Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: A focus on the Asia-Pacific region.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency or dysfunction is a rare genetic disorder that causes recurrent episodes of swelling in various parts of the body. Treatment goals of HAE aim to "normalize" life for all patients; however, lack of diagnostic facilities and limited access to effective treatment options in developing nations cause delays in diagnosis and place a significant burden on patients. In this review, we aim to highlight the burden of disease caused by C1-inhibitor HAE across the Asia-Pacific region, considering its epidemiology, morbidity and mortality, and socioeconomic and psychological impact. We also review the availability of guideline-recommended diagnostic facilities and treatments, and how patients are currently managed. Data were collected from published literature and HAE experts in the region, who provided information regarding diagnosis and management in their countries. Current practice was reviewed against international guidelines, as well as local guidelines/consensus used in Australia, Japan, and China. Suggestions are provided for improving the time to diagnosis in the region, increasing access to guideline-recommended treatments, and providing support to reduce the burden on patients and caregivers. There is an urgent need to improve HAE services and provide access to life-saving treatment in developing countries, and efforts should be made to increase awareness of guideline recommendations in high-income economies that do not currently provide long-term prophylactic treatments.

Asia Pacific perspectives on the second year of the COVID-19 pandemic: A follow-up survey.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic is currently in its third year. This follow-up survey was commissioned by the Asia Pacific Association of Allergy Asthma and Clinical Immunology (APAAACI) Task Force on COVID-19 to compare and contrast changes in the epidemiology, clinical profile, therapeutics and public health measures of the pandemic in the Asia Pacific region. METHODS: A questionnaire-based survey comprising 32 questions was electronically sent out to all 15 member countries of APAAACI using Survey Monkey® from 1 December 2021 to 28 February 2022. RESULTS: Seventeen responses were received from 14/15 (93.4%) member countries and 3 individual members. Mild-to-moderate COVID-19 predominated over severe infection, largely contributed by COVID-19 vaccination programmes in the region. The incidence of vaccine adverse reactions in particular anaphylaxis from messenger ribonucleic acid (mRNA) vaccines was no longer as high as initially anticipated, although perimyocarditis remains a concern in younger males. Novel therapeutics for mild-to-moderate disease including neutralizing antibodies casirivimab/imdevimab (REGEN-COV®) and sotrovimab (Xevudy®), anti-virals Paxlovid® (nirmatrelvir and ritonavir) and Molnupiravir pre-exposure prophylaxis for high-risk persons with Tixagevimab and Cilgavimab (Evusheld) are now also available to complement established therapeutics (e.g., remdesivir, dexamethasone and baricitinib) for severe disease. In the transition to endemicity, public health measures are also evolving away from containment/elimination strategies. CONCLUSIONS: With access to internationally recommended standards of care including public health preventive measures, therapeutics and vaccines among most APAAACI member countries, much progress has been made over the 2-year period in minimizing the morbidity and mortality from COVID-19 disease.

Clinical features and outcomes from the Singapore Sjögren's syndrome study.

OBJECTIVE: To study the clinical features, treatment and outcomes of primary Sjögren's Syndrome (pSS) in a Singapore cohort from an outpatient rheumatology clinic. METHODS: Computerised Physician Order entry records of patients who fulfilled the 2016 ACR-EULAR classification criteria for pSS between 1993 and 2013 were retrospectively analysed. RESULTS: There were 102 patients, of which 96 (94.1%) were females, and 91 (89.2%) Chinese. Mean age at diagnosis was 49.3 ± 11.8 years, mean disease duration was 9.0 ± 4.6 years. The most common manifestations were keratoconjunctivitis sicca (99.0%), xerostomia (96.1%), arthralgia/arthritis (56.9%). Exocrine glandular enlargement comprised parotidomegaly (28, 27.5%), with concurrent submandibular and lacrimal gland enlargement in one. The nervous system (15.7%) was the most commonly affected internal organ, with peripheral nervous system (peripheral neuropathy, mononeuritis multiplex) involvement more common than central. Hydroxychloroquine was most frequently used (88.2%), followed by methotrexate (7.8%) and azathioprine (6.9%). Pulsed intravenous (IV) methylprednisolone 500 mg/day for 3 days was used in 5 patients followed by oral (4) or IV cyclophosphamide (1) for cardiomyopathy and interstitial lung disease (1), and neurological involvement (4). These comprised neuromyelitis optica, transverse myelopathy, cranial neuropathy, mononeuritis multiplex and/or peripheral neuropathy alone or in combination. Intravenous immunoglobulins (2.0%) was used for sensory neuropathy and mononeuritis multiplex; rituximab (1.0%) in 1 patient for treatment of non-Hodgkin's B-cell lymphoma. There were no deaths. CONCLUSION: Musculoskeletal manifestations were common, with the nervous system (peripheral more than central) the most common internal organ involved. Lymphoma was uncommon despite up to one-third of the cohort developing glandular enlargement.

Food-induced anaphylaxis morbidity: Emergency department and hospitalization data support preventive strategies.

BACKGROUND: Anaphylaxis is a recognized public health issue. There is no doubt that food-induced anaphylaxis (FIA) has tremendous impact on the quality of life of patients and their families and increases direct and indirect costs. FIA is associated with increasing rates of emergency department admissions and hospitalizations and implies the risk of death. Morbidity epidemiological data are a key to tailor public health actions to this non-communicable disease. The aim of this article was to review published morbidity epidemiological data relating to FIA and potential risk factors, in order to provide evidence-based recommendations to reduce the risk of severe adverse outcomes. METHODS: We identified published studies available in PUBMED/MEDLINE (1966-2020), EMBASE (1980-2020) and CINAHL (1982-2020). The systematic review was carried out using MeSH terms related to FIA ED admissions and hospitalizations. RESULTS: A total of 25 articles were selected, 80% published in the last 5 years. After critical analysis of methodological and clinical characteristics reported in the data selected, we were able to propose preventive strategies. CONCLUSION: Anaphylaxis is a recognized public health issue. FIA is associated with increasing rates of ED admissions and hospitalizations and imply in risk of death. More than reviewing and critically interpreting the key patterns related to FIA morbidity published data, we proposed strategies in order to promote quality care of patients suffering from FIA. Our World Health Organization Collaborative Center is deeply involved in this process, and we believe that the proposed strategies will inform future healthcare policies on anaphylaxis. The long-term objective would be to improve clinical care and quality of life of patients and their families, and develop risk-stratified, cost-effective preventive measures.

Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid arthritis.

BACKGROUND: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. METHODS: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. RESULTS: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512). CONCLUSION: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.

Impact of Value-Driven Healthcare Strategies for Biosimilar Adoption: The Singapore Story.

BACKGROUND: Healthcare sustainability is a global challenge. Various value-driven healthcare strategies have been implemented by Singapore's national health technology assessment (HTA) agency, the Agency for Care Effectiveness (ACE). Considering the high and growing expenditure on biologics, strategies have been implemented to drive the use of biosimilars. As Singapore has reached the 5-year mark since the subsidy listing of the first monoclonal antibody biosimilar infliximab, this review aimed to evaluate the impact of these strategies on the changes in adoption rates, utilisation, spending and cost savings for biosimilars in the public healthcare sector. METHODS: A retrospective cross-sectional study was conducted using aggregated drug utilisation data from all public healthcare institutions. Five monoclonal antibodies with biosimilars, namely infliximab, adalimumab, trastuzumab, rituximab and bevacizumab, were included in this study. The outcomes evaluated were the monthly trends for utilisation volume, proportion attributed to biosimilar use, and drug spending up to December 2022. The simulated cost savings associated with biosimilar adoption were also reported. RESULTS: After subsidy implementation, an upward trend in biosimilar use and proportion attributed to biosimilar adoption was observed, while spending reduced substantially. The adoption rate of most biosimilars reached more than 95% within 1 year of listing. Drugs with more than one approved biosimilar brand at the time of subsidy listing reported substantial price reductions of over 80%. Overall, spending for the five monoclonal antibodies have significantly reduced after biosimilar subsidy listing, with an estimated cumulative cost savings of $136 million over 5 years. CONCLUSION: Value-driven healthcare strategies implemented in Singapore's public healthcare institutions have contributed to high adoption rates of biosimilars and have improved affordable access through lower treatment costs. This in turn has led to significant cost savings to the healthcare system.

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore.

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

Drug-induced Stevens Johnson syndrome and toxic epidermal necrolysis: Interpreting the systematic reviews on immunomodulatory therapies.

Drug-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are non-immunoglobulin E-mediated severe cutaneous adverse reactions with a high risk of morbidity, mortality, and physical and mental health impact. These are associated with certain high-risk drugs, human leukocyte antigen (HLA)-specific genotypes and ethnicities. HLA class I-restricted oligoclonal CD8 cytotoxic T-cell responses occur at the tissue level in SJS/TEN. Cytotoxic T cells are the T effector cells that result in keratinocyte apoptosis (cell death) mediated by T effector molecules granzyme B, perforin, granulysin, gamma interferon, tumor necrosis factor-alpha, and lipocalin-2. The clinical hallmarks of SJS/TEN include fever, ≥2 mucosal involvements (ocular, oral, and genital), and positive Nikolsky sign with epidermal detachment. Systematic reviews on immunomodulatory treatments remain limited by the paucity of randomized controlled trials, heterogeneity of studies, and non-standardization of outcome measures. Preventive HLA genotype screening before the prescription of carbamazepine and allopurinol may further reduce the incidence of SJS/TEN. The role of immunomodulatory treatments in SJS/TEN is at present not supported by robust evidence from systematic reviews given the lack of randomized controlled trials. The evidence for improved survival with off-label use of corticosteroids plus intravenous immunoglobulins, ciclosporin plus intravenous immunoglobulins, and ciclosporin alone has not been demonstrated by network meta-analyses and meta-regression. In the real-world clinical setting, systemic corticosteroids (in SJS and overlap SJS/TEN), ciclosporin, and etanercept (in TEN) appear to be the off-label treatments currently most widely used.

Delabelling multiple antibiotic allergy: Practical issues.

With the growing incidence of multi-drug resistant organisms, delabelling incorrect antibiotic allergies has become an integral part of antimicrobial stewardship worldwide. For example, around 90% of penicillin allergy labels are found to be inaccurate following a full allergy work-up, which deprive patients the use of effective first-line penicillin antibiotics and increase the risk of antimicrobial resistance with the use of other extended spectrum non-penicillin antimicrobials. Significant numbers of adult and paediatric patients over time are labelled with multiple penicillin and non-penicillin antibiotic allergies often during inappropriate antimicrobial use, resulting in a label of "multiple antibiotic allergy". In contrast to delabelling penicillin allergy where oral direct provocation tests can be used for low-risk, mild reactions, and sensitivity/specificity/positive and negative predictive values of skin tests have been demonstrated, diagnostic tests for multiple antibiotic allergy often require the use of a combination of in-vivo and in-vitro tests across different antimicrobial classes for evaluation. Shared decision making with patients and informed consent are also needed when prioritising which drugs to delabel first, balancing the risks, benefits of testing vs. interim use of alternative antibiotics. Similar to delabelling penicillin allergy, the cost-effectiveness of delabelling multiple drug allergies is unknown.

Inflammatory Arthritis Among Military Servicemen From a Rheumatology Center in Singapore.

INTRODUCTION: Musculoskeletal disorders are one of the most common reasons military servicemen seek medical care during their line of duty. This study aims to review the clinical profile and outcomes of military personnel with inflammatory arthritis (IA) referred to a specialist rheumatology center in Singapore. MATERIALS AND METHODS: Consecutive new case referrals from the Singapore Armed Forces medical centers during the study period January 1, 2010, to December 31, 2019, were retrospectively studied. RESULTS: There were 123 referrals, comprising 112 (91.1%) males, with the majority being Chinese (110, 89.4%). The mean age was 25.5 ± 11.1 years. The most common diagnoses were gout (including chronic tophaceous gout; 34, 27.6%), spondyloarthritis (18, 14.6%), palindromic rheumatism (8, 6.5%), rheumatoid arthritis (4, 3.3%), and juvenile idiopathic arthritis (4, 3.3%). Among servicemen with gout, all were male, the majority (31, 91.3%) were Chinese, and mean age was 34.1 ± 8.8 years. Mean body mass index (BMI) was 27.5 ± 3.9 kg/m2, of which 41.2% had moderate-risk and 47.1% high-risk BMI for cardiovascular disease and diabetes mellitus (DM). Comorbidities included hyperlipidemia (14), hypertension (6), and type 2 DM (3). Urate lowering therapy was initiated in 27 (79.4%) patients, comprising allopurinol (85.2%), probenecid (11.1%), and their combination (3.7%). One patient developed allopurinol-induced hepatitis; none had severe cutaneous adverse reactions. Among the remaining patients with IA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) used were sulfasalazine (8), methotrexate (4), hydroxychloroquine (4), and leflunomide (2). Biologic DMARDs used in five patients comprised adalimumab (3) and golimumab (2). CONCLUSION: Servicemen with IA and good functional status can still be physically fit and deployable into certain combat and service support vocations. This will optimize manpower resources in military organizations with a shrinking young workforce.

Epidemiology of the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases that affect the skeletal muscles and can also involve the skin, joints, lungs and heart. The epidemiology of IIM is obscured by changing classification criteria and the inherent shortcomings of case identification using healthcare record diagnostic coding. The incidence of IIM is estimated to range from 0.2 to 2 per 100,000 person-years, with prevalence from 2 to 25 per 100,000 people. Although the effects of age and gender on incidence are known, there is only sparse understanding of ethnic differences, particularly in indigenous populations. The incidence of IIM has reportedly increased in the twenty-first century, but whether this is a genuine increase is not yet known. Understanding of the genetic risk factors for different IIM subtypes has advanced considerably. Infections, medications, malignancy and geography are also commonly identified risk factors. Potentially, the COVID-19 pandemic has altered IIM incidence, although evidence of this occurrence is limited to case reports and small case series. Consideration of the current understanding of the epidemiology of IIM can highlight important areas of interest for future research into these rare diseases.

Evaluating immune responses to pneumococcal vaccines.

Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

APAAACI clinical pathway on direct provocation testing for penicillin allergy delabeling.

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential. Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP. Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong. Results: The clinical pathway was piloted employing a "hub-and-spoke" approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist's care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT. Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists.

Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions.

The underlying immunological mechanisms of immediate-type hypersensitivity reactions (HSR) to COVID-19 vaccines are poorly understood. We investigate the mechanisms of immediate-type hypersensitivity reactions to the Pfizer BNT162b2 vaccine and the response of antibodies to the polyethylene glycol (PEG)ylated lipid nanoparticle after two doses of vaccination. Sixty-seven participants, median age 35 and 77.3% females who tolerated two doses of the BNT162b2 vaccine (non-reactors), were subjected to various blood-sampling time points. A separate group of vaccine reactors (10 anaphylaxis and 37 anonymised tryptase samples) were recruited for blood sampling. Immunoglobulin (Ig)G, IgM and IgE antibodies to the BNT162b2 vaccine, biomarkers associated with allergic reaction, including tryptase for anaphylaxis, complement 5a(C5a), intercellular adhesion molecule 1 (ICAM-1) for endothelial activation and Interleukin (IL)-4, IL-10, IL-33, tumour necrosis factor (TNF) and monocyte chemoattractant protein (MCP-1), were measured. Basophil activation test (BAT) was performed in BNT162b2-induced anaphylaxis patients by flow cytometry. The majority of patients with immediate-type BNT162b2 vaccine HSR demonstrated raised C5a and Th2-related cytokines but normal tryptase levels during the acute reaction, together with significantly higher levels of IgM antibodies to the BNT162b2 vaccine (IgM 67.2 (median) vs. 23.9 AU/mL, p < 0.001) and ICAM-1 when compared to non-reactor controls. No detectable IgE antibodies to the BNT162b2 vaccine were found in these patients. The basophil activation tests by flow cytometry to the Pfizer vaccine, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (DMG-PEG) and PEG-2000 were negative in four anaphylaxis patients. Acute hypersensitivity reactions post BNT162b2 vaccination suggest pseudo-allergic reactions via the activation of anaphylatoxins C5a and are independent of IgE-mechanisms. Vaccine reactors have significantly higher levels of anti-BNT162b2 IgM although its precise role remains unclear.

Global disparities in availability of epinephrine auto-injectors.

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis - both acute and preventative - varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.