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Hepatology Research 2015; 45: 595–600
doi: 10.1111/hepr.12380
Case Report
Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case Daisuke Hokuto, Ichiro Yamato, Takeo Nomi, Satoshi Yasuda, Shinsaku Obara, Takatsugu Yamada, Kawaguchi Chihiro and Yoshiyuki Nakajima Department of Surgery, Nara Medical University, Nara, Japan
Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected
sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.
INTRODUCTION
May 2010. There were no clear causes of this dilation on images, so he was kept under observation. In September 2011, he developed cholangitis and magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the lower bile duct and irregularity of the intrahepatic bile duct (Fig. 1a). The cholangitis was cured by
E
OSINOPHILIC CHOLANGITIS IS a rare disease caused by eosinophilic infiltration into the wall of the bile duct. Imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. However, eosinophilic cholangitis is typically improved by treatment with steroids, so its accurate diagnosis is very important. We report a case of eosinophilic cholangitis coexisting with idiopathic thrombocytopenic purpura (ITP). Treatment with steroid for the ITP affected the progress of the eosinophilic cholangitis.
Key words: eosinophilic cholangitis, eosinophilic cholecystitis, idiopathic thrombocytopenic purpura
a
b
CASE REPORT
I
N A 73-YEAR-OLD man who had been treated for diabetes mellitus and had a postoperative status of prostatic cancer and right renal cell carcinoma from another hospital, dilation of intrahepatic bile ducts was identified by abdominal computed tomography (CT) in
Correspondence: Dr Daisuke Hokuto, Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Email: [email protected] Conflict of interest: The authors have no conflict of interest. Received 27 May 2014; revision 19 June 2014; accepted 23 June 2014.
© 2014 The Japan Society of Hepatology
Figure 1 (a) Findings of magnetic resonance cholangiopancreatography. Stricture of the lower bile duct and irregularity of the intrahepatic bile duct were seen. (b) Findings of endoscopic retrograde cholangiopancreatography. Stricture of the lower bile duct was seen, and scraping cytology showed no malignancy.
595
596 D. Hokuto et al.
Hepatology Research 2015; 45: 595–600\
antibiotics, and he was referred to our hospital under the diagnosis of cancer of the bile tract in October 2011. Endoscopic retrograde cholangiopancreatography revealed stenosis of the lower bile duct (Fig. 1b), and scraping cytology showed no malignancy. We followed him by MRCP every 3 months and there was no remarkable change in the images. In that same period, thrombocytopenia was seen in his peripheral blood and he was diagnosed with ITP. He was treated using prednisolone, and recovery from the thrombocytopenia occurred. On the other hand, the proportion of eosinophils in his peripheral blood exhibited an inverse course compared with the platelet count (Fig. 2a). In November 2012, the administration of prednisolone at a dose
(a)
of 10 mg/day was unexpectedly interrupted. In December 2012, he frequently exhibited cholangitis. In that period, we thought that the main cause of the cholangitis was benign stenosis of the distal bile duct. Endoscopic retrograde biliary drainage (ERBD) was performed. However, the ERBD tube was removed unexpectedly 2 weeks after insertion. The patient was admitted with high fever (38.5°C) and jaundice (serum bilirubin, 4.1 mg/dL) on 1 January 2013. CT revealed wall thickening and swelling of the gallbladder. We diagnosed him with acute cholecystitis due to stenosis of the lower bile duct (Fig. 3). We assessed that the stenosis was a benign lesion, and complete resection of the stenotic legion required pancreatoduodenectomy.
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Figure 2 (a) Changes in the proportion of eosinophils and platelet count in peripheral blood. While prednisolone was administrated, the proportion of eosinophils was low and the platelet count was high. (b) Changes in the serum alkaline phosphatase (ALP) level. On 12 December 2012, sudden interruption of the administration of prednisolone caused a severe increase of the ALP level, which was not improved even after operation. Re-administration of prednisolone decreased the ALP level. (c,d) Changes in the serum γ-glutamyltransferase (γ-GT) and total bilirubin levels. Their courses were similar to that of the ALP level. (a) , eosinophils (%); , platelets (×10/μL); (b) , ALP (IU/L); (c) , γ-GT (IU/L); (d) , total bilirubin (mg/dL).
© 2014 The Japan Society of Hepatology
Eosinophilic cholangitis
Hepatology Research 2015; 45: 595–600\
In addition, we performed cholecystectomy and choledochojejunostomy on 4 January 2013. We resected the common bile duct between the superior border of the pancreas and the hepatic side of the cystic duct. Minor bile leakage occurred, but the patient was discharged on postoperative day 42. Pathologically, marked eosinophilic infiltration along with abundant lymphocytes and plasma cell were observed in the surgically resected bile duct and gallbladder (Fig. 4). Even after the operation, the levels of serum bilirubin, alkaline phosphatase (ALP), and γ-glutamyltransferase (γ-GT) were still higher than normal. In addition, the proportion of eosinophils in peripheral blood was markedly higher than normal. Finally, we diagnosed him with eosinophilic cholangitis, and prednisolone started to be administrated at 20 mg/day. The proportion of eosinophils immediately normalized, and the levels of serum bilirubin, ALP and γ-GT improved slowly (Fig. 2b–d). The dose of prednisolone was decreased
597
a
×100 b
a
×400
Figure 4 Microscopic findings of bile duct showed marked eosinophilic infiltration (hematoxylin–eosin, original magnifications: [a] ×100; [b] ×400).
b
gradually, and its administration was stopped in October 2013. Retrospectively, we considered that the frequent cholangitis in December 2012 and the acute cholecystitis on 1 January 2013 had been caused by the sudden interruption of prednisolone at a dose of 10 mg/day.
DISCUSSION
E
Figure 3 Findings of computed tomography. (a) Wall thickening and stenosis of the distal bile duct were seen. (b) Edema and swelling in the wall of the gallbladder were also seen.
OSINOPHILIC CHOLANGITIS WAS first reported as a disease involving eosinophilic infiltration into the bile duct and/or gallbladder with eosinophilia of peripheral blood in 1985.1 Only 31 cases have been reported, as determined from a search of PubMed (1985 to April 2014), and a strategy for its diagnosis and treatment has not been well established. Eosinophilic
© 2014 The Japan Society of Hepatology
Year
1985 1990
1990 1993 1997 1997 2000 2001
2001 2001
2009 2009
2009 2010
2010
2012 2014
2013
1992 1995 2003 2003 2005 2007 2007 2007 2008 2009 2009 2013 2014
First author
Butler1 Platt3
Rosengart4 Grauer5 Song6 Tenner7 al-Abdulla8 Rodgers9
Shanti10 Shanti10
Chen11 Miura12
© 2014 The Japan Society of Hepatology
Raptou13 Dubay14
Nashed15
Kroemer16 Seown17
Our case
Scheurlen18 Schoonbroodt19 Jimenez-Saenz20 Vauthey21 Duseja22 Jeyamani23 Jeyamani23 Matsumoto24 Sussman25 Horiuchi26 Iwamuro27 Kimura28 Vainer29 30 20 67 44 16 13 26 38 52 45 66 48 15
73
49 63
33
24 29
55 46
57 33
48 41 48 38 42 50
32 42
Sex
M F F M F M M F M M F M M
M
M M
M
M F
M M
F M
M M F F F F
M F
Age
5 057 1 411 2 068 1 550 11 340 1 500 5 900 719 13 300 9 914 14 315 2 264 Not mentioned
6 500
Not mentioned 1 900
108
1 471 630
823 117
79 261
246 1 647 408 2 200 1 674 Not mentioned
14 212 Not mentioned
Eosinophils (/uL)
Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct
Stricture of distal bile duct
Stricture of distal bile duct Stricture of distal bile duct
Stricture of proximal bile duct
Stricture of intrahepatic bile duct Stricture of proximal bile duct
Stricture of proximal bile duct Stricture of distal bile duct
Stricture of distal bile duct Stricture of proximal bile duct
Stricture of proximal bile duct Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct
Diffuse biliary stricture Diffuse biliary stricture
Image of bile duct
Table 1 The 31 reported cases of eosinophilic cholangitis in PubMed (1985 to April 2014)
Absent Absent Present Absent Absent Absent Absent Absent Present Absent Absent Absent Absent
Present
Absent Absent
Absent
Absent Absent
Present Present
Absent Absent
Present Absent Present Present Present Absent
Present Absent
Cholecystitis
Done Done Done Done Done Done Done Done Done Done Done Done Done
Done (after operation)
– –
–
– –
Done (after operation) –
– –
– Done (after operation) – Done (after operation) Done (after operation) –
– –
Treatment with corticosteroids
Cholecystectomy Choledochotomy + cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Choledochotomy + cholecystectomy Choledochotomy Choledochotomy + cholecystectomy Cholecystectomy Pylorus-preserving pancreatoduodenectomy Left hepatectomy Choledochotomy + cholecystectomy Choledochotomy + cholecystectomy Pancreatoduodenectomy Choledochotomy + cholecystectomy Choledochotomy + cholecystectomy – – – – – – – – – – – – –
Operation
598 D. Hokuto et al. Hepatology Research 2015; 45: 595–600\
Eosinophilic cholangitis
Hepatology Research 2015; 45: 595–600\
infiltration causes wall thickening and stenosis of the bile duct, and consequently liver dysfunction, jaundice and cholangitis occur. Imaging of eosinophilic cholangitis is categorized into two different patterns.2 One shows diffuse biliary strictures similar to primary sclerosing cholangitis, and the other shows local wall thickening and stricture of the bile duct, similar to cancer of the bile tract. Differentiation of eosinophilic cholangitis or primary sclerosing cholangitis and cancer of the bile tract is difficult using imaging alone. However, the improvement of cholangitis by treatment with steroids and eosinophilia of peripheral blood are features only found in eosinophilic cholangitis. Among the reported cases of eosinophilic cholangitis, 18 underwent an operation1,3–17 and 13 did not (Table 1).2,18–28 A total of 12 resected cases were diagnosed as suspected cancer of the bile tract upon the identification of local wall thickening or stricture of the bile duct, and five resected cases were diagnosed as cholecystitis with diffuse biliary stricture. However, most of them were diagnosed as eosinophilic cholangitis after operation due to histological findings of the resected specimen and a retrospective finding of eosinophilia of peripheral blood; five of these cases did not show improvement of cholangitis after operation, so steroid treatment was added. Most imaging findings of unresected cases were diffuse biliary stricture type (11/ 13), and severe eosinophilia (>1000/μL) was observed in most unresected cases (12/13). Unresected cases were not diagnosed as cancer of the bile tract because their imaging findings were rather similar to primary sclerosing cholangitis and severe eosinophilia may be associated with eosinophil-related disease. All of the unresected cases were treated with steroids and the clinical course was stable. In our case, there was coexistence of stenosis of the distal bile duct and diffuse biliary strictures in the intrahepatic bile duct. First, we did not diagnose the case as cancer of the bile tract because imaging findings of the narrow segment of the bile duct did not change for over 2 years, and scraping cytology showed no malignancy. Moreover, he did not exhibit eosinophilia of peripheral blood because he had been diagnosed with ITP and treated with prednisolone. Unexpected cessation of the administration of prednisolone at 10 mg/day caused severe worsening of the eosinophilic cholangitis; as a result, acute cholecystitis developed. At that point, we did not consider eosinophilic cholangitis. Cholecystectomy and choledochojejunostomy were performed under a diagnosis of acute cholecystitis due to benign stenosis of the lower bile duct. Even after operation, the
599
severe cholangitis was not improved. Finally, we diagnosed the patient with eosinophilic cholangitis due to the existence of eosinophilia of peripheral blood and eosinophilic infiltration into the resected bile duct and gallbladder. The surgically resected bile duct was not in the same portion as the bile duct stricture. However, eosinophilic infiltration was observed in the resected bile duct. This is supported by imaging of the bile duct that showed not only stricture of the lower bile duct, but also extensive irregularity from the lower bile duct to the intrahepatic bile duct, and the range of eosinophilic cholangitis was thought to be wide. Treatment with prednisolone was initiated, and the subsequent clinical course was stable. A relationship between Helicobacter pylori infection and eosinophilic disease has been reported.29 In our case, serum antibody of H. pylori was not observed. In addition, no other parasite infection, autoimmune disease, except ITP, or malignant tumor was observed. Differentiation of eosinophilic cholangitis and immunoglobulin (Ig)G4-related cholangitis is an interesting issue. We stained a resected specimen using IgG4 antibody, and there were few IgG4 positive cells. In addition, the serum IgG4 level was in the normal range (63.6 mg/dL). Conservative treatment using steroids is effective for eosinophilic cholangitis, and its prognosis is good. Therefore, accurate diagnosis of eosinophilic cholangitis is important in the treatment of diseases of the bile tract. In the diagnosis of bile duct strictures and cholangitis, the presence of eosinophilia has to be considered.
REFERENCES 1 Butler TW, Feintuch TA, Caine WP, Jr. Eosinophilic cholangitis, lymphadenopathy, and peripheral eosinophilia: a case report. Am J Gastroenterol 1985; 80: 572–4. 2 Kimura Y, Yamashita Y, Mikami S et al. [Eosinophilic cholangitis from almost normal appearance to the bile duct sclerosis similar to primary sclerosing cholangitis]. Nihon Shokakibyo Gakkai Zasshi 2013; 110: 271–81. 3 Platt ML, Kiesling VJ, Jr, Vaccaro JA. Eosinophilic ureteritis associated with eosinophilic cholangitis: a case report. J Urol 1990; 144: 127–9. 4 Rosengart TK, Rotterdam H, Ranson JH. Eosinophilic cholangitis: a self-limited cause of extrahepatic biliary obstruction. Am J Gastroenterol 1990; 85: 582–5. 5 Grauer L, Padilla VM, 3rd, Bouza L, Barkin JS. Eosinophilic sclerosing cholangitis associated with hypereosinophilic syndrome. Am J Gastroenterol 1993; 88: 1764–9. 6 Song HH, Byun JY, Jung SE, Choi KH, Shinn KS, Kim BK. Eosinophilic cholangitis: US, CT, and cholangiography findings. J Comput Assist Tomogr 1997; 21: 251–3.
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7 Tenner S, Roston A, Lichtenstein D, Brooks D, Herlihy E, Carr-Locke D. Eosinophilic cholangiopathy. Gastrointest Endosc 1997; 45: 307–9. 8 al-Abdulla NA, Schulick RD, Regan F. Hypereosinophilic sclerosing cholangitis: findings using half-Fourier magnetic resonance imaging. Hepatogastroenterology 2000; 47: 359– 61. 9 Rodgers MS, Allen JP, Koea JB, McCall JL. Eosinophilic cholangitis: a case of “malignant masquerade”. HPB 2001; 3: 235–9. 10 Shanti CM, Lucas CE, Tyburski JG, Soulen RL, Lucas DR. Eosinophilic abscess and eosinophilic pseudotumor presenting as bile duct masses: a report of 2 cases. Surgery 2001; 130: 104–8. 11 Chen WH, Yu CC, Wu CC, Jan YJ. Eosinophilic cholangitis with obstructive jaundice mimicking bile duct carcinoma. J Hepatobiliary Pancreat Surg 2009; 16: 242–5. 12 Miura F, Asano T, Amano H et al. Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis. World J Gastroenterol 2009; 15: 1394–7. 13 Raptou G, Pliakos I, Hytiroglou P, Papavramidis S, Karkavelas G. Severe eosinophilic cholangitis with parenchymal destruction of the left hepatic lobe due to hydatid disease. Pathol Int 2009; 59: 395–8. 14 Dubay D, Jhala N, Eloubeidi M. Eosinophilic cholangitis. Clin Gastroenterol Hepatol 2010; 8: A22. 15 Nashed C, Sakpal SV, Shusharina V, Chamberlain RS. Eosinophilic cholangitis and cholangiopathy: a sheep in wolves clothing. HPB Surg 2010; 2010: 906496. 16 Kroemer A, Sabet-Baktach M, Doenecke A et al. Eosinophilic cholangitis and wirsungitis as cause of simultaneous bile duct obstruction and pancreatitis. Z Gastroenterol 2012; 50: 766–70. 17 Seow-En I, Chiow AK, Tan SS, Poh WT. Eosinophilic cholangiopathy: the diagnostic dilemma of a recurrent biliary stricture. Should surgery be offered for all? BMJ Case Rep 2014. doi: 10.1136/bcr-2013-202225. [Epub ahead of print].
© 2014 The Japan Society of Hepatology
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18 Scheurlen M, Mork H, Weber P. Hypereosinophilic syndrome resembling chronic inflammatory bowel disease with primary sclerosing cholangitis. J Clin Gastroenterol 1992; 14: 59–63. 19 Schoonbroodt D, Horsmans Y, Laka A, Geubel AP, Hoang P. Eosinophilic gastroenteritis presenting with colitis and cholangitis. Dig Dis Sci 1995; 40: 308–14. 20 Jimenez-Saenz M, Villar-Rodriguez JL, Torres Y et al. Biliary tract disease: a rare manifestation of eosinophilic gastroenteritis. Dig Dis Sci 2003; 48: 624–7. 21 Vauthey JN, Loyer E, Chokshi P, Lahoti S. Case 57: eosinophilic cholangiopathy. Radiology 2003; 227: 107–12. 22 Duseja A, Nada R, Dhiman RK et al. Eosinophilic cholangiopathy – a case report. Dig Dis Sci 2005; 50: 1422–5. 23 Jeyamani R, Ramakrishna BS, Kurian G. Eosinophilic cholangiopathy – a report of two cases. Indian J Gastroenterol 2007; 26: 190–1. 24 Matsumoto N, Yokoyama K, Nakai K et al. A case of eosinophilic cholangitis: imaging findings of contrast-enhanced ultrasonography, cholangioscopy, and intraductal ultrasonography. World J Gastroenterol 2007; 13: 1995–7. 25 Sussman DA, Bejarano PA, Regev A. Eosinophilic cholangiopathy with concurrent eosinophilic colitis in a patient with idiopathic hypereosinophilic syndrome. Eur J Gastroenterol Hepatol 2008; 20: 574–7. 26 Horiuchi K, Kakizaki S, Kosone T et al. Marked eosinophilia as the first manifestation of sclerosing cholangitis. Intern Med 2009; 48: 1377–82. 27 Iwamuro M, Yamamoto K, Kawamoto H, Terada R, Ogawa T, Nose S. Eosinophilic cholangitis with initial clinical features indistinguishable from IgG4-related cholangitis. Intern Med 2009; 48: 1143–7. 28 Vainer E, Vainer G, Jacob H, Faroja M. Eosinophilic cholangitis diagnosed endoscopically. Endoscopy 2014; 46 (Suppl 1): E95–96. 29 Papadopoulos AA, Tzathas C, Polymeros D, Ladas SD. Symptomatic eosinophilic gastritis cured with Helicobacter pylori eradication. Gut 2005; 54: 1822.
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Hepatology Research 2015; 45: 595–600
doi: 10.1111/hepr.12380
Case Report
Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case Daisuke Hokuto, Ichiro Yamato, Takeo Nomi, Satoshi Yasuda, Shinsaku Obara, Takatsugu Yamada, Kawaguchi Chihiro and Yoshiyuki Nakajima Department of Surgery, Nara Medical University, Nara, Japan
Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected
sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.
INTRODUCTION
May 2010. There were no clear causes of this dilation on images, so he was kept under observation. In September 2011, he developed cholangitis and magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the lower bile duct and irregularity of the intrahepatic bile duct (Fig. 1a). The cholangitis was cured by
E
OSINOPHILIC CHOLANGITIS IS a rare disease caused by eosinophilic infiltration into the wall of the bile duct. Imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. However, eosinophilic cholangitis is typically improved by treatment with steroids, so its accurate diagnosis is very important. We report a case of eosinophilic cholangitis coexisting with idiopathic thrombocytopenic purpura (ITP). Treatment with steroid for the ITP affected the progress of the eosinophilic cholangitis.
Key words: eosinophilic cholangitis, eosinophilic cholecystitis, idiopathic thrombocytopenic purpura
a
b
CASE REPORT
I
N A 73-YEAR-OLD man who had been treated for diabetes mellitus and had a postoperative status of prostatic cancer and right renal cell carcinoma from another hospital, dilation of intrahepatic bile ducts was identified by abdominal computed tomography (CT) in
Correspondence: Dr Daisuke Hokuto, Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Email: [email protected] Conflict of interest: The authors have no conflict of interest. Received 27 May 2014; revision 19 June 2014; accepted 23 June 2014.
© 2014 The Japan Society of Hepatology
Figure 1 (a) Findings of magnetic resonance cholangiopancreatography. Stricture of the lower bile duct and irregularity of the intrahepatic bile duct were seen. (b) Findings of endoscopic retrograde cholangiopancreatography. Stricture of the lower bile duct was seen, and scraping cytology showed no malignancy.
595
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Hepatology Research 2015; 45: 595–600\
antibiotics, and he was referred to our hospital under the diagnosis of cancer of the bile tract in October 2011. Endoscopic retrograde cholangiopancreatography revealed stenosis of the lower bile duct (Fig. 1b), and scraping cytology showed no malignancy. We followed him by MRCP every 3 months and there was no remarkable change in the images. In that same period, thrombocytopenia was seen in his peripheral blood and he was diagnosed with ITP. He was treated using prednisolone, and recovery from the thrombocytopenia occurred. On the other hand, the proportion of eosinophils in his peripheral blood exhibited an inverse course compared with the platelet count (Fig. 2a). In November 2012, the administration of prednisolone at a dose
(a)
of 10 mg/day was unexpectedly interrupted. In December 2012, he frequently exhibited cholangitis. In that period, we thought that the main cause of the cholangitis was benign stenosis of the distal bile duct. Endoscopic retrograde biliary drainage (ERBD) was performed. However, the ERBD tube was removed unexpectedly 2 weeks after insertion. The patient was admitted with high fever (38.5°C) and jaundice (serum bilirubin, 4.1 mg/dL) on 1 January 2013. CT revealed wall thickening and swelling of the gallbladder. We diagnosed him with acute cholecystitis due to stenosis of the lower bile duct (Fig. 3). We assessed that the stenosis was a benign lesion, and complete resection of the stenotic legion required pancreatoduodenectomy.
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Figure 2 (a) Changes in the proportion of eosinophils and platelet count in peripheral blood. While prednisolone was administrated, the proportion of eosinophils was low and the platelet count was high. (b) Changes in the serum alkaline phosphatase (ALP) level. On 12 December 2012, sudden interruption of the administration of prednisolone caused a severe increase of the ALP level, which was not improved even after operation. Re-administration of prednisolone decreased the ALP level. (c,d) Changes in the serum γ-glutamyltransferase (γ-GT) and total bilirubin levels. Their courses were similar to that of the ALP level. (a) , eosinophils (%); , platelets (×10/μL); (b) , ALP (IU/L); (c) , γ-GT (IU/L); (d) , total bilirubin (mg/dL).
© 2014 The Japan Society of Hepatology
Eosinophilic cholangitis
Hepatology Research 2015; 45: 595–600\
In addition, we performed cholecystectomy and choledochojejunostomy on 4 January 2013. We resected the common bile duct between the superior border of the pancreas and the hepatic side of the cystic duct. Minor bile leakage occurred, but the patient was discharged on postoperative day 42. Pathologically, marked eosinophilic infiltration along with abundant lymphocytes and plasma cell were observed in the surgically resected bile duct and gallbladder (Fig. 4). Even after the operation, the levels of serum bilirubin, alkaline phosphatase (ALP), and γ-glutamyltransferase (γ-GT) were still higher than normal. In addition, the proportion of eosinophils in peripheral blood was markedly higher than normal. Finally, we diagnosed him with eosinophilic cholangitis, and prednisolone started to be administrated at 20 mg/day. The proportion of eosinophils immediately normalized, and the levels of serum bilirubin, ALP and γ-GT improved slowly (Fig. 2b–d). The dose of prednisolone was decreased
597
a
×100 b
a
×400
Figure 4 Microscopic findings of bile duct showed marked eosinophilic infiltration (hematoxylin–eosin, original magnifications: [a] ×100; [b] ×400).
b
gradually, and its administration was stopped in October 2013. Retrospectively, we considered that the frequent cholangitis in December 2012 and the acute cholecystitis on 1 January 2013 had been caused by the sudden interruption of prednisolone at a dose of 10 mg/day.
DISCUSSION
E
Figure 3 Findings of computed tomography. (a) Wall thickening and stenosis of the distal bile duct were seen. (b) Edema and swelling in the wall of the gallbladder were also seen.
OSINOPHILIC CHOLANGITIS WAS first reported as a disease involving eosinophilic infiltration into the bile duct and/or gallbladder with eosinophilia of peripheral blood in 1985.1 Only 31 cases have been reported, as determined from a search of PubMed (1985 to April 2014), and a strategy for its diagnosis and treatment has not been well established. Eosinophilic
© 2014 The Japan Society of Hepatology
Year
1985 1990
1990 1993 1997 1997 2000 2001
2001 2001
2009 2009
2009 2010
2010
2012 2014
2013
1992 1995 2003 2003 2005 2007 2007 2007 2008 2009 2009 2013 2014
First author
Butler1 Platt3
Rosengart4 Grauer5 Song6 Tenner7 al-Abdulla8 Rodgers9
Shanti10 Shanti10
Chen11 Miura12
© 2014 The Japan Society of Hepatology
Raptou13 Dubay14
Nashed15
Kroemer16 Seown17
Our case
Scheurlen18 Schoonbroodt19 Jimenez-Saenz20 Vauthey21 Duseja22 Jeyamani23 Jeyamani23 Matsumoto24 Sussman25 Horiuchi26 Iwamuro27 Kimura28 Vainer29 30 20 67 44 16 13 26 38 52 45 66 48 15
73
49 63
33
24 29
55 46
57 33
48 41 48 38 42 50
32 42
Sex
M F F M F M M F M M F M M
M
M M
M
M F
M M
F M
M M F F F F
M F
Age
5 057 1 411 2 068 1 550 11 340 1 500 5 900 719 13 300 9 914 14 315 2 264 Not mentioned
6 500
Not mentioned 1 900
108
1 471 630
823 117
79 261
246 1 647 408 2 200 1 674 Not mentioned
14 212 Not mentioned
Eosinophils (/uL)
Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct
Stricture of distal bile duct
Stricture of distal bile duct Stricture of distal bile duct
Stricture of proximal bile duct
Stricture of intrahepatic bile duct Stricture of proximal bile duct
Stricture of proximal bile duct Stricture of distal bile duct
Stricture of distal bile duct Stricture of proximal bile duct
Stricture of proximal bile duct Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Diffuse biliary stricture Stricture of proximal bile duct
Diffuse biliary stricture Diffuse biliary stricture
Image of bile duct
Table 1 The 31 reported cases of eosinophilic cholangitis in PubMed (1985 to April 2014)
Absent Absent Present Absent Absent Absent Absent Absent Present Absent Absent Absent Absent
Present
Absent Absent
Absent
Absent Absent
Present Present
Absent Absent
Present Absent Present Present Present Absent
Present Absent
Cholecystitis
Done Done Done Done Done Done Done Done Done Done Done Done Done
Done (after operation)
– –
–
– –
Done (after operation) –
– –
– Done (after operation) – Done (after operation) Done (after operation) –
– –
Treatment with corticosteroids
Cholecystectomy Choledochotomy + cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Choledochotomy + cholecystectomy Choledochotomy Choledochotomy + cholecystectomy Cholecystectomy Pylorus-preserving pancreatoduodenectomy Left hepatectomy Choledochotomy + cholecystectomy Choledochotomy + cholecystectomy Pancreatoduodenectomy Choledochotomy + cholecystectomy Choledochotomy + cholecystectomy – – – – – – – – – – – – –
Operation
598 D. Hokuto et al. Hepatology Research 2015; 45: 595–600\
Eosinophilic cholangitis
Hepatology Research 2015; 45: 595–600\
infiltration causes wall thickening and stenosis of the bile duct, and consequently liver dysfunction, jaundice and cholangitis occur. Imaging of eosinophilic cholangitis is categorized into two different patterns.2 One shows diffuse biliary strictures similar to primary sclerosing cholangitis, and the other shows local wall thickening and stricture of the bile duct, similar to cancer of the bile tract. Differentiation of eosinophilic cholangitis or primary sclerosing cholangitis and cancer of the bile tract is difficult using imaging alone. However, the improvement of cholangitis by treatment with steroids and eosinophilia of peripheral blood are features only found in eosinophilic cholangitis. Among the reported cases of eosinophilic cholangitis, 18 underwent an operation1,3–17 and 13 did not (Table 1).2,18–28 A total of 12 resected cases were diagnosed as suspected cancer of the bile tract upon the identification of local wall thickening or stricture of the bile duct, and five resected cases were diagnosed as cholecystitis with diffuse biliary stricture. However, most of them were diagnosed as eosinophilic cholangitis after operation due to histological findings of the resected specimen and a retrospective finding of eosinophilia of peripheral blood; five of these cases did not show improvement of cholangitis after operation, so steroid treatment was added. Most imaging findings of unresected cases were diffuse biliary stricture type (11/ 13), and severe eosinophilia (>1000/μL) was observed in most unresected cases (12/13). Unresected cases were not diagnosed as cancer of the bile tract because their imaging findings were rather similar to primary sclerosing cholangitis and severe eosinophilia may be associated with eosinophil-related disease. All of the unresected cases were treated with steroids and the clinical course was stable. In our case, there was coexistence of stenosis of the distal bile duct and diffuse biliary strictures in the intrahepatic bile duct. First, we did not diagnose the case as cancer of the bile tract because imaging findings of the narrow segment of the bile duct did not change for over 2 years, and scraping cytology showed no malignancy. Moreover, he did not exhibit eosinophilia of peripheral blood because he had been diagnosed with ITP and treated with prednisolone. Unexpected cessation of the administration of prednisolone at 10 mg/day caused severe worsening of the eosinophilic cholangitis; as a result, acute cholecystitis developed. At that point, we did not consider eosinophilic cholangitis. Cholecystectomy and choledochojejunostomy were performed under a diagnosis of acute cholecystitis due to benign stenosis of the lower bile duct. Even after operation, the
599
severe cholangitis was not improved. Finally, we diagnosed the patient with eosinophilic cholangitis due to the existence of eosinophilia of peripheral blood and eosinophilic infiltration into the resected bile duct and gallbladder. The surgically resected bile duct was not in the same portion as the bile duct stricture. However, eosinophilic infiltration was observed in the resected bile duct. This is supported by imaging of the bile duct that showed not only stricture of the lower bile duct, but also extensive irregularity from the lower bile duct to the intrahepatic bile duct, and the range of eosinophilic cholangitis was thought to be wide. Treatment with prednisolone was initiated, and the subsequent clinical course was stable. A relationship between Helicobacter pylori infection and eosinophilic disease has been reported.29 In our case, serum antibody of H. pylori was not observed. In addition, no other parasite infection, autoimmune disease, except ITP, or malignant tumor was observed. Differentiation of eosinophilic cholangitis and immunoglobulin (Ig)G4-related cholangitis is an interesting issue. We stained a resected specimen using IgG4 antibody, and there were few IgG4 positive cells. In addition, the serum IgG4 level was in the normal range (63.6 mg/dL). Conservative treatment using steroids is effective for eosinophilic cholangitis, and its prognosis is good. Therefore, accurate diagnosis of eosinophilic cholangitis is important in the treatment of diseases of the bile tract. In the diagnosis of bile duct strictures and cholangitis, the presence of eosinophilia has to be considered.
REFERENCES 1 Butler TW, Feintuch TA, Caine WP, Jr. Eosinophilic cholangitis, lymphadenopathy, and peripheral eosinophilia: a case report. Am J Gastroenterol 1985; 80: 572–4. 2 Kimura Y, Yamashita Y, Mikami S et al. [Eosinophilic cholangitis from almost normal appearance to the bile duct sclerosis similar to primary sclerosing cholangitis]. Nihon Shokakibyo Gakkai Zasshi 2013; 110: 271–81. 3 Platt ML, Kiesling VJ, Jr, Vaccaro JA. Eosinophilic ureteritis associated with eosinophilic cholangitis: a case report. J Urol 1990; 144: 127–9. 4 Rosengart TK, Rotterdam H, Ranson JH. Eosinophilic cholangitis: a self-limited cause of extrahepatic biliary obstruction. Am J Gastroenterol 1990; 85: 582–5. 5 Grauer L, Padilla VM, 3rd, Bouza L, Barkin JS. Eosinophilic sclerosing cholangitis associated with hypereosinophilic syndrome. Am J Gastroenterol 1993; 88: 1764–9. 6 Song HH, Byun JY, Jung SE, Choi KH, Shinn KS, Kim BK. Eosinophilic cholangitis: US, CT, and cholangiography findings. J Comput Assist Tomogr 1997; 21: 251–3.
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7 Tenner S, Roston A, Lichtenstein D, Brooks D, Herlihy E, Carr-Locke D. Eosinophilic cholangiopathy. Gastrointest Endosc 1997; 45: 307–9. 8 al-Abdulla NA, Schulick RD, Regan F. Hypereosinophilic sclerosing cholangitis: findings using half-Fourier magnetic resonance imaging. Hepatogastroenterology 2000; 47: 359– 61. 9 Rodgers MS, Allen JP, Koea JB, McCall JL. Eosinophilic cholangitis: a case of “malignant masquerade”. HPB 2001; 3: 235–9. 10 Shanti CM, Lucas CE, Tyburski JG, Soulen RL, Lucas DR. Eosinophilic abscess and eosinophilic pseudotumor presenting as bile duct masses: a report of 2 cases. Surgery 2001; 130: 104–8. 11 Chen WH, Yu CC, Wu CC, Jan YJ. Eosinophilic cholangitis with obstructive jaundice mimicking bile duct carcinoma. J Hepatobiliary Pancreat Surg 2009; 16: 242–5. 12 Miura F, Asano T, Amano H et al. Resected case of eosinophilic cholangiopathy presenting with secondary sclerosing cholangitis. World J Gastroenterol 2009; 15: 1394–7. 13 Raptou G, Pliakos I, Hytiroglou P, Papavramidis S, Karkavelas G. Severe eosinophilic cholangitis with parenchymal destruction of the left hepatic lobe due to hydatid disease. Pathol Int 2009; 59: 395–8. 14 Dubay D, Jhala N, Eloubeidi M. Eosinophilic cholangitis. Clin Gastroenterol Hepatol 2010; 8: A22. 15 Nashed C, Sakpal SV, Shusharina V, Chamberlain RS. Eosinophilic cholangitis and cholangiopathy: a sheep in wolves clothing. HPB Surg 2010; 2010: 906496. 16 Kroemer A, Sabet-Baktach M, Doenecke A et al. Eosinophilic cholangitis and wirsungitis as cause of simultaneous bile duct obstruction and pancreatitis. Z Gastroenterol 2012; 50: 766–70. 17 Seow-En I, Chiow AK, Tan SS, Poh WT. Eosinophilic cholangiopathy: the diagnostic dilemma of a recurrent biliary stricture. Should surgery be offered for all? BMJ Case Rep 2014. doi: 10.1136/bcr-2013-202225. [Epub ahead of print].
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18 Scheurlen M, Mork H, Weber P. Hypereosinophilic syndrome resembling chronic inflammatory bowel disease with primary sclerosing cholangitis. J Clin Gastroenterol 1992; 14: 59–63. 19 Schoonbroodt D, Horsmans Y, Laka A, Geubel AP, Hoang P. Eosinophilic gastroenteritis presenting with colitis and cholangitis. Dig Dis Sci 1995; 40: 308–14. 20 Jimenez-Saenz M, Villar-Rodriguez JL, Torres Y et al. Biliary tract disease: a rare manifestation of eosinophilic gastroenteritis. Dig Dis Sci 2003; 48: 624–7. 21 Vauthey JN, Loyer E, Chokshi P, Lahoti S. Case 57: eosinophilic cholangiopathy. Radiology 2003; 227: 107–12. 22 Duseja A, Nada R, Dhiman RK et al. Eosinophilic cholangiopathy – a case report. Dig Dis Sci 2005; 50: 1422–5. 23 Jeyamani R, Ramakrishna BS, Kurian G. Eosinophilic cholangiopathy – a report of two cases. Indian J Gastroenterol 2007; 26: 190–1. 24 Matsumoto N, Yokoyama K, Nakai K et al. A case of eosinophilic cholangitis: imaging findings of contrast-enhanced ultrasonography, cholangioscopy, and intraductal ultrasonography. World J Gastroenterol 2007; 13: 1995–7. 25 Sussman DA, Bejarano PA, Regev A. Eosinophilic cholangiopathy with concurrent eosinophilic colitis in a patient with idiopathic hypereosinophilic syndrome. Eur J Gastroenterol Hepatol 2008; 20: 574–7. 26 Horiuchi K, Kakizaki S, Kosone T et al. Marked eosinophilia as the first manifestation of sclerosing cholangitis. Intern Med 2009; 48: 1377–82. 27 Iwamuro M, Yamamoto K, Kawamoto H, Terada R, Ogawa T, Nose S. Eosinophilic cholangitis with initial clinical features indistinguishable from IgG4-related cholangitis. Intern Med 2009; 48: 1143–7. 28 Vainer E, Vainer G, Jacob H, Faroja M. Eosinophilic cholangitis diagnosed endoscopically. Endoscopy 2014; 46 (Suppl 1): E95–96. 29 Papadopoulos AA, Tzathas C, Polymeros D, Ladas SD. Symptomatic eosinophilic gastritis cured with Helicobacter pylori eradication. Gut 2005; 54: 1822.
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