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Case Report

Acute Acalculous Cholecystitis Due to a Primary Epstein Barr Virus Infection in a Pediatric Patient

1
Pediatric Surgery Unit, Department of Pediatrics, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08041 Barcelona, Spain
2
Pediatric Unit, Department of Pediatrics, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, 08041 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Submission received: 23 April 2020 / Accepted: 1 February 2021 / Published: 6 February 2021

Abstract

:
Epstein–Barr virus (EBV) is estimated to infect more than 98% of adults worldwide and is one of the most common human viruses. Acute acalculous cholecystitis (AAC) of the gallbladder is an atypical complication of infectious mononucleosis caused by EBV. Conservative management has been described in the context of AAC caused by EBV. A surgical approach must be considered in the case of acute complications such as perforation or gallbladder gangrene. We present the case of a 10-year-old female patient with AAC due to infectious mononucleosis syndrome caused by primary EBV infection.

1. Introduction

Acute acalculous cholecystitis (AAC) is a gallbladder infection not related to gallstones, leading to serious consequences. AAC is caused by gallbladder stasis from hypomotility that leads to increased intraluminal pressures in the gallbladder wall, resulting in ischemia, inflammation, and potential necrosis [1]. Only 5–10% of acute cholecystitis cases are AAC in adults, and they have higher morbidity and mortality than calculous cholecystitis. Acute inflammatory gallbladder diseases including ACC are relatively uncommon in pediatric patients [2].
Acute infection with Epstein–Barr virus (EBV) is a common disease mainly affecting adolescents and young adults and it is usually asymptomatic; it often presents as typical infectious mononucleosis symptoms such as fever, sore throat, cervical lymphadenopathy, and hepatosplenomegaly. Hepatic involvement is very common and AAC may occur during acute primary EBV infection, which is rarely encountered in the pediatric population [3].
To date, only 24 cases of AAC caused by EBV infection have been reported in pediatrics [4]. In this report, we present a case of primary EBV infection complicated by AAC in a 10-year-old patient.

2. Case Report

A 10-year-old female was brought to the emergency department complaining of a 7-day history of low-grade fever up to 38.5 °C, sore throat, mild cough, sharp abdominal pain, mainly in the right abdominal area, and nausea. Physical examination revealed sensitivity to palpation in the right hypochondriac and lumbar regions and epigastrium, normal bowel sounds, and no abdominal distention.
Additionally, bilateral cervical and axillary lymphadenopathy, tonsillar hypertrophy without exudates, and a palpable hepatosplenomegaly were noticed, and there was no conjunctival icterus.
Laboratory studies showed a white blood cell count of 7200 × 103 per microliter (μL) (4.5–14.5 × 103/μL), a C-reactive protein level of 16.2 milligrams per deciliter (mg/dL) (3–5 mg/dL), a total bilirubin level of 29 μg/L (0–17 μg/L) with direct bilirubin of 10 μg/L (0–6 μg/L), an alkaline phosphatase (ALP) level of 642 units per liter (U/L) (35–110 U/L), gamma-glutamyl transferase (GGT) levels of 297 U/L (1–48 U/L), glutamic-pyruvic transaminase (GPT) levels of 301 U/L (1–31 U/L), and glutamic-oxaloacetic transaminase (GOT) levels of 279 U/L (1–31 U/L).
Formal abdominal ultrasonography revealed a thickening of the gallbladder wall (4.5 mm) and pericholecystic edema (Figure 1). Distention of the gallbladder was not evident, and no stones or dilatation of the biliary tract were reported. Based on these findings, the diagnosis of acute acalculous cholecystitis was made and the patient was admitted to the pediatrics department for further investigation and treatment.
The patient was treated with fasting and intravenous rehydration. Her cardiovascular and respiratory function remained stable. Blood and urine cultures were negative. Serological tests, both heterophile antibody test and IgM antibodies against EBV capsid antigen, confirmed the diagnosis of infectious mononucleosis. Serological tests for hepatitis A, B, C, CMV, HIV, and Toxoplasma gondii were negative.
Two days after admission, the patient had a good clinical status, fever was resolved, enteral nutrition was restarted, and the abdominal pain had also disappeared. In the laboratory test on day 3, a total bilirubin (B) level of 19 μg/L with direct bilirubin of 7 μg/L, an alkaline phosphatase (ALP) level of 199 units per liter (U/L), gamma-glutamyl transferase (GGT) levels of 48 U/L, glutamic-pyruvic transaminase (GPT) levels of 19 U/L and glutamic-oxaloacetic transaminase (GOT) levels of 22 U/L were observed.
The patient was discharged on day 4 with a good clinical status. Two weeks later, a clinical control in the outpatient department revealed no clinical or laboratory abnormalities and an abdominal ultrasound revealed a total remission of the previous abnormal findings.
After 6 months of follow up, the patient remains asymptomatic.

3. Discussion

Epstein–Barr virus (EBV) infection can lead to infectious mononucleosis syndrome with the typical symptoms of fever, pharyngitis, lymphadenopathy, and hepatosplenomegaly. However, cholecystitis is not usually considered part of a primary EBV infection and ultrasound scan (USS) of the liver and gallbladder is not routinely performed [5]. In our case, we performed the USS in order to identify a possible inflammation of the appendix because abdominal pain on the right abdominal side.
Acute acalculous cholecystitis (AAC) is a gallbladder infection not related to gallstones. It is more frequently found in males and represents 5–10% of all cases of acute cholecystitis in adults. Cholecystitis in children is not common (Tsakayannis et al. estimated 1.3 pediatric cases for every 1000 cases in adults) and 30–50% of these patients are AAC [6]. To our knowledge, only a few cases of EBV-associated AAC have been described in pediatric patients (Table 1).
Among the age-related predisposing diseases, systemic infectious diseases such as EBV were the most common ones in middle childhood and adolescence [25].
The exact pathogenesis of EBV-associated AAC is unclear; EBV-associated hepatitis is recognized as an important cause of cholestasis, suggesting that acute infection may induce the bile stasis and subsequent gallbladder inflammation that led to the development of AAC [22].
In children, AAC occurs more frequently during the course of infectious diseases such as sepsis, gastroenteritis (including Vibrio cholerae, Salmonella spp, Shigella spp, and Giardia lamblia), pneumonia (especially due to Mycoplasma pneumoniae), cytomegalovirus primary infection, hepatitis A, Dengue, infection secondary to non-tuberculous mycobacteria, leptospirosis, Q-fever, Candida, malaria, and HIV infection. It has also been associated with the use of parenteral nutrition, post-surgery, extensive burns, and after trauma. In healthy patients such as the related case, this form of cholecystitis is even less frequent [6,26].
The diagnosis of AAC in children remains a clinical challenge, especially in critical patients. Clinical, laboratory, and imaging findings will finally lead to diagnosis. Clinical presentation has been reviewed, concluding that right upper quadrant abdominal pain and fever remains the most common symptoms. Sore throat and pharyngitis, cervical lymphadenopathy, abdominal tenderness, and Murphy’s sign are also common findings. Elevation of GGT, GOT, ALP, and bilirubin in various degrees was also reported [27]. After three days of hospital stay, our patient presented decreasing GGT, GPT and GOT values within the reference range. After two weeks of follow up, B and ALK were also normalized.
We performed a review of the abdominal sonographic findings in pediatric patients with EBV-associated AAC, and it has been related the sonographic gallbladder wall thickening greater than 3 mm, hepatomegaly, splenomegaly, increased periportal echogenicity, and periportal lymph nodes [28]. Pericholecystic fluid (halo) or subserosal edema, intramural gas or hydrops and the presence of echogenic bile have also been described. In uncertain cases, computed tomography and cholescintigraphy using 99mTc are reasonable imaging alternatives to establish the diagnosis [26,28].
In children with AAC due to EBV, medical treatment should be considered the management of choice; excellent recovery without surgical treatment is generally expected. The use of intravenous antibiotics is controversial, and emergency surgical intervention should only be considered if ultrasonographic abnormalities persist or worsen on follow-up examinations [23]. In our case, we proposed intravenous fluids, nonsteroidal anti-inflammatory drugs, and rest, with excellent recovery in two days.
The incidence of complications in AAC for EBV is low when prompt and accurate diagnosis and treatment are performed. If the diagnosis is delayed or incorrect, complications such as perforation and gangrene have been described. Graber et al. presented the case of a 15-year-old female who underwent laparoscopic cholecystectomy for EBV-associated AAC and died after surgery due to unexplained postoperative complications. Furthermore, poor predictors of AAC mortality include the presence of thrombocytopenia, anemia, gallbladder sludge, associated hepatitis, and sepsis plus hepatitis [24,29].

4. Conclusions

Despite AAC being a rare complication of infectious mononucleosis for EBV in children, a high index of suspicion is important for the diagnosis, especially in patients without a relevant past medical history. Our patient recovered fully with conservative treatment without antibiotics. Surgical intervention has not been described as the procedure of choice of ACC for EBV, and should be considered only in severe cases that are not responding to conservative therapy.

Author Contributions

Conceptualization, C.L.V.; methodology, C.L.V., F.B.; validation, S.B.G.; formal analysis, C.L.V., I.G., N.B.L., F.B., M.Q.G.; investigation, C.L.V.; F.B.; writing—original draft, C.L.V. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Balmadrid, B. Recent advances in management of acalculous cholecystitis. F1000Research 2018, 7, 1660. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Poddighe, D.; Sazonov, V. Acute acalculous cholecystitis in children. World J. Gastroenterol. 2018, 24, 4870–4879. [Google Scholar] [CrossRef]
  3. Kim, A.; Yang, H.R.; Moon, J.S.; Chang, J.Y.; Ko, J.S. Epstein-Barr Virus Infection with Acute Acalculous Cholecystitis. Pediatr. Gastroenterol. Hepatol. Nutr. 2014, 17, 57–60. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Young, C.; Lampe, R. Primary Epstein-Barr Virus Infection in an Adolescent Female Complicated by Acute Acalculous Cholecystitis. Cureus 2019, 11, e5044. [Google Scholar] [CrossRef] [Green Version]
  5. Agergaard, J.; Larsen, C. Acute acalculous cholecystitis in a patient with primary Epstein-Barr virus infection: A case report and literature review. Int. J. Infect. Dis. 2015, 35, 67–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Iglesias, C.; Lorenzo, G.; Rodríguez, L.; Gautreaux, S.; Mora, M. Acute acalculous cholecystitis in a patient without underlying pathology. An. Pediatr. 2014, 81, 271–272. [Google Scholar]
  7. Yoshie, K.; Ohta, M.; Okabe, N.; Komatsu, T.; Umemura, S. Gallbladder wall thickening associated with infectious mononucleosis. Abdom. Imaging 2004, 29, 694–695. [Google Scholar] [CrossRef]
  8. Lagona, E.; Sharifi, F.; Voutsioti, A.; Mavri, A.; Markouri, M.; Attilakos, A. Epstein-Barr Virus Infectious Mononucleosis Associated with Acute Acalculous Cholecystitis. Infection 2007, 35, 118–119. [Google Scholar] [CrossRef]
  9. Prassouli, A.; Panagiotou, J.; Vakaki, M.; Giannatou, I.; Atilakos, A.; Garoufi, A.; Papaevangelou, V. Acute acalculous cholecystitis as the initial presentation of primary Epstein-Barr virus infection. J. Pediatr. Surg. 2007, 42, e11–e13. [Google Scholar] [CrossRef] [PubMed]
  10. Gora-Gebka, M.; Liberek, A.; Bako, W.; Szarszewski, A.; Kamińska, B.; Korzon, M. Acute acalculous cholecystitis of viral etiology—A rare condition in children? J. Pediatr. Surg. 2008, 43, e25–e27. [Google Scholar] [CrossRef] [PubMed]
  11. Pelliccia, P.; Savino, A.; Cecamore, C.; Di Marzio, D.; Chiarelli, F.; Primavera, A.; Schiavone, C. Imaging spectrum of EBV-infection in a young patient. J. Ultrasound 2008, 11, 82–84. [Google Scholar] [CrossRef] [Green Version]
  12. Attilakos, A.; Prassouli, A.; Hadjigeorgiou, G.; Lagona, E.; Kitsiou-Tzeli, S.; Galla, A.; Stasinopoulou, A.; Karpathios, T. Acute acalculous cholecystitis in children with Epstein–Barr virus infection: A role for Gilbert’s syndrome? Int. J. Infect. Dis. 2009, 13, e161–e164. [Google Scholar] [CrossRef] [Green Version]
  13. Arya, S.O.; Saini, A.; El-Baba, M.; Salimnia, H.; Abdel-Haq, N. Epstein Barr Virus—Associated Acute Acalculous Cholecystitis: A Rare Occurrence but Favorable Outcome. Clin. Pediatr. 2010, 49, 799–804. [Google Scholar] [CrossRef] [PubMed]
  14. Aydın, T.T.; Tanır, G.; Özel, A.; Timur, Ö.M.; Ekşioğlu, A.S. A case of acute acalculous cholecystitis during the course of reactive Epstein-Barr virus infection. Turk. J. Gastroenterol. 2013, 24, 571–572. [Google Scholar] [CrossRef]
  15. Fretzayas, A.; Moustaki, M.; Attilakos, A.; Brozou, T.; Nicolaidou, P. Acalculous Cholecystitis or Biliary Dyskinesia for Epstein-Barr Virus Gallbladder Involvement? Prague Med. Rep. 2014, 115, 67–72. [Google Scholar] [CrossRef] [Green Version]
  16. Poddighe, D.; Cagnoli, G.; Mastricci, N.; Bruni, P. Acute acalculous cholecystitis associated with severe EBV hepatitis in an immunocompetent child. BMJ Case Rep. 2014, 2014. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Suga, K.; Shono, M.; Goji, A.; Matsuura, S.; Inoue, M.; Kawahito, M.; Mori, K. A case of acute acalculous cholecystitis complicated by primary Epstein-Barr virus infection. J. Med. Investig. 2014, 61, 426–429. [Google Scholar] [CrossRef] [Green Version]
  18. Alkhoury, F.; Diaz, D.; Hidalgo, J. Acute acalculous cholecystitis (AAC) in the pediatric population associated with Epstein-Barr Virus (EBV) infection. Case report and review of the literature. Int. J. Surg. Case Rep. 2015, 11, 50–52. [Google Scholar] [CrossRef] [Green Version]
  19. Shah, S.; Schroeder, S. A rare case of primary EBV infection causing acute acalculous cholecystitis. J. Pediatr. Surg. Case Rep. 2015, 3, 285–288. [Google Scholar] [CrossRef] [Green Version]
  20. Branco, L.; Vieira, M.; Couto, C.; Coelho, M.D.; Laranjeira, C. Acute acalculous cholecystitis by Epstein-Barr virus infection: A rare association. Infect. Dis. Rep. 2015, 7, 6184. [Google Scholar] [CrossRef] [Green Version]
  21. Majdalani, M.; Milad, N.; Sahli, Z.; Rizk, S. Acute acalculous cholecystitis in a Lebanese girl with primary Epstein-Barr viral infection. BMJ Case Rep. 2016, 2016. [Google Scholar] [CrossRef]
  22. Say, D.S.; Chaparro, J.; Koning, J.L.; Sivagnanam, M. Fever and Jaundice in a Previously Healthy Teenager. Clin. Pediatr. 2016, 55, 1081–1084. [Google Scholar] [CrossRef] [Green Version]
  23. Rodà, D.; Huici, M.; Ricart, S.; Vila, J.; Fortuny, C.; Alsina, L. Cholecystitis and nephrotic syndrome complicating Epstein–Barr virus primary infection. Paediatr. Int. Child Health 2016, 37, 1–4. [Google Scholar] [CrossRef]
  24. Graber, M.L.; Berg, D.; Jerde, W.; Kibort, P.; Olson, A.P.; Parkash, V. Learning from tragedy: The Julia Berg story. Diagnosis 2018, 5, 257–266. [Google Scholar] [CrossRef]
  25. Yi, D.Y.; Chang, E.J.; Kim, J.Y.; Lee, E.H.; Yang, H.R. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children. J. Korean Med. Sci. 2016, 31. [Google Scholar] [CrossRef] [Green Version]
  26. Ntelis, K.; Mazarakis, D.; Sapountzis, A.; Zissi, D.; Sparangi, S.; Xidia, N.; Velissaris, D. Acute Acalculous Cholecystitis Associated with Epstein–Barr Infection: A Case Report and Review of the Literature. Case Rep. Med. 2020, 2020, 1–6. [Google Scholar] [CrossRef] [Green Version]
  27. Yesilbag, Z.; Karadeniz, A.; Kaya, F.O. Acute acalculous cholecystitis: A rare presentation of primary Epstein-Barr virus infection in adults-case report and review of the literature. Case Rep. Infect. Dis. 2017, 2017, 5790102. [Google Scholar] [CrossRef] [PubMed]
  28. Yi, D.Y.; Kim, J.Y.; Yang, H.R. Ultrasonographic Gallbladder Abnormality of Primary Epstein-Barr Virus Infec-tion in Children and Its Influence on Clinical Outcome. Medicine (Baltimore) 2015, 94, e1120. [Google Scholar] [CrossRef] [PubMed]
  29. Lu, Y.A.; Chiu, C.H.; Kong, M.S.; Wang, H.I.; Chao, H.C.; Chen, C.C. Risk factors for poor outcomes of children with acute acalculous cholecystitis. Pediatr. Neonatol. 2017, 58, 497–503. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Figure 1. Abdominal ultrasonography showing a thickening of the gallbladder wall of 4.5 mm and pericholecystic edema.
Figure 1. Abdominal ultrasonography showing a thickening of the gallbladder wall of 4.5 mm and pericholecystic edema.
Pediatrrep 13 00011 g001
Table 1. Cases of Epstein–Barr virus-associated acute acalculous cholecystitis in pediatric patients.
Table 1. Cases of Epstein–Barr virus-associated acute acalculous cholecystitis in pediatric patients.
AuthorYearAgeSexAntibioticSurgeryFavorable Outcome
Yoshie et al. [7]200415F-NoYes
Lagona et al. [8]20074FNoNoYes
Prassouli et al. [9]200713FYesNoYes
Gora-Gebka et al. [10]20089FYesNoYes
Gora-Gebka et al. [10]20084FYesNoYes
Pelliccia et al. [11]200814FNoNoYes
Attilakos et al. [12]20095FYesNoYes
Attilakos et al. [12]20094MNoNoYes
Arya et al. [13]201016FYesNoYes
Aydin Teke et al. [14]20138FNoNoYes
Fretzayas et al. [15]201411F-NoYes
Fretzayas et al. [15]201412F-NoYes
Kim et al. [3]201410FYesNoYes
Poddighe et al. [16]20147FYesNoYes
Suga et al. [17]20146FYesNoYes
Alkhoury et al. [18]201515FNoNoYes
Shah et al. [19]20156FYesNoYes
Branco et al. [20]201516MYesNoYes
Majdalani et al. [21]201616FYesNoYes
Say et al. [22]201614FYesNoYes
Rodà et al. [23]20172MYesNoYes
Graber et al. [24]201815FYesYesNo
Young et al. [4]201914FYesNoYes
Present case202010FNoNoYes
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MDPI and ACS Style

Leganés Villanueva, C.; Goruppi, I.; Brun Lozano, N.; Bianchi, F.; Quinteiro González, M.; Boronat Guerrero, S. Acute Acalculous Cholecystitis Due to a Primary Epstein Barr Virus Infection in a Pediatric Patient. Pediatr. Rep. 2021, 13, 86-90. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13010011

AMA Style

Leganés Villanueva C, Goruppi I, Brun Lozano N, Bianchi F, Quinteiro González M, Boronat Guerrero S. Acute Acalculous Cholecystitis Due to a Primary Epstein Barr Virus Infection in a Pediatric Patient. Pediatric Reports. 2021; 13(1):86-90. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13010011

Chicago/Turabian Style

Leganés Villanueva, Carlos, Ilaria Goruppi, Nuria Brun Lozano, Federica Bianchi, María Quinteiro González, and Susana Boronat Guerrero. 2021. "Acute Acalculous Cholecystitis Due to a Primary Epstein Barr Virus Infection in a Pediatric Patient" Pediatric Reports 13, no. 1: 86-90. https://0-doi-org.brum.beds.ac.uk/10.3390/pediatric13010011

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