Allergic Triggers Research Articles

Anaesthesia-related anaphylaxis: investigation and follow-up

The European Academy of Allergy and Immunology (EAACI) redefined anaphylaxis as a severe, life-threatening, generalized, or systemic hypersensitivity reaction, sub-divided into ‘allergic’ and ‘non-allergic’ reactions. Allergic anaphylaxis has an incidence between 1/5000–1/20 000 with a 3:1 female preponderance. Despite initially increased reporting of adverse events to new drugs (Weber effect), there is generally under reporting to databases (e.g. the UK yellow card system). Anaphylaxis-related mortality is 3–6% and an additional 2% have a poor neurological outcome. Allergic anaphylaxis implies an immunological reaction (IgE, IgG, or complement mediated). Antigen exposure results in mast cell and basophil bound antibody formation. Subsequent antigen exposure causes mast cell degranulation and the release of mediators including histamine, tryptase, leukotrienes, and prostaglandins. In ‘non-allergic’ reactions, mast cell and basophil degranulation are caused by direct drug action with no immune trigger. The term ‘anaphylactoid’ is now obsolete and encompassed non-IgE-mediated and non-allergic reactions. The immunological mechanism is important as skin prick testing identifies only IgEmediated hypersensitivity. Lack of skin changes does not necessarily exclude a drug as the allergic trigger. Immediate management

CD4-Positive T-Cell Recruitment in Primary-Provoked Localized Vulvodynia

To better understand the potential disease triggers of neurogenic inflammation in provoked localized vulvodynia (PLV), our objective was to determine whether the types of infiltrating lymphocytes were different in vestibular biopsies from women with primary PLV, secondary PLV, and unaffected controls. Secondary retrospective analysis of archived vestibular biopsies from a series of adult premenopausal women with primary PLV (n = 10), secondary PLV (n = 10), and unaffected controls (n = 4) was performed. All study patients had severe entry dyspareunia for more than 1 year. Subjects were excluded if pregnant, or they had a known infection, or history of generalized vulvodynia. Biopsies were performed during the midfollicular phase. Lymphocyte subtypes were highlighted in histologic sections using antibodies against CD3, CD4, and CD8 and scored as the mean number of T-cell subtypes per high-power field. Flow cytometry was also used to test fresh biopsies from a de novo prospective series of primary PLV (n = 4) and unaffected controls (n = 2). Unaffected control biopsies showed more CD8-positive than CD4-positive T cells, similar to previous reports of the gynecologic tract. In contrast, biopsies from women with primary PLV showed significantly more CD4-positive T cells than those from women with secondary PLV and unaffected controls (p = .003). This observation was further supported by flow cytometry. CD4-positive T cells are more numerous in vestibular biopsies from premenopausal women with primary PLV. This may be important because subtypes of CD4-positive T cells are specifically recruited by infectious, allergic, or autoimmune triggers. Future studies distinguishing these subtypes may lead to new insights into this common disease.

Diagnostic yield of allergy testing in Pediatric Eosinophilic Esophagitis: a 10 year experience at a tertiary care centre

Background Eosinophilic Esophagitis (EoE) is a disease in children characterized by esophageal dysfunction and eosinophilic infiltration [1]. Patients frequently present with an atopic history; therefore, allergy testing by both skin prick and food patch testing are often performed. However, the utility of allergy testing remains unclear [1,3]. Treatment with topical corticosteroids may be needed for clinical and histologic improvement if allergic triggers are not identified [1,2]. However, the natural history of EoE suggests that this condition is chronic and may recur when corticosteroids are withdrawn [2]. Therefore, treatment with dietary/aeroallergen avoidance is preferable to reduce the need for oral corticosteroids, while preventing exacerbation of EoE [3]. This study aims to describe the atopic characteristics of a pediatric cohort with EoE over a 10 year period at a tertiary care center.

Dietary Interventions for Atopic Disorders

There are a number of atopic conditions that involve mast cells ranging from common allergies to arthritis and chronic pelvic pain syndrome. In addition to the well known allergic triggers, many food substances, drugs, as well as physical and mental stressful conditions could trigger mast cell activation in the absence of any allergic diathesis. The chronicity and morbidity of these conditions and the concern for the "adverse side effects" of the available therapeutic agents has prompted the widespread use of complementary and alternative medicines (CAM). One of the most common CAM interventions in the treatment of allergies is the use of dietary supplements that may contain specific compounds such as chondroitin sulfate, bioflavonoids or various herb extracts including Forsythia, Gingko, and Echinacea. The basis of such use has evolved from clinical anecdotal observations over time, to a growing number of in vitro and some in vivo studies that support the use of some of these compounds, especially select flavonoids.

A Preliminary Randomized Controlled Trial:Educational Intervention For Treatment Of Hispanic and African American Adults With Asthma: Allergen Triggers, Peak Flow, and Spirometry

A Preliminary Randomized Controlled Trial:Educational Intervention For Treatment Of Hispanic and African American Adults With Asthma: Allergen Triggers, Peak Flow, and Spirometry

Nocturnal Asthma In Latino Children Is Associated With Severe Disease and Allergenic Triggers (GALA II Study)

Nocturnal Asthma In Latino Children Is Associated With Severe Disease and Allergenic Triggers (GALA II Study)

Allergen Avoidance in Asthma: Is There a Role?

Asthma is a heterogeneous disease with symptoms that fluctuate in scale and severity throughout life. Whilst allergic triggers have been implicated in both its development and subsequent exacerbations, there is no conclusive evidence that allergen avoidance in infancy prevents subsequent development of asthma. Recent studies suggest that allergen avoidance is not an important management strategy in established asthma.

Eosinophilic Esophagitis and Ige-Mediated Allergy in Children: Specific Ige by Component-Based-Allergen Microarray

Background: Atopy is prevalent in eosinophilic esophagitis (EoE) but the relative role of airborn and food allergens in the etiopathogenesis is still incompletely understood; allergic immediate and delayed reactions are involved. Objective: We characterized the sIgE profile by a component-based allergen microarray with highly purified allergens in EoE in comparison with traditional sIgE assay and we evaluated a possible correlation between clinical features and sIgE results. Methods: In 30 consecutive patients diagnosed with EoE, three diagnostic tests were performed: skin prick test (SPT), ImmunoCAPi£¨ i€ sIgE and an allergen component microarray chip called ImmunoCAPi£¨ ISAC. The ISAC chips cover 103 recombinant or purified allergen molecules including food, airborn and cross-reactive allergens. Results: Out of the 30 patients, 15, 16 and 17 of the patients were sensitized as assess with SPT, ISAC and ImmunoCAPi£¨ respectively. Thirteen of the patients were multi-sensitized. The three diagnostic methods were in good agreement for all patients; the ISAC method provided new information in 8 patients, not revealed by the traditional tests, either by detection of panallergens or unsuspected triggering allergens. Conclusions: sIgE detection by the ISAC microarray revealed that airborne allergens and panallergens are more frequently involved than food allergens in our population. The ISAC data were in agreement with both traditional tests and doctor’s diagnosis/open challenge and revealed new information that can improve understanding of the EoE pathogenesis and management. Key message: immune-solid phase allergen chip (ISAC) gives new information about cross reactive molecules and identification of panallergens, which are not possible to obtain from traditional test.

Characterizing Rhinitis Subtypes

Allergic rhinitis (AR) is estimated to affect 20-25% of the United States population and thus accounts for a significant portion of our annual total health care expenditure, especially when one includes all of the concomitant disorders associated with rhinitis such as asthma and sinusitis. Given the prevalence of chronic rhinitis, the significant comorbidities associated with this condition, its overall health burden, and dissatisfaction by allergy sufferers with treatment outcomes, it is essential that the allergist and otolaryngologist develop a consensus approach for the evaluation, diagnosis, and treatment of chronic rhinitis subtypes. This study was designed to achieve this end point. Investigators have taken several clinical, physiological, and mechanistic approaches toward better characterizing rhinitis subtypes. An accurate diagnosis directed at differentiating AR, nonallergic rhinitis, and mixed rhinitis is essential to ensure that treatment(s) prescribed will lead to more favorable clinical outcomes. An accurate history taking into account age of symptom onset, family history, quantification of inciting allergic and/or nonallergic triggers, and seasonality followed by aeroallergen skin testing to assess atopic status has been shown to be the most useful approach for clearly differentiating rhinitis subtypes. Other cellular, cytokine, genetic, and physiological markers have thus far been proven to be less useful. Ultimately, treatment response to medications will be most effective when they are individualized to the patient's diagnosis.

Are We There Yet? Recent Progress in the Molecular Diagnosis and Novel Antifungal Targeting of Aspergillus fumigatus and Invasive Aspergillosis

Are we there yet? Every parent has heard this inexorable question, but it is especially wrenching to hear it from a patient with a fatal illness. When someone, or someone's child, is diagnosed with invasive aspergillosis (IA) caused by Aspergillus fumigatus, the outcome has historically been bleak. In 2013, the field is erupting with exciting advances on multiple scientific fronts. But whether those research findings will improve clinical outcomes is still unclear—does your spouse, child, or neighbor now live or die with this disease? Medical breakthroughs over the last few decades surrounding cancer and transplantation, the main underlying conditions of those afflicted with IA, have been nothing short of astonishing. However, this revolution has also spawned a plethora of immunocompromised patients to inhale fungal spores and develop IA. For many patients with an absent immune system, the second leading cause of death, just behind cancer remission or transplant failure, is infection. The leading infectious cause of death is invasive fungal infections, and the most common mortal fungal infection is A. fumigatus. So have we sufficiently advanced scientifically for today's clinical needs in order to diagnose and treat IA—are we there yet? A. fumigatus is both a beautiful and frustrating fungus. The beauty lies in the pathogen's ability to readily adapt its niche based on the host. The same fungus that lives in compost piles can shear pulmonary blood vessels in immunosuppressed patients, masquerade as an allergic trigger in an ectopic individual, or hide as a saprophyte and slowly sap the strength from an unsuspecting normal host. The frustration with this fungus is the current difficulty in early and accurate diagnosis, a limited number of effective antifungal treatments coupled with the growing emergence of antifungal resistance, and some persistent basic mechanistic questions surrounding its growth and regulation.

Skin Sensitivity to Aeroallergens in Allergic Rhinitis

ABSTRACT Background Allergic rhinitis is a common IgE-mediated inflammatory condition of the nasal mucosa. Skin prick test (SPT) remains the most useful test for detecting specific allergic triggers associated with allergic rhinitis. Objective Our objective was to study the sensitivity to common aeroallergens in allergic rhinitis patients using SPT Materials and methods We conducted SPT to 65 common aeroallergens on 100 patients more than 12 years of age with symptoms suggestive of allergic rhinitis. Results Sixty-one patients (61%) tested positive for at least one aeroallergen, of which, 54 patients (88.52%) showed polysensitization while seven patients (11.48%) showed monosensitization. The most common aeroallergen group implicated in SPT positivity was insects (48%); housefly (34%) being the most commonly implicated insect. Conclusion This study highlights a high prevalence of sensitivity to aeroallergens in the Indian scenario. It stresses upon the fact that environmental control measures might still prove to be the mainstay of treatment in our scenario, owing to housefly being the most commonly implicated aeroallergen. How to cite this article Mishra M, Chakravarti A, Kumar R. Skin Sensitivity to Aeroallergens in Allergic Rhinitis. Clin Rhinol An Int J 2013;6(2):64-66.

Ca2+-dependent Structural Changes in the B-cell Receptor CD23 Increase Its Affinity for Human Immunoglobulin E

Immunoglobulin E (IgE) antibodies play a fundamental role in allergic disease and are a target for therapeutic intervention. IgE functions principally through two receptors, FcεRI and CD23 (FcεRII). Minute amounts of allergen trigger mast cell or basophil degranulation by cross-linking IgE-bound FcεRI, leading to an inflammatory response. The interaction between IgE and CD23 on B-cells regulates IgE synthesis. CD23 is unique among Ig receptors in that it belongs to the C-type (calcium-dependent) lectin-like superfamily. Although the interaction of CD23 with IgE is carbohydrate-independent, calcium has been reported to increase the affinity for IgE, but the structural basis for this activity has previously been unknown. We have determined the crystal structures of the human lectin-like head domain of CD23 in its Ca(2+)-free and Ca(2+)-bound forms, as well as the crystal structure of the Ca(2+)-bound head domain of CD23 in complex with a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). Together with site-directed mutagenesis, the crystal structures of four Ca(2+) ligand mutants, isothermal titration calorimetry, surface plasmon resonance, and stopped-flow analysis, we demonstrate that Ca(2+) binds at the principal and evolutionarily conserved binding site in CD23. Ca(2+) binding drives Pro-250, at the base of an IgE-binding loop (loop 4), from the trans to the cis configuration with a concomitant conformational change and ordering of residues in the loop. These Ca(2+)-induced structural changes in CD23 lead to additional interactions with IgE, a more entropically favorable interaction, and a 30-fold increase in affinity of a single head domain of CD23 for IgE. Taken together, these results suggest that binding of Ca(2+) brings an extra degree of modulation to CD23 function.

Home Asthma Triggers: Barriers to Asthma Control in Chicago Puerto Rican Children

We sought objectively to measure, summarize, and contextualize the asthma triggers found in the homes of urban high-risk Puerto Rican children and adolescents with asthma in Chicago. Data were from the baseline home assessments of Project CURA. Research assistants interviewed caregivers, conducted a home visual inspection, and collected saliva samples for cotinine analysis. A trigger behavior summary score was created. The housing inspected was old with multiple units and obvious structural deficiencies. Many allergic and irritant triggers were observed. Having a controller medicine or private insurance was associated with lower trigger behavior summary scores; caregiver depression, caregiver perceived stress, and child negative life events were associated with high trigger scores. The final multivariate model retained had a controller medicine, private insurance, and caregiver perceived stress. The data from this high-risk cohort identified modifiable areas where environmental interventions could reduce morbidity in Puerto Rican children and adolescents.

Habitual Snoring in Children with Previous Allergic Sensitization

Previous studies have reported a high prevalence of allergy in children with Habitual Snoring (HS), but the relationship between allergy in the early years of life and the subsequent development of this Sleep Disordered Breathing (SDB) is yet to be elucidated. The purpose of the present study was to determine the role of early, under 36 months of age, allergic sensitization to food (with or without sensitization to airborne allergens) in determining the development of HS 8-10 years after. One hundred and forty-eight children (10-14 years, mean age 12 years) with a history of food allergy were selected. Under the age of 36 months, atopic status was assessed by skin prick test for a panel of airborne and food allergens. Questionnaires filled in by parents were used to collect information on children's snoring and associated symptoms. HS was defined as snoring three or more times per week. At 1-3 years of age 54 children were positive to food allergens alone, and 94 were positive also to airborne allergens. After 8-10 years of life, when patients were aged between 10 and 14 years, habitual snoring was reported in 37 children. Furthermore, among the 54 children under three years of age sensitized only to food, 8 became HS while of the 94 children sensitized to both food and inhalants allergens 29 developed HS. The difference between those two groups was statistically significant (p=0.04). We reported a significant risk of developing HS in children with early allergic sensitization. Specifically this risk was higher when food allergy was associated with inhalant allergy. The onset of upper airway inflammation due to allergic triggers in subjects under three years of age may be related to the subsequent development of SDB after 8-10 years.

Testing children for allergies: why, how, who and when

AbstractAllergic diseases are common in childhood and can cause a significant morbidity and impaired quality‐of‐life of the children and their families. Adequate allergy testing is the prerequisite for optimal care, including allergen avoidance, pharmacotherapy and immunotherapy. Children with persisting or recurrent or severe symptoms suggestive for allergy should undergo an appropriate diagnostic work‐up, irrespective of their age. Adequate allergy testing may also allow defining allergic trigger in common symptoms. We provide here evidence‐based guidance on when and how to test for allergy in children based on common presenting symptoms suggestive of allergic diseases.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

Chronic Urticaria: Indian Context—Challenges and Treatment Options

Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal) is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management.

Current perspectives on airway inflammation and remodelling in asthma and allergic rhinitis

1 Division of Allergy, Department of Pediatrics. Nippon Medical School, Tokyo, Japan. Review Article Braz J Allergy Immunol. 2013;1(5):243-52. Current perspectives on airway inflammation and remodelling in asthma and allergic rhinitis Ruby Pawankar, MD, PhD, FRCP, FAAAI1 The development of AR and asthma requires an interaction between the environment, immune system and genetic susceptibility. While pollen-induced rhinitis is the most characteristic IgEmediated allergic disease, in perennial allergic rhinitis the allergic triggers are more continuous, and lead to ongoing inflammation. Several cells and mediators orchestrate and maintain this inflammation. Although histamine is still one of the major mediators of the allergic reaction, many other mediators produced by different cell types are involved. Thus, the intricate interaction amongst these mediators, cytokines, chemokines, neuropeptides, adhesion molecules and various cells in the form of a complex network leads to the development of specific symptoms and the non specific hyperreactivity of allergic rhinitis. Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways which include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. While AR and asthma share several similarities in the inflammatory cell and mediator profiles and responses, remodeling as seen in asthma is not characteristic of AR. In asthma, the relationships of airway inflammation, remodeling and lung function are becoming better understood. A variety of inflammatory cells and structural cells play a role in orchestrating the inflammation and structural changes in asthma. Increased airway responsiveness is a surrogate marker of inflammation and may reflect the development of structural changes in the airways. Such persistent increased bronchial responsiveness indicates remodeling which is partly resistant to therapy.

Anaphylaxis to cow's milk formula containing short-chain galacto-oligosaccharide

On the basis of the proven prebiotic effects of oligosaccharides in cow's milk formula (CMF) in infants, CMFs are supplemented with oligosaccharides. We present a series of 5 cases of cow's milk-tolerant but atopic patients with a history of respiratory allergies. All had anaphylaxis after the ingestion of CMF supplemented with short-chain galacto-oligosaccharide (scGOS). The allergen trigger was investigated. Clinical histories were collated. Skin prick tests (SPTs) and basophil activation tests (BATs) were carried out with the eliciting CMF that triggered anaphylaxis, with or without supplemented prebiotics (scGOS) and with scGOS fractions containing oligosaccharides of different chain lengths. The median age of presentation was 6 years (range, 5-38 years). Anaphylaxis occurred within 30 minutes of the first known exposure to CMF supplemented with prebiotics in all patients. Only 1 patient was subjected to oral challenge, which resulted in an anaphylactic reaction. All patients demonstrated IgE sensitization through SPTs and BATs to scGOS and fractions of scGOS containing 3 sugar units or greater but not to cow's milk or long-chain fructo-oligosaccharide. Eight child control subjects tolerant to regular ingestion of scGOS-supplemented CMF and 1 adult volunteer were found to have negative results to scGOS through SPTs and BATs. In addition, invitro BATs with donor basophils sensitized with sera from 2 of the 3 reported cases showed reactions to scGOS. The scGOS-induced basophil activation was inhibited in the presence of wortmannin, a phosphatidylinositol 3-kinase inhibitor. This study describes an unusual form of IgE-mediated anaphylaxis triggered by low-molecular-weight oligosaccharides in scGOS. The primary sensitizer for this phenomenon requires further investigation.

Differential Diagnostic Aspects Are Lacking

Acute abdomen requires emergency treatment, including emergency diagnostic evaluation. In the introduction of their review article, the authors say that “While […] around 1% of all patients with acute abdomen have AMI [acute mesenteric ischemia], AMI is the cause of acute abdomen in up to 10% of patients aged over 70”, without explaining differential diagnostic aspects. Intestinal angioedema with massive mucosal swelling presents with similar symptoms; this seems to be neither more common nor rarer than AMI. Intestinal angioedema can have allergic triggers but can also be caused by taking angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (many cases have been documented in the literature) or be provoked by non-steroidal anti-inflammatory drugs. An individual case of intestinal angioedema has been described in a patient after taking a calcium antagonist (1). Hereditary angioedema (HAE, a defect in C1-INH synthesis), angioedema with normal concentrations of C1-esterase-inhibitor but functional insufficiency, and angioedema based on acquired C1-esterase-inhibitor deficiency (acquired angioedema, AA) as well as idiopathic angioedema should also be included in the differential diagnostic evaluation. While a patient’s medical history can provide an early indication of angioedema due to medication, diet, or hereditary causes and thus prevent unnecessary laparotomy, hereditary angioedema and other forms need to be confirmed using specific laboratory-based examination. In case of clinical suspicion, this should include immunological determination of C1-INH, functional determination of C1-INH, measurement of C1, C2, C4, CH50, and, if required, measurement of autoantibodies against C1-INH (2). Adding intestinal angioedema as a differential diagnosis to the well-known range of causes for acute abdomen might be worth mentioning, in order to clearly differentiate from vascular-ischemic causes.