Burden of allergic disease among ethnic minority groups in high-income countries.

The COVID-19 pandemic raised acute awareness regarding inequities and inequalities and poor clinical outcomes amongst ethnic minority groups. Studies carried out in North America, the UK and Australia have shown a relatively high burden of asthma and allergies amongst ethnic minority groups. The precise reasons underpinning the high disease burden are not well understood, but it is likely that this involves complex gene-environment interaction, behavioural and cultural elements. Poor clinical outcomes have been related to multiple factors including access to health care, engagement with healthcare professionals and concordance with advice which are affected by deprivation, literacy, cultural norms and health beliefs. It is unclear at present if allergic conditions are intrinsically more severe amongst patients from ethnic minority groups. Most evidence shaping our understanding of disease pathogenesis and clinical management is biased towards data generated from white population resident in high-income countries. In conjunction with standards of care, it is prudent that a multi-pronged approach towards provision of composite, culturally tailored, supportive interventions targeting demographic variables at the individual level is needed, but this requires further research and validation. In this narrative review, we provide an overview of epidemiology, sensitization patterns, poor clinical outcomes and possible factors underpinning these observations and highlight priority areas for research.

Peptide allergen-specific immunotherapy for allergic airway diseases-State of the art.

Allergen-specific immunotherapy (AIT) is the only means of altering the natural immunological course of allergic diseases and achieving long-term remission. Pharmacological measures are able to suppress the immune response and/or ameliorate the symptoms but there is a risk of relapse soon after these measures are withdrawn. Current AIT approaches depend on the administration of intact allergens, often comprising crude extracts of the allergen. We propose that the challenges arising from current approaches, including the risk of serious side-effects, burdensome duration of treatment, poor compliance and high cost, are overcome by application of peptides based on CD4+ T cell epitopes rather than whole allergens. Here we describe evolving approaches, summarize clinical trials involving peptide AIT in allergic rhinitis and asthma, discuss the putative mechanisms involved in their action, address gaps in evidence and propose future directions for research and clinical development.

Is direct oral amoxicillin challenge a viable approach for 'low-risk' patients labelled with penicillin allergy?

Spurious penicillin allergy (PenA) is a major public health problem. Up to 10% of the population and 20% of inpatients are labelled with PenA, but only <5%-10% have a proven allergy following comprehensive investigations. PenA tests are labour intensive and require specialist input, which may not be readily available due to limited allergy services. Therefore, patients with PenA receive alternative antibiotics that are associated with higher rates of iatrogenic infections, antimicrobial resistance and a longer hospital stay with consequent increased costs. Recent evidence suggests that a supervised 'direct' oral amoxicillin challenge (without performing allergy tests) is a safe option in low-risk patients (those least likely to be allergic based on history). Patient selection for this procedure is based on a careful guideline-based risk stratification process. Further research is needed to validate this intervention in routine clinical practice and explore potential facilitators and barriers to implementation in different healthcare settings.

Idiopathic anaphylaxis.

Idiopathic anaphylaxis (IA) or spontaneous anaphylaxis is a diagnosis of exclusion when no cause can be identified. The exact incidence and prevalence of IA are not known. The clinical manifestations of IA are similar to other known causes of anaphylaxis. A typical attack is usually acute in onset and can worsen over minutes to a few hours. The pathophysiology of IA has not yet been fully elucidated, although an IgE-mediated pathway by hitherto unidentified trigger/s might be the main underlying mechanism. Elevated concentrations of urinary histamine and its metabolite, methylimidazole acetic acid, plasma histamine and serum tryptase have been reported, consistent with mast cell activation. There is some evidence that corticosteroids reduce the frequency and severity of episodes of IA, consistent with a steroid-responsive condition. Important differential diagnoses of IA include galactose alpha-1,3 galactose (a carbohydrate contained in red meat) allergy, pigeon tick bite (Argax reflexus), wheat-dependent exercise-induced anaphylaxis, Anisakis simplex allergy and mast cell disorders. Other differential diagnoses include "allergy-mimics" such as asthma masquerading as anaphylaxis, undifferentiated somatoform disorder, panic attacks, globus hystericus, vocal cord dysfunction, scombroid poisoning, vasoactive amine intolerance, carcinoid syndrome and phaeochromocytoma. Acute treatment of IA is the same as for other forms of anaphylaxis. Long-term management is individualized and dictated by frequency and severity of symptoms and involves treatment with H1 and H2 receptor blockers, leukotriene receptor antagonist and consideration for prolonged reducing courses of oral corticosteroids. Patients should possess an epinephrine autoinjector with an anaphylaxis self-management plan. There are anecdotal reports regarding the use of omalizumab. For reasons that remain unclear, the prognosis of IA is generally favourable with appropriate treatment and patient education. If remission cannot be achieved, the diagnosis should be reconsidered.

"It's not an illness, it's just bad luck": The impact of anaphylaxis on quality of life in adults.

BACKGROUND: An increasing number of adults are being diagnosed with anaphylaxis, but its impact on health-related quality of life (HRQol) is not known. OBJECTIVE: The aim of this study was to explore the impact of anaphylaxis on HRQoL of newly diagnosed adults. METHODS: Interviews were conducted with 13 adults (aged 40-71; five males) with anaphylaxis (meeting WAO diagnostic criteria) to drugs, food, venom or spontaneous anaphylaxis, recruited using purposive sampling from allergy clinics in Birmingham, UK. Data were transcribed verbatim and analysed using thematic analysis. RESULTS: Four themes were generated from the analysis: the journey from fear to frustration; the need to maintain a healthy identity; control over uncertainty; and the supportive role of others. Participants described their first experiences of anaphylaxis as frightening. Managing the condition was associated with frustration and anxiety, in part due to uncertainty regarding when anaphylaxis might occur. Participants did not consider their allergy as an illness and wanted to retain an identity as a healthy person. They felt a strong need to have control over their anaphylaxis so that it did not take over their lives. The support from others was extremely important, but a lack of understanding of anaphylaxis sometimes hindered that support. CONCLUSIONS AND CLINICAL RELEVANCE: Anaphylaxis has an adverse impact on the HRQoL of adults irrespective of the cause. More information about anaphylaxis and its management from healthcare professionals may help patients gain a sense of control over their condition and reduce the worry and anxiety associated with it.

Fatal drug reaction to andexanet alfa: a case report.

Andexanet alfa is a recombinant, modified factor Xa (FXa) molecule that is used for the reversal of the anticoagulant effect of oral anti-FXa anticoagulants in patients with major haemorrhage. Here, we present a case of an 85-year-old man taking rivaroxaban for atrial fibrillation, who presented with an acute, upper gastrointestinal bleed. He was stabilised with red cell transfusion and then received a 400 mg bolus of andexanet alfa. Within minutes of this, he developed chest tightness, shortness of breath, ischaemic electrocardiographic changes and then cardiac arrest from which he could not be resuscitated. The onset of symptoms was clearly temporally related to andexanet alfa administration and the differential diagnosis includes anaphylaxis with Kounis syndrome, or myocardial infarction. Although infusion site reactions have been reported and are relatively common, this is to date the first case of a fatal drug reaction andexanet alfa. This knowledge can be factored into physicians' risk-benefit decisions when treating patients with oral anti-FXa anticoagulant-associated major haemorrhage.

Food-dependent exercise-induced anaphylaxis: is wheat unique?

This review draws comparisons between wheat-dependent exercise-induced anaphylaxis (WDEIA) and other food-dependent exercise-induced anaphylaxis (FDEIAs) and discusses the importance of co-factors in its pathophysiology. FDEIA remains an enigmatic condition since it was first described 30 years ago. The sporadic and unpredictable nature of its reactions has puzzled clinicians and scientists for decades, but recent studies on WDEIA have enlightened us about the pathophysiology of this condition. The identification of defined allergic epitopes such as Tri a 19, α-gliadin, ß-gliadin and γ-gliadin in WDEIA enables it to become the perfect model for studying FDEIA, but WDEIA is by no means a unique condition. On a larger scale, FDEIA represents a crucial link between IgE-mediated and anaphylactoid reactions and provides supportive evidence for the concept of 'summation anaphylaxis' and the need to overcome the 'allergen threshold'. Future work should focus on identifying more of the FDEIA epitopes and understanding their distinct molecular properties. The development of a biomarker in order to identify patients susceptible to co-factor influences would be invaluable.

Development and Validation of the Anaphylaxis Quality of Life Scale for Adults.

BACKGROUND: Anaphylaxis is a severe and potentially life-threatening allergic reaction that can have a detrimental impact on quality of life (QoL). There are no validated scales to measure the impact of anaphylaxis on QoL of adults. OBJECTIVE: The aim of this study was to develop and assess the reliability and validity of a QoL scale for adults with anaphylaxis (Anaphylaxis Quality of Life Scale for Adults [A-QoL-Adults]). METHODS: All participants were recruited from a specialist allergy clinic and had a confirmed diagnosis of anaphylaxis (as per the World Allergy Organization diagnostic criteria) to food, drugs, venom, or latex or had spontaneous anaphylaxis. Interviews were conducted with 13 adults; data were analyzed using thematic analysis to extract items for a QoL scale. A prototype QoL scale was then completed by 115 participants alongside validated scales to measure generic QoL (World Health Organization Quality of Life Scale [Brief Version] [WHOQoL BREF]), anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), and stress (Perceived Stress Scale [PSS]). RESULTS: The A-QoL-Adults scale has 21 items demonstrating excellent internal reliability (Cronbach α = 0.96). Factor analysis produced 3 subscales: Emotional Impact; Social Impact; and Limitations on Life. Each has excellent internal reliability (0.92, 0.92, and 0.91, respectively). Poorer anaphylaxis-related QoL (total A-QoL-Adults score and subscale scores) correlated significantly with poorer general QoL and greater anxiety, depression, and stress (all P < .01 with medium-to-large effect sizes). CONCLUSIONS: The A-QoL-Adults scale is a reliable measure of QoL in adults with anaphylaxis and shows good construct validity. It will offer health care professionals a means to further understand the impact of anaphylaxis on adult patients and could help direct and monitor allergy management and the need for further psychological intervention.

Risk factors for systemic reactions to bee venom in British beekeepers.

BACKGROUND: There is a high incidence of systemic reactions (SRs) to bee stings in beekeepers, but the factors predisposing individuals to such responses are not well understood. OBJECTIVES: To identify factors that predispose British beekeepers to SRs and to investigate how beekeepers access specialist services after SRs to bee venom. METHODS: A link to an online survey was published in the bimonthly magazine and on the Web site of the British Beekeepers Association. The demographic results are presented using descriptive analysis, and a logistic regression model was used to determine risk factors for SRs. RESULTS: There were 852 responses to the questionnaire of which 63% were from male beekeepers; the most common age range was 51 to 60 years. Twenty-eight percent of all responders had experienced a large local reaction and 21% had experienced a SR. Factors that predisposed beekeepers to SRs included female sex, having a family member with bee venom allergy, more than 2 years of beekeeping before a SR, and premedication with an antihistamine before attending the hives. A total of 44% of beekeepers with SRs attended the emergency department because of their symptoms, 16.6% were reviewed by an allergy specialist, and only 18% carried an adrenaline autoinjector. CONCLUSIONS: Logistic regression analysis identified a number of novel factors to be associated with the development of SRs. Rates of attendance at the emergency department, allergy specialist review, and carriage of adrenaline were low, highlighting a need for education in the beekeeping community and among health care professionals.

The role of a clinical pharmacist in spurious Penicillin allergy: a narrative review.

Background A label of penicillin allergy is held by 6-10% of the general population and 15-20% of inpatients. > 90% of these labels are found to be spurious after formal allergy assessment. Carrying an unnecessary label of penicillin allergy is not benign. Such patients may receive second line, more expensive antibiotics, representing a significant impediment to antimicrobial stewardship. Aim of the review To (a) Explain the burden of spurious penicillin allergy, and evaluate the safety of direct oral penicillin challenge in 'low risk' patients (b) appraise the place for a clinical pharmacist-led penicillin allergy de-labelling programme. Method Narrative review. Search engines: PubMed, Google Scholar and Cochrane reviews. Search criteria: English language; search terms: penicillin allergy, antimicrobial stewardship, antimicrobial resistance, clostridium difficile, vancomycin resistant enterococci, risk stratification, clinical pharmacist and direct oral provocation test Results Penicillin allergy labels are associated with: longer hospital stay, higher readmission rates, enhanced risk of surgical site infections, risk of Clostridioides difficile infection and Methicillin resistant Staphylococcus aureus infection, a delay in the first dose of an antibiotic in sepsis and higher healthcare costs. A direct oral penicillin challenge in 'low risk' patients has proven to be safe. Discussion Recent studies including those led by a clinical pharmacist have demonstrated safety of a direct oral penicillin challenge in 'low risk' patients. This intervention needs validation within individual health services. Conclusion Direct oral penicillin challenge reduces the adverse impact of spurious penicillin allergy. A pharmacist-led penicillin allergy de-labelling program needs further validation in prospective multi-centre studies.

Biomarkers in Human Anaphylaxis: A Critical Appraisal of Current Evidence and Perspectives.

Anaphylaxis is a type I hypersensitivity reaction that is potentially fatal if not promptly treated. It is a clinical diagnosis, although measurement of serial serum total mast cell tryptase (MCT) is gold standard and may help differentiate anaphylaxis from its mimics. The performance characteristics of MCT assays in anaphylaxis has been variable in previous studies, due to multiple factors including differences in the definition of anaphylaxis, methods of MCT interpretation, clinical setting of anaphylaxis, causative agents, and timing of blood sample. An international consensus equation for MCT to interpret mast cell activation has been proposed and recently validated in the context of peri-operative anaphylaxis during general anesthesia. There has been an interest in the detection of newer biomarkers in anaphylaxis including platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, and CCL-2. The key determinants of an ideal biomarker in anaphylaxis are half-life, sample handling and processing requirements, and cost. There may be a role for metabolomics and systems biology in the exploration of novel biomarkers in anaphylaxis. Future studies applying these approaches might provide greater insight into factors determining severity, clinical risk stratification, identification of mast cell disorders and improving our understanding of this relatively complex acute immunological condition. Post mortem MCT evaluation is used in Forensic Medicine during autopsy for cases involving sudden death or suspected anaphylaxis. Interpretation of post mortem MCT is challenging since there is limited published evidence and the test is confounded by multiple variables largely linked to putrefaction and site of sampling. Thus, there is no international consensus on a reference range. In this state of the art review, we will focus on the practical challenges in the laboratory diagnosis of anaphylaxis and critically appraise (a) performance characteristics of MCT in anaphylaxis in different clinical scenarios (b) the role for novel biomarkers and (c) post mortem MCT and its role in fatal anaphylaxis.

The concordance between component tests and clinical history in British adults with suspected pollen-food syndrome to peanut and hazelnut.

BACKGROUND: Mild oropharyngeal symptoms to peanut/hazelnut occur in ~30% of patients with pollen-food syndrome (PFS). Component tests are considered a useful adjunct to the diagnosis and may help differentiate PFS from those at a risk of anaphylaxis due to storage protein/lipid transfer protein (LTP) sensitisation. AIMS: To assess concordance between component tests and clinical history in suspected PFS to peanut/hazelnut in a specialist clinic. METHODS: Adult patients were classified into PFS (group 1, n=69) and PFS with mild systemic symptoms (group 2, n=45) based on clinical history. Specific IgE (sIgE) of ≥0.35 kUA/L was considered positive as per manufacturers' recommendation. Kappa (κ) inter-rater agreement was calculated for concordance between clinical classification and test profiles. RESULTS: Group 1 hazelnut: 85% monosensitised to Cor a1, 12% to storage protein/s or LTP and 3% negative to all components. Group 1 peanut: 41% monosensitised to Ara h8, 44% to storage protein/s or ±LTP and 15% negative to all components. Group 2 hazelnut: 67% monosensitised to Cor a1, 16% sensitised to storage protein/s and 17% negative to all components. Group 2 peanut: 19% monosensitised to Ara h8, 62% sensitised to storage protein/s and/or LTP and 19% negative to all components.SIgE to Ara h8 and Cor a1 were greater in group 1 versus group 2: (median (IQR) kUA/L; hazelnut: 12.1 (7.8-25.2) vs 2.4 (0.36-6.3), p<0.001; peanut: 2.4 (0.10-21.1) vs 0.3 (0-3), p<0.01)). CONCLUSION: Concordance between component tests and clinical history for adults with PFS was good for hazelnut (κ=0.63) but poor for peanut (κ=-0.12). Food challenges are warranted in discordant cases for an accurate diagnosis.

Anaphylaxis and Clinical Utility of Real-World Measurement of Acute Serum Tryptase in UK Emergency Departments.

BACKGROUND: British guidelines recommend that serial acute serum tryptase measurements be checked in all adults and a subset of children presenting with anaphylaxis. This is the first study reporting the clinical utility of acute serum tryptase in a "real-world" emergency department (ED) setting following the publication of the World Allergy Organization (WAO) criteria for anaphylaxis. OBJECTIVES: To (1) assess sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of acute serum tryptase in anaphylaxis; (b) determine factors associated with higher acute serum tryptase levels; and (c) audit compliance of acute serum tryptase measurement in the ED. METHODS: The methods used were retrospective electronic search for ED admissions to 3 acute care hospitals in Birmingham, UK, with anaphylaxis in 2012 using wide search terms followed by scrutiny of electronic clinical records and application of the WAO diagnostic criteria for anaphylaxis. Patients with an acute serum tryptase measurement were included in the analysis. RESULTS: Acute serum tryptase level was measured in 141 of 426 (33.1%) cases. Mean time from the onset of symptoms to the measurement of acute serum tryptase level was 4 hours 42 minutes (SD ± 05:03 hours) and no patients had serial measurements conforming to British guidelines. Acute serum tryptase level of more than 12.4 ng/mL (75th centile) was associated with a sensitivity, specificity, PPV, and NPV of 28%, 88%, 0.93, and 0.17, respectively. Multiple regression analysis showed that male sex (odds ratio, 2.66; P = .003) and hypotension (odds ratio, 7.08; P = .001) predicted higher acute serum tryptase level. CONCLUSIONS: An acute serum tryptase level of more than 12.4 ng/mL in an ED setting carries high PPV and specificity, but poor sensitivity and NPV.

Systemic reactions and anaphylaxis with an acute serum tryptase ≥14 µg/L: retrospective characterisation of aetiology, severity and adherence to National Institute of Health and Care Excellence (NICE) guidelines for serial tryptase measurements and specialist referral.

AIMS: To characterise patients with systemic reactions and anaphylaxis with an acute serum tryptase of ≥14 µg/L against recently published World Allergy Organisation (WAO) diagnostic criteria. To also perform a clinical audit to assess adherence to National Institute of Health and Care Excellence (NICE) guideline recommendations regarding serial tryptase measurements and specialist referral. METHODS: A systematic retrospective survey (2006-2010) was carried out (n=171; males=86; mean age±SD 48±20 years) and data were extracted from emergency department and specialist allergy clinic records. RESULTS: 34 patients (20%) had a grade 1 reaction, 61 (36%) grade 2, 46 (27%) grade 3 and 6 patients (4%) grade 4 (24 patients (13%) could not be graded due to lack of adequate clinical details) and 6% developed a biphasic response. Serial tryptase measurements were not available in 117 (69%) of the cohort. 97 (57%) patients were referred for specialist assessment, and 72 (74%) attended. 50% of cases were diagnosed with idiopathic systemic reactions/anaphylaxis and 28%, 14% and 8% triggered by drugs, foods and other allergies including disorders of mast cell overload, respectively. A weak positive correlation was detected between acute serum tryptase and severity. CONCLUSIONS: The correlation between acute serum tryptase and severity of anaphylaxis/systemic reactions is weak. A significant proportion of patients with raised acute serum tryptase had mild reactions which did not meet WAO criteria for anaphylaxis and this may reduce the specificity of the test. The commonest aetiology in this cohort was idiopathic followed by drug and food allergies. NICE guidelines relating to serial tryptase measurements and specialist referral were not followed, and there is an urgent need to raise the awareness among clinicians involved in the management of anaphylaxis.