- Email: [email protected]
Acute Acalculous Cholecystitis Caused by Epstein-Barr Virus Infection
Case Report
Acute Acalculous Cholecystitis Caused by Epstein-Barr Virus Infection Joe Dylewski, M.D., Director of Microbiology and Infectious Diseases, St. Mary’s Hospital, Montreal, Quebec, Canada
Introduction Infection with Epstein-Barr virus (EBV) can present in a myriad of ways aside from classical infectious mononucleosis (IM). Hemolytic anemia, acute renal failure, cholestatic jaundice, and Guillain-Barré syndrome can be manifestations of an acute infection with EBV (1). Involvement of the liver is common, and a transient elevation of hepatocellular enzymes occurs in 80% of people with IM (2). An unusual complication of EBV infection is the development of acute acalculous cholecystitis (AAC), which can mimic a surgical emergency (3-7). A case is presented of acalculous cholecystitis caused by an acute infection with EBV. The diagnostic and management issues of this disease are reviewed.
Case History A 22-year-old female was seen in the emergency department with a 2-day history of fever and right upper quadrant pain. For 1 week, she had also noticed a painful swelling in the left groin. On examination, her temperature was 39°C with a pulse of 110 beats/ min and a blood pressure of 100/80. She did not appear to be in acute distress, but there was extreme tenderness in the right upper quadrant. A painful 1.5-cm swelling in the left inguinal area was palpable. Throat and neck examinations were normal. Initial blood tests showed slightly elevated values for serum aspartate transaminase (AST) at 105 IU/L (normal, 10 to 42) and serum alanine transaminase (ALT) at 70 IU/L (normal, 5 to 60) with a normal serum bilirubin. The total white blood cell count (WBC) was 3.8 × 109/L with 1.5 × 109/L neutrophils, 0.5 × 109/L monocytes, and 1.7 × 109/L lymphocytes Mailing Address: Joe Dylewski, M.D., Director of Microbiology and Infectious Diseases, St. Mary’s Hospital, Montreal Quebec, Canada, H3T 1M5. Tel.: 514345-3511, ext 3075. Fax: 514-734-2607. E-mail: [email protected]
Clinical Microbiology Newsletter 34:1,2012
(1.0 × 109/L atypical lymphocytes). A slide agglutination test for heterophile antibody (Monogen; Biokit, Barcelona, Spain) was negative. A tentative diagnosis of acute cholecystitis was made, and the patient was started on intravenous cefazolin and metronidazole pending imaging studies. An abdominal ultrasound was performed, which revealed a 5-mm thickening of the gall bladder wall and the presence of pericholecystic fluid. There were no stones or enlargement of the common bile duct. A computed tomography (CT) scan of the abdomen confirmed the presence of pericholecystic fluid with hyperemia of the gall bladder wall. Mild splenomegaly with multiple small retroperitoneal, periportal, mesenteric, and bilateral inguinal adenopathy was present. Repeat blood studies done 12 h after the initial test showed a WBC of 4.9 × 109/L with 1.8 × 109/L neutrophils, 0.5 × 109/L monocytes, and 2.4 × 109/L lymphocytes (1.0 × 109/L atypical lymphocytes). A repeat slide agglutination test was weakly positive for heterophile antibody. The AST increased to 142 IU/L, and the ALT was 89 IU/L. IgM antibody to cytomegalovirus was negative. Specific EBV serologic studies showed the absence of IgG antibodies to early and viral capsid antigens (VCA), but there was a positive result for EBV VCA IgM antibody, confirming a diagnosis of acute EBV infection. The patient was discharged and seen again 2 days later, at which time her pain and fever had resolved.
Discussion Although liver involvement is common, inflammation of the gall bladder has also been described during IM. In a series of 39 patients (19 confirmed cases of acute EBV infection) with a mononucleosis-like syndrome who underwent ultrasound examinations, 6 were found to have thickening of the gall bladder wall, and this finding correlated with a longer duration of © 2012 Elsevier
hospitalization (8). The diagnosis of AAC is dependent on a combination of at least two of the following criteria: gall bladder wall thickening of greater than 3 mm, distension of the gall bladder, localized sensitivity, sludge, and pericholecystic fluid (9). The pathophysiology of disease is believed to be a combination of bile stasis and localized inflammation and ischemia. In only a small number of cases has primary infection with EBV been documented to cause AAC (3-7). A recent review (6) contained only 11 cases, 3 of which were in patients 20 years of age or older. Nine of these cases had evidence of tonsillitis or pharyngitis. This case is unusual in the absence of throat discomfort or cervical adenopathy and by her older age. All but one of the previous cases occurred in females. There is also a postulated association of AAC caused by EBV with Gilbert’s syndrome (hereditary unconjugated hyperbilirubinemia), which was attributed to increased exposure to a less water-soluble bilirubin monoglucoronide (5), but this association has not been confirmed. Acute EBV infection can be diagnosed by a combination of clinical and laboratory examinations. However, the classic presentation of fever, sore throat, and lymphadenopathy has a sensitivity of only 68.2% and a specificity of 41.9% for EBV infection (2). The presence of lymphocytosis with many atypical lymphocytes increases the likelihood of an IM diagnosis, and a positive test for heterophile antibodies, in this context, confirms the diagnosis. The gold standard remains finding IgM antibodies to EBV VCA, which are present within 7 days of symptom onset in 90% of cases and virtually always detectable within 2 weeks of illness (2). Radiologic diagnosis of AAC can be achieved by demonstration of gall bladder wall thickening/hyperemia, biliary sludge, and/or pericholecytic fluid, using either ultrasound or CT scanning (9). The management of AAC caused by 0196-4399/00 (see frontmatter)
7
EBV is supportive. Some patients have initially received broad-spectrum antibiotics, but there is no consensus that this is required once the causative agent has been established. The clinical course of AAC caused by EBV appears to be milder than AAC caused by other infectious agents (6); however, there is a report of a spontaneous perforation caused by EBV-associated AAC with complete resolution (7). References 1. Johannsen, E.C. and K.M. Kaye. 2010. Epstein-Barr virus (infectious mononucleosis, Epstein-Barr virus-associated malignant diseases, and other diseases), p. 1989-2010. In G.L. Mandell, J.E. Bennett, and R. Dolin (ed.), Mandell,
8
0196-4399/00 (see frontmatter)
2.
3.
4.
5.
Douglas and Bennett’s principles and practice of infectious diseases, 7th ed. Churchill, Livingstone, Elsevier. Philadelphia, PA. Odumade, O.A., K.A. Hogquist, and H.H. Balfour, Jr. 2011. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin. Microbiol. Rev. 24:193-209. Lagona, E. et al. 2007. Epstein-Barr virus infectious mononucleosis associated with acalculous cholecystitis. Infection 35:118-119. Iaria, C. et al. 2008. Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature. Int. J. Infect. Dis. 12:391-395. Attilakos, A. et al. 2009. Acute acalculous cholecystitis in children with
© 2012 Elsevier
Epstein-Barr virus infection: a role for Gilbert’s syndrome? Int. J. Infect. Dis. 13:e161-e164. 6. Arya, S.O. et al. 2010. Epstein-Barr virus-associated acute acalculous cholecystitis: a rare occurrence but favorable outcome. Clin. Pediatr. 49:799-804. 7. Chalupa, P., M. Kaspar, and M. Holub. 2009. Acute acalculous cholecystitis with pericholcystitis in a patient with Epstein-Barr virus infectious mononucleosis. Med. Sci. Monit. 15:CS30-CS33. 8. Yamada, K. and H. Yamada. 2001. Gallbladder wall thickening in mononucleosis syndromes. J. Clin. Ultrasound 29:322325. 9. Deitch, E.A. and J.M. Engel. 1981. Acute acalculous cholecystitis: ultrasonic diagnosis. Am. J. Surg. 142:290-292.
Clinical Microbiology Newsletter 34:1,2012
Acute Acalculous Cholecystitis Caused by Epstein-Barr Virus Infection Joe Dylewski, M.D., Director of Microbiology and Infectious Diseases, St. Mary’s Hospital, Montreal, Quebec, Canada
Introduction Infection with Epstein-Barr virus (EBV) can present in a myriad of ways aside from classical infectious mononucleosis (IM). Hemolytic anemia, acute renal failure, cholestatic jaundice, and Guillain-Barré syndrome can be manifestations of an acute infection with EBV (1). Involvement of the liver is common, and a transient elevation of hepatocellular enzymes occurs in 80% of people with IM (2). An unusual complication of EBV infection is the development of acute acalculous cholecystitis (AAC), which can mimic a surgical emergency (3-7). A case is presented of acalculous cholecystitis caused by an acute infection with EBV. The diagnostic and management issues of this disease are reviewed.
Case History A 22-year-old female was seen in the emergency department with a 2-day history of fever and right upper quadrant pain. For 1 week, she had also noticed a painful swelling in the left groin. On examination, her temperature was 39°C with a pulse of 110 beats/ min and a blood pressure of 100/80. She did not appear to be in acute distress, but there was extreme tenderness in the right upper quadrant. A painful 1.5-cm swelling in the left inguinal area was palpable. Throat and neck examinations were normal. Initial blood tests showed slightly elevated values for serum aspartate transaminase (AST) at 105 IU/L (normal, 10 to 42) and serum alanine transaminase (ALT) at 70 IU/L (normal, 5 to 60) with a normal serum bilirubin. The total white blood cell count (WBC) was 3.8 × 109/L with 1.5 × 109/L neutrophils, 0.5 × 109/L monocytes, and 1.7 × 109/L lymphocytes Mailing Address: Joe Dylewski, M.D., Director of Microbiology and Infectious Diseases, St. Mary’s Hospital, Montreal Quebec, Canada, H3T 1M5. Tel.: 514345-3511, ext 3075. Fax: 514-734-2607. E-mail: [email protected]
Clinical Microbiology Newsletter 34:1,2012
(1.0 × 109/L atypical lymphocytes). A slide agglutination test for heterophile antibody (Monogen; Biokit, Barcelona, Spain) was negative. A tentative diagnosis of acute cholecystitis was made, and the patient was started on intravenous cefazolin and metronidazole pending imaging studies. An abdominal ultrasound was performed, which revealed a 5-mm thickening of the gall bladder wall and the presence of pericholecystic fluid. There were no stones or enlargement of the common bile duct. A computed tomography (CT) scan of the abdomen confirmed the presence of pericholecystic fluid with hyperemia of the gall bladder wall. Mild splenomegaly with multiple small retroperitoneal, periportal, mesenteric, and bilateral inguinal adenopathy was present. Repeat blood studies done 12 h after the initial test showed a WBC of 4.9 × 109/L with 1.8 × 109/L neutrophils, 0.5 × 109/L monocytes, and 2.4 × 109/L lymphocytes (1.0 × 109/L atypical lymphocytes). A repeat slide agglutination test was weakly positive for heterophile antibody. The AST increased to 142 IU/L, and the ALT was 89 IU/L. IgM antibody to cytomegalovirus was negative. Specific EBV serologic studies showed the absence of IgG antibodies to early and viral capsid antigens (VCA), but there was a positive result for EBV VCA IgM antibody, confirming a diagnosis of acute EBV infection. The patient was discharged and seen again 2 days later, at which time her pain and fever had resolved.
Discussion Although liver involvement is common, inflammation of the gall bladder has also been described during IM. In a series of 39 patients (19 confirmed cases of acute EBV infection) with a mononucleosis-like syndrome who underwent ultrasound examinations, 6 were found to have thickening of the gall bladder wall, and this finding correlated with a longer duration of © 2012 Elsevier
hospitalization (8). The diagnosis of AAC is dependent on a combination of at least two of the following criteria: gall bladder wall thickening of greater than 3 mm, distension of the gall bladder, localized sensitivity, sludge, and pericholecystic fluid (9). The pathophysiology of disease is believed to be a combination of bile stasis and localized inflammation and ischemia. In only a small number of cases has primary infection with EBV been documented to cause AAC (3-7). A recent review (6) contained only 11 cases, 3 of which were in patients 20 years of age or older. Nine of these cases had evidence of tonsillitis or pharyngitis. This case is unusual in the absence of throat discomfort or cervical adenopathy and by her older age. All but one of the previous cases occurred in females. There is also a postulated association of AAC caused by EBV with Gilbert’s syndrome (hereditary unconjugated hyperbilirubinemia), which was attributed to increased exposure to a less water-soluble bilirubin monoglucoronide (5), but this association has not been confirmed. Acute EBV infection can be diagnosed by a combination of clinical and laboratory examinations. However, the classic presentation of fever, sore throat, and lymphadenopathy has a sensitivity of only 68.2% and a specificity of 41.9% for EBV infection (2). The presence of lymphocytosis with many atypical lymphocytes increases the likelihood of an IM diagnosis, and a positive test for heterophile antibodies, in this context, confirms the diagnosis. The gold standard remains finding IgM antibodies to EBV VCA, which are present within 7 days of symptom onset in 90% of cases and virtually always detectable within 2 weeks of illness (2). Radiologic diagnosis of AAC can be achieved by demonstration of gall bladder wall thickening/hyperemia, biliary sludge, and/or pericholecytic fluid, using either ultrasound or CT scanning (9). The management of AAC caused by 0196-4399/00 (see frontmatter)
7
EBV is supportive. Some patients have initially received broad-spectrum antibiotics, but there is no consensus that this is required once the causative agent has been established. The clinical course of AAC caused by EBV appears to be milder than AAC caused by other infectious agents (6); however, there is a report of a spontaneous perforation caused by EBV-associated AAC with complete resolution (7). References 1. Johannsen, E.C. and K.M. Kaye. 2010. Epstein-Barr virus (infectious mononucleosis, Epstein-Barr virus-associated malignant diseases, and other diseases), p. 1989-2010. In G.L. Mandell, J.E. Bennett, and R. Dolin (ed.), Mandell,
8
0196-4399/00 (see frontmatter)
2.
3.
4.
5.
Douglas and Bennett’s principles and practice of infectious diseases, 7th ed. Churchill, Livingstone, Elsevier. Philadelphia, PA. Odumade, O.A., K.A. Hogquist, and H.H. Balfour, Jr. 2011. Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin. Microbiol. Rev. 24:193-209. Lagona, E. et al. 2007. Epstein-Barr virus infectious mononucleosis associated with acalculous cholecystitis. Infection 35:118-119. Iaria, C. et al. 2008. Acute acalculous cholecystitis during the course of primary Epstein-Barr virus infection: a new case and a review of the literature. Int. J. Infect. Dis. 12:391-395. Attilakos, A. et al. 2009. Acute acalculous cholecystitis in children with
© 2012 Elsevier
Epstein-Barr virus infection: a role for Gilbert’s syndrome? Int. J. Infect. Dis. 13:e161-e164. 6. Arya, S.O. et al. 2010. Epstein-Barr virus-associated acute acalculous cholecystitis: a rare occurrence but favorable outcome. Clin. Pediatr. 49:799-804. 7. Chalupa, P., M. Kaspar, and M. Holub. 2009. Acute acalculous cholecystitis with pericholcystitis in a patient with Epstein-Barr virus infectious mononucleosis. Med. Sci. Monit. 15:CS30-CS33. 8. Yamada, K. and H. Yamada. 2001. Gallbladder wall thickening in mononucleosis syndromes. J. Clin. Ultrasound 29:322325. 9. Deitch, E.A. and J.M. Engel. 1981. Acute acalculous cholecystitis: ultrasonic diagnosis. Am. J. Surg. 142:290-292.
Clinical Microbiology Newsletter 34:1,2012