Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy.

State of the art in AIT: The patients' perspective.

BACKGROUND: On the occasion of the 110th anniversary of allergen-specific immunotherapy (AIT), the question arises of "how do patients feel about AIT?". MATERIALS AND METHODS: Informed by questions and feedback provided to MeinAllergiePortal, an online survey with a target of 130 responses was devised and offered for completion by readers. All visitors of MeinAllergiePortal categories addressing inhalant allergies were invited to participate in the survey. Participants were grouped and analyzed by their AIT completion status. The survey was ended once target was met. RESULTS: 121 of 132 participants were familiar with AIT. 1) A majority of patients who completed AIT would choose the therapy again; 2) Physicians do not seem to discuss AIT with all patients with significant symptoms; 3) Adverse reactions appear to be a major reason why patients terminate AIT prematurely; 4) Lack of time, or early response, as often supposed, does not seem to be a major factor leading to discontinuation of AIT. CONCLUSION: Patients' experience and understanding of symptoms (both related to allergic disease, or expected AIT-related adverse events) appear to be key factors related to AIT engagement and adherence. Given the importance of adherence for AIT efficacy, improved education and support strategies may assist patients achieve their treatment goals.

Thunderstorm asthma in seasonal allergic rhinitis: The TAISAR study.

BACKGROUND: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. OBJECTIVE: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. METHODS: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR. RESULTS: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV1 value of 90% or lower to be biomarkers of increased H-TA risk. CONCLUSION: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study.

BACKGROUND: Ocrelizumab safety outcomes have been well evaluated in clinical trials and open-label extension (OLE) studies. However, risk factors for infection in patients with multiple sclerosis (MS) receiving ocrelizumab have not been extensively studied in the real-world setting. OBJECTIVE: The aim of this study was to examine factors determining risk of self-reported infections and antimicrobial use in patients receiving ocrelizumab for MS. METHODS: A retrospective, observational cohort study was conducted in patients receiving ocrelizumab at the Royal Melbourne Hospital. Infection type and number were reported by patients, and the associations of potential clinical and laboratory risk factors with self-reported infection and antimicrobial use were estimated using univariate and multivariable logistic regression models. RESULTS: A total of 185 patients were included in the study; a total of 176 infections were reported in 89 patients (46.1%), and antimicrobial use was identified in 47 patients (25.3%). In univariate analyses, a higher serum IgA was associated with reduced odds of infection (OR 0.44, 95% CI 0.25-0.76). In multivariable analyses, older age (OR 0.94, 95% CI 0.88-0.99), higher serum IgA (OR 0.37, 95% CI 0.17-0.80) and higher serum IgG (OR 0.81, 95% CI 0.67-0.99) were associated with reduced odds of infection. Older age (OR 0.85, 95% CI 0.75-0.96) and higher serum IgA (OR 0.23, 95% CI 0.07-0.79) were associated with reduced odds of antimicrobial use, whilst longer MS disease duration (OR 1.22, 95% CI 1.06-1.41) and higher Expanded Disability Status Scale (EDSS) score (OR 1.99, 95% CI 1.02-3.86) were associated with increased odds of antimicrobial use. CONCLUSIONS: Higher serum IgA and IgG and older age were associated with reduced odds of infection. Our findings highlight that infection risk is not uniform in patients with MS receiving ocrelizumab and substantiate the need to monitor immunoglobulin levels pre-treatment and whilst on therapy.

Using crowd-sourced allergic rhinitis symptom data to improve grass pollen forecasts and predict individual symptoms.

Seasonal allergic rhinitis (AR), also known as hay fever, is a common respiratory condition brought on by a range of environmental triggers. Previous work has characterised the relationships between community-level AR symptoms collected using mobile apps in two Australian cities, Canberra and Melbourne, and various environmental covariates including pollen. Here, we build on these relationships by assessing the skill of models that provide a next-day forecast of an individual's risk of developing AR and that nowcast ambient grass pollen concentrations using crowd-sourced AR symptoms as a predictor. Categorical grass pollen forecasts (low/moderate/high) were made based on binning mean daily symptom scores by corresponding categories. Models for an individual's risk were constructed by forward variable selection, considering environmental, demographic, behaviour and health-related inputs, with non-linear responses permitted. Proportional-odds logistic regression was then applied with the variables selected, modelling the symptom scores on their original five-point scale. AR symptom-based estimates of today's average grass pollen concentration were more accurate than those provided by two benchmark forecasting methods using various metrics for assessing accuracy. Predictions of an individual's next-day AR symptoms rated on a five-point scale were correct in 36% of cases and within one point on this scale in 82% of cases. Both outcomes were significantly better than chance. This large-scale AR symptoms measurement program shows that crowd-sourced symptom scores can be used to predict the daily average grass pollen concentration, as well as provide a personalised AR forecast.

Multicenter Australian Study to Determine Criteria for Low- and High-Risk Penicillin Testing in Outpatients.

BACKGROUND: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain. OBJECTIVE: To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing. METHODS: In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition. RESULTS: A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9). CONCLUSIONS: History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.

Crowd-sourced allergic rhinitis symptom data: The influence of environmental and demographic factors.

Allergic Rhinitis (AR) affects over half a billion people worldwide with an estimated prevalence of 1 in 5 individuals in developed countries. Although ambient pollen exposure is a causal factor in AR, the symptom-exposure relationship is typically not studied in the broader community but in small, well-characterised cohorts drawn from clinical populations. To identify relationships between AR symptoms in the community and a range of environmental factors, we used a database containing over 96,000 symptom score reports collected over a 3-year period (2014-2016) through freely available smartphone apps released in two Australian cities, Melbourne and Canberra. Ambient pollen levels and symptom scores were strongly related, with grass pollen explaining most of the symptom variation. Other factors correlated with higher symptom scores included temperature (R > 0.73) and wind speed (R > 0.75). In general, worse symptom scores were reported by younger participants, women, and those who had taken medication for AR in the preceding 24 h. The strength of this relationship varied between the two cities. Smartphone-based symptom surveys offer a cost-effective means of studying real-world risk factors for AR in a broader 'extra-clinical' population.

Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults.

Background: Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. Results: 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. Conclusion: Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.