Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms

Juan José Yepes-Nuñez, Gordon H. Guyatt, Luis Guillermo Gómez-Escobar, Lucia C. Pérez-Herrera, Alexandro W.L. Chu, Renata Ceccaci, Ana Sofía Acosta-Madiedo, Aaron Wen, Sergio Moreno-López, Margaret MacDonald, Mónica Barrios, Xiajing Chu, Nazmul Islam, Ya Gao, Melanie M. Wong, Rachel Couban, Elizabeth Garcia, Edgardo Chapman, Paul Oykhman, Lina ChenTonya Winders, Rachel Netahe Asiniwasis, Mark Boguniewicz, Anna De Benedetto, Kathy Ellison, Winfred T. Frazier, Matthew Greenhawt, Joey Huynh, Elaine Kim, Jennifer LeBovidge, Mary Laura Lind, Peter Lio, Stephen A. Martin, Monica O'Brien, Peck Y. Ong, Jonathan I. Silverberg, Jonathan Spergel, Julie Wang, Kathryn E. Wheeler, Lynda Schneider, Derek K. Chu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. Objective: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. Methods: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard 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 the quality of evidence. Results: Twenty-three randomized controlled trials 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 Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 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 was 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.

Original languageEnglish
Pages (from-to)147-158
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jan 2023
Externally publishedYes


  • Atopic dermatitis (atopic eczema)
  • DLQI
  • GRADE approach
  • adverse events
  • aeroallergen
  • allergen immunotherapy (AIT)
  • allergy
  • evidence-based medicine
  • house dust mite
  • itch (pruritus)
  • meta-analysis
  • multidisciplinary
  • quality of life
  • sleep disturbance
  • subcutaneous immunotherapy (SCIT)
  • sublingual immunotherapy (SLIT)
  • systematic review


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