- Email: [email protected]
Staphylococcal Liver Abscess and Acute Cholecystitis in a Patient With Crohn's Disease Receiving Infliximab
Staphylococcal Liver Abscess and Acute Cholecystitis in a Patient With Crohn’s Disease Receiving Infliximab Tushar R. Patel, M.D., Kepal N. Patel, M.D., Andrew H. Boyarsky, M.D.
We present an unusual case of empyema of the gallbladder associated with a pyogenic liver abscess in a patient with Crohn’s disease on Infliximab. It manifested by weakness, weight loss, and vague abdominal pain, which eventually localized to the right upper quadrant 4 days prior to admission. Diagnostic evaluation, which included ultrasonography and computed tomography, revealed cholelithiasis, gallbladder wall thickening, and a low-attenuation, complex mass in the left hepatic lobe. Cholecystectomy and open drainage of the liver abscess were successfully performed. There are few reports of intrahepatic abscess associated with Crohn’s disease. The relationship between acute cholecystitis and Crohn’s disease has also been documented. However, this report documents the unusual complication of pyogenic liver abscess secondary to acute cholecystitis in the unique population of Crohn’s disease patients on Infliximab. ( J GASTROINTEST SURG 2006;10:105–110) 쑖 2006 The Society for Surgery of the Alimentary Tract KEY WORDS: Crohn’s, infliximab, cholecystectomy, liver abscess
The prevalence of cholelithiasis in the general population is a well-known and established fact. The estimated prevalence of gallstones has been determined by ultrasonography to range from 11% to 15% in women and 3% to 11% in men under 50 years of age. Gallstone formation increases with age, with a prevalence as high as 50% in women and 15% in men 60 years of age or older. Individuals with a family history of gallstones; who belong to certain ethnic groups (i.e., Native Americans); who have obesity, diabetes, small bowel malabsorptive syndromes, rapid weight loss, or multiparity; and those on hyperalimentation are at increased risk of developing gallstones.1 The relationship between inflammatory bowel disease and biliary tract disease has also been well documented.2 A common complication of symptomatic cholelithiasis is acute calculus cholecystitis, which usually results from impaction of a gallstone in the cystic duct or the neck of the gallbladder that completely obstructs the organ. Pyogenic abscesses represent the most common type of hepatic abscess encountered in the United States.3 The incidence may approximate as high as
20 cases per 100,000 patient admissions. Patients with Crohn’s disease have a higher incidence of liver abscess (114–297 per 100,000) than the general population.4 Infliximab (Remicade) is a chimeric (humanmouse) monoclonal antibody targeted at human tumor necrosis factor-α (TNF-α), a proinflammatory cytokine that may be important in the pathogenesis of Crohn’s disease. Although Infliximab’s mechanism of action is incompletely understood, its action is thought to target the immune system by its ability to bind precursor cell-surface TNF, perhaps leading to monocyte apoptosis. Infliximab antagonizes the biological activity of TNF-α by binding to it on macrophage and T-cell surfaces. The most frequent adverse effects of Infliximab are headache, nausea, and upper respiratory tract infections, and some anecdotal case reports of an increased propensity in Staphylococcus auerus infections. We recently successfully treated a patient with Crohn’s disease who presented with a true intrahepatic abscess associated with acute cholecystitis. This patient was also being treated with Infliximab.
From the Department of Surgery, Division of General Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey. Reprint requests: Andrew H. Boyarsky, M.D., One Robert Wood Johnson Place, Division of General Surgery, P.O. Box 19 MEB-456, New Brunswick, NJ 09803-0019. e-mail: [email protected]
쑖 2006 The Society for Surgery of the Alimentary Tract Published by Elsevier Inc.
1091-255X/06/$—see front matter doi:10.1016/j.gassur.2005.04.006
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CASE REPORT A 28-year-old man with a 19-year history of Crohn’s disease presented to his primary care physician with complaints of vague abdominal pain, a 10pound weight loss, and weakness over the past 3 months. The pain localized to the right upper quadrant 4 days prior to admission. The pain was unremitting, sharp, and nonradiating and was associated with nausea, without vomiting, fevers, chills, or diaphoresis. He denied changes in his bowel habits or any urinary symptoms. His past medical history was significant only for Crohn’s disease. His medications included Pentasa, Prilosec, and Infliximab, which he had been receiving for 7 months prior to this current illness for episodic inflammatory flare-ups intractable to standard therapies. Physical examination revealed a thin male in no acute distress. Pertinent physical findings disclosed no evidence of scleral icterus or jaundice. His abdomen was soft and mildly distended with moderate right upper quadrant tenderness. No masses were palpable, and rectal examination was negative for occult blood. Laboratory results were as follows: white blood cell count, 9.0 K/mm3 (4.0–10.0); total bilirubin, 0.4 mg/dl (0.1–1.2); alkaline phosphatase, 337 IU/L (37– 107); AST, 18 IU/L (12–45); ALT, 21 IU/L (3–40); amylase, 34 U/L (44–128) and lipase, 62 U/L (40– 175). Right upper quadrant ultrasonography revealed a thickened gallbladder wall, no pericholecystic fluid, multiple small filling defects consistent with cholelithiasis, no intrahepatic ductal dilatation, and a common bile duct measuring 4 mm in diameter. An abnormal hypoechoic intrahepatic lesion measuring approximately 6 × 4 × 6 cm was noted posterior and medial to the gallbladder. Abdominal computed tomography scan, which was performed to further delineate this intrahepatic finding (Fig. 1), revealed a complex low-attenuation mass in the lateral segment of the left hepatic lobe. This was consistent with an abscess. The gallbladder demonstrated uniform wall thickening with pericholecystic inflammatory changes. Several distal small bowel loops were found to be thickened, presumably secondary to active Crohn’s disease. Based on these findings and the patient’s clinical examination, he was taken to the operating room with the diagnosis of acute cholecystitis with an intrahepatic abscess. Upon exploration, he was found to have gallbladder empyema. No gross perforation was noted. In the lateral segment of the left lobe of the liver, an obvious mass was palpable clearly separate from the gallbladder. Needle aspiration was performed, which revealed a purulent fluid collection. An incision was made over the mass, and using the
Fig. 1. Computed tomography scan of the abdomen revealing acute cholecystitis and evidence of a hepatic abscess.
liver finger-fracture technique, the abscess was drained and cultures were obtained. Two drains were left in place, and the wound was copiously irrigated. The small bowel in this area appeared mildly inflamed, but no perforation or intraloop abscess was noted. The patient’s postoperative course was remarkably uneventful. He was initially kept on broad-spectrum antibiotics until the intraoperative culture results were obtained. Pentasa and Prilosec were continued, while the Infliximab was discontinued. Intraoperative cultures grew S. aureus (methicillin sensitive) from both gallbladder and the liver. Antibiotics were appropriately manipulated, and he was kept on oral antibiotic therapy for 4 weeks. Echocardiography revealed no evidence of valvular heart disease. The patient was discharged on postoperative day 6, tolerating oral intake, on oral antibiotics, with home wound care. Pathologic examination of the gallbladder revealed acute cholecystitis with areas of focal wall necrosis and cholelithiasis. DISCUSSION Hepatic abscess is a relatively rare problem. The most common cause of pyogenic liver abscess is ascending cholangitis secondary to benign or malignant biliary tract obstruction. Other causes include portal vein bacteremia or pylephlebitis resulting from intestinal infections such as appendicitis or diverticulitis; hepatic artery bacteremia from systemic infections such as endocarditis; direct extension from adjacent infections such as gangrenous cholecystitis, pancreatic abscess, or subhepatic abscess; Crohn’s disease; secondary infections of traumatic hepatic hematomas; necrosis of hepatic neoplasms; and cryptogenic, in which no obvious cause can be identified (Table 1).
Vol. 10, No. 1 2006
Staphylococcal Liver Abscess and Acute Cholecystitis
Crohn’s disease is associated with various hepatobiliary disorders, including pericholangitis, sclerosing cholangitis, granulomatous hepatitis, and cholelithiasis.5–7 Liver abscess is rare; only 30 reported cases of Crohn’s disease with liver abscess could be identified with variable data8 (Table 2). Crohn’s disease may predispose a small subset of these patients to aggressive microbial invasion of the portal venous system with seeding of the hepatic parenchyma.5 Indeed, frequent portal venous bacteremia has been documented in inflammatory bowel disease.9 The more common and well-known complications of Crohn’s disease, such as fistulization, perforation, and intra-abdominal abscess formation, create conditions known to otherwise be favorable to the development of liver abscess.10,11 The frequent use of adrenal corticosteroid therapy, malnutrition, and the presumed underlying immunologic abnormalities in Crohn’s disease may also play a role.12 It has been well established that patients with Crohn’s disease, regardless of gender and age, have almost a doubled risk of developing cholelithiasis compared with the general population.13 The prevalence has been reported to be between 13% and 34%.13–15 The pathogenesis of gallstones and the increased incidence in Crohn’s disease is unknown. Cholesterol gallstones account for more than 80% of the gallstones in the Western world; however, patients with Crohn’s disease are more prone to pigment (calcium bilirubinate) than cholesterol gallstone formation. Previous reports have demonstrated normal cholesterol saturation with increased content of bilirubin in the bile of patients having had an ileal resection due to Crohn’s disease.16 Patients with more extensive Crohn’s disease, especially those including the duodenum, may have impaired mucosal release of cholecystokinin and, as a consequence, decreased gallbladder motility.17–20 In this case, Crohn’s disease quite possibly precipitated the formation of gallstones and cholecystitis,
107
Table 2. Reported Cases of Liver Abscesses in Patients With Crohn’s Disease Author
Year
Associated Clinical Findings
Snavely JR
1946
Taylor FW Lerman B Sparberg M Zarnow H Watts HD Nelson A Labatto S Hatoff DE Brositus TA
1949 1962 1965 1976 1978 1979 1980 1983 1983
Macpherson DS Valero V Teague M Kotengi H Vakil N*
1985 1985 1988 1991 1994
Diarrhea and abdominal tenderness Pylephlebitis Suppurative pylephlebitis Hepatic abscess alone Duodenobiliary fistula Multiple hepatic abscesses Hepatic abscess alone Hepatic abscess alone Perineal Crohn’s disease Streptococcus meningitis intermedius Hepatic abscess alone Thoracic empyema Hepatic abscess alone Hepatic abscess alone Staphylococcal hepatic abscess with cutaneous infection
Modified from Vakil N, Hayne G, Sharma A, Hardy DJ, Slutsky A. Liver abscess in Crohn’s disease. Am J Gastroenterol 89:1090–1095, 1994. *Retrospective review; all other publications are case reports.
leading to empyema of the gallbladder and an intrahepatic abscess. Hepatic abscess secondary to cholecystitis usually occurs as a direct extension of infection. Local factors such as chronic inflammation and gallbladder wall ischemia as well as systemic factors, such as immunosuppression, may all be contributory to abscess formation. The finding of S. aureus as the organism growing from both the gallbladder and abscess culture sites further supports our belief that both processes were related. There have been reports of S. aureus being cultured from pyogenic liver abscesses in Crohn’s
Table 1. Causes and prognostic indicators of liver abscesses Causes of Liver Abscesses
Cryptogenic (40%) Biliary tract obstruction (37%) Portal bacteremia (11%) Systemic bacteremia (6%) Direct extension (4%) Other (2%)
Types of Organisms
Poor Patient Prognostic Indicators
Gram-negative aerobes (50–70%) Gram-positive aerobes (30%) Anaerobes (40–50%) Fungal (26%) Sterile (7%)
Age ⬎70, WBC ⬎20,000, albumin ⬍2 Increasing bilirubin, SGOT Multiple abscesses, aerobic abscess Diabetes, septicemia, malignancy Biliary etiology, complication Polymicrobial bacteremia
Data from Seeto RK, Rockey DC. Pyogenic liver abscess: Changes in etiology, management and outcome. Medicine 1996;75:99–113; Garrison RN, Polk HC. Liver abscess and subphrenic abscess. In: Blumgart LH, ed. Surgery of the liver and biliary tract, 2nd ed. Edinburgh: Churchill Livingstone, 1994. p. 1091–1102; Zinner MJ, Schwartz SI, Ellis H. Liver abscess and hydatid cyst disease. In: Zinner MJ, Schwartz SI, Ellis H, eds. Maingot’s Abdominal Operations, 10th ed. Stamford, CT: Appleton & Lange, 1997.
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patients, but these patients reported cutaneous infections in the weeks preceding the diagnosis of the abscess. The common organisms involved with pyogenic hepatic abscesses are listed in Table 1. The historical standard treatment of a solitary pyogenic liver abscess is surgical drainage with identification and correction of the underlying process coupled with systemic antibiotics for 2–6 weeks to treat concurrent smaller and undiagnosed purulent collections within the liver.21–24 Medical treatment with antibiotics alone can be successful early in the
course of the disease, in patients with small multiple abscesses (⬍1.5-cm diameter) and when there is no surgically correctable factor. Computed tomography– or ultrasonography-guided percutaneous drainage can be successful in poor-risk patients or in patients with a solitary abscess, who do not have other indications for surgical exploration. Laparoscopy has been used for both diagnosis and drainage when percutaneous attempts have failed.25 In this case, our patient had an obvious surgically correctable etiological factor and thus a clear indication for
PYOGENIC HEPATIC ABSCESS
Clinical suspicion
Empiric BroadSpectrum Antibiotics
Computed tomography, diagnostic aspiration
Intraabdominal Source?
No
Solitary or Few, Large abscesses
Percutaneous Drainage And Antibiotics
Yes
Multiple small abscesses
Antibiotics alone
Surgical Drainage, ± percutaneous drainage, Treat Underlying Source
Treatment failure
Identify and Treat Source Fig. 2. Treatment algorithm for patients with pyogenic hepatic abscess. Adapted from Glasgow RE, Mulvihil SJ. Hepatic abscess. In: Cameron JL, ed. Current Surgical Therapy, 6th ed. St. Louis, MO: Mosby, 1998. p. 314–321.
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exploration. Figure 2 presents and summarizes a treatment algorithm for patients with a pyogenic hepatic abscess. If untreated, nearly all pyogenic liver abscesses prove fatal. Modern diagnostic imaging, antibiotics, and aggressive early surgical or percutaneous drainage have further improved mortality statistics to 80–90% survival. Several factors, such as delayed diagnosis, undrained or poorly drained collections, multiple small undrainable abscesses, and untreated primary etiologic sites, however, are still associated with a poor prognosis in patients with pyogenic hepatic abscesses (Table 1). A heightened awareness of the risks of Infliximab use is crucial in patients with chronic infections or iatrogenic induced immunodeficiency. TNF-α, a major proinflammatory cytokine, plays an important role in host defense against infection. Inhibition of its activity could therefore be anticipated to augment the risk of infection in patients with preexisting abnormalities of immune regulation. Infliximab’s anti– TNF-α properties target the immune system, raising concerns about the potential for immune sensitization and immunosuppressive sequelae.26 The relationship between cytokine inhibition and infection may also be associated with comorbidities such as diabetes mellitus, heart disease, disability, and concurrent immunosuppressive medication.27 Many cases have been reported where the use of Infliximab therapy has been associated with unusual bacterial infections such as Escherichia coli colitis, aseptic streptococcal meningitis, and staphylococcal intramyocardial inflammation. In the latter case, a chronic inflammatory process was activated by infliximab, suggesting in this case that an underlying chronic biliary infection was further stimulated by this immunosuppressive drug.28–30 CONCLUSION Pyogenic hepatic abscess can be a challenging clinical problem and, despite modern modalities, is still associated with a rather high morbidity and mortality. Patients with Crohn’s disease are more prone to liver abscess formation and are also at higher risk of developing cholelithiasis. An increased use of Infliximab may put these patients at increased risk of developing an unusual bacteriologic flora potentially leading to acute cholecystitis with or without a hepatic abscess. Appropriate diagnostic evaluations and aggressive treatment should improve the prognosis for this potentially life-threatening complication. REFERENCES 1. Diehl AK. Epidemiology and natural history of gallstone disease. Gastroenterol Clin North Am 1991;20:1–19.
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2. Lorusso D, Silvana L, Mossa A, et al. Cholelithiasis in inflammatory bowel disease. Dis Colon Rect 1990;33:791–794. 3. Attili AF, DeSantis A, Capri R, et al. The natural history of gallstones: The GREPCO experience. Hepatology 1995;21: 656–660. 4. Teague M, Baddour LM, Wruble LD. Liver abscess: A harbinger of Crohn’s disease. Am J Gastroenterol 1998; 83:1412–1414. 5. Mir-Madjlessi SH, McHenry MC, Farmer RG. Liver abscess in Crohn’s disease: Report of four cases and review of the literature. Gastroenterology 1986;91:987–993. 6. Allan RN. Extra-intestinal manifestations of inflammatory bowel disease. Clin Gastroenterol 1983;12:617–632. 7. Christophi C, Hughes ER. Hepatobiliary disorders in inflammatory bowel disease. Surg Gynecol Obstet 1985;160: 189–193. 8. Vakil N, Hayne G, Sharma A, Hardy DJ, Slutsky A. Liver abscess in Crohn’s disease. Am J Gastroenterol 1994;89: 1090–1095. 9. Brooke BN, Slaney G. Portal bacteremia in ulcerative colitis. Lancet 1958;1:1206–1207. 10. Lerman B, Garlock JH, Janowitz HD. Suppurative pylephlebitis with multiple liver abscesses complicating regional ileitis. Review of literature 1940-1960. Ann Surg 1962;155:441–448. 11. Taylor FW. Regional enteritis complicated by pylephlebitis and multiple liver abscesses. Am J Med 1949;7:838–840. 12. Kirsner JB, Shorter RG. Recent developments in non-specific inflammatory bowel disease (second of two parts). N Engl J Med 1982;306:837–848. 13. Baker AL, Kaplan MM, Norton RA, et al. Gallstones in inflammatory bowel disease. Dig Dis 1974;19:109–112. 14. Anderson H, Bosaeus I, Fasth S, et al. Cholelithiasis and urolithiasis in Crohn’s disease. Scand J Gastroenterol 1987;22: 253–256. 15. Hutchinson R, Tyrrell PNM, Kumar D, et al. Pathogenesis of gallstones in Crohn’s disease. An alternative explanation. Gut 1994;35:94–97. 16. Lapidus A, Bangstad M, Astrom M, et al. The prevalence of gallstone disease in a defined cohort of patients with Crohn’s disease. Am J Gastroenterol 1999;94:1261–1266. 17. Heaton KW, Read AE. Gallstones in patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 1969;3:494–496. 18. Brink MA, Slors JFM, Keulemans YCA, et al. Enterohepatic cycling of bilirubin: A putative mechanism for pigment gallstone formation in ileal Crohn’s disease. Gastroenterology 1999;116:1420–1427. 19. Lapidus A, Einarsson C. Bile composition in patients with ileal resection due to Crohn’s disease. Inflamm Bowel Dis 1998;4:89–94. 20. Dawes L, Stryker S, Rege R, et al. Gallbladder bile composition in Crohn’s disease. Surg Forum 1991;42:188–189. 21. Klatchko BA, Schwartz SI. Diagnostic and therapeutic approaches to pyogenic abscess of the liver. Surg Gynecol Obstet 1989;168:332–334. 22. Miedema BW, Dineen P. The diagnosis and treatment of pyogenic liver abscess. Ann Surg 1984;200:328–335. 23. Bertel CK, van Heerden JA, Sheedy PF. Treatment of pyogenic hepatic abscesses: Surgical vs. percutaneous drainage. Arch Surg 1986;121:554. 24. Robert JH, Mirescu D, et al. Critical review of the treatment of pyogenic hepatic abscess. Surg Gynecol Obstet 1992; 174:97. 25. Bakalakos EA, Melvin WS, Kirkpatrick R. Liver abscess secondary to intrahepatic perforation of the gallbladder,
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presenting as a liver mass. Am J Gastroenterol 1996;91: 1644–1646. 26. Hanauer SB. Review article: Safety of infliximab in clinical trials. Aliment Pharmacol Ther 1999;13:16–22. 27. Bresnihan B, Cunnane G. Infection complications associated with the use of biologic agents. Rheum Dis Clin North Am 2003;29:185–202.
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28. Reichardt P, et al. Possible activation of an intramyocardial inflammatory process (Staphylococcus aureus) after treatment with infliximab in a boy with Crohn disease. Eur J Pediatr 2002;161:281–283. 29. D’Haens GR. Infliximab (Remicade), a new biological treatment for Crohn’s disease. Dig Liver Dis 1999;31:519–520. 30. Garnett WR, Yunker N. Treatment of Crohn’s disease with infliximab. Am J Health System Pharmacy 2001;58:307–316.
We present an unusual case of empyema of the gallbladder associated with a pyogenic liver abscess in a patient with Crohn’s disease on Infliximab. It manifested by weakness, weight loss, and vague abdominal pain, which eventually localized to the right upper quadrant 4 days prior to admission. Diagnostic evaluation, which included ultrasonography and computed tomography, revealed cholelithiasis, gallbladder wall thickening, and a low-attenuation, complex mass in the left hepatic lobe. Cholecystectomy and open drainage of the liver abscess were successfully performed. There are few reports of intrahepatic abscess associated with Crohn’s disease. The relationship between acute cholecystitis and Crohn’s disease has also been documented. However, this report documents the unusual complication of pyogenic liver abscess secondary to acute cholecystitis in the unique population of Crohn’s disease patients on Infliximab. ( J GASTROINTEST SURG 2006;10:105–110) 쑖 2006 The Society for Surgery of the Alimentary Tract KEY WORDS: Crohn’s, infliximab, cholecystectomy, liver abscess
The prevalence of cholelithiasis in the general population is a well-known and established fact. The estimated prevalence of gallstones has been determined by ultrasonography to range from 11% to 15% in women and 3% to 11% in men under 50 years of age. Gallstone formation increases with age, with a prevalence as high as 50% in women and 15% in men 60 years of age or older. Individuals with a family history of gallstones; who belong to certain ethnic groups (i.e., Native Americans); who have obesity, diabetes, small bowel malabsorptive syndromes, rapid weight loss, or multiparity; and those on hyperalimentation are at increased risk of developing gallstones.1 The relationship between inflammatory bowel disease and biliary tract disease has also been well documented.2 A common complication of symptomatic cholelithiasis is acute calculus cholecystitis, which usually results from impaction of a gallstone in the cystic duct or the neck of the gallbladder that completely obstructs the organ. Pyogenic abscesses represent the most common type of hepatic abscess encountered in the United States.3 The incidence may approximate as high as
20 cases per 100,000 patient admissions. Patients with Crohn’s disease have a higher incidence of liver abscess (114–297 per 100,000) than the general population.4 Infliximab (Remicade) is a chimeric (humanmouse) monoclonal antibody targeted at human tumor necrosis factor-α (TNF-α), a proinflammatory cytokine that may be important in the pathogenesis of Crohn’s disease. Although Infliximab’s mechanism of action is incompletely understood, its action is thought to target the immune system by its ability to bind precursor cell-surface TNF, perhaps leading to monocyte apoptosis. Infliximab antagonizes the biological activity of TNF-α by binding to it on macrophage and T-cell surfaces. The most frequent adverse effects of Infliximab are headache, nausea, and upper respiratory tract infections, and some anecdotal case reports of an increased propensity in Staphylococcus auerus infections. We recently successfully treated a patient with Crohn’s disease who presented with a true intrahepatic abscess associated with acute cholecystitis. This patient was also being treated with Infliximab.
From the Department of Surgery, Division of General Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey. Reprint requests: Andrew H. Boyarsky, M.D., One Robert Wood Johnson Place, Division of General Surgery, P.O. Box 19 MEB-456, New Brunswick, NJ 09803-0019. e-mail: [email protected]
쑖 2006 The Society for Surgery of the Alimentary Tract Published by Elsevier Inc.
1091-255X/06/$—see front matter doi:10.1016/j.gassur.2005.04.006
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CASE REPORT A 28-year-old man with a 19-year history of Crohn’s disease presented to his primary care physician with complaints of vague abdominal pain, a 10pound weight loss, and weakness over the past 3 months. The pain localized to the right upper quadrant 4 days prior to admission. The pain was unremitting, sharp, and nonradiating and was associated with nausea, without vomiting, fevers, chills, or diaphoresis. He denied changes in his bowel habits or any urinary symptoms. His past medical history was significant only for Crohn’s disease. His medications included Pentasa, Prilosec, and Infliximab, which he had been receiving for 7 months prior to this current illness for episodic inflammatory flare-ups intractable to standard therapies. Physical examination revealed a thin male in no acute distress. Pertinent physical findings disclosed no evidence of scleral icterus or jaundice. His abdomen was soft and mildly distended with moderate right upper quadrant tenderness. No masses were palpable, and rectal examination was negative for occult blood. Laboratory results were as follows: white blood cell count, 9.0 K/mm3 (4.0–10.0); total bilirubin, 0.4 mg/dl (0.1–1.2); alkaline phosphatase, 337 IU/L (37– 107); AST, 18 IU/L (12–45); ALT, 21 IU/L (3–40); amylase, 34 U/L (44–128) and lipase, 62 U/L (40– 175). Right upper quadrant ultrasonography revealed a thickened gallbladder wall, no pericholecystic fluid, multiple small filling defects consistent with cholelithiasis, no intrahepatic ductal dilatation, and a common bile duct measuring 4 mm in diameter. An abnormal hypoechoic intrahepatic lesion measuring approximately 6 × 4 × 6 cm was noted posterior and medial to the gallbladder. Abdominal computed tomography scan, which was performed to further delineate this intrahepatic finding (Fig. 1), revealed a complex low-attenuation mass in the lateral segment of the left hepatic lobe. This was consistent with an abscess. The gallbladder demonstrated uniform wall thickening with pericholecystic inflammatory changes. Several distal small bowel loops were found to be thickened, presumably secondary to active Crohn’s disease. Based on these findings and the patient’s clinical examination, he was taken to the operating room with the diagnosis of acute cholecystitis with an intrahepatic abscess. Upon exploration, he was found to have gallbladder empyema. No gross perforation was noted. In the lateral segment of the left lobe of the liver, an obvious mass was palpable clearly separate from the gallbladder. Needle aspiration was performed, which revealed a purulent fluid collection. An incision was made over the mass, and using the
Fig. 1. Computed tomography scan of the abdomen revealing acute cholecystitis and evidence of a hepatic abscess.
liver finger-fracture technique, the abscess was drained and cultures were obtained. Two drains were left in place, and the wound was copiously irrigated. The small bowel in this area appeared mildly inflamed, but no perforation or intraloop abscess was noted. The patient’s postoperative course was remarkably uneventful. He was initially kept on broad-spectrum antibiotics until the intraoperative culture results were obtained. Pentasa and Prilosec were continued, while the Infliximab was discontinued. Intraoperative cultures grew S. aureus (methicillin sensitive) from both gallbladder and the liver. Antibiotics were appropriately manipulated, and he was kept on oral antibiotic therapy for 4 weeks. Echocardiography revealed no evidence of valvular heart disease. The patient was discharged on postoperative day 6, tolerating oral intake, on oral antibiotics, with home wound care. Pathologic examination of the gallbladder revealed acute cholecystitis with areas of focal wall necrosis and cholelithiasis. DISCUSSION Hepatic abscess is a relatively rare problem. The most common cause of pyogenic liver abscess is ascending cholangitis secondary to benign or malignant biliary tract obstruction. Other causes include portal vein bacteremia or pylephlebitis resulting from intestinal infections such as appendicitis or diverticulitis; hepatic artery bacteremia from systemic infections such as endocarditis; direct extension from adjacent infections such as gangrenous cholecystitis, pancreatic abscess, or subhepatic abscess; Crohn’s disease; secondary infections of traumatic hepatic hematomas; necrosis of hepatic neoplasms; and cryptogenic, in which no obvious cause can be identified (Table 1).
Vol. 10, No. 1 2006
Staphylococcal Liver Abscess and Acute Cholecystitis
Crohn’s disease is associated with various hepatobiliary disorders, including pericholangitis, sclerosing cholangitis, granulomatous hepatitis, and cholelithiasis.5–7 Liver abscess is rare; only 30 reported cases of Crohn’s disease with liver abscess could be identified with variable data8 (Table 2). Crohn’s disease may predispose a small subset of these patients to aggressive microbial invasion of the portal venous system with seeding of the hepatic parenchyma.5 Indeed, frequent portal venous bacteremia has been documented in inflammatory bowel disease.9 The more common and well-known complications of Crohn’s disease, such as fistulization, perforation, and intra-abdominal abscess formation, create conditions known to otherwise be favorable to the development of liver abscess.10,11 The frequent use of adrenal corticosteroid therapy, malnutrition, and the presumed underlying immunologic abnormalities in Crohn’s disease may also play a role.12 It has been well established that patients with Crohn’s disease, regardless of gender and age, have almost a doubled risk of developing cholelithiasis compared with the general population.13 The prevalence has been reported to be between 13% and 34%.13–15 The pathogenesis of gallstones and the increased incidence in Crohn’s disease is unknown. Cholesterol gallstones account for more than 80% of the gallstones in the Western world; however, patients with Crohn’s disease are more prone to pigment (calcium bilirubinate) than cholesterol gallstone formation. Previous reports have demonstrated normal cholesterol saturation with increased content of bilirubin in the bile of patients having had an ileal resection due to Crohn’s disease.16 Patients with more extensive Crohn’s disease, especially those including the duodenum, may have impaired mucosal release of cholecystokinin and, as a consequence, decreased gallbladder motility.17–20 In this case, Crohn’s disease quite possibly precipitated the formation of gallstones and cholecystitis,
107
Table 2. Reported Cases of Liver Abscesses in Patients With Crohn’s Disease Author
Year
Associated Clinical Findings
Snavely JR
1946
Taylor FW Lerman B Sparberg M Zarnow H Watts HD Nelson A Labatto S Hatoff DE Brositus TA
1949 1962 1965 1976 1978 1979 1980 1983 1983
Macpherson DS Valero V Teague M Kotengi H Vakil N*
1985 1985 1988 1991 1994
Diarrhea and abdominal tenderness Pylephlebitis Suppurative pylephlebitis Hepatic abscess alone Duodenobiliary fistula Multiple hepatic abscesses Hepatic abscess alone Hepatic abscess alone Perineal Crohn’s disease Streptococcus meningitis intermedius Hepatic abscess alone Thoracic empyema Hepatic abscess alone Hepatic abscess alone Staphylococcal hepatic abscess with cutaneous infection
Modified from Vakil N, Hayne G, Sharma A, Hardy DJ, Slutsky A. Liver abscess in Crohn’s disease. Am J Gastroenterol 89:1090–1095, 1994. *Retrospective review; all other publications are case reports.
leading to empyema of the gallbladder and an intrahepatic abscess. Hepatic abscess secondary to cholecystitis usually occurs as a direct extension of infection. Local factors such as chronic inflammation and gallbladder wall ischemia as well as systemic factors, such as immunosuppression, may all be contributory to abscess formation. The finding of S. aureus as the organism growing from both the gallbladder and abscess culture sites further supports our belief that both processes were related. There have been reports of S. aureus being cultured from pyogenic liver abscesses in Crohn’s
Table 1. Causes and prognostic indicators of liver abscesses Causes of Liver Abscesses
Cryptogenic (40%) Biliary tract obstruction (37%) Portal bacteremia (11%) Systemic bacteremia (6%) Direct extension (4%) Other (2%)
Types of Organisms
Poor Patient Prognostic Indicators
Gram-negative aerobes (50–70%) Gram-positive aerobes (30%) Anaerobes (40–50%) Fungal (26%) Sterile (7%)
Age ⬎70, WBC ⬎20,000, albumin ⬍2 Increasing bilirubin, SGOT Multiple abscesses, aerobic abscess Diabetes, septicemia, malignancy Biliary etiology, complication Polymicrobial bacteremia
Data from Seeto RK, Rockey DC. Pyogenic liver abscess: Changes in etiology, management and outcome. Medicine 1996;75:99–113; Garrison RN, Polk HC. Liver abscess and subphrenic abscess. In: Blumgart LH, ed. Surgery of the liver and biliary tract, 2nd ed. Edinburgh: Churchill Livingstone, 1994. p. 1091–1102; Zinner MJ, Schwartz SI, Ellis H. Liver abscess and hydatid cyst disease. In: Zinner MJ, Schwartz SI, Ellis H, eds. Maingot’s Abdominal Operations, 10th ed. Stamford, CT: Appleton & Lange, 1997.
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patients, but these patients reported cutaneous infections in the weeks preceding the diagnosis of the abscess. The common organisms involved with pyogenic hepatic abscesses are listed in Table 1. The historical standard treatment of a solitary pyogenic liver abscess is surgical drainage with identification and correction of the underlying process coupled with systemic antibiotics for 2–6 weeks to treat concurrent smaller and undiagnosed purulent collections within the liver.21–24 Medical treatment with antibiotics alone can be successful early in the
course of the disease, in patients with small multiple abscesses (⬍1.5-cm diameter) and when there is no surgically correctable factor. Computed tomography– or ultrasonography-guided percutaneous drainage can be successful in poor-risk patients or in patients with a solitary abscess, who do not have other indications for surgical exploration. Laparoscopy has been used for both diagnosis and drainage when percutaneous attempts have failed.25 In this case, our patient had an obvious surgically correctable etiological factor and thus a clear indication for
PYOGENIC HEPATIC ABSCESS
Clinical suspicion
Empiric BroadSpectrum Antibiotics
Computed tomography, diagnostic aspiration
Intraabdominal Source?
No
Solitary or Few, Large abscesses
Percutaneous Drainage And Antibiotics
Yes
Multiple small abscesses
Antibiotics alone
Surgical Drainage, ± percutaneous drainage, Treat Underlying Source
Treatment failure
Identify and Treat Source Fig. 2. Treatment algorithm for patients with pyogenic hepatic abscess. Adapted from Glasgow RE, Mulvihil SJ. Hepatic abscess. In: Cameron JL, ed. Current Surgical Therapy, 6th ed. St. Louis, MO: Mosby, 1998. p. 314–321.
Vol. 10, No. 1 2006
exploration. Figure 2 presents and summarizes a treatment algorithm for patients with a pyogenic hepatic abscess. If untreated, nearly all pyogenic liver abscesses prove fatal. Modern diagnostic imaging, antibiotics, and aggressive early surgical or percutaneous drainage have further improved mortality statistics to 80–90% survival. Several factors, such as delayed diagnosis, undrained or poorly drained collections, multiple small undrainable abscesses, and untreated primary etiologic sites, however, are still associated with a poor prognosis in patients with pyogenic hepatic abscesses (Table 1). A heightened awareness of the risks of Infliximab use is crucial in patients with chronic infections or iatrogenic induced immunodeficiency. TNF-α, a major proinflammatory cytokine, plays an important role in host defense against infection. Inhibition of its activity could therefore be anticipated to augment the risk of infection in patients with preexisting abnormalities of immune regulation. Infliximab’s anti– TNF-α properties target the immune system, raising concerns about the potential for immune sensitization and immunosuppressive sequelae.26 The relationship between cytokine inhibition and infection may also be associated with comorbidities such as diabetes mellitus, heart disease, disability, and concurrent immunosuppressive medication.27 Many cases have been reported where the use of Infliximab therapy has been associated with unusual bacterial infections such as Escherichia coli colitis, aseptic streptococcal meningitis, and staphylococcal intramyocardial inflammation. In the latter case, a chronic inflammatory process was activated by infliximab, suggesting in this case that an underlying chronic biliary infection was further stimulated by this immunosuppressive drug.28–30 CONCLUSION Pyogenic hepatic abscess can be a challenging clinical problem and, despite modern modalities, is still associated with a rather high morbidity and mortality. Patients with Crohn’s disease are more prone to liver abscess formation and are also at higher risk of developing cholelithiasis. An increased use of Infliximab may put these patients at increased risk of developing an unusual bacteriologic flora potentially leading to acute cholecystitis with or without a hepatic abscess. Appropriate diagnostic evaluations and aggressive treatment should improve the prognosis for this potentially life-threatening complication. REFERENCES 1. Diehl AK. Epidemiology and natural history of gallstone disease. Gastroenterol Clin North Am 1991;20:1–19.
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presenting as a liver mass. Am J Gastroenterol 1996;91: 1644–1646. 26. Hanauer SB. Review article: Safety of infliximab in clinical trials. Aliment Pharmacol Ther 1999;13:16–22. 27. Bresnihan B, Cunnane G. Infection complications associated with the use of biologic agents. Rheum Dis Clin North Am 2003;29:185–202.
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