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

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

Topical treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVES: We systematically synthesized the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to September 5, 2022 for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using seven classes-group 1 being most potent. OSF: https://osf.io/q5m6s. RESULTS: 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty, pimecrolimus improved six of seven outcomes-among the best for two; high-dose tacrolimus (0.1%) improved five-among the best for two; low-dose tacrolimus (0.03%) improved five-among the best for one. With moderate-to-high certainty, group 5 TCS improved six-among the best for three; group 4 TCS and delgocitinib improved four-among the best for two; ruxolitinib improved four-among the best for one; group 1 TCS improved three-among the best for two. These interventions did not increase harms. Crisaborole and difamilast were intermediately effective, but uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective

Systemic treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We systematic synthesized the benefits and harms of AD systemic treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT, from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. OSF: https://osf.io/e5sna. RESULTS: 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty, high-dose upadacitinib was among the most effective for five of six patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for two outcomes. These JAK inhibitors were among the most harmful in increasing adverse events. With high-certainty, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest-modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. The efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes but also among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and favorable safety

Hantavirus Reservoirs: Current Status with an Emphasis on Data from Brazil

Since the recognition of hantavirus as the agent responsible for haemorrhagic fever in Eurasia in the 1970s and, 20 years later, the descovery of hantavirus pulmonary syndrome in the Americas, the genus Hantavirus has been continually described throughout the World in a variety of wild animals. The diversity of wild animals infected with hantaviruses has only recently come into focus as a result of expanded wildlife studies. The known reservoirs are more than 80, belonging to 51 species of rodents, 7 bats (order Chiroptera) and 20 shrews and moles (order Soricomorpha). More than 80genetically related viruses have been classified within Hantavirus genus; 25 recognized as human pathogens responsible for a large spectrum of diseases in the Old and New World. In Brazil, where the diversity of mammals and especially rodents is considered one of the largest in the world, 9 hantavirus genotypes have been identified in 12 rodent species belonging to the genus Akodon, Calomys, Holochilus, Oligoryzomys, Oxymycterus, Necromys and Rattus. Considering the increasing number of animals that have been implicated as reservoirs of different hantaviruses, the understanding of this diversity is important for evaluating the risk of distinct hantavirus species as human pathogens