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Medical Journal Review

February 2023

WAO Reviews – Editors' Choice

The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.

Allergy: Mechanistic insights into new methods of prevention and therapy
Akdis CA, Akdis M, Boyd SD et al
Science Translational Medicine 2023;15(679):eadd2563

In this review, Akdis and colleagues explore the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. The authors note that our current understanding of the impact of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments regarding the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.

Skin care interventions in infants for preventing eczema and food allergy
Kelleher MM, Cro S, Cornelius V et al
Cochrane Database of Systemic Reviews 2021;2(2):CD013534

In the Cochrane analysis, Kelleher et al evaluate the efficacy of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Applying standard Cochrane methods, they found that skin care treatments in babies, specifically using moisturizers on the skin during the first year of life, probably do not prevent babies from developing eczema; may increase the chance of food allergy; and probably increase the chance of skin infection. The authors note that this review looked at the prevention of eczema and food allergy only and that such interventions are still important to treat eczema.

Digitally-enabled, patient-centred care in rhinitis and asthma multimorbidity: The ARIA-MASK-air® approach
Bousquet J, Anto JM, Sousa-Pinto B et al
Clinical and Translational Allergy 2023;13(1):e12215

MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® data has enabled novel phenotype discovery and characterization, as well as insights into the management of allergic rhinitis. MASK‐air® data show that most rhinitis patients: (i) are not adherent and do not follow guidelines, (ii) use as‐needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms, and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, and educational performance) is not always improved by medications. A combined symptom‐medication score (ARIA‐EAACI‐CSMS) has been validated for clinical practice and trials. The authors note that the implications of this app results should lead to change management in rhinitis and asthma.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms
Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG et al
Journal of Allergy and Clinical Immunology 2023 151(1):147-158

It is known that 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 in triggering AD remains unclear. Thus the objective of this study was to systematically examine the evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD utilizing the GRADE approach to determine the quality of the evidence. The authors found 23 randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (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 quality of life (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. Overall, they found that SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL, but SCIT increases adverse effects more than SLIT.

Cutaneous manifestations of COVID-19 and COVID-19 vaccination
Nakashima C, Kato M, Otsuka A
Journal of Dermatology 2023; Published online ahead of print

Although this new COVID-19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. The authors note that the manifestations of COVID-19 can be classified into seven categories: (i) chilblain-like skin eruption (e.g., COVID toes), (ii) urticaria-like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster.

In this review Nakashima and colleagues examine the various cutaneous adverse reactions that have been observed with COVID-19 infection and after COVID-19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune-mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain-like lesions and herpes zoster after COVID-19 mRNA vaccination have been reported, and the mechanism has been partly elucidated. The authors note that some COVID-19-associated skin reactions are indistinguishable from drug eruptions and close by stressing that in the future, the mechanisms of COVID-19 infection- or COVID-19 vaccine-associated skin reactions need to be elucidated and verification of causal relationships is required.

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