Showing papers in "Current Opinion in Allergy and Clinical Immunology in 2020"

Th2 inflammatory responses in the development of nasal polyps and chronic rhinosinusitis

Abstract: Purpose of reviewPathogenesis of nasal polyp has been largely studied based on innate and adaptive immunity of sinonasal mucosa. So far, various factors have been identified that trigger an inflammatory response in the pathogenesis of nasal polyps. In this review, we summarized recently updated info

Primary immune regulatory disorders: a growing universe of immune dysregulation.

Abstract: Purpose of review Primary immune regulatory disorders (PIRD) are a growing subset of diseases referred to as inborn errors of immunity. Unlike classical primary immune deficiency disorders that typically present with severe, recurrent, or unusual infections, the clinical manifestations of PIRD are dominated by immune-mediated diseases (autoimmunity, autoinflammation/hyperinflammation, lymphoproliferation, malignancy, and severe atopy). This review introduces the concept of PIRD including clinical phenotypes, treatments, and new PIRD-associated gene defects. Recent findings The number of genetic defects associated with PIRD is rapidly growing. The identified genes often encode proteins that play critical roles in regulating the immune response to various triggers. Understanding the molecular mechanisms underlying PIRD has shed light on the clinical phenotypes and has helped to identify targeted therapies. In some cases, hematopoietic cell transplant (HCT) has been successfully employed as a cure. Summary It is important to recognize the broad clinical manifestations of PIRD as patients may have symptoms atypical of classical 'immunodeficiency'. Because of their diverse immune dysregulation problems, they are often primarily managed by other subspecialists. Immunologists can help connect the diverse immune-mediated pathologies to a gene defect. This, in turn, can play a significant role in directing clinical management, selecting effective therapy, and deciding on appropriateness of HCT.

The role of epigenetics in allergy and asthma development.

Abstract: Purpose of reviewEpigenetic mechanisms are known to play a crucial role in the pathogenesis of asthma, allergic rhinitis, atopic dermatitis, food allergy, and other allergic disorders, especially through mediating the effects of the environmental factors, well recognized allergy-risk modifiers. The

Global immunoglobulin supply: steaming towards the iceberg?

Abstract: Purpose of review This review describes how plasma is sourced for fractionation into plasma-derived medicinal products (PDMPs), such as immunoglobulin (Ig) together with differences between plasma from whole blood (recovered plasma) and from plasmapheresis (source plasma) in terms of global plasma supply. Specific areas of growth in immunoglobulin use are identified alongside novel therapies, which may reduce demand for some immunoglobulin indications. Recent findings There has been a 6--8% annual growth in immunoglobulin use. Secondary immunodeficiency alongside improved recognition and diagnosis primary immunodeficiency disorders are drivers whereas the novel neonatal Fc receptor inhibitors (FcRni) may reduce demand for some immunomodulatory indications. Summary There is a significant geographical imbalance in global supply of plasma with 65% collected in the United States. This results in a dependency of other countries on United States supply and argues for both more plasma supply and greater regionally balanced plasma collection. In addition, progress towards a transparent, regulated and well tolerated framework for the coexistence of unpaid and compensated plasma donations is needed as unpaid donation will not be sufficient. These discussions should be informed by the needs of patients for this life-saving therapy, the care of donors and the safety of plasma and PDMPs.

Tolerance mechanisms in allergen immunotherapy.

Abstract: Purpose of review: Allergen immunotherapy is the only treatment modality which alters the natural course of allergic diseases by restoring immune tolerance against allergens. Deeper understanding of tolerance mechanisms will lead to the development of new vaccines, which target immune responses and promote tolerance. Recent findings: Successful allergen immunotherapy (AIT) induces allergen-specific peripheral tolerance, characterized mainly by the generation of allergen-specific Treg cells and reduction of Th2 cells. At the early phase, AIT leads to a decrease in the activity and degranulation of mast cells and basophils and a decrease in inflammatory responses of eosinophils in inflamed tissues. Treg cells show their effects by secreting inhibitory cytokines including interleukin (IL)-10, transforming growth factor-β, interfering with cellular metabolisms, suppressing antigen presenting cells and innate lymphoid cells (ILCs) and by cytolysis. AIT induces the development of regulatory B cells producing IL-10 and B cells expressing allergen-specific IgG4. Recent investigations have demonstrated that AIT is also associated with the formation of ILC2reg and DCreg cells which contribute to tolerance induction. Summary: Research done so far, has shown that multiple molecular and cellular factors are dysregulated in allergic diseases and modified by AIT. Studies should now focus on finding the best target and ideal biomarkers to identify ideal candidates for AIT.

Systemic biomarkers of eosinophilic chronic rhinosinusitis.

Abstract: Purpose of review The current understanding of eosinophilic chronic rhinosinusitis (CRS) has developed rapidly over the past decades. Classification of CRS based on the inflammatory endotype more accurately reflects the underlying pathophysiology and better directs treatment. Corticosteroids and more recently biologic agents, target the eosinophil inflammatory that drives this subtype of CRS. Tissue sampling is not always accessible or available and surrogate markers are sought to define this endotype of CRS. The purpose of this review is to assess current systemic predictors of eosinophilic CRS (eCRS) diagnosis. Recent findings Blood eosinophils are a moderate surrogate predictor of eCRS. A blood eosinophil count of more than 0.24 × 10/l predicts eCRS with tissue eosinophilia of more than 10 eosinophils per high-power field. It has been further shown that a blood eosinophil count more than 0.45 × 10/l is associated with need for long-term systemic therapy following endoscopic sinus surgery. Other biomarkers reviewed include IgE, eosinophilic cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, IL-5, periostin, eotaxin-3 and IL-16. Summary There remains limited data surrounding the prognostic use of biomarkers in eCRS. However, peripheral eosinophilia best predicts the eosinophilic density that best predicts the eCRS phenotype. In addition, it is also prognostic of need for more intensive therapy. Simple haematoxylin and eosin stained sinus mucosa still remains the most reliable tissue for assessment and is more accessible than bronchial biopsies.

Hymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia.

Abstract: Purpose of review To discuss the association between the common dominantly inherited genetic trait hereditary alpha-tryptasemia (HαT) and hymenoptera venom-induced anaphylaxis (HVA). Recent findings Elevated BST has been correlated with more severe systemic anaphylaxis in humans in a number of settings - most notably in HVA. Clonal mast cell disease, in particular, systemic mastocytosis, is frequently associated with elevated BST, and is a major risk factor for severe HVA. However, clonal mast cell diseases are believed to be rare, whereas HVA is relatively more common. HαT affects an estimated 3-5% of Western populations and is the common cause for elevated BST in these individuals. An association between HαT and severe HVA, as well as clonal mast cell disease has recently been demonstrated wherein this trait modifies reaction severity in venom allergic individuals. A mechanism underlying this association has been proposed through the identification of naturally occurring heterotetrameric tryptases and characterization of their unique physical attributes. Summary Here we discuss the long-standing association between elevated BST and HVA severity, how HαT fits into this landscape, and review the clinical and mechanistic evidence that supports HαT as a modifier of HVA.

The role of atopy in asthma development and persistence.

Abstract: Purpose of review Asthma is the most common chronic disease in pediatric age. Childhood-onset asthma, as opposed to adult-onset asthma, is typically characterized by a personal and often a family history of atopy and related markers of type 2-mediated inflammation. However, the interplay between atopy and asthma development is more complex than a linear dose-response relationship. Recent findings Family and personal history of atopic diseases have been confirmed as major risk factors for asthma occurrence and persistence in children. Early life and multiple sensitizations to aeroallergens significantly increase the risk of asthma development in school age. Early life lower respiratory tract viral infections, especially caused by rhinovirus, also increase the susceptibility to atopic asthma in childhood. Human rhinovirus type C receptor CDHR3 polymorphisms have been shown to affect receptor epithelial expression, activation, and asthma development and exacerbation severity in children. Atopic sensitization and respiratory viral infections can synergistically enhance the susceptibility to asthma through multiple mechanisms, including the IgE-mediated inhibition of innate antiviral responses to rhinovirus. Emerging evidence shows that several nonatopic factors are also involved in the asthma pathogenesis in genetically predisposed individuals, including early life exposure to environmental factors, and lung and gut microbiome composition. Summary The current review outlines recent data on the complex role of atopy in asthma pathogenesis and persistence, and addresses new research topics such as the role of epigenetics and the lung microbiome.

Can patients with oral allergy syndrome be at risk of anaphylaxis

Abstract: Purpose of review Oral allergy syndrome, also known as pollen-food syndrome (PFS), is a condition usually associated with adults and characterized by mild transient oropharyngeal symptoms. The purpose of this review is to determine whether systemic or anaphylactic reactions do occur and if so, who is affected and what are the triggers. Recent findings An increasing number of studies demonstrate that PFS occurs all age groups, and a significant number of affected adults do experience systemic and anaphylactic reactions. The upsurge in the adoption of vegan lifestyles, increase in consumption of fruits and vegetables including smoothies and juices, and use of plant foods in nutritional or body-building supplements, could exacerbate this. Changes in pollen and pollution levels, cofactors and sensitization to other plant food allergens may also be involved. Summary While the majority of those with PFS will continue to experience mild symptoms, all individuals should be properly advised regarding the dangers of concentrated or unusual forms of plant food allergens such as smoothies, juices, soy/nut milks and nutritional supplements. Further well characterized studies are needed to determine risk factors for severe reactions, and sensitization patterns to pollens and plant food allergens.

The role of IL-17, IL-23 and IL-31, IL-33 in allergic skin diseases.

Abstract: Purpose of review Allergic skin diseases such as urticaria, atopic dermatitis and allergic contact dermatitis are among the most common skin diseases with severe socioeconomic consequences The pathogenesis of allergic skin diseases is complex This review provides an overview of cytocines IL-17, IL-23, IL-31 and IL-33 Recent findings Current research results show a variety of immunological processes in the pathogenesis of the allergic skin diseases, including the role of cytokines In addition to the Th1 and Th2 immune response, the immune response via Th17 is becoming increasingly important in allergic skin diseases but also the cytokines IL-23, IL-31 and IL-33 have been discussed in the literature recently Different cytokines promote in a kind of orchestra the different symptoms seen in the different allergic skin diseases, including pruritus, dermatitis, mast cell mediator release and inflammation Summary We are still in the early stages of understanding pathophysiology of allergic skin diseases and the role of various cytokines in the immune system With the development of targeted antibodies against the proinflammatory cytokines, the variety of normal therapeutic options can be expected to evolve

Systemic and breath biomarkers for asthma: an update.

Abstract: Purpose of reviewFinding suitable biomarkers to phenotype asthma, identify individuals at risk of worsening and guide treatment is highly prioritized in asthma research. We aimed to provide an analysis of currently used and upcoming biomarkers, focusing on developments published in the past 2 years.

Rubella virus-associated chronic inflammation in primary immunodeficiency diseases.

Abstract: Purpose of the review The aim of this article is to summarize recent data on rubella virus (RuV) vaccine in chronic inflammation focusing on granulomas in individuals with primary immunodeficiencies (PIDs). Recent findings The live attenuated RuV vaccine has been recently associated with cutaneous and visceral granulomas in children with various PIDs. RuV vaccine strain can persist for decades subclinically in currently unknown body site(s) before emerging in granulomas. Histologically, RuV is predominately localized in M2 macrophages in the granuloma centers. Multiple mutations accumulate during persistence resulting in emergence of immunodeficiency-related vaccine-derived rubella viruses (iVDRVs) with altered immunological, replication, and persistence properties. Viral RNA was detected in granuloma biopsies and nasopharyngeal secretions and infectious virus were isolated from the granuloma lesions. The risk of iVDRV transmissibility to contacts needs to be evaluated. Several broad-spectrum antiviral drugs have been tested recently but did not provide significant clinical improvement. Hematopoietic stem cell transplantation remains the only reliable option for curing chronic RuV-associated granulomas in PIDs. Summary Persistence of vaccine-derived RuVs appears to be a crucial factor in a significant proportion of granulomatous disease in PIDs. RuV testing of granulomas in PID individuals might help with case management.

Adverse reactions to vancomycin and cross-reactivity with other antibiotics.

Abstract: PURPOSE OF REVIEW: Glycopeptide antibiotics such as vancomycin are frequently utilized to treat resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus The current literature on glycopeptide and lipoglycopeptide structure, hypersensitivity and potential cross-reactivity was reviewed, highlighting implications for safe prescribing RECENT FINDINGS: Structurally similar, glycopeptides could theoretically cross-react Immediate reactions to vancomycin include non-IgE-mediated reactions (eg red man syndrome) and IgE-mediated hypersensitivity (eg anaphylaxis), sharing clinical features Vancomycin can activate mast cells via MAS-related G-protein-coupled receptor X2, an IgE-independent receptor implicated in non-IgE reactions In-vivo and in-vitro testing for suspected IgE-mediated reactions to glycopeptides remain ill-defined Vancomycin is increasingly recognized to cause severe cutaneous adverse reactions (SCAR), with drug reaction with eosinophilia and systemic symptoms (DRESS) predominantly reported Vancomycin DRESS has been associated with HLA-A32:-01, with a number needed to prevent of 1 in 74 Data demonstrating cross-reactivity amongst glycopeptides and lipoglycopeptides is limited to case reports/series SUMMARY: Further studies and in-vivo/in-vitro diagnostics are required for better differentiation between IgE and non-IgE glycopeptide reactions Despite its association with vanomycin DRESS, utility of pharmacogenomic screening for HLA-A32: 01 is ill-defined Although HLA-A32:01 has been associated with vancomycin DRESS, its utility for pharmacogenomic screening is ill defined Further clinical and immunological cross-reactivity data for glycopeptide/lipoglycopeptide antibiotics is required

Childhood asthma in the new omics era: challenges and perspectives.

Abstract: PURPOSE OF REVIEW Childhood asthma is a heterogeneous inflammatory disease comprising different phenotypes and endotypes and, particularly in its severe forms, has a large impact on the quality-of-life of patients and caregivers. The application of advanced omics technologies provides useful insights into underlying asthma endotypes and may provide potential clinical biomarkers to guide treatment and move towards a precision medicine approach. RECENT FINDINGS The current article addresses how novel omics approaches have shaped our current understanding of childhood asthma and highlights recent findings from (pharmaco)genomics, epigenomics, transcriptomics, and metabolomics studies on childhood asthma and their potential clinical implications to guide treatment in severe asthmatics. SUMMARY Until now, omics studies have largely expanded our view on asthma heterogeneity, helped understand cellular processes underlying asthma, and brought us closer towards identifying (bio)markers that will allow the prediction of treatment responsiveness and disease progression. There is a clinical need for biomarkers that will guide treatment at the individual level, particularly in the field of biologicals. The integration of multiomics data together with clinical data could be the next promising step towards development individual risk prediction models to guide treatment. However, this requires large-scale collaboration in a multidisciplinary setting.

Mechanism and diagnosis of protein contact dermatitis.

Abstract: Purpose of review Protein contact dermatitis (PCD) is a chronic eczema because of immediate hypersensitivity to protein and not related to haptens. As it has to be diagnosed by prick tests, it is probably under-recorded and under-estimated that is why it is important for dermatologists, allergists and occupational physicians to better know this peculiar contact dermatitis. Recent findings Some recent series have emphasized that PCD is mainly an occupational dermatosis, mainly observed in food handlers. Summary PCD is a chronic eczematous dermatitis, possibly exacerbated by work, suggested if associated with inflammatory perionyxis (paronychial inflammation) and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have in most of the cases negative results. Prick-by-prick tests with fresh material are recommended. The product has to be 'pricked', for instance the food, and immediately after the forearm is pricked. In case of multisensitization revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. History of atopy found in 56--68% of the patients has to be checked for. Most of the cases are observed among food-handlers but PCD can also be because of nonedible plants, latex, hydrolyzed proteins or animal proteins.

Vitamin D: can the sun stop the atopic epidemic?

Abstract: PURPOSE OF REVIEW To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms. RECENT FINDINGS The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake. Vitamin D deficiency is linked to an increased incidence of allergic disease and asthma. These associations are generally strongest in early life. The capacity of vitamin D to enhance antimicrobial pathways, promote peripheral immunological tolerance and maintain mucosal barrier integrity may underlie these associations. Interventional studies have addressed the capacity of vitamin D supplementation in utero and early life to reduce the incidence of disease. Ancillary studies have provided insights into potential biological mechanisms linked to these effects. SUMMARY Observational studies show an inverse association between vitamin D levels and development of food allergy and asthma. Secondary analyses of two recent interventional studies suggest that achieving vitamin D sufficiency throughout pregnancy reduces the incidence of asthma/recurrent wheeze at 3 years. Longitudinal studies of vitamin D requirements in utero and postnatally, better understanding of factors that influence bioavailability of vitamin D and mechanistic insights into vitamin D effects on neonatal-specific immune pathways are awaited.

Current advances on the microbiome and role of probiotics in upper airways disease.

Abstract: Purpose of review The prevalence of chronic upper airway inflammatory diseases such as allergic rhinitis and chronic rhinosinusitis (CRS) is increasing markedly posing a potential health threat globally. The involvement of the upper respiratory microbiota in chronic inflammatory diseases of the upper airways has been of considerable interest. The purpose of this review is to understand the characteristics of upper respiratory microbiota in both healthy and chronic inflammatory diseases of the upper airways like allergic rhinitis and CRS and to know the potential role of interventions with probiotics. Recent findings We present here the studies on the nasal microbiota in healthy infants, allergic rhinitis, and CRS. The results demonstrate that there are stable and unstable profiles of microbiota during infancy. Decreased diversity or an imbalance of the microbial composition could be an important factor in the development of both allergic rhinitis and CRS. We also discuss here several recent animal and human studies that demonstrate the effect of probiotics in allergic rhinitis and chronic rhinosinusitis. Results from human studies (clinical trials) have demonstrated that probiotics may be effective for allergic rhinitis, but there are no consistent results in human CRS trials. Summary Several strains of probiotics revealed potential efficacy for allergic rhinitis but not for CRS. Large clinical trials are essential to establish robust data on probiotics for chronic inflammatory upper airways diseases like allergic rhinitis and CRS.

Microbiota in non-IgE-mediated food allergy.

Abstract: PURPOSE OF REVIEW To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy. RECENT FINDINGS The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota. SUMMARY Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.

Food allergy: how expensive are they?

Abstract: Purpose of review Food allergy remains a disease of global public health significance well known to impact social, emotional, and financial well being. This review aims to summarize the existing literature focused on the direct, indirect, and intangible costs of food allergy at the household and healthcare system levels, and begin to discuss how emerging treatment and prevention strategies may be leveraged to comprehensively care for the food allergic population with the efficient use of health resources. Recent findings Food allergy imposes significant costs to multiple stakeholders and largely impact families at the household level. Recent studies elucidate the need to balance the household management of food allergy with the efficient use of health resources. Overall, it remains critical that safe foods and medications remain affordable while further exploring the cost-effectiveness of early introduction, emerging food allergy therapies, and the wider use of stock epinephrine to adequately meet the public health needs of the food-allergic community. Summary Better understanding how the cost of food allergy impacts populations will help to inform more progressive policies aimed at lessening socioeconomic disparities and ultimately improve quality of life for children and adults with food allergies.

Current state of occupational latex allergy.

Abstract: Purpose of review During the 1980s, natural rubber latex (NRL) emerged as a major cause of occupational allergy and asthma, especially in healthcare workers using powdered NRL gloves. Increased recognition of NRL allergies and transfer of research findings into prevention strategies resulted into an almost elimination of this health problem. Here, the current knowledge on allergens, their use in diagnostics, prevalence data of occupational NRL allergy and the status of prevention strategy are summarized. Recent findings While the current studies conducted in high-income countries show that prevention measures have reduced NRL allergy, this does not yet apply worldwide. For latex allergy diagnosis, it is important that recombinant allergens as reliable tools are available, because in several European countries and the United States, NRL skin prick test extracts and powdered latex gloves for bronchial challenge test are no longer commercially available, leading to a deficit in diagnostic tools. Due to the fact that latex is suitable with good properties as a raw material for gloves, alternatives with significantly lower protein content and without cross-reactive structures to latex proteins are sought. Summary Awareness of the sensitization risk associated with the use of latex gloves should still be present in all occupational settings.

Atopic dermatitis and its relation to food allergy.

Abstract: Purpose of review To present the most recent evidence on atopic dermatitis and its relation to food allergy. Recent findings Atopic dermatitis is a chronic inflammatory disorder of the skin characterized by impaired skin barrier because of multifactorial causes including genetic factors, immune dysregulation, and skin microbiome dysbiosis. Infants with temporary skin barrier disruption and/or persistent atopic dermatitis are particularly at risk of developing food allergy (during the so-called atopic march), with up to half of patients demonstrating positive food-specific IgE and one-third of severe cases of atopic dermatitis having positive symptoms on oral food challenge. A high proportion of children with atopic dermatitis exhibit asymptomatic sensitization to foods, and skin testing to identify potential food triggers is not recommended unless the patient has a history suggestive of food allergy and/or moderate-to-severe atopic dermatitis unresponsive to optimal topical care. Indeed, indiscriminate testing can lead to a high proportion of false-positive tests and harmful dietary evictions. Promising strategies to prevent food allergy in children with atopic dermatitis include early skincare with emollients and treatment with topical steroid, and early introduction of highly allergenic foods. Summary Further studies are required to identify risk factors for atopic dermatitis to help prevent the development of food allergy in this high-risk population.

Artificial intelligence and the hunt for immunological disorders.

Abstract: Purpose of review Artificial intelligence has pervasively transformed many industries and is beginning to shape medical practice. New use cases are being identified in subspecialty domains of medicine and, in particular, application of artificial intelligence has found its way to the practice of allergy-immunology. Here, we summarize recent developments, emerging applications and obstacles to realizing full potential. Recent findings Artificial/augmented intelligence and machine learning are being used to reduce dimensional complexity, understand cellular interactions and advance vaccine work in the basic sciences. In genomics, bioinformatic methods are critical for variant calling and classification. For clinical work, artificial intelligence is enabling disease detection, risk profiling and decision support. These approaches are just beginning to have impact upon the field of clinical immunology and much opportunity exists for further advancement. Summary This review highlights use of computational methods for analysis of large datasets across the spectrum of research and clinical care for patients with immunological disorders. Here, we discuss how big data methods are presently being used across the field clinical immunology.

Biological agents for severe asthma: the evolution of the at-home self-injection approach.

Abstract: Purpose of review New biological agents, in addition to the well-established omalizumab, have been nowadays introduced into clinical practice for severe asthma This suggested the possibility of an at-home self-administration, as currently happening for other biological agents for immune-mediated diseases Recent findings In the very recent years, there were structured clinical trials investigating the self at home administrations of biologicals for severe asthma, showing with different principles, a possible advantage and convenience for the patient, and a socioeconomic saving Summary The literature analysis currently shows that the at-home self-administration of biologicals for severe asthma is a promising approach to improve the treatment of such disease

Eosinophilic esophagitis as a complication of food oral immunotherapy.

Abstract: Purpose of review Food oral immunotherapy (OIT) has emerged as way to mitigate serious allergic reactions including life-threatening anaphylaxis related to accidental ingestion. However, gastrointestinal-related adverse effects of OIT have been reported and are often cited as reasons for discontinuation of therapy. We summarize recent research on the prevalence of eosinophilic esophagitis (EoE) in patients undergoing OIT. Recent findings We examined 12 recent studies on OIT for peanut, milk, walnut, egg, and wheat, which enrolled a total of 620 patients. Gastrointestinal symptoms were common during OIT, and while generally mild, 24 (3.9%) patients from the reviewed studies reported gastrointestinal symptoms that were significant enough to prompt discontinuation of OIT. Of these, two (0.3% of the total 620 patients or 8.3% of those with gastrointestinal symptoms) patients had biopsy-confirmed EoE. One of these patients was subsequently found to also have ulcerative colitis that had been previously undiagnosed. Summary EoE is a rare but concerning side effect of OIT. More research is needed to better elucidate both the OIT-related and patient-related factors that may predispose individuals to develop EoE. The presence of comorbid conditions and/or preexisting subclinical esophageal eosinophilia may account for some of cases of EoE identified during OIT.

Allergic conjunctivitis in children: current understanding and future perspectives.

Abstract: Purpose of review The rising global burden of allergic diseases, particularly in the pediatric population, is of serious concern. Ocular allergy is one of the most common ocular pathologies met in clinical practice. A large proportion of children and adolescents suffer from allergic eye diseases (AEDs), which affect their quality of life. The available treatments and surgical modalities have their limitations and side effects. Therefore, the development of novel and alternate strategies is the need of the hour and requires a timely review of currently available knowledge. Recent findings The current review covers the incidence and prevalence of AEDs, factors influencing occurrence and severity of AED (age, sex, socioeconomic status etc.), underlying mechanisms, role of allergy testing and immunotherapy in children, development of diagnostic markers and novel therapies including cells and molecules. Summary Understanding the demographics, clinical patterns and risk factors of AED can help formulate appropriate preventive and therapeutic strategies for the effective management of this common cause of ocular morbidity. The future therapeutics for AED seems to rely primarily on cells (mesenchymal stem cells, Tregs, mast cells), cell products, molecules with immunosuppressive potential and immunotherapy.

Host-microbiome intestinal interactions during early life: considerations for atopy and asthma development.

Abstract: PURPOSE OF REVIEW The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobes Bifidobacteria and Bacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma. RECENT FINDINGS Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases. SUMMARY Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host-microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility.

Biologicals for severe asthma: what we can learn from real-life experiences?

Abstract: Purpose of reviewSevere asthma is a serious disease affecting about 5–10% of asthmatic patients. Often patients with this kind of asthma requires periodical courses or daily intake of oral corticosteroids, to control symptoms. In the last few years several biological drugs have been developed with t

Eosinophilic gastroenteritis: epidemiology, diagnosis, and treatment.

Abstract: Purpose of review Although several reviews concerning diagnosis and treatment of eosinophilic esophagitis (EoE) have been presented, there are few in regard to eosinophilic gastroenteritis (EGE). Fortunately, findings related to epidemiology, as well as diagnosis and treatment of this disease have recently been increasing. Recent findings The rates of incidence of both EoE and EGE have been reported to be increasing. For accurate diagnosis, plasma concentrations of thymic stromal lymphopoietin and IL-33 may be useful as biomarkers, though consensus has not been reached, while increased eosinophil infiltration in gastrointestinal tissue remains a critical factor. Topical glucocorticoid administration, an elimination diet, and molecular target therapy with neutralizing antibodies are potentially effective therapies that have recently been evaluated. Summary As seen with other allergic diseases, EGE seems to be increasing. Several research projects regarding diagnosis and treatment of the disease are currently in progress.

Angioedema without urticaria: novel findings which must be measured in clinical setting.

Abstract: Purpose of review Angioedema without urticaria is composed of an increasing subtype's variety and presents a challenging diagnosis. This review summarizes the subtypes recently described and subsequent new findings helpful within their classification. Recent findings New methods to measure cleaved high molecular weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Three new subtypes of hereditary angioedema (HAE) with normal C1 inhibitor were described in the past two years: HAE due to mutation in plasminogen gene, in kininogen gene, and in angiopoietin-1 gene; implicating the fibrinolytic and contact systems, and the regulation of vasculature, respectively. The understanding of some mechanisms in angioedema has been improved, compatible to the dominant-negative for some C1 inhibitor variants; furthermore, the increased activation of truncated F12 mutants by plasma kallikrein; and the diminished binding of angiopoietin-1 to its receptor. Summary The validation of biomarkers for the contact system activation could be beneficial in differentiating bradykinin - from histaminergic-mediated angioedema. Currently, the available laboratorial tests are still somewhat restricted to the evaluation of the complement activation and the mediators of nonhistaminergic and nonbradykinin-mediated angioedema remain to be identified.

Precision medicine in cow's milk allergy.

Abstract: Purpose of review The aim of this review is to describe the role of precision medicine in the diagnosis, treatment, and monitoring of cow's milk allergy. Recent findings The development of 'omics' sciences in the field of food allergy has led to a better understanding of the allergenicity of cow's milk proteins and significant advances in the knowledge of the pathogenesis and mechanisms of cow's milk allergy. Omics-based technologies allow the practitioner to better differentiate cow's milk allergy subtypes and to predict cow's milk allergy (CMA) persistence over time. Precision medicine extends the role of the oral food challenge, to determine the individual's threshold doses, and to establish tolerance to baked milk products. Other than symptom relief, dietary strategies are currently being investigated for the potential to induce tolerance. Oral immunotherapy offers a treatment option for patients with severe and persistent IgE-mediated CMA. Individual baseline-immune profiles may be predictive of cow's milk oral immunotherapy safety and efficacy.Patient data derived from current technology, in combination with the patient's history, can be translated into treatments targeted at patient-tailored interventions. Summary The identification of novel biomarkers may improve diagnostic accuracy and also predict patient responsiveness to treatments. Integration of patient data will become increasingly important as omics technologies become more widely used in the clinical setting.