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Acute acalculous cholecystitis as the initial presentation of primary Epstein-Barr virus infection
Journal of Pediatric Surgery (2007) 42, E11 – E13
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Acute acalculous cholecystitis as the initial presentation of primary Epstein-Barr virus infection Alexia Prassoulia,*, John Panagiotoua, Marina Vakakib, Irene Giannatoua, Achilleas Atilakosa, Anastasia Garoufia, Vassiliki Papaevangeloua a
Second Department of Pediatrics, University of Athens, bPanagiotis and Aglaia KyriakouQ Children’s Hospital, 15773 Athens, Greece b Department of Radiology, bPanagiotis and Aglaia KyriakouQ Children’s Hospital, 15773 Athens, Greece Index words: Epstein-Barr virus; EBV; Acute acalculous cholecystitis; Infectious mononucleosis
Abstract The case of a 13-year-old girl with primary Epstein-Barr virus (EBV) infection and concomitant cholestatic hepatitis, which initially presented as acute acalculous cholecystitis (AAC), is described. The diagnosis of AAC was documented by clinical and ultrasonographic criteria, whereas acute EBV infection was confirmed serologically. AAC may develop during the course of acute EBV infection, especially in patients with cholestatic hepatitis. D 2007 Elsevier Inc. All rights reserved.
Infection with Epstein-Barr virus (EBV) during childhood is mainly asymptomatic, whereas infectious mononucleosis, with clinical signs such as fever, pharyngitis, lymphadenopathy, hepatospenomegaly, and hepatocellular dysfunction, occurs in at least 50% of adolescents and adults with primary infection [1]. Isolated gallbladder wall thickening is commonly noted during ultrasonographic examination in patients with acute viral hepatitis [2]. Furthermore, isolated gallbladder wall thickening has been described during the course of mononucleosis syndromes and has been proposed as a sign of the severity of the illness [3]. However, acute acalculous cholecystitis (AAC) as an atypical clinical presentation of primary EBV infection has not been described in childhood.
* Corresponding author. Tel.: +30 2107726495, +30 6977472448 (Mobile); fax: +30 2106108829. E-mail address: [email protected] (A. Prassouli). 0022-3468/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.11.004
1. Case report A 13-year-old girl was admitted to our hospital with a 5day history of fever and chills, malaise, vomiting, and abdominal pain. She had no significant medical history, and her immunizations were up-to-date. She was a well-developed white adolescent girl who appeared pale, fatigued, and jaundiced. Vital signs upon admission were as follows: temperature, 39.68C; heart rate, 96 beats per minute; respiratory rate, 20/min; and blood pressure, 120/65 mm Hg. Scleral icterus, mild pharyngeal erythema, and abdominal tenderness, localized over the right upper quadrant, were noted on physical examination. There was a painful fullness in the right hypochondrium, which was considered as a positive Murphy’s sign. The liver was palpable 2 cm under costal margin, but her spleen was not enlarged. Laboratory evaluation on admission revealed a white blood cell count of 13.8 109/L (35% neutrophils, 53% lymphocytes, and 12% monocytes); hemoglobin, 10.5 g/dL;
E12
Fig. 1 Longitudinal sonogram of the gallbladder. A small sludge ball (arrow head) and thickened gallbladder wall with intramural sonolucent striations (arrows) are demonstrated.
platelet count, 241,000/lL; alanine aminotransferase, 674 U/L (5-45 U/L); aspartate aminotransferase, 394 U/L (5-45 U/L); alkaline phosphatase 721 U/L (b248 U/L); cglutamyltransferase, 352 U/L (b33); lactate dehydrogenase, 616 U/L (b300 U/L); total serum bilirubin, 4 mg/dL with a direct fraction of 3.5 mg/dL; albumin, 3.5 g/dL; amylase, 31 U/L (28-100 U/L); lipase, 96 U/L (b130 U/L); erythrocyte sedimentation rate, 10 mm/h; and C-reactive protein, 37 mg/L (b10 mg/L). Results of direct and indirect Coomb’s test were negative. Coagulation studies were within the reference range. Blood, stool, and urine cultures showed no growth. Ultrasonographic examination of the abdomen showed marked thickening of the gallbladder wall measuring 13.6 mm, intramular sonolucent striations, and presence of sludge within the gallbladder, with no evidence of stones or dilatation of the biliary tract (Fig. 1). In addition, there was tenderness over the gallbladder, the socalled positive sonographic Murphy’s sign. These findings in combination with clinical and laboratory data were compatible with the diagnosis of AAC in our patient. Because the cause of AAC was not obvious, a broad spectrum antibiotic (cefotaxime, tombramycin, and metronidazol) treatment was administered intravenously. In addition, feeding was stopped, whereas aggressive hydration was commenced. On the third hospital day, the patient’s abdominal pain improved, but she was persistently febrile. The spleen became palpable 2 cm below the costal margin, while at the same time, exudative tonsillopharyngitis with moderate anterior cervical lymphadenopathy was noticed. Follow-up ultrasonographic examination did not show any worsening of the cholocystitis. Repeated white blood cell count showed atypical lymphocytosis (15%). Infectious mononucleosis was suspected and diagnosed by serologic tests. Heterophile antibodies were present as detected by Monospot test. IgM and IgG antibodies against EpsteinBarr viral capsid antigen were both positive; IgG antibodies against the early Epstein-Barr viral antigen were
A. Prassouli et al. also positive, whereas IgG antibodies for EBV nuclear antigen were negative. Serologic studies for other viral agents such as hepatitis A, B, and C viruses, cytomegalovirus, human immunodeficiency virus, adenovirus, and enteroviruses were negative. Furthermore, no parasitic infection was identified, and serologic tests for Brucella species, Salmonella typhi, Leptospira species, Mycoplasma species, Rickettsia rickettsii, and Coxiella burnetii, were also negative. On the fifth hospital day, the abdominal pain resolved, the patient’s energy level and appetite improved, but the fever persisted. Repeated ultrasonographic examinations showed a progressive improvement in the first ultrasonographic findings. Complete subsidence of gallbladder’s inflammation was observed on the 10th hospital day. Thus, our patient recovered uneventfully without needing surgical intervention. Fever regressed gradually 2 weeks after the onset of the symptoms and was attributed to acute EBV primary infection. The antibiotic treatment was discontinued after 7 days of treatment. Patient was discharged on the 14th day of admission in good clinical condition and with considerable improvement in biochemical results. During a follow-up of 5 months, she was in good condition without any complaint. Hepatospenomegaly and all liver chemistry abnormalities had resolved, whereas EBV nuclear antigen IgG antibodies became positive, confirming the diagnosis of the EBV primary infection.
2. Discussion Gallbladder disease is rare in the pediatric age group. Acute acalculous cholecystitis is an inflammatory process of the gallbladder in the absence of gallstone, which accounts for 30% to 50% of the pediatric cholecystitis cases [4]. Most cases of AAC in children occur during the course of infectious diseases. Reported pathogens include streptococci (groups A and groups B), Gram-negative organisms, particularly Salmonella and Leptospira interrogans, hepatitis A virus, and parasites [5-7]. In addition, AAC may rarely follow abdominal trauma or burn injury or may be associated with a systemic vasculitis [5]. However, there have been no published reports of AAC occurring as the initial presentation of primary EBV infection in childhood. In the literature, no clear consensus appears as to the sonographic criteria for AAC. Criteria as gallbladder wall thickening over 3 mm, globular distention of gallbladder, localized tenderness (sonographic Murphy’s sign), sludge, pericholecystic fluid, and striated gallbladder wall have been used for the diagnosis of AAC. Each of these features is nonspecific; nevertheless, the combination of 2 or more of the above criteria in the appropriate clinical setting is considered to be diagnostic [6,8-10].
Acute acalculous cholecystitis Our patient initially presented with pain in the right hypochondrium, fever, jaundice, and vomiting. This clinical onset, in association with the presence of ultrasonographic findings, such as thickening of gallbladder wall (13.6 mm), intramular sonolucent striations, positive sonographic Murphy’s sign, and presence of sludge within the gallbladder supported the diagnosis of AAC. During her hospitalization, she developed the typical features of infectious mononucleosis. Extensive laboratory evaluation documented acute EBV primary infection and ruled out other possible infectious agents. The co-occurrence of EBV primary infection and AAC in the absence of other predisposing factors strongly suggests an etiologic link between the 2 conditions. Although both bile stasis and direct invasion of the gallbladder have been proposed, the exact pathogenesis of AAC remains uncertain. Bile stasis of various etiology has been implicated as a possible mechanism resulting to gallbladder inflammation [11]. Our patient had cholestatic hepatitis with jaundice and markedly elevated activities of c-glutamyltransferase and alkaline phosphatase owing to serologically confirmed acute EBV infection, whereas imaging studies excluded biliary obstruction. Recently, EBV-induced hepatitis has been recognized as an important cause of cholestasis even in the absence of clinical signs of infectious mononucleosis [12,13]. Thus, one could postulate that, in the above-presented patient, EBV-related cholestasis induced gallbladder inflammation and the development of AAC. One other possible pathogenetic mechanism is the direct invasion of the gallbladder. Such mechanism has been documented by Mourani et al [7] in a case of AAC owing to viral hepatitis A, where the viral antigen was detected in most epithelial cells of the gallbladder of their patient. This mechanism was not proved in a previous report of 2 children with hydrops of the gallbladder and EBV infection. One of them underwent cholecystectomy, where in situ hybridization of the gallbladder wall for EBV was negative [14]. In our patient, we were not able to investigate such mechanism because she did not undergo cholecystectomy. Therapeutic management strategies for AAC range from nonoperative treatment to cholecystostomy or cholecystectomy [4]. Recently, Imamoglu et al [8] developed an algorithm for the treatment of children with AAC. According to this algorithm, emergency operative intervention was considered when the previously determined ultrasonographic criteria deteriorated or persisted on the follow-up ultrasonographic examinations. The authors concluded that initially nonoperative treatment of childhood AAC is safe and effective in most cases. Our patient was monitored closely with serial ultrasonographic examinations, where progressive regression of the abnormal findings was documented, simultaneously with improvement in her clinical condition. Thus, no surgical intervention was
E13 required. The persistence of the fever, despite the broad spectrum antibiotic therapy, was attributed to EBV infectious mononucleosis. To our knowledge, this is the first described case of primary EBV infection initially presented as AAC. The presence of AAC in our patient was well documented by clinical and ultrasonographic criteria, whereas acute EBV infectious mononucleosis was confirmed serologically. We suggest that AAC may develop during the course of acute EBV infectious mononucleosis, especially in patients with cholestatic hepatitis. With the widespread use of abdominal ultrasonography in the proper clinical setting, the incidence of AAC during EBV infection could be larger than reported. Thus, clinicians should be familiar with the possible involvement of gallbladder during EBV infection to avoid unnecessary invasive procedures or overuse of antibiotics.
References [1] Macsween KF, Crawford DH. Epstein-Barr virus—recent advances. Lancet Infect Dis 2003;3:131 - 40. [2] Maudgal DP, Wansbrough-Jones MH, Joseph AE. Gallbladder abnormalities in acute infectious hepatitis. Dig Dis Sci 1984; 29:257 - 60. [3] Yamada K, Yamada H. Gallbladder wall thickening in mononucleosis syndromes. J Clin Ultrasound 2001;29:322 - 5. [4] Tsakayannis DE, Kozakewich HPW, Lillehi CW. Acalulcous cholecystitis in children. J Pediatr Surg 1996;31:127 - 31. [5] Suchy FJ. Diseases of the gallbladder. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics. 16th ed. Philadelphia7 W.B. Saunders Company; 2000. p. 1223 - 4. [6] Thambidorai CR, Shyamala J, Sarala R, et al. Acute acalculous cholecystitis associated with enteric fever in children. Pediatr Infect Dis J 1995;14:812 - 3. [7] Mourani S, Dobbs SM, Genta RM, et al. Hepatitis A virus–associated cholecystitis. Ann Intern Med 1994;120:398 - 400. [8] Imamoglu M, Sarihan H, Sari A, et al. Acute acalculous cholecystitis in children: diagnosis and treatment. J Pediatr Surg 2002;37:36 - 9. [9] Siegel MJ. Gallbladder and biliary tract. In: Siegel MJ, editor. Pediatric Sonography. 3rd ed. Philadelphia7 Lippincott Williams & Wilkins; 2002. p. 275 - 304. [10] Cohan RH, Mahony BS, Bowie JD. et al. Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis. Radiology 1987;164:31 - 5. [11] Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr Gastroenterol Rep 2003;5:302 - 9. [12] Shaukat A, Tsai HT, Rutherford R, et al. Epstein-Barr virus induced hepatitis: An important cause of cholestasis. Hepatol Res 2005; 33:24 - 6. [13] Massei F, Palla G, Ughi C, et al. Cholestasis as a presenting feature of acute Epstein-Barr virus infection. Pediatr Infect Dis J 2001;20: 721 - 2. [14] Dinulos J, Mitchell DK, Egerton J, et al. Hydrops of gallbladder associated with Epstein-Barr virus infection: a report of two cases and review of the literature. Pediatr Infect Dis J 1994; 13:924 - 9.
www.elsevier.com/locate/jpedsurg
Acute acalculous cholecystitis as the initial presentation of primary Epstein-Barr virus infection Alexia Prassoulia,*, John Panagiotoua, Marina Vakakib, Irene Giannatoua, Achilleas Atilakosa, Anastasia Garoufia, Vassiliki Papaevangeloua a
Second Department of Pediatrics, University of Athens, bPanagiotis and Aglaia KyriakouQ Children’s Hospital, 15773 Athens, Greece b Department of Radiology, bPanagiotis and Aglaia KyriakouQ Children’s Hospital, 15773 Athens, Greece Index words: Epstein-Barr virus; EBV; Acute acalculous cholecystitis; Infectious mononucleosis
Abstract The case of a 13-year-old girl with primary Epstein-Barr virus (EBV) infection and concomitant cholestatic hepatitis, which initially presented as acute acalculous cholecystitis (AAC), is described. The diagnosis of AAC was documented by clinical and ultrasonographic criteria, whereas acute EBV infection was confirmed serologically. AAC may develop during the course of acute EBV infection, especially in patients with cholestatic hepatitis. D 2007 Elsevier Inc. All rights reserved.
Infection with Epstein-Barr virus (EBV) during childhood is mainly asymptomatic, whereas infectious mononucleosis, with clinical signs such as fever, pharyngitis, lymphadenopathy, hepatospenomegaly, and hepatocellular dysfunction, occurs in at least 50% of adolescents and adults with primary infection [1]. Isolated gallbladder wall thickening is commonly noted during ultrasonographic examination in patients with acute viral hepatitis [2]. Furthermore, isolated gallbladder wall thickening has been described during the course of mononucleosis syndromes and has been proposed as a sign of the severity of the illness [3]. However, acute acalculous cholecystitis (AAC) as an atypical clinical presentation of primary EBV infection has not been described in childhood.
* Corresponding author. Tel.: +30 2107726495, +30 6977472448 (Mobile); fax: +30 2106108829. E-mail address: [email protected] (A. Prassouli). 0022-3468/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2006.11.004
1. Case report A 13-year-old girl was admitted to our hospital with a 5day history of fever and chills, malaise, vomiting, and abdominal pain. She had no significant medical history, and her immunizations were up-to-date. She was a well-developed white adolescent girl who appeared pale, fatigued, and jaundiced. Vital signs upon admission were as follows: temperature, 39.68C; heart rate, 96 beats per minute; respiratory rate, 20/min; and blood pressure, 120/65 mm Hg. Scleral icterus, mild pharyngeal erythema, and abdominal tenderness, localized over the right upper quadrant, were noted on physical examination. There was a painful fullness in the right hypochondrium, which was considered as a positive Murphy’s sign. The liver was palpable 2 cm under costal margin, but her spleen was not enlarged. Laboratory evaluation on admission revealed a white blood cell count of 13.8 109/L (35% neutrophils, 53% lymphocytes, and 12% monocytes); hemoglobin, 10.5 g/dL;
E12
Fig. 1 Longitudinal sonogram of the gallbladder. A small sludge ball (arrow head) and thickened gallbladder wall with intramural sonolucent striations (arrows) are demonstrated.
platelet count, 241,000/lL; alanine aminotransferase, 674 U/L (5-45 U/L); aspartate aminotransferase, 394 U/L (5-45 U/L); alkaline phosphatase 721 U/L (b248 U/L); cglutamyltransferase, 352 U/L (b33); lactate dehydrogenase, 616 U/L (b300 U/L); total serum bilirubin, 4 mg/dL with a direct fraction of 3.5 mg/dL; albumin, 3.5 g/dL; amylase, 31 U/L (28-100 U/L); lipase, 96 U/L (b130 U/L); erythrocyte sedimentation rate, 10 mm/h; and C-reactive protein, 37 mg/L (b10 mg/L). Results of direct and indirect Coomb’s test were negative. Coagulation studies were within the reference range. Blood, stool, and urine cultures showed no growth. Ultrasonographic examination of the abdomen showed marked thickening of the gallbladder wall measuring 13.6 mm, intramular sonolucent striations, and presence of sludge within the gallbladder, with no evidence of stones or dilatation of the biliary tract (Fig. 1). In addition, there was tenderness over the gallbladder, the socalled positive sonographic Murphy’s sign. These findings in combination with clinical and laboratory data were compatible with the diagnosis of AAC in our patient. Because the cause of AAC was not obvious, a broad spectrum antibiotic (cefotaxime, tombramycin, and metronidazol) treatment was administered intravenously. In addition, feeding was stopped, whereas aggressive hydration was commenced. On the third hospital day, the patient’s abdominal pain improved, but she was persistently febrile. The spleen became palpable 2 cm below the costal margin, while at the same time, exudative tonsillopharyngitis with moderate anterior cervical lymphadenopathy was noticed. Follow-up ultrasonographic examination did not show any worsening of the cholocystitis. Repeated white blood cell count showed atypical lymphocytosis (15%). Infectious mononucleosis was suspected and diagnosed by serologic tests. Heterophile antibodies were present as detected by Monospot test. IgM and IgG antibodies against EpsteinBarr viral capsid antigen were both positive; IgG antibodies against the early Epstein-Barr viral antigen were
A. Prassouli et al. also positive, whereas IgG antibodies for EBV nuclear antigen were negative. Serologic studies for other viral agents such as hepatitis A, B, and C viruses, cytomegalovirus, human immunodeficiency virus, adenovirus, and enteroviruses were negative. Furthermore, no parasitic infection was identified, and serologic tests for Brucella species, Salmonella typhi, Leptospira species, Mycoplasma species, Rickettsia rickettsii, and Coxiella burnetii, were also negative. On the fifth hospital day, the abdominal pain resolved, the patient’s energy level and appetite improved, but the fever persisted. Repeated ultrasonographic examinations showed a progressive improvement in the first ultrasonographic findings. Complete subsidence of gallbladder’s inflammation was observed on the 10th hospital day. Thus, our patient recovered uneventfully without needing surgical intervention. Fever regressed gradually 2 weeks after the onset of the symptoms and was attributed to acute EBV primary infection. The antibiotic treatment was discontinued after 7 days of treatment. Patient was discharged on the 14th day of admission in good clinical condition and with considerable improvement in biochemical results. During a follow-up of 5 months, she was in good condition without any complaint. Hepatospenomegaly and all liver chemistry abnormalities had resolved, whereas EBV nuclear antigen IgG antibodies became positive, confirming the diagnosis of the EBV primary infection.
2. Discussion Gallbladder disease is rare in the pediatric age group. Acute acalculous cholecystitis is an inflammatory process of the gallbladder in the absence of gallstone, which accounts for 30% to 50% of the pediatric cholecystitis cases [4]. Most cases of AAC in children occur during the course of infectious diseases. Reported pathogens include streptococci (groups A and groups B), Gram-negative organisms, particularly Salmonella and Leptospira interrogans, hepatitis A virus, and parasites [5-7]. In addition, AAC may rarely follow abdominal trauma or burn injury or may be associated with a systemic vasculitis [5]. However, there have been no published reports of AAC occurring as the initial presentation of primary EBV infection in childhood. In the literature, no clear consensus appears as to the sonographic criteria for AAC. Criteria as gallbladder wall thickening over 3 mm, globular distention of gallbladder, localized tenderness (sonographic Murphy’s sign), sludge, pericholecystic fluid, and striated gallbladder wall have been used for the diagnosis of AAC. Each of these features is nonspecific; nevertheless, the combination of 2 or more of the above criteria in the appropriate clinical setting is considered to be diagnostic [6,8-10].
Acute acalculous cholecystitis Our patient initially presented with pain in the right hypochondrium, fever, jaundice, and vomiting. This clinical onset, in association with the presence of ultrasonographic findings, such as thickening of gallbladder wall (13.6 mm), intramular sonolucent striations, positive sonographic Murphy’s sign, and presence of sludge within the gallbladder supported the diagnosis of AAC. During her hospitalization, she developed the typical features of infectious mononucleosis. Extensive laboratory evaluation documented acute EBV primary infection and ruled out other possible infectious agents. The co-occurrence of EBV primary infection and AAC in the absence of other predisposing factors strongly suggests an etiologic link between the 2 conditions. Although both bile stasis and direct invasion of the gallbladder have been proposed, the exact pathogenesis of AAC remains uncertain. Bile stasis of various etiology has been implicated as a possible mechanism resulting to gallbladder inflammation [11]. Our patient had cholestatic hepatitis with jaundice and markedly elevated activities of c-glutamyltransferase and alkaline phosphatase owing to serologically confirmed acute EBV infection, whereas imaging studies excluded biliary obstruction. Recently, EBV-induced hepatitis has been recognized as an important cause of cholestasis even in the absence of clinical signs of infectious mononucleosis [12,13]. Thus, one could postulate that, in the above-presented patient, EBV-related cholestasis induced gallbladder inflammation and the development of AAC. One other possible pathogenetic mechanism is the direct invasion of the gallbladder. Such mechanism has been documented by Mourani et al [7] in a case of AAC owing to viral hepatitis A, where the viral antigen was detected in most epithelial cells of the gallbladder of their patient. This mechanism was not proved in a previous report of 2 children with hydrops of the gallbladder and EBV infection. One of them underwent cholecystectomy, where in situ hybridization of the gallbladder wall for EBV was negative [14]. In our patient, we were not able to investigate such mechanism because she did not undergo cholecystectomy. Therapeutic management strategies for AAC range from nonoperative treatment to cholecystostomy or cholecystectomy [4]. Recently, Imamoglu et al [8] developed an algorithm for the treatment of children with AAC. According to this algorithm, emergency operative intervention was considered when the previously determined ultrasonographic criteria deteriorated or persisted on the follow-up ultrasonographic examinations. The authors concluded that initially nonoperative treatment of childhood AAC is safe and effective in most cases. Our patient was monitored closely with serial ultrasonographic examinations, where progressive regression of the abnormal findings was documented, simultaneously with improvement in her clinical condition. Thus, no surgical intervention was
E13 required. The persistence of the fever, despite the broad spectrum antibiotic therapy, was attributed to EBV infectious mononucleosis. To our knowledge, this is the first described case of primary EBV infection initially presented as AAC. The presence of AAC in our patient was well documented by clinical and ultrasonographic criteria, whereas acute EBV infectious mononucleosis was confirmed serologically. We suggest that AAC may develop during the course of acute EBV infectious mononucleosis, especially in patients with cholestatic hepatitis. With the widespread use of abdominal ultrasonography in the proper clinical setting, the incidence of AAC during EBV infection could be larger than reported. Thus, clinicians should be familiar with the possible involvement of gallbladder during EBV infection to avoid unnecessary invasive procedures or overuse of antibiotics.
References [1] Macsween KF, Crawford DH. Epstein-Barr virus—recent advances. Lancet Infect Dis 2003;3:131 - 40. [2] Maudgal DP, Wansbrough-Jones MH, Joseph AE. Gallbladder abnormalities in acute infectious hepatitis. Dig Dis Sci 1984; 29:257 - 60. [3] Yamada K, Yamada H. Gallbladder wall thickening in mononucleosis syndromes. J Clin Ultrasound 2001;29:322 - 5. [4] Tsakayannis DE, Kozakewich HPW, Lillehi CW. Acalulcous cholecystitis in children. J Pediatr Surg 1996;31:127 - 31. [5] Suchy FJ. Diseases of the gallbladder. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics. 16th ed. Philadelphia7 W.B. Saunders Company; 2000. p. 1223 - 4. [6] Thambidorai CR, Shyamala J, Sarala R, et al. Acute acalculous cholecystitis associated with enteric fever in children. Pediatr Infect Dis J 1995;14:812 - 3. [7] Mourani S, Dobbs SM, Genta RM, et al. Hepatitis A virus–associated cholecystitis. Ann Intern Med 1994;120:398 - 400. [8] Imamoglu M, Sarihan H, Sari A, et al. Acute acalculous cholecystitis in children: diagnosis and treatment. J Pediatr Surg 2002;37:36 - 9. [9] Siegel MJ. Gallbladder and biliary tract. In: Siegel MJ, editor. Pediatric Sonography. 3rd ed. Philadelphia7 Lippincott Williams & Wilkins; 2002. p. 275 - 304. [10] Cohan RH, Mahony BS, Bowie JD. et al. Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis. Radiology 1987;164:31 - 5. [11] Barie PS, Eachempati SR. Acute acalculous cholecystitis. Curr Gastroenterol Rep 2003;5:302 - 9. [12] Shaukat A, Tsai HT, Rutherford R, et al. Epstein-Barr virus induced hepatitis: An important cause of cholestasis. Hepatol Res 2005; 33:24 - 6. [13] Massei F, Palla G, Ughi C, et al. Cholestasis as a presenting feature of acute Epstein-Barr virus infection. Pediatr Infect Dis J 2001;20: 721 - 2. [14] Dinulos J, Mitchell DK, Egerton J, et al. Hydrops of gallbladder associated with Epstein-Barr virus infection: a report of two cases and review of the literature. Pediatr Infect Dis J 1994; 13:924 - 9.