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Medical Journal Review

October 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.

The immunology of long COVID
Altmann DM, Whettlock EM, Liu S et al
Nature Reviews Immunology 2023;23(10):618-634

Estimated numbers of long COVID-19 vary greatly; however, at least 10% of patients infected with COVID appear to develop long COVID. The disease burden spans from mild symptoms to profound disability, making this a huge, new health-care challenge. The authors of this review suggest that long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, including multiorgan, multisystem and relapsing–remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have also been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic etiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways. This review details the present available data.

Don’t we overestimate drug allergies in children?
E.Podlecka D, Jerzyńska J, Brzozowska A
International Journal of Occupational Medicine and Environmental Health 2023:169848

Approximately 10% of parents report hypersensitivity to at least 1 drug in their children. Yet, few are truly confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests. One hundred thirteen children, aged 4–18 years, referred to Pediatrics and Allergy Clinic in Łódź, Poland, due to an adverse reaction during treatment underwent a history, skin prick tests, intradermal test and drug provocation test. Of the 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to β-lactams, nonsteroid anti-inflammatory drugs, and local anesthetics in only 19 patients (16.8%). The authors found that a previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash. Overall, this study reinforces confirming true drug allergy in children presenting with a history of potential drug induced reaction.

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease
Visca D, Centis R, Pontali E, et al
International Journal of Tuberculosis and Lung Disease 2023;27(10):729-741

A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified in attempt to develop a “best standard” of care for COVID-19 patients. Relying upon the Delphi process 45 experts completed  a 5-point Likert scale indicated level of agreement with the draft standards resulting in four consensus standards (with 100% agreement). Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ‡4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR program should be based on feasibility, effectiveness and cost-effectiveness criteria, organized according to local health services and tailored to an individual patient’s needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.

Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental

Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh)
Brockow K, Wurpts G, Trautmann A et al
Allergologie Select 2023;7:122-139

In this updated “Guideline for allergological diagnosis of drug hypersensitivity reactions”, the authors conclude that drug hypersensitivity reactions presenting as urticaria/anaphylaxis within 1 (– 6) hours after drug administration (“immediate reactions”) or as exanthem several hours to days later (“delayed reactions”) should be clarified allergologically (strong consensus). Appropriate allergological diagnostics should be used to try to prove the involvement of the immune system (allergy) (strong consensus). The clinical symptoms of an allergic reaction are usually much more severe than those of a non-allergic/intolerance reaction. The experts recommend allergological diagnostics be utilized to identify patients at risk unambiguously in a timely manner to prevent unjustified restrictions in drug therapy. They suggest that allergy diagnostics should be performed within 4 weeks to 6 months after the reaction (strong consensus). The classification of a drug reaction and thus the planning of allergy diagnostics should be based on the clinical picture, the time course (chronology), and the suspected causative drug (strong consensus). If the result of a validated skin and/or laboratory test is clearly positive in conjunction with a matching medical history, the trigger(s) can be considered sufficiently confirmed (strong consensus). If no diagnosis is possible after the skin and laboratory diagnostics, controlled provocation testing should be sought after a risk-benefit assessment (strong consensus). The result of the allergological diagnosis should be explained in detail to the patient (strong consensus). A diagnosed allergic or non-allergic hypersensitivity to one or more drugs should be documented in a drug allergy passport to ensure that this drug(s) will be avoided in the future; in individual cases, if known and considered useful, tolerated alternative drugs can also be mentioned in the allergy passport (strong consensus).

Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review
Bernstein JA, Llanos JP, Hunter G et al
Advances in Therapy 2023;40(11):4721-4740

Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Unfortunately, randomized controlled trials (RCTs) of these therapies have differed in design, with varying baseline blood eosinophil count (BEC) and not surprisingly divergent results. This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. To do so, the authors performed a literature search to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. It should be noted that baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only. In patients with allergic severe asthma and BECs of >260 cells/lL or > 300 cells/lL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of <260 cells/lL or <300 cells/lL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. The authors suggest that differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably. The authors suggest that these differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.

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