Epstein-Barr Virus Infectious Mononucleosis Associated with Acute Acalculous Cholecystitis

Hepatitis with mild transient elevations in serum aminotransferases is often reported in Epstein–Barr virus (EBV) infectious mononucleosis, while mild jaundice develops in approximately 5% of cases and may result from cholestasis or virus-induced hemolysis [1]. Isolated gallbladder wall thickening has been described in patients with EBV infectious mononucleosis [2]. However, acute acalculous cholecystitis (AAC) associated with EBV infectious mononucleosis has not been reported. A previously healthy, 4-year-old girl was admitted to our hospital with a 4-day history of fever, decreased appetite, malaise, vomiting and mild abdominal pain. The sclerae were icteric, while exudative tonsillopharyngitis and bilateral cervical adenopathy were noticed, with the largest nodes measuring 2 cm in diameter. Abdominal examination revealed a nondistended abdomen with normally active bowel sounds and mild tenderness localized over the right upper quadrant. The liver was palpable 3 cm under costal margin, while the spleen edge was palpable 2 cm below the left costal margin. The remaining physical findings were normal. Laboratory investigations on admission revealed a white blood cell count of 22.1 × 109/l (25% atypical lymphocytes), hemoglobin 13.1 g/dl, alanine aminotransferase 304 U/l (5–45 U/l), aspartate aminotransferase 188 U/l (5–45 U/l), alkaline phosphatase 236 U/ l (38–148 U/l), gamma-glutamyltransferase 241 U/l (7–32 U/l), total serum bilirubin 4.6 mg/dl (direct fraction 3.6 mg/dl), erythrocyte sedimentation rate 23 mm/ h and C-reactive protein 8 mg/l (0–5 mg/l). Abdominal ultrasonography showed hepatospenomegaly and, in addition, thickening of the gallbladder wall measuring 9 mm, with no presence of stones, sludge or dilatation of the biliary tract. IgM and IgG antibodies against Epstein–Barr viral capsid antigen (VCA) were positive, whereas IgG antibodies for Epstein–Barr nuclear antigen (EBNA) were negative. In addition, detection of EBV-DNA in serum, using real-time PCR, was positive. Serological studies excluded ongoing infection caused by other viral agents such as hepatitis A, B, C viruses, cytomegalovirus, human immunodeficiency virus, adenovirus and enteroviruses. During the first 7 days of hospitalization the child remained febrile, but in a good general condition. Because of her abdominal pain the patient was monitored with serial abdominal ultrasonography. On the seventh hospital day the abdominal ultrasound examination revealed a distended enlarged thick-walled gallbladder containing sludge (Figure 1). In addition there was tenderness over the gallbladder, the so-called positive sonographic Murphy’s sign. Laboratory investigations at that time were as follows: white blood cell count of 11.1 × 109/l (10% atypical lymphocytes); alanine aminotransferase, 219 U/l (5–45 U/l); aspartate aminotransferase, 141 U/l (5–45 U/l); alkaline phosphatase 204 U/l (38–148 U/l); gamma-glutamyltransferase, 184 U/l (7–32 U/l) and C-reactive protein, 1 mg/l (0–5 mg/l). Blood and stool cultures were negative. No parasitic or group A streptococci infection was identified, while serological tests for Brucella species, Salmonella typhi, Leptospira species and Mycoplasma species were negative. AAC was confirmed, oral feeding was stopped, aggressive hydration was initiated and follow-up ultrasonographic examination of the abdomen was obtained. On the tenth hospital day, abdominal pain and fever had resolved, while gallbladder sonography was normal. The patient was discharged on the 13th day of admission, and during a follow-up of 7 months the child has been in good condition without recurrence. Abdominal ultrasonography 5 months after the admission was normal. AAC is rare in childhood and most cases occur during the course of infectious diseases such as septicemia, salmonellosis, brucellosis or A virus hepatitis. Criteria such as gallbladder wall thickening over 3 mm, distention of gallbladder, localized tenderness, pericholecystic fluid and sludge have been used for the diagnosis of AAC. The combination of two or more of the above criteria, in the appropriate clinical setting, is considered to be diagnostic [3].