DOI: 10.1148/radiol.2271010938
(Radiology 2003;227:107-112.)
© RSNA, 2003
Case 57: Eosinophilic Cholangiopathy1
Jean-Nicolas Vauthey, MD,
Evelyne Loyer, MD,
Parag Chokshi, MD and
Sandeep Lahoti, MD
1 From the Departments of Gastrointestinal Medical Oncology (P.C., S.L.), Surgical Oncology (J.N.V.), and Radiology (E.L.), University of Texas M.D. Anderson Cancer Center, Box 444, 1515 Holcombe Blvd, Houston, TX 77030. Received May 17, 2001; revision requested June 26; revision received August 27; accepted October 3. Address correspondence to J.N.V. (e-mail: jvauthey@mdanderson.org).
Index terms: Abdomen, CT, 70.1211, 70.12112, 70.12115 • Bile duct radiography, 76.11, 76.122 • Bile ducts, diseases, 76.7612 • Diagnosis Please • Gallbladder, diseases, 762.7612
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HISTORY
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A 44-year-old man was admitted to the hospital because of a 2-month history of fatigue, intermittent right upper quadrant abdominal and epigastric pain, and a 10-lb (4.5-kg) weight loss. One week before admission he had also developed obstructive jaundice. Physical examination disclosed no abnormalities except for scleral icterus and mild tenderness in the right upper quadrant of the abdomen. Liver function test results included increased alkaline phosphatase and total bilirubin levels. The total white blood cell count was 5 x 109/L (normal range, 4.0–11.0 x 109/L), with a differential cell count of 57% neutrophils (normal range, 42%–66%), 31% eosinophils (normal range, 1%–4%), and 12% lymphocytes (normal range, 24%–44%). Serologic test results for hepatitis A, B, and C were negative. Serologic test results for the human immunodeficiency virus and for Cryptosporidium organisms in the stool were negative. Results of stool tests for cysts and parasites were negative. Findings at transverse computed tomography (CT) of the abdomen and endoscopic retrograde cholangiography(ERC) showed a distal common bile stricture. A biliary stent was placed, and the patient was referred for consideration for pancreaticoduodenectomy. Multiphasic contrast material–enhanced CT of the abdomen with 3-mm reconstruction (Figs 1, 2) and repeat ERC (after stent removal) with common bile duct brushing (Fig 3) were performed. Endoscopic ultrasonography (US)–guided fine-needle aspiration of the common bile duct and celiac nodes yielded only scant cells. Brushing of the common bile duct was negative for malignant cells.
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Figure 1a. Contrast-enhanced transverse spiral CT scans of the abdomen. (a) Scan obtained at the level of the gallbladder fossa shows thickening of the wall of the gallbladder (arrowheads) and of the common hepatic duct (open arrows). Numerous small nodes are seen along the left gastric vein (short arrows). There is a stent (long arrow) in the common bile duct. (b) Scan obtained at the level of the fissure for the ligamentum venosum (umbilical fissure) shows diffuse low attenuation (arrowheads) of the portal tracts.
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Figure 1b. Contrast-enhanced transverse spiral CT scans of the abdomen. (a) Scan obtained at the level of the gallbladder fossa shows thickening of the wall of the gallbladder (arrowheads) and of the common hepatic duct (open arrows). Numerous small nodes are seen along the left gastric vein (short arrows). There is a stent (long arrow) in the common bile duct. (b) Scan obtained at the level of the fissure for the ligamentum venosum (umbilical fissure) shows diffuse low attenuation (arrowheads) of the portal tracts.
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Figure 2a. Contrast-enhanced transverse CT scans obtained at the level of the pancreas. (a) Scan shows that there is enlargement of the pancreatic head (arrows) without a mass. (b) Scan shows numerous small solid lesions (arrows) in the kidneys.
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Figure 2b. Contrast-enhanced transverse CT scans obtained at the level of the pancreas. (a) Scan shows that there is enlargement of the pancreatic head (arrows) without a mass. (b) Scan shows numerous small solid lesions (arrows) in the kidneys.
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Figure 3. Right posterior oblique ERC image shows diffuse tapered irregular narrowing of the distal common bile duct (arrowheads). Dilatation of the biliary tree proximal to the stricture and strictures (arrows) involving the intrahepatic ducts are visible.
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IMAGING FINDINGS
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Contrast-enhanced spiral CT of the abdomen with 3-mm reconstruction indicated diffuse thickening of the wall of the common hepatic duct extending to the intrahepatic ducts and thickening of the gallbladder wall (Fig 1a). A biliary stent was seen in the distal common bile duct; there was no hyperattenuating gallstone. There was low attenuation along the intrahepatic portal tracts, but the liver was otherwise normal (Fig 1b). The pancreatic head was enlarged but of normal attenuation and texture, and no mass could be identified (Fig 2a). Numerous small nodes were seen along the gastroepiploic vessels, in the gastrohepatic ligament, and along the splenic vessels (Fig 1a). At CT, mildly enlarged kidneys were depicted, and they contained multiple small hypoattenuating solid masses and wedge-shaped hypoattenuating areas (Fig 2b). At US, the kidneys were enlarged without definite masses.
At ERC after removal of the plastic stent, diffuse irregular tapered narrowing of the distal common bile duct was observed. The intrahepatic ducts were narrowed at the ductal confluences, without the classical beaded appearance of sclerosing cholangitis (Fig 3).
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DISCUSSION
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Eosinophilic cholangiopathy is a rare benign cause of biliary obstruction. To our knowledge, only 15 cases have been reported in the literature (1–12) (Table). The disease is characterized by a dense transmural eosinophilic infiltration of the biliary tract. Eosinophilic cholangiopathy can affect only the gallbladder (ie, eosinophilic cholecystitis); the gallbladder and bile ducts simultaneously; or, as reported in three cases, only the bile ducts (ie, eosinophilic cholangitis) (3,5,10). The cause is unknown. In more than half of the reported cases, the eosinophilic infiltration was not limited to the biliary tract but affected other organs as well. Eosinophilic cholangiopathy is part of a spectrum of diseases defined by eosinophilic infiltration of tissues and organs with or without peripheral eosinophilia. In this spectrum of diseases, all patients have in common an unexplained eosinophilic proliferation, but the severity and prognosis of the disease vary.
Several syndromes have been described in an attempt to classify this group of disorders. The idiopathic hypereosinophilic syndrome is characterized by persistence of eosinophil counts of at least 1.5 x 109/L for at least 6 months or any eosinophilia leading to death within 6 months, lack of a recognized cause for the eosinophilia, and organ system involvement or dysfunction due to eosinophilic infiltration or eosinophilia-associated damage. However, a wide spectrum of clinical expression is observed, from minor skin involvement to life-threatening cardiovascular, hematologic, and neurologic manifestations (13). Eosinophilic gastroenteritis is another entity characterized by eosinophilic infiltration of the wall of the gastrointestinal tract. Eosinophilic gastroenteritis is distinguished by involvement of one or more segments of the gastrointestinal tract, the presence of gastrointestinal symptoms, lack of a recognized cause for the eosinophilic infiltration, lack of extra digestive involvement, and inconstant peripheral eosinophilia (14). Clinically, however, the characteristics of hypereosinophilic syndrome and eosinophilic gastroenteritis overlap, as illustrated in the Table.
Regardless of the clinical presentation, the pathogenesis of eosinophilic infiltration is poorly understood. Patients with a more benign presentation tend to have immunologic abnormalities indicative of hypersensitivity (13). With eosinophilic cholangiopathy the disease appears to follow a benign course even when there is multifocal involvement. In 10 of 15 patients with eosinophilic cholangiopathy, treatment was limited to cholecystectomy; of the remaining five patients, four received steroids and only one required chemotherapy (Table). Our case is an illustration of multiple organ system involvement in association with eosinophilic cholangiopathy.
When eosinophilic cholangiopathy is limited to the gallbladder, the differential diagnosis will be acalculous cholecystitis. The diagnosis of eosinophilic cholecystitis is relevant in the absence of associated gallstones because treatment with steroids may avert the need for cholecystectomy. US findings of acalculous cholecystitis include luminal distension; thickened gallbladder wall, sometimes with striation; pericholecystic fluid; Murphy sign; lack of contractability; and sludge (15,16). The CT findings are similar, with the addition of stranding, pericholecystic edema, and decreased attenuation in the adjacent liver, which indicated perihepatitis.
The diagnosis of acalculous cholecystitis can be difficult because a thickened gallbladder wall at US or CT may be a result of nonbiliary causes, such as cardiac and renal failure, hepatitis, ascites, hypoalbuminemia, pancreatitis, and lymphatic obstruction (15). It can also be commonly seen in patients treated with interleukin 2 (17). Other conditions associated with a thickened gallbladder wall that need to be considered, at least from the radiographic standpoint, are as follows: hypertrophic cholecystosis, gallbladder carcinoma, and leukemic infiltration (18).
Acalculous cholecystitis is frequently caused by ischemia, and this usually occurs in debilitated patients (19). Acalculous cholecystitis can also be caused by infections, such as Helicobacter and Salmonella infections and, in the immunocompromised host, cytomegalovirus and cryptosporidiosis infections. Hypersensitivity cholecystitis with eosinophilic infiltration of the gallbladder wall after treatment with antibiotics has been reported (15). The diagnosis of eosinophilic cholecystitis cannot be suggested before surgery, unless peripheral eosinophilia is present.
Unlike the diagnosis of cholecystitis, the diagnosis of eosinophilic cholangiopathy is an essential consideration in the evaluation of cholangiopathy. Segmental or diffuse thickening of the wall of the biliary tree is a nonspecific feature directly visualized with cross-sectional imaging. It is seen with inflammatory and neoplastic processes and, as such, encompasses conditions that require different treatment. Thickening of the wall of the biliary tree usually but not always leads to biliary obstruction. The clinical evaluation in this setting should determine the likelihood of a benign or malignant process and help define the role of surgery.
With eosinophilic cholangiopathy, the bile duct wall is thickened, with or without biliary dilatation, at CT or US. Irregularities of the wall of the common bile duct and intrahepatic ducts are seen at ERC or transhepatic cholangiography. The ducts may be narrowed with a beaded pattern, which is suggestive of primary sclerosing cholangitis. If the disease is more focal, the dominant concern will be that of cholangiocarcinoma. Rosengart et al (3) reported a case of eosinophilic cholangiopathy mimicking a Klatskin tumor, and Tenner et al (1) reported the case of a patient with an isolated stricture of the common bile duct. The difficulty may be compounded if there is gastrointestinal tract involvement, which indicates the possibility of ulcerative colitis or Crohn disease associated with primary sclerosing cholangitis. Diffuse involvement can also be seen with lymphoma and metastatic disease. Rarely, patients with lymphoma have peripheral eosinophilia at presentation.
As in eosinophilic cholecystitis, there is no specific radiographic sign to suggest the diagnosis of eosinophilic cholangiopathy. If the patient has eosinophilia and/or extrabiliary involvement, the suspicion that the diagnosis is eosinophilic cholangiopathy will be high. Extrabiliary involvement has been previously reported in five of 15 patients with eosinophilic cholangiopathy (Table). Involvement of the gastrointestinal and urinary tracts, bone marrow, pancreas, and lymph nodes can occur. Renal involvement was reported in only one patient in the form of interstitial eosinophilic nephritis (11). With hypereosinophilic syndrome, renal involvement is rare (13). In one review, approximately 20% of the patients with hypereosinophilic syndrome had renal involvement (20). Interstitial nephritis and glomerular involvement have also been reported (13). We did not find any previous report of macroscopic lesions, such as the small masses seen at CT in our patient.
For our patient, the differential diagnosis included lymphoma with biliary, renal, and nodal involvement and acquired immunodeficiency syndrome cholangitis with renal infection. Collagen vascular disorders also may be associated with bile duct stricture and eosinophilia. Cholangiocarcinoma was also considered, but the regional extent with involvement of the entire biliary tree and lack of hepatic parenchymal atrophy would be unusual. Brushing of the common bile duct did not reveal malignant cells. Endoscopic US-guided fine-needle aspiration of the common bile duct and celiac nodes yielded only scant cells. CT-guided core biopsy of the liver revealed portal inflammation with scant eosinophils in the portal spaces. Serologic test results for human immunodeficiency virus and tests for Cryptosporidium organisms in the stool were negative. Special stains for lymphoma and for amyloidosis were negative (21). Further work-up included a search for parasites and immunologic studies to exclude collagen vascular disorders.
The diagnosis of eosinophilic cholangiopathy was determined on the basis of the anatomic findings, the presence of peripheral eosinophilia, the scant eosinophilic infiltration of the periportal spaces, and the lack of other causes. Extrabiliary involvement, pancreatic and renal, was established indirectly in view of the resolution of the radiologic abnormalities with steroid therapy. The patient was treated with prednisone, 40 mg a day for 8 weeks, with a rapid response. The patient gained 20 lb (9 kg), and his performance status was improved. At follow-up CT and ERC, the findings indicated improvement in resolution of the biliary strictures and resolution of the pancreatic and renal abnormalities (Figs 4, 5). The abnormalities that were indicated with liver function tests and the eosinophilia resolved. The biliary stricture resolved after 8 weeks of treatment. Periportal infiltration remained for a year (Fig 4b). The steroid dose was tapered during 3 months, and the patient has remained well without therapy for 18 months. The CT findings, hematologic abnormalities, and liver function tests results have now all returned to normal.
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Figure 4a. Contrast-enhanced transverse CT scans of the abdomen obtained after steroid treatment. (a) Scan at the level of the gallbladder fossa shows resolution of the thickening of the wall of the gallbladder (arrowheads) and common hepatic duct (open arrow). (b) Scan shows area of low attenuation (arrowheads) centered on the portal tracts remains. At follow-up 1 year later, scans showed complete resolution of the periportal infiltration. (c) Scan obtained at the level of the pancreas shows that the pancreatic head (arrows) returned to normal and the renal lesions disappeared.
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Figure 4b. Contrast-enhanced transverse CT scans of the abdomen obtained after steroid treatment. (a) Scan at the level of the gallbladder fossa shows resolution of the thickening of the wall of the gallbladder (arrowheads) and common hepatic duct (open arrow). (b) Scan shows area of low attenuation (arrowheads) centered on the portal tracts remains. At follow-up 1 year later, scans showed complete resolution of the periportal infiltration. (c) Scan obtained at the level of the pancreas shows that the pancreatic head (arrows) returned to normal and the renal lesions disappeared.
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Figure 4c. Contrast-enhanced transverse CT scans of the abdomen obtained after steroid treatment. (a) Scan at the level of the gallbladder fossa shows resolution of the thickening of the wall of the gallbladder (arrowheads) and common hepatic duct (open arrow). (b) Scan shows area of low attenuation (arrowheads) centered on the portal tracts remains. At follow-up 1 year later, scans showed complete resolution of the periportal infiltration. (c) Scan obtained at the level of the pancreas shows that the pancreatic head (arrows) returned to normal and the renal lesions disappeared.
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This case underscores the need for a high index of suspicion regarding a disorder with combined eosinophilic infiltration of the biliary tract and peripheral eosinophilia. Eosinophilic cholangiopathy is a rare cause of obstructive jaundice and can resolve completely with steroid therapy. The diagnosis can be determined on the basis of clinical evaluation and careful evaluation of imaging findings. The eosinophilic infiltration of the portal space may be subtle and needs to be searched for specifically by the pathologist.
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FOOTNOTES
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Part 1 of this case appeared 4 months previously and may contain larger images.
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REFERENCES
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- Tenner S, Roston A, Lichtenstein D, et al. Eosinophilic cholangiopathy. Gastrointest Endosc 1997; 45:307-309.[CrossRef][Medline]
- Albot G, Poilleux F, Oliver C. Les cholécystites a éosinophiles. Presse Med 1949; 57:558-559.[Medline]
- Rosengart TK, Rotterdam H, Ranson JH. Eosinophilic cholangitis: a self-limited cause of extrahepatic biliary obstruction. Am J Gastroenterol 1990; 85:582-585.[Medline]
- Leegaard M. Eosinophilic cholecystitis. Acta Chir Scand 1980; 146:295-296.[Medline]
- Song HH, Byun JY, Jung SE, et al. Eosinophilic cholangitis: US, CT, and cholangiography findings. J Comput Assist Tomogr 1997; 21:251-253.[CrossRef][Medline]
- Fox H, Mainwaring AR. Eosinophilic infiltration of the gallbladder. Gastroenterology 1972; 63:1049-1052.[Medline]
- Butler TW, Feintuch TA, Caine WP, Jr. Eosinophilic cholangitis, lymphadenopathy, and peripheral eosinophilia: a case report. Am J Gastroenterol 1985; 80:572-574.[Medline]
- Kerstein MD, Sheahan DG, Gudjonsson B, et al. Eosinophilic cholecystitis. Am J Gastroenterol 1976; 66:349-352.[Medline]
- Platt ML, Kiesling VJ, Jr, Vaccaro JA. Eosinophilic ureteritis associated with eosinophilic cholangitis: a case report. J Urol 1990; 144:127-129.[Medline]
- Scheurlen M, Mork H, Weber P. Hypereosinophilic syndrome resembling chronic inflammatory bowel disease with primary sclerosing cholangitis. J Clin Gastroenterol 1992; 14:59-63.[Medline]
- Grauer L, Padilla VM, III, Bouza L, et al. Eosinophilic sclerosing cholangitis associated with hypereosinophilic syndrome. Am J Gastroenterol 1993; 88:1764-1769.[Medline]
- Schoonbroodt D, Horsmans Y, Laka A, et al. Eosinophilic gastroenteritis presenting with colitis and cholangitis. Dig Dis Sci 1995; 40:308-314.[CrossRef][Medline]
- Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjomson BH. NIH conference: the idiopathic hypereosinophilic syndrome—clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med 1982; 97:78-92.[Abstract/Free Full Text]
- Talley NJ, Shorter RG, Phillips SF, et al. Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut 1990; 31:54-58.[Abstract/Free Full Text]
- Teffey SA. Sonography of complex gallbladder disease. Appl Radiol 1992; 22:32-42.
- Zeman RK. Cholelithiasis and cholecystitis. In: Gore RM, Levine MS, eds. Textbook of gastrointestinal radiology. 2nd ed. Philadelphia, Pa: Saunders, 1994; 1321-1345.
- Premkumar A, Walworth CM, Vogel S, et al. Prospective sonographic evaluation of interleukin-2-induced changes in the gallbladder. Radiology 1998; 206:393-396.[Abstract/Free Full Text]
- Finlay DE, Mitchell SL, Letourneau JG, et al. Leukemic infiltration of the gallbladder wall mimicking acute cholecystitis. AJR Am J Roentgenol 1993; 160:63-64.[Free Full Text]
- Babb RR. Acute acalculous cholecystitis: a review. J Clin Gastroenterol 1992; 15:238-241.[Medline]
- Chusid MJ, Dale DC, West BC, et al. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine 1975; 54:1-27.[Medline]
- Irie H, Honda H, Kaneko K, et al. Primary malignant lymphoma in the porta hepatis: a case report. Abdom Imaging 1996; 21:448-450.[CrossRef][Medline]
Congratulations to the 41 individuals who submitted the most likely diagnosis (eosinophilic cholangitis/eosinophilic cholangiopathy) for Diagnosis Please, Case 57. The names and locations of the individuals, as submitted, are as follows:
- Gholamali Afshang, MD, Tinley Park, Ill
- Dr Jorge Ahualli, Tucumán, Argentina
- Albert J. Alter, Madison, Wis
- Edward L. Baker, MD, San Francisco, Calif
- Ken Baliga, Rockford, Ill
- Farid Ben Chehida, MD, Tunis-Jabari, Tunisia
- Hanna Blom Breivik, MD, Drammen, Norway
- Peter Buetow, MD, Bellingham, Wash
- Manuel Cabal Naranjo, MD, Yucatan, Mexico
- Nelson M. G. Caserta, MD, São Paulo, Brazil
- Antonio Cavalcanti, MD, São Paulo, Brazil
- James W. Cole, MD, Cincinnati, Ohio
- André Noël Dardenne, MD, Brussels, Belgium
- Manoel de Souza Rocha, MD, São Paulo, Brazil
- Mustafa Kemal Demir, MD, Ataköy, Istanbul, Turkey
- Ian Doris, Hamilton, Ontario, Canada
- Mario Finazzo, Palermo, Italy
- Yukihiro Hama, MD, Tokorozawa, Japan
- Eric Kinder, MD, Seattle, Wash
- John T. Lim, MD, Newport Coast, Calif
- N. B. S. Mani, MD, Nassau, Bahamas
- Luis Mendez-Uriburu, Tucumán, Argentina
- Karl F. R. Neufang, MD, Euskirchen, Germany
- Michael O’Loughlin, MD, West Hartford, Conn
- Sanford M. Ornstein, MD, Phoenix, Ariz
- David M. Panicek, MD, New York, NY
- Harish Panicker, MD, Detroit, Mich
- Danny Rappaport, Toronto, Ontario, Canada
- James Ravenel, MD, Charleston, SC
- Taro Shimono, MD, Osaka, Japan
- Paolo Siotto, MD, Cagliari, Italy
- Stephen Horatio Slawson, RPh, MD, Peoria, Ill
- Kouichi Sugiyama, Shizuoka, Japan
- Ingrid Svergja, MD, Drammen, Norway
- Douglas L. Teich, MD, Brookline, Mass
- Eugene Tong, MD, Austin, Tex
- Meriç Tüzün, Ankara, Turkey
- Christopher Vittore, MD, Rockford, Ill
- Jeff West, MD, Jacksonville, Fla
- Joe Yut, Olathe, Kan
- Jeffrey H. Zapolsky, MD, Oshkosh, Wis
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HISTORY
IMAGING FINDINGS
