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Cholangitis
Acute cholecystitis is an acute inflammatory disease of the gallbladder, often caused by gallstones; however, many factors (eg, ischaemia, motility disorders, chemical injury, infections by micro-organism, protozoon and parasites, collagen disease, and allergic reactions) are also involved. [1] The term hepatic fever was used for the first time by Charcot in his report published in 1887. Intermittent fever accompanied by chills, right upper quadrant abdominal pain, and jaundice have been established as Charcots triad. [1] Acute obstructive cholangitis was defined by Reynolds and Dargan in 1959 as a syndrome consisting of lethargy or mental confusion and shock, as well as fever, jaundice, and abdominal pain caused by biliary obstruction. These five symptoms were then called Reynolds' pentad. [1] Bile is normally sterile; however, if the common bile duct (CBD) is obstructed the flow of bile is reduced (biliary stasis) and infection can occur. Infection can also flow in a retrograde direction up the CBD as a result of acute cholecystitis or instrumentation such as endoscopic retrograde cholangiopancreatography (ERCP). The most common in the UK are Klebsiella spp., Escherichia coli , Enterobacter spp., enterococci and streptococci. More than one organism may be involved. Outside the UK, cholangitis can be caused by roundworm and liver fluke.

NB: primary sclerosing cholangitis is an aetiologically unrelated idiopathic condition which is dealt with in a
separate article.

Epidemiology [1]
Up to 9% of patients admitted to hospital with gallstone disease have acute cholangitis. [2] 0.5-2.4% of patients develop cholangitis after ERCP. The racial distribution pattern follows to some extent the races in which there is a high prevalence of gallstones - ie fair-skinned people of Northern European descent, Hispanics, native Americans and Pima Indians. The male to female ratio is equal. The median age of presentation is 50-60. Malignant disease (bile duct tumours, gallbladder tumours, ampullary tumours, pancreatic tumours and duodenal tumours) accounts for 10-30% of cases with acute cholangitis.

Aetiology [3] [4]

Obstruction of the gallbladder or bile duct due to stones ERCP Tumours - pancreatic cancer, cholangiocarcinoma, ampullary cancer, porta hepatis tumours or metastasis Bile duct stricture or stenosis Choledochocele (cyst or diverticulum of the CBD) AIDS cholangiopathy Parasitic infection - roundworm, liver fluke

Presentation
50-70% of patients present with classic Charcot's triad of jaundice, fever and right upper quadrant pain. In elderly patients, the abdominal pain may be poorly localised.

Page 2 of 4 Acute cholangitis is graded in severity from grade I (mild), grade II (moderate) and grade III (severe). Severe acute cholangitis is acute cholangitis associated with at least one of cardiovascular, neurological, respiratory, renal, hepatic and/or haematological dysfunction. [1] 10-20% of patients also present with the additional features of hypotension due to septic shock and mental confusion - the Reynolds' pentad. The patient may also report acholic (putty-coloured) stools and pruritus. A history of gallstones, CBD stones, recent cholecystectomy, ERCP or other invasive procedures, HIV or AIDS may assist the diagnosis. Some patients present with several attacks, usually in association with untreated biliary stones (recurrent pyogenic cholangitis). Physical signs may include fever, right upper quadrant tenderness, jaundice, mental status changes, hypotension and tachycardia. Peritonism is an unusual sign and should stimulate the search for an alternative diagnosis.

Diagnostic criteria for acute cholangitis [1]

A. Systemic inflammation: Fever and/or shaking chills Laboratory data: evidence of inflammatory response - eg, abnormal white blood cell count, raised CRP B. Cholestasis Jaundice Laboratory data: abnormal LFTs; increased serum ALP, AST, ALT and gamma-GT levels C. Imaging Biliary dilatation Evidence of the aetiology on imaging (eg, stricture, stone, stent) Suspected diagnosis: 1 item in A. and 1 item in either B. or C. Definite diagnosis: 1 item in A. and 1 item in B. and 1 item in C.

Differential diagnosis
Gallstones and cholecystitis Diverticular disease Hepatitis - eg, viral hepatitis, drug-induced hepatitis Mesenteric ischaemia Pancreatitis Other causes of septic shock Cirrhosis Liver failure Liver abscess Acute appendicitis Perforated peptic ulcer Pyelonephrosis

Investigations
Blood tests
FBC: the white cell count is usually raised. Inflammatory markers: ESR and CRP may be raised. LFTs: typically show pattern of obstructive jaundice. Kidney function tests and electrolytes: associated renal dysfunction. Blood cultures. Amylase may be raised and then often indicates involvement of the lower part of the common bile duct.

Page 3 of 4 If bile fluid is available (eg, biliary drainage through intervention has occurred), a sample should be sent for culture.

Imaging
When acute cholangitis is suspected, diagnostic assessment includes abdominal X-ray (kidneys, ureters and bladder (KUB)) and abdominal ultrasound, followed by CT scan, MRI, magnetic resonance cholangiopancreatography (MRCP) and hepatobiliary iminodiacetic acid (HIDA) scan. [1]

Management
The initial management consists of fluid resuscitation, correction of coagulopathy, and administration of broadspectrum antibiotics. [4] Resuscitation may be required for patients with septic shock and due attention should be given to oxygenation and correction of fluid and electrolyte imbalance. Vital signs should be monitored. Parenteral antibiotics should be administered once blood cultures have been taken. The drugs selected should be effective against anaerobes and Gram-negative organisms. Most patients with acute cholangitis respond to antibiotic therapy, but endoscopic biliary drainage is ultimately required to treat the underlying obstruction. [3] The type and timing of biliary drainage is based on the severity of the clinical presentation, and the availability and feasibility of drainage techniques. The international symposium on acute cholangitis recommended the following: [1] Stage I - observation Stage II - early biliary drainage Stage III - urgent biliary drainage Endoscopic biliary drainage is recommended for acute cholangitis. Percutaneous transhepatic biliary cholangitis drainage may be considered as an alternative when endoscopic biliary drainage is difficult. [1] Further surgery may be required electively once the patient stabilises, if the initial cause has not been dealt with at the time of emergency surgery. [4] Open surgical drainage is rarely performed. In patients with acute cholangitis due to unresectable neoplasms like cancer of the pancreatic head, hepaticojejunostomy can be performed as bypass surgery only in patients without severe acute cholangitis. [1] Recurrent pyogenic cholangitis may require more radical surgery such as liver resection. [5]

Complications
Patients with severe sepsis can develop liver abscesses and liver failure, bacteraemia and Gramnegative sepsis. Severe acute cholangitis may cause septic shock, acute kidney injury and cardiovascular, neurological, respiratory, renal, hepatic and/or haematological dysfunction. Patients treated with percutaneous or endoscopic drainage can develop intra-abdominal or percutaneous bleeding, sepsis, fistulae and bile leakage.

Prognosis
The mortality rate is about 10%. [6] A poor prognosis is associated with: Age older than 50 years, female gender High malignant strictures; cholangitis following percutaneous transhepatic cholangiography Hypotension, acute kidney injury, liver abscess Cirrhosis, inflammatory bowel disease Failure to respond to antibiotics and conservative therapy A white cell count on admission of 20 x 10 9/L and total bilirubin of 880 mol/L [6]

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Further reading & references

1. Takada T, Strasberg SM, Solomkin JS, et al; TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2013 Jan;20(1):1-7. doi: 10.1007/s00534-012-0566-y. 2. What if it's acute cholangitis?; Drug Ther Bull. 2005 Aug;43(8):62-4. 3. Lee JG; Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. 2009 Sep;6(9):533-41. doi: 10.1038/nrgastro.2009.126. Epub 2009 Aug 4. 4. Mosler P; Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep. 2011 Apr;13(2):166-72. doi: 10.1007/s11894-010-0171-7. 5. Al-Sukhni W, Gallinger S, Pratzer A, et al; Recurrent pyogenic cholangitis with hepatolithiasis--the role of surgical therapy in North America. J Gastrointest Surg. 2008 Mar;12(3):496-503. Epub 2007 Nov 13. 6. Rosing DK, De Virgilio C, Nguyen AT, et al; Cholangitis: analysis of admission prognostic indicators and outcomes. Am Surg. 2007 Oct;73(10):949-54. Original Author: Dr Laurence Knott Last Checked: 02/08/2013 Current Version: Dr Colin Tidy Document ID: 1949 Version: 25 Peer Reviewer: Dr Adrian Bonsall EMIS

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