Rare Presentation of Eosinophilic Cholangitis in a 32-Year-Old Man

ABSTRACT

Eosinophilic cholangitis (EC) is a rare condition characterized by eosinophilic infiltration of the bile ducts, often mimicking diseases like primary sclerosing cholangitis or cholangiocarcinoma. We report the case of a 32-year-old man with severe epigastric pain and elevated liver function tests. Initial imaging revealed common bile duct dilation and multiple strictures, initially suggestive of primary sclerosing cholangitis. Multiple endoscopic retrograde cholangiopancreatographies with brushings showed benign cytology but revealed polysomy on fluorescence in situ hybridization. A biopsy confirmed EC. High-dose corticosteroids led to significant clinical improvement. This case underscores the importance of considering EC in the differential diagnosis of biliary diseases, as timely diagnosis and treatment can lead to excellent outcomes.

INTRODUCTION

Obstructive jaundice occurs when a blockage in the bile ducts impedes the normal flow of bile from the liver to the intestines, leading to symptoms such as jaundice, abdominal pain, pruritus, dark urine, and pale stools.¹ Common etiologies include gallstones, biliary strictures, primary sclerosing cholangitis (PSC), and malignancies like cholangiocarcinoma.² Eosinophilic cholangitis (EC) is a rare inflammatory disorder characterized by eosinophilic infiltration of the biliary tree, causing bile duct obstruction.³ Due to its rarity and nonspecific presentation, EC is often overlooked in the differential diagnosis of obstructive jaundice. Here, we report the case of a 32-year-old man presenting with symptoms of biliary obstruction who was ultimately diagnosed with EC.

CASE REPORT

A 32-year-old man with a history of major depressive disorder presented with a 3-day history of severe postprandial epigastric pain radiating to the lower chest. He reported belching, nausea, constipation, and reduced appetite but denied fever, vomiting, or hematochezia. Laboratory tests revealed significant transaminitis and hyperbilirubinemia (total bilirubin 2.7 mg/dL, direct bilirubin 2.1 mg/dL, alkaline phosphatase 263 U/L, aspartate transaminase 286 U/L, alanine transaminase 659 U/L). His complete blood count at presentation showed white blood cells 3.59 × 10³/µL, hemoglobin 14.8 g/dL, platelets 310 × 10³/µL, neutrophils 49%, lymphocytes 34%, monocytes 10%, eosinophils 6%, and basophils 1%. An abdominal ultrasound showed a collapsed, thick-walled gallbladder without cholelithiasis and borderline common bile duct dilation up to 6 mm.

Magnetic resonance cholangiopancreatography suggested irregularities in the biliary tree consistent with PSC and choledocholithiasis in the right posterior hepatic ducts and common hepatic duct (Figure 1). Endoscopic retrograde cholangiopancreatography (ERCP) was performed but was complicated by difficult biliary cannulation, necessitating the placement of pancreatic and cystic duct stents (Figure 1). Due to multiple unsuccessful attempts at biliary cannulation and concern for potential creation of a false tract, a decision was made to place a stent the cystic duct to protect the patient from developing cholecystitis. In addition, a pancreatic duct stent was placed to facilitate further attempts at biliary access. Sphincterotomy was also performed to improve bile drainage. Subsequent ERCP revealed a severe inflammatory biliary stricture in the common hepatic duct and sludge in the biliary tree (Figure 2). Cytology was benign, but fluorescence in situ hybridization (FISH) indicated polysomy.

Figure 1.

(A) Magnetic resonance cholangiopancreatography with abnormal configuration of the mid common bile duct with abrupt caliber change as well as intrahepatic biliary ductal dilatation, suggesting stricture, (B) intra operative fluoroscopic image depicting multiple dilated bile ducts suggesting strictures, (C) postendoscopic retrograde cholangiopancreatography stenting fluoroscopic image depicting bile ducts, which appear patent and relieve of obstruction.

Figure 2.

SpyGlass cholangioscopy view showing an inflammatory stricture within the common bile duct.

A repeat ERCP with cholangioscopy showed diffuse irregularity and beading of the intrahepatic ducts, raising concerns for PSC vs autoimmune cholangiopathy. Serum immunoglobulin G4 (IgG4) levels were mildly elevated at 106.1 mg/dL. Biopsies revealed biliary mucosa with significant eosinophilic infiltration (∼100 eosinophils per high-power field). These findings were consistent with EC (Figure 3).

Figure 3.

Histological section from bile duct biopsy showing dense infiltration of eosinophils within the bile duct wall, accompanied by inflammatory cell infiltration.

The patient was started on prednisone 40 mg daily for 4 weeks, followed by a gradual taper. He reported significant symptom improvement, and follow-up ERCP 2 months later showed marked improvement in the biliary strictures. Repeat biopsies demonstrated a reduction in eosinophilic infiltration (<50 eosinophils/high-power field). Liver function tests normalized, and the patient remained symptom-free during follow-up.

DISCUSSION

First described by Leegaard et al in 1980, EC is an exceedingly rare inflammatory cause of obstructive jaundice.^1,2 Histopathologically, EC is characterized by dense eosinophilic infiltrate in the bile ducts, leading to biliary obstruction. While peripheral eosinophilia is a notable feature, it is absent in approximately 35% of cases. The exact prevalence of EC is not well-established due to its rarity and potential underdiagnosis, with only 31 cases having been identified between 1985 and 2014.^2,3 Although the etiology of EC remains unclear, it has been associated with allergic conditions, autoimmune diseases, parasitic infections, and drug reactions.⁴

EC poses significant diagnostic challenges due to its clinical presentation and imaging findings, which often mimic those of more common biliary diseases such as PSC, cholangiocarcinoma, and IgG4-related sclerosing cholangitis (SC).^5,6 Walter et al reported that EC was present in 2.2% of all patients with SC. Notably, among patients with SC and irritable bowel syndrome in whom no other etiology was identified, EC accounted for 30% of cases.²

In our patient, IgG4 levels were elevated, raising concerns for IgG4-related SC. However, histological analysis did not reveal the lymphoplasmacytic infiltrate that is characteristic of IgG4-related disease, making this distinction crucial in confirming the diagnosis of EC.⁷

Currently, there is no consensus on the diagnostic criteria for EC. Matsumoto et al proposed a diagnostic triad that includes biliary ducts wall thickening or stenosis, eosinophilic infiltration on biopsy, and resolution of biliary abnormalities with or without steroid therapy.⁸ Our patient fulfilled all 3 criteria. Imaging studies, including magnetic resonance cholangiopancreatography and ERCP, demonstrated biliary wall thickening and stenosis. Histopathological analysis confirmed significant eosinophilic infiltration of the bile ducts. After corticosteroid therapy, the patient showed notable clinical and radiological improvement, indicating reversibility of the biliary abnormalities. As such we can infer that referral to an expert center for eosinophilic content assessment in indeterminate biliary strictures should be considered in cases where standard diagnostics fail to establish a clear etiology. Criteria for referral may include (i) persistent or recurrent biliary strictures without a definitive cause on imaging and histology; (ii) peripheral eosinophilia or elevated serum IgE in the absence of an alternative explanation; (iii) clinical suspicion of EC in the setting of steroid responsiveness; and (iv) need for specialized histopathologic evaluation, including eosinophil quantification and IgG4 immunostaining, to differentiate EC from malignancy or IgG4-related disease. Expert centers may also offer advanced cholangioscopy or molecular diagnostics to further characterize the stricture. Failure to make a timely diagnosis of EC can lead to significant complications. EC is characterized by eosinophilic infiltration of the biliary tract, which can cause biliary strictures, fibrosis, and obstruction. If left untreated, these conditions can mimic more severe diseases such as PSC or cholangiocarcinoma, leading to unnecessary surgical interventions. There have been no documented cases in the literature to our knowledge that ended up needing transplantation. In our study, FISH analysis was performed due to the initial concern for cholangiocarcinoma, given the biliary strictures resembling malignancy. In PSC, polysomy detected by FISH is associated with a higher risk of cholangiocarcinoma.⁹ However, its significance in EC is unclear. Despite the presence of polysomy in our patient, multiple biopsies showed no malignancy, and corticosteroid therapy led to clinical and radiologic improvement, suggesting an inflammatory rather than neoplastic process. This highlights the need to interpret FISH results cautiously in non-PSC biliary strictures.

The management of EC remains a topic of debate due to its rarity and lack of standardized guidelines. Some literature suggests that surgical resection, such as Roux-en-Y hepaticojejunostomy, offers a definitive approach to prevent recurrence and avoid complications from prolonged steroid use.^10,11 However, this invasive approach carries significant risks, prompting many clinicians to recommend a trial of corticosteroids to achieve complete symptom resolution before considering surgery.^5,11–13 Our patient's positive response to steroid therapy supports the effectiveness of noninvasive medical management in achieving symptom resolution and reversing biliary abnormalities. That being said, the choice of corticosteroid therapy in EC should be individualized based on disease severity and patient-specific factors. Prednisone, with its higher systemic bioavailability, is often preferred in severe cases requiring broader immunosuppression.¹⁴ Budesonide, due to its extensive first-pass hepatic metabolism, offers a safer alternative with fewer systemic side effects and has been successfully used in EC.¹² Given the lack of standardized guidelines, treatment decisions should balance disease severity, patient comorbidities, and the risk of steroid-related adverse effects. About biliary strictures, such as those seen in PSC or postliver transplantation, repeat ERCP with balloon dilation is often required. For example, in PSC, repeated balloon dilatation is common, with some patients requiring multiple procedures over several years to manage dominant strictures.^7,15 Given the lack of specific data on EC, it is reasonable to infer that a similar approach may be necessary, with repeat ERCP and balloon dilation performed as needed based on clinical response and recurrence of symptoms. However, precise numbers or percentages specific to EC cannot be provided from current literature. The last resort for these strictures is probably surgery; however, surgical intervention in EC is primarily considered in cases of suspected malignancy, as EC can closely mimic cholangiocarcinoma, leading to surgical resection when malignancy cannot be excluded.² In addition, severe disease progression, including worsening biliary strictures or associated cholecystitis, may require surgical intervention if medical therapy fails.³ In some cases, persistent strictures unresponsive to steroids necessitate surgical or endoscopic management to relieve obstruction.¹²

This case underscores the importance of including EC in the differential diagnosis of biliary obstruction. Timely recognition and treatment with corticosteroids can lead to favorable outcomes, reducing the need for invasive procedures and unnecessary surgeries. Increasing awareness of EC among clinicians is crucial to enhance diagnostic accuracy and optimize patient care. Continued documentation of similar cases and further research are essential to establish standardized diagnostic criteria and treatment protocols for this rare condition, ultimately improving outcomes for affected patients.

DISCLOSURES

Author contributions: H. Khataniar was the primary author. He was involved in critical revision of the manuscript and approved the final version of submission. M. Ruiz was involved in literature review and drafting of the initial manuscript. H. Habib created the final version of the manuscript for submission. A. Dharia and S. Magoo assisted in editing the case report and critical revision of the manuscript. A. Kulkarni was actively involved in the acute care and follow-up of the patient. He was also involved in critical revision of the manuscript. H. Khataniar is the article guarantor.

Financial disclosure: None to report.

Previous presentation: This case was presented at the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania on October 24th, 2024.

Informed consent was obtained for this case report.