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 < 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.

Combination therapy of omalizumab with house dust mite immunotherapy in chronic spontaneous urticaria associated with sensitization to dust mites-case series

Chronic spontaneous urticaria (CSU) is a heterogeneous disorder with recurrent pruritic wheals and/or angioedema. The anti-immunoglobulin E (omalizumab) is used in CSU patients resistant to four-fold second-generation anti-histamines. Most clinical trials have experienced relapse after stopping omalizumab treatment. Here, we present a case series of five cases of chronic atopic urticarial concomitant allergic rhinitis and asthma which have shown immunologically significant positivity to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Disease control was achieved (Urticaria Activity Score 7 <6) in four cases by combination therapy of omalizumab with house dust mite (HDM) Allergen Immunotherapy (AIT) and remained sustained for three years on follow-up even after discontinuation of AIT for one year. We hypothesize that this combined therapy may contribute to enhanced clinical efficacy, safety, and faster achievement of disease control in CSU.

Safety and clinical efficacy of bilastine in reduction of pruritus in patients with chronic spontaneous urticaria

Objective — to evaluate the efficacy/safety of bilastine in relieving pruritus in patients with chronic spontaneous urticaria. Materials and methods. This prospective randomized study included 50 adult patients aged 18 to 59 years with chronic spontaneous urticaria and pruritus with an intensity of more than 4 points by the visual analog scale of pruritus assessment in the last 3 days and more than 16 points by the Urticaria activity score 7 (UAS7) which assessed chronic urticaria intensity for the last week.Patients received bilastine orally at a dose of 20 mg once a day for 8 weeks. Patients who did not respond to therapy within the first 2 weeks subsequently received bilastine at a dose of 40 mg per day (two 20 mg tablets) till the end of the study (for 6 weeks). Results and discussion. The mean age of patients was 39.61 years with standard deviation (SD) of 12.33 years. In the group of patients who responded positively to the initial therapy, within 8 weeks, the pruritus intensity scoring level decreased significantly to 0.46 (95 % CI: 0.14—0.78) points (p < 0.05). The patients who received a double dose of bilastine also revealed a decrease in the intensity of pruritus and on average on the 8th week of treatment had 0.48 (95 % CI: 0.26—0.70) points (p < 0.05).The study reported 14 adverse events (AE) that occurred during bilastine treatment in 10 (23.8 %) patients. All of them were classified as mild and the most common was headache, registered in 12 (85.7 %) cases. No moderate or severe AEs were reported during the study. Conclusions. 8 week treatment with bilastine has demonstrated proven clinical efficacy both in reducing the urticaria activity index according to UAS7 and in reducing the intensity of pruritus in the absence of moderate and severe AEs. Patients who did not respond to starting therapy after doubling the bilastine dose also significantly decreased the urticaria activity index according to UAS7 and reduced the intensity of pruritus. At the same time, increasing the dose of the drug did not lead to an increase in the frequency of AEs.

Exploring Machine Learning Techniques to Predict the Response to Omalizumab in Chronic Spontaneous Urticaria

Background: Omalizumab is the best treatment for patients with chronic spontaneous urticaria (CSU). Machine learning (ML) approaches can be used to predict response to therapy and the effectiveness of a treatment. No studies are available on the use of ML techniques to predict the response to Omalizumab in CSU. Methods: Data from 132 CSU outpatients were analyzed. Urticaria Activity Score over 7 days (UAS7) and treatment efficacy were assessed. Clinical and demographic characteristics were used for training and validating ML models to predict the response to treatment. Two methodologies were used to label the data based on the response to treatment (UAS7 ³ 6): (A) at 1, 3 and 5 months; (B) classifying the patients as early responders (ER), late responders (LR) or non-responders (NR) (ER: UAS 7 ³ 6 at first month, LR: UAS 7 ³ 6 at third month, NR: if none of the previous conditions occurred). Results: ER were predominantly characterized by hypertension, while LR mainly suffered from asthma and hypothyroidism. A slight positive correlation (R2 = 0.21) was found between total IgE levels and UAS7 at 1 month. Variable Importance Analysis (VIA) reported D-dimer and C-reactive proteins as the key blood tests for the performance of learning techniques. Using methodology (A), SVM (specificity of 0.81) and k-NN (sensitivity of 0.8) are the best models to predict LR at the third month. Conclusion: k-NN plus the SVM model could be used to identify the response to treatment. D-dimer and C-reactive proteins have greater predictive power in training ML models.

The Role of Bradykinin Receptors in the Etiopathogenesis of Chronic Spontaneous Urticaria

Background and Objectives: Chronic spontaneous urticaria (CSU) is a distressing skin condition, which manifests as red, swollen, itchy, and sometimes painful hives or wheals appearing on skin. Recently, CSU has been associated with bradykinin release, which was previously discovered to be the main trigger of hereditary angioedema attacks. To study the role of bradykinin receptors 1 (BR1) and 2 (BR2) in the etiopathogenesis of CSU. Materials and Methods: A total of 60 individuals, 30 patients with CSU and 30 healthy subjects, were recruited to the study. CSU was diagnosed in accordance with the standardized protocol of dermatological assessment of skin symptoms. The level of bradykinin receptors was determined in populations of CD3+, CD4+, and CD8+ lymphocytes as well as in CD14++CD16−, CD14++CD16+ and CD14+CD16+ monocytes. In addition, urticaria activity score summed over 7 days (UAS-7) was assessed and correlated with BR1 and BR2 expression. Results: A statistically significant higher concentration of BR1 expression in lymphocytes was found in patients with CSU, compared to the control group (p < 0.001). Moreover, a statistically significant positive correlation was observed between UAS-7 and BR1/BR2 expression in CD14++CD16− cells (p = 0.03, R = 0.4). Conclusions: Bradykinin receptors are elevated in selected populations of lymphocytes in symptomatic CSU patients compared to healthy controls, indicating their role in the etiopathogenesis of the disease.

Oral mini-pulse steroid therapy in severe chronic urticaria

Background: Treatment of chronic urticaria can be difficult at times. The present study aimed to evaluate the efficacy of oral mini-pulse (OMP) therapy with methylprednisolone in management of severe chronic urticaria (CU). Methods and material: 100 patients with severe chronic urticaria, not controlled with maximum dose of a second generation antihistamine, were enrolled in the study after an informed written consent. All patients were treated with methylprednisolone 16 mg tablet on two consecutive days of a week for 2 months along with levocetirizine 5 mg tablet once daily. All patients were reviewed at 0, 2, 4, and 8 weeks with urticaria activity score (UAS). Results: The study comprised of 100 patients (33 males and 67 females) with severe chronic urticaria. 29 patients (29%) had raised TSH levels while Autologous Serum Skin Test was positive in 37 patients. Mean UAS in patients treated with OMP was 5.76 at baseline which reduced to 0.6 at the end of treatment period. Conclusion: Mean UAS showed a significant decline following OMP therapy with methylprednisolone. Most of the patients maintained the benefits of therapy at the end of follow up period of 4 months.

COVID-19 Disease Leading to Chronic Spontaneous Urticaria Exacerbation: A Romanian Retrospective Study

(1) Background: The COVID-19 pandemic has resulted in the exacerbation of various chronic diseases. Due to the potential impact of SARS-CoV-2 on mast cells, we aimed to analyze the relevance of COVID-19 disease on chronic spontaneous urticaria (CSU) clinical presentation and biological profile. (2) Methods: This study is a retrospective case series of patients with CSU diagnosed and treated in the Allergy Department of the Professor Doctor Octavian Fodor RIGH, (Cluj-Napoca, Romania). Patients were assessed for disease activity and level of control with the weekly urticaria activity score and the visual analogue scale. Results were correlated with COVID-19 severity and with nonspecific markers of inflammation during and after the SARS-CoV-2 infection. (3) Results: SARS-CoV-2 impacted a significant proportion (33%) of the CSU patients, of which 71% developed a moderate-severe form of COVID-19. Most of the patients (68%) had moderate-severe forms of CSU and 65% took AH1 treatment (one dose, two-fold dose or four-fold dose). The rest of them (35%) received the second-line treatment (40.3% Omalizumab, 53% Prednisolone and 4.8% Cyclosporine). In Omalizumab treated group of UCS patients we observed that COVID-19 disease was not severe. We established a positive correlation between the severity of the infection and that of the CSU clinical presentation, with most bothersome symptoms of urticaria being experienced by moderate to severe COVID-19 CSU patients (47%). Inflammatory markers were positively correlated (p = 0.01) with a more severe clinical profile of CSU, in accordance with our hypothesis that the level of inflammation triggered by COVID-19 disease has a role in CSU exacerbation. The non-specific inflammatory markers, such as CRP, were positively associated with the UAS7 score (R2 = 0.363; p = 0.001). An increased rate of exacerbation of CSU was observed in moderate-severe COVID-19 infection. 4) Conclusions: COVID-19 disease can result in the exacerbation of chronic spontaneous urticaria, more likely in moderate to severe forms of infection.

Clinical difference between single subtype and mixed subtype chronic urticaria: A retrospective study

Background: The subtypes of chronic urticaria share a common clinical expression, but may show differences phenotypically. Meanwhile, two or more different subtypes of chronic urticaria can coexist in any given patient which may involve different phenotypes. Aims: The study aims to compare the two phenotypes in terms of demographics, clinical profile and treatment response. Methods: In this retrospective study, 2678 chronic urticaria patients were divided into the single subtype chronic urticaria group and mixed subtype chronic urticaria group as was appropriate.The differences in the clinical features, possible causes, urticaria activity score of seven days, dermatology life quality index score, laboratory investigations and response to treatments were evaluated among the two groups. Results: An obvious female predominance was detected in chronic urticaria, especially in mixed subtype chronic urticaria patients. Of the 2678 chronic urticaria patients, there were 837(31.25%) mixed subtype chronic urticaria. Chronic spontaneous urticaria combined with symptomatic dermographism was the most common group in the mixed subtype chronic urticaria. Patients with mixed subtype chronic urticaria were more likely to have associated chest tightness/shortness of breath and showed greater urticaria activity. In patients with single subtype chronic urticaria, the positive rate of family history with allergic rhinitis, asthma or urticaria was lower. Based on evaluation of the treatment, control with second-generation antihistamines at licensed doses was achieved in only 38.83% of mixed subtype chronic urticaria patients, compared with 56.32% of patients with single subtype. Limitations: First, this study was a single-center design retrospective study. Second, omalizumab treatment was not included. Third, the differences between different subtypes of mixed subtype chronic urticaria were not discussed in detail. Conclusion: This study showed that mixed subtype chronic urticaria had some distinct features. Comprehensive knowledge about it may help us define effective therapeutic strategies and improve symptom control and the quality of life for chronic urticaria patients.

Psychological burden of COVID-19 on mild and moderate chronic spontaneous urticarial

Background: The impact of coronavirus disease 2019 (COVID-19) related mental health status on chronic spontaneous urticaria (CSU) has not been addressed before. Objective: The aim of this study was to evaluate the depression, anxiety and stress levels, and the fear of COVID-19 in patients with mild-to-moderate CSU and to determine their impact on urticaria activity during the pandemic. Methods: A total of 509 patients with mild-to-moderate CSU were prospectively evaluated with validated scales, the Depression Anxiety Stress Scale 21 (DASS-21) and the Fear of COVID-19 Scale (FCV-19S) during the lockdown period (LP) and the return to normal period (RTNP). CSU activity was determined with the urticaria activity score summed over 7 days (UAS7) and medication scores (MS). UAS7 and MS before the pandemic were retrospectively collected from medical records. Results: The median UAS7 and MS were both significantly higher in the LP than in the median of related scores during the prepandemic period (p < 0.0001) and the RTNP (p < 0.0001). The mean FCV-19S and DASS-21 scores were both significantly higher in the LP than in the RTNP (p < 0.0001). The FCV-19S and the DASS-21 anxiety and stress subscales were significantly higher in women. The UAS7s were positively correlated with the FCV-19S and depression, anxiety, and stress subscale scores. Conclusion: Fear of COVID-19, anxiety, depression, and stress during the COVID-19 pandemic, especially when strict isolation measures are taken, have a significant impact on mental health and urticaria activity in patients with mild-to-moderate CSU, even though they are not infected. Psychological support for patients with CSU seems to be important to control disease activity during the pandemic.

Angioedema Coexisting Chronic Spontaneous Urticaria Negatively Influences Patients’ Sense of Coherence, What Results in Susceptibility to Anxiety Symptoms Occurrence

Background: Angioedema coexisting chronic spontaneous urticaria (CSU) is proved to result in patient anxiety occurrence, but the mechanisms and susceptibility patterns are unknown. Sense of coherence (SOC) is one of methods of coping with stress and is defined as a person’s general orientation toward life. We decided to assess SOC disturbances in CSU patients in the context of possible angioedema association. Methods: The study comprised 71 CSU subjects. To analyze disease activity, the Urticaria Activity Score seven-day assessment questionnaire (UAS7) was used. For anxiety assessment, the STAI questionnaire was used. The SOC-29 questionnaire, consisting of questions related to comprehensibility (SOC-C), manageability (SOC-M), and meaningfulness (SOC-Mf), was used to analyze SOC parameters (SOC-T). Results: In patients with coexisting angioedema, we observed statistically significantly lower values of SOC-Mf and SOC-T in comparison to the wheals only group. In the angioedema group, we noticed significant negative correlations between SOC-M and SOC-Mf, as well as SOC-T values and anxiety. In the wheals only group, we proved statistically significant correlations between SOC-Mf and SOC-T and anxiety assessed as a state. Conclusions: It is necessary to identify CSU patients manifesting angioedema as they are more likely to have impaired SOC. Lower SOC in this specific group of patients can be related to anxiety symptoms occurrence and should probably be an indication for psychological support.