|Year : 2017 | Volume
| Issue : 4 | Page : 81-85
Airway disease and environmental aeroallergens in eczematics approaching adulthood
Ellis Kam Lun Hon1, Meiruo Liu2, Benny Zee2
1 Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong, China
2 Division of Biostatistics, Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China
|Date of Web Publication||5-Feb-2018|
Ellis Kam Lun Hon
Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong
Source of Support: None, Conflict of Interest: None
Background: Atopic eczema (AE) is one of the most common skin diseases affecting children and adults worldwide. The “Atopic March” paradigm suggests AE is part of a complex condition with related airway disease. Objective: This study aimed to evaluate the prevalence of airway disease, environmental aeroallergens, and review factors associated with eczema severity and quality of life (QoL) when AE patients approached adulthood. Methods: Patients who were diagnosed with AE at a young age were included in the study and followed up till their adolescence at pediatric dermatology clinics from 2000 to 2017. Demographic characteristics, clinical laboratory parameters, treatment history, personal atopic history, as well as disease outcomes assessed by Nottingham Eczema Severity Score (NESS) and Children Dermatology Quality Life Index (CDLQI) were reviewed. Results: Three hundred and eighty-three patients (55.4% males) with latest NESS at mean (standard deviation) age 16.23 (2.50) years were reviewed. Personal history of asthma (45%), allergic rhinitis (74%), and family history of atopy were prevalent. Seventy-two percent of the patients were skin prick testing positive for house dust mite, 27% for cockroach, 33% for cat fur, and 13% for dog fur. Fourteen percent reported “smokers in family”. Multiple logistic regression showed “food avoidance ever” (adjusted odds ratio [OR] =3.00, 95% confidence interval [CI] =1.08–8.32; P = 0.035) and log-transformed immunoglobulin E (IgE) (adjusted OR = 1.45, 95% CI = 1.09–1.92; P = 0.011) were significantly associated with more severe AE. Linear regression showed “food avoidance ever” (β = 1.79, 95% CI = 0.34–3.24; P = 0.016), higher log-transformed IgE (β = 0.62; 95% CI = 0.22–1.03; P = 0.003), dog dander sensitization (β = 2.07, 95% CI = 0.24–3.89; P = 0.027), and severe disease (β = 2.97, 95% CI = 2.26–3.68; P < 0.001) were significantly associated with QoL impairment. Conclusions: A number of patients do not grow out of their eczema, and many of them have allergic rhinitis and asthma co-morbidities. Toward adulthood, AE severity and QoL are associated with food avoidance and high IgE, but generally independent of family or personal history of airway disease and allergen sensitization. Blood IgE measurement may help assess the risk for more severe eczema when patients are becoming adults.
Keywords: Adult, asthma, allergic rhinitis, aeroallergen, atopic eczema, Children Dermatology Life Quality Index, Nottingham Eczema Severity Score, prognosis
|How to cite this article:|
Lun Hon EK, Liu M, Zee B. Airway disease and environmental aeroallergens in eczematics approaching adulthood. Pediatr Respirol Crit Care Med 2017;1:81-5
|How to cite this URL:|
Lun Hon EK, Liu M, Zee B. Airway disease and environmental aeroallergens in eczematics approaching adulthood. Pediatr Respirol Crit Care Med [serial online] 2017 [cited 2018 May 21];1:81-5. Available from: http://www.prccm.org/text.asp?2017/1/4/81/224778
| Introduction|| |
Atopic eczema (AE) or atopic dermatitis is a chronically relapsing skin disorder affecting children and adults worldwide, with clinical symptoms of rash, inflammation, dry skin, and itch.,, It is one of the most common skin diseases with global prevalence of 7.9% according to a cross-sectional questionnaire survey (International Study of Asthma and Allergies in Childhood Phase Three [1999–2004]), which showed an increasing trend comparing to the global prevalence of 6.1% reported in Phase One (1992–1997). In Hong Kong, AE prevalence among children aged 6–7 years old increased from 3.9% to 4.6%, and among children aged 13–14 years old from 2.7% to 3.3%.
With the increasing prevalence of AE, there are grave individual and social sequelae in terms of quality of life (QoL), financial, academic, and occupational burdens.,, For children with AE, not only physical symptoms such as itching, scratching, and sleep disorder impact their daily life but also psychological pressure such as social isolation, low self-esteem, and low self-confidence., The impacts of eczema including economic burdens and QoL impairment are not only confined to the patients but also to their families. In most cases, families, especially parents with young AE patients would spend substantial financial costs, time, and effort in caring for them.
The etiology of eczema is complex, involving both genetic and environmental factors. Genetic mutation and environmental stimuli impair skin barrier, which ultimately manifests as eczema. Researches focusing on eczema etiology attract great attention because the elucidation of eczema pathophysiology would potentially lead to novel therapeutic strategies. The filaggrin gene (FLG) encoding a structural epidermal protein, along with a set of other proteins comprising epidermal differentiation complex, plays an important role in the intactness of skin barrier. Recent studies gave evidence that loss-of-function mutation in FLG gene is associated with eczema.,
Epidemiologic researches on eczema identified a number of environmental risk factors including climate, diet, lifestyle, microbial agents, aeroallergens, and stress. Aeroallergens such as house dust mite (HDM), pet fur, pollen, and smoke have been studied. Broad spectrum antibiotic abuse might alter gut microbiota and lead to eczema exacerbation. High fat, low fruit and fish intake might be associated with increasing risk of eczema, there is no consistent evidence on the protective effect of exclusive breastfeeding.
It is a popular notion adopted by some parents and clinicians that children will outgrow eczema when they reach adolescence, but some long-term follow-up studies do not concur with this point of view. In a cross-sectional and cohort study targeting long-term registry of childhood eczema in the United States, it is concluded that eczema is probably a lifelong disease which persists into the second decade of children's life. A Hong Kong study similarly shows that eczema may persist when children grow older. However, the follow-ups for both studies are too limited to draw conclusion on the progression of eczema when patients are reaching adulthood. According to the “Atopic March” paradigm, AE is part of a complex condition with related allergic hypersensitization involving the airways.,, This study aimed to evaluate the prevalence of airway disease, environmental aeroallergens, and factors associated with eczema severity and QoL when AE patients approach adulthood.
| Methods|| |
Demographic characteristics of AE patients who were followed at the pediatric dermatology clinics of a teaching hospital between 2000 and 2017 to at least 16 years of age were reviewed. Patients diagnosed with AE were included in the study. Clinical information was recorded by the physicians on their first visit by means of clinician history taking, questionnaires, and laboratory tests which included disease severity, QoL, family and personal history of atopy, household pets, smoking, and therapeutic data. Clinical laboratory parameters included blood immunoglobulin E (IgE) (highest if multiple measurements), eosinophil counts, and skin prick testing if available.
Eczema onset age, prematurity, family atopy history, pets keeping, food avoidance, history of treatment (traditional Chinese medicine [TCM], immunomodulant, and wet wrap), feeding (breastfeeding or formula feeding) were recorded in clinicians' consultations over the years.
Eczema severity is assessed by Nottingham Eczema Severity Score (NESS), which is a self-administered questionnaire with score ranging from 3 to 15, that divides patients into mild, moderate, and severe categories., The validated Cantonese version of NESS questionnaire shows good agreement with SCORing Atopic Dermatitis (SCORAD). The secondary outcome is assessed by Children Dermatology Life Quality Index (CDLQI), which is a questionnaire measuring the QoL of patients with skin disease. Validation of the Cantonese version CDLQI shows that CDLQI scores correlated with physician-rated disease severity with good test-retest correlation (P< 0.01).,
Patients younger than 10 years of age or older than 22 years (if no prior NESS measurement) were excluded, and the characteristics of included and excluded patients were compared to assure that there is no substantial difference between them.
One-way ANOVA (Kruskal–Wallis one-way ANOVA for nonparametric data) was conducted to assess the association between categorical (more than three levels) and continuous variables. For binary and continuous variables, two sample t-test (Mann–Whitney test for nonparametric data) was performed. Chi-square test (Fisher's Exact test for nonparametric data) was applied to investigate the association of categorical variables. Simple logistic regression was carried out to assess factors influencing odds for mild eczema versus moderate or severe disease. Multiple logistic regression was performed taking into account of sex, AE onset age, mother atopy status, breastfeeding ever, smoker in family ever, food avoidance ever, skin prick test (SPT), and highest IgE. Linear regression was performed to assess the effect of each factor with CDLQI. P< 0.05 was considered statistically significant. The University ethics committee approved this review.
| Results|| |
Totally 403 eczema patients were reviewed, 383 of whom with mean (standard deviation [SD]) age 16.23 (2.50) years were analyzed [Table 1].
|Table 1: Demographics and clinical factors associated with atopic eczema severity toward adulthood|
Click here to view
When these patients approached adulthood, 123 patients had mild eczema, 137 patients with moderate eczema, and 123 patients with severe eczema. The percentage of male increased with more severe disease, which was 48.4% in mild group, 57.4% in moderate group, and 61.7% in severe group (P = 0.037). AE onset age was significantly associated with eczema severity, and patients with early disease onset (usually <1-year-old) generally had more severe AE in adolescence. The proportion of patients with treatment history including wet wrap, TCM, immunomodulant, and food avoidance increased with more severe eczema level (P ≤ 0.001).
About 48.3% of eczema patients had asthma comorbidity, while the proportion did not differ between groups (P = 0.637); 78% of patients had allergic rhinitis, the difference of proportion between groups was not significant (P = 0.175).
64.6% of patients with mild eczema had reported they had food allergy, with 73.2% in moderate group, and 81.6% in severe group (P = 0.013).
Eosinophil percentage and highest IgE were both significantly associated with more severe eczema (Kruskal–Wallis test, P < 0.001).
SPT assessed sensitization to cat dander, dog dander, cockroach, house dust mite (HDM), and foods: 40.2% for cat, 16.0% for dog, and 33.7% for cockroach. Most patients were sensitized to HDM (88.4%). There was a significant association between HDM sensitization and eczema severity (P< 0.001). Sensitization to common foods occurred in 72.8% of patients, and the trend was not significantly associated with more severe disease (P = 0.085).
Multiple logistic regression was conducted to assess the adjusted odds ratio (OR) of mild eczema versus moderate or severe disease [Table 2]. Controlling for gender, AE onset age and mother atopy status, the adjusted OR for food avoidance ever was 3 (95% confidence interval [CI]: 1.08–8.32), and the adjusted OR for log-transformed IgE was 1.45 (95% CI: 1.09–1.92). None of the other clinical factors reached significance.
|Table 2: Multiple logistic regression analysis of patient characteristics on atopic eczema severity|
Click here to view
There were 247 patients with CDLQI data when they reached adolescence. Regression analysis showed that CDLQI increased by 1.79 point on average with food avoidance ever (P = 0.016) and by 0.62 per unit increase in log (IgE) (P = 0.003); CDLQI would increase or worsen by 2.07 points on average for patients with dog fur allergy (P = 0.027) [Table 3].
|Table 3: Simple linear regression analysis of patient characteristics on Children Dermatology Life Quality Index|
Click here to view
| Discussion|| |
We followed up patients toward adulthood with the mean (SD) age 16.23 (2.50) years and recorded NESS scores as primary outcome. Our study was compatible with previous study that AE severity when patients were reaching adulthood may be associated with gender, young-onset age, treatment history, IgE and blood eosinophil counts, HDM, foods, cat fur, and dog fur sensitization. Importantly, the majority of AE patients in this cohort were troubled with moderate-to-severe disease. The secondary outcome, CDLQI, is associated with food avoidance, highest IgE, and skin sensitization for dog fur. Common to both outcomes, however, regression analysis showed that many of the clinical parameters were not predictive of AE severity or QoL when patients are approaching adulthood. The only relevant parameters were history of food avoidance and the IgE levels. A high blood IgE level may be predictive of a more severe disease course and quality of life impairment when the child grows up.
Another important observation is that many patients do report airway co-morbidities of asthma and allergic rhinitis, and food and aeroallergen sensitization. However, airway disease is generally independent of AE severity and QoL. Nevertheless, another study reported significant relationship between AE severity, bronchial asthma, allergic rhinitis, and the duration of the skin lesions. Regardless, these associated atopic diseases are prevalent among AE patients.
For strength of the study, it is a long-term follow-up study, with focus on eczema severity toward adulthood. We recorded the clinical factors from early years and updated the clinical information from time to time. NESS was used as instrument to assess AE severity which is more appropriate in comparing long-term change of disease status than SCORAD which assesses AE severity within 1 week. CDLQI toward adulthood as the secondary outcome is another innovative point for our study.
For the weakness of the study, there are missing data for some factors, notably the laboratory tests. Also, many young children are not reaching adulthood after years of follow-ups and have to be excluded from this review. Some children may refuse laboratory tests, and hence only clinical parameters are available. Consequently, multiple regression is hard to perform due to considerable loss of power. Furthermore, genetic confounders or lifestyle and socioeconomic status confounders were not included. Inevitably, in the tertiary hospital setting, the population of subjects are likely to be biased toward more severe disease.
In terms of foods sensitization (as evidenced by SPT), the increasing trend with more severe eczema is consistent with other studies. Two-thirds of mild eczema patients are sensitive to foods by SPT.,,,, Considering that most children are not exposed to many foods before 3 years of age, interpreting the frequency of those who are sensitive to foods by SPT and reported foods allergen exposure after age 3 would be more meaningful. However, food sensitization does not equate with genuine food allergy. Food allergen sensitization as evidence by positive skin prick testing is not associated with more severe disease or worse quality of life in children with AE. Conversely, food avoidance, often indiscriminatively practiced, is associated with more severe disease and worse quality of life.
Many parents may report adverse food reactions in their children with AE. Although sensitization to food and aeroallergens are prevalent, it has been demonstrated that the prevalence of genuine food allergy is low and indiscriminate food avoidance does not alleviate symptoms of AE and airway allergies.,,,
| Conclusions|| |
A number of patients do not grow out of their eczema, and many of them have allergic rhinitis and/or asthma. AE may remain severe toward adulthood. AE severity and QoL are associated with food avoidance and high IgE, but generally independent of family or personal history of airway disease and allergen sensitization. As the age when the IgE was assessed was not standardized in this retrospective study, it is not sure if blood IgE measurement may truly help assess the risk for more severe eczema when patients are becoming adults. Nevertheless, higher IgE can serve as a marker of more severe atopy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Leung AK, Hon KL, Robson WL. Atopic dermatitis. Adv Pediatr 2007;54:241-73.
Leung A, Hon K. Atopic Dermatitis: A Review for the Primary Care Physician. Hauppauge, NY: Nova Science Publishers; c2011. p. 2011.
Leung TN, Chow CM, Chow MP, Luk DC, Ho KM, Hon KL, et al
. Clinical guidelines on management of atopic dermatitis in children. Hong Kong J Paediatr 2013;18:96-104.
Odhiambo JA, Williams HC, Clayton TO, Robertson CF, Asher MI; ISAAC Phase Three Study Group, et al.
Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three. J Allergy Clin Immunol 2009;124:1251-8.e23.
Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA, et al.
The burden of atopic dermatitis: Summary of a report for the National Eczema Association. J Invest Dermatol 2017;137:26-30.
Hon KL, Tsang YC, Pong NH, Luk DC, Lee VW, Woo WM, et al.
Correlations among steroid fear, acceptability, usage frequency, quality of life and disease severity in childhood eczema. J Dermatolog Treat 2015;26:418-25.
Lewis-Jones S. Quality of life and childhood atopic dermatitis: The misery of living with childhood eczema. Int J Clin Pract 2006;60:984-92.
Chamlin SL, Frieden IJ, Williams ML, Chren MM. Effects of atopic dermatitis on young American children and their families. Pediatrics 2004;114:607-11.
Zuberbier T, Orlow SJ, Paller AS, Taïeb A, Allen R, Hernanz-Hermosa JM, et al.
Patient perspectives on the management of atopic dermatitis. J Allergy Clin Immunol 2006;118:226-32.
Abhishek S, Palamadai Krishnan S. Epidermal differentiation complex: A Review on its epigenetic regulation and potential drug targets. Cell J 2016;18:1-6.
Cabanillas B, Novak N. Atopic dermatitis and filaggrin. Curr Opin Immunol 2016;42:1-8.
Stemmler S, Hoffjan S. Trying to understand the genetics of atopic dermatitis. Mol Cell Probes 2016;30:374-85.
Morren MA, Przybilla B, Bamelis M, Heykants B, Reynaers A, Degreef H, et al.
Atopic dermatitis: Triggering factors. J Am Acad Dermatol 1994;31:467-73.
Margolis JS, Abuabara K, Bilker W, Hoffstad O, Margolis DJ. Persistence of mild to moderate atopic dermatitis. JAMA Dermatol 2014;150:593-600.
Hon KL, Tsang YC, Poon TC, Pong NH, Kwan M, Lau S, et al.
Predicting eczema severity beyond childhood. World J Pediatr 2016;12:44-8.
Hon KL, Wang SS, Leung TF. The atopic march: From skin to the airways. Iran J Allergy Asthma Immunol 2012;11:73-7.
Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol 2003;112:S118-27.
Spergel JM. From atopic dermatitis to asthma: The atopic march. Ann Allergy Asthma Immunol 2010;105:99-106.
Emerson RM, Charman CR, Williams HC. The nottingham eczema severity score: Preliminary refinement of the Rajka and Langeland grading. Br J Dermatol 2000;142:288-97.
Hon KL, Kung JS, Wang M, Pong NH, Li AM, Leung TF, et al.
Clinical scores of sleep loss and itch, and antihistamine and topical corticosteroid usage for childhood eczema. Br J Dermatol 2016;175:1076-8.
Hon KL, Ma KC, Wong E, Leung TF, Wong Y, Fok TF, et al.
Validation of a self-administered questionnaire in Chinese in the assessment of eczema severity. Pediatr Dermatol 2003;20:465-9.
Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index (CDLQI): Initial validation and practical use. Br J Dermatol 1995;132:942-9.
Chuh AA. Validation of a Cantonese version of the children's dermatology life quality index. Pediatr Dermatol 2003;20:479-81.
Hon KL, Tsang KY, Leung TF. Relevance of cat and dog sensitization by skin prick testing in childhood eczema and asthma. Curr Pediatr Rev. 2017. doi: 10.2174/1573396313666170615085018.
Celakovská J, Bukač J. The severity of atopic dermatitis evaluated with the SCORAD index and the occurrence of bronchial asthma and rhinitis, and the duration of atopic dermatitis. Allergy Rhinol (Providence) 2016;7:8-13.
Emerson RM, Williams HC, Allen BR. Severity distribution of atopic dermatitis in the community and its relationship to secondary referral. Br J Dermatol 1998;139:73-6.
Hon KL, Wang SS, Wong WL, Poon WK, Mak KY, Leung TF, et al.
Skin prick testing in atopic eczema: Atopic to what and at what age? World J Pediatr 2012;8:164-8.
Hon KL, Leung TF, Lam MC, Wong KY, Chow CM, Fok TF, et al.
Which aeroallergens are associated with eczema severity? Clin Exp Dermatol 2007;32:401-4.
Hon KL, Leung TF, Lam MC, Wong KY, Chow CM, Ko WS, et al.
Eczema exacerbation and food atopy beyond infancy: How should we advise Chinese parents about dietary history, eczema severity, and skin prick testing? Adv Ther 2007;24:223-30.
Hon KL, Leung TF, Ching G, Chow CM, Luk V, Ko WS, et al.
Patterns of food and aeroallergen sensitization in childhood eczema. Acta Paediatr 2008;97:1734-7.
Hon KL, Tsang S, Wong CY, Tse PM, Wong C, To WH, et al.
Atopy in children with eczema. Indian J Pediatr 2010;77:519-22.
Hon KL, Leung TF. Food avoidance does not improve childhood eczema. Hong Kong Med J 2015;21:574-5.
Leung TF, Yung E, Wong YS, Lam CW, Wong GW. Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: Epidemiology, clinical spectrum and risk factors. Pediatr Allergy Immunol 2009;20:339-46.
Mahesh PA, Wong GW, Ogorodova L, Potts J, Leung TF, Fedorova O, et al.
Prevalence of food sensitization and probable food allergy among adults in India: The EuroPrevall INCO study. Allergy 2016;71:1010-9.
[Table 1], [Table 2], [Table 3]