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Atopic Eczema and Attention-Deficit/Hyperactivity Disorder in a Population-Based Sample of Children and Adolescents
To the Editor: Atopic eczema (AE, also known as atopic dermatitis) is the most prevalent chronic inflammatory condition in children.1 The prevalence of AE at age 6 years reaches 20% in Western countries.1 The typical itchy lesions may cause substantial psychosocial impairment and are a leading cause of sleep loss in childhood.2 Approximately every third child with AE develops asthma or allergic rhinitis.1
Attention-deficit/hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in childhood, with a worldwide prevalence greater than 5%, and imposes a significant economic burden.3-4 Higher prevalence rates of asthma in children with ADHD suggested a common etiology, but further research failed to identify any substantial pathophysiological relationship.5 However, previous studies did not control for AE as a possible confounding factor. We examined the relationship of AE with ADHD in a population-based sample, hypothesizing that AE is a potential cause or exacerbation factor of ADHD symptoms.
Methods
We performed a correlational study using the GKV-database Saxony, an anonymized, population-based administrative health care database with complete information on outpatient health care and sociodemographic characteristics of 600 000 individuals from Germany in 2003 and 2004. Ethics committee approval and waiver of consent were given by the appropriate institutions.
Children (age 6-12 years) and adolescents (age 13-17 years) documented as having AE (code L20 from the International Statistical Classification of Diseases, 10th Revision [ICD-10]) at least twice within the study period were individually matched for age and sex to randomly selected controls without AE. To minimize misclassification, we defined a priori that the ICD-10 code for ADHD (F90) had to be documented at least twice to classify patients as having ADHD.
Two logistic regression models were fitted to investigate the relationship of AE, allergic and psychiatric comorbidities, and sociodemographic factors (age and sex) with ADHD, using backward elimination. In the primary analysis, AE was modeled as a binary variable (presence vs absence). The secondary exploratory analysis treated the frequency of consultation due to AE (as a presumptive indicator of AE severity) as a continuous variable. Assuming a prevalence of ADHD of 5% among controls, the study had 80% power to detect an odds ratio (OR) of 1.56 (with a 2-sided  = .05). Data were analyzed using Stata version 8 (StataCorp, College Station, Texas).
Results
The study population consisted of 1436 patients with AE and 1436 matched controls (mean age, 12.6 years; 59.9% female). Patients with AE and controls were balanced in terms of sociodemographic characteristics and overall health care use (Table 1). The prevalence of ADHD was 5.2% among patients with AE and 3.4% among controls. In the unadjusted analysis, ADHD was significantly associated with AE (OR, 1.54; 95% confidence interval [CI], 1.06-2.22; P = .02) (Table 2). Allergic comorbidities were not significantly associated with ADHD (asthma OR, 1.72; 95% CI, 0.95-3.13; P = .07; allergic rhinitis OR, 1.46; 95% CI, 0.99-2.13; P = .055). Multivariable analysis showed that the association between AE and ADHD was independent of age, sex, and comorbid psychiatric disorder (adjusted OR, 1.47; 95% CI, 1.01-2.15; P = .046) and that the likelihood of prevalent ADHD increased with each physician visit due to AE (OR, 1.06; 95% CI, 1.00-1.11; P = .046) (Table 2).
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Table 1. Characteristics of Patients With Atopic Eczema and Matched Controls
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Table 2. Logistic Regression Analyses on Prevalent Attention-Deficit/Hyperactivity Disorder
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Comment
These findings suggest an independent association between AE and ADHD, possibly related to AE severity. However, the results require cautious interpretation. Residual confounding and misclassification of AE and ADHD cannot be ruled out. The observed association, if real, may be an association between ADHD with atopy in general, and not specific for AE. The clinical relevance of the observed association might be small. Because the cross-sectional design does not allow establishing causal relationships or determining the direction of the observed association, prospective studies are required. It remains unclear whether the observed association is due to shared etiological factors or whether secondary phenomena like itching, sleep disturbance, or psychosocial impairment in the course of AE induce or exacerbate ADHD symptoms in a subgroup of patients, with the potential for misclassifying AE symptoms as ADHD.2, 6
Author Contributions: Dr J. Schmitt had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: J. Schmitt, Romanos, N. M. Schmitt, Meurer, Kirch.
Acquisition of data: J. Schmitt, N. M. Schmitt, Kirch.
Analysis and interpretation of data: J. Schmitt, Romanos, N. M. Schmitt, Meurer, Kirch.
Drafting of the manuscript: J. Schmitt, Romanos.
Critical revision of the manuscript for important intellectual content: J. Schmitt, Romanos, N. M. Schmitt, Meurer, Kirch.
Statistical analysis: J. Schmitt.
Administrative, technical, or material support: Meurer, Kirch.
Study supervision: J. Schmitt, Meurer, Kirch.
Financial Disclosures: None reported.
Additional Contributions: The Regional Association of Statutory Health Insurance Physicians Saxony and the Saxony Compulsory Health Insurance, Allgemeine Ortskrankenkasse (AOK) Sachsen, provided technical support in data utilization. None of these organizations received any compensation for their support.
Jochen Schmitt, MD, MPH
jochen.schmitt{at}uniklinikum-dresden.de
Department of Dermatology
Medical Faculty Carl Gustav Carus
Technische Universität Dresden
Dresden, Germany
Marcel Romanos, MD
Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy
Hospital Clinic of the University of Wuerzburg
Wuerzburg, Germany
Natalie M. Schmitt, MD, MPH
Institute of Clinical Pharmacology
Michael Meurer, MD
Department of Dermatology
Wilhelm Kirch, MD
Institute of Clinical Pharmacology
Medical Faculty Carl Gustav Carus
Technische Universität Dresden
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5. Pelsser LM, Buitelaar JK, Savelkoul HF. ADHD as a (non) allergic hypersensitivity disorder: a hypothesis [published online April 25, 2008]. Pediatr Allergy Immunol. doi:10.1111/j.1399-3038.2008.00749.x.
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Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2009;301(7):724-726.
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