What is a Cholangitis attack and what are the symptoms?

June 11, 2006

My daugher who was diagnosed in March has not had any attacks and I'd

like to know what to exptect if she ever does. What do I look for,

where is the pain and what do we do if it happens? What is the cause?

Is it possible that some people with PSC never have an attack and is

it most common as the disease progress' or can they occur early on as

well?

Thanks

Kim,

June 11, 2006

Hi Kim

For me I started with gallbladder attacks, which continued after my gallbladder was removed. A typical cholangitis attack may or may not start with nausea, and a feeling of fullness. (Like your food will not digest). Then the pain comes next and then the fever. The pain usually hits right below your rib cage and radiates into the right upper quadarant of your body, sometimes radiating into the middle of your back. Some times it just feels like you shoulder is about to tear apart. The pain become so horrible that you cannot breathe and at this point your only resolve is pain medication until the episode stops. I have had episodes lasting from 2 hours to 3 days. I am amazed of the people who do not get cholangitis attacks and hopefully your child will be one of the lucky ones. I'll pray for your family.

June 11, 2006

Hi

Kim,

My son is 32 he was dx

in 1999, he is stage 4 and has never had an attack.

Barb in Texas

June 11, 2006

Hi

Kim,

My son is 32 he was dx

in 1999, he is stage 4 and has never had an attack.

Barb in Texas

June 12, 2006

> ... What do I look for, where is the pain and what do we do if it

> happens? What is the cause?

> Is it possible that some people with PSC never have an attack and

is

> it most common as the disease progress' or can they occur early on

> as well?

Kim,

I classify attacks into those with and without infection. Signs of

an infection are fever or chills. When these symptoms are present

you should always seek treatment. When I have had bacterial

cholangitis causing fevers and chills I have not had any pain

associated with the attacks (perhaps I am lucky in that way). I delt

with the attacks by taking oral antibiotics (alternating Cipro and

Augmentin) at the first sign of an attack. My doctor discussed going

on a permanent antibiotic rotation rather than just taking

antibiotics when attacks occurred, but we felt I could be responsive

to the signs of attacks and that full time antibiotics would

increase the chance of developing resistant bacteria. Bacterial

cholangitis is caused by the growth of bacterial in the bile when it

is not flowing freely. Think of stagnant pools of bile behind

strictures breeding up large quantities of bacteria.

Attacks without fever or chills are going to be most noticeable when

they cause pain. Jaundice, cola colored urine or pale stools just

don't focus your attention like pain does. The attacks may require

treatment if the pain is severe, long lasting or causing other

complications – nausea, vomiting, inability to hold anything down.

Blockage of the bile ducts causes this type of attack, which

subsides when the blockage clears. Generally, if you can stand the

pain there is nothing wrong with waiting for it to pass. In my

experience, these types of attacks evolved into pancreatitis

(probably because the blockage occurred near the end of the common

bile duct) with extreme pain, nausea and vomiting causing me to seek

treatment at the ER in the middle of the night.

The timing of attacks is extremely variable. My first blockage

occurred 3 years after high LFTs were observed and 15 years before I

received a transplant. I didn't have any bacterial cholangitis

attacks until after an ERCP and roux-en-y surgery conducted 6 years

after my first blockage . In retrospect I think one or the other of

those procedures allowed bacteria to infiltrate the bile duct system

and start the cycle of feverish attacks.

Tim R, dx 1989, tx 1998, PSC recurrence 2002, relisted with a 19

MELD

June 12, 2006

I would also like more information on cholangitis.

1.How often does cholangitis sponanously in PSC i.e without ERCP.

My experience is like Tim's; no infection until after ERCP

2. Does prophalactic antibiotic use save lives by preventing

infection or cost lives because of the development of resistance

Here is a copy of a medical " textbook " that reviews cholangitis in

general without respect to PSC.

Acute cholangitis

Nezam H Afdhal, MD

UpToDate performs a continuous review of over 350 journals and other

resources. Updates are added as important new information is

published. The literature review for version 14.1 is current through

December 2005; this topic was last changed on September 15, 2005.

The next version of UpToDate (14.2) will be released in June 2006.

INTRODUCTION — Acute cholangitis is a clinical syndrome

characterized by fever, jaundice, and abdominal pain that develops

as a result of stasis and infection in the biliary tract.

Cholangitis was first described by Charcot as a serious and life-

threatening illness; however, it is now recognized that the severity

can range from mild to life-threatening [1].

The clinical features and therapy of acute cholangitis will be

reviewed here. The etiologic agents, clinical features, and

management options are quite different in patients with AIDS and are

discussed separately. (See appropriate topic reviews).

PATHOGENESIS — Acute cholangitis is caused primarily by bacterial

infection. The organisms typically ascend from the duodenum;

hematogenous spread from the portal vein is a rare source of

infection [2].

The most important predisposing factor for acute cholangitis is

biliary obstruction and stasis secondary to biliary calculi or

benign stricture (show picture 1). Chronic biliary obstruction

raises the intrabiliary pressure, a central pathogenetic event in

the development of acute cholangitis. High pressure promotes the

migration of bacteria from the portal circulation into the biliary

tract and subsequent colonization. It also favors migration of

bacteria from bile into the systemic circulation, resulting in a

higher incidence of septicemia [2]. One study, for example,

demonstrated a significant correlation between biliary and serum

levels of endotoxins and the clinical severity of acute cholangitis

[3].

In addition, increased biliary pressure adversely affects a number

of host defense mechanisms including [2]:

Hepatic tight junctions

Kupffer cells

Bile flow

IgA production

Mechanism of bacterial entry into the biliary tract — The sphincter

of Oddi normally forms an effective mechanical barrier to duodenal

reflux and ascending bacterial infection. The continuous flushing

action of bile plus the bacteriostatic activity of bile salts also

help to maintain bile sterility. Secretory IgA and biliary mucous

probably function as antiadherent factors, preventing bacterial

colonization.

When the barrier mechanism is disrupted, as occurs after endoscopic

sphincterotomy, choledochal surgery, or biliary stent insertion,

pathogenic bacteria enter the biliary system at high concentrations.

Thus, cholangitis frequently develops after endoscopic or

percutaneous manipulation with incomplete biliary drainage or as a

late complication of stent blockage.

However, bacteria can also pass spontaneously through the sphincter

of Oddi in small numbers. The presence of a foreign body, such as a

stone or stent, can then act as a nidus for bacterial colonization.

Bile taken from patients without obstruction is sterile or nearly

sterile [4]. In comparison, approximately 70 percent of all patients

with gallstones have evidence of bacteria in the bile [4,5].

Patients with common duct stones have a higher probability of bile

culture positivity than those with gallstones in the gallbladder or

cystic duct [4].

Bacteria can also be cultured from gallstones. In one study, for

example, 80 percent of brown pigment stones were culture positive,

and 84 percent showed scanning electron microscopic evidence of

bacterial structures [6]. The organisms recovered in culture were

typical of those seen in cholangitis (enterococci — 40 percent;

Escherichia coli — 17 percent; Klebsiella spp — 10 percent),

although the ratio of enterococci and E. coli was inverted from that

usually found in infected bile.

Some features of bacteria that may enhance pathogenicity in this

setting include:

External pili in Gram negative Enterobacteriaceae, which facilitate

attachment to foreign surfaces such as a stone or stent.

A glycocalyx matrix composed of exopolysaccharides produced by

bacteria which protect the organisms from host defense mechanisms

and may hinder penetration of antibiotics [6].

Bacteriology — Culture of bile, ductal stones, and blocked biliary

stents are positive in over 90 percent of cases, yielding a mixed

growth of gram negative and gram positive bacteria. The most common

bacteria isolated are of colonic origin [7]:

Escherichia coli is the major gram negative bacterium isolated (25

to 50 percent), followed by Klebsiella (15 to 20 percent) and

Enterobacter species (5 to 10 percent).

The most common gram positive bacteria are Enterococcus species (10

to 20 percent).

Anaerobes, such as Bacteroides and Clostridia, are usually present

as a mixed infection. They are rarely the sole infecting organisms

and it is not clear if they play a role in acute cholangitis.

Recovery of anaerobes appears to be more common after repeated

infections or surgery on the biliary tree. The frequency of

anaerobic infection is underestimated by standard culture

techniques.

CLINICAL MANIFESTATIONS — The classic triad of Charcot — fever,

right upper quadrant pain, and jaundice — occurs in only 50 to 75

percent of patients with acute cholangitis [8]. Confusion and

hypotension can occur in patients with suppurative cholangitis,

producing Reynold's pentad, which is associated with significant

morbidity and mortality [9]. Hypotension may be the only presenting

symptom in elderly patients or those on corticosteroids, while

septic shock in severe cases can lead to multiorgan failure.

The differential diagnosis includes:

Biliary leaks

Liver abscess

Infected choledochal cysts

Oriental cholangiohepatitis

Cholecystitis

Mirizzi syndrome

Right lower lobe pneumonia/empyema

Laboratory tests — Routine laboratory tests typically reveal an

elevated white blood cell count with neutrophil predominance, and a

cholestatic pattern of liver function test abnormalities with

elevations in the serum alkaline phosphatase, gammaglutamyl

transpeptidase (GGT), and bilirubin (predominantly conjugated)

concentration. Serum amylase can be increased to three to four times

normal, suggesting an associated pancreatitis.

However, a pattern of acute hepatocyte necrosis can be seen in which

the aminotransferases may be as high as 1000 IU/L. This pattern

reflects microabscess formation in the liver. Liver biopsy in such

cases shows neutrophils in the cholangioles with small abscesses and

associated hepatocyte necrosis.

Blood cultures should be performed in all patients in whom

cholangitis is suspected. Cultures should also be obtained from bile

or stents removed at ERCP (endoscopic retrograde

cholangiopancreatography). Antibiotic therapy should be directed at

any organisms isolated from these cultures [7].

Diagnosis — We recommend ultrasonography as the first imaging study

in patients suspected of having cholangitis to look for CBD

dilatation and stones. However, ultrasonography may be negative when

only small stones are present in the bile ducts (which occurs in 10

to 20 percent of cases), and with acute obstruction when the bile

duct has not yet had time to dilate (show radiograph 1).

Ultrasonography should be followed by endoscopic retrograde

cholangiopancreatography (ERCP) both to confirm the diagnosis and to

intervene therapeutically with sphincterotomy, stone extraction, or

stent insertion (show radiograph 2). Occlusive cholangiography

should not be performed in patients with acute suppurative

cholangitis since it can promote the development of septicemia (show

endoscopy 1).

Magnetic resonance cholangiopancreatography (MRCP) is a newer

technique for the evaluation of CBD stones, particularly in the

patient who is postcholecystectomy or in whom ERCP was unsuccessful

or failed to completely delineate ductal abnormalities [10-12].

(See " Magnetic resonance cholangiopancreatography " ). In the presence

of a dilated CBD, this test has a 90 to 95 percent concordance with

ERCP in diagnosing CBD stones over 1 cm in diameter [10,11]. If

cholangitis is not severe and the risks of ERCP are high, then MRCP

may be useful, especially if no stones are demonstrated. If,

however, Charcot's triad is present, a therapeutic ERCP with

drainage of the obstruction should not be delayed.

Endoscopic ultrasound provides another means to visualize common

duct stones. While its role remains unclear, it may be useful in

patients in whom ERCP was unsuccessful or undesirable (such as

pregnant women) and those at increased risk for ERCP.

(See " Endoscopic ultrasonography in patients with suspected

choledocholithiasis " ).

TREATMENT — The mainstays of therapy are antibiotics and

establishment of biliary drainage. Other general measures include

fluids to maintain urine output, correction of coagulopathy, and

frequent monitoring of vital signs for evidence of sepsis. In cases

of suspected sepsis, monitoring for multiorgan failure from

endotoxemia is essential.

Antibiotics — Broad spectrum antibiotics are indicated initially to

cover gram-negative bacteria and enterococcus [7,13,14]. Antibiotics

that are effective in this setting include:

Ampicillin plus gentamicin

Carbapenems (imipenem or meropenem)

Fluoroquinolones (levofloxacin)

In sick patients, metronidazole is often added to cover anaerobes,

although the contribution of anaerobes to infection is low in

patients who have not had previous biliary tract instrumentation or

surgery. (See " Anaerobic bacterial infections " section on

microbiology of intraabdominal sepsis).

Imipenem or meropenem cover broadly, including gram-negative

organisms, enterococcus, and anaerobes. The fluoroquinolones have a

very low MIC against most gram-negative bacteria; while the newer

quinolones (eg, levofloxacin) have improved gram-positive coverage,

their efficacy in serious enterococcal infection is still

questionable because achievable serum levels are close to the MIC of

the organism. These drugs do have the advantage of being excreted

into an obstructed biliary system. One study found that

ciprofloxacin, administered as a single agent, was as effective as a

ceftazidime, ampicillin, and metronidazole regimen despite the very

limited potency of fluoroquinolones for anaerobes and enterococci

[15].

We recommend beginning with ampicillin (2 g every four hours

intravenously) and gentamicin (4 to 6 mg/kg IV once daily for

patients with normal renal function). Aminoglycosides should

generally not be used in patients with cirrhosis. The addition of

metronidazole is not usually required. For patients with impaired

renal function, levofloxacin (250 to 500 mg IV or PO once daily) can

be used. Therapy should be amended when the culture results are

available. Gentamicin is rarely administered for the full course of

therapy. Another gram-negative agent (with or without ampicillin) is

usually chosen after cultures return.

Some studies have suggested the use of an extended spectrum

penicillins with or without a beta-lactamase inhibitor (eg,

piperacillin [4 g IV every 6h], piperacillin-tazobactam [4/0.5 g IV

every 6 to 8h], ampicillin/sulbactam [3 g every six hours], or

ticarcillin-clavulanate [3.1 g every four hours]) as the backbone of

therapy since these drugs also have good activity against intestinal

anaerobes and lack the nephrotoxicity of aminoglycosides [16].

The total duration of therapy should correlate with the rapidity and

completeness of response with a minimum of one week or more often

two weeks, particularly in patients with bacteremia [7].

Biliary drainage — Eighty percent of patients with acute cholangitis

will respond to conservative management and antibiotic therapy.

Biliary drainage can then be performed on an elective basis. In 15

to 20 percent of cases, cholangitis fails to settle over the first

24 hours with conservative therapy alone, requiring urgent biliary

decompression. Indications for urgent biliary decompression include:

Persistent abdominal pain

Hypotension despite adequate resuscitation

Fever greater than 39ºC (102ºF)

Mental confusion, which is a predictor of poor outcome

Establishment of biliary drainage — Biliary drainage can be achieved

by ERCP, a direct percutaneous approach, or open surgical

decompression. Endoscopic sphincterotomy with stone extraction

and/or stent insertion is now the treatment of choice for

establishing biliary drainage in acute cholangitis (show radiograph

1). Common bile duct stones can be removed successfully in 90 to 95

percent of patients after sphincterotomy. (See " Endoscopic

management of bile duct stones: Standard techniques and mechanical

lithotripsy " ). Prior to injection of contrast, many endoscopists

aspirate the bile duct to remove bile and pus in attempt to

decompress the biliary system and reduce the risk of inducing

bacteremia with contrast injection.

Endoscopic drainage is associated with a significantly lower overall

rate of mortality and morbidity compared with surgical decompression

(4.7 to 10 percent versus 10 to 50 percent) [17-20]. As mentioned

above, occlusive cholangiography should not be performed in patients

with acute suppurative cholangitis since it can promote the

development of septicemia (show endoscopy 1).

In patients with underlying coagulopathy, which prevents a

sphincterotomy, those in whom drainage is inadequate due to the

presence of large stones, or those who are too ill to leave the

intensive care unit and undergo the procedure with fluoroscopy,

drainage can be achieved by insertion of a nasobiliary catheter.

This procedure permits active decompression of the CBD by aspiration

and provides a route for irrigation of the biliary system [21,22].

However, the catheters can become dislodged, particularly in elderly

or confused patients. An internal stent may be another option with a

lower risk of dislodgement, although it does not permit injection of

contrast or irrigation. A controlled trial suggested that an

internal stent permitted adequate drainage even when performed

without a sphincterotomy [23].

Stones more than 2 cm in diameter generally require lithotripsy for

fragmentation prior to removal. (See " Endoscopic management of bile

duct stones: Standard techniques and mechanical lithotripsy " ).

Intrahepatic stones can sometimes be removed with choledochoscopy

depending upon their size, number, and location.

(See " Cholangioscopy and pancreatoscopy " ).

Percutaneous drainage can be considered when ERCP is unavailable,

unsuccessful or contraindicated. A percutaneous cholecystostomy tube

may be an option in patients with an intact gallbladder.

Role of surgery — Emergency surgery for acute cholangitis has

largely been replaced by nonoperative biliary drainage. Once the

acute cholangitis is controlled, patients with difficult ductal

stones may undergo surgical exploration of the CBD for stone

removal. Elective surgery carries a very low morbidity and mortality

compared with emergency surgery. If emergent surgery is needed due

to failure of a nonsurgical drainage procedure, choledochotomy with

placement of a large-bore T tube carries a lower mortality compared

to cholecystectomy with CBD exploration [20].

Prognosis — With effective antibiotics and biliary drainage, the

prognosis for mild to moderate cholangitis is much improved.

However, the mortality rate remains very high (approximately 50

percent) for patients with severe cholangitis (Raynold's pentad).

SUMMARY AND RECOMMENDATIONS — Acute cholangitis is a clinical

syndrome characterized by fever, jaundice, and abdominal pain that

develops as a result of stasis and infection in the biliary tract.

The classic triad of Charcot — fever, right upper quadrant pain, and

jaundice — occurs in only 50 to 75 percent of patients [8].

Confusion and hypotension can occur in patients with suppurative

cholangitis, producing Reynold's pentad, which is associated with

significant morbidity and mortality [9]. Hypotension may be the only

presenting symptom in elderly patients or those taking

corticosteroids, while septic shock in severe cases can lead to

multiorgan failure.

The differential diagnosis includes:

Biliary leaks

Liver abscess

Infected choledochal cysts

Oriental cholangiohepatitis

Cholecystitis

Mirizzi syndrome

Right lower lobe pneumonia/empyema

The mainstays of therapy are antibiotics and establishment of

biliary drainage. Other general measures include fluids to maintain

urine output, correction of coagulopathy, and frequent monitoring of

vital signs for evidence of sepsis. In cases of suspected sepsis,

monitoring for multiorgan failure from endotoxemia is essential.

Broad spectrum antibiotics are indicated initially to cover Gram

negative bacteria and enterococcus [7,13,14]. Antibiotics that are

effective in this setting include:

Ampicillin plus gentamicin

Carbapenems (imipenem or meropenem)

Fluoroquinolones (levofloxacin)

In sick patients, metronidazole is often added to cover anaerobes,

although the contribution of anaerobes to infection is low in

patients who have not had previous biliary tract instrumentation or

surgery. (See " Anaerobic bacterial infections " section on

microbiology of intraabdominal sepsis).

We recommend beginning with ampicillin (2 g every four hours

intravenously) and gentamicin (4 to 6 mg/kg IV once daily for

patients with normal renal function) The addition of metronidazole

is not usually required. For patients with impaired renal function,

levofloxacin (250 to 500 mg IV or PO once daily) can be used.

Therapy should be amended when the culture results are available.

Gentamicin is rarely administered for the full course of therapy.

Another Gram negative agent (with or without ampicillin) is usually

chosen after cultures return. Given the absence of enterococcal

coverage and concerns about promoting resistance in Enterobacter

species, third generation cephalosporins should probably be reserved

to treat other Gram negative organisms after they have been

identified and susceptibilities determined.

Biliary drainage can be achieved by ERCP, a direct percutaneous

approach, or open surgical decompression. Endoscopic sphincterotomy

with stone extraction and/or stent insertion is now the treatment of

choice for establishing biliary drainage in acute cholangitis (show

radiograph 1). Common bile duct stones can be removed successfully

in 90 to 95 percent of patients after sphincterotomy.

(See " Endoscopic management of bile duct stones: Standard techniques

and mechanical lithotripsy " ).

With effective antibiotics and biliary drainage, the prognosis for

mild to moderate cholangitis is much improved. However, the

mortality rate remains very high (approximately 50 percent) for

patients with severe cholangitis (Raynold's pentad).

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New

June 12, 2006