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Background: Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking., Objective: To assess the clinical impact of adapting CSU international guidelines for CIndU management., Methods: We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of ≤11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT ≥12 points. Pharmacological steps were evaluated for at least 1 month, with the next step initiated in case of a UCT score ≤11 points., Results: We enrolled 194 patients with CIndU. Of them, 134 patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reach a UCT ≥12 points, with avoidance measures 23 (11.8%) patients, antihistamines 84 (43.2%), omalizumab 35 (18%), and cyclosporine 17 (8.7%)., Conclusions: This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for patients with CIndU who remain uncontrolled., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Short courses of adjunctive systemic corticosteroids are commonly used to treat acute urticaria and chronic urticaria flares (both with and without mast cell-mediated angioedema), but their benefits and harms are unclear., Objective: To evaluate the efficacy and safety of treating acute urticaria or chronic urticaria flares with versus without systemic corticosteroids., Methods: We searched the MEDLINE, EMBASE, CENTRAL, CNKI, VIP, Wanfang, and CBM databases from inception to July 8, 2023, for randomized controlled trials of treating urticaria with versus without systemic corticosteroids. Paired reviewers independently screened records, extracted data, and appraised risk of bias with the Cochrane 2.0 tool. We performed random-effects meta-analyses of urticaria activity, itch severity, and adverse events. We assessed certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach., Results: We identified 12 randomized trials enrolling 944 patients. For patients with low or moderate probability (17.5%-64%) to improve with antihistamines alone, add-on systemic corticosteroids likely improve urticaria activity by a 14% to 15% absolute difference (odds ratio [OR], 2.17, 95% confidence interval [CI]: 1.43-3.31; number needed to treat [NNT], 7; moderate certainty). Among patients with a high chance (95.8%) for urticaria to improve with antihistamines alone, add-on systemic corticosteroids likely improved urticaria activity by a 2.2% absolute difference (NNT, 45; moderate certainty). Corticosteroids may improve itch severity (OR, 2.44; 95% CI: 0.87-6.83; risk difference, 9%; NNT, 11; low certainty). Systemic corticosteroids also likely increase adverse events (OR, 2.76; 95% CI: 1.00-7.62; risk difference, 15%; number needed to harm, 9; moderate certainty)., Conclusions: Systemic corticosteroids for acute urticaria or chronic urticaria exacerbations likely improve urticaria, depending on antihistamine responsiveness, but also likely increase adverse effects in approximately 15% more., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU)., Objective: We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU., Methods: We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests., Results: A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation., Conclusion: In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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 H 1 -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., (Copyright © 2023. Published by Elsevier Inc.)

Background: Chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV) share several clinical features including the occurrence of wheals. As of yet, the criteria for differentiating the 2 disorders are not clearly defined., Objective: Here, we aimed to identify differences, similarities, and the likelihood for specific clinical features in patients with UV versus those with CSU., Methods: Across 10 Urticaria Centers of Reference and Excellence, 106 patients with skin biopsy-confirmed UV and 126 patients with CSU were prospectively recruited to complete a questionnaire on the clinical features, course, and response to treatment of their disease., Results: As compared with CSU, patients with UV more often experienced postinflammatory skin hyperpigmentation, wheals of ≥24-hour duration, eye inflammation, and fever (6.9, 4.0, 3.6, and 2.4 times, respectively). Clinical features that increased the risk for UV diagnosis when present at the onset of disease included wheals of ≥24-hour duration (7.3-fold), pain of the skin (7.0-fold), postinflammatory hyperpigmentation (4.1-fold), and fatigue (3.1-fold). The diagnostic delay was markedly longer for normocomplementemic UV as compared with hypocomplementemic UV and CSU (21 vs 5 vs 6 months, respectively). Oral corticosteroids and omalizumab were the most effective treatments in patients with UV and CSU, respectively. Patients with UV showed a higher need for immunosuppressive and anti-inflammatory therapies than patients with CSU., Conclusions: Long wheal duration, skin pain and hyperpigmentation, and systemic symptoms point to UV rather than CSU as the underlying disease and should prompt further diagnostic workup including a skin biopsy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab., Objective: We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU., Methods: PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis., Results: Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings., Conclusions: This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Data on real-life experience with omalizumab dose/interval adjustments are still limited, as well as on omalizumab discontinuation., Objective: To evaluate efficacy and safety of omalizumab dose/interval adjustment in a Portuguese cohort of patients with chronic spontaneous urticaria (CSU) and to characterize those who discontinued omalizumab., Methods: A retrospective study of patients who started omalizumab for CSU at a Portuguese Urticaria Center of Reference and Excellence (UCARE) was conducted between 2009 and 2021. Response criteria were based on a weekly Urticaria Activity Score (UAS7) <7 points (partial: UAS7 7-15 points; nonresponders: UAS7 >15 points) and minimal important difference >10 points., Results: A total of 138 patients were enrolled in the study; 83% of them were women, and the median age was 49 years (interquartile range: 40-58 years). On 300 mg q4 weeks, 96 (70%) patients were responders, 29 (21%) partial responders, and 13 (9%) nonresponders. After dose/interval adjustments (up to 600 mg q2 weeks), 108 (78%) were responders, 27 (20%) partial responders, and 3 (2%) nonresponders. No adverse events were reported. Updosing was more frequent in patients with angioedema, body mass index >30 kg/m 2 , positive basophil activation test, and autologous serum test. A total of 71 (51%) patients lengthened interval, presenting higher median pre-omalizumab D-dimer (0.2 vs 0 mcg/mL, P = .038) and C-reactive protein (0.3 vs 0.1 mg/dL, P = .030) values than those with a standard dose. In total, 37 patients (27%) stopped omalizumab, but 14 (38%) of them needed retreatment on average 11 months after discontinuation. Patients with angioedema and a longer omalizumab duration had higher chance of relapse., Conclusions: Omalizumab dose and/or interval adjustment is effective and safe and should be implemented in partial/nonresponders for response improvement and in responders for further discontinuation. A protocol for regimen adjustments is proposed., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The rapid development and rollout of vaccines against coronavirus disease 2019 (COVID-19) has led to more than half of the world's population being vaccinated to date. Real-world data have reported various adverse cutaneous reactions, including delayed-onset urticaria, which was highly ranked as a common manifestation across studies. However, the impact of these novel mRNA or viral vector COVID-19 vaccines on preexisting chronic spontaneous urticaria (CSU) remains largely unknown., Objective: To investigate the impact of COVID-19 vaccination on the clinical status of patients with relatively stable CSU who are undergoing omalizumab treatment and to identify risk factors for exacerbation., Methods: We conducted a questionnaire-based cross-sectional study in a tertiary hospital. Adult patients with relatively stable CSU under regular omalizumab treatments who had received at least one COVID-19 vaccination were included., Results: There were 105 study subjects who received 230 COVID-19 vaccinations between March and December 2021. Fifteen patients (14.3%) experienced aggravation of urticaria at least once after COVID-19 vaccination. The demographics and clinical characteristics of the patients were comparable regardless of the exacerbation of CSU. However, case-level analysis revealed that the presence of urticaria (vs none) before vaccination (odds ratio [OR] = 4.99; 95% CI, 1.57-15.82) and the development of systemic reactogenicity (OR = 4.57; 95% CI, 1.62-12.90) were associated with a higher risk for exacerbation., Conclusions: The novel COVID-19 vaccination induced exacerbation in more than one-tenth of patients with well-controlled CSU. The establishment of a proper management strategy during COVID-19 vaccination is necessary for patients with CSU., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The comparative safety and/or dosing regimens of individual second-generation H1-antihistamines (sgAHs) in patients with chronic urticaria (CU) remain poorly elucidated., Objective: To compare the safety profiles of individual sgAHs and/or dosing regimens in adolescents or adult patients with CU using a systematic review and network meta-analysis of all available evidence., Methods: With limited English publications, electronic databases and gray literature were searched for randomized clinical trials from inception, with searches last updated on January 20, 2023. Relevant safety outcomes included treatment unacceptability (all-cause discontinuation), tolerability (discontinuation due to any adverse events), adverse events, serious adverse events, central nervous system (CNS) side effects, and anticholinergic side effects. Regarding the network estimates, the probability of being associated with the highest adverse outcome risk was estimated for each treatment comparison., Results: Fifty-one randomized clinical trials with 14 individual sgAHs and different dosing regimens, involving 7502 participants, were included. On the basis of the findings from network meta-analyses, variations in sgAH treatment comparisons were observed regarding the unacceptability of treatment, tolerability, adverse events, and CNS side effects. There were no statistically significant differences between the results of sgAH treatment for serious adverse events and those for anticholinergic side effects. On the basis of the ranking of safety profiles, emedastine 4 mg, mizolastine 10 mg, and cetirizine 10 mg were the top 3 ranked treatments with unfavorable safety profiles associated with CNS side effects and any adverse events., Conclusions: These findings suggest evidence of variations in safety profiles among sgAHs for CU treatment, particularly in terms of adverse events and CNS side effects., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Chronic urticaria is a disease that can significantly impact a patient's quality of life and ability to function. There are effective treatment options, such as nonsedating antihistamines or biologics, but some patients do not respond to these therapies, or the therapies are not available or affordable to all patients. This review aims to summarize potential treatment strategies for patients (1) who do not respond to antihistamines and (2) cannot readily access or do not respond to biologics. The review emphasizes the importance of sound clinical practice, including correct diagnosis of chronic urticaria phenotypes, treatment of associated comorbidities, and consideration of add-on pharmacological and nonpharmacological approaches. Although some treatments may lack high-quality evidence, they may still be justifiable in certain cases, provided that there is shared decision-making, regular reassessment, and early recognition of adverse events., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states., Methods: CURE data were collected at baseline and 6-monthly follow-ups (FU). Assessments included CSU states using the Urticaria Control Test (UCT), weekly Urticaria Activity Score (UAS7), and Physician Global Assessment (PhyGA) of treatment response. Complete response to treatment (CR, UAS7 = 0), complete control of disease (CC, UCT = 16), and PhyGA = CR were assessed, plus the Dermatology Life Quality Index and the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q 2 oL) sleep domain., Results: Overall, 2078 patients were included. At baseline, 9.8%, 17.9%, and 42.3% of patients had UCT = 16, UAS7 = 0, or PhyGA = CR, respectively, which increased at FU1 and FU2. Patients with higher UCT scores had better sleep and HRQoL. The presence of angioedema without wheals, episodic disease, omalizumab treatment, and male sex were associated with CC (P < .05). Among 469 patients who achieved CC or CR, 16.4% (n = 77) showed CC or CR with all 3 instruments. Agreement between UCT = 16 and UAS7 = 0 measurements was moderate (κ = 0.581), but poor between UCT = 16 and PhyGA = CR (κ = 0.208)., Conclusions: Few patients had CR/CC of their CSU at baseline entry. Disease control strongly related to good sleep and better HRQoL; therefore, it is important to aim for CR in CSU treatment. Patient-reported UCT and UAS7 assessments demonstrated a more accurate measurement of CSU state versus physician assessments., (Copyright © 2022. Published by Elsevier Inc.)

Background: Chronic spontaneous urticaria (CSU) not controlled by optimized doses of antihistamines is referred to as refractory CSU. Add-on therapies recommended by guidelines include omalizumab, immunosuppressive, and anti-inflammatory agents., Objectives: The objective of the study was to assess the real-world effectiveness of different add-on treatment options for refractory CSU in 2 large clinical practices., Methods: A retrospective chart review was conducted in 264 patients with refractory CSU not adequately controlled for ≥6 weeks with optimized doses of second-generation histamine-1 blockers. Omalizumab and hydroxychloroquine were the most frequently prescribed add-on therapies, allowing comparisons of clinical outcomes for these 2 agents. Complete response included absent or infrequent urticaria and patient satisfaction with treatment. Partial response was reduced hives, but requiring a second add-on therapy. Sustained response was complete response to an add-on therapy for ≥1 year., Results: Omalizumab add-on treatment was significantly more likely to be associated with a complete response versus hydroxychloroquine. Complete sustained response at 1 year was observed in 82% (111 of 134) of patients on omalizumab and 66% (73 of 111) on hydroxychloroquine as the first add-on therapy (P < .01). Patients with thyroid disease had a poorer response to add-on treatments (45% responded vs 63%; P = .03). In patients with incomplete responses to first add-on interventions (n = 45), 65% and 62% subsequently had complete responses to omalizumab and hydroxychloroquine, respectively., Conclusions: Although omalizumab was superior, hydroxychloroquine achieved a complete response in two-thirds of treated patients. Given a favorable safety profile, hydroxychloroquine should be considered as an add-on treatment for refractory CSU., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Treatment of chronic spontaneous urticaria (CSU) is responsive to H1 antihistamines administered up to four times the recommended US Food and Drug Administration dose in approximately 50% of patients. However, when patients do not respond to these first-line agents, evidence-based guidelines using Grading of Recommendations, Assessment, Development, and Evaluations methodology have provided direction for second- and third-line treatments that can effectively treat patients with CSU. Some patients remain refractory to these advanced treatments; therefore, alternative treatments with a lower certainty of evidence may be necessary. Regardless of the therapies used to treat CSU patients, it is essential for clinicians to be knowledgeable about the mechanism of action, efficacy, and safety and monitoring recommendations of the treatments prescribed. This review provides a comprehensive review of the adverse effects and monitoring recommendations for agents in use for CSU treatment as well as those currently undergoing investigation for CSU treatment., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Cholinergic urticaria (UCOL) is a highly disabling inducible urticaria triggered by an increase in core body temperature., Objective: To explore the safety and efficacy of omalizumab in controlling UCOL., Methods: We conducted a multicenter randomized mixed double-blind and open-label (first 4 months blinded followed by 8 months open-label) placebo-controlled clinical trial in 22 patients suffering from UCOL who were unresponsive to a double dose of antihistamines. We performed an exercise challenge test during each visit as our main outcome variable., Results: The overall rate of exercise challenge test negative at week 48 was 31.3%, with an average increase in exercise challenge test negative rate of 2.9% points (95% CI, 1.5-4.2) per visit. Statistically significant differences in the negative exercise challenge test rate between the placebo and active intervention groups were not observed during the blinded period (first 4 months of the study). However, from the fourth dose, a progressive improvement was observed. When comparing before and after treatment, statistically significant improvements in all secondary outcome measures were noted after 4 doses (UCOL score: P = .0015; visual analog scale score: P = .0108; days with symptoms: P = .0125) and after 8 doses (UCOL score: P = .0005; chronic urticaria quality of life questionnaire: P = .0105; visual analog scale score: P = .0008; and days with symptoms: P = .0144). In the follow-up visit after the cessation of treatment, the symptoms reappeared, with positive exercise challenge test result and significant increases in all variables. Only 4 of 22 patients remained asymptomatic after 3 months of no treatment. No adverse effects were reported., Conclusions: This randomized mixed double-blind and open-label placebo-controlled trial showed evidence of the safety and potential efficacy of omalizumab in patients with UCOL., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)