Acute pancreatitis complicating dengue hemorrhagic fever

Abstract

Dengue infection can have spectrum of manifestations, often with an unpredictable clinical progression and outcome. There have been increasing reports of atypical manifestations. Abdominal pain or tenderness and persistent vomiting (warning signs) are present in the majority of cases with severe dengue prior to clinical deterioration. We report a 10-year-old child who presented with fever, persistent vomiting, and abdominal pain. A diagnosis of acute pancreatitis was made. This is a very infrequently reported complication of dengue hemorrhagic fever.

Keywords:
Dengue hemorrhagic fever; Acute pancreatitis; Persistent vomiting.

INTRODUCTION

Dengue infection is a disease entity that can have different clinical presentations and often demonstrates an unpredictable clinical progression and outcome. There have been increasing reports of dengue fever (DF) and dengue hemorrhagic fever (DHF) with atypical manifestations due to involvement of liver, kidneys, heart, or nervous system (expanded dengue syndrome)¹. These atypical manifestations may be potentially serious and may result in increased rates of morbidity and mortality. Therefore, clinicians should be aware of these atypical manifestations. Acute pancreatitis is a rare complication of DF². We report a case of acute pancreatitis complicating DHF; this is a very infrequently reported complication.

CASE REPORT

A 10-year-old girl, known with autoimmune hemolytic anemia, presented with a one-day history of fever, vomiting, and body aches. On examination, her vital signs were stable. Abdominal examination revealed a 2cm hepatomegaly and a palpable spleen. Examination of other systems was unremarkable. The investigations and the course of her illness are depicted in Table 1 and Figure 1. She developed persistent vomiting with abdominal pain. A diagnosis was made of acute pancreatitis complicating DHF. She was managed conservatively and was discharged in a stable condition after 19 days of hospitalization.

TABLE 1
Investigation chart.

• Blood culture and urine culture: sterile; dengue serology: NS1 antigen positive, IgM positive, IgG negative; Peripheral smear for malarial parasite, Widal test, Weil-Felix test, Typhidot-M, and HIV test: all negative; serology for hepatotrophic viruses (hepatitis A, B, C, E): negative. On day 7, echocardiogram: normal. Arterial blood gas: pH 7.30, pCO₂ 32mmHg, pO₂ 52.8mmHg, HCO₃ 15.5mmol/L; kidney function tests (urea, creatinine, Na⁺ , K⁺ ): normal on days 1, 3, 7 and 8. Total proteins and albumin: normal On day 8: PT=16.9 (control=14.2) seconds; APTT=33 (control=29) seconds; INR=1.24. Hb: hemoglobin; TLC: total leucocyte count; AST: aspartate transaminase; ALT: alanine transaminase; N: neutrophils; L: lymphocytes; NS1: nonstructural protein 1; IgM: immunoglobulin M; IgG: Immunoglobulin G; HIV: Human immunodeficiency virus; PT: prothrombin time; APTT: Activated partial thromboplastin time; INR: International normalised ratio.

FIGURE 1
Sequence of events after admission

DISCUSSION

In DF, abdominal and gastrointestinal symptoms are common^{3) (4}. Presentation with an acute abdomen in DF may pose a diagnostic dilemma and is a challenge for the treating clinician. In DHF, up to 40% of patients may present with abdominal pain³. Abdominal pain or tenderness and persistent vomiting are classified as warning signs¹. These symptoms (abdominal pain and vomiting) have been noted in the majority of patients with severe dengue infection prior to clinical deterioration⁵. Hence, there is a need for close monitoring of children with DF who display such warning signs. In a retrospective review of 8,559 patients with DF, 67% had abdominal and gastrointestinal symptoms. The most common symptom was nausea (52%), followed by abdominal pain (36%), and vomiting (29%)⁴. In dengue infection, the causes of abdominal pain include hepatitis, pancreatitis, acalculous cholecystitis, and peptic ulcer disease³. Acute pancreatitis is a rare complication of DF². In a study of DF by Khanna et al., the various causes of abdominal pain were reported to include acute hepatitis [n = 20 (36.4%)], acalculous cholecystitis [n = 9 (16.4%)], acute pancreatitis [n = 8 (14.5%)], appendicitis [n = 3 (5.5%)], spontaneous bacterial peritonitis [n = 2 (3.6%)], enteritis [n = 8 (14.5%)], peptic ulcer disease [n = 2 (3.6%)], and gastric erosions [n = 3 (5.5%)]³.

Acute pancreatitis in children is associated with significant morbidity and mortality⁶. It was reported that of 589 cases of acute pancreatitis in children, viral infections accounted for 10%⁶. In a study by Setiawan et al., 29% (43/148) of children with DHF who experienced epigastric pain had an enlarged pancreas. However, serum levels of amylase and lipase were measured in only 20 children. The authors noticed slight increase in 6 (75%) of 8 patients with mild DHF and in 10 (83%) of 12 patients with severe DHF. All children with mild DHF had a normal-sized pancreas and in all 10 severe cases children with increased serum levels of amylase and lipase had an enlarged pancreas⁷.

In a previous study, 14 out of 328 cases of DHF/dengue shock syndrome (DSS) had an acute abdomen; causes included acute cholecystitis (n = 10), nonspecific peritonitis (n = 3), and acute appendicitis (n = 1); none had acute pancreatitis⁸. In a study conducted in Pakistan, however, 43 (12%) out of 357 patients with DF had an acute abdomen and three (0.8%) had acute pancreatitis. All three patients with acute pancreatitis developed acute respiratory distress syndrome, and two died⁹. In our patient, DHF was diagnosed according to the World Health Organization's (WHO) criteria. She presented with fever, a bleeding tendency, thrombocytopenia (platelets <100 × 10⁹/L), and ascites, and her serology results were positive for nonstructural protein 1 (NS1) antigen and dengue immunoglobulin M (IgM) antibodies. She had continuous persistent vomiting that started one day prior to admission and stopped three days before discharge. Her initial abdominal sonogram and liver enzymes levels were normal. Given that the child's epigastric pain and associated persistent vomiting were not relieved by parenteral pantoprazole, and that she was hypotensive, we suspected acute pancreatitis and ordered serum amylase and lipase testing, and a repeat abdominal ultrasound. We diagnosed acute pancreatitis in view of clinical symptoms (abdominal pain and vomiting), hypotension, enlargement of the pancreas on ultrasound examination without features of hepatobiliary disorders, and increased serum amylase and lipase levels. We started antibiotics empirically for pneumonia and acute pancreatitis. Serum amylase and lipase levels decreased after one week. In DHF, the involvement of the pancreas may be due to direct viral invasion, secondary to host immune reactivity, or due to hypotension².

Like septic shock, acute pancreatitis can be fatal¹⁰. As such, DHF/DSS can also cause mortality if not treated. Therefore, acute pancreatitis as a complication of DHF is dangerous, and clinicians should know when to suspect in patients with DF. Acute pancreatitis as a complication of DHF may be underdiagnosed due to lack of awareness¹⁰. Hence, clinicians might not request serum amylase or lipase investigation, despite abdominal pain and vomiting. Lee et al. compared 14 patients with hyperlipasemia (one with additional hyperamylasemia) and 57 without hyperlipasemia/hyperamylasemia among 71 DHF patients who presented with abdominal pain. They found that three patients in the hyperlipasemia group had pancreatitis, all of whom had enzyme elevation > 3 times the of normal¹¹. In acute pancreatitis, serum amylase usually rises within a few hours of the onset of symptoms and return to normal values within 3-5 days. However, because of sensitivity, specificity, and positive and negative predictive value limitations, serum amylase alone cannot reliably be used to diagnose acute pancreatitis; the more specific serum lipase test is preferred. Serum lipase remains increased for a longer period than amylase after disease presentation¹². Abdominal pain and vomiting are common in DF, especially in severe DF. Even though important common causes include acute gastritis, hepatitis, and acalculous cholecystitis, acute pancreatitis should be kept in mind as one of the causes. Simple investigations like serum lipase, amylase (levels more than 3 times the upper limit of normal), and abdominal ultrasound will establish the diagnosis. In a patient with dengue illness who has abdominal pain, it is probably justified to estimate and monitor serum lipase and amylase levels and to perform serial abdominal sonography.

To conclude, clinicians should be alert when there are warning symptoms (abdominal pain and persistent vomiting) in patients with DF, and should order testing of serum lipase and amylase levels along with abdominal sonography. Even though acute pancreatitis is a rare complication, early diagnosis and prompt treatment is necessary to prevent morbidity and mortality.

References

• ¹
  World Health Organization Regional Office for South-East Asia. Comprehensive Guidelines for Prevention and Control of Dengue and Dengue Haemorrhagic Fever. Revised and expanded edition. World Health Organization: 2011. 196p.
• ²
  Wijekoon CN, Wijekoon PW. Dengue hemorrhagic fever presenting with acute pancreatitis. Southeast Asian J Trop Med Public Health 2010; 41:864-866.
• ³
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• ⁴
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• ⁷
  Setiawan MW, Samsi TK, Wulur H, Sugianto D, Pool TN. Epigastric pain and sonographic assessment of the pancreas in dengue hemorrhagic fever. J Clin Ultrasound 1998; 26:257-259.
• ⁸
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• ¹¹
  Lee IK, Khor BS, Kee KM, Yang KD, Liu JW. Hyperlipasemia/pancreatitis in adults with dengue haemorrhagic fever. Pancreas 2007; 35:381-382.
• ¹²
  Tenner S, Baillie J, DeWitt J, Vege SS. Management of acute pcreatitis. Am J Gastroenterol 2013; 108:1400-1415.

Publication Dates

• Publication in this collection
  Sep-Oct 2016

History

• Received
  28 Apr 2016
• Accepted
  12 July 2016