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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.
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.
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 Charcot's triad.
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.
- Up to 9% of patients admitted to hospital with gallstone disease have acute cholangitis.
- Approximately 1% 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 years.
- Malignant disease (bile duct tumours, gallbladder tumours, ampullary tumours, pancreatic tumours and duodenal tumours) accounts for 10-30% of cases with acute cholangitis.
- Obstruction of the gallbladder or bile duct due to stones.
- 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.
- 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.
- 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.
- 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
- A. Systemic inflammation:
- A-1. Fever and/or shaking chills - temperature >38 °C.
- A-2. Laboratory data: evidence of inflammatory response - abnormal white blood cell counts, increase of serum C-reactive protein levels and other changes indicating inflammation.
- B. Cholestasis:
- B-1. Jaundice.
- B-2. Laboratory data: abnormal LFTs - increased serum ALP, γGTP (GGT), AST and ALT levels.
- C. Imaging:
- C-1. Biliary dilatation.
- C-2. Evidence of the aetiology on imaging (stricture, stone, stent, etc).
Suspected diagnosis: one item in A + one item in either B or C.
Definite diagnosis: one item in A, one item in B and one item in C.
- Gallstones and cholecystitis.
- Diverticular disease.
- Hepatitis - eg, viral hepatitis, drug-induced hepatitis.
- Mesenteric ischaemia.
- Other causes of septic shock.
- Liver failure.
- Liver abscess.
- Acute appendicitis.
- Perforated peptic ulcer.
- 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.
- If bile fluid is available (eg, biliary drainage through intervention has occurred), a sample should be sent for culture.
When acute cholangitis is suspected, diagnostic assessment includes abdominal X-ray (kidneys, ureters and bladder (KUB)) and abdominal ultrasound. Contrast-enhanced dynamic CT is the best method of diagnosing acute cholangitis, followed by MRI. Magnetic resonance cholangiopancreatography (MRCP) may also be necessary to detect non-calcified biliary stones.
The initial management consists of fluid resuscitation, correction of coagulopathy, and administration of broad-spectrum antibiotics.
- 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.
- Prevailing guidelines recommend treatment according to severity. By assessing the clinical picture, blood test results and imaging against the criteria laid down in the 2007 guidelines (and updated in 2013), it is possible to classify the severity of the condition as follows:
- Stage I - mild
- Stage II - moderate
- Stage III - severe
- The 2013 Tokyo guidelines furthermore acknowledged that determining severity against criteria could create some difficulty in reality. They advised that emergency biliary drainage should be carried out at any time when the condition becomes severe, as indicated by the development of:
- Shock (reduced blood pressure).
- Consciousness disturbance.
- Acute lung injury.
- Acute renal injury.
- Hepatic injury.
- Disseminated intravascular coagulation (DIC).
- Treatment for sepsis should be instituted according to prevailing guidelines.
- Management according to severity is as follows:
- Stage 1 - antimicrobial therapy, percutaneous, endoscopic or operative intervention for non-responders, depending on aetiology.
- Stage 2 - early percutaneous or endoscopic drainage with a T-tube. Endoscopic biliary drainage is recommended for acute cholangitis. More definitive surgery depending on aetiology will be required once the patient is stabilised.
- Stage 3 - treatment of organ failure (respiratory/circulatory) with ventilatory support, vasopressors, etc. Urgent percutaneous or endoscopic drainage or, in severe cases, decompression of the bile duct with a T-tube. Definitive treatment will be required once the clinical picture improves.
- Patients with severe sepsis can develop liver abscesses and liver failure, bacteraemia and Gram-negative 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.
The mortality rate is reported to be between 17% and 40%, depending on accompanying medical problems and age. Early endoscopic drainage after stabilisation of the patient significantly improves the prognosis. Failure to respond to conservative therapy and underlying malignant aetiology are unfavourable factors.
Further reading and references
Lee SP, Roberts JR, Kuver R; The changing faces of cholangitis. F1000Res. 2016 Jun 175. pii: F1000 Faculty Rev-1409. doi: 10.12688/f1000research.8745.1. eCollection 2016.
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 Jan20(1):1-7. doi: 10.1007/s00534-012-0566-y.
Cameron P et al; Textbook of Adult Emergency Medicine, 2014.
What if it's acute cholangitis?; Drug Ther Bull. 2005 Aug43(8):62-4.
Szary NM, Al-Kawas FH; Complications of endoscopic retrograde cholangiopancreatography: how to avoid and manage them. Gastroenterol Hepatol (N Y). 2013 Aug9(8):496-504.
Lee JG; Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. 2009 Sep6(9):533-41. doi: 10.1038/nrgastro.2009.126. Epub 2009 Aug 4.
Mosler P; Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep. 2011 Apr13(2):166-72. doi: 10.1007/s11894-010-0171-7.
Buyukasik K et al; Diagnostic and Therapeutic Value of ERCP in Acute Cholangitis, Gastroenterology, 2013.
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