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:
FeatureFrequency
Abdominal pain (epigastric, may radiate to back)Most common
Nausea and vomitingCommon
Peripheral blood eosinophilia~70% of cases
Elevated serum amylase/lipasePresent
Atopic history~50%
Obstructive jaundice (pancreatic head mass)Occasional
Diarrhea, weight loss (if co-existing EGE)Variable
EP can present as:
  1. Acute recurrent pancreatitis - most common presentation
  2. Pancreatic mass lesion - mimicking cancer (especially pancreatic head involvement)
  3. 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)

FeatureEPAIP Type 1 (IgG4-related)
Peripheral eosinophiliaCommonLess common
Serum IgG4NormalElevated
HistologyEosinophilic infiltrateLymphoplasmacytic + storiform fibrosis
Other EGIDMay co-existNo

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
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