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Medical Journal Review

August 2021

WAO Reviews – Editors’ Choice

Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.

Latent tuberculosis: Two centuries of confusion
Behr MA, Kaufmann E, Duffin J et al
American Journal of Respiratory and Critical Care Medicine 2021;204(2):142-148

This is a very interesting review of latent tuberculosis (LTB). It is a very important topic, with approximately 25% of the world’s population latently affected with Mycobacterium tuberculosis. LTB infection (LTBI) is defined by the presence of immunoreactivity to tuberculosis antigens in the absence of clinical and radiologic manifestations of tuberculosis (TB) disease. Current thinking is that LTB infection (LTBI) can reactivate even decades after infection and cause transmissible disease. Thankfully, recent analyses of studies spanning 5 decades have found that the majority of TB-immunoreactive individuals have cleared their infection while retaining immunological memory of it. In this paper, the authors explore the evidence supporting this case.

The practical dietary management of food protein-induced enterocolitis syndrome
Groetch M, Baker MG, Durban R et al
Annals of Allergy Asthma & Immunology 2021;127(1):28-35

Food protein-induced enterocolitis syndrome (FPIES) is a non−IgE-mediated food allergy with potential risk of malnutrition related to the early onset of disease and frequent avoidance of cow’s milk, as well as the possibility of multiple food triggers. This publication explores the literature to provide an evidence-based, practical approach to the dietary management of FPIES. The authors found that children with FPIES are at risk of malnutrition owing to suboptimal oral intake, limited food choices, and knowledge deficits related to feeding. They specifically found that children with 3 or more FPIES triggers seem to be at increased risk for poor weight gain and developing food aversion. Furthermore, caregivers of children with FPIES also report a high degree of psychosocial burden. The authors note that dietary and nutritional management of FPIES requires appropriate avoidance of the trigger food(s) without “excessive” avoidance, guidance on early introduction of safe and nutritious complementary foods, and progressive advancement of skill-appropriate food textures that will provide the feeding skill development. Furthermore, close growth monitoring of children with FPIES is warranted to identify potential growth retardation.

Bifidobacteria-mediated immune system imprinting early in life
Henrick BM, Rodriguez L, Lakshmikanth T et al
Cell 2021;184(15):3884-3898

Research has demonstrated that immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes, which in turn benefit the host’s immune system. Such bacteria have co-evolved with humans, but sadly have become increasingly rare in modern societies. In this paper, the authors demonstrate that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon b (IFNb) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.

Update of the S2k guideline on the management of IgE-mediated food allergies
Worm M, Reese I, Ballmer-Weber B et al
Allergologie Select 2021;5(1):195-243
Full text in PubMed Central:

This is an update of the 2015 S2k guideline on the management of IgE-mediated food allergies. An interdisciplinary expert panel accomplished consensus of this revision. It takes into account the methodological guidelines of the Association of the Scientific Medical Societies (AWMF) for the development of guidelines for diagnostics and therapy and corresponds to an S2k guideline according to the three-stage concept of the AWMF, resulting in a wonderful resource for clinicians caring for patients with food allergies.

Identification of novel biomarkers to distinguish bradykinin-mediated angioedema from mast cell-/histamine-mediated angioedema
Bindke G, Gehring M, Wieczorek D et al
Allergy 2021; Published online ahead of print (20 July)

The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. In this study Bindke et al identify clinical and laboratory parameters to explore AE subtypes by prospectively enrolling 40 AE patients [15 hereditary (HAE), 13 ACE inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE)]. Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay. While they were unable to identify an improved clinical diagnostic criteria – not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/ histamine-mediated CSU-AE they did find that FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function. The authors stress that Tie-2 appears to be a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only.

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