Esosinopholic pancreatitis
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eosinophilic pancreatitis
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eosinophilic pancreatitis diagnosis treatment
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PMID: 34026218
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PMID: 31120859
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PMID: 41801837
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Eosinophilic Pancreatitis (EP)
Definition and Overview
Eosinophilic pancreatitis is an extremely rare form of pancreatitis defined by predominantly eosinophilic infiltration of pancreatic tissue (>10 eosinophils per high-power field on histology), after secondary causes have been excluded. It accounts for less than 1% of all pancreatitis cases and is prone to misdiagnosis as pancreatic cancer or autoimmune pancreatitis due to overlapping clinical and imaging features.
EP exists on a spectrum with broader eosinophilic GI disorders (EGIDs):
- Isolated EP - eosinophilic infiltration limited to the pancreas
- EP associated with eosinophilic gastroenteritis (EGE) - pancreatic involvement as part of diffuse GI eosinophilic infiltration
- EP in hypereosinophilic syndrome (HES) - multi-organ eosinophilic infiltration including pancreas
Etiology and Pathogenesis
EP is believed to be driven by Th2-mediated immune mechanisms, similar to other EGIDs:
- Th2 cytokines (IL-4, IL-5, IL-13, eotaxin) recruit and activate eosinophils in the pancreatic tissue
- IL-5 is the primary cytokine promoting eosinophil proliferation, maturation, and survival
- About 50% of patients have an atopic history (allergic rhinitis, asthma, eczema, food allergy)
- Food antigens may trigger disease in sensitized individuals
- Mast cells play a co-pathogenic role alongside eosinophils
Secondary causes that must be excluded before diagnosing primary EP:
- Parasitic/helminthic infections (Ascaris, toxocara, anisakis)
- Drug hypersensitivity
- Inflammatory bowel disease
- Myeloproliferative disorders / hypereosinophilic syndrome
- IgG4-related disease (autoimmune pancreatitis type 1)
- Polyarteritis nodosa / eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss)
Clinical Features
EP typically presents acutely or as recurrent episodes of pancreatitis:
| Feature | Frequency |
|---|---|
| Abdominal pain (epigastric, may radiate to back) | Most common |
| Nausea and vomiting | Common |
| Peripheral blood eosinophilia | ~70% of cases |
| Elevated serum amylase/lipase | Present |
| Atopic history | ~50% |
| Obstructive jaundice (pancreatic head mass) | Occasional |
| Diarrhea, weight loss (if co-existing EGE) | Variable |
EP can present as:
- Acute recurrent pancreatitis - most common presentation
- Pancreatic mass lesion - mimicking cancer (especially pancreatic head involvement)
- Chronic pancreatitis with ductal changes
A 2026 case report (Li et al., Am J Case Rep 2026) described a 68-year-old man with recurrent severe abdominal pain, found on EUS-FNA to have ~15 eosinophils/HPF in the pancreas, co-existing with subclinical EGE discovered on routine upper endoscopy.
Diagnosis
Diagnosis is challenging and often delayed. The key elements are:
1. Laboratory Findings
- Peripheral eosinophilia (>500 cells/mm³, often markedly elevated)
- Elevated serum amylase and lipase
- Elevated serum IgE in atopic patients
- Serum IgG4 should be checked to exclude IgG4-related pancreatitis (which may coexist)
2. Imaging
- CT/MRI: diffuse or focal pancreatic enlargement, peripancreatic edema, pancreatic duct dilation, rarely a mass lesion
- MRCP: may show ductal abnormalities
- EUS: can detect focal lesions; allows FNA for tissue diagnosis
3. Histopathology (definitive)
-
10 eosinophils/HPF on pancreatic tissue
- Eosinophilic infiltration of acini, ductal epithelium, and interstitium
- Obtained via EUS-guided fine-needle aspiration (EUS-FNA) or surgical biopsy
- Many patients historically underwent surgery to exclude malignancy before EP was recognized
4. Diagnostic Criteria (Sun et al. 2021)
Based on a review of 19 cases, proposed criteria include:
- Recurrent or acute pancreatitis with no other cause
- Peripheral eosinophilia
- Exclusion of secondary causes
- Histological confirmation of eosinophilic infiltration (>10/HPF)
- Response to corticosteroid therapy
Distinguishing EP from Autoimmune Pancreatitis (AIP Type 1)
| Feature | EP | AIP Type 1 (IgG4-related) |
|---|---|---|
| Peripheral eosinophilia | Common | Less common |
| Serum IgG4 | Normal | Elevated |
| Histology | Eosinophilic infiltrate | Lymphoplasmacytic + storiform fibrosis |
| Other EGID | May co-exist | No |
Treatment
EP responds dramatically and rapidly to corticosteroids - this is both therapeutic and diagnostically supportive.
First-line:
- Prednisolone/prednisone 0.5-1 mg/kg/day orally for 2-6 weeks, then taper
- Symptoms typically resolve within days to weeks
- Pancreatic duct dilation and imaging abnormalities resolve with treatment
Adjunct/dietary:
- Elemental diet or elimination diet (especially if food allergens are identified by skin prick testing or specific IgE)
- Allergen avoidance if a specific trigger is identified
Refractory or steroid-dependent disease:
- Azathioprine or 6-mercaptopurine as steroid-sparing agents
- Lirentelimab (anti-Siglec-8 monoclonal antibody, targeting eosinophils and mast cells) is a promising emerging therapy showing efficacy in EGIDs broadly - Goldman-Cecil Medicine, 7th ed.
- Benralizumab (anti-IL-5 receptor alpha) trials are underway for EGIDs including EP
Surgery is generally NOT required but was historically performed due to misdiagnosis as cancer.
Prognosis
- Response to steroids is usually excellent
- Relapses are common when steroids are tapered, necessitating maintenance therapy or steroid-sparing agents
- A 2019 systematic review (Pinte & Baicus, Rom J Intern Med 2019) analyzing 45 patients found that those with co-existing EGE on histology tended to avoid unnecessary surgery, while isolated EP patients frequently underwent pancreatic resection before the diagnosis was established
- Long-term prognosis is generally favorable with appropriate immunosuppression
Key Takeaways
- EP is a rare but important diagnosis to consider in any patient with pancreatitis + peripheral eosinophilia, especially with atopy
- It is frequently misdiagnosed as pancreatic cancer or AIP, leading to unnecessary surgery
- EUS-FNA is the preferred minimally invasive method for histological confirmation
- Corticosteroids are curative in most cases
- Always exclude secondary causes: parasites, drugs, HES, IgG4-related disease, EGPA
Sources:
- Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th ed. (Eosinophilic Gastritis, Enteritis, and Gastroenteritis)
- Goldman-Cecil Medicine, International Edition
- Sun Y et al., Gastroenterol Rep 2021 - Review of pathophysiology, diagnosis, and treatment (PMID 34026218)
- Pinte L & Baicus C, Rom J Intern Med 2019 - Systematic review, EP vs EGE-associated pancreatitis (PMID 31120859)
- Li X et al., Am J Case Rep 2026 - Recurrent EP with EGE, 2026 (PMID 41801837)
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