Management Of Chronic Spontaneous Urticaria Research Articles

A Practical Approach to Diagnosing and Managing Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is an unpredictable inflammatory skin condition characterized by the spontaneous onset of itchy wheals, angioedema, or both, which occurs for longer than 6weeks overall. Despite the relatively straightforward diagnostic algorithm for CSU, relying primarily on a detailed medical history and only limited laboratory tests, patients often wait years to be diagnosed, with many cycling through different healthcare practitioners before a diagnosis is made. Even then, current treatment options for CSU are limited, with approximately half of patients resistant to standard-of-care second-generation antihistamines at standard or higher doses. As such, there is an unmet need for improved, streamlined management for patients with CSU. Here, we review the evidence-based diagnostic algorithm for CSU, consider the required steps of the diagnostic workup, and provide practical, real-world advice on the management of CSU to improve the timely diagnosis and care of patients with this debilitating disease.

The autologous serum skin test (ASST) predicts the response to anti-IgE treatment in Chronic Spontaneous Urticaria patients: a prospective study.

Background. Chronic spontaneous urticaria (CSU), characterized by recurrent itchy wheals and angioedema for > 6 weeks, is a quite common disease that may heavily impair the quality of life. Omalizumab, an anti-IgE mAb, has much improved the management of CSU but patients' response to the drug may vary and predictive markers are still largely missing. We investigated the predictive value of the autologous serum skin test (ASST) on omalizumab response. Methods. 15 patients with severe CSU eligible for omalizumab treatment were prospectively studied submitting them to ASST and to complete blood count, D-dimer, anti-thyroid peroxidase antibodies, and total IgE measurement before the start of the treatment. Results. 14/15 (93%) responded brilliantly to omalizumab at 3 months assessment. 7 responded in less than 1 month ("early responders") and 7 only after multiple administrations ("late responders"). Of 9 patients scoring positive on ASST, 7 (78%) were late, and 2 (22%) early responders to omalizumab (p = 0.021). Of 6 patients scoring negative on ASST, 5 were early omalizumab responders and 1 did not respond. The PPV and NPV of the ASST for a "late" response to omalizumab were 78% and 100%, respectively. Total IgE were significantly higher in early responders. Conclusions. Although larger prospective studies are needed to confirm these results, this study confirms previous retrospective investigations that the positive ASST appears to predict a slow response to omalizumab in CSU patients.

Levocetirizine versus Bilastine as Monotherapy in the Management of Chronic Spontaneous Urticaria: A Randomised Controlled Trial

Introduction: Chronic urticaria is defined as the almost daily occurrence of wheals and pruritus for a minimum of six weeks, adversely affecting the quality of life and necessitating management with a drug with better efficacy and a high safety profile. This study was designed to determine how monotherapy with newer antihistamines benefits chronic spontaneous urticaria by producing earlier and longer periods of remission. Additionally, the study aimed to assess the adverse effects associated with the drugs. Aim: To compare the efficacy of Levocetirizine and Bilastine in chronic spontaneous urticaria. Materials and Methods: The study was a single-blinded randomised controlled trial conducted in the Department of Dermatology at Madras Medical College, Chennai, Tamil Nadu, India over 24 months from January 2020 to December 2021. A total of 163 patients with chronic urticaria were randomly divided into two groups: Group A with 82 patients and group B with 81 patients. The patients were treated with tablet Levocetirizine 5 mg and tablet Bilastine 20 mg for six months (with up-dosing to four-fold maximum) in Group A and Group B, respectively. The treatment response was assessed using the Urticaria Activity Score (UAS) at each follow-up. Patients were followed-up for an additional six months to observe the time of recurrence. Total 15 patients were lost to follow-up and were consequently excluded from the statistical analysis. Results: At the end of six months, the improvement observed in UAS was statistically similar in both groups (p-value=0.513). The time taken for remission was shorter with Levocetirizine (11.19±5.31 weeks) compared to Bilastine (14.59±5.02 weeks). Recurrence occurred earlier with Bilastine compared to Levocetirizine. Conclusion: Levocetirizine and Bilastine are equally effective in controlling urticaria at the end of six months of treatment. Patients on Levocetirizine experienced earlier remission as well as late recurrence compared to those on Bilastine.

42777 Dupilumab as Add-On Therapy for Management of Chronic Spontaneous Urticaria: A Single Center Retrospective Study

42777 Dupilumab as Add-On Therapy for Management of Chronic Spontaneous Urticaria: A Single Center Retrospective Study

44231 Variability in Treatment Patterns across Specialties in the Management of Chronic Spontaneous Urticaria (CSU): A Real-World Survey in the US

44231 Variability in Treatment Patterns across Specialties in the Management of Chronic Spontaneous Urticaria (CSU): A Real-World Survey in the US

Current perspectives and future directions in the management of chronic spontaneous urticaria and their link to disease pathogenesis and biomarkers.

Chronic spontaneous urticaria (CSU) is a relatively common, persistent, debilitating inflammatory skin disorder, having a global point prevalence ~0.5-1%. This disorder considerably worsens the patient's quality of life, and also poses a burden for the society. It is primarily an IgE mediated mast cell disorder, histamine being the principal mediator. So, the current treatment recommendations are aimed at antagonizing the effect of histamine, block mast cell activation by reducing IgE, or immunomodulate the inflammatory response. However, almost one in five CSU patients remain uncontrolled with the current safe treatments comprising antihistamines and add-on anti-IgE omalizumab. Thus, newer and more targeted therapeutic strategies are needed to overcome this unmet need, based on the various interlinked ligands and receptors involved in disease pathogenesis. Considerable progress has been made in understanding the pathogenesis of CSU, beyond the IgE-FceR1-mast cell axis, which has enabled the development of newer and more targeted promising therapeutic strategies. Several biomarkers are also being evaluated which would better define the disease characteristics and foretell treatment outcome even before its initiation. This would enable specific and targeted precision therapy based on disease characteristics, with better effectiveness-safety ratio. The present article discusses the current understanding about CSU, and recent up-to-date perspectives pertaining to disease pathogenesis, emerging treatments, and their link to biomarkers. These authors hope that the article would be helpful for all specialists and CSU treating physicians, in providing optimum care to their patients, based on latest evidence and concepts.

Embracing Digital Health Solutions: The Pivotal Role of the CRUSE App in Chronic Spontaneous Urticaria Management

Embracing Digital Health Solutions: The Pivotal Role of the CRUSE App in Chronic Spontaneous Urticaria Management

Journal club: Recent therapeutic developments in the management of chronic spontaneous urticaria.

Journal club: Recent therapeutic developments in the management of chronic spontaneous urticaria.

Management of Autoimmune urticaria in a patient with Myasthenia Gravis, a challenging case.

The pathophysiology of chronic spontaneous urticaria (CSU) is not yet fully understood; however, increasing evidence supports the association between CSU and autoimmunity. Myasthenia gravis (MG) is an autoimmune neuromuscular disorder. MG management relies on using immunosuppressants and avoiding certain medications that can precipitate an MG crisis. The coexistence of CSU and MG was described in the literature on elderly patients. Herein we present a challenging case regarding the management of CSU in a young female with MG. A 22-year-old lady known to have Myasthenia gravis post thymectomy, with a history of multiple MG crises, presented to the Allergy Clinic with recurrent itchy hives typical for urticaria without associated angioedema. Despite being on Azathioprine and low-dose steroids for MG treatment, she had an active CSU disease, UAS7:32, UCT: 5. The neurologist advised against the use of regular oral antihistamines because they might exacerbate MG. Although we do not have serum autologous skin testing, basophil activation test, or IgG autoantibodies for a definitive definition of autoimmune CSU (aiCSU), the patient has some features supporting the diagnosis of aiCSU (see Table 1). In addition, she has a normal total IgE level, normal C3, C4, negative RF, ANA, ANCA, anti-TPO, and anti-thyroglobulin antibodies. After the discussion with the neurologist, we started her on Omalizumab 300 mg every four weeks, which was increased to 450 mg every two weeks with partial control of CSU. She was started on rituximab to treat MG with improvement in CSU. To the best of our knowledge, limited data describing the association between MG and CSU in young patients. Moreover, there is insufficient data on the safety of antihistamines in patients with MG, which are the first line of treatment for CSU. There are clinical and laboratory biomarkers that help in identifying CSU endotypes. Recognition of aiCSU endotype is essential as it helps predict disease course and response to treatment. Moreover, careful therapeutic interventions in patients with CSU and coexistent autoimmune diseases are warranted to achieve efficacy and reduce drug interactions and adverse effects.

Ligelizumab: A novel molecule in the management of chronic spontaneous urticaria

The next-generation high affinity monoclonal immunoglobulin E (IgE) inhibitor Ligelizumab is being tested in clinical studies to treat chronic spontaneous urticaria (CSU). In 2020, the US Food and Drug Administration (FDA) designated Ligelizumab (QGE031) as a breakthrough therapy for patients with chronic idiopathic urticaria; however, FDA clearance has not yet been granted, despite the phase 3 trial’s completion. Recent clinical investigations have shown that it has a considerable affinity for the high-affinity IgE receptor (FcRI) on the surface of immune cells, which is quite beneficial in the management of the distressing symptoms of CSU. Studies have been done comparing Ligelizumab to Omalizumab, the current standard of care for treating CSU that is refractory. While omalizumab is more effective than Ligelizumab at inhibiting IgE: CD23 interactions, Ligelizumab exhibits stronger inhibition of IgE binding to FcRI, basophil activation, IgE synthesis by B cells, and passive systemic anaphylaxis. To learn about this molecule’s extended characteristics, long-term efficacy and safety, and potential uses in other dermatological disorders, more clinical data is needed.

Real-World Indian Experience of Switchover to Bilastine 40 mg/day in CSU Patient Refractory to Other Antihistamines at Double Dose.

Although second-generation antihistamines (SGAHs) are recommended as first-line drugs in chronic spontaneous urticaria (CSU), symptom relief has been reported in <50% of patients at licensed doses and up to fourfold dosing is recommended for these patients. Bilastine (SGAH), at licensed doses and higher doses, is efficacious in CSU. However, large-scale real-world data is scarce. To report the real-world evidence of the safety and effectiveness of bilastine at a double dose (40-mg per day) in CSU management. In this retrospective questionnaire-based study carried out from February 2022 to July 2022, a pre-validated questionnaire was used to gather data on patients with CSU in dermatology practice from 62 centres across India. Adult patients of either gender diagnosed with CSU and switched over to bilastine 40 mg/day due to a non-satisfactory response (UCT score <12) to other antihistamines at double dose were considered for analysis. Based on UCT scores, patients were classified as responders (UCT ≥12) and non-responders at follow-up assessment at 2 weeks as compared to baseline. 177 patients with a mean disease duration of 2.11 ± 1.48 years were included in the final analysis, with 53% females and 47% males. At the end of two weeks, 74/177 (42%) patients were classified as responders, and 103/177 (58%) were non-responders to Bilastine 40 mg/day. The mean change of UCT score from 5.0 ± 2.2 at baseline to 8.08 ± 5.41 (62% improvement) was significant (P < 0.001). Sedation was reported by ten patients without any discontinuation of treatment. Bilastine 40 mg/day was effective and well-tolerated in controlling CSU symptoms refractory to antihistamines at double doses.

Chronic Spontaneous Urticaria in Hong Kong: Clinical Characteristics, Real-World Practice and Implications for COVID-19 Vaccination

The real-world management and clinical characteristics of chronic spontaneous urticaria (CSU) in Hong Kong and its implications for coronavirus disease 2019 (COVID-19) vaccination are unknown. We investigated the clinical characteristics of patients with CSU and the role of an immunologist-led Urticaria Clinic as well as the impact of CSU on COVID-19 vaccine uptake in Hong Kong. Longitudinal clinical data of 257 CSU patients were collected and analyzed. Association analyses were performed to identify the relationships between variables and factors associated with COVID-19 vaccine uptake. After the immunologist review, the Weekly Urticaria Activity Score (UAS7) was significantly lower than baseline (median: 0.00 vs. 12.0, P < 0.001). Changes in UAS7 were significantly greater among patients with baseline UAS7 ≥ 16 compared to those with UAS7 < 16 (median: -24.0 vs. -2.00, P < 0.001). CSU patients had lower COVID-19 vaccination rates than the general population with only 176 (68.5%) and 165 (65.0%) receiving at least one dose and 2 doses of vaccination, respectively. The presence of concomitant suspected drug allergy was associated with lower COVID-19 vaccine uptake (odds ratio [OR], 0.47; P = 0.010), while regular pharmacological treatment was associated with higher COVID-19 vaccine uptake among CSU patients (OR, 3.79; P = 0.010). A dedicated immunologist-led Urticaria Clinic may effectively improve CSU management and outcomes in Hong Kong.

Clinical and laboratory parameters associated with treatment response to third-line therapies in chronic refractory urticaria: A real world study from northern India.

Current guidelines recommend omalizumab and cyclosporine for management of chronic spontaneous urticaria (CSU) refractory to anti-histamines. Identification of clinico-epidemiological characteristics predictive of treatment response with both modalities which will aid therapy selection. Clinical records of CSU patients receiving omalizumab and cyclosporine from May 1, 2016 to December 31, 2020 were reviewed retrospectively. Patients with a minimum follow-up duration of 4 months were included in the analysis. Treatment response was defined as >90% recorded reduction in Urticaria Activity Score-7 (UAS7) as compared to baseline 4 months after treatment initiation. Records of 1364 CSU patients were reviewed. A total of 56 patients who received omalizumab and 132 patients who received cyclosporine fulfilled the inclusion criteria. Treatment response was observed in 46 out of 56 (82.1%) patients in the omalizumab cohort and 106 out of 132 (80.3%) patients in the cyclosporine cohort (P=0.76). Factors significantly associated with response to omalizumab included high baseline serum IgE levels (P=0.028), lesser disease duration (P=0.001), and absence of prior immunosuppressant use (P=0.024). Factors predictive of cyclosporine response included high baseline UAS7 (P=0.048), low baseline IgE levels (P=0.047), and normal baseline D-dimer levels (P=0.027). Concomitant inducible urticaria, atopy, and angioedema were associated with non-response in both groups (P ≤ 0.05). Incidence of adverse events was slightly higher in cyclosporine group (28.7%) as compared to omalizumab group (19.5%, P=0.19). This study highlights several clinical parameters and laboratory markers that may be utilized to predict treatment response and aid in prognostication of patients with CSU.

Exacerbation of Chronic Spontaneous Urticaria Symptoms in COVID-19 Patients, Case Report.

Chronic spontaneous urticaria (CSU) is characterized by wheals lasting more than 6 weeks and can be accompanied by angioedema. Treatment of the disease varies depending on the severity and includes first-line therapeutics such as non-sedative antihistamines. Second- and third-line treatments are used in severe and uncontrolled form of CSU. Environmental exposure and infections could trigger worsening symptoms. The goal of this study is to assess the effect of SARS-CoV-2 infection on CSU symptoms and the efficacy of the second- and third-line therapeutics for CSU management in COVID-19 patients. Our findings show that SARS-CoV-2 infection exacerbates CSU symptoms. Worsening of disease was indicated by decreased Urticaria Control Test (UCT) and increased Urticaria Activity Score (UAS). Treatment management was modified by switching to second- and third-line therapeutics; however, therapeutic control was achieved only in one patient. Our data demonstrates that SARS-CoV-2 infection contributes to the severity of CSU. Symptoms of CSU are more challenging to manage and require changes in treatment protocol, including second- and third-line therapeutics. We believe that severe inflammation triggered by SARS-CoV-2 infection contributes to the worsening of CSU symptoms.

Value-Based, Cost-Effective Care: The Role of the Allergist-Immunologist

Asthma and allergic disease impact millions of patients and are associated with high costs. Up to 30% of all medical care involves wasted spending. Across the spectrum of care provided by the allergist-immunologist, there are opportunities to improve value and reduce medical waste. Several examples highlight this reality. Evidence suggests that most patients may receive cost-effective care in the management of chronic spontaneous urticaria without the need for laboratory testing. For patients with asthma, although a single maintenance and reliever therapy approach may be cost-effective, insurance-mandated therapy changes are not, and may harm patients. Biologics may be very effective in improving asthma control but are too expensive for this indication-as demonstrated by cost-effectiveness analyses and highlighted by the Institute of Clinical and Economic Review, which concluded that the value-based price for asthma biologics ranges between $6500 and 14,3000 per year. Early introduction may prevent food allergy, but screening before first introduction is neither necessary nor cost-effective, although early salvage food oral immunotherapy may result in improved quality of life and cost savings. Evidence does not support the presence of allergic disease as a risk factor for anaphylaxis to coronavirus disease 2019 vaccination, and risk-stratified vaccination approaches do not appear cost-effective. Allergen immunotherapy is a very cost-effective treatment option. The practice of allergy-immunology has continued to evolve in recent years and can provide a leading example of high-value practice.

Current and Future Approaches in Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies.

Chronic spontaneous urticaria (CSU) considerably alters patients’ quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms “anti-IgE antibodies”, “omalizumab”, “ligelizumab”, and “chronic spontaneous urticaria”. The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients’ quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.

Online Education Yields Significant Gains in Physicians' Knowledge of Diagnosis and Management of Chronic Spontaneous Urticaria

We developed an online CME activity titled: “A Call to Action for Improving Disease Control in Chronic Spontaneous Urticaria: From Guidelines to Clinical Practice”. We hypothesized that participation in this online CME education would lead to improved knowledge of guideline recommendations for the management of CSU and competence related to timely diagnosis and appropriate management of CSU.

Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey.

The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU in clinical practice. A study-specific questionnaire was administered to a group of physicians (N.=21) with a specialist interest in CSU from different areas of Italy (group A) and also to other physicians (N.=25) who manage CSU only occasionally in their clinical activity (group B). In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Management of chronic spontaneous urticaria: Real-world Indian perspective

Objectives: There are multiple guidelines for chronic spontaneous urticaria (CSU) by various dermatological associations, but in real-world practice in India, different approaches have been noted. In this paper, we courted to determine these different approaches in CSU management, adherence to various CSU guidelines, and the reasons for deviation from guidelines amidst dermatologists in India. Materials and Methods: A net-based questionnaire was created and validated by five panelists experienced in CSU management and then was circulated to all dermatologists in India in August 2020 for real-world management scenario. Results: We received 880 completed response out of 2235 response. Most of the dermatologists (97%) were aware of some urticaria guidelines. Although many of them follow guidelines about three forth of them reported to deviate from it sometimes. The most common reason for deviation was rely on clinical experience as opted by 53% of respondents. Dermatologists who follow guidelines also investigate routinely in terms of complete blood count, the erythrocyte sedimentation rate, and thyroid-stimulating hormone as compared to those who do not. About 70.5% of the dermatologist prescribe second-generation antihistamine (SGAH) at approved dose as the first line of treatment whereas 63.6% up dose it as second line of treatment. Surprisingly, 68% prescribe first-generation antihistamine in the evening and SGAH in the morning as combination therapy in CSU. Conclusion: From the findings of the present study, it can be strongly implied that guidelines play a vital role in delivering superior attributes of patient care although 75% of dermatologists deviated from it. Main reasons for deviance are reliability on self-clinical proficiency and consideration of economic impediments. Both these factors need to be worked upon by continuous medical education of dermatologists and more pharmaco-economic research.

Comparative assessment of quality of life in chronic spontaneous urticaria receiving second generation anti histamines: A real world study

Objectives: Chronic spontaneous urticaria (CSU) is correlated with a high detrimental effect on the quality of life (QoL). Antihistamines are the first choice drugs in the management of CSU. QoL is important in the evaluation of the efficacy of antihistamines, as these are the most commonly used in CSU. Materials and Methods: In this comparative, three-arm study, patients with CSU were randomized to standard dose of either bilastine, fexofenadine, or levocetirizine for a period of 4 weeks. Patients were assessed for improvement in their QoL based on chronic urticaria QoL questionnaire (CU-Q2oL) questionnaire and urticaria activity score (UAS). Results: Fifty-eight CSU patients were randomized to bilastine (n = 23), fexofenadine (n = 18) and levocetrizine (n = 17) groups. There was significant improvement in CU-Q2oL and UAS score in all the groups during study period. 83%, 72%, and 65% patients reported improvement in CU-Q2oL score in bilastine, fexofenadine, and levocetrizine group, respectively. Bilastine was associated with significant improvement in CU-Q2oL compared to fexofenadine and levocetrizine (P &lt; 0.05). Mean reduction in UAS score was 86%, 77%, and 68% in bilastine, fexofenadine and levocetrizine group respectively. The difference was statistically insignificant between the groups. The CU-Q2oL total score correlated more strongly (r = 0.62; P = 0.001) with the UAS7 in bilastine group than fexofenadine (r = 0.57; P = 0.01) and levocetrizine groups (r = 0.53; P = 0.02). Conclusion: The results of the study proved that, in CSU patients, QoL was improved significantly with bilastine as compared to fexofenadine and levocetirizine.