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Caroli's Disease hshish K. Gupta, Aradhana Gupta, V.K. Bhardwaj and Maya Chansoria 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. [Indian J Pediatr 2006; 73 (3) : 233-235] E-ma# :
[email protected];
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Key words : Carofi disease; Abdominal pain: Central dot sign Caroli's disease, first described by Jacques Caroli (1958) is a rare c o n g e n i t a l c o n d i t i o n c h a r a c t e r i z e d by nonobstructive saccular or fusiform multi-focal segmental dilatation of the i n t r a - h e p a t i c bile ducts. ~ M o d e 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 s u g g e s t e d an autosomal dominant mode of inheritance. 3 This disease usually p r e s e n t s with r e c u r r e n t c h o l a n g i t i s and hepatomegaly? CASE R E P O R T
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 a p p a r e n t l y healthy, without any history of liver and kidney diseases. fie belonged to a backward ~aste (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 e x p e c t e d w e i g h t of 25.80 kg (54% of expected weight) and height 106 cm as against expected height of 12,8.1 cm (82% of the expected height). Abdomen was soft and non tender9 Liver was palpable 5 cm below right costal margin with span of 8 cm in the right mid
Correspondence and Reprint requests : Dr. V.K. Bhardwaj, 2132,
Wright Town,Jabalpur-482 002. Indian Journal of Pediatrics, Volume 73--March, 2006
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 (Fig. 1)~ All other systems were clinically normal. Laboratory investigations showed anemia (Hb 9 gin%), elevated polymorphonuclear cells (TLC 10.8 x 103/~1with polymorph 76.4%) and raised ESR (30 mm at the end of 1 hour). Red b l o o d c o r p u s c l e s w e r e m i c r o c y t i c a n d 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 n o r m a l HbA2 (2.4%). Liver f u n c t i o n tests s h o w e d direct hyperbilirubinemia ~otal 2.25 rag/dl, direct 1.25 rag/dl,
Fig. 1. Clinical photograph of the patient showing hepatospleno-
megaly 233
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Ashish K. Gupta et al indirect I mg/d[), reversed A / G ratio (total Protein 7.14 gm/dl, albumin 3.10 g m / d l 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 D o p p l e r s t u d y s h o w e d evidence of multiple intrahepatic dilated biliary radicals (Fig. 2). CT scan showed bizarre, saccular dilatation of intrahepatic bile ducts involving almost all subsegments of Bismuth and C o r i n a u d s in v a r y i n g degree, most severely affecting right superior segment. Some of the cysts s h o w e d small internal h y p e r d e n s e - e n h a n c i n g nodule like focus consistenl with the Central Dot sign. (Fig. 3). 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 h o m o g e n o u s in
Fig. 2. CT scan showing Bizarre saccular dilatation of intrahepatic bile ducts most severely attecting right superior segment
Fig. 3. CT scan with contrast enhancement showing central dot sign. 234
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 s h o w any evidence of portal h y p e r t e n s i o n . 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, s.~Kidney lesions include renal tubular ectasia (medullary sponge kidney, cortical cyst), lesions of adult recessive polycystic kidhey 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. * incidence of Caroli s y n d r o m e is more than pure form of Caroli disease. * C h i l d r e n with Caroli disease m a y e x p e r i e n c e symptoms of intermittent abdominal pain, cholangitis, cholelithiasis, biliary abscess, septicemia and liver cirrhosis. Malignant complication (Cholangio carcinoma) is found in approximately 7% of cases. ~~ A m y l ~ d o s i s is also described as a complication of Caroli's disease, u The diagnosis of Caroli's disease in children involves recognition of the symptoms of liver d y s f u n c t i o n and i m a g i n g studies. I m a g i n g studies include abdominal sonography, CT scan, endoscopic r e t r o g r a d e c h o l a n g i o g r a p h y (ERC), p e r c u t a n e o u s t r a n s h e p a t i c c h o l a n g i o g r a p h y (PTC) and m a g n e t i c resonance cholangiography (MRC). I2 CT scan shows Central Dot sign in these patients2 3 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 p a t h o g n o m i c f i n d i n g in Caroli's disease ~',~' and it can also be demonstrated on USG. '" 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 a p p r o p r i a t e antibiotics. In case of i n t r a h e p a t i c cholelithiasis, litholytic therapy with Urso-deoxycholic acid is indicated. ~7 Partial hepatec~omy has also been shown to be effective if the biliary lesion is predominantly confined to discrete area and appears to increase the risk of malignancy2 ~ Diffuse involvement of both the lobes can be t r e a t e d with c o n s e r v a t i v e m a n a g e m e n t , Indian Journal of Pediatrics, Volume 73--March, 2006
Caroli's Disease endoscopic therapy (sphincterotomy for clearance of intra-hepatic s t o n e s ) , i n t e r n a l b i l i a r y b y p a s s p r o c e d u r e and in c a r e f u l l y selected cases w i t h liver t r a n s p l a n t a t i o n . ~" The child d i s c u s s e d in this r e p o r t is p u r e f o r m of Caroli disease w i t h n o e v i d e n c e of p e r i p o r t a l fibrosis a n d renal cystic d i s e a s e . T h e c h i l d a p p a r e n t l y a p p e a r s to b e a sporadic case of this disease. He also had sickle-cell disease w h i c h p a r t l y c o n t r i b u t e d to his clinical p i c t u r e . A l t h o u g h C a r o l i ' s d i s e a s e is a rare c o n g e n i t a l a n o m a l y , it should b e i n c l u d e d in d i f f e r e n t i a l d i a g n o s i s in c h i l d r e n presenting with abdominal pain and hepatomegaly.
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