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{{Cholangitis}}
{{Cholangitis}}


==Overview==
==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]].
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==
==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==  
==Classification==  
Acute cholangitis is classified into grade I, II or III, depending on the severity of the condition.
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==
==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==
==Differential Diagnosis==
Cholangitis must be differentiated from other causes of [[infection]] in the [[common bile duct]] as well as [[inflammation]] and infection of [[cholecystitis]].
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==
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]].
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==
==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.
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==
==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.
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==
==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]]) as well as evidence of acute cholangitis ([[fever]] accompanied by chills and shivering, [[jaundice]], and [[abdominal pain]]), and 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.
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===
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.
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===
===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]].
[[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===
===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.
There are no x-ray findings associated with acute cholangitis.


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


===MRI===
===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.
There are no MRI findings associated with acute cholangitis.


===Ultrasound===
===Ultrasound===
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===Other Imaging Findings===
===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.
There are no other imaging findings associated with cholangitis


===Other Diagnostic Studies===
===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]].
[[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===
===Diagnostic Criteria===
Shown below are the diagnostic criteria for acute cholangitis according to Tokyo guidelines:<ref name="Mayumi-2013">{{Cite journal  | last1 = Mayumi | first1 = T. | last2 = Someya | first2 = K. | last3 = Ootubo | first3 = H. | last4 = Takama | first4 = T. | last5 = Kido | first5 = T. | last6 = Kamezaki | first6 = F. | last7 = Yoshida | first7 = M. | last8 = Takada | first8 = T. | title = Progression of Tokyo Guidelines and Japanese Guidelines for management of acute cholangitis and cholecystitis. | journal = J UOEH | volume = 35 | issue = 4 | pages = 249-57 | month = Dec | year = 2013 | doi =  | PMID = 24334691 }}</ref>
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 "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.
*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"
{| class="wikitable"
!Clinical Manifestations!! Changes from the baseline
!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
| '''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
| '''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)
| '''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===
===Severity Assessment Criteria===
The severity assessment criteria for acute cholangitis according to Tokyo guidelines is as follows.
The severity assessment criteria for acute cholangitis according to Tokyo guidelines are as follows:


====Grade III Acute Cholangitis====
====Grade III Acute Cholangitis====
Grade III or severe acute cholangitis is characterized by the onset of dysfunction in at least one of the following:
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
*Cardiovascular system: decreased blood pressure that necessitates the administration of dopamine (>5 μg/kg/min) or norepinephrine
*Neurological system: abnormal consciousness
*Neurological system: abnormal consciousness
*Respiratory system: PaO2/FiO2 ratio <300
*Respiratory system: PaO2/FiO2 ratio <300
Line 87: Line 100:


====Grade II Acute Cholangitis====
====Grade II Acute Cholangitis====
Grade II or moderate acute cholangitis is characterized by the presence of any two of the following:
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>
* Abnormal WBC count: >12,000/mm<sup>3</sup>, <4,000/mm<sup>3</sup>
Line 96: Line 109:


====Grade I Acute Cholangitis====
====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.
Grade I, or mild acute cholangitis, does not meet the criteria of either grade II (moderate) or grade III (severe) acute cholangitis.


==Treatment==
==Treatment==
===Medical Therapy===
===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]].
[[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===
Surgery is not the mainstay of improving the outcome of cholangitis. Initial management in patients can be conserved through proper [[antibiotics]], as the majority of them can resolve symptoms.
Surgery is not recommended for the treatment of cholangitis.


===Primary Prevention===
===Primary Prevention===
Although reestablishing biliary drainage is the mainstay of treatment, [[antibiotics]] play an important role in the management of cholangitis.
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===
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==References==
==References==
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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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