Carloi’s Disease [الأرشيف] - قصر العيني

nabilprofelgen

05-11-2004, 04:42 PM

Carloi’s Disease<o:p></o:p>

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BackGround: Caroli disease/syndrome is a rare congenital disorder of the intrahepatic bile ducts. It is characterized by intrahepatic dilatation of the biliary tree, thought to be the result of a pathologic developmental process known as a ductal plate malformation (DPM). Caroli disease/syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD), and both the hepatic and renal processes are thought to reflect a developmental process, albeit in the context of different organs. A rare association with autosomal dominant polycystic kidney disease (ADPKD) has also been reported. <o:p></o:p>

The term Caroli disease is applied if the hepatic disease is limited to ectasia or segmental dilatation of the larger intrahepatic ducts. This form is much less common than Caroli syndrome, in which malformations of smaller bile ducts and congenital hepatic fibrosis are also present. <o:p></o:p>

Pathophysiology: The precursor of the intrahepatic biliary tree is a double-layered sleeve of cells known as the ductal plate (DP). The DP first arises from hepatocyte precursors surrounding hilar portal vein vessels at 8 weeks' gestation, and more peripheral regions of the DP then develop sequentially. During the remainder of gestation, a process of DP remodeling occurs in which small areas of the double layer separate to form tubules, which join to form the intrahepatic biliary tree, while the remaining regions of the DP involute. Caroli disease/syndrome is a subcategory of diseases thought to originate from failures of this process known collectively as DPM. <o:p></o:p>

In Caroli disease, DPM occurs at the level of the larger intrahepatic ducts (ie, left and right hepatic ducts, segmental ducts), resulting in dilatation and ectasia. The resulting biliary stasis may lead to cholelithiasis, cholangitis, and sepsis, as well as an increased risk of cholangiocarcinoma. <o:p></o:p>

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In Caroli syndrome, DPM occurs at all levels of bile duct formation. In the more peripheral biliary tree, DPM is associated with portal vein malformations as well as fibrosis of the portal tracts and/or fibrous bands extending across adjacent portal tracts. These findings are typical of congenital hepatic fibrosis (CHF); therefore, Caroli syndrome is thought to exist in the same spectrum of disease as CHF. <o:p></o:p>

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· In the <st1:country-region><st1:place>US</st1:place></st1:country-region>: Because Caroli disease/syndrome rarely occurs in the <st1:country-region><st1:place>United States</st1:place></st1:country-region>, the exact frequency is unknown. Caroli syndrome (large and small bile duct ectasia with CHF) is much more common than Caroli disease (large bile duct ectasia only). <o:p></o:p>

Mortality/Morbidity: Patients with Caroli disease/syndrome may experience recurrent episodes of cholangitis and are also at risk for associated bacteremia and sepsis. <o:p></o:p>

· Patients with Caroli syndrome may experience cholangitis, as do those with Caroli disease, but they may also manifest the complications of portal hypertension observed in CHF. <o:p></o:p>

· Both Caroli disease and Caroli syndrome are associated with ARPKD, and patients may have varying degrees of renal cysts, interstitial fibrosis, and renal failure. <o:p></o:p>

· Both Caroli disease and Caroli syndrome are associated with risk of cholangiocarcinoma at a rate of 100 times that of the general population. <o:p></o:p>

***: Symptoms of Caroli disease/syndrome are more common in females. <o:p></o:p>

Age: Symptoms appear first in adults, although childhood and neonatal cases have been reported<o:p></o:p>

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History: <o:p></o:p>

· History of intermittent abdominal pain may be present, reflecting episodes of bile stasis or bile stone passage.<o:p></o:p>

· Patients with cholangitis may report fever and right upper quadrant abdominal pain.<o:p></o:p>

· Portal hypertension in Caroli syndrome may result in hematemesis or melena.<o:p></o:p>

· Because Caroli disease/syndrome is associated with ARPKD and appears to be inherited in an autosomal recessive manner, a family history of kidney or liver disease may be present.<o:p></o:p>

Physical: <o:p></o:p>

· Hepatomegaly is present.<o:p></o:p>

· Splenomegaly occurs.<o:p></o:p>

· Right upper quadrant tenderness is occasionally present.<o:p></o:p>

· Abdominal mass or masses occur if large polycystic kidneys are present.<o:p></o:p>

· Jaundice rarely is present.<o:p></o:p>

Causes: <o:p></o:p>

· A genetic cause is likely, given the association with ARPKD, but specific causative mutations have not been identified.<o:p></o:p>

· Caroli disease/syndrome appears to be inherited in an autosomal recessive manner.<o:p></o:p>

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Lab Studies: <o:p></o:p>

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Bilirubin usually is within the reference range.<o:p></o:p>

Transaminases may be slightly elevated.<o:p></o:p>

CBC may reveal thrombocytopenia and leukopenia if portal hypertension and hypersplenism are present. An elevated WBC count or erythrocyte sedimentation rate (ESR) may indicate cholangitis.<o:p></o:p>

Creatinine and BUN should be obtained to detect associated renal disease.<o:p></o:p>

Imaging Studies: <o:p></o:p>

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Ultrasonography is the best initial imaging study because it reveals the irregular dilatation of the large intrahepatic bile ducts typical of Caroli disease/syndrome. Extrahepatic biliary dilatation may also be present as a result of prior cholelithiasis. Doppler evaluation of the liver can be used to detect portal hypertension. Kidneys can also be assessed for evidence of polycystic kidney disease.<o:p></o:p>

Computed tomographic imaging may also be used, particularly if ultrasound cannot be obtained because of bowel gas or body habitus.<o:p></o:p>

Hepatobiliary scintigraphy and magnetic resonance cholangiography have also been used in the diagnosis of Caroli disease/syndrome.<o:p></o:p>

Procedures: <o:p></o:p>

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Liver biopsy and culture should be performed in cases of suspected chronic cholangitis.<o:p></o:p>

Endoscopic retrograde cholangiopancreatography has been used in identification and treatment of biliary stones in patients with Caroli disease/syndrome, but it is associated with a risk of cholangitis postprocedure.<o:p></o:p>

Portosystemic shunting may be indicated in patients who have portal hypertension.<o:p></o:p>

Histologic Findings: Liver biopsy reveals the typical pattern of DPM, with bile duct ectasia, portal vein malformations, and fibrosis. In Caroli syndrome, DPM is evident throughout the liver, whereas only larger intrahepatic ducts are affected in the much more rare Caroli disease. <o:p></o:p>

TREATMENT :<o:p></o:p>

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· Medical Care: The use of ursodeoxycholic acid can decrease the frequency of complications due to cholelithiasis. Broad-spectrum antibiotic coverage, including anaerobic coverage, is indicated in cases of cholangitis. <o:p></o:p>

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· Surgical Care: Surgical treatment may be necessary for recurrent or refractory cholangitis. Obstructing stones can be removed and bile flow can be maintained via hepaticojejunostomy or external drainage. <o:p></o:p>

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In cases of localized stasis, lobectomy can be curative and can also reduce the risk of cholangiocarcinoma.<o:p></o:p>

In severe cases of refractory or chronic cholangitis or in cases of liver failure, transplantation may be considered.<o:p></o:p>

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MEDICATION :<o:p></o:p>

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Ursodiol can promote the dissolution of intrahepatic stones and promote bile flow in Caroli disease/syndrome. <o:p></o:p>

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Broad-spectrum antibiotics are used in the treatment of cholangitis associated with Caroli disease/syndrome.<o:p></o:p>

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Drug Category: Gallstone dissolution agents -- Used to dissolve gallbladder stones. Enhances bile salt–dependent biliary flow. Also acts as choleretic agents and may prove to be a valuable addition to therapy in repeated and refractory cholangitis. Drug Name<o:p></o:p>

Ursodiol (Urso, Actigall) -- Also called ursodeoxycholic acid. A naturally occurring bile acid that is used to dissolve radiolucent gallstones. Suppresses hepatic cholesterol synthesis, cholesterol secretion, and inhibits cholesterol intestinal absorption. It has little inhibitory effect on synthesis and secretion into bile of endogenous bile acids and does not appear to affect phospholipid secretion into bile. It alters bile composition from supersaturated to unsaturated. Ursodiol-rich bile solubilizes cholesterol by increasing the concentration level at which saturation of cholesterol occurs. Shown to promote bile flow in cholestatic conditions associated with a patent extrahepatic biliary system. <o:p></o:p>

Adult Dose 8-10 mg/kg/d <st1:place>PO</st1:place> divided bid/tid <o:p></o:p>

Pediatric Dose Administer as in adults <o:p></o:p>

Contraindications Documented hypersensitivity; bile pigment or radiopaque stones; stones >20 mm diameter; extrahepatic biliary tree obstruction <o:p></o:p>

Interactions Aluminum-containing antacids, cholestyramine, and colestipol may decrease absorption <o:p></o:p>

Pregnancy B - Usually safe but benefits must outweigh the risks. <o:p></o:p>

Precautions Stone dissolution may take several months, and stone recurrence may occur; use with caution in patients with a nonvisualized gall bladder and those with chronic liver disease; GI effects include nausea, vomiting, diarrhea, or constipation; dermatologic effects include a rash; monitor hepatic enzymes <o:p></o:p>

Drug Category: Antibiotic agents -- Broad-spectrum antibiotics are used to treat cholangitis. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Drug Name<o:p></o:p>

Ampicillin and sulbactam (Unasyn) -- Drug combination of beta-lactamase inhibitor with ampicillin. Used to treat infections involving skin, enteric flora, and anaerobes. Provides broad gram-positive and anaerobic coverage. Should be combined with an agent with gram-negative coverage, such as an aminoglycoside. <o:p></o:p>

Adult Dose 1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin <o:p></o:p>

Pediatric Dose 3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h<o:p></o:p>

>12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin <o:p></o:p>

Contraindications Documented hypersensitivity <o:p></o:p>

Interactions Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of <st1:place>PO</st1:place> contraceptives <o:p></o:p>

Pregnancy B - Usually safe but benefits must outweigh the risks. <o:p></o:p>

Precautions Adjust dose in patients with renal impairment; potential cross-sensitivity to other beta-lactams <o:p></o:p>

Drug Name<o:p></o:p>

Gentamicin (Garamycin) -- Used to treat cholangitis. An aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. <o:p></o:p>

Adult Dose 5-6 mg/kg/d IV divided q8h; dosage and frequency must be adjusted based on serum drug levels <o:p></o:p>

Pediatric Dose Dosage and frequency must be adjusted based on serum drug levels<o:p></o:p>

Postnatal age <7 days:<o:p></o:p>

<28 weeks gestational age: 2.5 mg/kg IV q24h<o:p></o:p>

28-34 weeks gestational age: 2.5 mg/kg IV q18h<o:p></o:p>

>34 weeks gestational age: 2.5 mg/kg IV q12h<o:p></o:p>

Postnatal age >7 days:<o:p></o:p>

1200-2000 grams: 2.5 mg/kg IV q12h<o:p></o:p>

>2000 grams: 2.5 mg/kg IV q8h<o:p></o:p>

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<10 years: 2.5 mg/kg IV q8h<o:p></o:p>

>10 years: 5-6 mg/kg/d IV divided q8h <o:p></o:p>

Contraindications Documented hypersensitivity <o:p></o:p>

Interactions Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents (thus, prolonged respiratory depression may occur); coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly) <o:p></o:p>

Pregnancy D - Unsafe in pregnancy <o:p></o:p>

Precautions Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose and frequency in renal insufficiency and impairment <o:p></o:p>

FOLLOW-UP <o:p></o:p>

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· Further Inpatient Care: <o:p></o:p>

Indications for hospitalization<o:p></o:p>

Suspected cholangitis or sepsis<o:p></o:p>

Obstructing cholelithiasis requiring invasive intervention<o:p></o:p>

· Further Outpatient Care: <o:p></o:p>

Liver function tests and transaminases can be monitored as an outpatient.<o:p></o:p>

Ultrasonography can be used to monitor stones.<o:p></o:p>

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Prognosis: <o:p></o:p>

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 · Hepatic manifestations<o:p></o:p>

In the minority of patients who have intrahepatic ductal ectasia without associated CHF (ie, Caroli disease), the prognosis is determined largely by the frequency and severity of episodes of cholangitis, which may result in sepsis or death. Progressive liver failure may also develop, possibly requiring liver transplantation.<o:p></o:p>

Patients with both ductal ectasia and CHF (ie, Caroli syndrome) are subject to the risks and consequences of recurrent cholangitis as described above. They are also at risk for the complications of portal hypertension, namely variceal bleeding, hypersplenism, and thrombocytopenia.<o:p></o:p>

· Renal manifestations<o:p></o:p>

The degree of polycystic kidney disease associated with Caroli disease/syndrome is variable.<o:p></o:p>

Patients who present with renal disease as neonates or infants are more likely to have severe disease with enlarged cystic kidneys and progressive renal failure.<o:p></o:p>

Others may have normal-appearing kidneys or minimal cystic changes with only mild deficits in renal function.<o:p></o:p>

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Medical/Legal Pitfalls: <o:p></o:p>

Patients diagnosed with Caroli disease/syndrome should be screened for associated renal anomalies and impaired renal function.<o:p></o:p>

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Differential :<o:p></o:p>

· Cholelithiasis<o:p></o:p>

· Congenital Hepatic Fibrosis<o:p></o:p>

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<o:p> و يجعله عامر
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