Introduction
Atopic dermatitis (AD) is one of the most common childhood skin disorders. This disorder is characterized by itchy eczematous lesions and intermittent disease flare-ups. AD can be associated with psychological stress, low self-esteem, and sleep deprivation leading to a significant reduction of the quality of life of patients and families.[1]
AD is quite common in western countries where it affects up to 20% of children.[23] There has been an increase in the prevalence of AD in Asian and African countries also.[45]
The pathophysiology of AD involves a complex interplay between a dysfunctional epidermal barrier, skin microbiome abnormalities, and a predominantly Type-2-skewed immune deregulation.
Birth cohort studies done to evaluate the influence of genetic and environmental factors for AD points toward the genetic influence on AD. It has been shown that inheritance may be preferentially through the maternal line.[6]
Many environmental factors can provoke the worsening of AD in individual patients. Those factors can be cited as irritants, climatic factors, infections, psychological stress, food allergens, aeroallergens, and contact allergens in sensitized patients.[2]
Allergens responsible for flare-ups may differ in different geographical settings.
Genome-wide association study of self-reported food allergies done in Japan has identified shrimp and peach-specific loci in the HLA-DR/DQ gene region.[7]
Peanut allergy is common in European countries. In a study done by Howe et al. significant associations with peanut allergy were reported for the HLA Class II DR beta 1, DQ beta 1(HLA-DQB1) and Dermatophagoids pteronyssinus DP beta 1(HLA-DPB1) gene polymorphisms.[8]
Comparing food allergens and aeroallergens as the predominant culprit in AD, different studies have come up with contrasting results.
Some studies have demonstrated the predominance of food allergens, Where Cow’s milk (CM), hen’s egg, peanut, wheat, soy, nuts, and fish are responsible for >90% of food allergy in children with AD.[9] While certain other studies done on patients with AD have shown significant IgE sensitization to aeroallergens.[1011]
Suspicion of food allergens as a factor responsible for flare-ups may lead to food restrictions.
Not all food induces AD symptoms.[12] Nondiagnosis and incorrect diagnosis of food allergens may lead to a restricted diet. A restricted diet continued due to incorrect diagnosis, can thus delay the growth of the atopic children and possibly cause nutritional deficiency.[1314] If the allergen is not identified correctly, it will invariably delay the successful treatment of AD.
The detection of aero and food allergen sensitization is done using Skin prick testing (SPT) and serum-specific IgE levels. When there is a severe skin disease, or if the patient is on continuous medications also if the risk for anaphylaxis is high, SPT does not serve the purpose, and serum-specific IgE levels will be helpful to detect the culprit allergen.[159] Yet, serum-specific IgE involves laboratory testing, takes time to give the results and cost factor is high. In contrast, SPT provides quick results, has greater flexibility, and comparatively it is of low cost.[15]
There is a dearth of studies on allergen sensitization pattern in patients with AD in Sri Lanka. This study was designed with the aim of identifying the patterns of aero and food allergen sensitization in patients with AD.
Objective
The objective is to assess the food and aeroallergen sensitization pattern of children with AD.
Materials and Methods
Setting
This study was done at the pediatric dermatology clinics of Sirimavo Bandaranayaka Specialised Children’s Hospital, and National Hospital Kandy, Sri Lanka, from April 2019 to December 2019.
Inclusion criteria
Consecutive patients referred to the clinic during the period were screened. Patients over 1 year of age and clinically diagnosed to have AD by a consultant dermatologist, were recruited for the study.
Sample size
The sample size was calculated as 100 by the following formula ;)
in order to achieve a precision of 10% and power of 90%.[16]
Prior to the recruitment of children to the study, informed written consent was obtained from the parents.
Basic demographic information including age, gender, time of diagnosis of AD, severity by means of the SCORAD score, family history of AD, and details about food allergy were collected. After recruitment to the study, the SPT was carried out for all the patients.
Skin prick test procedure
SPT was conducted in accordance with the standards stipulated by the Global Allergy and Asthma European Network.[15] Patients were requested to refrain from the use of oral antihistamines for 5 days preceding, to avoid interference with the test and interpretation of the results. All the SPTs were carried out by the same investigator who had special training and experience in techniques of allergen testing. Commercial extracts of CM, egg white, peanut, Dermatophagoids pteronyssinus, cat epithelium, and Aspergillus fumigatus were used in the SPT.
The location of each prick was marked with a pen on the forearm to properly identify test results. Test solutions were applied to the volar aspect of the forearm, at least 2–3 cm from the wrist and the antecubital fossa. The distance between two SPTs was kept more than 2 cm to prevent cross contamination. A drop of each test solution was placed on the skin in identical order for each subject tested and immediately pricked by means of a single-head metal lancet. The single-head metal lancet was pressed through the drop of allergen extract. There the lancet was held against the skin with equal pressure applied for each test being careful not to induce bleeding. A new lancet was utilized for each allergen to prevent cross-contamination. Excess solution from drops on the skin was blotted using a clean tissue. No cross-contamination was assured to prevent problems of results and interpretation. All the patients were tested for CM, EW, peanut, Dermatophagoides pteronyssinus, cat epithelium, and AF. Histamine and normal saline were taken as positive and negative controls, respectively. The results of all the tests were read in 15 min using a timed alarm. Positive and negative controls were measured first by means of a horizontal marked ruler in mm. The histamine control was used to ensure that the test materials were applied correctly. And to exclude negative SPT results due to potentially interfering medications taken by the test subject. The largest diameter of the wheal of each particular test was measured. Wheal measuring 3 mm or more, than the negative control was taken as a positive result.[15]
Analysis
The data were analyzed using the percentages, Fisher’s exact test, chi square test and Pearson correlation tests. The statistical software used was SPSS version 22.
Ethical clearance
Ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Peradeniya (No: 2018/EC/46), Sri Lanka.
Results
A total of 100 patients underwent SPT. Out of them, 60% were over 5 years of age. Moreover, 60% had AD for over 1-year duration. Meanwhile, 25% had a positive family history of AD. Moderate-to-severe AD was found in 89% of the patients [Refer Table 1].
Table 1: Demographic table
Forty-one percent of the parents of AD patients were in the belief that their children are having food allergy. And had food restrictions on the suspicion of food allergy.
In this study, it was found that 62 (62%) of the patients were positive for at least one allergen. Results of the SPT revealed positivity for DP in over half of the patients (53%). Second common allergen sensitization was for cat epithelia (15%) followed by Aspergillus (9%). However, it was interesting to find very low positivity for food allergens. CM-9%, peanut-1%, and EW-2% [Refer Table 2].
Table 2: Skin prick test results
The most common allergen sensitizations, (HDM and CE) were analyzed further for any association with gender, age, and family history of AD. However, there was no significant difference noted in HDM positivity with gender, family history of AD, or age [Refer Table 3].
Table 3: Association with allergen sensitization and disease background
Wheal sizes of SPT for each allergen were analyzed for any association with age. It was interesting to note that there was a significant positive correlation with wheal sizes of HDM with age (P = 0.007) [Refer Table 3 and Figure 1].
Figure 1: Age versus skin prick test wheal size.
Discussion
Spectrum of allergen sensitization: Food allergy versus aeroallergen, the contrast of tropics with temperate countries
In this study, nearly two-thirds of patients (62%) have positivity for at least one allergen. The largest number of patients (53%) demonstrate sensitization toward house dust mite-D. pteronyssinus.
Research conducted in other tropical and European countries have shown similar as well as contrasting results.
Studies done in Brunei and Brazil have revealed that the most prevalent allergens as D. pteronyssinus followed by Dermatophagoides farinae and Blomia tropicalis.[1117]
In a study carried out in Hong Kong with 816 subjects, 90% had atopic sensitization to at least one aeroallergen and 69% to at least one food allergen.[18] Again, the HDMs were the most prevalent allergen.[18]
These studies are in contrast to many European and American studies which demonstrate a higher prevalence of sensitization toward food-related allergens.[19] In a study carried out in Europe and North America food allergy has been well documented in approximately one-third of children with moderate-to-severe AD. The incidence and the type of food allergy vary with age. The most common food allergens in infants are CM, hen’s egg, peanut, and soy, whereas, in older children it is wheat, fish, tree nuts, and shellfish.[9]
Similarly, in a study done in Korea, the highest sensitization was found for food allergens. 76.4% was found positive for EW followed by 58.4% for milk. While 49.1% were positive for aeroallergens, D. farinae, and 46.6% for D. pteronyssinus.[20] Furthermore, a study carried out in Taiwan, in children younger than 2 years, AD was associated with food allergens.[21]
The aeroallergen predominance found in our study and those studies done in Brazilians and Brunei versus the food allergen predominance found in studies done in Europe, US, Korea, and Taiwan is interesting to note. It could be explained as a difference between tropical and temperate climates, yet Taiwan which is a subtropical island does not exactly fit into that explanation.
Alternatively, it could be viewed as a difference between lifestyles. Korea and Taiwan in the current day have a more western-influenced lifestyle as opposed to the tropical countries concerned.
The current study revealed that the sensitivity for food allergens in patients with AD is very low (<9%). A possible explanation may reside in exclusive breastfeeding in the first 6 months of life. In previous research, it has been revealed that exclusive breast feeding of ≥4 months might have a preventive effect on the development of food allergy in children.[22]
The different sensitization patterns in different countries emphasize the importance of research to establish sensitization patterns in different geographical areas. The finding of aeroallergen predominant sensitization pattern in the current study is clinically important in managing patients. The low positivity for milk, egg, and peanut has a significant clinical relevance. Many parents tend to think that children are allergic to those food items when faced with an atopic illness. And try to limit the consumption of many food varieties. This could lead to nutritional deficiencies as well as poor quality of life, as the child is being deprived of childhood delicacies. Hence, in clinical decision making, it is important to have a good knowledge on common allergen sensitizations pattern. At the same time, this knowledge is important in educating both the patient and the parents. Which is pivotal in having a good disease control with a good quality of life for the child.
Age and skin prick test wheal size
The current study has shown that the wheal size of HDM has a highly significant positive correlation with age. In a previous study by Chauveau et al., it has been found that skin allergenic reactivity is transient at 1 year and increased as children grew older.[12] This has clinical implications. The wheal sizes in younger children could be smaller than adults. It should be interpreted carefully to avoid any false negativity. Studies with larger sample size is needed to identify age-related cut off values for SPT wheal sizes.
Age and house dust mite sensitivity
Several studies have shown differences in allergen sensitization in different age groups. The HDM sensitization is more prevalent in older children than infants with AD.[9] A study done in Hong Kong has found that aeroallergens are more prevalent than food allergen sensitization among children older than 10 years.[18]
In a study done in Taiwan, it has been found that the age correlates negatively with food allergens and positively with aeroallergens (P < 0.04).[21] However, in our study, there is no significant difference in HDM sensitivity among children younger and older than 5 years. The clinical importance is that HDM sensitization needs to be suspected in children with AD regardless of age.
Burden of house dust mite sensitivity in atopic dermatitis, house dust mite exposure prevention, and immunotherapy
The current study has shown the burden of HDM sensitization in children with AD.
A study done by Teplitsky et al. has also shown that patients with AD showed a higher prevalence of mites on their skin than did healthy individuals, which could be involved in allergic sensitization and disease exacerbation.[23]
These findings indicate a possible role for HDM exposure prevention and HDM immunotherapy in successful secondary prevention and control of the disease.
Controversies around house dust mite exposure prevention
However, guidelines of care for the management of AD published in 2013 by the working group Eichenfield et al. mentions that “patients with AD are often sensitized to HDMs, yet there is no strong evidence to show that dust mite avoidance strategies prevent AD.”[24]
This statement is based on a study done by Harris et al.[25] In this study, concentrations of HDM and CE have been estimated in dust samples from the household at 8 weeks after birth. Then, subsequent eczema has been assessed at 8 years of age with no assessment in between.
The risk of subsequent eczema has been determined according to different levels (quintiles) of allergen exposure at 8 weeks from birth. It has been determined that there is no clear exposure–disease relationship between allergen exposure in early life and subsequent AD. Yet it is questionable as this recommendation is based on a single-point assessment of allergen exposure, especially in the presence of other studies which reveals that aeroallergen sensitivity showing a positive correlation with age.[21] The current study also shows a highly significant positive correlation of HDM wheal size with age.
Thus there is a need for robust studies to determine the HDM exposure prevention and primary and secondary prevention of AD.
Conclusion
Moderate and severe AD in children shows significant association with HDM and CE sensitivity. When patients presented with flared up symptoms of AD, clinician get tasked with finding a causal etiology. Going by the current findings, it is quite possible to get a positive answer for the key question, if SPT is done for HDM and CE. Thus, the findings of this paper is likely to facilitate the clinical management of AD.
Declaration of consent
The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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