Caroli's disease
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《美国医学杂志》
Department of Pediatrics, NSCB Medical College, Jabalpur, India
Abstract
Caroli's disease is a rare congenital disorder, and occasional cases have been reported from Japan and other parts of Asia. It comprises of congenital dilation of the lower (segmental) intrahepatic bile duct. Cholangitis liver, cirrhosis and cholangiocarcinoma are its potential complication. A case of caroli's disease in an 8-years-old boy with bilobar involvement of liver, (specially affecting right superior lobe) presenting with intermittent abdominal pain, fever and hepatosplenomegaly is reported here.
Keywords: Caroli disease; Abdominal pain; Central dot sign
Caroli's disease, first described by Jacques Caroli (1958) is a rare congenital condition characterized by non-obstructive saccular or fusiform multi-focal segmental dilatation of the intra-hepatic bile ducts.[1] Mode of inheritance is still unclear but in majority of cases it is transmitted in autosomal recessive fashion.[2] One recent observation in a family from Japan suggested an autosomal dominant mode of inheritance.[3] This disease usually presents with recurrent cholangitis and hepatomegaly.[4]
Case Report
An 8-year-old boy presented with complaints of pain in abdomen with fever and yellow discoloration of urine for 15 days. Fever was reportedly associated with chills and rigors. He received chloroquine, antibiotics, and one blood transfusion for low hemoglobin level in the last 15 days. He was the fourth child of non-consanguineous marriage. His siblings and parents were apparently healthy, without any history of liver and kidney diseases. He belonged to a backward caste (Sahu) from Dindori District of Madhya Pradesh. There was no history of long medical illness. On physical examination, he was afebrile and had mild pallor, icterus and conjunctival xerosis. Anthropometry was suggestive of malnutrition; weight 14 kg as against expected weight of 25.80 kg (54% of expected weight) and height 106 cm as against expected height of 128.1 cm (82% of the expected height). Abdomen was soft and non tender. Liver was palpable 5 cm below right costal margin with span of 8 cm in the right mid clavicular line. It was nontender, firm and had a smooth surface with well-defined margins. A firm spleen was palpable, 4 cm below costal margin along its long axis. There was no evidence of free fluid in abdomen Figure1. All other systems were clinically normal.
Laboratory investigations showed anemia (Hb 9 gm%), elevated polymorphonuclear cells (TLC 10.8 x 10 3μl with polymorph 76.4%) and raised ESR (30 mm at the end of 1 hour). Red blood corpuscles were microcytic and hypochromic (MCV-62 fl, MCH 22 pg and MCHC 35.3%). Sickling test was positive and Hb electrophoresis revealed sickle cell disease with high HbS concentration (HbS 83.93%), increased HbF (13.67%) and normal HbA2 (2.4%). Liver function tests showed direct hyperbilirubinemia (total 2.25 mg/dl, direct 1.25 mg/dl, indirect I mg/dl), reversed A/G ratio (total Protein 7.14 gm/dl, albumin 3.10 gm/dl and globulin 4.2 gm/dl), and marginally elevated SGPT (50 Unit/ml), with normal SGOT (40 Unit/ml) and raised prothromibin time (18 seconds, control 11 seconds). Urine test was negative for urobilinogen and bile salt.
Ultrasonography showed multiple cystic lesions in the right lobe of liver and Color Doppler study showed evidence of multiple intrahepatic dilated biliary radicals Figure2. CT scan showed bizarre, saccular dilatation of intrahepatic bile ducts involving almost all subsegments of Bismuth and Corinauds in varying degree, most severely affecting right superior segment. Some of the cysts showed small internal hyperdense-enhancing nodule like focus consistent with the Central Dot sign. Figure3. Hepatic parenchyma was homogenous without evidence of periportal fibrosis and normal portal vein diameter. Gall bladder was distended but did not show any calculi. Spleen was enlarged and homogenous in density, with normal splenic vein size. Liver biopsy for exclusion of associated congenital hepatic fibrosis was not done since clinical examination and imaging studies did not show any evidence of portal hypertension. Both kidneys were normal in shape and size. Diagnosis of pure form of Caroli disease with sickle-cell disease was made and the child was treated conservatively with antibiotics. Parents were counseled and advised to come for regular follow-up.
Discussion
Caroli disease occurs in two forms: (i) pure form (Caroli disease) characterized by ectasias of intrahepatic bile ducts without other histologic abnormalities, and (ii) combined form (Caroli syndrome) in which ectasia of intrahepatic bile ducts is associated with periportal fibrosis (the later corresponding to congenital hepatic fibrosis) and renal cystic disease.[5],[6] Kidney lesions include renal tubular ectasia (medullary sponge kidney, cortical cyst), lesions of adult recessive polycystic kidney disease, or rarely autosomal dominant polycystic kidney disease.[7] Both conditions result from malformation of embryonic ductal plate at different level of the biliary tree.[8] incidence of Caroli syndrome is more than pure form of Caroli disease.[9]
Children with Caroli disease may experience symptoms of intermittent abdominal pain, cholangitis, cholelithiasis, biliary abscess, septicemia and liver cirrhosis. Malignant complication (Cholangio carcinoma) is found in approximately 7% of cases.[10]
Amyloidosis is also described as a complication of Caroli's disease.[11] The diagnosis of Caroli's disease in children involves recognition of the symptoms of liver dysfunction and imaging studies. Imaging studies include abdominal sonography, CT scan, endoscopic retrograde cholangiography (ERC), percutaneous transhepatic cholangiography (PTC) and magnetic resonance cholangiography (MRC) .[12]
CT scan shows Central Dot sign in these patients.[13] The fibrovascular bundles containing portal vein radical and a branch of hepatic artery bridging the saccule appear as central dots or linear streak. This Central Dot sign described on CT scan is suggested as a pathognomic finding in Caroli's disease[14],[15] and it can also be demonstrated on USG.[16]
There is no cure for Caroli's disease. The treatment is focused on supporting children through the infections and other associated problems. Cholangitis is treated with appropriate antibiotics. In case of intrahepatic cholelithiasis, litholytic therapy with Urso-deoxycholic acid is indicated.[17] Partial hepatectomy has also been shown to be effective if the biliary lesion is predominantly confined to discrete area and appears to increase the risk of malignancy.[18] Diffuse involvement of both the lobes can be treated with conservative management, endoscopic therapy (sphincterotomy for clearance of intra-hepatic stones), internal biliary bypass procedure and in carefully selected cases with liver transplantation.[19]
The child discussed in this report is pure form of Caroli disease with no evidence of periportal fibrosis and renal cystic disease. The child apparently appears to be a sporadic case of this disease. He also had sickle-cell disease which partly contributed to his clinical picture. Although Caroli's disease is a rare congenital anomaly, it should be included in differential diagnosis in children presenting with abdominal pain and hepatomegaly.
References
1. Miller WJ, Sechtin AG, Campbell WL, Pecters PC "Imaging findings in caroli disease". Am J. Roentgenol 1995; 165 : 333- 337.
2. F.J. Suchy in Richard E Behrman, RM Kliegman, HB Jenson, eds. Nelson Text Book of Paediatrics . 17th edn. Philaldelphia; Saunders 2004; 1343.
3. Tsuchida Y, Sato T, Sanjo K, Etoh T, Hata K, Tera Waki K et al. "Evaluation of long term results of caroli disease: 21 years observation of a family with autosomal dominant inheritance and review of the literature" . Hepatosplenomegaly 1995; 42 : 175-181.
4. Taylar AC, Palmer KR. Caroli's disease. Eur J Gastroenter 1998; 10: 105-108.
5. Mall JC, Chahremani GG, Boyer JL, Carolis disease associated with congenital hepatic fibrosis and renal tubular ectasia. Gastroenterology 1974; 66: 1029-1053.
6. Bernstein J, Slovis TI. Polycystic disease of the kidney. In Elderman CM Jr eds Paediatric Kidney Disease. Vol. 2, I Boston; Little Brown; 1992: 1139-1153.
7. David S. Memel, Dannis M Balfe and Richard C, Semlka In Joseph KT Lee, SS Sagel, RJ Stanley JP Heiken eds. Computed Tomography with MRl Correlation 3rd edn. Vol. 2. Philadelphia, Lippincott-Raven, 1998; 817-818.
8. Sherlock, Sheila. Cystic disease of the liver. In : Schiffs disease of liver. 8th edn. Philadelphia; Lipin Cott Raven 1999; 1083-1089.
9. Summerfield JA, NagaFuchi Y, Sherlock S, Cadatalch J, Scheuer PJ. Hepatobiliary Fibropolycystic disease. A clinical and histological Review of 51 patients. J Hepatol 1986; 2 : 141-156.
10. Bismuth H, Krissat J. Chodedochal cystic malignancies. Ann Oncol 1999; 10 : 94-98.
11. Fevery J, Tanghe W, Kerremans R et al. Congellital Dilatation of the intrahepatic bile ducts associated with the development of Amyloidosis.s 1972 : 13: 604-609.
12. Angela D Lavy, Charles A Rohrmann JR, Linda A Murakat: & Gael J Lonergan. Caroli Disease: Radiological spectrum with pathologic correlation. Am J Roentgenol 2002; 179 : 1053-1057.
13. Bruce P Parker. The Hepatobiliary system. In FN Silverman, J P Kuhn eds. Caffeys- Pediatric X-ray diagnosis: An Integrated imaging approach 9th edn. Vol. 2 Louis; Mosby, 1993; 928.
14. Kaiser JA, Hall JC, Salmen BJ, Parkar JJ. Diagnosis of caroli's disease by computed tomography report of 2 cases. Radiology 1979; 132 : 661-664.
15. Choi BI, Yeon KM, Kim SH, Han MC : "Caroli disease central dot sign in CT". Radiology 1990; 174 : 161-163.
16. MLN Moorthy. I Venkata Ratnam, P Chandra Mohan, MD Riyaz Khan R Prabhakar Rao. Images: "Central dot sign" on ultrasound-Diagnostic of caroli disease. Ind J Radiol Imag 2000; 10.
17. Ros E, Navarros, Bru C, Crilbert R, Bianchi L, Bruguera M. Ursodeoxycholic acid treatment of primary hepatolothiasis in caroli syndrome. Lancet 1993; 342: 404-406.
18. Reymond MJ, Herguet C, Danan C, et al. Partial hepatectomy in the treatment of caroli disease. Diag Dis Sci 1984; 29: 367 - 310.
19. Jonas MM, Perez Atayede AR. In Suchy FJ, Sokol RJ, Balistrei WF. eds. Liver disease in children. 2nd edn. Philadelphia; Lippincott, Williams and Wilkins; 2001; 904-905.(Gupta Ashish K, Gupta Ara)
Abstract
Caroli's disease is a rare congenital disorder, and occasional cases have been reported from Japan and other parts of Asia. It comprises of congenital dilation of the lower (segmental) intrahepatic bile duct. Cholangitis liver, cirrhosis and cholangiocarcinoma are its potential complication. A case of caroli's disease in an 8-years-old boy with bilobar involvement of liver, (specially affecting right superior lobe) presenting with intermittent abdominal pain, fever and hepatosplenomegaly is reported here.
Keywords: Caroli disease; Abdominal pain; Central dot sign
Caroli's disease, first described by Jacques Caroli (1958) is a rare congenital condition characterized by non-obstructive saccular or fusiform multi-focal segmental dilatation of the intra-hepatic bile ducts.[1] Mode of inheritance is still unclear but in majority of cases it is transmitted in autosomal recessive fashion.[2] One recent observation in a family from Japan suggested an autosomal dominant mode of inheritance.[3] This disease usually presents with recurrent cholangitis and hepatomegaly.[4]
Case Report
An 8-year-old boy presented with complaints of pain in abdomen with fever and yellow discoloration of urine for 15 days. Fever was reportedly associated with chills and rigors. He received chloroquine, antibiotics, and one blood transfusion for low hemoglobin level in the last 15 days. He was the fourth child of non-consanguineous marriage. His siblings and parents were apparently healthy, without any history of liver and kidney diseases. He belonged to a backward caste (Sahu) from Dindori District of Madhya Pradesh. There was no history of long medical illness. On physical examination, he was afebrile and had mild pallor, icterus and conjunctival xerosis. Anthropometry was suggestive of malnutrition; weight 14 kg as against expected weight of 25.80 kg (54% of expected weight) and height 106 cm as against expected height of 128.1 cm (82% of the expected height). Abdomen was soft and non tender. Liver was palpable 5 cm below right costal margin with span of 8 cm in the right mid clavicular line. It was nontender, firm and had a smooth surface with well-defined margins. A firm spleen was palpable, 4 cm below costal margin along its long axis. There was no evidence of free fluid in abdomen Figure1. All other systems were clinically normal.
Laboratory investigations showed anemia (Hb 9 gm%), elevated polymorphonuclear cells (TLC 10.8 x 10 3μl with polymorph 76.4%) and raised ESR (30 mm at the end of 1 hour). Red blood corpuscles were microcytic and hypochromic (MCV-62 fl, MCH 22 pg and MCHC 35.3%). Sickling test was positive and Hb electrophoresis revealed sickle cell disease with high HbS concentration (HbS 83.93%), increased HbF (13.67%) and normal HbA2 (2.4%). Liver function tests showed direct hyperbilirubinemia (total 2.25 mg/dl, direct 1.25 mg/dl, indirect I mg/dl), reversed A/G ratio (total Protein 7.14 gm/dl, albumin 3.10 gm/dl and globulin 4.2 gm/dl), and marginally elevated SGPT (50 Unit/ml), with normal SGOT (40 Unit/ml) and raised prothromibin time (18 seconds, control 11 seconds). Urine test was negative for urobilinogen and bile salt.
Ultrasonography showed multiple cystic lesions in the right lobe of liver and Color Doppler study showed evidence of multiple intrahepatic dilated biliary radicals Figure2. CT scan showed bizarre, saccular dilatation of intrahepatic bile ducts involving almost all subsegments of Bismuth and Corinauds in varying degree, most severely affecting right superior segment. Some of the cysts showed small internal hyperdense-enhancing nodule like focus consistent with the Central Dot sign. Figure3. Hepatic parenchyma was homogenous without evidence of periportal fibrosis and normal portal vein diameter. Gall bladder was distended but did not show any calculi. Spleen was enlarged and homogenous in density, with normal splenic vein size. Liver biopsy for exclusion of associated congenital hepatic fibrosis was not done since clinical examination and imaging studies did not show any evidence of portal hypertension. Both kidneys were normal in shape and size. Diagnosis of pure form of Caroli disease with sickle-cell disease was made and the child was treated conservatively with antibiotics. Parents were counseled and advised to come for regular follow-up.
Discussion
Caroli disease occurs in two forms: (i) pure form (Caroli disease) characterized by ectasias of intrahepatic bile ducts without other histologic abnormalities, and (ii) combined form (Caroli syndrome) in which ectasia of intrahepatic bile ducts is associated with periportal fibrosis (the later corresponding to congenital hepatic fibrosis) and renal cystic disease.[5],[6] Kidney lesions include renal tubular ectasia (medullary sponge kidney, cortical cyst), lesions of adult recessive polycystic kidney disease, or rarely autosomal dominant polycystic kidney disease.[7] Both conditions result from malformation of embryonic ductal plate at different level of the biliary tree.[8] incidence of Caroli syndrome is more than pure form of Caroli disease.[9]
Children with Caroli disease may experience symptoms of intermittent abdominal pain, cholangitis, cholelithiasis, biliary abscess, septicemia and liver cirrhosis. Malignant complication (Cholangio carcinoma) is found in approximately 7% of cases.[10]
Amyloidosis is also described as a complication of Caroli's disease.[11] The diagnosis of Caroli's disease in children involves recognition of the symptoms of liver dysfunction and imaging studies. Imaging studies include abdominal sonography, CT scan, endoscopic retrograde cholangiography (ERC), percutaneous transhepatic cholangiography (PTC) and magnetic resonance cholangiography (MRC) .[12]
CT scan shows Central Dot sign in these patients.[13] The fibrovascular bundles containing portal vein radical and a branch of hepatic artery bridging the saccule appear as central dots or linear streak. This Central Dot sign described on CT scan is suggested as a pathognomic finding in Caroli's disease[14],[15] and it can also be demonstrated on USG.[16]
There is no cure for Caroli's disease. The treatment is focused on supporting children through the infections and other associated problems. Cholangitis is treated with appropriate antibiotics. In case of intrahepatic cholelithiasis, litholytic therapy with Urso-deoxycholic acid is indicated.[17] Partial hepatectomy has also been shown to be effective if the biliary lesion is predominantly confined to discrete area and appears to increase the risk of malignancy.[18] Diffuse involvement of both the lobes can be treated with conservative management, endoscopic therapy (sphincterotomy for clearance of intra-hepatic stones), internal biliary bypass procedure and in carefully selected cases with liver transplantation.[19]
The child discussed in this report is pure form of Caroli disease with no evidence of periportal fibrosis and renal cystic disease. The child apparently appears to be a sporadic case of this disease. He also had sickle-cell disease which partly contributed to his clinical picture. Although Caroli's disease is a rare congenital anomaly, it should be included in differential diagnosis in children presenting with abdominal pain and hepatomegaly.
References
1. Miller WJ, Sechtin AG, Campbell WL, Pecters PC "Imaging findings in caroli disease". Am J. Roentgenol 1995; 165 : 333- 337.
2. F.J. Suchy in Richard E Behrman, RM Kliegman, HB Jenson, eds. Nelson Text Book of Paediatrics . 17th edn. Philaldelphia; Saunders 2004; 1343.
3. Tsuchida Y, Sato T, Sanjo K, Etoh T, Hata K, Tera Waki K et al. "Evaluation of long term results of caroli disease: 21 years observation of a family with autosomal dominant inheritance and review of the literature" . Hepatosplenomegaly 1995; 42 : 175-181.
4. Taylar AC, Palmer KR. Caroli's disease. Eur J Gastroenter 1998; 10: 105-108.
5. Mall JC, Chahremani GG, Boyer JL, Carolis disease associated with congenital hepatic fibrosis and renal tubular ectasia. Gastroenterology 1974; 66: 1029-1053.
6. Bernstein J, Slovis TI. Polycystic disease of the kidney. In Elderman CM Jr eds Paediatric Kidney Disease. Vol. 2, I Boston; Little Brown; 1992: 1139-1153.
7. David S. Memel, Dannis M Balfe and Richard C, Semlka In Joseph KT Lee, SS Sagel, RJ Stanley JP Heiken eds. Computed Tomography with MRl Correlation 3rd edn. Vol. 2. Philadelphia, Lippincott-Raven, 1998; 817-818.
8. Sherlock, Sheila. Cystic disease of the liver. In : Schiffs disease of liver. 8th edn. Philadelphia; Lipin Cott Raven 1999; 1083-1089.
9. Summerfield JA, NagaFuchi Y, Sherlock S, Cadatalch J, Scheuer PJ. Hepatobiliary Fibropolycystic disease. A clinical and histological Review of 51 patients. J Hepatol 1986; 2 : 141-156.
10. Bismuth H, Krissat J. Chodedochal cystic malignancies. Ann Oncol 1999; 10 : 94-98.
11. Fevery J, Tanghe W, Kerremans R et al. Congellital Dilatation of the intrahepatic bile ducts associated with the development of Amyloidosis.s 1972 : 13: 604-609.
12. Angela D Lavy, Charles A Rohrmann JR, Linda A Murakat: & Gael J Lonergan. Caroli Disease: Radiological spectrum with pathologic correlation. Am J Roentgenol 2002; 179 : 1053-1057.
13. Bruce P Parker. The Hepatobiliary system. In FN Silverman, J P Kuhn eds. Caffeys- Pediatric X-ray diagnosis: An Integrated imaging approach 9th edn. Vol. 2 Louis; Mosby, 1993; 928.
14. Kaiser JA, Hall JC, Salmen BJ, Parkar JJ. Diagnosis of caroli's disease by computed tomography report of 2 cases. Radiology 1979; 132 : 661-664.
15. Choi BI, Yeon KM, Kim SH, Han MC : "Caroli disease central dot sign in CT". Radiology 1990; 174 : 161-163.
16. MLN Moorthy. I Venkata Ratnam, P Chandra Mohan, MD Riyaz Khan R Prabhakar Rao. Images: "Central dot sign" on ultrasound-Diagnostic of caroli disease. Ind J Radiol Imag 2000; 10.
17. Ros E, Navarros, Bru C, Crilbert R, Bianchi L, Bruguera M. Ursodeoxycholic acid treatment of primary hepatolothiasis in caroli syndrome. Lancet 1993; 342: 404-406.
18. Reymond MJ, Herguet C, Danan C, et al. Partial hepatectomy in the treatment of caroli disease. Diag Dis Sci 1984; 29: 367 - 310.
19. Jonas MM, Perez Atayede AR. In Suchy FJ, Sokol RJ, Balistrei WF. eds. Liver disease in children. 2nd edn. Philadelphia; Lippincott, Williams and Wilkins; 2001; 904-905.(Gupta Ashish K, Gupta Ara)