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

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\u27s 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

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

BackgroundAtopic 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. ObjectiveWe systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. MethodsAs 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. ResultsTwenty-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. ConclusionsSCIT 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

The timing and spatiotemporal patterning of Neanderthal disappearance

The timing ofNeanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology.Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at 50,000 years ago. Here we apply improved accelerator mass spectrometry 14C techniques to construct robust chronologies from 40 key Mousterian and Neanderthal archaeological sites, ranging fromRussia to Spain. Bayesian agemodelling was used to generate probability distribution functions to determine the latest appearancedate. Weshow that theMousterian ended by 41,030\u201339,260 calibrated years BP (at 95.4%probability) across Europe. We also demonstrate that succeeding \u2018transitional\u2019 archaeological industries, one ofwhich has been linked with Neanderthals (Chatelperronian), end at a similar time. Our data indicate that the disappearance of Neanderthals occurred at different times in different regions. Comparing the data with results obtained from the earliest dated AMH sites in Europe, associated with the Uluzzian technocomplex5, allows us to quantify the temporal overlap between the two human groups. The results reveal a significant overlap of 2,600\u20135,400 years (at 95.4%probability). This has important implications formodels seeking to explain the cultural, technological and biological elements involved in the replacement of Neanderthals byAMHs. A mosaic of populations in Europe during the Middle to Upper Palaeolithic transition suggests that there was ample time for the transmission of cultural and symbolic behaviours, as well as possible genetic exchanges, between the two groups