Self-management plans in patients with hereditary angioedema : strategies, outcomes and integration into clinical care

Chronic conditions, whether genetic or acquired, impose a significant burden on health care systems with high utilisation of hospital and emergency department resources. Self-management is increasingly recognised as one of the pillars in models of care for those with long-term medical conditions. Hereditary angioedema (HAE) is a rare genetic disorder inherited in an autosomal dominant fashion. It is characterised by the occurrence of unpredictable attacks of swelling (angioedema) affecting many body parts including subcutaneous tissues, the gut mucosa and the upper airway. For those affected, it is associated with a high burden of illness and poor quality of life as a result of its unpredictability and the threat of asphyxiation from upper airway oedema or severe pain from abdominal involvement. Prompt recognition and appropriate treatment are necessary to avoid the pain and suffering associated with attacks and to manage life-threatening laryngeal swellings that around 50% of HAE patients will experience in their lifetime. Since the early 2000s, a number of very effective, albeit expensive, treatment options have become available, at least in some countries. Utilisation of these options within a written patient self-management plan provides the most satisfactory treatment outcomes and improves patient quality of life. Successful self-management depends on a productive partnership between patient and health care professional, with patient education the cornerstone of a successful outcome. This is a dynamic process, particularly in a condition such as HAE where frequency and severity of attacks may vary given different life circumstances

Urticaria and mimickers of urticaria

Urticaria is a common skin condition encountered across various specialties in medicine, especially in dermatology and allergy/immunology practice. It has a heterogeneous presentation hence it is unsurprising that many skin conditions may be confused with urticaria. Urticaria may present as acute or chronic urticaria, the latter can be further categorised into chronic spontaneous and chronic inducible. In this article, we explore, explain, and summarise various skin lesions that are considered mimickers of urticaria, to promote understanding of each of the conditions highlighted, improve recognition, and reduce misdiagnosis

'Cephalosporin allergy' label is misleading

Penicillins and cephalosporins can cause a similar spectrum of allergic reactions at a similar rate. Cross-reactive allergy between penicillins and cephalosporins is rare, as is cross-reaction within the cephalosporin group. Patients should therefore not be labelled ‘cephalosporin-allergic’. Cross-reactive allergy may occur between cephalosporins (and penicillins) which share similar side chains. Generally, a history of a penicillin allergy should not rule out the use of cephalosporins, and a history of a specific cephalosporin allergy should not rule out the use of other cephalosporins. Specialist advice or further investigations may be required when the index reaction was anaphylaxis or a severe cutaneous adverse reaction, or when the antibiotics in question share common side chains. When recording a drug allergy in the patient’s records, it is important to identify the specific drug suspected (or confirmed), along with the date and nature of the adverse reaction. Records need to be updated after a negative drug challenge

Parent perceptions in managing children with food allergy : an Australian perspective

Introduction: Food allergy affects up to 10% of Australian children, and living with food allergic children can be challenging for parents. This study explored parental perceptions and knowledge as they navigate a new reality of keeping their child safe. Methods: Parents of children with food allergies completed an online food allergy survey in 2015. Questions explored health knowledge, skills, and attitudes (KSAs) as well as quality of life (QoL) through the inclusion of the Food Allergy Quality of Life — Parental Burden instrument (FAQL-PB). Notification of the survey included advertisements to more than 700 randomly selected Australia-wide preschools, 44 allergy specialists, and Allergy & Anaphylaxis Australia. Responses were tabulated and analysed. Results: Of the 400 participants who logged on, 357 commenced the survey and 318 finished. Questionnaire analysis showed that 44.1% of parents (n = 135) hesitated to use an adrenaline auto-injector and may be influenced by a classification system where symptom severity is not universally understood. While 79% would sign up to a national Anaphylaxis Registry, intention to participate in clinical trials using vaccines was disclosed by only 56%. Allergen labelling and community acceptance continue to be the most challenging aspects of managing a food allergy, and 50% of parents reported that food allergy played a role in choosing a preschool or primary school. Overall, quality of life for participants was influenced more by gender (male) and age of the child than where they lived — capital city or regional location; however, regional participants were more frustrated over lack of appreciation relating to the seriousness of food allergy (p = 0.010). Conclusion: Results highlight the need for educational strategies for both the food allergy community and public, particularly in regional areas, since there is a perceived lack of appreciation as to the seriousness of food allergy. Educational resources and relevant networks are required to support parents and caregivers in the management of children with food allergy

Dupilumab-associated ocular surface disease : an interdisciplinary decision framework for prescribers in the Australian setting

Background/Objectives: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. Methods: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. Results: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6–22.1% (clinical trials programme), 0.5–70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. Conclusions: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate–severe DAOSD and high-risk patients

WAO guideline for the management of hereditary angioedema

Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists

Effect of exacerbation history on clinical response to dupilumab in moderate-to-severe uncontrolled asthma

Background The phase 3 LIBERTY ASTHMA QUEST study (ClinicalTrials.gov: NCT02414854) in patients with uncontrolled, moderate-to-severe asthma has demonstrated the efficacy and safety of dupilumab 200 and 300 mg every 2 weeks versus placebo. This post hoc analysis assessed the effect of dupilumab on efficacy outcomes and asthma control across a range of historical exacerbation rates in patients with type 2-high asthma. Methods Annualised severe exacerbation rates over the 52-week treatment period, pre-bronchodilator forced expiratory volume in 1 s (FEV1) at weeks 12 and 52, and the five-item Asthma Control Questionnaire (ACQ-5) score at weeks 24 and 52 were assessed in patients with ≥1, ≥2 or ≥3 exacerbations in the previous year. Subgroups were stratified by baseline blood eosinophils ≥150 or ≥300 cells·μL-1 or baseline exhaled nitric oxide fraction ≥25 ppb and baseline inhaled corticosteroid (ICS) dose. Results Across all type 2-high subgroups, dupilumab versus placebo significantly reduced severe exacerbations by 54–90%, with greater improvements in patients with more exacerbations prior to study initiation. Similarly, improvements in FEV1 (least squares (LS) mean difference versus placebo: ≥1 exacerbations, 0.15–0.25 L; ≥2 exacerbations, 0.12–0.32 L; ≥3 exacerbations, 0.09–0.38 L; majority p<0.05) and ACQ-5 score (LS mean difference range: ≥1 exacerbations, -0.30 to -0.57; ≥2 exacerbations, -0.29 to -0.56; ≥3 exacerbations, -0.43 to -0.61; all p<0.05) were observed, irrespective of prior exacerbation history, across all subgroups. Conclusions Dupilumab significantly reduced severe exacerbations and improved FEV1 and asthma control in patients with elevated type 2 biomarkers irrespective of exacerbation history and baseline ICS dose

Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV1) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. Methods: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL−1, ≥300 eosinophils·µL−1, ≥25 ppb fractional exhaled nitric oxide (FeNO), and both ≥150 eosinophils·µL−1 and ≥25 ppb FeNO, at baseline. Results: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV1 (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV1 (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s−1, respectively) and pre-bronchodilator FEV1/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV1 slope of change (weeks 4–52) was significant (0.04 L·year−1; p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or FeNO levels for most outcomes. Conclusions: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation

Consensus on treatment goals in hereditary angioedema : a global Delphi initiative

Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. Methods: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Results: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients’ lives. Conclusions: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients