Non-Skin-Related Symptoms are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results from CURE.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin-related symptoms (NSRS), including recurrent unexplained fever, joint/bone/muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (e.g., urticarial vasculitis or autoinflammatory disorders) or without wheals (e.g., infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry (CURE) of 2,521 patients with CSU who were ≥16 years old. RESULTS: One-third of CSU patients (31.2%, 786/2,521) had ≥1 NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having ≥1 of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR]=1.7 and 1.5), wheals of ≥24 hours duration (aOR=2.5), sleep disturbance (aOR=2.4), anxiety (aOR=2.8), comorbid atopic dermatitis (aOR=2.1), gastrointestinal disease (aOR=1.8), elevated leukocytes (aOR=1.7) and erythrocyte sedimentation rate (aOR=1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (UAS7, median: 21 vs. 14, p=0.009), longer disease duration (years, median: 2 vs. 1, p=0.001), presence of angioedema (74.6% vs. 58.7%, p<0.001), worse quality of life (CU-Q2oL, median: 42 vs. 29, p<0.001) and more frequent poor control of CSU (78% vs. 69%, p<0.001). CONCLUSION: The presence of NSRS in a subpopulation of CSU patients points to a need for better control of the disease, exclusion of comorbid conditions and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

An update on the use of antihistamines in managing chronic urticaria.

INTRODUCTION: Urticaria, a mast cell-mediated skin disease, manifests as acute or chronic, with the latter divided into spontaneous and inducible types and requires individualized management, including identifying triggers and comorbidities. Antihistamines, particularly the second generation group, form the mainstay of primary treatment plans consisting of dosage adjustments and/or in combination with other treatment modalities depending on underlying disease control. AREAS COVERED: A literature search was conducted using 'antihistamines,' 'urticaria,' 'pharmacogenomics,' 'genomics,' 'biomarkers' and 'treatment response' as key words. In this review, we focus on the comprehensive understanding and application of antihistamines in managing adult and adolescent patients with chronic urticaria. EXPERT OPINION: Using antihistamines to treat urticaria is set to change significantly, focusing more on personalized medicine and identifying key biomarkers to enhance treatment response prediction. These changes aim to make treatments more specific and cost-effective by avoiding unnecessary tests. Applying new approaches in everyday clinical care faces challenges like proving the biomarkers' reliability, updating current guidelines, and incorporating individualized treatments into standard procedures. Efforts should now concentrate on finding easy-to-use biomarkers, improving access to pharmacogenomics, understanding why some patients are resistant to treatment, and creating more specific treatment options based on patient needs.

Monitoring recurrent angioedema: Findings from the Turkish angioedema control test validation study.

BACKGROUND: Determination of control level in recurrent angioedema (RAE) is necessary to guide management. Here, we validated a Turkish version of the angioedema control test (AECT) for 4-week (AECT-4wk) and for 3-month (AECT-3mth) and assessed their utility in monitoring RAE. METHOD: The recommended structured translation process for patient-reported outcome measures was completed. The final versions were administered to 51 patients with mast cell-mediated angioedema (MMAE) and 38 patients with hereditary angioedema, and the minimal clinically important difference (MCID) was determined. Additionally, anchor surveys comprising angioedema activity score for 28 days (AAS-28 day), visual analog score for angioedema control, Likert scale for the control level from the patient's perspective (LS-AEC), angioedema quality of life, short form-12 (SF-12) and patients' assessment of treatment sufficiency were applied. RESULTS: The Turkish AECT versions showed good convergent validity with a substantial correlation with anchor tools and known-group validity. Excellent internal consistency and reproducibility were observed. Equal or more than 10 of 16 points scored with the AECT-4wk and AECT-3mth identified patients with well-controlled disease. The disease activity, control and burden parameters were consistent with the disease control level defined depending on the cut-off point 10 of AECT. Three-point changes in AECT-4wk and -3 mt could detect MCID in disease control in all patients. CONCLUSIONS: Turkish AECT versions are valid and reliable tools for assessing and monitoring disease control in patients with RAE. The use of the Turkish versions of the AECT in routine patient care, clinical trials and angioedema research is recommended.

A global perspective on stepping down chronic spontaneous urticaria treatment: Results of the Urticaria Centers of Reference and Excellence SDown-CSU study.

BACKGROUND: Although there have been significant advances in the treatment of chronic spontaneous urticaria (CSU) in recent years, there remains a lack of clear guidance on when and how to step down treatment in responders. This study aims to investigate stepping down approaches of different steps of CSU treatment from a global perspective. METHODS: "Stepping down chronic spontaneous urticaria treatment" (SDown-CSU) is an international, multicenter, observational, cross-sectional, survey-based study of the Urticaria Centers of Reference and Excellence (UCARE) network. The questionnaire included 48 questions completed by physicians in the UCARE network. RESULTS: Surveys completed by 103 physicians from 81 UCAREs and 34 countries were analyzed. Seventy-eight percent of the participants responded that they had a national urticaria management guideline written by their professional societies and 28% responded that they had to operate under a regulatory guideline proposed by central health funding organizations. Seventy-two and 58.7% of these national recommendations do not contain any detailed information on when and/or how CSU treatment should be discontinued. There was a lack of detailed information on antihistamines and cyclosporine in particular. A predefined maximum duration was generally not applicable to omalizumab and cyclosporine (81% and 82%, respectively). Nearly all UCAREs step down omalizumab within 6 months from the first controlled status and 42% discontinue cyclosporine after 6 months regardless of the control status. CONCLUSIONS: The findings from the SDown-CSU study clearly highlight a global need for guidance on the process of stepping down treatment in CSU. Additionally, the study offers a step-down algorithm applicable to all stages of CSU treatment.

CRUSE® -An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE® , the Chronic Urticaria Self Evaluation app, aims to address this unmet need. METHODS: CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations. RESULTS: CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days. CONCLUSIONS: The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.

TOX, TWIST1, STAT4, and SATB1 protein expressions in early-stage mycosis fungoides.

BACKGROUND: Diagnosis of early mycosis fungoides (eMF) is challenging and often delayed as many of its clinical and histopathologic features may mimic various benign inflammatory dermatoses (BIDs). The products of the thymocyte selection-associated high mobility group box (TOX), twist family BHLH transcription factor 1 (TWIST1), signal transducer and activator of transcription 4 (STAT4), and special AT-rich sequence-binding protein 1 (SATB1) genes function as transcription factors and are involved in the pathogenesis of MF. OBJECTIVES: We aim to determine the diagnostic value of TOX, TWIST1, STAT4, and SATB1 protein expressions in eMF. METHODS: This non-randomized, controlled, prospective analytic study was conducted by performing immunohistochemistry staining with TOX, TWIST1, STAT4, and SATB1 polyclonal antibodies in lesional skin biopsies of eMF and BID patients. Nuclear staining of lymphocytes was compared between eMF and BIDs, and the capacity of these antibodies to predict eMF was determined. RESULTS: Immunostainings with anti-TWIST1 showed an increase in protein expression (p = 0.003) and showed a decrease with anti-SATB1 antibodies in eMF compared to BIDs (p = 0.005) while anti-TOX and anti-STAT4 antibodies did not exhibit significant differences (p = 0.384; p = 0.150). Receiver operating characteristic analysis showed that immunohistochemical evaluations of TWIST1 and SATB1 protein expressions can differentiate eMF (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.605-0.851, p = 0.002; AUC: 0.686, 95% CI: 0.565-0.807, p = 0.013). CONCLUSIONS: TWIST1 and SATB1 are potential diagnostic markers for the histologic diagnosis of eMF.

Online depiction of urticaria is often flawed and does not reflect the spectrum of clinical manifestation.

BACKGROUND: The internet is a popular source of health information including images of disease manifestations. Online photographs of skin lesions may aid patients in identifying their disease, if these pictures are of good quality and of the disease they claim to show. If not, patients may be at risk of delayed diagnosis, misdiagnosis, and suboptimal treatment. For urticaria, the mismatch rate and quality of online pictures are unknown. The objective of this study was therefore to evaluate the content and quality of online images of urticaria. METHODS: The search term "urticaria" was applied on Google Images and Shutterstock. The top 100 photographs from each search engine were retrieved on October 9th, 2022. Illustrations, drawings, and heavily edited photographs were excluded. Each image was evaluated for patient characteristics, characteristics of urticarial lesions, and image quality. RESULTS: Across 194 unique images of urticaria (after removing duplicates), 35 (18.0%) did not depict urticarial lesions and 38 (19.6%) were ambiguous. Less than two thirds of images 121 (62.4%) showed bona fide urticarial lesions. Pictures of urticarial lesions under-represented children and did not reflect female preponderance of the disease. Images predominantly depicted urticaria lesions on Caucasian skin (59.8%) and typical of spontaneous rather than inducible urticaria. Only 3 (1.5%) pictures showed angioedema, a common clinical sign in patients with urticaria. The overall quality of online urticaria pictures was mostly good or very good. CONCLUSION: Physicians and patients should be aware that one in five online pictures of urticaria does not show urticarial skin lesions and children, females, non-Caucasian patients, inducible urticaria, and angioedema are under-represented. These findings should prompt efforts to improve the accuracy and representativeness of online urticaria pictures.

CRUSE - What the first 100 days have taught us.

Introduction: Health apps play an increasing role in everyday healthcare, especially for chronic diseases. The Chronic Urticaria Self Evaluation (CRUSE) is a new mobile health app for chronic spontaneous urticaria (CSU) patients, which replaces disease tracking via paper and pen, thus making disease monitoring more convenient, increasing tracking compliance, and improving data quality and access. Methods: CRUSE enables patients to complete patient-reported outcome measures on their smartphone and send the results, along with current medication and pictures, to their treating physician via email. CRUSE captures the urticaria (UAS) and angioedema activity (AAS) scores and the urticaria and angioedema control tests (UCT and AECT). In this work, a descriptive analysis of CRUSE users and reported days was performed. The global network of Urticaria Centers of Reference and Excellence (UCARE) provides the app and its data. Results: CRUSE is now available in Germany, Switzerland, Austria, the UK, Italy, Spain, France, and Turkey. Of 620 newly registered users (from July 1st until November 18th of 2022), 72 % were female, and the mean age was 36.6 years (17 - 78 years). The average daily UAS and AAS value (mean ± standard deviation) were 2.1 ± 1.9 and 7.2 ± 3.3, respectively. Most CRUSE patients had poorly controlled disease, with mean UCT values of 7.0 ± 4.4 and mean AECT values of 8.1 ± 4.5. Conclusion: The first days of patients with CSU using CRUSE confirm the high need for an app that helps to monitor disease activity, impact, and control. The first results indicate low levels of disease control in most CRUSE users, with low UCT and AECT values. Future analyses will assess follow-up documentation data and evaluate the effects of treatment changes on CSU activity, impact, and control.

The many faces of pediatric urticaria.

Urticaria is a common disease that can affect individuals of all age groups, with approximately one-quarter of the population experiencing it at least once in their lifetime. Lesions characterized by erythema and itchy hives can appear anywhere on the body. These can vary in size ranging from millimeters to centimeters, and typically clear within 24 h. About 40% of patients with urticaria have accompanying angioedema, which involves localized deep tissue swelling. Urticaria usually occurs spontaneously and is classified into acute and chronic forms, with the latter referring to a condition that lasts for more than 6 weeks. The prevalence of chronic urticaria in the general population ranges from 0.5% to 5%, and it can either be inducible or spontaneous. The most common form of pediatric urticaria is acute and is usually self-limiting. However, a broad differential diagnosis should be considered in children with urticaria, particularly if they also have accompanying systemic complaints. Differential diagnoses of pediatric urticaria include chronic spontaneous urticaria, chronic inducible urticaria, serum sickness-like reaction, urticarial vasculitis, and mast cell disorders. Conditions that can mimic urticaria, including but not limited to cryopyrinopathies, hyper IgD syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPs), and Schnitzler syndrome should also be considered. The many faces of pediatric urticaria can be both easy and confusing. A pragmatic approach relies on clinical foresight and understanding the various forms of urticaria and their potential mimickers. This approach can pave the way for an accurate and optimized diagnostic approach in children with urticaria.

Smartphone photographs of chronic urticaria taken by patients are of good quality and useful in the clinic.

BACKGROUND: Chronic urticaria (CU) is characterized by transient wheals and angioedema, which are often not present when patients see their treating physician. AIM: To evaluate the diagnostic value of smartphone photographs captured by patients prior to their first visit at an urticaria outpatient clinic. METHODS: A survey regarding the quality and utility of smartphone photographs of urticarial skin lesions in patients with CU attending the outpatient clinic for the first time was conducted. Up to three random patient-selected photographs of skin lesions were evaluated by a physician. RESULTS: Of 148 patients, 118 (79.7%) had taken photographs of their skin lesions prior to the consultation, and 75% took photographs with the intention of presenting it to their physician. The photographs were of wheals in 90% of the cases, and angioedema in 8%. In total, 72% of the smartphone photographs had the skin lesion in focus, 64% had good resolution, 48% had good lighting. Only 9% of the smartphone photographs were blurred, 10% had bad lighting, 4% had bad resolution, and 8% did not have the lesion in focus. Moreover, 86% of the smartphone photographs were found to be useful for clinical evaluation. At least one photograph of good/very good quality was presented by 86% of the patients, and 97% had at least one photograph that was useful for clinical evaluation. CONCLUSION: Patients with CU often take smartphone photographs of their skin lesions on their own initiative prior to their first consultation to present the photographs to their physician. These smartphone photographs are very often of good quality and suitable for clinical evaluation.

Differential diagnosis between urticarial vasculitis and chronic spontaneous urticaria: An international Delphi survey.

BACKGROUND: Urticarial vasculitis (UV) should be differentiated from chronic spontaneous urticaria (CSU) in patients initially presenting with recurrent wheals, although criteria for differential diagnosis remain ill-defined. OBJECTIVES: To set the goals, define criteria and unmet needs in UV diagnosis and differential diagnosis with CSU, and explore the possibility of coexistence of both diseases. METHODS: Thirteen experts experienced in UV research participated in a Delphi survey of European Academy of Allergy and Clinical Immunology taskforce. This Delphi survey involved three rounds of anonymous responses to n = 32 questions with the aim to aggregate the experts' opinions and to achieve consensus. Urticaria specialists (n = 130, most from Urticaria Centers of Reference and Excellence) evaluated the consensus statements and recommendations in the fourth and final round. RESULTS: The panel agreed that essential criteria to guide a skin biopsy in patients with recurrent wheals should include at least one of the following features: wheal duration >24 h, bruising/postinflammatory hyperpigmentation, and systemic symptoms. Leukocytoclasia and fibrin deposits were identified as a minimum set of UV histological criteria. As agreed by the panel members, CSU and normocomplementemic UV (NUV) may coexist in some patients. CONCLUSIONS: The use of established criteria for the diagnosis and differential diagnosis of UV in patients with recurrent wheals can help guide the diagnostic approach and prompt earlier treatment. Further studies should investigate whether CSU and NUV are different entities or part of a disease spectrum.

COVID-19 and Its Impact on Common Diseases in the Allergy Clinics.

Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has various effects on asthma, allergic rhinitis, atopic dermatitis, and urticaria and may change the course of the disease depending on the severity of the infection and control status of the disease. Conversely, these diseases may also impact the course of COVID-19. Patients with chronic urticaria and atopic dermatitis may have COVID-19-induced disease exacerbations and biological treatments reduce the risk of exacerbations. Poor asthma control is linked to severe COVID-19 while allergic asthma is associated with lower risk of death and a lower rate of hospitalization due to COVID-19 compared with nonallergic asthma. The use of intranasal corticosteroids is associated with lower rates of hospitalization due to COVID-19 in patients with allergic rhinitis, whereas the effect of inhaled corticosteroids is confounded by asthma severity. These observations reinforce the importance of keeping allergic diseases under control during pandemics. The use of biologicals during COVID-19 is generally regarded as safe, but more evidence is needed. The pandemic substantially changed the management of allergic disorders such as home implementation of various biologicals, allergen immunotherapy, food introduction, and increased use of telemedicine and even home management of anaphylaxis to reduce emergency department burden and reduce risk of infection. Physicians need to be aware of the potential impact of COVID-19 on allergic diseases and educate their patients on the importance of continuing prescribed medications and adhering to their treatment plans to maintain optimal control of their disease.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment-Results From CURE.

BACKGROUND: Patients with chronic spontaneous urticaria (CSU) have spontaneous wheals (W), angioedema (AE), or both, for longer than 6 weeks. Clinical differences between patients with standalone W, standalone AE, and W and AE (W+AE) remain incompletely understood. OBJECTIVE: To compare W, AE, and W+AE CSU patients regarding demographics, disease characteristics, comorbidities, disease burden, and treatment response. METHODS: Baseline data from 3,698 CSU patients in the ongoing, prospective, international, multicenter, observational Chronic Urticaria REgistry (CURE) were analyzed (data cut: September 2022). RESULTS: Across all CSU patients, 59%, 36%, and 5% had W+AE, W, and AE, respectively. The W+AE patients, compared with W and AE patients, showed the lowest male-to-female ratio (0.33), higher rates of concomitant psychiatric disease (17% vs 11% vs 6%, respectively), autoimmune disease (13% vs 7% vs 9%, respectively), and nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity (9% vs 5% vs 2%, respectively) and the highest disease impact. The W patients, compared with W+AE and AE patients, showed the lowest rates of concomitant hypertension (15% vs 21% vs 40%, respectively) and obesity (11% vs 16% vs 17%, respectively), the highest rate of concomitant inducible urticaria (24% vs 22% vs 6%, respectively), and shorter W duration. The AE patients, compared with W+AE and W patients, were older at disease onset, showed longer AE duration, and the best response to increased doses of H1-antihistamines (58% vs 24% vs 31%, respectively) and omalizumab (92% vs 67% vs 60%, respectively). CONCLUSIONS: Our findings provide a better understanding of CSU phenotypes and may guide patient care and research efforts that aim to link them to pathogenic drivers.

Autoreactive IgE: Pathogenic role and therapeutic target in autoimmune diseases.

Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.

Effect of Puberty, Menstruation, Pregnancy, Lactation, and Menopause on Chronic Urticaria Activity.

BACKGROUND: Chronic urticaria (CU) is a systemic disorder which is characterized by recurrent wheals and/or angioedema lasting more than 6 weeks. Sex hormones have been suggested to play a role in CU pathogenesis, however, their clinical implications have not been adequately described in the literature. OBJECTIVE: To determine whether conditions that change sex hormone levels such as puberty, menstruation, pregnancy, breastfeeding, and menopause affect the course of CU. METHODS: This cross-sectional questionnaire study was conducted on female CU patients at Okmeydani Training and Research Hospital UCARE Center between 2016 and 2017. The open-ended questionnaire consisted of questions evaluating the effects of hormonal changes on disease course. RESULTS: A total of 111 female CU patients were included in the analysis. During the perimenstrual period, CU symptoms worsened in 29% of patients but improved in 4.8%. The disease course did not change in the majority of patients during puberty, pregnancy, lactation, or menopause (100%, 96%, 83.8%, and 95.6%, respectively). CONCLUSIONS: Contrary to expectations, a change in sex hormone levels had no effect on the course of CU in the majority of cases. However, disease activity increased in one-third of CU patients during the perimenstrual period.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

How Infection and Vaccination Are Linked to Acute and Chronic Urticaria: A Special Focus on COVID-19.

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.

Chronic spontaneous urticaria: new evidences on the role of autoimmunity.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU). RECENT FINDINGS: Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors. SUMMARY: Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.