Tag Archives: GI

Cholangitis: Pearls & Pitfalls

Author: Rachel Ely, DO, MHA, EMT-P (EM Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)


A 61-year-old male presents to your ED with one week of epigastric pain and vomiting.  He tells you that he had a cholecystectomy earlier this year, and his current pain is very similar to what prompted his gallbladder removal.  He also says that his girlfriend mentioned that his eyes seemed “yellow”, and he complains of whole-body pruritis.   He has vomited multiple times at home, and he is having difficulty answering your questions because of persistent nausea.  His vitals on presentation are BP 171/99, HR 70, RR 16, oral temp 98.5, SpO2 99%.  On exam, you notice obvious scleral and sublingual icterus, as well as generalized jaundice of the skin.  His abdomen is mildly distended, with tenderness in the right upper quadrant without guarding or rebound tenderness. What should you be considering? What are the keys to evaluation and management?


Cholangitis is a life-threatening infection of the biliary tract.  It was first described in 1877, and for many decades the mortality secondary to cholangitis approached 100%.1  Identification and treatment of cholangitis has significantly improved over the last century, however there is still progress to be made.  Challenges include not only early recognition of biliary infection, but also identification of those patients requiring emergent versus urgent biliary decompression.2  With these advances in identification and management, mortality has been cut to approximately 10%.1

For another great case and background on cholangitis, please see http://www.emdocs.net/cholangitis-deadly-cause-of-right-upper-quadrant-abdominal-pain/

General Physiology & Risk Factors

Cholangitis is a result of biliary obstruction and bacterial growth in the bile.1  Bacteria, primarily E. coli, Klebsiella species, and Enterococcus species, are thought to ascend from the duodenum into the common hepatopancreatic duct in the setting of ductal obstruction.3  Intraductal pressures increase as a result of obstruction, leading to a disruption of the tight junctions in the hepatic cellular architecture and serving as a route for bacteria to enter the bloodstream.1,4  Characteristics which predispose patients to the development of cholangitis include primarily bile duct stones and manipulation of the biliary tree such as ERCP or surgery.  Less common risk factors include orthotopic liver transplantation, primary sclerosing cholangitis, and AIDS-related cholangiopathy.1,4  Malignancy is a common cause of biliary obstruction; however, it is less likely to develop cholangitis primarily as a result of malignant obstruction rather than as a result of biliary manipulation to relieve a malignant obstruction.4  Patients with indwelling biliary stents, or who have recently had instrumentation of their biliary tree, are more likely to have infection with Enterococcus, Pseudomonas, MRSA, or VRE.5


Charcot’s triad of fever, right upper quadrant pain, and jaundice yields a 25% sensitivity for the detection of ascending cholangitis.6  Reynold’s pentad, which adds hypotension and altered mental status to the classic triad, is present in only of 5-7% of cases.4  The most common presenting signs and symptoms are fever, which is observed in about 90% of patients, and abdominal pain, seen in approximately 80% of patients. Cholangitis should be suspected in patients with fever, altered mental status, occult sepsis, or an otherwise unexplained elevated bilirubin, especially in the setting of biliary stones or recent biliary instrumentation. Because cholangitis is nearly uniformly fatal without appropriate treatment, it must remain high on the differential in adult patients with unexplained fever.7,8


While no specific laboratory study is in itself indicative of cholangitis, elevation of liver function tests can be suggestive.  Specifically, elevation of both GGT and alkaline phosphatase is approximately 90% sensitive for acute cholangitis.8  While elevations of white blood cell count, ESR, and CRP are non-specific, in the right clinical context this is highly suggestive of overwhelming systemic disease.9  Up to 70% of patients with cholangitis will have positive blood cultures, and while the IDSA does not recommend routine blood culture collection in mild community-acquired intra-abdominal infection, it should certainly be considered in those with severe disease or recent instrumentation.4,10

CT is the imaging study of choice to visualize the biliary system in suspected cholangitis. While ultrasound is often the preferred modality to visualize the biliary system, CT can better characterize complications such as hepatic abscess and can identify external sources of obstruction such as malignancy.4,7,11  CT carries an 87% sensitivity in actually identifying the etiology of biliary obstruction.12  Findings such as intra- and extrahepatic ductal dilation, duct wall thickening, liver enhancement, and the presence of gallstones can be suggestive of cholangitis.  The finding of papillitis, or inflammation at the ampulla of Vater, and the presence of an ampullary stone on CT can also be indicative of cholangitis.13

Diagnostic Criteria and Classification

Because elevated LFTs, leukocytosis, and imaging evidence of biliary dilation can be indicative of other disease processes (such as cholecystitis or choledocholithiasis), attempts have been made to develop a set of diagnostic criteria for cholangitis.  The Tokyo Guidelines are the best-known criteria and offer a sensitivity of 91.8% and specificity of 77.7% in derivation studies, though external validation studies have yet to be published.14,15  Three diagnostic categories are used to apply the tool: indicators of systemic inflammation, evidence of cholestasis, and imaging evidence.  One indicator of systemic inflammation plus either imaging evidence or cholestasis evidence should prompt strong suspicion of cholangitis. Criteria to indicate inflammation are fever or shaking chills, white blood cell count less than 4,000 or greater than 10,000, or C-reactive protein greater than 1.  Cholestasis can be indicated by total bilirubin greater than or equal to 2 mg/dL, or alkaline phosphatase, GGT, AST, or ALT above 1.5 times the upper limit of normal. Finally, imaging is considered confirmatory if biliary dilation or other evidence of a likely inciting etiology of obstruction and subsequent cholangitis, such as biliary stent, stricture, or malignancy.14 

Table 1 TG13 Diagnostic Criteria for Acute Cholangitis.14

Category Threshold
A. Systemic Inflammation
Fever or Shaking Chills Body Temperature >38°C
Laboratory evidence of inflammatory response WBC <4,000 or >10,000

CRP >1

B. Cholestasis
Jaundice T-Bili ³2 mg/dL
Abnormal LFT Alk Phos >1.5 x upper limit normal

GGT >1.5x upper limit normal

AST >1.5x upper limit normal

ALT >1.5x upper limit normal

C. Imaging
Biliary dilatation
Evidence of etiology on imaging
Diagnosis should be suspected if one item from A plus one item from B or C are present

Diagnosis is considered definite if one item from, A, B and C are present.


Early identification and appropriate management of cholangitis is imperative because of its impressive mortality risk if not aggressively treated.  Often, these patients present with evidence of sepsis and should be treated accordingly with fluid resuscitation and antibiotics.  However, ultimately the presence of biliary obstruction is the factor allowing cholangitis to occur, and this obstruction must be relieved.  While convention teaches that earlier biliary decompression is better, there have been some attempts to stratify the severity of disease in order to prioritize the urgency of decompression, as discussed below.

Antibiotic selection

As discussed, the most common organisms isolated in ascending cholangitis are E. coli, Klebsiella species, and Enterococcus species, but because these patients have often had recent biliary instrumentation and likely other nosocomial exposures, initial antibiotic therapy should remain broad.  The most current Infectious Diseases Society of America guidelines, published in 2009, recommends metronidazole plus either a carbapenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin, or cefepime, with the addition of vancomycin in those with likely health-care associated biliary infection.16  However, the most recent Tokyo treatment guidelines, published in 2013, warn against the use of fluoroquinolones because of increasing regional E. coli resistance to these agents.10

The Tokyo Guidelines recommend a severity-based hierarchy of antibiotic selection.  Criteria for grading disease can be found in the table below.  Mild or Grade I disease might be managed with a cephalosporin or ertapenem, or a fluoroquinolone in regions where resistance patterns are favorable.  Grade II disease options include piperacillin/tazobactam, a third or fourth generation cephalosporin, or ertapenem.  Finally, antibiotic coverage for severe (Grade III) disease or health-care associated infections include piperacillin/tazobactam, third or fourth generation cephalosporin, imipenem/cilastatin or meropenem, aztreonam plus metronidazole, plus vancomycin in addition to any of these options.4,10

Table 2 TG13 Severity Criteria for Acute Cholangitis14

Grade III:  Severe

Dysfunction in at least one of following systems:

Cardiovascular Hypotension requiring dopamine ³5 mcg/kg/min, or any dose of norepinephrine
Respiratory PaO2/FiO2 ratio <300
Renal Oliguria, or serum creatinine >2.0 mg/dl
Hepatic INR > 1.5
Hematologic Platelet Count <100,000/mm3
Grade II: Moderate

Any two of the following

Abnormal WBC count >12,000/mm3 or <4,000/mm3
High Fever ³39°C
Advanced Age ³75 years
Hyperbilirubinemia Total bilirubin ³5 mg/dL
Hypoalbuminemia <70% lower limit normal
Grade I:  Mild
Does not meet criteria of Severe or Moderate at diagnosis.

Biliary Decompression

In certain cases of mild infection, patients may respond well to medical management alone.  However, this remains the exception rather than the rule, and identifying these patients remains a challenge that requires further study.  The 2007 and 2013 Tokyo Guidelines suggest that their disease stratification, discussed above, may aid in the decision of performing immediate or delayed biliary decompression, or whether decompression is necessary at all in cases of mild disease.6,10  The TG13 authors make no hard and fast recommendations about severity-based management, other than emphasizing that those with Grade III disease require near-immediate biliary decompression.10


In nearly all cases, patients with cholangitis will require admission, and many will require ICU care for continued resuscitation and vasopressor support in cases of septic shock. However, source control is important to changing the course of disease, and this will require relief of the biliary obstruction.  The most common option is bile duct stenting or stone removal via endoscopic retrograde cholangiopancreatography (ERCP).2  In cases in which this is not possible, such as in malignant obstruction or extremely unstable patients, percutaneous drainage of the gallbladder may be a better temporizing measure.17  Open surgical biliary decompression carries a higher morbidity and mortality than ERCP, but may be required in certain unique situations.4  In most cases the first consult should be to gastroenterology, as ERCP is the typical first step in decompression, however it is important to recognize that inpatient care is likely to be multidisciplinary, potentially including general surgery, gastroenterology, interventional radiology, and medical or surgical intensivists.

Case Conclusion

Your patient is not febrile, and the white blood cell count is 10.6.  Knowing this, you reflexively move cholangitis lower on your differential list. However, the direct bilirubin returns at 7.0, and an alkaline phosphatase of 894 supports an obstructive lesion.  The lab seems to be having difficulty analyzing the lipase because of the elevated bilirubin.   You start with an ultrasound to evaluate for retained or spontaneous common bile duct stone; however, this study is grossly normal with the exception of heterogeneity of the pancreatic head, thought to be incidental.  Seeking an explanation for the patient’s pain and obvious jaundice, you order a CT of the abdomen and pelvis, and you are surprised when you see this image:


 CT demonstrating choledocholithiasis and extra- and intra-hepatic ductal dilatation.  Case courtesy of Dr. Roberto Schubert, Radiopaedia.org, rID/ 16704.

Your radiologic skills don’t typically allow you to pick out the common bile duct on CT, and the inflammation you see here clues you in that this patient may actually be harboring infection on top of his biliary obstruction.  The lack of fever and leukocytosis initially threw you, but you soon realize that this patient meets the three diagnostic criteria for cholangitis per the Tokyo guidelines.  You start piperacillin/tazobactam and metronidazole, give a fluid bolus, and call gastroenterology for consult and internal medicine for admission.  When you follow up on the patient a few days later, you learn that the patient underwent ERCP with sphincterotomy, and stones and purulent fluid were drained from the common bile duct, confirming the diagnosis of cholangitis.  His cholangitis and concurrent pancreatitis quickly resolved, and he is discharged on hospital day five.

Pearls & Takeaways

  • Cholangitis can be subtle and only rarely presents with the classic triad of fever, jaundice, and right upper quadrant pain
  • While ultrasound can be useful, CT is often required to support the diagnosis and can often identify the source of obstruction
  • While early antibiotics are important, most patients require biliary decompression
  • Consult gastroenterology early, and the patient may require ICU-level care
  • The Tokyo Guidelines (TG13) may help support your working diagnosis in subtle cases, and can also help to stratify severity of disease. In the future, we may be able to use this severity stratification to guide urgency of biliary decompression.

References/Further Reading

1         Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:15–26. doi:10.1007/s00534-006-1152-y.

2         Salek J, Livote E, Sideridis K, Bank S. Analysis of risk factors predictive of early mortality and urgent ERCP in acute cholangitis. J Clin Gastroenterol 2009;43:171–5. doi:10.1097/MCG.0b013e318157c62c.

3         Van den Hazel SJ, Speelman P, Tytgat GNJ, Dankert J, Van Leeuwen DJ. Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis. Clin Infect Dis 1994;19:279–86. doi:10.1093/clinids/19.2.279.

4         Attasaranya S, Fogel EL, Lehman GA. Choledocholithiasis, Ascending Cholangitis, and Gallstone Pancreatitis. Med Clin North Am 2008;92:925–60. doi:10.1016/j.mcna.2008.03.001.

5         Tanaka A, Takada T, Kawarada Y, Nimura Y, Yoshida M, Miura F, et al. Antimicrobial therapy for acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:59–67. doi:10.1007/s00534-006-1157-6.

6         Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA, et al. New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo guidelines. J Hepatobiliary Pancreat Sci 2012;19:548–56. doi:10.1007/s00534-012-0537-3.

7         Block J, Lawrence LM FR. The Atlas of Emergency Radiology. In: Block J, Jordanov MI, Stack LB TR, editor. Atlas Emerg. Radiol., New York, NY: McGraw-Hill; 2013, p. Chapter 7.

8         Mosler P. Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep 2011;13:166–72. doi:10.1007/s11894-010-0171-7.

9         Qin Y-S, Li Q-Y, Yang F-C, Zheng S-S. Risk factors and incidence of acute pyogenic cholangitis. Hepatobiliary Pancreat Dis Int 2012;11:650–4. doi:10.1016/S1499-3872(12)60240-9.

10       Gomi H, Solomkin JS, Takada T, Strasberg SM, Pitt HA, Yoshida M, et al. TG13 antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:60–70. doi:10.1007/s00534-012-0572-0.

11       Schubert R. Choledocholithiasis | Radiology Case | Radiopaedia.org n.d. http://radiopaedia.org/cases/choledocholithiasis-4.

12       Balthazar EJ, Birnbaum BA, Naidich M. Acute cholangitis: CT evaluation. J Comput Assist Tomogr n.d.;17:283–9.

13       Lee NK, Kim S, Lee JW, Kim CW, Kim GH, Kang DH, et al. Discrimination of suppurative cholangitis from nonsuppurative cholangitis with computed tomography (CT). Eur J Radiol 2009;69:528–35. doi:10.1016/j.ejrad.2007.11.031.

14       Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA, et al. TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013;20:24–34. doi:10.1007/s00534-012-0561-3.

15       Yokoe M, Takada T, Mayumi T, Yoshida M, Hasegawa H, Norimizu S, et al. Accuracy of the Tokyo Guidelines for the diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan. J Hepatobiliary Pancreat Sci 2011;18:250–7. doi:10.1007/s00534-010-0338-5.

16       Solomkin, Joseph S.  et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010;50:133–64. doi:10.1086/649554.

17       Lee CC, Chang IJ, Lai YC, Chen SY, Chen SC. Epidemiology and prognostic determinants of patients with bacteremic cholecystitis or cholangitis. Am J Gastroenterol 2007;102:563–9. doi:10.1111/j.1572-0241.2007.01095.x.


Cholangitis: Deadly Cause of Right Upper Quadrant Abdominal Pain

Author: George C. Willis, MD, FAAEM, FACEP (Director of Undergraduate Medical Education, Department of Emergency Medicine, University of Maryland School of Medicine) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital)

Case 1

A 54-year-old female presents to the emergency department (ED) complaining of right upper quadrant (RUQ) abdominal pain.  She had presented two months prior with similar symptoms and was diagnosed with cholelithiasis. She was discharged home with pain medications and surgical follow up.  However, her symptoms returned and are more severe this visit. She is vomiting, has a fever of 39.2 °C and is tachycardic at 131 beats per minute (bpm). A quick bedside RUQ ultrasound reveals gallstones but no wall thickening, sludge, or pericholecystic fluid.  She is once again diagnosed with cholelithiasis. Luckily, though, the surgeon-on-call agrees to admit the patient and perform a cholecystectomy the following morning.  Upon reassessing the patient, however, something seems missing.  Despite medications and intravenous fluids, she does not look well and she remains febrile and tachycardic. What are you missing in this acutely ill patient?

Case 2

Emergency Medical Services (EMS) brings an 84-year-old male from his nursing home with a chief complaint of altered mental status. The patient has a history of dementia and other chronic medical conditions. You look through his nursing home paperwork, which includes a discharge summary from four months ago that describes hospitalization in which he received a cholecystectomy.

On exam, the patient is non-verbal from a previous stroke and is unable to provide any history.  He is febrile, tachycardic, tachypneic, and hypotensive.  You initiate a suspected sepsis workup which includes intravenous fluid resuscitation, bloodwork, imaging studies, and broad-spectrum antibiotics.  You suspect a urinary tract infection as the culprit of his symptoms as his chronic indwelling catheter is crusted over. An aspiration pneumonia is also considered given his coarse lung sounds on exam.

Surprisingly, however, the patient’s urinalysis (UA) and chest x-ray are normal. His white blood cell count (WBC) is 22,000, his lactate is rising despite fluid resuscitation and he remains hypotensive.  A diagnosis of meningitis is considered and a lumbar puncture may be next. However, cholangitis remains in your differential given the patient’s recent cholecystectomy.


Around 10-15% of patients worldwide have gallstones, with the majority experiencing little to no symptoms.1 Out of these patients, only 2-3% will experience obstructive complications, which includes pancreatitis, cholecystitis, and cholangitis.1,2 Acute or ascending cholangitis is a rare disease characterized by an infection of the common bile duct (CBD). It can be life-threatening if not treated appropriately. Although biliary stone disease is the most common etiology, there are other causes of cholangitis including previous biliary tree instrumentation, biliary stenosis, helminthic infections, and neoplastic disease.3,4 The prevalence of cholangitis is equal between both genders and occurs more commonly after the fifth decade of life.

So how does this disease process manifest?  Recall that the intrahepatic biliary ducts and the cystic duct join to form the common bile duct that drains bile into the duodenum via the Sphincter of Oddi.  Normally, the biliary system is a low-pressure, forward flow system that flushes any bacteria out into the duodenum.  In cholangitis, an obstruction occurs in the common bile duct and cessation of forward flow causes increased pressure in the biliary tract.  Consequently, bacteria from the duodenum have easier access to the biliary parenchyma and the bloodstream, thus predisposing the patient to local and systemic infection.

When Jean-Martin Charcot first described cholangitis in the late 1800s, the mortality was 100%.  Subsequently, advances in biliary drainage techniques and newer antibiotic regimens have lowered the current mortality to anywhere between 5 and 30%.  Currently, the most common cause of death is multi-organ failure and irreversible circulatory collapse.3,4  Delay in diagnosis and management are key contributors to the persistently high mortality rates even to this day. In two studies, endoscopic retrograde cholangiopancreatography (ERCP) studies that were delayed were associated with increase in-hospital lengths of stays and worsened morbidity and mortality rates.5,6

Diagnostic Dilemma

Up until recently, physicians had to rely on their clinical exam to diagnose cholangitis.  For years, the presence of the classic signs and symptoms of Charcot’s triad or Reynold’s pentad had been the only criteria to confirm the diagnosis.  Charcot’s triad includes right upper quadrant abdominal pain, fever, and jaundice, while the addition of mental status change and hypotension constitutes Reynold’s pentad.  Charcot’s triad is anywhere between 72 and 95% specific for cholangitis, although there is about an 11% false positive rate in cholecystitis.7,8 Reynold’s pentad signifies more severe disease, but it is rare and shows up in less than 10% of patients with cholangitis.8  Despite its low sensitivity rate of 26%, providers were forced to use the absence of Charcot’s triad to rule out the diagnosis of cholangitis. 7

Reliance on Charcot’s triad alone is problematic.  All three parts of Charcot’s triad appear in only 50-70% of patients with cholangitis.9 Therefore, patients may only present with one or two symptoms of Charcot’s triad.  Abdominal pain is the most common complaint and is seen in about 80% of patients with cholangitis.8,10 However, patients, especially elderly patients, may present without abdominal pain. They may also present with clinical manifestations of sepsis alone, leading the provider to search for more common sources of sepsis.  These patients may also be unable to provide any history of abdominal pain due to baseline cognitive disorders, mechanical ventilation, sepsis causing altered sensorium, and medications.  A 2005 study looking at delays in the diagnosis of elderly patients with cholangitis found that those who presented atypically (i.e., with falls or confusion) took, on average, nine days to receive the proper diagnosis. It also took 16 days to perform a therapeutic ERCP compared to only 4 days in those patients who presented with abdominal pain.11

Similarly, fever and jaundice are also variable in presentation.  Studies show that anywhere between 40 and 80% of patients with cholangitis will have fever.8,10 Fever can be absent due to a number of factors including lower baseline core body temperature (especially in the elderly), medications, and immunosuppression.  Jaundice may not manifest itself initially. It is also less common than abdominal pain and fever, occurring in 50-70% of patients with cholangitis.8 One study looked at biliary dilatation in patients diagnosed with cholangitis and found that 18% had no biliary dilatation.12 Subsequently, this group of patients had lower bilirubin levels than those with biliary dilatation. Thus, this group of patients were  less likely to have clinically-evident jaundice, despite having similar elevations in liver transaminases.12 Another study found that 16% of elderly patients are also less likely to manifest jaundice despite significant hyperbilirubinemia.11

So reliance on clinical signs alone is not helpful and thus, imaging is recommended. Ultrasound is typically the initial study to evaluate patients with RUQ abdominal pain.  Unfortunately, while it is very good at detecting gallbladder stones and biliary duct dilatation, it is poor at visualizing choledocholithiasis and it can miss other possible etiologies of CBD dilatation.10 Computed tomography (CT) is adequate for visualizing CBD dilatation and is much better at diagnosing etiologies for CBD dilation, including CBD stones.10,13 However, CT has a sensitivity of about 60% for diagnosing the findings in cholangitis and will miss a fair number of cholangitis patients.13-15

Evidence-Based Diagnostic Criteria

Due to a lack of evidence-based criteria for diagnosing acute cholangitis, a group of hepatobiliary specialists drafted the Tokyo Guidelines in 2007 (TG07).8 These guidelines established a new set of diagnostic criteria for diagnosing cholangitis. The  criteria included Charcot’s triad, but also added laboratory values and imaging findings to supplement those cases where Charcot’s triad was not completely present. These additional studies include (1) evidence of an inflammatory response defined by an elevated C-reactive protein (CRP), an abnormal white blood cell count, or other markers of inflammation, (2) evidence of abnormal liver function tests defined by elevations in aspartate aminotransferase (AST), alanine transaminase (ALT), or alkaline phosphatase, or (3) imaging evidence of biliary dilatation or an etiology of obstruction.8 Subsequent studies have validated these criteria externally with good results, showing a sensitivity of 64% and a specificity of 69%.16 These criteria have been cited well over 200 times since the original Tokyo Guidelines publication and have become the gold standard worldwide for diagnosing cholangitis.17

However, by 2012, a committee of hepatobiliary specialists reconvened in Japan and performed their own multicenter retrospective trial to revise TG07. In their study, they found the TG07 criteria to have a sensitivity of 83% and specificity of 80% with a 12% false positive rate in cases of acute cholecystitis.7 They sought to improve the sensitivity and specificity further and decrease the false positive rate, and thus, developed the Tokyo Guidelines 2013 (TG13).  These criteria are as following:

1) Fever >38 deg. C and/or chills

2) Lab evidence of inflammation (WBC < 4 or > 12, CRP > 1)1) Jaundice (Total bilirubin > 2)

3) Lab evidence of abnormal liver transaminases (AST, ALT, GGT, Alk phos >    1.5 X normal

4) Biliary dilatation on imaging

5) Evidence of etiology (i.e. malignancy, stenosis) on imaging

*Suspected diagnosis = 1 item in A + 1 item in B or C

**Definite diagnosis = 1 item in A, B, and C18

Using the TG13, the sensitivity increased to 91% and the specificity only decreased slightly to 78% and the false positive rate decreased to 5%.18 The TG13 criteria can be applied to patients with and without abdominal pain who present with undifferentiated sepsis. Now, practitioners have reliable criteria consisting of data that is obtainable in an emergency department workup.

Bottom line: Ruling in or out the diagnosis of cholangitis is no longer based on clinical exam alone.  The addition of imaging and bloodwork to the clinical exam are much more reliable.

ED Management

Resuscitation, antibiotics and consultation for early biliary decompression are the mainstays of cholangitis treatment. Resuscitation is important to maintain hemodynamic stability. Hemodynamic stability is also necessary to make sure that antibiotics perfuse the infected regions, namely the biliary tree.  Cardiac and blood pressure monitoring should be reassessed frequently as tachycardia and hypotension due to sepsis can quickly develop.  Patients should be treated early with intravenous fluids and, if needed, vasoactive agents.  Laboratory studies directed at cholangitis are important, but other laboratory markers for sepsis will help with directing therapy as well.  Obtain serial lactate measurements, venous blood gas for acid-base disturbance, and urine output measurements to help direct any hemodynamic therapy.  Blood cultures are not routinely useful unless disease severity is high where multi-organ dysfunction is present.  Although blood cultures are positive in anywhere between 22 and 71% of cholangitis cases, typical causative organisms are not known to cause vegetations and are often susceptible to the antibiotic regimen.19,20 Therefore, blood cultures often do not provide any additional information.

Antibiotic regimens should be directed toward Gram-negative species and, less commonly, anaerobes and Gram-positive species.  Cultures taken from biliary fluid and blood in patients with cholangitis reveal Escherichia coli in more than 50% of cases.  Other culprits are typically other Gram-negative species and anaerobic species.  In recent years, there has been an increase in resistance of Gram-negative bacilli to typical antimicrobials and occasional Gram-positive organisms (i.e. Enterococcus), especially in hospital-acquired infections. Antibiotics need to be effective at treating the causative organisms but also need to be concentrated in the bile in order to be effective.  First generation cephalosporins and fluoroquinolones are adequate in mild disease.20 Once organ failure begins to manifest, coverage for hospital-acquired infections should occur.  Third or fourth generation cephalosporins or piperacillin-tazobactam are better options. Vancomycin or linezolid should be administered to cover Gram-positive organisms and metronidazole should be given to cover anaerobes.20 The carbapenems or aztreonam are acceptable alternatives.

Early biliary decompression will also help with source control.  Before antimicrobial therapy was introduced, biliary decompression was the only way to treat cholangitis.  Gastroenterology consultation for ERCP should occur early if suspicion is high.  ERCP is usually effective at diagnosing and relieving obstructions that may be present.

Take Home Points

– Always think about cholangitis in any ill-appearing patient with RUQ pain or undifferentiated sepsis.

-Charcot’s triad and Reynold’s pentad are not reliable. Absence of these clinical findings does not rule out cholangitis.  Use the total picture with clinical exam, labwork, and imaging studies.

Early antibiotics and consultation for biliary decompression are mainstays of therapy.

References / Further Reading

  1. Sekimoto M, Takada T, Kawarada Y, et al. Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):11-14.
  2. Williams EJ, Green J, Beckingham I, et al. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008;57(7):1004-1021.
  3. Kimura Y, Takada T, Kawarada Y, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):15-26.
  4. Kimura Y, Takada T, Strasberg SM, et al. TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013;20(1):8-23.
  5. Khashab MA, Tariq A, Tariq U, et al. Delayed and unsuccessful endoscopic retrograde cholangiopancreatography are associated with worse outcomes in patients with acute cholangitis. Clin Gastroenterol Hepatol. 2012;10(10):1157-1161.
  6. Navaneethan U, Gutierrez NG, Jegadeesan R, et al. Delay in performing ERCP and adverse events increase the 30-day readmission risk in patients with acute cholangitis. Gastrointest Endosc. 2013;78(1):81-90.
  7. Kiriyama S, Takada T, Strasberg SM, et al. TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos). Journal of hepato-biliary-pancreatic sciences. 2013;20(1):24-34.
  8. Wada K, Takada T, Kawarada Y, et al. Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):52-58.
  9. Takada T, Kawarada Y, Nimura Y, et al. Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Surg. 2007;14(1):1-10.
  10. Mosler P. Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep. 2011;13(2):166-172.
  11. Rahman SH, Larvin M, McMahon MJ, Thompson D. Clinical presentation and delayed treatment of cholangitis in older people. Dig Dis Sci. 2005;50(12):2207-2210.
  12. Hong MJ, Kim SW, Kim HC, Yang DM. Comparison of the clinical characteristics and imaging findings of acute cholangitis with and without biliary dilatation. Br J Radiol. 2012;85(1020):e1219-1225.
  13. Balthazar EJ, Birnbaum BA, Naidich M. Acute cholangitis: CT evaluation. J Comput Assist Tomogr. 1993;17(2):283-289.
  14. Kim SW, Shin HC, Kim HC, Hong MJ, Kim IY. Diagnostic performance of multidetector CT for acute cholangitis: evaluation of a CT scoring method. Br J Radiol. 2012;85(1014):770-777.
  15. Lee NK, Kim S, Lee JW, et al. Discrimination of suppurative cholangitis from nonsuppurative cholangitis with computed tomography (CT). Eur J Radiol. 2009;69(3):528-535.
  16. Yokoe M, Takada T, Mayumi T, et al. Accuracy of the Tokyo Guidelines for the diagnosis of acute cholangitis and cholecystitis taking into consideration the clinical practice pattern in Japan. Journal of hepato-biliary-pancreatic sciences. 2011;18(2):250-257.
  17. Takada T, Strasberg SM, Solomkin JS, et al. TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013;20(1):1-7.
  18. Kiriyama S, Takada T, Strasberg SM, et al. New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo Guidelines. Journal of hepato-biliary-pancreatic sciences. 2012;19(5):548-556.
  19. Tanaka A, Takada T, Kawarada Y, et al. Antimicrobial therapy for acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):59-67.
  20. Gomi H, Solomkin JS, Takada T, et al. TG13 antimicrobial therapy for acute cholangitis and cholecystitis. Journal of hepato-biliary-pancreatic sciences. 2013;20(1):60-70.

Splenic Infarction in Mononucleosis: Pearls and Pitfalls

Author: Kristen Kann, MD (EM Staff Physician, SAUSHEC, USAF) // Edited by: Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF) and Alex Koyfman, MD (@EMHighAK)

An 18 year-old male recently diagnosed with infectious mononucleosis by Monospot presents to the Emergency Department complaining of three days of left upper quadrant pain. He denies any recent trauma or participation in contact sports. His review of systems is otherwise negative, with no fever, nausea, rashes, or other complaints noted. He appears mildly uncomfortable on exam but otherwise is in no acute distress. His initial vital signs include BP 119/55, HR 97, RR 16, T 98.8F, Sat 99%, and a pain scale of 6/10. His lungs and heart are normal, but his abdominal exam is significant for moderate left upper quadrant tenderness to palpation without rebound or guarding. No organomegaly is appreciated on exam. The remainder of his physical exam is unremarkable, including skin and lymph nodes.

A review of recent workup reveals a splenic ultrasound three days prior to the patient’s presentation, which he reports coincided with the onset of the left upper quadrant pain. The ultrasound was significant for multiple hypodensities in the spleen and splenomegaly.



The spleen is a large reticuloendothelial organ in the left upper quadrant that functions to filter red blood cells, produce antibodies (specifically IgM), and remove antibody-coated bacteria from the bloodstream.

The spleen can become infarcted when flow from the splenic artery or one of its branches is interrupted, causing hypoperfusion of splenic segments and eventual tissue death. Causes of splenic infarction can be broken down into three main categories: hematologic conditions that result in splenomegaly, systemic thromboembolic conditions, and trauma.

Splenomegaly occurs with splenic enlargement. The differential for splenomegaly is very large and includes diseases that increase demand for splenic filtration (autoimmune hemolytic anemia, polycythemia vera, spherocytosis, early sickle cell anemia, thalassemias), certain infectious diseases (infectious mononucleosis, AIDS, CMV, and malaria, among others), and splenic infiltration (sarcoidosis, myelofibrosis, metastatic disease, amyloidosis, leukemias, and lymphomas). Infectious mononucleosis was previously diagnosed in this patient and was his only known risk factor. Splenic infarction has been reported as a rare complication of infectious mononucleosis/Epstein Barr Virus infection, but the incidence is unknown.

The vascular network of the spleen can also become the site of thromboembolic disease, such as in the case of malignancy, antiphospholipid antibody syndrome, infectious endocarditis, atrial fibrillation, and sickle cell disease. Interestingly, splenic infarction has been reported in patients with sickle cell trait who were otherwise asymptomatic but presented with left upper quadrant pain after heavy exertion at altitude.

Trauma that affects the blood flow to the spleen, either directly or as a result of compression (ex. splenic hematomas) can also cause splenic infarction. In addition, the Emergency Physician may encounter a patient who has symptomatic splenic infarction after splenic artery embolization.

Rarely, the splenic artery can become torsed in “wandering spleen syndrome,” a rare condition seen in children and young adults in which the spleen is more mobile than usual, leading to infarction of the entire spleen.



Patients with splenic infarction can present in a myriad of ways. Up to 30% may be completely asymptomatic, especially those with nonmalignant hematologic conditions. The most common signs and symptoms in patients with complaints include left sided abdominal pain, fever, nausea/vomiting, elevated LDH, and leukocytosis. While abdominal tenderness to palpation is relatively easy to elicit, splenomegaly is notoriously difficult to appreciate on physical exam. One study compared percussion and palpation by physicians with the gold standard of ultrasonographic measurement and found palpation to have a sensitivity of 56-71% for splenomegaly, with similar results for percussion. Thus, the Emergency Physician should not rely on physical exam alone to exclude splenomegaly, and certainly not to exclude splenic infarction, as there are many causes that can occur in normal or even shrunken spleens (such as advanced sickle cell anemia).



For a patient in whom you suspect splenic infarction, the basic work up should likely include a complete blood count and LDH, with a consideration for peripheral blood smears and manual differentials based on the suspicion for underlying causes. Initial imaging can include ultrasound or computed tomography. Ultrasound has the benefit of being radiation free, relatively fast, and being able to reliably exclude splenomegaly, though some splenic infarcts may be hard to visualize if they are very small and/or more centrally located in the abdomen. Computed tomography, though it does involve an IV dye load and radiation, has the advantage of visualizing the entire spleen while also showing the rest of the abdominal organs in the cases in which the differential is broad.



For the vast majority of splenic infarctions, the main concerns for the Emergency Physician are the determination of the underlying cause and providing proper disposition. If there is no obvious cause already known, but the patient is stable, pain is well controlled, and follow up can be reliably obtained, most patients can be discharged home with outpatient follow up, either with their primary care physician or a hematologist. If the patient is hemodynamically unstable, or if there is evidence of splenic rupture or abscess associated with the infarction, then consultation with Surgery or Interventional Radiology for further treatment and admission should be obtained. While many cases of splenic rupture can be managed non-operatively, the patient will require close observation and consideration for splenic artery embolization or splenectomy. Splenic abscess will require antibiotics as well as drainage or splenectomy. In any patient with a significant portion of their spleen affected by infarction, resultant functional hyposplenia should be anticipated, and the patient will need follow up to provide the appropriate vaccinations and monitoring.



The Emergency Department workup for this patient consisted of a complete blood count, a comprehensive metabolic profile, and coagulation studies in addition to a CT scan of the abdomen with IV contrast, as requested by radiology. A CT was selected to better characterize the total number and size of the lesions and to evaluate for any complications such as abscess or rupture. Laboratory work up was all within normal limits, and the CT scan revealed multiple peripheral small wedge-shaped hypodensities within the spleen measuring up to 1.9 cm. The patient remained hemodynamically stable throughout his ED stay, and his pain was well controlled. He was counseled to continue to avoid contact sports and to return to the Emergency Department for any increase in pain, fever, or other concerns. He was discharged with Hematology follow up. His clinical course remained unremarkable, and given the large portion of unaffected splenic tissue, he did not require any additional vaccines.

Screen Shot 2016-02-21 at 7.00.28 PM




Splenic infarction is a rare complication of infectious mononucleosis, and a rare disease in general, but should be considered in the ED differential of patients with left upper quadrant pain. Special consideration for this diagnosis should be given to those patients with a history of conditions predisposing to splenomegaly, a history of thromboembolic disease, and in those with a history of abdominal trauma. Management for most patients will consist of supportive case and avoidance of splenic injury (no contact sports), while some patients will require admission and consideration for splenectomy, especially if splenic abscess or splenic rupture develop.


References / Further Reading

-Harrison’s Principles of Internal Medicine 19ed

-Tintinalli’s Emergency Medicine 8ed

-Sabiston Textbook of Surgery

-The clinical spectrum of splenic infarction.

Nores M, Phillips EH, Morgenstern L, Hiatt JR

Am Surg. 1998;64(2):182.

PMID: 9486895

-Splenic infarction: an update on William Osler’s observations.

Lawrence YR, Pokroy R, Berlowitz D, Aharoni D, Hain D, Breuer GS

Isr Med Assoc J. 2010;12(6):362.

PMID: 20928991

-Splenic infarction: 10 years of experience.

Antopolsky M, Hiller N, Salameh S, Goldshtein B, Stalnikowicz et al .

Am J Emerg Med 2009;27:262–5.