• Users Online: 338
  • Print this page
  • Email this page


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 3  |  Issue : 3  |  Page : 219-223

Clinico-Aetiological profile of children with fever and rash with special reference to dengue


Department of Pediatrics, Gandhi Medical College, Bhopal, Madhya Pradesh, India

Date of Submission31-Mar-2022
Date of Decision02-Jun-2022
Date of Acceptance11-Jul-2022
Date of Web Publication28-Dec-2022

Correspondence Address:
Dr. Bharati Choubey
Department of Paediatrics, Gandhi Medical College, Bhopal, Madhya Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JME.JME_27_22

Rights and Permissions
  Abstract 


Aim: Fever with rash is a common presentation in paediatric patients with a variety of differential diagnosis ranging from minor to life-threatening illnesses. Establishing an early diagnosis particularly of dengue infection, especially in a resource-limited setting is essential to reduce morbidity and mortality. The aim of this study is to evaluate the clinico-aetiological profile of children admitted with fever and rash and to find out different clinical and laboratory parameters for diagnosing dengue infection using screening tests. Methods: It is an observational cross-sectional study. All consecutive patients admitted to tertiary care centre during the study period (n = 120) between age group 1 month and 12 years were evaluated with detailed history and clinical examination and relevant investigations. For screening dengue infection, various clinical and laboratory parameters were used to find the best combination comprising the desired sensitivity, specificity, positive and negative predictive values (NPV) and likelihood ratio. Results: The most commonly affected age group was below 5 years. Among 120 patients, 64% had a laboratory-confirmed diagnosis out of which 45% patients were of viral aetiology, 10% patients had bacterial aetiology and 9% had non-infectious aetiology. Among viral infections, 18 patients were diagnosed as dengue immunoglobulin M enzyme-linked immunosorbent assay positive. Headache (100%), was the most common symptom followed by diarrhoea (83.3%), vomiting (83.3%) and altered sensorium (72.2%) in dengue-positive patients. All dengue patients had thrombocytopenia, 88.9% had leucopenia and liver function tests deranged in 77.8% of patients. The highest sensitivity and specificity values were found in the combination of fever, maculopapular rash, headache, absence of cough and thrombocytopenia (55.6% and 94.12%, respectively), followed by fever, maculopapular rash, headache, no cough, thrombocytopenia and leucopenia (with 50% sensitivity and 100% specificity). Both combinations also showed the highest values for positive and NPVs, positive likelihood ratio and maximum area under the curve using a receiver operating characteristic. Conclusion: Establishing the diagnosis of fever with rash in children can be challenging. A combination of parameters such as fever, maculopapular rash, headache, absence of cough, thrombocytopenia and leucopenia can be used as a screening tool for early diagnosis of dengue infection in a resource-limited setting.

Keywords: Children, dengue, fever, rash


How to cite this article:
Thakur S, Patil R, Choubey B, Shrivastava J. Clinico-Aetiological profile of children with fever and rash with special reference to dengue. J Med Evid 2022;3:219-23

How to cite this URL:
Thakur S, Patil R, Choubey B, Shrivastava J. Clinico-Aetiological profile of children with fever and rash with special reference to dengue. J Med Evid [serial online] 2022 [cited 2023 Feb 1];3:219-23. Available from: http://www.journaljme.org/text.asp?2022/3/3/219/365876




  Introduction Top


Fever with rash is a common finding in paediatric patients. In most cases, the disease is mild that resolves naturally while in some cases, it may be the first and the sole manifestation of a life-threatening condition.[1] In some cases, diagnosis can be made on clinical grounds but many times it is difficult to diagnose it even after days of clinical observation and laboratory work up.[2]

Attribution of the rash to a specific disease is based on its morphology, day of appearance, the pattern of spread to different parts of the body and disappearance as well as a thorough history, including information on prodromal symptoms, previous illness, immunisation status, contact with infected persons, travel history and use of medication and assessment of overall health and physical examination. This will all help reaching our diagnosis and choose an appropriate treatment.[3]

There are a large number of infectious and non-infectious conditions presenting as exanthematous fever majority being infectious causes. Among infectious causes, viral exanthems are the most common.[1],[2],[3] Vaccine-preventable diseases such as varicella, measles and rubella are a major public health concern. Dengue and chikungunya caused by arbovirus are other life-threatening exanthematous illnesses which are responsible for explosive epidemics during the monsoon season in India.[4]

Dengue infection is caused by the dengue virus, which has four serotypes – DEN-1, DEN-2, DEN-3 and DEN-4. DEN-2 virus is the most threatening of the four serotypes.[5] It is estimated that annually 390 million dengue infections occur worldwide, of which 25% manifest clinically. Approximately, 500,000 people with severe dengue require hospitalisation each year worldwide, and about 2.5% of those affected succumb to the illness.[6] The reported number of dengue cases in India has increased from 18,860 in 2011 to 101,192 in 2018; however, the case fatality ratio has declined from 3.3% in 1996 to 0.2% in 2018.[7] In 2020, India's case fatality ratio for dengue was 0.06, i.e., 6% of the total cases reported were severe, frequently leading to death.[8]

The aim of this study was to evaluate the clinico-aetiological and laboratory profile of patients admitted with fever and rash and to determine whether fever with maculopapular rash and some other clinical and laboratory parameters can be used as a screening tool for diagnosing dengue infection in resource-limited settings.


  Methods Top


This was a hospital-based observational cross-sectional study, in which all children aged between 1 month and 12 years admitted with fever and rash (onset within 7 days of onset of fever) were included from April 2020 to March 2021. Ethical clearance was obtained from the ethical clearance committee and written informed consent was taken from the parents/guardians. The patients were evaluated with detailed history and examination, morphology and distribution of rash, vaccination status, socioeconomic status, residence, nutrition, history of travel, drug intake, insect/animal bite and contact with a known case. The blood samples were evaluated for complete blood picture, total leucocyte count, differential leucocyte count, liver and renal function tests, haematocrit, blood cultures and serum examination for viral markers. The samples were processed at laboratory of the department of microbiology and department of pathology. Dengue was suspected when a high fever (40°C/104°F) is accompanied by two of the following symptoms during the febrile phase: severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands and rash.[6] Laboratory positive dengue case was defined as dengue immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA)-positive and laboratory-negative dengue case was defined as dengue IgM ELISA negative.[6] Anaemia was defined according to cut offs for haemoglobin and haematocrit proposed by the WHO.[9] Thrombocytopenia was defined as a platelet count below 150 × 109/L, the 2.5th lower percentile of the normal platelet count distribution.[10] Standard age-specific leucocyte differential cut offs were taken.[11]

Statistical analysis

The collected data were transformed into variables, coded and entered into Microsoft Excel. Data were analysed and statistically evaluated.

Quantitative data were expressed in mean ± standard deviation or median with interquartile range and depending on normality distribution, the difference between two comparable groups was tested by Student's t-test (unpaired) or Mann–Whitney U-test. Qualitative data were expressed in percentage and statistical differences between the proportions were tested by the Chi-square test or Fisher's exact test. From the data set, our study used different clinical features and laboratory parameters to find the best combination comprising the desired sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the likelihood ratio, these clinical and laboratory features were evaluated repeatedly, and for each combination, we test our dataset separately. Kappa value was calculated to see the agreement of these clinical and laboratory features. The receiver operating characteristic (ROC) curve was prepared using these combinations of clinical features and laboratory parameters to predict dengue. P < 0.05 was considered statistically significant.


  Results Top


The study enrolled 120 children with fever with rash, out of which the majority belonged to the age group 1 month to 3 years (43.3%), followed by 33.3% and 23.3% patients in the age range of 5–12 years and 3–5 years, respectively, the mean age being 4.2 ± 3.3 years. The male-to-female preponderance was noted with a ratio of 1.8:1. About 95.8% of patients were resident of rural area and majority belonged to socio-economic Class IV [Table 1].
Table 1: Distribution of patients according to demographic variables

Click here to view


Aetiology for the majority of the cases was observed to be viral (45%), followed by undetermined cases (35%), followed by bacterial (10%) and others (10%) which included non-infectious aetiologies such as drug reactions, Henoch–Schönlein purpura, idiopathic thrombocytopenic purpura, Kawasaki disease, leukaemia and multisystem inflammatory syndrome in children. Most common viral aetiology was dengue (15.0%), chikungunya (9.2%) and varicella (12.5%) [Table 2].
Table 2: Distribution according to definitive aetiology

Click here to view


Among dengue-positive patients, the most commonly affected age group was between 5 and 12 years (94.4%) and were predominantly males (61.1%), 55.6% of patients had maculopapular rash and 38.9% had petechial rash. All patients had headache and 83.3% of patients presented with diarrhoea and vomiting. None of the patients reported haemorrhage [Table 3].
Table 3: Clinical features in dengue negative and dengue-positive participants

Click here to view


All patients had thrombocytopenia and 88.9% of patients had leucopenia. There was no mortality among laboratory-positive dengue patients [Table 4].
Table 4: Laboratory findings in non-dengue patients and dengue IgM ELISA-positive patients

Click here to view


The various combinations of the two to six different clinical and laboratory signs involving fever and maculopapular rashes showed sensitivity and specificity ranges from 50%–55.56% to 45.1%–100%, respectively. The highest sensitivity and specificity values were found in the combination of fever, maculopapular rash, headache, no cough and thrombocytopenia (55.6% and 94.12%), followed by fever, maculopapular rash, headache, no cough, thrombocytopenia and leucopenia (with 50% sensitivity and 100% specificity). Both combinations also showed the highest values for PPV, NPV and positive likelihood ratio. Kappa agreement value was also moderate using both combinations (0.52 and 0.63, respectively) [Table 5].
Table 5: The performance of the clinical and laboratory features as a diagnostic tool in suspected dengue patients

Click here to view


Using ROC curve maximum area under the curve (AUC) was seen by fever, maculopapular rash, headache, no cough, thrombocytopenia and leucopenia (AUC 0.75 [95% CI: 0.59–0.90]) followed by fever, maculopapular rash, headache, no cough and thrombocytopenia (AUC 0.74 [95% CI: 0.60–0.89]) [Figure 1].
Figure 1: ROC curve using the different combinations of clinical and laboratory features for prediction of dengue. ROC: Receiver operating characteristic

Click here to view



  Discussion Top


In our study, out of 120 cases, laboratory-confirmed diagnosis could be established in 77 cases (64.2%), the remaining being undetermined. Therefore, a stepwise approach based on proper history taking and clinical examination including the morphology of rash will help to identify the aetiology without relying upon laboratory investigations and serological tests (specially resource-limited setup).

Dengue fever deserves a special mention which results in epidemic, especially during the monsoon season in India. It can cause illness ranging from mild symptoms to life-threatening dengue haemorrhagic fever or dengue shock syndrome.[12] As there is no vaccine or specific drug of choice against dengue infection, supportive management is the standard of care. Diagnosing dengue is often difficult because the initial symptoms are non-specific and also viraemia may be below detectable levels.[13]



In this study, the male: female ratio was 1.8:1. Dengue (21%) was the most common viral infection followed by varicella (12.5%) and chikungunya (9.2%). This study correlates well with the study done by Sultana and Kavitha Latha where the male: female ratio was 1.2:1 and 21% of patients were dengue positive, followed by chikungunya (9.3%) and varicella (12%).[14]

Osmani et al. found IgM positivity in 79.5% of dengue cases and 58.3% of chikungunya cases. Fever (100%) was the most common symptom followed by a rash (79.5%), headache (48.3%) and arthralgia (23.6%) in dengue patients.[15] Flamand et al. studied the severity of dengue epidemics in French Guiana. Among the 1356 cases, 216 (16%) were classified according to the WHO 2009 classification as dengue without warning signs (WS), 926 (68%) were classified as dengue with WS and 214 (16%) were classified as severe dengue. Fluid accumulation, aspartate aminotransferase counts >193 IU/L and platelet counts <75,000 cells/mm3 were associated with dengue severity.[16] Prabhavathi et al. concluded that out of 100 cases dengue fever was 36%. The most common presenting symptom was fever, nausea and vomiting. Pain abdomen, hepatomegaly, splenomegaly, bleeding and jaundice were seen in dengue with WS and severe dengue group. The mean white blood count was low to normal in all three groups. Platelet count was low in all groups.[17] Basurko et al. reported that a morbilliform maculopapular rash appeared in 19 children. The median time of appearance was 5 days. The platelet count was significantly higher among patients with a rash than those without a rash. Twenty-one per cent of patients with a rash had platelet counts below 25,000/mm3 versus 5% of patients without a rash. The absence of rash in children was predictive of severe dengue fever with a sensitivity of 84% and PPV of 88%.[18]

Clinical manifestations give out important information. According to the present study, a child coming with fever and maculopapular rash during the monsoon season will have 55.5% chance of testing dengue positive if the infection is truly present. Similarly, if we add up headache, absence of cough, presence of thrombocytopenia and leucopenia to these symptoms, specificity, positive as well as NPV of the test will increase with a decrease in sensitivity. Ramos et al.(2009) concluded that the presence of high fever, petechial rash or mucosal bleed in absence of cough and other respiratory symptoms has a very high PPV of confirmed dengue infection.[19]

Thus, these combined symptoms and blood counts can be used as a screening tool to diagnose dengue infection. However, laboratory confirmation is still necessary for the accurate diagnosis of dengue infection.

Identification of dengue cases in the initial phases can help in better management of the patient and subsequent prevention of the spreading of the disease. Prevention strategies include source reduction, vector control and personal protection measures.

Limitations

This study was limited to a single centre. The sample size of our study was small and included only admitted children, the prevalence in the general population could not be defined accurately.


  Conclusion Top


Maculopapular rash was noted in the majority of the participants with dengue in this study. Combined symptoms of fever, maculopapular rash, headache, absence of cough, thrombocytopenia and leucopenia can be used as a screening tool to detect dengue infection.

Acknowledgement

We extend our gratitude towards the late Prof. Dr. Jayshree Nadkarni for her general support, and we also acknowledge the laboratory services provided by the Department of Microbiology and Department of Pathology of Gandhi Medical College Bhopal, Madhya Pradesh, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kang JH. Febrile illness with skin rashes. Infect Chemother 2015;47:155-66.  Back to cited text no. 1
    
2.
Petruzella F, Easter JS. Pediatric emergency medicine literature 2020. Am J Emerg Med 2021;43:123-33.  Back to cited text no. 2
    
3.
Mohammed J. Fever and rash syndrome. J Pediatr Rev 2013;1:42-54.  Back to cited text no. 3
    
4.
Sarkar R, Mishra K, Garg VK. Fever with rash in a child in India. Indian J Dermatol Venereol Leprol 2012;78:251-62.  Back to cited text no. 4
  [Full text]  
5.
World Health Organization. Dengue Haemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. 2nd ed. Geneva, Switzerland: World Health Organization; 1997. p. 12-47.  Back to cited text no. 5
    
6.
Dengue and Severe Dengue. Available from: https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue. [Last accessed on 2021 Nov 04].  Back to cited text no. 6
    
7.
Bajwala VR, John D, Rajasekar D, Eapen A, Murhekar MV. Burden of dengue with related entomological and climatic characteristics in Surat City, Gujarat, India, 2011-2016: An analysis of surveillance data. Am J Trop Med Hyg 2020;103:142-8.  Back to cited text no. 7
    
8.
India: Case Fatality Ratio of Dengue 2020.” Statista. Available from: https://www.statista.com/statistics/1132498/india-case-fatality-ratio-of-dengue/. [Last accessed on 2021 Nov 04].  Back to cited text no. 8
    
9.
WHO Scientific Group on Nutritional Anaemias & World Health Organization. Nutritional Anaemias: Report of a WHO Scientific Group [meeting held in Geneva from 13 to 17 March 1967]. World Health Organization; 1968.  Back to cited text no. 9
    
10.
Izak M, Bussel JB. Management of thrombocytopenia. F1000Prime Rep 2014;6:45.  Back to cited text no. 10
    
11.
Hughes H, Kahl L. The Harriet Lane Handbook. 21st ed. Philadeia, PA: Elsevier; 2018. p. 373.  Back to cited text no. 11
    
12.
Gubler D. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11:480-96.  Back to cited text no. 12
    
13.
Dengue; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK143157/?report=reader#!po=25.0000. [Last accessed on 2022 Mar 28].  Back to cited text no. 13
    
14.
Sultana A, Kavitha Latha ML. Serological profile of febrile rash in patients at a tertiary care hospital in Telangana. Trop J Path Micro 2018;4:545-50.  Back to cited text no. 14
    
15.
Osmani H, Fatima A, Huneza A, Fatima S. Evaluating the febrile patient with rash in case of dengue, chickunguniya and measles in Gandhi Hospital: 2017 – 2018. Int J Contemp Med Res 2019;6:C5-8.  Back to cited text no. 15
    
16.
Flamand C, Fritzell C, Prince C, Abboud P, Ardillon V, Carvalho L, et al. Epidemiological assessment of the severity of dengue epidemics in French Guiana. PLoS One 2017;12:e0172267.  Back to cited text no. 16
    
17.
Prabhavathi R, Madhusudan S R, Suman M G, Govindaraj M, Puttaswamy M. Study of clinical and laboratory predictive markers of dengue fever and severe dengue in children. Pediatr Rev Int J Pediatr Res 2017;4:397-404.  Back to cited text no. 17
    
18.
Basurko C, Alvarez EC, Djossou F, Ardillon V, Demar M, Villeneuve C, et al. The predictive value of a maculopapular rash in children hospitalized for dengue fever in Cayenne, French Guiana. Trans R Soc Trop Med Hyg 2012;106:773-5.  Back to cited text no. 18
    
19.
Ramos MM, Tomashek KM, Arguello DF, Luxemburger C, Quiñones L, Lang J, et al. Early clinical features of dengue infection in Puerto Rico. Trans R Soc Trop Med Hyg 2009;103:878-84.  Back to cited text no. 19
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed386    
    Printed12    
    Emailed0    
    PDF Downloaded49    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]