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{{Cholangitis}}


==Overview==
==Overview==
Cholangitis is an [[infection]] of the [[bile duct]], which transports [[bile]] from the [[liver]] to the [[intestines]] and the [[gallbladder]]. Symptoms include [[fever]], [[right upper quadrant pain]], and [[jaundice]] due to the infection of the bile duct and [[inflammation]] of the [[biliary tree]], which is usually the result of obstruction and [[stasis]].


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==
*Dr. Jean-Martin Charcot, a French physician, is credited with discovering the disease in the late 19th century. He referred to the condition as "hepatic fever."
**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. B. M. Reynolds and Dr. Everett L. Dargan changed Charcot's triad to Reynold's pentad.
*Until 1968, the mainstay of treatment of cholangitis was [[surgery]], with exploration of the [[bile duct]] and excision of [[gallstones]], until the advent of [[endoscopic retrograde cholangiopancreatography]] (ERCP).
 
==Classification==
Acute cholangitis is classified into grade I, II, or III, depending on the severity of the condition.


==Historical Perspective==
==Pathophysiology==  
Cholangitis was first described as a life-threatening disorder in 1877 by Charcot.  In 1955, Reynolds and Dargan recognized that [[septic shock]] and mental status changes portended a poor outcome. (Reynolds’s Pentad). <ref>Kadakia S.  Biliary Tract Emergencies.  Med Clin North Amer. 1993, 77(5) 1015-1036. PMID 8371614</ref> <ref>Carpenter H. Bacterial and Parasitic Cholangitis. May Clin Proc. 1998, 73:473-478. PMID 9581592</ref> <ref>Leese T, Neoptolemos JP, Baker AR.  Management of acute cholangitis and the impact of endoscopic sphincterotomy. Br J Surg. 1986, 73:988. PMID 3790964</ref> <ref>Lai ECS, Mok FPT, Tan ESY.  Endoscopic biliary drainage for severe acute cholangitis.  NEJM 1992, 326:1582-6. PMID 1584258</ref>
Cholangitis involves two main factors: an increase in the bacterial presence and elevated intraductal pressure in the [[bile duct]], both of which allow for the [[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==
==Causes==
Cholangitis is usually caused by a [[bacterial infection]], which can occur when the duct is blocked by something, such as a [[gallstone]] or [[tumor]]. The [[infection]] causing this condition may also spread to the [[liver]].
Cholangitis is usually caused by a [[bacterial infection]], which can occur due to blockage in the [[duct]], such as from 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 from [[inflammation]] and infection of [[cholecystitis]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Parasites are commonly associated with cholangitis outside of the United States. Parasites associated with cholangitis include the Ascaris, Opisthorchis, Clonorchis, Fasciola and Echinococcus. Ascaris is thought to be the etiologic agent of recurrent pyogenic cholangitis (Oriental cholangiohepatitis) found in Hong Kong, Southeast Asia, Columbia, Italy and South Africa. As they migrate to the biliary tree, they bring gut flora with them predisposing to bacterial infection. Dying worms lead to [[inflammation]], [[granulomatous]] scarring and [[fibrosis]] which may lead to [[biliary cirrhosis]]. Opisthorchis and Clonorchis are transmitted by raw fish in Asia, Europe and Siberia and “frequently” lead to the development of [[cholangiocarcinoma]]. Fasciola is transmitted by colonized watercress and does not predispose to cholangiocarcinoma.
Cholangitis is most prevalent in adults, with roughly 20% of the adult 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 underscore the necessity for standardized diagnostic, treatment, and severity assessment criteria.
 
==Screening==
There are no established screening processes for [[cholangitis]] or [[cholangiocarcinoma]], a cancer associated with this disease. There are methods to detect the early onset of both diseases.
 
==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]]) or evidence of acute cholangitis, as well as 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. Prognosis is usually good with treatment, but poor without it.


==Diagnosis==
==Diagnosis==
===History and Symptoms===
===History and Symptoms===
The classical clinical manifestation of [[Cholangitis]] is described by [[Charcot's triad]] and includes [[fever]], right upper quadrant pain, and [[jaundice]]. In suppurative cholangitis [[hypotension]], and [[confusion]] can occur. The pentad of presentation is then called as Reynold's pentad. Reynold's pentad is associated with significant morbidity, and mortality.
A positive history of [[gallstones]] and [[common bile duct]] stones, recent [[cholecystectomy]], endoscopic manipulation or [[endoscopic retrograde cholangiopancreatography]] (ERCP), [[cholangiogram]] and history of [[HIV]] or [[AIDS]]. Symptoms of cholangitis include [[fever]], [[abdominal pain]], [[nausea and vomiting]], [[Jaundice|jaundice/yellowish discoloration of skin]], [[acholic stools]]/pale stools, [[pruritus]], [[malaise]], and [[confusion]]
 
===Physical Examination===
[[Charcot's triad]], which includes [[abdominal pain]], [[jaundice]], and [[fever]], describes three common findings in cholangitis. Reynold's pentad, which includes Charcot's triad and two other symptoms, [[septic shock]] and [[mental confusion]], also provides common markers in a physical examination for cholangitis. Cholangitis is associated with significant [[morbidity]] and [[mortality]].
 
===Laboratory Findings===
===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.
Laboratory tests provide useful clues in the diagnosis of [[cholangitis]]. Some commonly conducted tests include [[complete blood count]], [[basic metabolic panel]], [[liver function tests]], [[blood culture]], and other body fluid cultures.
 
===X-Ray===
There are no x-ray findings associated with acute cholangitis.
 
===CT===
===CT===
CT has a higher sensitivity (63%) and is better to localize the site of obstruction.
CT scans may be helpful in locating, with high sensitivity, the site of the obstruction responsible for a case of cholangitis.
==Diagnosis==
 
===MRI===
There are no MRI findings associated with acute cholangitis.
 
===Ultrasound===
[[Ultrasounds]] (US) are the primary imaging modality for cholangitis. An US is both sensitive and specific in demonstrating biliary dilatation.
 
===Other Imaging Findings===
There are no other imaging findings associated with cholangitis
 
===Other Diagnostic Studies===
[[Endoscopic retrograde cholangiopancreatography]] ([[ERCP]]) is considered a gold standard test for biliary obstruction. [[Magnetic resonance cholangiopancreatography]] (MRCP) and Percutaneous transhepatic cholangiography (PTCA) are the most sensitive techniques to correctly determine the underlying cause and level of biliary obstruction in patients with acute cholangitis when [[ERCP]] fails.
 
===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.
 
{| class="wikitable"
!Clinical Manifestations!! Changes from the baseline
|-
| '''Systemic inflammation'''|| ♦ Fever >38℃ and/or shaking chills<br>♦ Evidence of inflammatory response:<br> - WBC (×1000/μl) <4, or >10 <br> - CRP (mg/dl) ≥1
|-
| '''Cholestasis'''|| ♦ Jaundice with total bilirubin ≥2 (g/dl)<br>♦ Abnormal liver function tests:<br>- ALP (IU) >1.5×STD <br>- γGTP (IU) >1.5×STD <br>- AST (IU) >1.5×STD <br>- ALT (IU) >1.5×STD
|-
| '''Imaging findings'''|| ♦ Biliary dilatation<br>♦ 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 are 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 necessitates 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/mm<sup>3</sup>
 
====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/mm<sup>3</sup>, <4,000/mm<sup>3</sup>
* 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 either 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|Imipenem-Cilastatin]], [[Meropenem]], [[Doripenem]], [[Piperacillin-Tazobactam]], [[Ciprofloxacin]], [[Levofloxacin]], or [[Cefepime]].
 
===Surgery===
Surgery is not recommended for the treatment of cholangitis.
 
===Primary Prevention===
===Primary Prevention===
Treatment of [[gallstones]], [[tumors]], and infestations of parasites may reduce the risk for some people. A metal or plastic [[stents]] within the bile system may be needed to prevent recurrence.
Although re-establishing biliary drainage is the main focus 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.


==References==
==References==
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{{Reflist|2}}
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Latest revision as of 20:55, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2],Farwa Haideri [3]

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Overview

Cholangitis is an infection of the bile duct, which transports bile from the liver to the intestines and the gallbladder. Symptoms include fever, right upper quadrant pain, and jaundice due to the infection of the bile duct and inflammation of the biliary tree, which is usually the result of obstruction and stasis.

Historical Perspective

Classification

Acute cholangitis is classified into grade I, II, or III, depending on the severity of the condition.

Pathophysiology

Cholangitis involves two main factors: an increase in the bacterial presence and elevated intraductal pressure in the bile duct, both of which allow for the 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 due to blockage in the duct, such as from 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 from inflammation and infection of cholecystitis.

Epidemiology and Demographics

Cholangitis is most prevalent in adults, with roughly 20% of the adult 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 underscore the necessity for standardized diagnostic, treatment, and severity assessment criteria.

Screening

There are no established screening processes for cholangitis or cholangiocarcinoma, a cancer associated with this disease. There are methods to detect the early onset of both diseases.

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) or evidence of acute cholangitis, as well as 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. Prognosis is usually good with treatment, but poor without it.

Diagnosis

History and Symptoms

A positive history of gallstones and common bile duct stones, recent cholecystectomy, endoscopic manipulation or endoscopic retrograde cholangiopancreatography (ERCP), cholangiogram and history of HIV or AIDS. Symptoms of cholangitis include fever, abdominal pain, nausea and vomiting, jaundice/yellowish discoloration of skin, acholic stools/pale stools, pruritus, malaise, and confusion

Physical Examination

Charcot's triad, which includes abdominal pain, jaundice, and fever, describes three common findings in cholangitis. Reynold's pentad, which includes Charcot's triad and two other symptoms, septic shock and mental confusion, also provides common markers in a physical examination for cholangitis. Cholangitis is associated with significant morbidity and mortality.

Laboratory Findings

Laboratory tests provide useful clues in the diagnosis of cholangitis. Some commonly conducted tests include complete blood count, basic metabolic panel, liver function tests, blood culture, and other body fluid cultures.

X-Ray

There are no x-ray findings associated with acute cholangitis.

CT

CT scans may be helpful in locating, with high sensitivity, the site of the obstruction responsible for a case of cholangitis.

MRI

There are no MRI findings associated with acute cholangitis.

Ultrasound

Ultrasounds (US) are the primary imaging modality for cholangitis. An US is both sensitive and specific in demonstrating biliary dilatation.

Other Imaging Findings

There are no other imaging findings associated with cholangitis

Other Diagnostic Studies

Endoscopic retrograde cholangiopancreatography (ERCP) is considered a gold standard test for biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) and Percutaneous transhepatic cholangiography (PTCA) are the most sensitive techniques to correctly determine the underlying cause and level of biliary obstruction in patients with acute cholangitis when ERCP fails.

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 are 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 necessitates 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 either 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 recommended for the treatment of cholangitis.

Primary Prevention

Although re-establishing biliary drainage is the main focus 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.

References


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