Indian Journal of Paediatric Dermatology

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 22  |  Issue : 3  |  Page : 231--235

Mucocutaneous manifestations in dengue: A study among children at a tertiary care center in South India


Jogin Veeresh1, Sambasiviah Chidambara Murthy1, Banavasi Vishwanath2,  
1 Department of Dermatology and Venereology, Vijayanagar Institute of Medical Sciences, Ballari, Karnataka, India
2 Department of Pediatrics, Vijayanagar Institute of Medical Sciences, Ballari, Karnataka, India

Correspondence Address:
Sambasiviah Chidambara Murthy
Department of Dermatology and Venereology, Vijayanagar Institute of Medical Sciences, Ballari, Karnataka
India

Abstract

Introduction: Dengue, a viral illness, is a major public health problem. Mucocutaneous manifestations are known to occur in this illness. Over the past three decades, there has been a dramatic global increase in the incidence of dengue fever (DF). Our objective was to study the frequency and pattern of mucocutaneous manifestations of DF in children. Methodology: A total of 210 consecutive cases, which were serologically confirmed and admitted to pediatric ward over a period of 12 months (January to December 2018), were included. A detailed clinical history, examination and relevant investigations were carried out. Data were entered into a pro forma and analyzed using simple statistical methods and Chi-square test (wherever applicable). Results: The most common age group affected was 4.1–8 years with a mean age of 6.3 ± 3.9 years. Male children were more commonly affected, with majority from urban areas. Maximum cases were noted during the months from October to December, i.e., winter season. Mucocutaneous findings were noted in 112 (53.3%) cases. Cutaneous rash was present in 43 (20.1%) cases. The most common site involved was trunk, followed by face and others. Macular erythema was the most common type of rash. Onset of rash was more commonly seen in children with depleted platelet count. Ocular and oral mucosae were involved in 56 (26.7%) and 42 (20.1%) cases, respectively. Conclusion: Mucocutaneous manifestations are relatively common in children with dengue. Cutaneous rash may be a useful clinical clue for early diagnosis of dengue. Awareness of mucocutaneous manifestations helps in early recognition and proper management of dengue.



How to cite this article:
Veeresh J, Murthy SC, Vishwanath B. Mucocutaneous manifestations in dengue: A study among children at a tertiary care center in South India.Indian J Paediatr Dermatol 2021;22:231-235


How to cite this URL:
Veeresh J, Murthy SC, Vishwanath B. Mucocutaneous manifestations in dengue: A study among children at a tertiary care center in South India. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Aug 5 ];22:231-235
Available from: https://www.ijpd.in/text.asp?2021/22/3/231/319977


Full Text



 Introduction



Dengue viruses are single-stranded RNA arboviruses, belonging to the Flaviviridae family. Infection caused by any of the four serological types of dengue viruses (dengue 1–4) causes dengue fever (DF) and dengue hemorrhagic fever (DHF), which represents an increasingly important public health problem in Western Pacific regions and Southeast Asia.[1]

Mucocutaneous manifestations are increasingly recognized in patients with dengue.[2] The pattern of mucocutaneous manifestations may vary depending on several factors. Increasing number of dengue cases, with more number of admissions in pediatric age group, was found, based on the previous records, available at our hospital, which is a referral center, run by state government. There are only a very few reports in Indian as well as foreign literature on mucocutaneous manifestations of DF, which is further rarer in pediatric age group. Hence, we conducted this study among children admitted with dengue, in our hospital. The purpose of our study was to observe the frequency and pattern of mucocutaneous manifestations in children with DF.

 Methodology



This was a descriptive, case-series study. After obtaining an Institutional Ethical Committee clearance (IEC/18/2018-19), a total of 210 successive cases, which were serologically confirmed and admitted to pediatric ward over a period of 12 months (January to December 2018), were included. Data were collected by the first author, on a day-to-day basis, by visiting the pediatric ward. The data related to study variables was collected using a structured, pretested, and validated questionnaire, from the case records and interviewing one of the parents, after taking due consent and assent. The questionnaire was validated by conducting a pilot study to test the appropriateness of the questions intended to get the information which can fulfill our objective. A detailed clinical history with emphasis on fever, onset and evolution of skin lesions, was taken. A thorough mucocutaneous and systemic examinations were done. Cutaneous lesions were identified as facial flushing, macular erythema, maculopapular, and purpuric/ecchymotic rash involving different body areas. Mucosal lesions included conjunctival injection, lip and oral mucosal congestion and epistaxis. Study variables were divided into background information such as age, sex, and place. Symptomatology components such as fever, headache, swelling of face, cough, epistaxis, convulsions, vomiting loose stools, and pain abdomen. Variables related to cutaneous lesions included duration of onset of rash, morphology, distribution, relation to fever, and associated pruritus. All children ≤15 years, admitted for DF with NS1 or immunoglobulin M (IgM) positivity or both, willing to participate in study were included. Those with dengue-like illness with negative NS1 and IgM, were excluded. Based on the age, children were grouped into <1 year, 1–4, 4.1–8, 8–12, and more than 12 years. Those children coming from places with a population more than 50,000 were considered as urban, while <50,000 as rural. Relevant investigations such as complete hemogram, blood sugar levels, liver function tests, renal function tests, urine routine, serum electrolytes, dengue serology (NS1 Ag, IgM, and IgG Ab) were done for all. Skin biopsy was done in a single child, after obtaining an informed consent, to study the histopathological features of the rash. Data were entered into an Excel sheet. After appropriate data filtration, it was analyzed using SPSS software version 20 (IBM SPSS statistics for windows, version 20.0: IBM Corp., Armonk, NY). O. Descriptive statistics like percentage/proportion, mean, ratio and standard deviation were used to describe study variables. Inferential statistics like Chi-square was applied to know the association between study variables. A P < 0.05 at 95% confidence limit was considered to be statistically significant.

 Results



Among a total of 210 children included, there were 118 (56.2%) male and 92 (43.8%) female children. Their age distribution is shown [Table 1]. The most common age group affected by dengue was, 4.1–8 years followed by 1–4 years. The youngest patient was 3.6 months and the oldest; 14 years of age (mean age, 6.3 ± 3.9 years). Although both sexes were affected, male children were more commonly affected (male to female ratio, 1.2:1). Patients hailed from both urban (118; 56.2%) and rural (92; 43.8%) areas, although children hailing from urban areas were more commonly affected. Maximum number of cases, 137 (65.2%) were noted during months, from October to December (winter season). Fever was present universally in all cases followed by cough, headache, swelling of face, epistaxis, headache, cough, and convulsions. Gastrointestinal symptoms were present in 108 (51.4%) cases. Vomiting was the most common symptom, followed by loose stools and pain abdomen. Pruritus was an uncommon manifestation. Skin involvement in the form of rash, was seen in 43 (20.5%) cases. The mean duration of onset of rash after fever was 2.5 ± 2 days. Most common site affected by rash was trunk, followed by face, and other parts [Table 2]. Macular erythema [Figure 1] was the most common type of rash, followed by maculopapular and purpuric rash [Table 3]. Palms and soles were less frequently affected by rash. Oral involvement was seen in 42 patients (20.1%) [Figure 2] and ocular mucosal involvement in 56 (26.7%) and nasal involvement in one child (2%). Onset of rash was more commonly seen in children with depleted platelet count. We found onset of rash to be more common in children with platelet count <50,000 (P = 0.00165) [Table 4]. The proportion of rash was more in infants (30.4%) and in the age group of 8–12 years (25.6%) compared to other age groups [Table 5]. However, this distribution of rash with respect to different age groups was not found to be statistically significant (P = 0.433). Rash was more common among female children, with male to female ratio of 0.79:1. Rash was seen in both urban (26; 60.5%) and rural (17; 39.5%) children, however, children hailing from urban areas were more commonly affected by rash and it was statistically insignificant (P = 0.606). Biopsy from a 9-year old female child, showed, moderately dense superficial perivascular infiltrate of lymphocytes, histiocytes, occasional eosinophils with focal interface vacuolar change and occasional necrotic keratinocytes. The epidermis also showed mild spongiotic psoriasiform changes and focal parakeratosis [Figure 3].{Table 1}{Table 2}{Table 3}{Table 4}{Table 5}{Figure 1}{Figure 2}{Figure 3}

 Discussion



Dengue is one of the most important human arboviral diseases transmitted by arthropod vectors. Annually, there occurs an estimated 50–100 million cases of DF, and 2,50,000-5,00,000 cases of DHF in the world. Over half of the world's population live in areas at risk of infection. DF and DHF are caused by the four dengue viruses DEN 1, 2, 3, and 4, which are closely related antigenically. Infection with one serotype provides life-long immunity to that virus but not to the others. Dengue viruses are maintained in an urban transmission cycle in tropical and subtropical areas by the mosquito Aedes aegypti, a species closely associated with human habitation.[3]

Cutaneous manifestations may be seen in 50%–82% cases of DF. A maculopapular, scarlatiniform, or morbilliform rash has been observed in the febrile phase of the disease. Petechial and hemorrhagic manifestations have also been reported. Mucosal involvement has been estimated to occur in 15%–30% of patients.[2] Skin lesions may be the presenting feature of DF and can be helpful in the diagnosis of the disease. Hence, a clear understanding of these skin manifestations is required for clinicians to diagnose and treat the condition accordingly.[2]

Regarding serological profile, all of our cases were positive for NS1 Ag or IgM Ab or both. The study made use of two commercial kits available, namely the Marathwada Reference Laboratory (MRL), Aurangabad, enzyme-linked immunosorbent assay (ELISA), Pan Bio ELISA kits, which have shown high degree sensitivity and specificity in the global testing center and are highly recommended for the purpose. Serology with clinical presentation and other investigations forms the mainstay of diagnosis. IgM ELISA has always been one of the gold standard test for diagnosis.[4] Dengue like illness can also be seen in various other disease such as Chikungunya, O' nyong nyong fever, west nile fever. Hence, we included only children with positive serology for dengue. Uptil now, only a few studies involving both children and adults are available regarding the spectrum of cutaneous features of dengue infection.[2]

Although high incidence of DF has been described in children, there are no studies done exclusively on them. The 4–8 years of age group was predominantly affected in our study, accounting for 33.8% of the total cases. The mean age affected was lower in our study compared to earlier studies.[2],[5],[6] The mean age of 6.3 ± 3.9 years was seen in our study. In an earlier study from Pakistan, involving both adult and child population, majority of patients (48%) were in range of 21–40 years.[5] Another similar study from Pakistan had majority belonging to the age group of 21–30 years, with a mean age of 34.88 ± 15.14 years.[2] Another study from Lahore, Pakistan showed, the most common age group affected to be 11–20 years, with a mean age of 31 ± 15 years.[6] This difference in the mean age of involvement is due to the difference in the age groups of population studied.

The incidence of DF in our study was more among male children, similar to earlier studies.[2],[5],[7] This can be attributed to the more outdoor playful activity tendencies seen in children.[8] We found children hailing from urban areas to be more commonly affected, similar to other studies.[9] Rapid urbanization, population growth, increase in usage of nonbiodegradable products that can serve as sites for mosquito larva proliferation and global warming are the factors hypothesized for increasing incidence of DF in urban area.[9]

Maximum number of cases were registered during months from October to December, accounting 65.2% of total cases in our study. Earlier studies had proved monsoon and post monsoon months as a period of maximum activity of Aedes aegypti.[10],[11] This trend well correlates with post monsoon surge of dengue illness. The seasonality of transmission of dengue with increased activity in the post monsoon season was seen in our study also. This is due to the presence of stagnating water sources following heavy rainfall favoring breeding of the mosquito vectors resulting in an increased incidence of dengue. Otherwise also, the cases were recorded throughout the year including dry months, again pointing towards round the year activity of mosquito vector. Even minimal collection of water sources can favor breeding of vectors thereby helping in the maintenance of the vector population throughout the year. The disease may be considered as perennial, although the peak occurs during the postmonsoon season. Vijayakumar, et al. showed that Dengue IgM positive cases were prevalent throughout the year except for a few occasional months.[8]

The overall mucocutaneous involvement was seen in 53.3% of cases, while only skin involvement was seen in 20.5% of cases. In an earlier study involving both adults and children,[6] mucocutaneous affection was found to be 77.1%, which showed slightly higher involvement. Skin alone was found to be involved in 6.25% of their cases which was lower than our study. Among the mucous membrane involvement, oral mucosal was involved in 66.7%, ocular in 70.8%, and nasal involvement in 5% of their patients which was much higher than our patients. Another similar study from Pakistan showed 68% mucocutaneous involvement.[5] They found cutaneous involvement in 38% of their patients, which was slightly more than our study, while mucosal involvement alone was seen 28% of their patient, almost similar to our study. These differences could be due to variations in sampling methods, population studied and racial factors.

The mean duration of appearance of rash after fever was 2.47 ± 2 days. Macular erythema was the most common type of rash, which was seen in majority, followed by maculopapular rash and purpuric lesion. Macular erythema (flushing) typically occurs within 24–48 h of onset of fever and is thought to be the result of capillary dilatation. The second rash usually occurs 3 to 6 days after onset of fever and is characterized by asymptomatic maculopapular or morbilliform eruption. In some cases, multiple lesions coalesce to form large area of confluent erythema with rounded islands of sparing, which is described as “white islands in sea of red” and is thought to be due to immune response to virus. Some patients display only the initial rash and recover completely, while others develop the more generalized eruption. The generalized rash characteristically starts on the dorsum of hands and feet, spreads to arms, legs, and torso. It lasts for several days and subsides without desquamation. Maculopapular rash and purpuric lesion was observed in one male child each, but DF has been rarely mentioned as cause of purpuric lesion. Hence, DF should keep in mind as cause, while evaluating a case of purpura. Palms and soles involvement were less common.[5],[12]

Earlier study by Khan et al., observed exanthema in 38% of patients. Macular erythema was the commonest exanthema seen in 39% of patients, followed by facial flushing (20%), petechiae (20%), maculopapular rash (19%), and ecchymosis (2%). Macular erythema or flushing was the earliest and commonest exanthema observed.[5] In another similar study, rash was seen in 42.9% of patients. Generalized maculopapular rash was seen in 31.7%, papular rash in 11.2%, petechiae in 20%, and ecchymosis in 13.8%.[2] Another study from Pakistan found skin rash in 83.33% patients, 1–6 days after onset of fever. Morbilliform rash and morbilliform rash with purpura was seen in 64.58% and 12.5% of patients, respectively.[6] This difference could possibly be due to the variations in sampling methods, population, environmental, and racial factors. We took a biopsy in a 9-year-old girl, from a representative area, which showed the involvement of both epidermis and dermis. None of the previous studies have attempted to study the histological features. This is possibly due to the bleeding tendencies among these patients.

Mucosal involvement was seen 32.9% of our cases. Ocular mucosa was more commonly involved followed by oral mucosa. Palpebral conjunctival injection, oral mucosal congestion involving buccal mucosa, erythema, and crusting of lips were the findings in our study. Similar pattern was observed in previous studies, while features like small vesicles on soft palate, erythema, and crusting of tongue, were not seen by us.[13]

In an earlier study, enanthema was seen in 28% of patients. Erosion of hard palate was the commonest enanthema, seen in 49% of patients.[5] Another study showed that mucosa were involved in 40.66% patients; 52.46% patients had involvement of more than one mucosa. Oral mucosa (43.58%) was most frequently involved. The major finding was erythema of the buccal mucosa and palate. Nasal, conjunctival, and genital mucosal involvement were observed in 20.15%, 16.92%, and 1.54% of their patients, respectively.[2]

Another similar study from Pakistan showed mucous membrane involvement with or without skin involvement in 85.38% of patients. Among various mucous membranes involved, congestion of oral mucous membrane was observed in 66.7%, conjunctival injection and nasal mucous membrane congestion with bleeding was seen in 70.88% and 5% of patients, respectively. Gingival hyperemia and bleeding were seen in two of their patients.[6]

Most of the patients with mucocutaneous manifestations were asymptomatic, only a few cases complained of itching in our study. In a study by Azfar et al., generalized pruritus was observed in 69.2% patients. This was followed by burning sensations in hands and feet seen in 64.6% of patients.[2] There are no studies conducted on mucocutaneous manifestations of DF exclusively in children, to compare, to the best of our knowledge.

Onset of rash was more common in children with depleted platelet count. Rash was more commonly seen in those with platelet count < 50,000 (P = 0.00165). Onset of rash may be an indirect cutaneous indicator of depleted platelet count. However, Khan et al., observed no relationship between the onset rash and platelet count.[5] Our study had a limitation in that, the sample size was small.

 Conclusion



Dengue is a common childhood viral exanthema, with varied mucocutaneous features. Mucocutaneous involvement was seen in 55.3% of our cases. Macular erythema was the commonest pattern of rash, followed by maculopapular and purpuric lesion. Onset of rash may be directly related to the depletion of platelet count. Awareness of mucocutaneous manifestations helps in early recognition and proper management of dengue.

Acknowledgment

We would like to thank Dr. Raghavendra B, Department of Preventive and Social Medicine, for his valuable statistical advice and Dr. Uday Khopkar, Mumbai, for his valuable histopathological opinion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Cam BV, Fonsmark L, Hue NB, Phuong NT, Poulsen A, Heegaard ED. Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever. Am J Trop Med Hyg 2001;65:848-51.
2Azfar NA, Malik LM, Jamil A, Jahangir M, Majid A, Ashraf M, et al. Cutaneous manifestations in patients of dengue fever. J Pak Assoc Dermatol 2012;22:320-4.
3Rigau-Pérez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. Dengue and dengue haemorrhagic fever. Lancet 1998;352:971-7.
4Guzmán MG, Kourí G. Dengue diagnosis, advances and challenges. Int J Infect Dis 2004;8:69-80.
5Khan AR, Khan SR, Sohail M. Frequency of mucocutaneous manifestations in dengue fever patients. KJMS 2018;11:118-21.
6Mahboob A, Iqbal Z, Javed R, Taj A, Munir A, Saleemi MA, et al. Dermatological manifestations of dengue fever. J Ayub Med Coll Abbottabad 2012;24:52-4.
7Guha-Sapir D, Schimmer B. Dengue fever: New paradigms for a changing epidemiology. Emerg Themes Epidemiol 2005;2:1.
8Vijayakumar TS, Chandy S, Sathish N, Abraham M, Abraham P, Sridharan G. Is dengue emerging as a major public health problem? Indian J Med Res 2005;121:100-7.
9Murray NE, Quam MB, Wilder-Smith A. Epidemiology of dengue: Past, present and future prospects. Clin Epidemiol 2013;5:299-309.
10Narayanan M, Aravind MA, Thilothammal N, Prema R, Sargunam CS, Ramamurty N. Dengue fever epidemic in Chennai – A study of clinical profile and outcome. Indian Pediatr 2002;39:1027-33.
11Gomber S, Ramachandran VG, Kumar S, Agarwal KN, Gupta P, Gupta P, et al. Hematological observations as diagnostic markers in dengue hemorrhagic fever – A reappraisal. Indian Pediatr 2001;38:477-81.
12Thomas EA, John M, Kanish B. Mucocutaneous manifestations of dengue fever. Indian J Dermatol 2010;55:79-85.
13Roopashri G, Vaishali MR, David MP, Baig M, Navneetham A, Venkataraghavan K. Clinical and oral implications of dengue fever: A review. J Int Oral Health 2015;7:69-73.