Cholangitis overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farwa Haideri [2]
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Overview
Cholangitis is a clinically defined syndrome of fever, right upper quadrant pain and jaundice caused by infection of bile and inflammation of the biliary tree, usually due to obstruction and stasis.
Historical Perspective
First credited by Dr. Jean-Martin Charcot, Charcot's triad of fever, jaundice, and right upper quadrant abdominal pain is the classical presentation of cholangitis. By adding septic shock and mental status changes to the list of symptoms, Dr. Reynolds and Dr. Dargan changed Charcot's triad to Reynold's pentad. Until 1968, treatment of cholangitis was predominantly surgery, with exploration of the bile duct and excision of gallstones, until the ascendancy of endoscopic retrograde cholangiopancreatography (ERCP).
Classification
Acute cholangitis is classified into grade I, II or III, depending on the severity of the condition.
Pathophysiology
Cholangitis involves two main factors: bacterial increase and elevated intraductal pressure in the bile duct, both which allow for translocation of bacteria or endotoxins in the vascular system. Bacterial contamination alone does not usually result in cholangitis. Increased pressure in the biliary system, from obstruction in the bile duct, widens the spaces between the cells lining the duct, which brings bacterially contaminated bile into the bloodstream.
Causes
Cholangitis is usually caused by a bacterial infection, which can occur when there is blockage in the duct, such as a gallstone or tumor. The infection causing this condition may also spread to the liver.
Differential Diagnosis
Cholangitis must be differentiated from other causes of infection in the common bile duct as well as inflammation and infection of cholecystitis.
Epidemiology and Demographics
Cholangitis is most prevalent in adults, with roughly 20% of the population suffering from some form of abdominal pain from gallstones passing through the bile duct into the digestive tract.
Risk Factors
Common risk factors in the development of cholangitis are gallstones, sclerosing cholangitis, and HIV. Variations in treatment and risk factors influence mortality rates in patients with cholangitis, and these rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria.
Screening
There are no accepted screening programs for cholangitis or cholangiocarcinoma, a cancer associated with this disease. Methods do exist to detect the early onset of both diseases, though.
Natural History, Complications, and Prognosis
Patients who show early signs of multiple organ failure (renal failure, disseminated intravascular coagulation, alterations in the level of consciousness, and shock), evidence of acute cholangitis, and those who do not respond to conservative treatment, should receive systemic antibiotics and undergo emergent biliary drainage. Unless early and appropriate biliary drainage is performed and systemic antibiotics are administered, death will occur. The outcome is usually good with treatment, but poor without it.
Diagnosis
History and Symptoms
Obtaining the history is the most important aspect of making a diagnosis of cholangitis. It provides insight into cause, precipitating factors and associated comorbid conditions.
Physical Examination
Charcot's triad, which includes abdominal pain, jaundice, and fever is a set of three common findings in cholangitis. Reynold's pentad, which includes Charcot's triad and two other symptoms, septic shock and mental confusion, are also common markers in a physical examination for cholangitis. It is associated with significant morbidity and mortality.
Laboratory Findings
Laboratory tests provide useful clues in the diagnosis of cholangitis. Some commonly conducted tests are complete blood count, basic metabolic panel, liver function tests, blood culture, and other body fluid culture.
X-Ray
X-rays are not the most useful tool in diagnosing cholangitis and are mainly used to obtain a visual impression of the biliary system once an endoscopic retrograde cholangiopancreatography (ERCP) has been conducted.
CT
CT scans have a high sensitivity in localizing the site of obstruction for cholangitis.
MRI
Magnetic resonance imaging (MRI) has become the standard method for morphological examination of the bile ducts, particularly for diagnosing cholangitis. T1-weighted and T2-weight sequences offer different results.
Ultrasound
Ultrasounds (US) are the primary imaging modality for cholangitis. An US is both sensitive and specific in demonstrating biliary dilatation.
Other Imaging Findings
Magnetic resonance cholangiopancreatography (MRCP) and endoscopic sonography (EUS) are the most sensitive techniques to correctly determine the underlying cause and level of biliary obstruction in patients with acute cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) is also considered a gold standard test for biliary obstruction.
Other Diagnostic Studies
Blood tests to check levels of liver enzymes are the first step in diagnosing cholangitis. Doctors can confirm the diagnosis using cholangiography, which provides pictures of the bile ducts.
Diagnostic Criteria
Shown below are the diagnostic criteria for acute cholangitis according to Tokyo guidelines:
- The diagnosis is "suspected" in the case of the presence of one item in systemic inflammation with one item in either cholestasis or imaging findings.
- The diagnosis is "definite" in the case of the presence of one item in systemic inflammation, one item in cholestasis and one item in imaging.
| Clinical Manifestations | Changes from the baseline |
|---|---|
| Systemic inflammation | ♦ Fever >38℃ and/or shaking chills ♦ Evidence of inflammatory response: - WBC (×1000/μl) <4, or >10 - CRP (mg/dl) ≥1 |
| Cholestasis | ♦ Jaundice with total bilirubin ≥2 (g/dl ♦ Abnormal liver function tests: - ALP (IU) >1.5×STD - γGTP (IU) >1.5×STD - AST (IU) >1.5×STD - ALT (IU) >1.5×STD |
| Imaging findings | ♦ Biliary dilatation ♦ Evidence of the etiology (stricture, stone, stent etc.) on imaging (abdominal X-ray: KUB, abdominal USG, CT scan, MRI, MRCP and HIDA scan) |
Severity Assessment Criteria
The severity assessment criteria for acute cholangitis according to Tokyo guidelines is as follows.
Grade III Acute Cholangitis
Grade III or severe acute cholangitis is characterized by the onset of dysfunction in at least one of the following:
- Cardiovascular system: decreased blood pressure that necessitate the administration of dopamine (>5 μg/kg/min) or norepinephrine
- Neurological system: abnormal consciousness
- Respiratory system: PaO2/FiO2 ratio <300
- Renal system: serum creatinine >2.0 mg/dl, decreased urine output
- Hepatic system: PT-INR >1.5
- Hematological system: platelet count < 100,000/mm3
Grade II Acute Cholangitis
Grade II or moderate acute cholangitis is characterized by the presence of any two of the following:
- Abnormal WBC count: >12,000/mm3, <4,000/mm3
- Fever ≥39°C
- Age ≥75 years
- Elevated total bilirubin ≥5 mg/dl
- Decreased albumin level <0.7 x STD
Grade I Acute Cholangitis
Grade I or mild acute cholangitis does not meet the criteria of neither grade II (moderate) or grade III (severe) acute cholangitis.
Treatment
Medical Therapy
Antimicrobial therapy is indicated for acute cholangitis. Patients with community- acquired mild to moderate disease are treated with Cephalosporins. All other patients are treated with a combination of Metronidazole and either Imipenem-Cilastatin, Meropenem, Doripenem, Piperacillin-Tazobactam, Ciprofloxacin, Levofloxacin, or Cefepime.
Surgery
Surgery is not the preferred technique to improve the outcome of cholangitis. Initial management in patients can be conserved through proper antibiotics, as the majority of them can resolve symptoms.
Primary Prevention
Although reestablishing biliary drainage is the mainstay of treatment, antibiotics play an important role in the management of cholangitis.
Secondary Prevention
Secondary prevention strategies for cholangitis include continued treatment of predisposing causes in appropriate patients.
Cost-Effectiveness of Therapy
The most cost-effective technique to diagnose cholangitis is an ultrasound.