Genetic, Clinical, and Environmental Factors Associated With Persistent Atopic Dermatitis in Childhood

被引:53
作者
Thorsteinsdottir, Sunna [1 ]
Stokholm, Jakob [1 ,2 ,3 ]
Thyssen, Jacob P. [2 ]
Norgaard, Sarah [1 ]
Thorsen, Jonathan [1 ]
Chawes, Bo L. [1 ]
Bennelykke, Klaus [1 ]
Waage, Johannes [1 ]
Bisgaard, Hans [1 ]
机构
[1] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood COPS, Copenhagen, Denmark
[2] Univ Copenhagen, Herlev & Gentofte Hosp, Dept Dermatol & Allergy, Copenhagen, Denmark
[3] Naestved Hosp, Dept Pediat, Naestved, Denmark
关键词
EARLY-LIFE; ASTHMA; BIRTH; ECZEMA; RISK; FILAGGRIN; CHILDREN; SKIN; PREVALENCE; VARIANTS;
D O I
10.1001/jamadermatol.2018.4061
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
IMPORTANCE Knowledge about factors associated with persistence of atopic dermatitis (AD) during childhood is sparse. OBJECTIVE To explore heritable, environmental, and clinical factors associated with persistent AD based on 13 years' follow-up of an at-risk birth cohort. DESIGN, SETTING. AND PARTICIPANTS In the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC(2000)) clinical birth cohort study, 411 children born to mothers with asthma were followed up until the age of 13 years at a clinical research unit in Copenhagen, Denmark, from August 1998 to June 2015. Atopic dermatitis was diagnosed prospectively during close clinical follow-up according to the criteria of Hanifin and Rajka. Data were gathered on parental history, social circumstances, and environmental factors through parent interviews. The cohort was followed up with biannual visits to the clinic until the age of 7 years and were seen again at age 13 years. Data were analyzed from August 2015 to January 2018. MAIN OUTCOMES AND MEASURES Atopic dermatitis was diagnosed using Hanifin and Rajka major and minor criteria, and severity was determined by Scoring Atopic Dermatitis (SCORAD) index, with possible scores from 0 to 83, with higher scores indicating more severe AD. RESULTS Of the 411 children in the cohort, 203 (49.4%) were male and 186 (45.3%) were diagnosed with AD before the age of 13 years; 40 of 166 children (24.1%) had persistent AD at the age of 13 years, and 126 (76.0%) experienced remission. Factors associated with persistent AD to age 13 years included heritability, environmental exposures, asthma and allergic sensitization, clinical presentation at the time of diagnosis, the composition of Hanifin and Rajka diagnostic minor criteria, and AD severity according to SCORAD. A higher AD genetic risk score was associated with an increased the risk for persistent AD (multivariable odds ratio [OR], 1.8; 95% Cl, 1.1-2.9; P =.02), together with paternal asthma (multivariable OR, 3.7; 95% CI, 1.2-11.5; P =.02); paternal AD (multivariable OR, 6.2; 95% CI, 1.17-23.2; P =.007), and higher social circumstances (multivariable OR, 1.6; 95% CI, 1.0-2.5; P =.05). Particular clinical presentations at time of diagnosis were also associated with specific minor criteria of Hanifin and Rajka (Dennie-Morgan and anterior neck folds, white dermographism, intolerance to wool, itching when sweating, tendency to skin infection, food intolerance, and food allergy) (OR, 2.6; 95% CI, 1.1-6.2; P =.03) as well as increased severity at diagnosis (OR, 1.1; 95% CI, 1.0-1.1; P = .007). CONCLUSIONS AND RELEVANCE In a birth cohort of children at risk for asthma who received close clinical follow-up to age 13 years, known genetic AD risk variants, paternal asthma and AD, high social circumstances, diagnostic minor criteria, and disease severity at onset were associated with persistent AD at age 13 years. These findings may be applied in clinical practice to evaluate the likely disease course for individual patients.
引用
收藏
页码:50 / 57
页数:8
相关论文
共 46 条
[1]   Development and comorbidity of eczema, asthma and rhinitis to age 12-data from the BAMSE birth cohort [J].
Ballardini, N. ;
Kull, I. ;
Lind, T. ;
Hallner, E. ;
Almqvist, C. ;
Ostblom, E. ;
Melen, E. ;
Pershagen, G. ;
Lilja, G. ;
Bergstrom, A. ;
Wickman, M. .
ALLERGY, 2012, 67 (04) :537-544
[2]   Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood [J].
Barker, Jonathan N. W. N. ;
Palmer, Colin N. A. ;
Zhao, Yiwei ;
Liao, Haihui ;
Hull, Peter R. ;
Lee, Simon P. ;
Allen, Michael H. ;
Meggitt, Simon J. ;
Reynolds, Nicholas J. ;
Trembath, Richard C. ;
McLean, W. H. Irwin .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (03) :564-567
[3]   The use of the twin model to investigate the genetics and epigenetics of skin diseases with genomic, transcriptomic and methylation data [J].
Bataille, V. ;
Lens, M. ;
Spector, T. D. .
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2012, 26 (09) :1067-1073
[4]   Developmental Profiles of Eczema, Wheeze, and Rhinitis: Two Population-Based Birth Cohort Studies [J].
Belgrave, Danielle C. M. ;
Granell, Raquel ;
Simpson, Angela ;
Guiver, John ;
Bishop, Christopher ;
Buchan, Iain ;
Henderson, A. John ;
Custovic, Adnan .
PLOS MEDICINE, 2014, 11 (10)
[6]   Intermittent inhaled corticosteroids in infants with episodic wheezing [J].
Bisgaard, H ;
Hermansen, MN ;
Loland, L ;
Halkjaer, LB ;
Buchvald, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (19) :1998-2005
[7]   Childhood asthma after bacterial colonization of the airway in neonates [J].
Bisgaard, Hans ;
Hermansen, Mette Northman ;
Buchvald, Frederik ;
Loland, Lotte ;
Halkjaer, Liselotte Brydensholt ;
Bonnelykke, Klaus ;
Brasholt, Martin ;
Heltberg, Andreas ;
Vissing, Nadja Hawwa ;
Thorsen, Sannie Vester ;
Stage, Malene ;
Pipper, Christian Bressen .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (15) :1487-1495
[8]   Risk analysis of early childhood eczema [J].
Bisgaard, Hans ;
Halkjaer, Liselotte B. ;
Hinge, Rikke ;
Giwercman, Charlotte ;
Palmer, Colin ;
Silveira, Lori ;
Strand, Matthew .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009, 123 (06) :1355-1360
[9]   Family history and risk of atopic dermatitis in children up to 4 years [J].
Böhme, M ;
Wickman, M ;
Nordvall, SL ;
Svartengren, M ;
Wahlgren, CF .
CLINICAL AND EXPERIMENTAL ALLERGY, 2003, 33 (09) :1226-1231
[10]   Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth [J].
Bonnelykke, Klaus ;
Pipper, Christian B. ;
Tavendale, Roger ;
Palmer, Colin N. A. ;
Bisgaard, Hans .
PEDIATRIC ALLERGY AND IMMUNOLOGY, 2010, 21 (06) :954-961