Biomarkers to predict therapeutic response in chronic spontaneous urticaria: a review.

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.

UCOMB-real life data: treatment strategies for chronic urticaria patients with comorbidities.

BACKGROUND: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. METHODS: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. RESULTS: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. CONCLUSIONS: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Real-life effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a common, chronic inflammatory condition with a substantial negative impact on the quality of life. Dupilumab, the first biologic approved for the treatment of moderate-to-severe AD, binds IL-4Rα and inhibits signaling of both IL-4 and IL-13. This study aimed to determine the real-life effectiveness and safety of dupilumab treatment in patients with moderate-to-severe AD. The results of the study indicates high effectiveness and safety of dupilumab in real-life conditions. The treatment was continued during the COVID-19 pandemic in most of the patients without any adverse outcome. The rate of conjunctivitis was higher compared to clinical trials, nevertheless treatment was not discontinued in any patients due to adverse effects.

Remission of chronic spontaneous urticaria following omalizumab with gradually extended dosing intervals: Real-life data.

Omalizumab is a well-established treatment option in chronic spontaneous urticaria unresponsive to antihistamines at standard or higher doses. However, characteristics of the remission and relapse following the withdrawal of omalizumab remain largely unknown. We aimed to define the characteristics of remission in CSU following omalizumab with gradually lengthened dosing intervals in this retrospective study of 102 patients who were treated with at least 3 doses of omalizumab between 2013 and 2020. Of 102 patients, 70 (68.6%) showed a CR to omalizumab at standard doses. Omalizumab could be discontinued in 47 of 70 patients using gradually lengthened dosing intervals. Following a mean follow-up duration of 12.2 months, 25 (58.1%) patients were still in remission while 18 (41.9%) had relapse (Follow-up data were not available in 4 patients). The relapses were unresponsive to antihistamines in 14 patients (77.7%), however, re-treatment with omalizumab led to complete control of symptoms. The patients younger than 40 were more likely to relapse. Despite the need for comparison with fixed-dosing intervals in larger, prospective studies, the results of this study imply that omalizumab with gradually extended dosing intervals might provide a long duration of remission in CSU.

Public interest in dermatologic symptoms, conditions, treatments, and procedures during the COVID-19 pandemic: Insights from Google Trends.

Coronavirus disease 2019 (COVID-19) pandemic had substantial effect both on daily life and medical practice. Internet data have been used to analyze the trends in public interest in various medical conditions and treatments. The aim of this study is to analyze the public interest in dermatologic symptoms, conditions, treatments, and procedures during the COVID-19 pandemic. Google Trends was queried for a total of 120 dermatological search queries. Three periods of 2020 ([March 15-May 9], [May 10-July 4], and [July 5-October 31]) were compared with the previous 4 years (2016-2019). A significantly decreased interest in skin cancers and certain dermatologic conditions (eg, pityriasis rosea and scabies) was observed throughout the study period. Whereas a significant increase of interest in dry skin, hair shedding, oily hair, atopic dermatitis, and hand eczema was detected during the study. An initial decrease in interest was followed by a significant increase for acne, comedones, melasma, rosacea, botox, dermaroller, and peeling. The study demonstrated a significant impact of the COVID-19 pandemic on the public interest in dermatology. The present results would help to create healthcare policies and information sources, which can meet the public demand. The reasons for the observed trends and their effect on patient outcomes might be of interest for future studies.

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

INTRODUCTION: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. AIM: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. MATERIALS AND METHODS: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. RESULTS: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. CONCLUSIONS: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.

Netherton syndrome: Temporary response to dupilumab.

Netherton syndrome (NS) is an orphan disease characterized by congenital ichthyosis, hair abnormalities, and atopy, with limited treatment options. We achieved temporary improvement only during the initial 6 weeks of treatment with dupilumab, which differs from the sustained improvement observed in 2 other recently published cases. Although the clinical presentation of atopy and increased pre-allergic cytokines in NS patients suggest that dupilumab may be beneficial, larger studies are required.

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.

Real-life data on the effectiveness and safety of omalizumab in monotherapy or combined for chronic spontaneous urticaria: a retrospective cohort study.

Background: The real-life data on the effectiveness and safety of omalizumab in chronic spontaneous urticaria (CSU) with validated methods are scarce. There is also a lack of information on the use of combination treatments.Methods: A retrospective cohort study was done to evaluate the effectiveness and safety of omalizumab in real-life conditions. The patients with CSU treated with omalizumab between 2015 and 2018 were included. The response to therapy was evaluated using urticaria activity score over 7 days (UAS7) and urticaria control test (UCT).Results: A total of 106 patients were included. A complete response (CR) (UAS7:0) and a well-controlled activity (WCA) (UAS7:1 to <6) were observed in 50 (47.2%) and 35 (33%) patients, respectively. The number of patients with an UCT score ≥12 was also significantly increased. Higher rates of CR/WCA were observed with omalizumab monotherapy compared to combination with antihistamines. The combination of dapsone, colchicine, and omalizumab provided additional benefit in a small group.Conclusion: Treatment with omalizumab provided a rapid and sustainable improvement in real-life settings. The use of omalizumab as monotherapy or combined with antihistamines does not show differences in the treatment response. The combination of omalizumab with immunomodulatory agents might be of benefit in selected cases.

Advanced Glycation End Products, a Potential Link between Psoriasis and Cardiovascular Disease: A Case-control Study.

CONTEXT: Advanced glycation end products (AGEs) promote oxidative stress and inflammation by altering structure and function of proteins. They are excessively produced mainly in hyperglycemia, chronic inflammation and are involved in the development of atherosclerosis and cardiovascular disease. AIMS: The aim of this study was to investigate whether skin AGEs levels were increased and had relation to premature atherosclerosis in patients with psoriasis. SUBJECTS AND METHODS: Fifty-two psoriasis patients and 20 healthy controls (HC) were included. AGEs were determined by skin autofluorescence (SAF) analysis. High-sensitive C-reactive protein (hsCRP) and carotid intima-media thickness (CIMT) were also investigated. Physical activity and dietary patterns were determined. STATISTICAL ANALYSIS USED: Fisher's exact test, two-sample t-tests, Mann-Whitney-U test, Pearson correlation, Spearman correlation, and Wilcoxon test. RESULTS: SAFs were increased in psoriasis patients (1.8 arbitrary units [AUs]) compared to that in HC (1.6 AUs) (P = 0.057). Median CIMT values of HC and psoriasis groups were 0.43 (0.28-0.79), and 0.59 (0.44-0.98) respectively and the differences were significant (P = 0.001); hsCRP levels were not different between groups. CONCLUSIONS: Skin AGE accumulation was found to have a correlation with CIMT in psoriasis patients providing evidence for the role of AGEs in premature atherosclerosis.

The impact of omalizumab on quality of life and its predictors in patients with chronic spontaneous urticaria: Real-life data.

BACKGROUND: Omalizumab is a third-line treatment for chronic spontaneous urticaria (CSU). However, the real-life data on the impact of omalizumab on CSU-related quality of life (QoL) remain scarce. OBJECTIVES: To investigate the impact of omalizumab on QoL and its predictors in CSU. A retrospective cohort study was done. The response to therapy was evaluated using urticaria activity score over 7 days (UAS7) and urticaria control test (UCT); the impairment in QoL was assessed using dermatology life quality index (DLQI) and chronic urticaria quality of life questionnaire (CU-Q2oL). RESULTS: Forty-two patients were included. All scores improved from baseline to first month and remained stable at the third month of treatment (p < .001). The gender, age, and angioedema had no significant effect on QoL, but the complete responders (UAS7:0-1) had better improvement rates in all scores compared to others. The baseline UAS7, DLQI, and CU-Q2oL scores were lower at the baseline in complete responders (p = .0001). CONCLUSIONS: A rapid and continual improvement in QoL was obtained with omalizumab treatment. A better UAS7, UCT, DLQI, and CU-Q2oL score at the baseline might be a predictor of a better response to omalizumab and more improvement in QoL.

Acute generalized exanthematous pustulosis due to ceftriaxone: Report of a pediatric case with recurrence after positive patch test.

Acute generalized exanthematous pustulosis (AGEP) is seen uncommonly in children and sometimes shows atypical clinical features in this population. Patch testing can be used effectively in children for the confirmation of the culprit drug in cases of multiple drug use. Here, we report a rare, pediatric case of ceftriaxone-induced AGEP confirmed by patch testing with subsequent recurrence of the skin eruption.

The efficacy and safety of targeted narrowband UVB therapy: a retrospective cohort study

Background/aim: Phototherapy is a safe and effective treatment modality for numerous dermatological conditions. Recently, targeted phototherapy modalities have gained importance due to their advantages over conventional phototherapy.This retrospective study aimed to evaluate the safety and efficacy of targeted narrowband UVB phototherapy in patients with dermatological disorders Materials and methods: This single-center study included 173 patients who were treated with targeted narrowband UVB phototherapy. Demographic features, phototherapy parameters, and adverse effects were evaluated in all patients, and the treatment response was assessed in patients who attended at least one follow-up visit. Results: A total of 173 patients (102 females; 71 males) with vitiligo, alopecia areata, lichen simplex chronicus, palmoplantar psoriasis, and psoriasis vulgaris were included in the study. Among 73 patients, with whom the treatment was finalized by physician, an excellent response was obtained in 10%, 52.9%, 53.8%, 28.6%, and 40% of patients with vitiligo, alopecia areata, lichen simplex chronicus, palmoplantar psoriasis, and psoriasis, respectively. The treatment was generally well tolerated and was discontinued in only two patients due to adverse effects. Conclusion: This study demonstrates that targeted narrowband UVB therapy is a safe and effective treatment alternative, particularly for alopecia areata, lichen simplex chronicus, and palmoplantar and plaque-type psoriasis.

The Real-Life Effectiveness and Safety of Omalizumab Updosing in Patients With Chronic Spontaneous Urticaria.

BACKGROUND: Omalizumab is a third-line treatment for chronic spontaneous urticaria (CSU). Studies investigating the use of higher doses of omalizumab in patients unresponsive to regular doses are limited. OBJECTIVES: This study aims to investigate the effectiveness and safety of omalizumab 450 mg in CSU. METHODS: A retrospective cohort study was conducted. The response to therapy was evaluated using the Urticaria Activity Score over 7 days (UAS7) and the Urticaria Control Test (UCT). Patients showing complete response (CR) (UAS7: 0-1) to omalizumab 300 mg (Group 1) and patients receiving at least 3 doses of omalizumab 450 mg (Group 2) between 2016 and 2018 were included. RESULTS: A total of 72 patients (Group 1: 59; Group 2: 13) were included. In Group 2, the mean UAS7 score decreased from 18.6 to 5.1 and the mean UCT score increased from 8.6 to 12 after a mean 4.3 courses of 450 mg omalizumab treatment. Of the 13 patients in Group 2, 6 had CR and 3 had good disease control (UAS7: 2-6). The rate of patients with low baseline IgE levels (< 43 IU/mL) was significantly higher in Group 2. CONCLUSIONS: Higher doses of omalizumab are effective and safe in patients with CSU that is unresponsive to omalizumab 300 mg. Lower baseline total IgE levels might be used as a predictor of nonresponse to omalizumab and the need for higher doses.