Allergy Asthma and Clinical Immunology最新文献

An increasing number of patients are presenting to allergists with concerns about mast cell activation syndrome (MCAS), often in the context of persistent, unexplained, multisystem symptoms. This review aims provide a practical, stepwise approach to the diagnosis and management of MCAS, based on the consensus criteria established by the European Competence Network on Mastocytosis-American Initiative on Mast Cell Diseases, an international consortium of leading experts in mast cell disorders endorsed by major scientific organizations. The first step is to evaluate whether the clinical presentation is consistent with MCAS, recognizing that the prototypical presentation is idiopathic anaphylaxis. Symptoms should be severe, episodic, typical of mast cell activation, and involve at least two organ systems. The next step is to exclude secondary causes of mast cell activation, particularly cofactor-dependent food allergy and nonsteroidal anti-inflammatory drug hypersensitivity. Objective evidence of mast cell activation must then be obtained, preferably by identifying an acute increase in serum tryptase (on a sample drawn within four hours of an episode) compared to baseline. Alternatively, urinary metabolites of mast cell mediators can be assessed by comparing baseline values with those obtained 3-6 h post-event. Importantly,elevated baseline values in serum tryptase or urinary metabolites are not diagnostic of MCAS, nor do normal values exclude the diagnosis. In patients with idiopathic anaphylaxis, evaluation for a clonal mast cell disorder is recommended. This includes measuring baseline serum tryptase, testing for the KIT p.D816V mutation in peripheral blood (using high-sensitivity assays, if available), and calculating a mast cell clonality prediction score. A bone marrow biopsy should be considered for those with a high probability of mast cell clonality. Management includes instructing patients to treat acute episodes with an epinephrine auto-injector, particularly when anaphylaxis criteria are met. For patients with recurrent episodes, prophylactic therapy may be initiated, starting with H1-antihistamines and stepping-up as needed. While most patients have a favourable clinical course, some may require multiple medications to prevent or attenuate episodes. Future research should focus on validating and refining diagnostic and therapeutic strategies. In clinical practice, expanding access to key diagnostic tools-such as urinary mediator assays, sensitive KIT mutation testing, and tryptase genotyping-would facilitate and improve care of those patients.

In this letter, we report that ragweed-allergic participants with nasal Staphylococcus aureus carriage (n = 7) exhibited significantly smaller reductions in Peak Nasal Inspiratory Flow from baseline at 3 h (P = 0.013) and 5 h (P = 0.008) post-nasal allergen challenge compared to non-carriers (n = 12). There was no significant difference between carriers and non-carriers in the initial response within the first three hours following the challenge (all P > 0.05). Carriers also reported significantly lower Total Nasal Symptom Scores (P = 0.015) and Total Rhinoconjunctivitis Symptom Scores (P = 0.021) at 48 h. These findings suggest that S. aureus carriage does not exacerbate allergic responses and may instead be associated with more rapid symptom resolution.

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that effects both pediatrics and adult patients in Canada and is increasing in prevalence. No Canadian focused best practice recommendations currently exist to guide clinical practice.

Methods: The study used a modified Delphi technique to develop evidence and expert opinion-based recommendations for providing care for patients with EoE. The Delphi process consisted of 3 rounds of quantitative surveys and qualitative consensus meetings. Experts were included in the Delphi if they had experience caring for EoE patients in Canada within one of the following professional groups: allergist, adult gastroenterologists, pathologists, pediatric gastroenterologists, and dieticians.

Results: Delphi rounds were completed between May 1, 2024, and June 30, 2024. A total of 31 experts in EoE care from across Canada were recruited to participate in the Delphi consensus process. All participants completed all three rounds of Delphi surveys. The final statement includes 38 recommendations for the care of patients with EoE organized into three sections: definition, diagnosis, and management. A Table of research gaps is provided to stimulate further knowledge development on this topic.

Conclusion: This consensus statement includes actionable recommendations to support quality care of patients with EoE at any age across Canada. We encourage EoE centers in Canada to come together in a multi-disciplinary form to not only provide clinical care but also do much needed research on Canadian specific topics and gaps in EoE care.

Background: Dextromethorphan (DM) is a cough suppressant that is widely available in many prescribed and over-the-counter medications. Both immediate and delayed hypersensitivity reactions have been reported following the ingestion of DM. Anaphylaxis to DM is rare, with only three reported cases in the literature. Among these, skin prick testing for DM yielded a positive result in one case, a negative result in another, and was not performed in the third.

Case presentation: We present a rare case of anaphylaxis linked to DM, confirmed by skin testing. The patient experienced a severe allergic reaction after taking Vicks Dayquil Complete®, a common over-the-counter cold and flu medicine that contains acetaminophen, DM, phenylephrine hydrochloride, and guaifenesin. Among these, only DM triggered a positive response on skin testing.

Conclusion: This case highlights an uncommon allergy to a combination cold medicine, with skin testing identifying DM as the cause.

Background: Oral food challenges (OFCs) are considered the gold standard for diagnosis of food protein-induced enterocolitis syndrome (FPIES), a non-immunoglobulin E mediated gastrointestinal food allergy characterized by delayed, repetitive vomiting, lethargy, and sometimes diarrhea, primarily affecting infants and young children. Our modified approach to OFCs involves smaller, gradually increased doses to mitigate the risk of severe reactions. We aimed to measure the successful completion of this OFC protocol.

Methods: In a retrospective chart review, patients age < 18 years, who had 1 + episode of acute FPIES between 2015 and 2023 were identified using an allergy clinic database. Patients underwent OFCs with home up dosing every 2-4 weeks. Steps included 1%, 2%, 5%, 10%, 20%, 30%, 40%, 60%, 80%, and 100% of the final serving amount. The primary outcome was successful completion, i.e. absence of severe reactions during the OFC protocol and 1 year after. Data were analysed using logistic regression and reported as odds ratios (OR) and 95% confidence intervals (95% CI). Results were adjusted for multiple allergic comorbidities, age of FPIES onset, and biological sex.

Results: Among 47 patients who began the OFC protocol, 38 (80.85%) completed it without significant reactions. Of the 9 (19.14%) who did not complete the protocol, 4 (44.4%) paused due to reactions, and 5 (55.6%) paused due to non-FPIES symptoms. The 4 reactors paused due to mild-to-moderate reactions; there were no severe reactions during the protocol. There were no significant associations identified between OFC completion and severity of symptoms (OR 1.05; 95% CI 0.24-4.71; p = 0.94); age at onset of symptoms (OR 0.99; 95% CI 0.94-1.02; p = 0.58); or age of starting OFC (OR 1.00; 95% CI 0.98-1.02; p = 0.90). Patients who reacted to milk tended to be less likely to complete the protocol than those reacting to other foods (OR 0.28; 95% CI 0.07-1.06; p = 0.06).

Conclusions: This study supports the potential for a home-based gradual approach to OFCs in FPIES, evidenced by a high completion rate and no severe reactions.

Background: Hypersensitivity reactions to iodinated contrast media (ICM) are rare but can be life-threatening. Management typically involves avoidance of the offending agent and the use of alternative imaging strategies. The phenomenon of a transient refractory period-wherein a patient does not exhibit an allergic response upon re-exposure to the allergen shortly after an initial reaction-has been proposed but is not well-documented in the context of ICM.

Case presentation: We report the case of a 56-year-old woman who experienced an anaphylaxis associated cardiac arrest following administration of iopamidol 370 (Niopam 370) during a computed tomography pulmonary angiogram (CTPA). She was resuscitated, intubated, and stabilized with noradrenaline. Two hours later, she underwent a second CT scan using iopamidol 300 (Niopam 300) without any obvious immediate hypersensitivity reaction. Subsequent skin testing was positive for both Niopam 370 and Niopam 300, but negative for alternative agents - iodixanol (Visipaque) and iohexol (Omnipaque).

Conclusions: This case suggests the presence of a transient refractory period following a severe hypersensitivity reaction to ICM, during which re-exposure to the allergen does not elicit an immediate response. Understanding this phenomenon could have significant implications for the management of urgent imaging needs in patients with known ICM hypersensitivity.

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but potentially life-threatening hypersensitivity reaction characterized by skin rash, fever, lymphadenopathy, hematologic abnormalities, and organ involvement. Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is used to treat ovarian, fallopian tube, or primary peritoneal cancer. Although niraparib is associated with cutaneous toxicities, no severe cutaneous adverse reactions (SCARs) have been reported until now.

Case presentation: We present a case of DRESS syndrome in a 73-year-old woman with high-grade serous ovarian cancer treated with niraparib. After 20 days of therapy, she developed a widespread maculopapular rash. Despite discontinuation of niraparib and treatment with corticosteroids, she exhibited pruritus, facial edema, lymphadenopathy, eosinophilia, and impaired liver and renal function. A RegiSCAR score of 6 confirmed the diagnosis of DRESS. Patch testing to niraparib 1% in DMSO was positive when performed nine weeks after DRESS resolution.

Conclusions: This is the first reported case of DRESS by hypersensitivity due to niraparib. This case highlights the importance of recognizing DRESS as a potential adverse reaction to niraparib and the efficacy of early corticosteroid intervention. Further research is needed to understand and mitigate the risk.

Introduction: Asthma inhalers are significant contributors of greenhouse gas emissions. However, less is known about the potentially avoidable carbon footprint i.e. medication wastage and oversupply. We aimed to analyse dispensing patterns and carbon footprints of asthma inhalers, quantify medication wastage, and identify determinants of medication oversupply.

Methods: We reviewed the asthma-related dispensation records from 2015 to 2019, in an anonymised, cluster-wide repository linking electronic medical, pharmacy and administrative records, containing patient and visit details on demographics, comorbidities, GINA step, and site of care. Medication wastage, a visit-level measure, was defined as the number of inhalers dispensed in excess of the quantity required during each refill interval. Medication oversupply, a patient-level aggregated measure defined by medication possession ratio (MPR) > 1.2, where MPR equals total dispensed days (summed across all maintenance inhalers) divided by the follow-up period. All analyses were performed using R Studio.

Results: 205,337 inhaler units were dispensed over the study period, contributing an estimated 1,541,591 kgCO2e. The most frequently prescribed inhalers were SABA MDIs (79,007 units; 38.5%), followed by ICS-LABA MDIs (46,335 units; 22.6%), ICS MDIs (36,635 units; 17.8%), ICS-LABA DPIs (33,730 units; 16.4%), and ICS DPIs (9,630 units; 4.7%). ICS-LABA MDIs remained the greatest contributor of carbon footprint, with annual carbon emissions nearly doubling from 114,476 kgCO2e in 2015 to 214,575 kgCO2e in 2019. A total of 6,427 canisters were dispensed in excess of refill intervals, accounting for 46,798 kgCO2e. Beclomethasone MDIs accounted for the majority of wasted inhalers. In a multinomial regression analysis, patients receiving care in primary care settings were significantly more likely to be oversupplied medications compared to those in specialist care (OR 1.93, 95% CI 1.49-2.51).

Conclusion: ICS-LABA MDIs are the predominant source of inhaler-related carbon footprint, with additional contribution from excessive dispensation of inhalers.

Background: Unverified drug allergy labels are common and associated with significant patient harm, yet infrastructure and testing practices vary across clinical settings in Canada.

Objective: To characterize variability in drug allergy management among allergists in Canada and identify setting-specific barriers to drug allergy testing and desensitization.

Methods: We developed a peer-reviewed 40-item survey, distributed via the Canadian Society of Allergy and Clinical Immunology, to assess practice patterns, testing modalities, and perceived barriers among allergists. Descriptive statistics and Fisher's exact test were used to evaluate responses by practice setting.

Results: Sixty-six allergists responded (30% estimated response rate), with 48.4% solely practicing in community clinics and 21.9% solely in hospital-based clinics. While 87.9% performed some form of drug allergy testing, hospital-based allergists were significantly more likely to perform intradermal (81.1% vs. 48.7%, p = 0.004) and patch testing (38.2% vs. 8.8%, p = 0.009), as well as non-oral drug challenges (63.6% vs. 20.0%, p = 0.0005). Common barriers included a lack of nursing support and inadequate reimbursement.

Conclusion: Drug allergy management practices vary substantially across Canada, with drug allergy testing being more frequently performed by allergists practicing in hospital-based clinics than by those in community-based clinics. Findings support the need for equitable access to testing infrastructure and system-level investments in improving drug allergy testing services.

Background: Mastocytosis is driven by a clonal expansion of mast cells, commonly triggered by the KIT D816V mutation which is present in over 90% of adult patients. Individuals with indolent systemic mastocytosis (ISM) frequently experience recurrent anaphylaxis and mast cell mediator-related symptoms, leading to substantial morbidity. In rare cases, progression to more severe subtypes, such as smoldering systemic mastocytosis (SSM), can occur.

Case presentation: We describe one patient with ISM and another with ISM transitioning to SSM, both treated with the selective KIT D816V inhibitor avapritinib at a daily dose of 25 mg. Following initiation of avapritinib, both patients exhibited a marked reduction in serum tryptase levels and complete remission of maculopapular cutaneous mastocytosis. Additionally, joint pain, gastrointestinal symptoms, and neurocognitive complaints decreased. Sustained clinical improvement over follow-up periods of 9 and 12 months was consistently reflected in disease-specific patient-reported outcome measures (PROMs).

Conclusions: Regular clinical and laboratory monitoring, including serum tryptase and KIT D816V mutation assessment in peripheral blood, is essential in all ISM patients to detect early signs of disease progression. In refractory cases, avapritinib is a promising therapeutic option that can reduce mast cell burden, alleviate symptoms, and enhance overall quality of life.