Canadian Allergy & Immunology Today

Emerging Biologics in the Management of Atopic Dermatitis

2025-05-23T15:06:39+00:00

Atopic dermatitis (AD) is a chronic, relapsing and remitting inflammatory skin disease marked by intense pruritus that significantly impacts the daily activities and quality of life of those affected. Topical therapies such as topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) have been the mainstay of treatment and may offer symptomatic relief. However, their efficacy is often suboptimal, they carry the potential for adverse effects, application adherence can be challenging, and they are not suitable for more widespread disease. Conventional systemic agents such as methotrexate and cyclosporine are used off-label for AD. However, these medications are associated with off-target toxicities and are generally unsuitable for long-term use due to safety concerns. Advances in understanding the immunopathogenesis of AD (Figure 1) have led to the development of multiple new therapies. These include biological agents that target these pathways by neutralizing specific cytokines or their receptors. This paper will review the therapies that have been recently approved or are currently in various stages of development.

Updates in Epinephrine Guidelines

2025-05-23T15:10:07+00:00

Epinephrine is the first line treatment for anaphylaxis, which is a serious allergic reaction that can rapidly progress and may cause death. As a nonselective adrenergic agonist, epinephrine rapidly works to increase vasoconstriction and peripheral vascular resistance, increase cardiac output, reverse bronchoconstriction and mucosal edema, and inhibit the release of mediators of inflammation from mast cells and basophils. The anaphylaxis guidelines developed by the Joint Task Force on Practice Parameters (JTFPP) in 2020, the World Allergy Organization (WAO) in 2020, and the European Academy of Allergy and Clinical Immunology (EAACI) in 2021 advise clinicians to prescribe self-injectable epinephrine to individuals at risk of anaphylaxis and educate them on when and how to administer it. In 2023, the JTFPP updated its anaphylaxis practice parameter to address seven key topic areas, including multiple questions and recommendations related to epinephrine prescription and use. The practice parameter authors graded each recommendation as conditional or strong, based in part on the certainty of the supporting evidence. We provide an overview of key recommendations and discuss their applications in the Canadian context.

It is important to note that in Canada, EpiPen^®autoinjectors are currently the sole epinephrine delivery devices available with premeasured doses of epinephrine for the emergency treatment of allergic reactions. These autoinjectors should be administered intramuscularly into the anterolateral thigh. Additional epinephrine devices may become available in the future, including the first epinephrine nasal spray (neffy^®). There is a wider variety of epinephrine devices available in the United States, including multiple brands of epinephrine autoinjectors (Adrenaclick^®, Auvi-Q^®, EpiPen^®/EpiPen^® Jr., and generic versions). Additionally, there is one brand of epinephrine prefilled syringe (Symjepi™) and one brand of nasal spray (neffy^®). Although the anaphylaxis practice parameter update was published before the U.S. Food and Drug Administration had approved neffy^®, we believe its recommendations for epinephrine prescription and use may be appropriately extended to include epinephrine nasal spray where it is available.

Use of the Rema Score to Distinguish Individuals with Systemic Mastocytosis From Those with Hereditary Alpha-tryptasemia

2025-05-23T15:13:47+00:00

Background: Systemic mastocytosis (SM) and hereditary alpha-tryptasemia (HαT) may present with overlapping clinical manifestations of mast cell activation, making them difficult to distinguish on clinical grounds. Diagnosing SM requires a bone marrow or tissue biopsy whereas HαT can be diagnosed with a buccal swab for genetic testing. Another potential method to differentiate SM from HαT is through a validated scoring system. For example, the Spanish Network on Mastocytosis, Red Española de Mastocitosis (REMA) score has been validated as a predictor of mast cell clonality in SM by using basal serum tryptase levels, clinical symptoms, and sex. This study aims to determine whether REMA scores can differentiate sufficiently between individuals with SM and HαT, thereby confidently ruling in or out the need for more invasive investigations such as bone marrow or tissue biopsy.

Methods: A retrospective chart review was conducted on 39 patients with SM and 24 patients with HαT to calculate their individual REMA scores. A two-sample Wilcoxon test was conducted to assess the difference in median REMA scores between patients with SM and those with HαT. Within the SM cohort, subgroup analysis was performed to compare REMA scores based on the KIT D816V mutation and SM subtype. The area under the curve was calculated to evaluate the discriminatory property of the REMA score.

Results: The Median REMA score within the SM cohort was 2 (0.50, 4.00) compared to -1 (-1.50 0.00) within the HαT cohort (p <0.001). REMA scores in patients with SM did not differ based on the KIT mutation status. A REMA score cut-off of 0.5 was able to distinguish SM and HαT with a specificity of 83.3% (67%,96%).

Conclusion: This novel comparison of REMA scores in patients with SM and HαT highlights a potential role for the calculated REMA score in informing decisions about the need for invasive testing for patients presenting with symptoms of mast cell activation. However, larger comparative studies are needed before incorporating REMA scoring into routine care.

The Evolving Therapeutic Landscape for Hereditary Angioedema in Canada: Clinical Advances and Unmet Needs

2025-05-23T15:17:27+00:00

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent, potentially life‑threatening episodes of swelling due to bradykinin overproduction. Advances in the understanding of molecular pathophysiology, coupled with the development of innovative therapies, are transforming the management of HAE. This underscores the need for strategic planning to incorporate emerging treatment modalities into the Canadian therapeutic framework for HAE.

An Update on Biologics in Pediatric Asthma: A Canadian Perspective

2025-05-23T15:20:27+00:00

Asthma is one of the most common chronic diseases in Canada, affecting approximately 11% of Canadians. Severe asthma, estimated to affect 5–10% of patients with asthma, is associated with a significant burden of disease‑related morbidity. In adults, typical management strategies include using combinations of inhaled corticosteroids, long-acting beta agonists, leukotriene receptor antagonists, long-acting muscarinic antagonists, and oral corticosteroids. However, in pediatric cases, particularly young children, our medication options are more limited. Although inhaled corticosteroids are effective for the majority of mild-to-moderate asthma cases, their efficacy in non-atopic asthma is limited. Furthermore, using inhaled corticosteroids at moderate-to-high doses can impair linear growth and lead to adrenal suppression. Given our growing recognition of asthma as a heterogenous disease, with multiple disease endotypes driven by distinct inflammatory pathways, there is an increasing demand for targeted therapies, particularly for patients with ongoing, uncontrolled disease (Figure 1). Type 2 (T2) high inflammation, characterized by elevated levels of IgE, interleukin (IL)-4, IL-5, and IL-13, alongside eosinophilia and atopy, remains the most well-defined endotype in school-age children and youth. With the advent of biologic medications, targeting T2‑high inflammatory pathways has become a critical component for managing uncontrolled, moderate‑to-severe asthma in children. This approach aims to improve treatment response and reduce adverse effects. This review will explore the biologic therapies currently available in Canada for moderate-to-severe pediatric asthma, discuss key considerations in selecting the optimal biologic, and outline future research directions to inform the optimal timing for initiating and discontinuing biologic treatments.