Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Are man-made hives valid thermal surrogates for natural honey bee nests (Apismellifera)?

Honey bees preferentially occupy thick walled tall narrow tree cavities and attach their combs directly to the nest wall, leaving periodic gaps. However, academic research and beekeeping are conducted in squat, thin walled man made hives, with a continuous gap between the combs and the walls and roof. Utilising a computational fluid dynamics (CFD) model of thermoregulating bees in complete nests in trees and thin walled man made hives, with the average size of tree comb gaps determined from honey bee occupied synthetic tree nests, this research compared the metabolic energy impacts of comb gaps and vertical movement of the thermoregulated brood area. This shows their heat transfer regimes are disparate, including: bee space above combs increases heat loss by up to ∼70%; hives, compared to tree nests, require at least 150% the density of honey bees to arrest convection across the brood area. Tree cavities have a larger vertical freedom, a greater thermal resistance and can make dense clustering redundant. With the thermal environment being critical to honey bees, the magnitude and scope of these differences suggest that some hive based behavioural research needs extra validation to be considered non-anthropogenic, and some bee keeping practices are sub-optimal.

Chronic spontaneous urticaria guidelines: What is new?

Urticaria is a heterogeneous inflammatory disorder that can be acute or chronic and is defined by the appearance of wheals, angioedema, or both. Very recently, the newest update and revision of the international European Academy of Allergy and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/Asia Pacific Association of Allergy Asthma Clinical Immunology guideline for the definition, classification, diagnosis, and management of urticaria was published. It aims to help primary care physicians and specialists in the management of their patients with urticaria. The guideline applied the Grading of Recommendations Assessment Development and Evaluations approach to developing consensus recommendations. These recommendations were then discussed in a Delphi conference that included more than 250 specialists in the field, and they are endorsed by more than 50 international societies. Here, we highlight changes from previous versions of the international urticaria guideline and their impact on clinical practice.

Urticaria and basophils.

Chronic spontaneous urticaria (CSU) is a common skin disease without an etiology in the vast majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports that skin mast cell IgE receptor activation is also involved in CSU. Accumulating evidence also supports a role for blood basophils in disease expression. Blood basopenia is noted in active CSU disease with the recruitment of blood basophils to skin lesion sites. Blood basophils further display altered IgE receptor mediated degranulation patterns in two phenotypes that improve in remission. In active CSU subjects, changes in IgE receptor signaling molecule expression levels accompany the altered degranulation function in blood basophils. The success of therapies targeting IgE in CSU patients have also shown that altered blood basophil phenotypes and enumeration have potential use as a disease biomarker.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Aeroallergens in Atopic Dermatitis and Chronic Urticaria.

PURPOSE OF REVIEW: While aeroallergens are a well-established trigger of asthma and allergic rhinitis, their role in allergic skin diseases such as atopic dermatitis and chronic urticaria remains controversial. This paper reviews the pathophysiology and clinical evidence for aeroallergens in these allergic skin diseases and summarizes current strategies for evaluation and management. RECENT FINDINGS: Current evidence implicates aeroallergens as triggers of cutaneous reactions in atopic dermatitis. Direct skin contact is the likely route of trigger. Aeroallergens may also trigger chronic urticaria, though mechanistic studies are limited. These allergens may cross the skin barrier and directly trigger neurons to release substance P, resulting in mast cell degranulation and dumping of histamine and prostaglandin D2. Many studies link aeroallergen sensitization to chronic urticaria, and case reports suggest the utility of avoidance strategies. The role of aeroallergens as a trigger is clear in atopic dermatitis and becoming emergent in chronic urticaria. Skin prick testing or serum-specific immunoglobulin E testing may be used to determine sensitivities. Management at this time centers on avoidance, and further studies are necessary to evaluate the efficacy of aeroallergen immunotherapy for both conditions.

The Classification, Pathogenesis, Diagnostic Workup, and Management of Urticaria: An Update.

Wheals and angioedema are the signature signs of urticaria, and itch is the key symptom. Urticaria, in most patients, is acute and resolves within days (acute urticaria, AU). Chronic urticaria (CU) can be of long duration and results not only in severely impaired quality of life but also has a socioeconomic impact due to work productivity impairment. In some patients with CU, the wheals and angioedema are induced exclusively by defined and definite triggers (chronic inducible urticaria, CIndU). In most patients with CU, wheals and angioedema develop unprompted, spontaneously (chronic spontaneous urticaria, CSU). The management of CU aims for the complete control and absence of its signs and symptoms. This is achieved, in most patients, by prophylactic treatment until spontaneous remission occurs. Modern, second-generation H1-antihistamines are the first-line therapy, with the option of updosing to fourfold, and omalizumab is used when this fails.

Successful management of chronic urticaria and food allergies in a pediatric population using integrative traditional Chinese medicine therapy: a case series.

BACKGROUND: Food allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still develops frequent, persistent, and difficult to treat hives (FPDTH) for which there is no curative therapy. Although these cases are rare, these patients are in most need of therapy. CASE PRESENTATIONS: This is a retrospective review of 3 pediatric patients with highly sensitive food allergies who initially presented with hives daily or every other day, or multiple times a day, but achieved marked remission after traditional Chinese medicine (TCM) therapies. Patient 1 (P1) is a 5-year-old who has experienced 140 reactions in his lifetime. Reactions were mostly hives with 4 episodes of anaphylaxis. P1 had used Prednisone 20 times, had an Epinephrine injection 4 times, and had 3 emergency room (ER) visits. Patient 2 (P2) is a 12-year-old who had experienced hives since age 3. Despite daily antihistamine use, P2 had > 730 reactions in his lifetime at the time of presentation including 2 episodes of anaphylaxis. He had been prescribed prednisone 4 times, an Epinephrine injection 2 times, and had 1 ER visit. Patient 3 (P3) is a 20-month-old girl who had experienced > 120 reactions including 1 episode of anaphylaxis. She was on daily desonide and frequently used an antihistamine, yet still had required a course of prednisone once, an Epinephrine injection once, and had 1 ER visit to manage her reaction. After presenting to our clinic, patients received internal and external TCM treatments, including herbal baths and creams (Remedy A-D) as basic remedies to reduce food reactions, including but not limited to frequent hives. Within 7-9 months of TCM treatment, remarkably all patients had complete remission of atopic symptoms. All three patients also experienced an improvement in other conditions including food intolerance, diarrhea, anxiety, eczema, and environmental allergies. After 1 year of treatment, all three patients had reductions in food-specific IgE levels that had been previously elevated, and additionally, P1 and P3, who initially had high total IgE levels, experienced a marked decrease in total IgE levels as well. All three patients continued to introduce foods into their diet that they previously had reactions to, and all 3 patients remain symptom-free. CONCLUSIONS: Three pediatric patients with a known history of multiple food sensitivities and physician-diagnosed food allergies that presented with FPDTH underwent a TCM regimen and experienced dramatic improvement in symptoms and reduction in their IgE levels. This regimen appears to be effective in FPDTH population although a further study in a controlled clinical setting is required.

A randomized controlled trial of adding intravenous corticosteroids to H1 antihistamines in patients with acute urticaria.

BACKGROUND: Acute urticaria is a common dermatological condition in emergency departments (EDs). The main therapy involves controlling pruritus with antihistamines. Although guidelines have promoted the use of corticosteroids in addition to H1 antihistamines, well-designed clinical trials evaluating this approach are scarce. METHODS: Adult ED patients with acute urticaria and a pruritus score > 5 on a visual analog scale (VAS) were randomized into three groups: (i) IV chlorpheniramine (CPM) treatment, (ii) IV CPM and IV dexamethasone (CPM/Dex) and (iii) IV CPM and IV dexamethasone with oral prednisolone as discharge medication for 5 days (CPM/Dex/Pred). The primary outcomes were self-reported pruritus VAS scores at 60 min after treatment. We also evaluated 1-week and 1-month urticaria activity scores for 7 days and adverse events. RESULTS: Seventy-five patients (25 per group) were enrolled. The VAS scores of all groups decreased, but no significant difference was found in the VAS scores at 60 min after treatment between patients in the CPM group (n = 25) and those who received both CPM and dexamethasone (n = 50). At the 1-week and 1-month follow-ups, active urticaria (indicated by the urticaria activity score at 7 days) was more prevalent in the CPM/Dex/Pred group (n = 25) than in the control group. CONCLUSIONS: The present study did not find evidence that adding IV dexamethasone improves the treatment of severe pruritus from uncomplicated acute urticaria. Oral corticosteroid therapy may be associated with persistent urticaria activity. Due to the lack of clinical benefits and the potential for side effects, using corticosteroids as an adjunctive treatment is discouraged.

Chronic Urticaria in Children: an Update on Diagnosis and Treatment.

PURPOSE OF REVIEW: Both adults and children are frequently affected by symptoms of itchy urticarial lesions that cause considerable distress and impact nearly all their daily activities. A comprehensive history is critical to identify the etiology in patients who have chronic spontaneous urticaria (CSU) (those with symptoms for > 6 weeks) and is more important than extensive laboratory serum tests. Unfortunately, most of the current treatment guidelines have been based on data from adult studies since there is rare data on children. These treatment algorithms have been subsequently used to extrapolate treatments for children. RECENT FINDINGS: Current treatment regiments do not achieve complete success in all patients, neither adults nor children. As the pathophysiology of chronic urticaria slowly becomes defined, novel therapies are being tested which target these individual molecular pathways to treat those that continue to experience symptoms. Future studies are required to establish the natural history, risks/benefits and efficacy of current medications, and biologics used to treat CSU in children.

Perspectives on Living with Chronic Spontaneous Urticaria: From Onset through Diagnosis and Disease Management in the US.

Chronic spontaneous urticaria is challenging to manage and substantially affects quality of life. This US, non-interventional qualitative study examined patients' clinical journeys and emotional burden from symptom onset through disease management. Chronic spontaneous urticaria patients participated in interviews and completed diaries focusing on disease and treatment history/perspectives, impact on personal/family life, and relationships with physicians/other healthcare providers. Physicians were interviewed about their views on disease management and patient care. Twenty-five patients, previously or currently receiving chronic spontaneous urticaria treatment(s), and 12 physicians participated. Key stages following symptom onset were identified: Crisis (associated with feelings of torment/disorientation/shock); Searching for answers (puzzlement/frustration/anxiety); Diagnosis (relief/satisfaction/fear/isolation); and Disease management (frustration/hope/powerlessness). Findings revealed patients' perceptions and experiences of chronic spontaneous urticaria, including living with a 'skinemy', experiencing their 'own personal hell' and feeling 'like an experiment'. Awareness of unmet needs in patient care/management identified in this study may ultimately improve patient support and enhance physicians' understanding of disease burden.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Chronic Urticaria: Comparisons of US, European, and Asian Guidelines.

PURPOSE OF REVIEW: Chronic urticaria is a common dermatological condition that has significant impact on quality of life. Multiple international societies have published guidelines, and although these guidelines generally agree on the definition of urticaria, as well as approach to diagnosis and management, there have been notable differences to date. These differences have been reconciled by the recent publication of the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO. RECENT FINDINGS: The 2017 revision and update to the guidelines for chronic urticaria are the most comprehensive consensus document to date, and reconcile previously existing differences between the US, European, and Asian guidelines. The purpose of our review is to present basic background on urticaria and discuss classification, diagnosis, and most importantly, management. We present differences from previous US, European, and Asian guidelines and reconcile the previous differences by summarizing the 2017 revision and update published by the EAACI/GA2LEN/EDF/WAO.

Urticaria: A comprehensive review: Epidemiology, diagnosis, and work-up.

Urticaria is a common clinical condition presenting with wheals (hives), angioedema, or both. Urticaria has a complex pathogenesis, along with a high disease burden, a significant impact on quality of life, and high health care costs. The first article in this continuing medical education series covers the definition, classification, epidemiology, diagnosis, and work-up of urticaria, taking into account the recent literature and the best available evidence.

Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria.

This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) and is published in Allergy 2014; 69:868-887.

The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update.

This guideline is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

A Patient Charter for Chronic Urticaria.

Chronic urticaria (CU) is the recurring development of wheals (aka "hives" or "welts"), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient's physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient-provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient-physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable.

Anaphylactic Shock Caused by Eating Buckwheat.

Background: Urticaria is a common disease with a marked influence on quality of life. The key cell involved is the mast cell, which can be activated by a vast variety of stimuli, and the major mediator is histamine. Allergic urticaria is a disorder with a large variety of causes: food, drugs, insect venom, skin contact with allergens, and physical exercise. Buckwheat consumption has increased in European countries and the USA because it is gluten-free. It can trigger anaphylactic shock if ingested, inhaled, or handled with the hands. Five common buckwheat allergens named Fag e1 to 5 (Fag e1, 2, and 3 are considered the major allergens) and two tartary buckwheat allergens named Fag t1 and Fag t2 have been described. Method: We present the case of a patient who experienced two anaphylactic shocks and in whom the etiological factor was buckwheat. The patient presented to the Allergology department for the evaluation of two episodes of severe allergic reactions that required emergency therapy, episodes that involved the loss of consciousness and were of major severity. At each anaphylactic shock, an ambulance was requested, and emergency therapy was administered, leading to the patient's recovery within a few hours. Diagnosis: Since each episode occurred a few minutes after eating, the diagnosis was established based on a detailed anamnesis and prick skin tests, followed by specific IgE dosages. Other foods consumed by the patient, assessed by prick skin testing and specific IgE dosages of suspected foods, were excluded as the etiological cause. Increased levels of buckwheat-specific immunoglobulin E were highlighted, thus identifying the etiological agent. The treatment of anaphylactic shock was performed urgently by the ambulance crew with adrenaline, infusion solutions, cortisone preparations, and antihistamines. Result: Following the treatment that was initiated, there was a partial remission of the lesions after a few hours. Conclusions: Buckwheat allergy is rare, but it produces symptoms that affect the skin, gastrointestinal tract, and respiratory tract, as well as anaphylaxis. In a professional environment, it can trigger allergic rhinitis, asthma, and hives. Although buckwheat allergens have been described, their clinical relevance has only been studied in a small number cases. In current practice, the only commercially available allergen is Beech e2 per the ImmunoCAP ISAC microarray. Diagnosis can be difficult in clinical practice. This reported case suggests the need for a thorough anamnesis, since buckwheat is consumed as a hidden allergen, and in Europe, it is not necessary to label foods containing this allergen.