Atypical manifestations of dengue fever in a recent dengue outbreak

Context: Dengue fever is highly prevalent in tropical and subtropical regions. The disease is caused by RNA virus, flavivirus and is transmitted by a mosquito to humans. Aims: The aim is to study the various atypical manifestations that can occur in dengue fever. Settings and Design: The patients presenting with acute febrile illness from September to December 2015 were admitted in a tertiary care hospital of North India and were screened for dengue fever. A total of 141 patients were screened for dengue fever out of which 61 patients were positive for dengue fever. A detailed history of each patient reporting to the hospital was taken followed by the general physical examination and systemic examination. Subjects and Methods: Complete blood count was performed in all patients and other investigations such as liver and kidney function test, chest X-ray, ultrasound, magnetic resonance imaging, and cerebrospinal fluid examination were done wherever required. Results: Atypical manifestations were present in 24 of 61 patients who were diagnosed positive for dengue fever (39.3%). Acalculous cholecystitis was the most common manifestation (32.7%), followed by encephalitis (6.5%) and hepatitis (3.2%). Transverse myelitis, acute respiratory distress syndrome, and renal failure had a frequency of 1.6%. There was no mortality as none of the patients had DSS in our study. Liver function tests (alkaline phosphatase and aspartate aminotransferase) were deranged in most patients (52.4%) out of which only 3.2% had raised serum bilirubin levels. Hepatomegaly was present in 19.6% of patients, and splenomegaly was observed in 3.2% of the patients. Conclusions: Dengue fever this year had various atypical manifestations – acalculous cholecystitis having the maximum occurrence. Neurological manifestations were also present. Transverse myelitis which is a rare manifestation was also observed.

Keywords: Acalculous cholecystitis, atypical manifestations, transverse myelitis

Dengue fever, a disease mainly of the tropical and subtropical regions, is caused by Dengue virus of genus flavivirus and family Flaviviridae (arbovirus). The virus is transmitted to the human body by the bite of female Aedes mosquito.

Dengue is a worldwide condition spread throughout the tropical and subtropical zones between 30°N and 40°S. It is endemic in Southeast Asia, the Pacific, East and West Africa, the Caribbean, and the Americas. Factors responsible for dengue spread include explosive population growth, unplanned urbanization with the inadequate public health system, poor vector control, increased international recreation, business, and military travel to endemic areas.

Manifestations of dengue fever are protean. Mild dengue is characterized by biphasic fever, skin rash, headache, retro-orbital pain, photophobia, cough, vomiting, myalgia, arthralgia, leukopenia, thrombocytopenia, and lymphadenopathy. Dengue hemorrhagic fever (DHF) is often a fatal disease and is usually associated with the secondary dengue infection but can appear during a primary infection, especially in infants who possess maternal IgG dengue antibody.

A probable case of dengue fever is acute febrile illness with two or more of following –a headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, and leukopenia.

A confirmed case of dengue fever is a case confirmed by laboratory criteria, that is, isolation of dengue virus from serum or autopsy samples; or demonstration of fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens in paired serum samples; or demonstration of dengue virus antigen in autopsy tissue, serum, or cerebrospinal fluid (CSF) samples by immunohistochemistry, immunofluorescence, or enzyme-linked immunosorbent assay (ELISA); or detection of dengue virus genomic sequences in autopsy tissue, serum, or cerebrospinal fluid by polymerase chain reaction.^[1]

As dengue and DHF are assuming global proportions, more and more atypical manifestations appear which might be underreported because of lack of awareness and thus needs a review.

Such awareness will be helpful in making an early diagnosis and for early therapeutic intervention. This study has been carried out to know the frequency of these uncommon manifestations during an epidemic of dengue fever in North India.

All the patients admitted with acute febrile illness in the medical unit of the hospital from September to December 2015 were screened for dengue fever. After a detailed history and complete clinical examination, following tests were carried out in those patients:

1. Complete blood count including hemoglobin, total leukocyte count, differential leukocyte count, and platelet count. Furthermore, peripheral smear was screened for malarial parasite
2. ELISA for IgM antibodies against dengue antigen in case patient presented after 4 days of illness or test for NS1 antigen by polymerase chain reaction in case patient has come within 2–3 days of illness
3. ELISA – optimal test for malarial antigen
4. Liver function test mainly aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and serum bilirubin
5. Blood urea and serum creatinine levels
6. Ultrasound examination in patient presenting with pain abdomen and hepatomegaly
7. CSF examination, computed tomography scan, and magnetic resonance imaging on patient presenting with altered sensorium or focal neurological deficit.

A total of 141 patients were screened for dengue fever, and 61 confirmed to have dengue fever. There were 40 male and 21 female, and the average age of male and female patients was 25.98 ± 12.96 years and 26.90 ± 11.07 years, respectively [Figure 1]. The average duration of fever was 5.23 ± 2.82 days.

In our study, 24 patients (39.3%) had atypical manifestations. The most common atypical manifestation was acalculous cholecystitis (20 patients), followed by neurological manifestations which include encephalitis (4 patients) and transverse myelitis (1 patient). Two patients had hepatitis, and acute kidney injury was observed in 1 patient, and one patient had acute respiratory distress syndrome (ARDS) [Figure 2].

Further analysis of our findings showed that acalculous cholecystitis was the most common manifestation (32.7%). This was followed by hepatomegaly (19.6%). Splenomegaly was present in 3.2% of the patients. These findings were confirmed by ultrasonography of abdomen [Figure 3]. Derangement of liver functions was present in most patients (52.4%). Elevated bilirubin levels were observed in 3.2% patients [Figure 4].

Neurological manifestations such as encephalitis were present in 6.5% of the patients. CSF examination performed in one patient showed raised sugar, raised protein, and pleocytosis.

Transverse myelitis and ARDS were the least common manifestations and were observed in 1.6% of the patients.

Abnormal kidney function in the form of raised urea and creatinine were observed in 6.5% of the total patients [Figure 5] and [Figure 6]. Most of these patients showed improvement in renal function except in one patient who had persistently increased urea and creatinine level. Kidney biopsy was done in the patient and showed acute cortical necrosis. Abnormal urine examination was observed in five patients.

Platelet count was below 10,000/μL in 9.8% of the patients. In 24.5% of the patients, platelet count varied within 10,000–20,000/μL. Platelet count in the range of 20,000–50,000/μL was observed in 45.5% of the patients. About 19.6% of the patients had a platelet count of more than 50,000/μL [Figure 7].

Dengue fever, a disease mainly of the tropical and subtropical regions, is caused by Dengue virus of genus flavivirus. Some 2.5 billion people in tropical and subtropical countries are at risk of the disease. An estimated 50 million infections occur worldwide annually, and about 500,000 people with DHF require hospitalization each year. About 2.5% of those affected die.^[1],[2]

Dengue epidemics are on the rise. In India, total number of cases reported in the year 2015 were 99,913 and 220 deaths were reported.^[3] Although it was not declared as an epidemic in 2015, still the number of cases reported were high. In India, the incidence of dengue has been increasing year after year. Every monsoon brings along an outbreak of dengue. Thus, it becomes essential to study the different manifestations of this disease.

Approximately 90% of the cases reported are children aged <5 years.^[2] In our study, most of the patients were in the age group of 15–20 years (19.6%).

In a study done by the European Centre for Disease Prevention and Control, the case rate was similar in males and females, with a male-to-female ratio of 1.14:1.^[4] Studies done by the WHO Western Pacific region showed a male preponderance in cases reported from Asia in contrast to the studies done in South America where it has been reported in equal proportions of male and female dengue cases or a greater proportion of female cases.^[4] In our study, the male patients outnumbered the female patients and the male-to-female ratio was 1.90:1.

In males, the age groups with maximum number of patients were 15–20 and 20–25 years, each group had 14.7% of the total number of patients. In females, the age group with maximum number of cases was 30–40 years which comprised of 9.8% of the total patients. Hence, in our study, there was more number of male patients as compared to female patients.

Typical manifestations of dengue fever are acute febrile illness with chills, body aches, myalgia, joint pain, petechial rash, and bleeding manifestations. Several studies of travelers or military personnel have reported these “classic” symptoms of dengue fever in 15%–60% of patients,^{[5],[6],[7],[8]} whereas in our study, classical symptoms were reported in 60.6% of the patients.

Atypical manifestations of dengue fever are hepatitis, acute kidney injury, ARDS, pancreatitis, febrile diarrhea, acalculous cholecystitis, myositis, myocarditis, conduction abnormalities, disseminated intravascular coagulation, and atrial fibrillation. Atypical manifestations also include neurological manifestations such as seizures, encephalitis, meningitis, transverse myelitis, and Guillain–Barré syndrome.

In our study, 39.3% of patients had atypical manifestations – acalculous cholecystitis was the most common manifestation (32.7%) followed by encephalitis (8.1%), hepatitis (3.2%), transverse myelitis (1.6%), acute renal failure (1.6%), and ARDS (1.6%).

In a study, 11 out of 40 patients of dengue fever had acute acalculous cholecystitis, that is, 28% as compared with Keng-liana Wu et al. who found dengue fever with acute acalculous cholecystitis in 7.6%. In another study done by S Bhatty et al., the incidence was 16.36% in dengue patients.^[9] In our study, atypical gastrointestinal manifestations including acalculous cholecystitis (32.7%) and hepatitis (3.2%) observed in 36.06% of the patients. Liver enzyme elevation is a common feature ^[13] was also apparent in our study (52.4%)

The incidence of neurological manifestations in patients diagnosed with DHF and severe dengue has been documented to vary from 3% in prospective DHF studies to 25% in retrospective studies.^[10],[11] In our study, the incidence was 8.1%.

Encephalitis is known to be one of the frequent presenting manifestations of dengue neurological disease, and its prevalence reported to be 4.2%,^[12] whereas in our study, its incidence is 6.5%. Spinal cord involvement is not frequent.^[13] In our study also, transverse myelitis was reported in one patient.

Acute renal failure is rare in dengue fever, and it mainly presents as shock-induced acute tubular necrosis,^[14] whereas in our study, one patient (1.6%) presented with renal failure and renal biopsy showed cortical infarct.

ARDS is one of the dreaded complications of DHF, secondary to increased alveolar-capillary membrane permeability leading to interstitial and alveolar edema ^[15] and was present in one patient of our study (1.6%).

A study like ours is a step forward in the identification and early recognition of both typical and atypical manifestations. However, dengue virus serology would have helped us correlate clinical manifestations with virus subtype.

Every monsoon in our country brings in a surge of patients presenting with symptoms of dengue. Dengue outbreaks have become very frequent in the past few years occurring almost every year. Thus, it becomes important to identify different typical and atypical manifestations of dengue fever. This would aid in the providing early treatment, and better care to the patients and further studies are needed to identify any specific serotype which may be responsible for the atypical manifestations.

Acknowledgment

We would like to thank Dr. Smita Nath, Senior resident, Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ATMPH.ATMPH_18_17

[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]