Atopy and Response to Omalizumab Treatment in Chronic Spontaneous Urticaria.

INTRODUCTION: The possible influence of sensitization to aeroallergens on omalizumab response in chronic spontaneous urticaria (CSU) has been insufficiently investigated. This study's aim was to investigate atopy's influence on omalizumab response in CSU patients. METHOD: Retrospective study of CSU patients followed at a Portuguese Urticaria Center of Reference and Excellence (UCARE), treated with omalizumab for at least 6 months, between 2015 and 2022. At T0, all patients underwent quantification of specific immunoglobulin E (IgE) for total extract of most prevalent aeroallergens (ImmunoCAP Thermo Fisher Scientific®) and were divided in 2 groups, according to their response to omalizumab during the first 16 weeks of treatment: responders (R) (UAS7 <7) versus partial (PR) (UAS7 = 7-15) and nonresponders (UAS7 >15). R were further classified as fast (FR) (4-6 weeks) and slow responders (SR) (12-16 weeks). Total serum IgE, circulating eosinophil, and basophil counts were compared between groups at T0. p < 0.05 was considered statistically significant (SPSS® v25.0). RESULTS: Ninety-six patients (80% female) were studied, mean age 49 ± 14 years. Median CSU duration pre-omalizumab was 3 (0.6-20) years and mean omalizumab treatment duration was 3.7 ± 2.3 years. 38 (40%) had concomitant chronic inducible urticaria and 72 (75%) angioedema. Based on positive results of the specific IgE assay, 35 patients (36%) were considered atopic. Most patients (n = 30; 86%) were sensitized to house dust mites (HDM) (Dermatophagoides farinae = 28, Dermatophagoides pteronyssinus = 27, Blomia tropicalis = 19, Lepidoglyphus destructor = 17), followed by pollens (n = 12; 34%) (mixture of grasses = 10, Olea europaea = 7, Parietaria officinalis = 6), epithelia (n = 9; 26%) (dog = 8, cat = 7), and fungi (Alternaria alternata = 4; 11%). Eight patients (23%) were monosensitized to HDM and 4 (11%) to pollens. No significant association was found between aeroallergen sensitization and CSU duration, concomitant chronic inducible urticaria, or angioedema. Atopic patients featured significantly higher levels of baseline total serum IgE than nonatopic (469 vs. 94 U/mL, respectively; p = 0.0009). Mean baseline counts of eosinophils and basophils were not significantly different between atopic and non-atopic, respectively: eosinophils (128 vs. 121/mm3) and basophils (26 vs. 28/mm3). Regarding response to omalizumab, most patients (58; 60%) were responders: FR - 46 (79%); SR - 12 (21%). There was no significant association between aeroallergen sensitization and omalizumab response or speed of response. CONCLUSIONS: As far as we know, this is the first study exploring the influence of atopy sensitization pattern on omalizumab response in CSU. According to our results, presence of atopy/sensitization pattern does not influence omalizumab response in CSU patients.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria. / [Artículo traducido] El papel de la terapia adyuvante en el tratamiento de la urticaria crónica espontánea.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitaminD, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

The Role of Adjuvant Therapy in the Management of Chronic Urticaria.

Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.

The effect of vitamin D add-on therapy on the improvement of quality of life and clinical symptoms of patients with chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria is a common distressing allergic skin disorder. Immune dysregulation, histamine release and mast cell degranulation are suggested as its underlying mechanisms. OBJECTIVE: Add-on therapy of vitamin D was evaluated in patients with chronic spontaneous urticaria to determine the quality of life and urticaria severity score. METHODS: In a prospective, double-blinded study, 80 participants with chronic spontaneous urticaria were randomized to low (4200 IU/week, group 1) and high (28,000 IU/week, group 2) vitamin D3 supplementation groups for 12 weeks. Demographic data; quality of life, urticaria severity and medication scores; 25-hydroxyvitamin D and anti-thyroid peroxidase antibody levels; and autologous serum skin test data were collected. RESULTS: Both groups showed significantly reduced total urticaria severity score; decrement in group 2 score was significant compared to group 1 at week 6 (P = 0.010). Quality of life score was also significantly reduced; decrement in group 2 score was significant compared to group 1 at both weeks 6 (P = 0.005) and 12 (P = 0.007). 25-hydroxyvitamin D levels were elevated significantly over the course of 12 weeks in both groups; however, the elevation in group 2 was significantly higher than group 1 at week 12 (P = 0.002). Medication score was significantly reduced, with no significant difference between groups. No association was observed between positive autologous serum skin test, angioedema and high level of Anti thyroperoxidase antibody with positive response to vitamin D. CONCLUSIONS: Add-on therapy with vitamin D (28,000 IU/week) can be considered as a safe and potentially beneficial treatment in patients with chronic spontaneous urticaria.

Asian herbal medicine and chronic urticaria: which are the therapeutic perspectives?

Chronic urticaria (CU) is a pathologic condition marked by the emergence of wheals, angioedema, or both for more than six weeks. The improper activation and degranulation of mast cells is the triggering event, which results in the production of various mediators such as histamine, leukotrienes, PAF, chemokines, and cytokines. Antihistamines are currently the most common pharmacological treatment for urticaria, but corticosteroids and monoclonal antibodies can also be employed. Patients who have been taking antihistamines for a long time are often looking for alternatives. Whole plants, portions of plants, or single extracted active compounds are all used in phytomedicine. Plant elements are frequently combined to create formulations that can be utilized to treat a variety of pathological disorders. Anti-inflammatory and/or anti-allergic properties are found in several herbs regularly used in herbal formulations. Antioxidant properties are also present in some of the constituents. Exogenous antioxidants have been shown to improve the progression of autoimmune disorders in numerous studies. The aim of this review is to identify the most common herbs used to treat chronic urticaria, and to characterize their efficacy, mechanisms of action, and risk/benefit ratio in comparison to western treatment, and also to find less often used formulations and assess their therapeutic efficacy, safety profile, and potential for wider use.[Figure: see text].

Factors Related to Omalizumab Drug Survival and Treatment Responses in Chronic Urticaria.

INTRODUCTION: This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice. METHODS: This study included 386 patients with chronic urticaria. Demographic characteristics, clinical features, laboratory parameters, and omalizumab treatment data were analyzed retrospectively. The 7-day urticaria activity score (UAS7) and urticaria control test (UCT) were used to assess disease severity and treatment responses. RESULTS: Well-controlled disease (UAS7 ≤6) was achieved in 59.3% of patients at a median of 2 months. Complete response was significantly higher in patients treated with omalizumab for ≥12 months (p < 0.001). Family history of asthma (p = 0.01) was less frequent, and disease duration (p = 0.041) was shorter in patients with well-controlled disease. Total treatment duration was longer in patients with relapse (p < 0.001) and serum Helicobacter pylori IgA positivity (p = 0.029). DISCUSSION/CONCLUSION: Treatment response is better in patients treated with omalizumab for ≥12 months. However, prolonged treatment does not prevent relapse. Our findings suggest that continuous or intermittent therapy is an appropriate alternative treatment option in patients with severe chronic urticaria; however, continuous therapy can be preferred to maintain the patient's quality of life.

Anti-type I allergic effects of Jing-Fang powder extracts via PI3K/Akt pathway in vitro and in vivo.

Jing-Fang powder (Schizonepeta tenuifolia Briq. and Saposhnikovia divaricata (Turcz.) Schischk.) was used to treat chronic bronchitis, asthma and chronic urticaria. Based on the preliminary results of screening research on the antiallergic effective parts of Jing-Fang powder, its ethyl acetate extract fractions (JFEE) and isolate D (JFEE-D) showed the best anti-allergic effect. RBL-2H3 cell activation degranulation model and mice passive cutaneous anaphylaxis (PCA) reaction model were used to investigate the effects and mechanisms of JFEE and JFEE-D on IgE-mediated type I allergic reactions. LC-MS was utilized to determine the composition of JFEE and JFEE-D. We found that JFEE and JFEE-D significantly reduced ß-HEX, histamine, IL-4, IL-6 levels in cell supernatants, and improved the degree and morphology of cell degranulation. JFEE and JFEE-D significantly inhibited the increase of ear vascular permeability and abnormal increase of serum IgE, TNF-α, IL-6 levels. JFEE and JFEE-D inhibited mRNA expression of PI3K and Akt and down-regulated protein expression of PI3K, Akt, p-Akt, and PLCγ1 in sensitized RBL-2H3 cells. The combined use of JFEE and JFEE-D with pathway inhibitor Wortmannin revealed synergistic down-regulation of PI3K, Akt, and p-Akt protein expression. The combined use of pathway agonist IGF-1, JFEE and JFEE-D down-regulated increase of p-Akt/Akt protein expression. Moreover, JFEE and JFEE-D significantly inhibited protein expression of PI3K, p-Akt and PLCγ1 in PCA model mice. These results show that JFEE and JFEE-D inhibit type I allergic reactions by inhibiting PI3K/Akt signaling pathway.

Moxibustion therapy for chronic spontaneous urticaria: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common disease in clinical, and often recrudescent. However, sometimes Western medicine treatments such as antihistamines cannot completely control the symptoms of CSU; therefore, more effective and optimized treatments are needed. Numerous studies have confirmed that moxibustion therapy is effective in treating CSU. Given that no relevant systematic reviews and meta-analysis have been carried out, we set out to prove the effect of moxibustion therapy for CSU. METHODS: This protocol will be conducted based on the PRISMA-P guidelines and comply with the recommendations of the Cochrane Collaboration Handbook for Systematic Reviews. We plan to search the subsequent databases: PubMed, Web of Science, EMBASE.com and Cochrane Library, China National Knowledge Infrastructure, WanFang Database, Chinese Science Journal Database, and China Biomedical Literature Database. The studies will be screened under the eligibility criterion. The quality of the studies will be assessed based on the Cochrane risk bias tool. Ultimately, Review Manager 5.3 will be used for statistical analysis. RESULTS: This research will comprehensively evaluate the effectiveness of moxibustion therapy for CSU, and provide a more reasonable and effective treatment plan for CUS. CONCLUSION: This research will bring new evidence for the efficacy of moxibustion therapy in the treatment of CSU and provide a basis for future clinical applications. INPLASY REGISTRATION NUMBER: INPLASY2020100045.

Targeted Therapy for Chronic Spontaneous Urticaria: Rationale and Recent Progress.

Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals, angioedema, or both for at least 6 weeks. It may persist for a long time-up to 50% of the patients have been reported to be symptomatic 5 years after the onset. Some patients can suffer more than one episode of CSU during their lifetime. Considering the recurrences, disabling symptoms, and significant impact on quality of life, proper and effective treatment of CSU is critical. The use of antihistamines (AHs) is still the mainstay of treatment. However, given the low rates of response to AHs (38.6% and 63.2% to standard doses and higher doses, respectively), the complete control of symptoms seems difficult to attain. The use of omalizumab for CSU has been a major breakthrough in the care of patients with CSU. However, the partial response and lack of response to omalizumab in a subgroup of patients, as high as 70% in some studies, make the development of alternative treatments desirable. Ever-increasing knowledge on the pathogenesis is making new target molecules available and enabling drug development for CSU. In addition to drug repurposing as in anti-IL-4/13, IL-5, and IL-17 antibodies, novel targeted therapy options such as ligelizumab and Bruton's tyrosine kinase inhibitors are currently undergoing clinical trials and will be available in the near future. This article reviews the current challenges in the treatment of CSU, the pathogenesis and potential target molecules, and the rationale for novel treatments and their rapidly developing status.

Pidotimod in allergic diseases.

The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active substances, commonly known as immunostimulants, have been introduced for the prevention and treatment of allergic diseases in pediatric population. Among the heterogeneous group of biologically active molecules to date available, pidotimod (Axil, Valeas S.p.A, Milan) is proved to be able to ameliorate both innate and adaptive immunity and enhances the immune system properties often impaired in patients with allergic disorders.

An update on biological therapies for pediatric allergic diseases.

Allergic diseases represent a global health burden. Patients with allergic diseases may experience disability, reduced quality of life and productivity, emotional distress, and social restrictions, especially in the most severe cases. Current advances in unveiling the pathogenesis of allergic disorders have paved the way for the development of novel therapeutic strategies. Biological drugs have been widely studied in pediatric allergic asthma, with strong evidence of efficacy and safety. Moreover, promising results derive from studies on other conditions such as atopic dermatitis, chronic spontaneous urticaria, and food allergy. This review analyzes recent evidence on the role of biologic therapies for allergic diseases, focusing on the pediatric age.

Time-Dependent Effects in Chronic Urticaria: A Time-Series Perspective of Omalizumab Treatment.

BACKGROUND: Chronic spontaneous urticaria (CSU, or CU) is a disease that significantly affects the quality of life of patients. It is a chronic disease and requires a specialized approach to diagnosis and treatment. In recent years, the disease has been of great interest due to the existence of new targeted therapeutic approaches. AIM: The present study aims at analyzing CU score concerning time, as a time-series. The authors have attempted to model the investigated time-series to unravel possible causative relationships. METHODS: 108 patients (25Males/83Females) admitted to our department were diagnosed with CU. CU was estimated on a score basis, which was used to define disease severity. Urticaria score was assessed on the basis of Urticaria Activity Score 7 (UAS7). The mean CU score, the mean CU score rate concerning the first month at diagnosis as well as the monthly CU score rate were calculated. RESULTS: Gender is a factor that influences CU score with time. In addition, there was a significant finding that time-series differ with the administration of monotherapy or complementary therapy. CONCLUSION: We have found that females are more prone to CU, while omalizumab monotherapy has more beneficial results as compared to the application of concurrent and maintenance therapies. Further, patients with co-morbidities were more likely to interrupt treatment. Finally, and most significantly, it was shown that monthly CU score rate manifested an oscillatory pattern, which was modelled with the sum of sines functions, highlighting a relative immunological pattern.

Patient experiences of using Chinese herbal medicine for psoriasis vulgaris and chronic urticaria: a qualitative study.

Background: Psoriasis vulgaris and chronic urticaria are common skin conditions with a significant health burden. Achieving long-term control remains a challenge, and some patients choose Chinese herbal medicine (CHM) to meet this need. Little is known about the motivators and experiences of using CHM for these skin conditions.Objectives: To determine the motivators for choosing CHM, and experience of using CHM for psoriasis vulgaris and chronic urticaria.Methods: We conducted semi-structured interviews with participants who had previously used CHM for these conditions. Interviews were transcribed for data analysis.Results: Twenty participants completed the interviews in Guangzhou (n = 16), China, and Melbourne (n = 4), Australia. Motivators included wanting an alternative to conventional medicine, beliefs about CHM and previous experience. Participants expected that CHM would be safer and could prevent relapse; this expectation was met for some participants. Preparing CHM decoctions was onerous, and CHM granules were more convenient.Conclusion: Beliefs, previous experience of using CHM, desire to prevent relapse, and safety are important motivators for choosing CHM in people with psoriasis vulgaris and chronic urticaria. Further clinical evidence is required to enable patients to make informed clinical decisions. Patient preferences should be considered in the context of available evidence when prescribing CHM.

Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamine.

The second-generation H1-antihistamines (sgAH) are the first-line symptomatic treatment of patients with chronic spontaneous urticaria (CSU). Up to 50% of the patients will not respond to licensed doses of sgAH. According to the guidelines, the dose of sgAH may be increased up to 4 times the conventional dose. However, even at higher doses, there is a subgroup of patients refractory to the antihistamine treatment. The purpose of this article was to review the different treatment options of antihistamine-refractory CSU patients. This revision examines the available literature for therapies used in chronic urticaria, including omalizumab, ciclosporin A, oral glucocorticoids, leukotriene receptor antagonists, H2 antihistamines, doxepin, dapsone, hydroxychloroquine, phototherapy, methotrexate, mycophenolate mofetil, azathioprine, autohemotherapy, intravenous immunoglobulins and rituximab, between others. After the exhaustive review of the medical literature only few high-quality studies have been identified, mostly for omalizumab. Omalizumab is an anti-immunoglobulin E monoclonal antibody, approved for the treatment of CSU, that has radically changed the management of the patients without good response to sgAH, allowing to reach complete responses in a high percentage of patients. Although actually the therapeutic management of CSU is more effective and safer than before 2014, there is place even for new and more effective treatments. A good number of partial responders and slow responders to omalizumab and a little percentage still of non-responders to available therapies stimulate the development of new drugs that will also be discussed.

Impact of Jumihaidokuto (Shi-Wei-Bai-Du-Tang) on Treatment of Chronic Spontaneous Urticaria: A Randomized Controlled Study.

OBJECTIVE: To study the effect of Jumihaidokuto (Shi-Wei-Bai-Du-Tang, ) in the management of chronic spontaneous urticaria. METHODS: A randomized two-arm, parallel group study was conducted to compare the effect of Jumihaidokuto (6 g daily) with a control for 8 weeks. Concomitant therapy (e.g., antihistamines) was continued. Twenty-one subjects with severe chronic urticaria were enrolled in this study. The primary treatment outcome was the severity score proposed by the Japanese Dermatological Association. Secondary outcomes were quality of life (Skindex-16), itch intensity (Visual Analogue Scale), and patients' subjective disability due to wheal or itch. After the subjects were randomly assigned to groups by block randomization, 10 received Jumihaidokuto, and 11 did not. All subjects had already taken antihistamines. RESULTS: Improvement was significant when comparing the severity score of the Jumihaidokuto group with that of the control group (P<0.01). Skindex-16 values for both groups gradually decreased in the same fashion. CONCLUSION: Concomitant use of Jumihaidokuto with antihistamine was more effective than antihistamine alone in the management of chronic idiopathic urticaria. (Trial Registration No. UMIN000007251).