Influenza imposes a significant burden of disease on children worldwide, resulting in increased rates of hospitalization and substantial morbidity and mortality. Additionally, children play a pivotal role in transmitting viral infections within communities1. Typically, children exhibit symptoms such as fever, cough, runny nose, sore throat, headache, muscle aches, and fatigue. Clinical signs commonly associated with influenza include clear nasal discharge, erythema of the nasal and throat membranes without exudate, and a temperature of = 37°C1. In children, symptoms like swollen lymph nodes in the neck and gastrointestinal issues such as abdominal pain, diarrhea, vomiting, and higher fevers are more prevalent as compared to adults1. Following infection, common complications may include bacterial pneumonia, seizures, other bacterial infections, and exacerbations of pre-existing respiratory conditions2,3,4. A study conducted by Bennet et al. in Sweden reported that 41% of children infected with the influenza virus experience various forms of complications.
Pancreatitis in the pediatric population occurs at 3-13 cases per 100,000 per year. According to a review article, approximately 8-10% of pediatric pancreatitis cases are attributed to viral infections, including hepatotropic viruses, herpes simplex virus, SAR-CoV-2, Coxsackie virus, cytomegalovirus, mumps, influenza virus, human immunodeficiency virus, varicella-zoster virus, and others5. While influenza infection has been documented in the literature as a cause of pancreatitis, there are only a few reported cases6. We present a case of acute pancreatitis in a child who tested positive for influenza A via polymerase chain reaction (PCR) on a throat swab. The patient was treated with Oseltamivir and responded positively to the treatment.
Case Report
A 3-year-old boy presented with abdominal pain and vomiting persisting since 2 days, accompanied by one-day history of fever. On examination, he weighed 9.6 kg (< 3rd percentile on the World Health Organization growth chart) and measured 86 cm in height (< 3rd percentile on WHO growth chart). His heart rate was 128 beats per minute, respiratory rate 26 breaths per minute, and oxygen saturation was 96% on room air. Abdominal examination revealed mild distension with tenderness, while other general and systemic examinations were unremarkable. Laboratory investigations showed a hemoglobin level of 12.6 g/dL, white cell count (WBC) of 5,870 cells/mm^3 (with polymorphs at 59.7%, lymphocytes at 31.2%, and monocytes at 7.4%), and a platelet count of 242 x 10^3 cells/mm^3. Additionally, the C-reactive protein level was 45.9 mg/dL, serum amylase was 774 U/L, and serum lipase was 447 U/L. Lipid profile results included a total cholesterol level of 80 mg/dL, serum triglyceride level of 50 mg/dL, high-density lipoprotein level of 33.1 mg/dL, very low-density lipoprotein level of 11.2 mg/dL, and low-density lipoprotein level of 35.7 mg/dL.
Abdominal ultrasonography revealed an enlarged and inflamed head of the pancreas, mild hepatomegaly, ascites, numerous enlarged non-necrotic mesenteric lymph nodes (with the largest measuring 1.6 cm), and an enlarged gall bladder containing sludge, multiple stones, and an edematous wall. On the second day of admission, the patient developed facial puffiness and reduced urine output. Nasopharyngeal swab PCR was positive for influenza A, while saliva PCR for mumps was negative. Tests for dengue and leptospirosis were also negative. Based on the clinical features and investigation findings, a diagnosis of acute pancreatitis secondary to influenza infection was made.
The patient was admitted to the pediatric intensive care unit, where oral intake was withheld. Treatment included oseltamivir tablets (30 mg twice daily for 5 days), continuous intravenous fluids, and analgesics. He showed improvement within twenty-four hours of treatment onset. Despite gallbladder findings, investigations for hemolysis were negative, including normal peripheral smear, negative direct Coombs test, normal osmotic fragility test, and normal high-performance liquid chromatography.
The patient remained under supportive care for 7 days and was discharged with complete symptom resolution. A magnetic resonance cholangiopancreatography (MRCP) performed two weeks after discharge showed no biliary abnormalities, residual pancreatitis changes, and no gallbladder, biliary tract, or pancreatic duct stones. The patient continues to be monitored on an outpatient basis.
Discussion
Acute pancreatitis commonly manifests with severe abdominal pain, nausea, and vomiting7. In children, acute pancreatitis is a relatively uncommon yet potentially serious condition. While many cases are mild and resolve without intervention, up to one-third of patients may experience moderate to severe disease or progress to recurrent or chronic pancreatitis6. Causes of acute pancreatitis in children often include gallstones, anatomical abnormalities, infections, trauma, or drug-related factors7.
In 2023, Sarshari et al. documented three cases of acute pancreatitis associated with influenza virus8: a 37-year-old male who developed pancreatitis following a brief prodrome of fever, malaise, and myalgia; a 19-year-old boy who developed pancreatitis shortly after an H1N1 infection during the 2009 pandemic; and a 42-year-old female who presented with shortness of breath, epigastric pain radiating to the back, and hyperglycemia8. Diagnosis in all three cases was based on clinical presentation, elevated serum amylase and lipase levels, evidence of influenza infection, and response to treatment.
Additionally, in 2023, a case of hemorrhagic pancreatitis secondary to influenza was reported in a pregnant female, diagnosed postmortem9. Ours is the first case to be reported in a child less than five years of age.
Recent studies have demonstrated the ability of the influenza virus to infect pancreatic cells and replicate within them. The resulting acute severe immune response and overproduction of pro-inflammatory cytokines contribute to pancreatic damage5. Since we could not do a pancreatic biopsy in our patient and were unable to do influenza PCR on the pancreatic tissue, we cannot be very certain on influenza virus being the cause of acute pancreatitis but the child responded to oseltamivir, suggesting that the influenza virus may be associated with acute pancreatitis in this patient.
The nucleic acid amplification test (NAAT), such as Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), is considered the gold standard for diagnosing influenza due to its high sensitivity and specificity9. In our case, Nasopharyngeal PCR was positive for influenza A and negative for mumps. Although initial ultrasonography revealed the presence of gallstones, a subsequent magnetic resonance cholangiopancreatography (MRCP) performed after 15 days showed no evidence of biliary stones, suggesting that pancreatitis was unlikely due to a biliary stone. Additionally, liver function tests were normal in the child.
Early diagnosis of acute pancreatitis, along with nutritional support, aggressive hydration, and pain management, are the mainstays of treatment for childhood pancreatitis6. Prophylactic antibiotics have not been advantageous in treating pancreatitis of infectious origin10. Oseltamivir, an antiviral medication, is the primary treatment for influenza in children and should be initiated in those at high risk of complications9. All three previously diagnosed patients received oseltamivir8, and our patient was treated similarly. All four patients showed rapid improvement upon receiving oseltamivir treatment.
Conclusion
In conclusion, although viral infections are acknowledged as a cause of pediatric pancreatitis, influenza-associated pancreatitis has been rarely documented. Long-term studies involving children are necessary to enhance our comprehension of the disease mechanism, management strategies, and preventive measures.
References
- Nayak J, Hoy G, Gordon A. Influenza in children. Cold Spring Harb Perspect Med [Internet]. 2021 [cited 2024 Apr 6];11(1):a038430.
- Bennet R, Hamrin J, Wirgart BZ, Östlund MR, Örtqvist Å, Eriksson M. Influenza epidemiology among hospitalized children in Stockholm, Sweden 1998–2014. Vaccine [Internet]. 2016;34(28):3298–302.
- Neuzil KM, Zhu Y, Griffin MR, Edwards KM, Thompson JM, Tollefson SJ, et al. Burden of interpandemic influenza in children younger than 5 years: A 25-year prospective study. J Infect Dis. 2002;185(2):147–52.
- Zambon M. Influenza surveillance and laboratory diagnosis. Textbook of Influenza. Wiley; 2013. p. 229–49.
- Qu C, Gao K, Li W. Viral infection and pediatric pancreatitis. Rev Esp Enferm Dig. 2020;112(10).
- Mehta MS. Acute pancreatitis in children: risk factors, management, and outcomes. Curr Opin Pediatr. 2023;35(5):590–5.
- Saeed SA. Acute pancreatitis in children: Updates in epidemiology, diagnosis and management. Curr Probl Pediatr Adolesc Health Care. 2020;50(8):100839.
- Sarshari B, Zareh-Khoshchehreh R, Keshavarz M, Sa DM, SeyedAlinaghi S, Asadzadeh AH, et al. The possible role of viral infections in acute pancreatitis: a review of literature. Gastroenterol Hepatol Bed Bench. 2023;16(3).
- Wickramasinghe CU, Sivasubramanium M, Muthugala R. Acute hemorrhagic pancreatitis following influenza infection: a case report. J Med Case Rep. 2023;17(1).
- Dharmapalan D. Influenza. Indian J Pediatr. 2020;87(10):828–32.
- Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, et al. Acute pancreatitis: Diagnosis and treatment. Drugs. 2022;82(12):1251–76.