Dengue fever or break bone fever or Dacca fever which is a mosquito-borne tropical disease caused by the dengue virus which is an RNA virus of the family Flaviviridae; genus Flavivirus [6]. Symptoms typically begin three to fourteen days after infection [7]. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash [6,7]. Recovery generally takes two to seven days [6]. In a small proportion of cases, the disease develops into a more severe dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs [6,7].
Dengue is spread by several species of female mosquitoes of the Aedes genus, principally Aedes aegypti [6,7]. The virus has four serotypes [8,9] (DEN 1, 2, 3, and 4. infection with one type usually gives lifelong immunity to that type, but only short-term immunity to the others [6]. Subsequent infection with a different type increases the risk of severe complications [6]. A number of tests are available to confirm the diagnosis including detecting antibodies or antigens or direct viral culture [7].
Typically, people infected with dengue virus are asymptomatic (80%) or have only mild symptoms such as an uncomplicated fever [10-12]. Others have more severe illness (5%), and in a small proportion it is life-threatening [10,12]. The incubation period (time between exposure and onset of symptoms) ranges from 3 to 14 days, but most often it is 4 to 7 days [13].
The characteristic symptoms of dengue are sudden-onset fever, headache (typically located behind the eyes), muscle and joint pains, and a rash. An alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains [10,14]. The course of infection is divided into three phases: febrile, critical, and recovery [15].
The febrile phase involves high fever, potentially over 40°C (104°F) and is associated with generalized pain and a headache; this usually lasts two to seven days [14,15]. Nausea and vomiting may also occur [25]. A rash occurs in 50–80% of those with symptoms [14,16]. in the first or second day of symptoms as flushed skin, or later in the course of illness (days 4-7), as a measles-like rash [16,17]. A rash described as "islands of white in a sea of red" has also been observed [18]. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, [15] as may some mild bleeding from the mucous membranes of the mouth and nose [14]. The fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days [17,18].
In some people, the disease proceeds to a critical phase as fever resolves [19]. During this period, there is leakage of plasma from the blood vessels, typically lasting one to two days [15]. This may result in fluid accumulation in the chest and abdominal cavity as well as depletion of fluid from the circulation and decreased blood supply to vital organs [19]. There may also be organ dysfunction and severe bleeding, typically from the gastrointestinal tract [15,20]. Shock (dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue; [20] however, those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk [20,21]. This critical phase, while rare, occurs relatively more commonly in children and young adults [19].
The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream [15]. This usually lasts two to three days [15]. The improvement is often striking and can be accompanied with severe itching and a slow heart rate [15,19]. Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin [19]. During this stage, a fluid overload state may occur; if it affects the brain, it may cause a reduced level of consciousness or seizures [20]. A feeling of fatigue may last for weeks in adults [22].
EDS is a terminology introduced by the WHO in 2012 to encompass the unusual manifestations of dengue involving severe damage to the liver, heart, kidneys or brain which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. They may be related to underlying co-morbidities, associated co-infections or prolonged shock. Certain high-risk groups such as pregnant, infants, geriatric group, patients with coronary artery disease, hemoglobinopathies and immunocompromised individuals are particularly susceptible to developing EDS. As clinicians, we must be aware of these atypical features so that we can suspect dengue early, especially during ongoing epidemics.
Acute Pancreatitis (AP) is an acute inflammatory process of the pancreas with varying involvement of other regional tissues or remote organs. While common causes of AP are gall stones and alcohol, infective agents also cause a small proportion of cases [23]. Viral infections that can cause pancreatitis are hepatitis B, hepatitis A, varicella, dengue, mumps. Pancreatitis in any infectious disease could be (a) definite pancreatitis if there is surgical or radiological evidence of pancreatitis, (b) probable pancreatitis if there is biochemical evidence in the form of more than three-fold elevated serum amylase or lipase and characteristic symptoms, or (c) possible pancreatitis if there is only asymptomatic biochemical evidence [24].
An infectious agent should be suspected as the cause of AP if the characteristic syndrome due to the infectious agent is present, which is seen in 70% of cases [25]. Criteria suggested for associating pancreatitis with an infective etiology include (a) finding the organism in pancreas or pancreatic duct, which is ‘definitive criteria’; (b) culture of the organism from the pancreatic juice or blood or serological evidence combined with characteristic clinical or epidemiological setting, which is ‘probable criteria’; and (c) culture of the organism from other body sites or serological evidence of infection, which is ‘possible criteria’ [22].
Abdominal pain is a common symptom (40%) in dengue infections and is more commonly associated with DHF. Some of the causes for abdominal pain in dengue infections include hepatitis, acute acalculous cholecystitis, acute pancreatitis, and colitis. Studies have reported the incidence of AP in dengue infections to be 14-29% [26].
Till date, there have been only a few case reports of acute pancreatitis complicating DF from across the world. Our patient also had severe dengue which was complicated by acute pancreatitis which was evident by raised serum amylase and lipase and ultrasound findings. Hyperlipasemia and enlarged pancreas have been known to occur in DF; but acute pancreatitis is an atypical and rare presentation [27-29]. The exact pathogenesis of pancreatic involvement in dengue is not known. The physiopathology behind the acute pancreatitis in this infection is not well understood although there are two hypotheses that had better explain this process: (1) the pancreatic compromise of the biliary pathway and (2) the small hemorrhages in the peritoneal cavity [30]. The first hypothesis suggests that the viral infection causes an autoimmune response to pancreatic islet cells, thus edema develops in the Vater's ampulla and obstructs the exit of pancreatic fluids [30]. The second hypothesis suggests that acute pancreatitis is caused by the direct inflammation and destruction of the pancreatic acinar by the same virus; this is mainly evidenced in dengue shock syndrome (grades III and IV of dengue hemorrhagic fever (DHF)) [4]. But it can be due to result of direct invasion by the virus itself causing inflammation and destruction of pancreatic acinar cells.
During a deep browse in the literature, we identified 15 articles reporting 17 patients with pancreatitis due to dengue fever. In summary, 76.5% (n=13) of cases were reported from Asia, 11.76% (n=2) from Latin America, and 5.9% (n=1) from Europe. Taiwan and Bangladesh were the countries with the highest reported cases, with 29.4% and 11.8%, respectively. The most prevalent serotype was DEN-1 in 64.71% of the cases and 35.3% of the cases did not report the serotype. The most frequent symptoms were fever (52.9%, nine cases), abdominal pain (47.1%, eight cases), vomiting (47.1%, eight cases), body pain (35.3%, six cases), chills (23.5%, four cases), and dyspnea (17.7%, three cases), and most of them were males (47.1%, eight cases). Regarding laboratory tests, 11.8% of the cases reported hypocalcemia, 41.2% had hyperlipasemia, 41.2% had hyperamylasemia, 35.3% had thrombocytopenia, 35.3% had dengue IgM and IgG positive detection, 11.8% had an NS1 positive antigen, 5.9% had edema of the thick gallbladder wall, 64.7% had low hematocrit, 5.9% had high pleural fluid amylase, 35.3% were dengue virus IgM positive and negative IgG, 5.8% of tests were of renal-derived function, 5.9% had lymphopenia, and 5.9% had hemoconcentration. About the pancreas examinations, 94.1% of the cases were diagnosed with pancreatitis with a CT scan and 5.9% reported hemorrhagic pancreatitis. The final diagnoses of the reported cases corresponded 64.71% to DHF grade I, 17.7% to DHF grade II, and 5.9% to DHF grade IV. In 70.6% of the cases, the patient was discharged, and 11.8% of them died.
Our patient never took alcohol or any offending drugs which could cause AP and had no gallstones on USG. The elevated enzymes, USG findings along with positive dengue NS1 antigen pointed towards the diagnosis on 2nd afebrile day. She was managed conservatively and improved dramatically. So far acute pancreatitis occurring during the critical phase of dengue has been reported [31].
