Skip to main content

Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature



Acute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.

Case presentation

A 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.


Acute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.


Epstein-Barr virus (EBV) infection is a common viral infection, especially in children; it could have an asymptomatic course or may present as flu syndrome characterized by fever, malaise, headache, lymphadenitis, and pharyngitis [1]. EBV infection usually causes an acute self-limiting disease and resolves spontaneously in a few weeks; however, it may be responsible for various complications of the respiratory, cardiovascular, genitourinary, gastrointestinal, and nervous systems, ranging from minor to severe to life threatening. EBV also plays a significant role in the pathogenesis of autoimmune diseases and neoplasms [2].

As regards gastrointestinal manifestations, enlarged spleen and liver, with elevated transaminase levels, are the most common symptoms. Acute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. EBV-associated acute pancreatitis is a rare condition and it may occur in children and adults. Here we report on a 3-year-old girl with acute pancreatitis due to EBV infection; a review about this topic was also conducted thereafter.

Case presentation

A 3-year-old female, previously in good health, was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. She did not complain of any other symptoms. Vital signs were normal. On physical examination, she appeared sick, with moderate epigastric tenderness. Laboratory investigations showed hemoglobin 13.8 g/dl, platelet 340,000/mm3, white blood cell count 16,600/mm3 (neutrophils 20%, monocytes 11%, and lymphocytes 69%), C-reactive protein 13,1 mg/dl (normal range < 0.5 mg/dl), aspartate aminotransferase 40 U/l, alanine aminotransferase 25 U/l, total bilirubin 0,11 mg/dl, amylase 913 U/l (normal range 30–100 U/l), and lipase 6450 U/l (normal range 3–32 U/l). Because of fair general conditions and elevated inflammatory markers, empirical antibiotic therapy with cefotaxime was started. Abdominal ultrasound revealed an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. She had no past history of abdominal trauma, surgery or cholecystitis and any familial history of pancreatitis or gallstones was reported. She did not receive any medications known to cause pancreatitis. Serological tests for mumps, parotitis, rubella, EBV, cytomegalovirus, varicella-zoster virus, herpes simplex virus, coxsackie virus, and mycoplasma were all negative, except for the presence of EBV VCA IgM and IgG (EBNA IgG negative). Exudative pharyngotonsillitis, cervical lymphadenopathy, and hepatosplenomegaly were not present. A diagnosis of EBV-associated acute pancreatitis was made; the patient was treated conservatively, including fasting for three days until the resolution of vomiting, peripheral parenteral nutrition support for seven days, and pain management with acetaminophen. An abdominal ultrasound, performed after five days, did not show any complications and antibiotic therapy was discontinued. She improved clinically, lipase and amylase levels progressively decreased, and enteral feeding was gradually resumed. She was discharged home on the fifteen day of hospitalization.

Discussion and conclusions

Acute pancreatitis is an inflammatory disorder of the pancreas; the incidence rate is 3–13 cases per 100,000 per year in the pediatric population [3, 4], and 5–60 cases per 100,000 persons per year in adulthood [5]. According to the American College of Gastroenterology guidelines, the diagnosis of acute pancreatitis is established by the presence of 2 of the 3 following criteria: (i) abdominal pain consistent with the disease, (ii) serum amylase and/or lipase greater than three times the upper limit of normal, and/or (iii) characteristic findings from abdominal imaging [6]. The most common etiology of acute pancreatitis is gallstones or microlithiasis; other causes include alcohol misuse, trauma, metabolic disorders (hypertriglyceridemia, hypercalcemia), infections (parotitis, mumps, influenza, herpes viruses, hepatitis viruses, coxsackie viruses, mycoplasma), systemic disease (hemolytic uremic syndrome, systemic lupus erythematosus, Henoch-Schönlein purpura, Kawasaki disease, inflammatory bowel diseases), and autoimmune pancreatitis [5, 7]. EBV infection is a rare cause of acute pancreatitis; the pathophysiology remains unclear: both direct viral infection and inflammatory process induced by the virus are plausible pathogenic mechanisms [8, 9].

A review of the English literature was performed: a PubMed search, using as keywords acute pancreatitis AND (EBV OR Epstein-Barr virus), revealed only 10 pediatric [8, 10,11,12,13,14,15,16,17,18] and 6 adult cases [9, 19,20,21,22,23]. As regards pediatric reports (Table I), median age and mean age was 12 and 11.8 years respectively (range 3–18), 36% were male and 64% were female. As regards pancreatitis symptoms, abdominal pain was described in all cases, vomiting in 55%, and nausea in 27%; eight patients (73%) also had mononucleosis symptoms, like fever, lymphadenitis, and pharyngitis. Amylase and/or lipase levels were increased up to three times the normal limit in 100% of the cases. In 5 children, there was evidence of acute pancreatitis on abdominal computerized tomography (CT), while only in our case, ultrasound (US) revealed an enlarged pancreas with a heterogeneous echotexture. The diagnosis of pancreatitis was confirmed in all patients, using the diagnostic criteria of the American College of Gastroenterology. Six children presented other complications related to EBV infection: the most common was cholestatic hepatitis (50%); cholecystitis, pneumonia, proctitis, portal vein thrombosis, and septic shock were also reported. Serological documentation for EBV infection was obtained in 10 cases, while in 1 child, the diagnosis was made clinically. All cases were treated with supportive care, that were fasting, intravenous fluids, parenteral nutrition, and/or pain management; in 1 patient, antibiotics and antivirals (meropenem, teicoplanin, and ganciclovir) were also used [17]. All children recovered.

Table I Clinical data of pediatric cases with EBV-associated acute pancreatitis reported in literature and our case

As regards adult patients (Table II), EBV-associated acute pancreatitis affects mainly young adults (range 21–45 years), with a slight female predominance (66%). All cases presented abdominal pain, associated sometimes with nausea, fever, and vomiting. In 3 patients (50%), signs and symptoms related to infectious mononucleosis were also observed. The diagnosis of EBV infection was made by positive serology in 5 patients; also in 2 cases, serum EBV-DNA was detected. Abdominal CT was executed in 5 patients, revealing signs of acute pancreatitis, such as enlarged and edematous pancreas; in 1 case, areas of necrosis were also noticed. All patients except one had complications related to systemic EBV infection, revealing a more severe clinical course in adults than children. The reported complications are hepatitis with or without cholestasis, gastritis, pneumonia with pleural effusion, ascites, pericardial effusion, autoimmune hemolytic anemia, and multi-organ failure. The patients were treated with symptomatic therapy; antibiotics, antivirals, and steroids were also administered in critical cases. All patients except one fully recovered.

Table II Clinical data of adult cases with EBV-associated acute pancreatitis reported in literature

In conclusion, EBV infection is characterized by clinical heterogeneity; multiple organs could be involved, also the pancreas, both in children and young adults. Active surveillance is needed for prompt diagnosis and early treatment. In patients with signs and symptoms of acute pancreatitis, EBV infection should always be considered, even in the absence of the typical clinical and hematological features of infectious mononucleosis. Generally, EBV-associated acute pancreatitis is characterized by a favorable prognosis, with a spontaneous resolution.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.



Epstein-barr virus


Computerized tomography




  1. Vouloumanou EK, Rafailidis PI, Falagas ME. Current diagnosis and management of infectious mononucleosis. Curr Opin Hematol. 2012;19:14–20.

    Article  CAS  Google Scholar 

  2. Bolis V, Karadedos C, Chiotis I, Chaliasos N, Tsabouri S. Atypical manifestations of Epstein-Barr virus in children: a diagnostic challenge. J Pediatr (Rio J). 2016;92(2):113–21.

    Article  Google Scholar 

  3. Morinville VD, Barmada MM, Lowe ME. Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible? Pancreas. 2010;39(1):5–8.

    Article  PubMed  Google Scholar 

  4. Park A, Latif SU, Shah AU, et al. Changing referral trends of acute pancreatitis in children: A 12-year single-center analysis. J Pediatr Gastroenterol Nutr. 2009;49(3):316–22.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Uc A, Husain SZ. Pancreatitis in Children. Gastroenterology. 2019;156(7):1969–78.

    Article  PubMed  Google Scholar 

  6. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis [published correction appears in Am J Gastroenterol. 2014 Feb;109(2):302].Am J Gastroenterol. 2013;108(9):1400–1416. doi:

  7. Lankisch PG, Apte M, Banks PA. Acute pancreatitis [published correction appears in Lancet. 2015 Nov 21;386(10008):2058]. Lancet. 2015;386(9988):85–96. doi:

  8. Hammami MB, Aboushaar R, Musmar A, Hammami S. Epstein-Barr virus-associated acute pancreatitis. BMJ Case Rep. 2019;12(11):e231744. Published 2019 Nov 14. doi:

  9. Zhu Z, Yin SJ, Kong ZB, et al. Pancreatitis Combined with Epstein-Barr Virus-induced Infectious Mononucleosis. Chin Med J (Engl). 2017;130(16):2001–2.

    Article  Google Scholar 

  10. Wislocki LC. Acute pancreatitis in infectious mononucleosis. N Engl J Med. 1966;275(6):322–3.

    Article  CAS  PubMed  Google Scholar 

  11. Hedström SA, Belfrage I. Acute pancreatitis in two cases of infectious mononucleosis. Scand J Infect Dis. 1976;8(2):124–6.

    Article  PubMed  Google Scholar 

  12. Werbitt W, Mohsenifar Z. Mononucleosis pancreatitis. South Med J. 1980;73(8):1094.

    Article  CAS  PubMed  Google Scholar 

  13. Koutras A. Epstein-Barr virus infection with pancreatitis, hepatitis and proctitis. Pediatr Infect Dis. 1983;2(4):312–3.

    Article  CAS  PubMed  Google Scholar 

  14. Khawcharoenporn T, Lau WK, Chokrungvaranon N. Epstein-Barr virus infection with acute pancreatitis. Int J Infect Dis. 2008;12(2):227–9.

    Article  PubMed  Google Scholar 

  15. Kang SJ, Yoon KH, Hwang JB. Epstein-barr virus infection with acute pancreatitis associated with cholestatic hepatitis. Pediatr Gastroenterol Hepatol Nutr. 2013;16(1):61–4.

    Article  PubMed  PubMed Central  Google Scholar 

  16. López-Ibáñez MC, Moreno-Conde M, Gallego-De-la-Sacristana-López-Serrano Á, García-Catalán-Gallego F, Villar-Ráez A. Acute pancreatitis as atypical manifestation of Epstein-Barr virus infection. Rev Esp Enferm Dig. 2013;105(7):437–8.

    Article  PubMed  Google Scholar 

  17. Galzerano A, Nisi F, Angela S, Ranucci F. Acute Epstein-Barr virus pancreatitis with thoracic-abdominal abscess and portal compression. Dig Liver Dis. 2014;46(6):574–5.

    Article  PubMed  Google Scholar 

  18. Narchi H, Bimal R, Epelman M, et al. Cholestatic hepatitis with pancreatitis as presenting features of Epstein-Barr virus infection. JMED Research. 2014;2014:1–4.

    Article  Google Scholar 

  19. Jahann D, Martin P. Epstein-Barr Virus Pancreatitis: 810. Am J Gastroenterol. 2012;107:S333–4.

    Article  Google Scholar 

  20. Cook J, Kothari M, Nguyen A. Epistein-Barr virus infection with concurrent pancreatitis and hepatitis: a rare disease entity. Am J Infect Dis. 2015;11(3):83.

    Article  CAS  Google Scholar 

  21. Singh S, Khosla P. A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult. J Infect Public Health. 2016;9(1):98–101.

    Article  CAS  PubMed  Google Scholar 

  22. Fiani E, Challita R, Badawaki H, Soukarieh K, Kyriakos Saad M, Saikaly E. Epstein–Barr Virus-Induced Acute Hepatitis, Pancreatitis, and Pneumonitis in a Young Immunocompetent Adult: A Case Report. EMJ Respir. 2021; doi/

  23. Huang L, Feng Z, Tang C. Gastrointestinal: A rare case of necrotic pancreatitis caused by Epstein-Barr virus [published online ahead of print, 2021 Nov 10]. J Gastroenterol Hepatol. 2021; doi:

Download references


Not applicable


No specific fundings were used for the current manuscript.

Author information

Authors and Affiliations



SS and MGua have participated in the diagnostic pathways and treatment. GAR, SS, and MGua wrote the paper. SA, GC, and MGiu revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Simona Scalzo.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Parent’s informed written consent was provided.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Accomando, S., Restivo, G.A., Scalzo, S. et al. Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature. Ital J Pediatr 48, 160 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: