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.
Chronic urticaria is a common and debilitating mast cell-driven skin disease presenting with itchy wheals, angio-oedema, or both. Chronic urticaria is classified as spontaneous (without definite ...triggers) and inducible (with definite and subtype-specific triggers; eg, cold or pressure). Current management guidelines recommend step-up administration of second-generation H1-antihistamines to four-fold the approved dose, followed by omalizumab and ciclosporin. However, in many patients, chronic urticaria does not respond to this linear approach due to heterogeneous underlying mechanisms. A personalised endotype-based approach is emerging based on the identification of autoantibodies and other drivers of urticaria pathogenesis. Over the past decade, clinical trials have presented promising options for targeted treatment of chronic urticaria with the potential for disease modification, including Bruton's tyrosine kinase inhibitors, anti-cytokine therapies, and mast cell depletion. This Therapeutics article focuses on the evidence for these novel drugs and their role in addressing an unmet need for personalised management of patients with chronic urticaria.
Introduction
The COVID‐19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.
Aim
To understand ...how CU patients are affected by the COVID‐19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID‐19.
Materials and Methods
Our cross‐sectional, international, questionnaire‐based, multicenter UCARE COVID‐CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.
Results
The COVID‐19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID‐19 patient care, which negatively impacted on the care of urticaria patients. The rate of face‐to‐face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19.
Conclusions
The COVID‐19 pandemic brings major changes and challenges for CU patients and their physicians. The long‐term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
The COVID‐19 pandemic severely impairs CU patient care, weekly number of patients decreased by more than 50%, and the rate of face‐to‐face consultations decreased by 62%. CU does not affect the course of COVID‐19 with only 4% of CU patients having a severe course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic.
Abbreviations: CU, chronic urticarial; COVID‐19, coronavirus disease 2019; UCARE: urticaria centers of reference and excellence.
Background
Drugs are a frequent cause of severe anaphylactic reactions. Here, we analyze a large dataset on drug induced anaphylaxis regarding elicitors, risk factors, symptoms, and treatment.
...Methods
Data from the European Anaphylaxis Registry (2007–2019) with 1815 reported cases of drug‐induced anaphylaxis were studied accordingly.
Results
Drugs are the third most frequent cause of anaphylaxis reported in the Anaphylaxis Registry. Among the eliciting groups of drugs analgesics and antibiotics were far most often reported. Female and senior patients were more frequently affected, while the number of children with DIA was low. DIA patients had symptoms affecting the skin and mucous membranes (n = 1525, 84.02%), the respiratory (n = 1300, 71.63%), the cardiovascular (n = 1251, 68.93%) and the gastrointestinal system (n = 549, 30.25%). Drugs caused significant more severe reactions, occurred more often in medical facilities and led to increased hospitalization rates in comparison to food and insect venom induced anaphylaxis. Adrenaline was used more often in patients with DIA than in anaphylaxis due to other causes. Patients with skin symptoms received more antihistamines and corticosteroids in the acute treatment, while gastrointestinal symptoms led to less adrenaline use.
Conclusion
The study contributes to a better understanding of DIA, with a large number of cases from Europe supporting previous data, e.g., analgesics and antibiotics being the most frequent culprits for DIA. Female gender and higher age are relevant risk factors and despite clear recommendations, the emergency treatment of DIA is not administered according to the guidelines.
This study analyzes data from the European Anaphylaxis Registry (2007–2019) with 1815 reported cases of drug‐induced anaphylaxis (DIA). We show that female gender and higher age are relevant DIA risk factors. DIA symptoms affect the skin and mucous membranes (84.0%), respiratory (71.6%), cardiovascular (68.9%), and gastrointestinal systems (30.3%). Intensive care admission and hospitalization rates are higher in DIA than in case of anaphylaxis caused by other elicitors (food‐ and insect venom‐induced).Abbreviations: DIA, drug‐induced anaphylaxis
Background
Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies ...on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.
Methods
An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.
Results
Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.
Conclusion
ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.
The COLD‐CE study was carried out at 32 UCAREs from 19 countries and four continents. Among 551 ColdU patients, 75% had positive local CST (i.e., typical ColdU) and ColdA occurred in 37% of the latter. For the first time, we propose the criteria for adrenaline autoinjector prescription for patients with typical ColdU.Abbreviations: ColdA, cold‐induced anaphylaxis; COLD‐CE, comprehensive evaluation of cold urticaria and other cold‐induced reactions, a study of the GA2LEN UCARE network; ColdU, cold urticaria; CST, cold stimulation testing; UCAREs, Urticaria Centers of Reference and Excellence
Background
Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown.
Aim
...To analyze the course and features of CU during and after pregnancy.
Patients and methods
PREG‐CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47‐item questionnaire completed by CU patients, who became pregnant within the last 3 years.
Results
A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively.
Conclusions
These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.
During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged; rate of angioedema decreased from 38.2% to 17.4%. CU exacerbations occurred most commonly in the third trimester (27.6%) or in the first trimester (22.8%). Of the patients whose urticaria improved during pregnancy, 50% experienced worsening after giving birth, whereas 33.6% and 16.4% reported no change. Abbreviations: CIndU, chronic inducible urticaria; CU, chronic urticaria; PREG‐CU, Pregnancy and Chronic Urticaria; UCARE, Urticaria Centers of Reference and Excellence
A Worldwide Antihistamine-Refractory Chronic Urticaria (CU) patient Evaluation (AWARE) is a non-interventional, multicenter study including patients from Europe, Central and Latin America, ...Asia-Pacific, and the Middle East. AWARE describes real-world evidence for CU, including clinical characteristics, treatment patterns and the impact on quality of life.
Over the 2-year study, therapy changes, angioedema occurrence, and patient-reported outcomes (PROs) were recorded over 9 visits, including dermatology life quality index (DLQI) and 7-day urticaria activity score (UAS7). Data were stratified into subgroups: chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), or CSU + CIndU.
Out of 4838 patients analyzed, 9.9% were receiving no treatment for their CU symptoms at baseline, and 20.4% were receiving first-line non-sedating H1-antihistamine at approved doses. The predominant baseline therapy was up-dosed non-sedating H1-antihistamines (25.5%). By Visit 2, omalizumab was the overall most commonly used therapy (29.6%), increasing to 30.1% by the end of the study. Baseline DLQI scores for patients with CSU, CIndU and CSU + CIndU were 8.3, 7.6 and 9.1, respectively; scores decreased over the study for CSU and CSU + CIndU patients, but fluctuated for CIndU patients. Baseline angioedema occurrence was higher in CSU and CSU + CIndU patients, reported in 45.4% and 45.5% of patients, respectively, compared to 17.0% in CIndU patients. By the final visit, angioedema had decreased to 11.9% and 11.2% for CSU and CSU + CIndU, respectively, and 9.6% for CIndU.
CU patients are undertreated at baseline; after entering the AWARE study, more patients received appropriate treatment. However, over two thirds are not escalated to third-line treatments.
The prevalence of atopic dermatitis (AD) is increasing in developing countries. Different worldwide guidelines have been proposed, but their applicability for AD specialists in Latin American (LA) ...countries is unknown.
The objective of this study was to explore the medical approach to treating AD in LA countries.
The study population comprised AD specialists (allergists and dermatologists). They completed an electronic survey containing questions about the health system, diagnostic criteria, and pharmacotherapy approach to treating AD. The survey was constructed and validated by the Atopic Dermatitis Committee of the Latin American Society of Allergy Asthma and Immunology (SLAAI) in Spanish and Portuguese. Each member was responsible for distributing the questionnaire through different networks in their respective countries.
A total of 284 AD specialists from 13 LA countries completed the questionnaire; among them, 67% were allergists and 33% were dermatologists. Less than 50% of the AD specialists strictly followed guideline recommendations. Among the AD specialists, the European and North American guidelines were more frequently used, and only 16% followed LA guidelines. Dermatologists used the local guidelines less frequently than allergists. Most physicians did not routinely use AD assessment tools (55%). The frequency of the diagnostic tests depends on symptom severity. The availability of some systemic treatments, such as biologics and JAK inhibitors, is not universal in all LA countries.
There were marked differences between the specialists, and these differences seemed to be affected by their specialty and each country´s healthcare system. New AD education strategies that consider the particularities of the region could allow patients to be more accurately managed. AD assessment tools may provide a way to enhance AD treatment and allow for shared decision-making, patient empowerment, and standardized care.
Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and ...vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways.
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