole 40 mg/day for 2 weeks with clinical improvement and persistence of mild duodenal thickening (Figure 1).

Figure 1.

Peripheral eosinophilia expressed in microL (µL) across the clinical course.

Eight months later, in another country, the patient presented again with abdominal pain. Ultrasound suggested appendiceal phlegmon and ascitic fluid. Peripheral eosinophilia reached 2590 eosinophils/µL. An appendectomy was performed, although the histopathologic analysis of the surgical specimen was not available. Abundant ascitic fluid was drained, showing normal biochemical analysis, though cell count was not performed. The patient's symptoms resolved, and the follow‐up ultrasound was normal, except for mild persistent duodenal thickening. Peripheral eosinophilia decreased to 403 eosinophils/µL 5 months postoperatively.

One year after surgery, he was admitted to our hospital with severe abdominal pain and intractable vomiting, with peripheral eosinophilia up to 1800 eosinophils/µL. Abdominal ultrasound and computed tomography (CT) showed marked thickening of the pylorus, gastric antrum, duodenum, and jejunum, and a small amount of free fluid (Figure 2). Upper and lower endoscopy were macroscopically and microscopically normal.

Figure 2.

Abdominal ultrasound showing: A: Mural thickening and hypercogenicity of the pyloric antrum. B: Mural thickening and hyperecogenicity of the first portion of the duodenum, with peripheral edema and a small amount of fluid around the duodenum. C: Abdominal computed tomography (CT) with coronal reformat shows thickening of the second (D2), third (D3), and fourth (D4) portions of the duodenum as well as the jejunum (J). Abdominal intraperitoneal fluid is also seen.

EGID with pyloric obstruction was suspected after ruling out other causes of eosinophilia (negative parasitic serology and stool microscopy, normal hematologic assessment). He was started on intravenous corticosteroids, with clinical improvement within 48 h. He was discharged on tapering oral prednisone and milk elimination diet as maintenance treatment.

Five months after corticosteroid withdrawal, he presented severe abdominal pain and vomiting, with peripheral eosinophilia up to 900 eosinophils/µL and ultrasound evidence of nonspecific enteritis with abundant ascites (Figure 3). Paracentesis of ascitic fluid revealed a leukocyte count of 4160 cells/µL with 70% eosinophils, confirming the diagnostic suspicion of extensive EGID involving the muscular and serosal layers.

Figure 3.

Abdominal ultrasound showing intraperitoneal ascites.

Oral prednisone was reinitiated and, due to rapid relapse despite the milk elimination diet, subcutaneous dupilumab at 300 mg/week was started leading to resolution of symptoms and normalization of peripheral eosinophilia.

At the 6‐month follow‐up, the patient was asymptomatic, with only mild mural thickening of the gastric antrum on ultrasound. Dupilumab was continued at a dose of 300 mg every 2 weeks. Despite limited clinical efficacy, a dairy‐free diet was maintained at the family's request. To date, there has been no recurrence of gastrointestinal symptoms after 11 months of treatment.

3. DISCUSSION

We report a case of extensive EGID (EoG, EoD, and EoJ) successfully treated with dupilumab. To our knowledge, this is the first reported case demonstrating the efficacy of this monoclonal antibody in EGIDs with serosal involvement and eosinophilic ascites.

EGIDs are rare diseases, with mucosal involvement being the most common presentation and muscle and serosal involvement being even rarer. EGIDs can cause a wide range of symptoms and signs, including abdominal pain, vomiting, diarrhea, bowel obstruction, bloating, ascites, malnutrition, or strictures. ³ Diagnosis requires a compatible clinical presentation, an eosinophilic infiltrate in gastric or intestinal biopsies exceeding normal values for each region of the gastrointestinal tract, and exclusion of other eosinophilia‐associated diseases. ³

In the present case, gastric and intestinal mucosal biopsies were normal, likely due to predominant muscular and serosal layer involvement. Although muscle biopsy was not performed due to the patient's clinical condition, eosinophil‐predominant ascitic fluid significantly aided in confirming the diagnosis. While peripheral eosinophilia lacks sensitivity and specificity to confirm the diagnosis of EGIDs, it proved useful for monitoring disease progression, as demonstrated in this case. ³

Regarding management, induction treatment with systemic corticosteroids is effective in the short term in most EGID patients, ³ but relapses are frequent and significantly impact their quality of life. Empirical elimination diets and topical corticosteroids are used as maintenance therapy to reduce prolonged systemic corticosteroid exposure; however, evidence supporting their efficacy is limited. ³ In this case, topical corticosteroids were unsuitable due to the presence of eosinophilic infiltration in deeper layers. Therefore, an empirical milk elimination diet was started, which failed to prevent relapse after corticosteroid withdrawal.

Dupilumab is a monoclonal antibody targeting IL‐4 and IL‐13 signaling that has shown efficacy and is approved for the treatment of eosinophilic esophagitis. Dupilumab may potentially be useful in EGIDs, as transcriptomic analysis of the stomach (EoG) and duodenum (EoD) has demonstrated upregulation of IL‐4, IL‐5, IL‐13, eotaxin‐3 (CCL26), and mast cell signature genes (CPA3), consistent with findings in patients with EoE. ¹

Evidence for the efficacy of dupilumab in EGIDs is limited to case reports and case series. ⁴ , ⁵ , ⁶ , ⁷ , ⁸ , ⁹ , ¹⁰ These reports show clinical, endoscopic, and histologic improvement in children and adults with EGIDs involving the gastrointestinal mucosa (including duodenal ulceration) and, in some cases, the muscular layer with pyloric stenosis. The extent of involvement varies, mainly affecting the stomach and small intestine. Our case is unique because of the extent of the involvement and the eosinophilic infiltration of deeper layers of the gastrointestinal tract, complicated by eosinophilic ascites. The patient initially responded to systemic corticosteroids but experienced a rapid recurrence of abdominal pain, vomiting, and ascites, necessitating hospitalization after corticosteroid withdrawal.

4. CONCLUSION

In our patient, administration of dupilumab was associated with sustained clinical, radiological, and hematologic response, without significant adverse events, suggesting its potential effectiveness in treating refractory EGIDs with serosal involvement.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

ETHICS STATEMENT

Informed written consent was obtained from parents for publication; they are aware of and agree with the intent for this article to be published.

Sánchez‐Ramírez A, García‐Díaz A, García‐Martínez de Bartolomé R, et al. Muscular and serosal eosinophilic gastritis and enteritis with eosinophilic ascites successfully treated with dupilumab. JPGN Rep. 2026;7:132‐136. 10.1002/jpr3.70113