Allergen Immunotherapy for Atopic Dermatitis: A Systematic Review and Meta-Analysis of Benefits and Harms

Juan José Yepes-Nuñez, Universidad de Los Andes, Bogota DC, Colombia; Fundacion Santa Fe de Bogota University, Bogota DC, Colombia.
Gordon H. Guyatt, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada.
Luis Guillermo Gómez-Escobar, Universidad de Los Andes, Bogota DC, Colombia.
Lucia C. Pérez-Herrera, Universidad de Los Andes, Bogota DC, Colombia.
Alexandro Chu, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Renata Ceccaci, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Ana Sofía Acosta-Madiedo, Universidad de Los Andes, Bogota DC, Colombia.
Aaron Wen, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Sergio Moreno-López, Universidad de Los Andes, Bogota DC, Colombia.
Margaret MacDonald, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Mónica Barrios, Universidad de Los Andes, Bogota DC, Colombia.
Xiajing Chu, Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
Nazmul Islam, Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar.
Ya Gao, Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada; Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
Melanie M. Wong, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Rachel Couban, Department of Health Research Methods, Evidence and Impact, Hamilton, Ontario, Canada.
Elizabeth Garcia, Fundacion Santa Fe de Bogota University, Bogota DC, Colombia.
Edgardo Chapman, Fundacion Santa Fe de Bogota University, Bogota DC, Colombia.
Paul Oykhman, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada.
Lina Chen, Department of Medicine, McMaster University, and Evidence in Allergy Group, Hamilton, Ontario, Canada; University of Ottawa, Ottawa, Canada.
Tonya Winders, Allergy & Asthma Network, Vienna, VA.
Rachel Netahe Asiniwasis, Origins Dermatology Centre, University of Saskatchewan, Regina, Saskatchewan, Canada.
Mark Boguniewicz, National Jewish Health, Denver, Colorado; University of Colorado School of Medicine, Aurora, Colorado.
Anna De Benedetto, Dept of Dermatology; University of Rochester Medical center, Rochester (NY).
Kathy Ellison, Westerville, Ohio.
Winfred T. Frazier, Department of Family Medicine, UPMC St. Margaret, Pittsburgh, Pennsylvania.
Matthew Greenhawt, University of Colorado School of Medicine, Aurora, Colorado.
Joey Huynh, Orthopedic Neurological Rehabilitation, Northridge, California.
Elaine Kim BscPhm, Toronto, Ontario.
Jennifer LeBovidge, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Mary Laura Lind, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona.
Peter Lio, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Document Type

Journal Article

Publication Date

9-30-2022

Journal

The Journal of allergy and clinical immunology

DOI

10.1016/j.jaci.2022.09.020

Keywords

DLQI; Evidence-Based Medicine; GRADE approach; Quality of Life; SCORAD; adverse events; aeroallergen; allergen immunotherapy (AIT); allergy; atopic dermatitis (atopic eczema); house dust mite; itch (pruritus); meta-analysis; multidisciplinary; sleep disturbance; subcutaneous immunotherapy (SCIT); sublingual immunotherapy (SLIT); systematic review

Abstract

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli (eg. allergens, irritants, microbes). The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: Systematically synthesize evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 AAAAI/ACAAI JTFPP AD Guideline update, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, GREAT and Web of Science (all databases) to December 2021 for randomized controlled trials (RCTs) comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard of care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares and adverse events. Raters independently screened, extracted data and assessed risk of bias in duplicate. We synthesized intervention effects using Frequentist and Bayesian random-effects models. The GRADE approach determined quality of the evidence. RESULTS: 23 RCTs including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing AD (SCORAD; RR 1.53 [95%CI 1.31-1.78]; 26% to 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index (DLQI) by 4 points or more (RR 1.44 [1.03-2.01]; 39% to 56%, absolute difference 17%; both outcomes moderate-certainty). Both routes of AIT increased adverse events (RR 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high-certainty). AIT's effect on sleep disturbance and eczema flares were very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared-decision making approach to optimally managing AD.

Department

Dermatology

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