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1.
The potential role of folate metabolism in interstitial cystitis.
Keagy, CD
International urogynecology journal. 2019;(3):363-370
Abstract
The topic of interstitial cystitis (IC), also known as painful bladder syndrome (PBS), and folate/one carbon metabolism has previously been unaddressed in research. This narrative review highlights a potential connection for those with mast cell-related IC and histamine-mediated pain that is explored through four conceptual sections. The first section focuses on the nature of mast cell involvement and histamine-mediated pain in some interstitial cystitis patients. The second section reviews the literature on folate status in wider allergic conditions. The third section addresses the role of folate and methylation in general in histamine excretion. Finally, folate metabolism and vascular function are addressed because of the vascular abnormalities present in some IC bladders.
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2.
Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy.
Hausmann, O, Daha, M, Longo, N, Knol, E, Müller, I, Northrup, H, Brockow, K
Molecular genetics and metabolism. 2019;(1-2):84-91
Abstract
OBJECTIVE To provide recommendations for managing hypersensitivity adverse events (HAEs) to an injectable enzyme substitution therapy (pegvaliase, a PEGylated phenylalanine ammonia lyase enzyme) in adult patients with phenylketonuria (PKU). METHODS Eight European academic immunology experts with a broad range of experience in hypersensitivity, anaphylaxis, and/or drug reactions, and two geneticists from the USA with pegvaliase experience convened for two advisory board meetings. Efficacy, safety, and immunological profile of pegvaliase were discussed with the objective of developing recommendations for the clinical management of HAEs associated with pegvaliase treatment. RESULTS Based on available immunogenicity data, it was concluded that pegvaliase induces a Type III hypersensitivity reaction, causing HAEs with peak event rates during induction/titration and a decline over time during maintenance therapy. The decline in HAEs with longer duration of therapy was considered to likely be driven by anti-drug antibody affinity maturation, reduced immune complex formation, and decreased complement activation over time. Immunology and PKU experts unanimously supported that the use of an induction, titration, and maintenance dosing regimen and implementation of several risk mitigation strategies contributed to the improvement of tolerability over time. Key risk mitigation strategies utilized in the Phase 3 clinical trials such as premedication with H1-receptor antagonists, allowance for a longer titration period after an HAE, patient education, and requirement to carry auto-injectable adrenaline (epinephrine) should be continued in clinical practice. A tool for administration of auto-injectable adrenaline in patients using pegvaliase was suggested. It was added that after the occurrence of a severe HAE a temporary dose reduction is more likely to improve tolerability than treatment interruption. CONCLUSIONS Overall, it was agreed that pegvaliase has a generally tolerable safety profile in adults with PKU. Importantly, the risk mitigation strategies utilized in the clinical trials were considered to support the continued use of key strategies for management in the commercial setting, such as a slow induction/titration dosing paradigm and premedication with H1-receptor antagonists. However, physicians and patients need to be aware of the risk of HAEs associated with pegvaliase; presence of a trained observer during early treatment may be beneficial in certain circumstances, and a requirement to carry auto-injectable adrenaline is recommended. Because pegvaliase offers the possibility to normalize diet, while maintaining blood phenylalanine within the recommended therapeutic range, safe use of this medication in the clinical setting is important. Ongoing monitoring of long-term clinical safety of patients on pegvaliase treatment in the commercial setting was recommended.
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3.
Early-life antibiotic exposure increases the risk of developing allergic symptoms later in life: A meta-analysis.
Ahmadizar, F, Vijverberg, SJH, Arets, HGM, de Boer, A, Lang, JE, Garssen, J, Kraneveld, A, Maitland-van der Zee, AH
Allergy. 2018;(5):971-986
Abstract
This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT), or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Early-life exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema, and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I2 : 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I2 : 74.2%, and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I2 : 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.
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4.
SAM syndrome is characterized by extensive phenotypic heterogeneity.
Taiber, S, Samuelov, L, Mohamad, J, Barak, EC, Sarig, O, Shalev, SA, Lestringant, G, Sprecher, E
Experimental dermatology. 2018;(7):787-790
Abstract
Severe skin dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a rare life-threatening inherited condition caused by bi-allelic mutations in DSG1 encoding desmoglein 1. The disease was initially reported to manifest with severe erythroderma, failure to thrive, atopic manifestations, recurrent infections, hypotrichosis and palmoplantar keratoderma. We present 3 new cases of SAM syndrome in 2 families and review the cases published so far. Whole exome and direct sequencing were used to identify SAM syndrome-causing mutations. Consistent with previous data, SAM syndrome was found in all 3 patients to result from homozygous mutations in DSG1 predicted to result in premature termination of translation. In contrast, as compared with patients previously reported, the present cases were found to display a wide range of clinical presentations of variable degrees of severity. The present data emphasize the fact that SAM syndrome is characterized by extensive phenotypic heterogeneity, suggesting the existence of potent modifier traits.
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5.
Management of anaphylaxis and allergies in patients with long QT syndrome: A review of the current evidence.
Welzel, T, Ziesenitz, VC, Seitz, S, Donner, B, van den Anker, JN
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2018;(5):545-551
Abstract
OBJECTIVE To develop a treatment algorithm for patients with long QT syndrome (LQTS) in case they need antiallergic medications for allergic reactions, including asthma and anaphylaxis. DATA SOURCES A literature review was performed to assess safety and to develop antiallergic treatment strategies for patients with LQTS. STUDY SELECTIONS LQTS is a heterogeneous group of myocardial repolarization disorders characterized by prolongation of the QT interval that potentially results in life-threatening torsades de pointes tachycardia. Data on pharmacologic treatment in case of anaphylaxis in LQTS are sparse. For this narrative review, all currently available articles on the use of antiallergic drugs for allergic reactions, anaphylaxis, and asthma in patients with LQTS were used. RESULTS Local allergic symptoms can be safely treated primarily with fexofenadine, levocetirizine, desloratadine, or cetirizine and, if needed, a short course of corticosteroids. In case of systemic symptoms, epinephrine should be administered. It may be less effective in patients with LQTS treated with β-blockers, necessitating the use of glucagon as add-on treatment. In case of lower airway obstruction, ipratropium bromide should be used, but if not effective, inhaled β2-adrenergic agents may be used. Continuous cardiac monitoring is indicated with the use of epinephrine and inhaled β2-adrenergic agents. The use of the latter also warrants intense monitoring of serum potassium levels. Clemastine and dimetindene should be avoided in patients with LQTS. CONCLUSION Patients with LQTS have a higher risk of life-threatening complications during the treatment of their allergic reactions because of the underlying disease and concomitant treatment with β-blockers. Treatment algorithms will certainly decrease these complications.
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6.
Food allergy.
Renz, H, Allen, KJ, Sicherer, SH, Sampson, HA, Lack, G, Beyer, K, Oettgen, HC
Nature reviews. Disease primers. 2018;:17098
Abstract
Food allergies manifest in a variety of clinical conditions within the gastrointestinal tract, skin and lungs, with the most dramatic and sometimes fatal manifestation being anaphylactic shock. Major progress has been made in basic, translational and clinical research, leading to a better understanding of the underlying immunological mechanisms that lead to the breakdown of clinical and immunological tolerance against food antigens, which can result in either immunoglobulin E (IgE)-mediated reactions or non-IgE-mediated reactions. Lifestyle factors, dietary habits and maternal-neonatal interactions play a pivotal part in triggering the onset of food allergies, including qualitative and quantitative composition of the microbiota. These factors seem to have the greatest influence early in life, an observation that has led to the generation of hypotheses to explain the food allergy epidemic, including the dual-allergen exposure hypothesis. These hypotheses have fuelled research in preventive strategies that seek to establish desensitization to allergens and/or tolerance to allergens in affected individuals. Allergen-nonspecific therapeutic strategies have also been investigated in a number of clinical trials, which will eventually improve the treatment options for patients with food allergy.
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7.
Association between Allergies and Hypercholesterolemia: A Systematic Review.
Manti, S, Cuppari, C, Marseglia, L, D'Angelo, G, Arrigo, T, Gitto, E, Leonardi, S, Salpietro, C
International archives of allergy and immunology. 2017;(2):67-76
Abstract
BACKGROUND There is controversy in the literature regarding the potential relationship between atopic predisposition (AP) and serum cholesterol levels. To this purpose, we reviewed human studies that investigated this possible link. METHODS Following PRISMA guidelines, a literature search of PubMed and Science Direct for peer-reviewed journal articles in English from January 2003, with updates through to August 2016, was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. RESULTS Of 601 reviewed reports, 18 were included in this systematic review. Fifteen studies assessed the relationship between AP and serum cholesterol levels. Due to the lack both of observational and cross-sectional studies from the literature search at this time (only 8 studies also analyzed confounding factors) there is a high possibility of confounding variables (familial and genetic predisposition, age, gender, BMI, comorbidity, and medication status) that could not be ruled out. CONCLUSION Existing studies are heterogeneous, making it difficult to draw broad conclusions. Future studies and more detailed analyses, considering confounding variables and including a larger and homogeneous population, are needed to strengthen the argument for a link between lipid metabolism and atopy.
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8.
Common food colorants and allergic reactions in children: Myth or reality?
Feketea, G, Tsabouri, S
Food chemistry. 2017;:578-588
Abstract
Various additives, including food colorants (FCs), are used in the food industry to make food appealing to consumers and to add variety. Despite the widespread usage of FCs, adverse reactions related to their consumption, including reactions triggered by immune (immediate and delayed-type hypersensitivity) and non-immune (intolerance) mechanisms, are considered rare. There is a discrepancy between the perception of patients and parents (7.4%) and the reported prevalence of adverse reactions to additives (0.01-0.23%), which is higher in atopic individuals (2-7%). Documented reactions are mild, involving mainly the skin, and, rarely, anaphylaxis. A major problem in diagnosing reactions to FCs is identification of the offending agent(s), which is based on careful dietary history taking. Allergy testing is usually unrevealing, except for reaction to some natural colorants. Treatment consists of avoidance of the offending colorant as no successful desensitization procedures have been reported.
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9.
Overview of systematic reviews in allergy epidemiology.
Genuneit, J, Seibold, AM, Apfelbacher, CJ, Konstantinou, GN, Koplin, JJ, La Grutta, S, Logan, K, Perkin, MR, Flohr, C, ,
Allergy. 2017;(6):849-856
Abstract
BACKGROUND There is a substantial body of evidence on the epidemiology of allergic conditions, which has advanced the understanding of these conditions. We aimed to systematically identify systematic reviews and meta-analyses on the epidemiology of allergic diseases to assess what has been studied comprehensively and what areas might benefit from further research. METHODS We searched PubMed and EMBASE up to 12/2014 for systematic reviews on epidemiological research on allergic diseases. We indexed diseases and topics covered and extracted data on the search characteristics of each systematic review. RESULTS The search resulted in 3991 entries after removing duplicates, plus 20 other items found via references and conference abstracts; 421 systematic reviews were relevant and included in this overview. The majority contained some evidence on asthma (72.9%). Allergic rhinitis, atopic eczema and food hypersensitivity were covered in 15.7%, 24.5% and 9.0%, respectively. Commonly studied risk factors for atopic eczema included dietary and microbial factors, while for asthma, pollution and genetic factors were often investigated in systematic reviews. There was some indication of differing search characteristics across topics. CONCLUSION We present a comprehensive overview with an indexed database of published systematic reviews in allergy epidemiology. We believe that this clarifies where most research interest has focussed and which areas could benefit from further research. We propose that this effort is updated every few years to include the most recently published evidence and to extend the search to an even broader list of hypersensitivity/allergic disorders.
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10.
Biologics for asthma and allergy.
Walsh, GM
Current opinion in otolaryngology & head and neck surgery. 2017;(3):231-234
Abstract
PURPOSE OF REVIEW The development of monoclonal antibody-based biologics targeted at inhibition of the Th2 cytokines interleukin-4, interleukin-5 and interleukin-13 represent potentially effective treatments for asthma and allergic diseases. This short review is based on English-language original articles in PubMed or MedLine that reported significant clinical findings on the evidence demonstrating the effectiveness or otherwise of the targeting of interleukin-4, interleukin-5 or interleukin-13 in asthma or allergic disease. RECENT FINDINGS Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level requiring specifically targeted treatments to block the key pathways of the disease. It is becoming apparent that significant clinical effects with anticytokine-based biologic therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. Biologics aimed at interleukin-4/13, interleukin-5 or immunoglobulin E are potentially effective treatments for patients with difficult to treat allergic disease. The development of reproducible and straightforward discriminatory biomarkers may aid identification of those patients most likely to benefit from treatment with these expensive interventions. SUMMARY Overall these biologics-based therapies are effective treatments for difficult to treat asthma and allergic disease with a safety profile comparable with placebo in the majority of published studies.