Validity, reliability and responsiveness of digital visual analogue scales for chronic spontaneous urticaria monitoring: A CRUSE® mobile health study.

BACKGROUND: CRUSE® is an app that allows patients with chronic spontaneous urticaria (CSU) to monitor their daily disease activity through the use of visual analogue scales (VASs). We aimed to determine the concurrent validity, reliability, responsiveness and minimal important difference (MID) of CRUSE® VASs. METHODS: We evaluated the properties of three daily VASs: VAS for how much patients were affected by their CSU ('VAS urticaria'), VAS for the impact of urticaria on work/school productivity ('VAS productivity') and the VAS of EQ-5D. Concurrent validity was assessed by measuring the association between each VAS and the Urticaria Activity Score (UAS). Intra-rater reliability was determined based on the data of users providing multiple daily questionnaires within the same day. Test-retest reliability and responsiveness (ability to change), respectively, were tested in clinically stable and clinically unstable users. MIDs were determined using distribution-based methods. RESULTS: We included 5938 patients (67,380 days). Concurrent validity was high, with VAS urticaria being more strongly associated with the UAS score than the remaining VASs. Intra-rater reliability was also high, with intraclass correlation coefficients (ICC) being above 0.950 for all VASs. Moderate-high test-retest reliability and responsiveness were observed, with reliability ICC being highest for VAS EQ-5D and responsiveness being highest for VAS urticaria. The MID for VAS urticaria was 17 (out of 100) units, compared to 15 units for VAS productivity and 11 units for VAS EQ-5D. CONCLUSION: Daily VASs for CSU available in the CRUSE® app display high concurrent validity and intra-rater reliability and moderate-high test-retest reliability and responsiveness.

Shedding Light on Shadows: A Cross-Sectional Analysis of Genital Psoriasis and Its Effects on Thai Individuals.

Background: Limited knowledge exists about genital psoriasis in Thai individuals. Objectives: This study aimed to assess the clinical features of genital psoriasis and its effects on quality of life and sexual health in Thai patients. Materials and Methods: A cross-sectional, self-administered question-based study was conducted at Siriraj Hospital. Participants were psoriasis patients older than 18 years of age with past or current genital involvement. The study assessed quality of life and sexual health. Results: Among the 50 patients, 33 (66%) were female. The mean (standard deviation) age was 45.4 (±13.4) years. Genital psoriasis was active in 34% of the participants. The mons pubis (48.5%) and labia majora (18.2%) were the most frequently affected sites in females, while in males, the penile shaft (52.9%) and glans (47.1%) were the most common sites. Itch-related symptoms predominated, affecting 82% of patients. The median dermatology life quality index score was 6.5 for females and 10 for males. A sexual health survey revealed that 54% of participants had low self-esteem. This issue was more pronounced in males, with 76.5% reporting lower self-esteem compared to 42.4% of females (P=0.022). Males were also more inclined to postpone or avoid marriage (47.1% vs. 15.6%, P=0.038) and more embarrassed about sexual activities (63.6% vs. 14.3%, P=0.017). In addition, males were more inclined to avoid sexual encounters due to their genital condition. Notably, 42.9% of all patients had never disclosed to a doctor that they had genital psoriasis. Conclusions: Genital psoriasis impacts quality of life and sexual function, with male patients being particularly impacted. Improved awareness of these issues among health professionals might increase patient satisfaction.

Clinical and Psychological Implications of Genital Vitiligo in a Thai Population.

BACKGROUND: The understanding of genital vitiligo among Thai individuals is limited. OBJECTIVES: This study evaluated the clinical presentation, quality of life, and sexual health consequences of genital vitiligo. METHODS: This cross-sectional, questionnaire-based study involving vitiligo patients aged 18 years or older with past or present genital involvement was conducted at Siriraj Hospital. It also measured aspects of sexual health and quality of life. RESULTS: The mean age of the 41 participants was 48.2 years, and 24 (58.5%) were males. All participants presented with genital vitiligo. In males, the penile shaft (45.8%), scrotum (45.8%), and glans (33.3%) were predominantly affected. In females, the mons pubis (64.7%), labia majora (23.5%), and labia minora (23.5%) were frequently involved. Both sexes reported afflictions in the pubic area (41.5%), inguinal region (36.6%), buttocks (34.1%), and oral mucosa (34.1%). Itching was the principal symptom in 26.8% of the patients. The median Dermatology Life Quality Index scores were significantly different (females 6, males 3.5). Compared with their male counterparts, females exhibited lower self-esteem (41.2% vs 29.2%), greater apprehension about marriage (11.8% vs 8.3%), and embarrassment about sexual activities (23.5% vs 16.7%). Remarkably, 65.9% of patients had not discussed their genital vitiligo with their doctors, and 51.2% of physicians had not inquired about or examined for genital involvement. CONCLUSIONS: Genital vitiligo adversely impacts quality of life and self-esteem, particularly among female patients. The lack of discourse between patients and physicians highlights a need for increased awareness and proactive clinical investigations to enhance patient care and satisfaction.

Revisiting serum storage protocols: assessing the impact of temperature variations on indirect immunofluorescence testing for pemphigus and bullous pemphigoid.

BACKGROUND: Indirect immunofluorescence (IIF) plays a crucial role in the diagnosis of pemphigus and bullous pemphigoid (BP) by detecting the presence of circulating autoantibodies in the serum of patients. The standard serum transportation method requires delivery to laboratories at 2-8 °C within a day and storage at -20 to -80 °C. However, this protocol poses logistical challenges. OBJECTIVES: We conducted a study to assess how temperature variations affect the effectiveness of IIF tests. METHODS: This case-control study analysed 203 serum specimens: 102 from patients with pemphigus and 101 from patients with BP. Specimens were stored at -80 °C (control), 24 °C, and 40 °C for seven days before analysis to investigate variations in IIF titres compared to the control conditions. RESULTS: In pemphigus serum, 95% at 24 °C and 76% at 40 °C showed no titre difference compared to controls. Similarly, 89% of BP serum at 24 °C and 82% at 40 °C matched the control titres. While 57 specimens across both groups experienced reduced titres, the decrease was primarily marginal (one-step reduction in 54 cases, two-step in 3), with no transition from positive to negative results. CONCLUSIONS: Storing serum at 24-40 °C for up to seven days before testing slightly influences IIF outcomes for pemphigus and BP. These findings could prompt a significant revision in the existing strict transport guidelines, ensuring efficient use of resources without sacrificing the accuracy of diagnostic tests.

Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment.

Chronic urticaria is a common and debilitating mast cell-driven skin disease presenting with itchy wheals, angio-oedema, or both. Chronic urticaria is classified as spontaneous (without definite triggers) and inducible (with definite and subtype-specific triggers; eg, cold or pressure). Current management guidelines recommend step-up administration of second-generation H1-antihistamines to four-fold the approved dose, followed by omalizumab and ciclosporin. However, in many patients, chronic urticaria does not respond to this linear approach due to heterogeneous underlying mechanisms. A personalised endotype-based approach is emerging based on the identification of autoantibodies and other drivers of urticaria pathogenesis. Over the past decade, clinical trials have presented promising options for targeted treatment of chronic urticaria with the potential for disease modification, including Bruton's tyrosine kinase inhibitors, anti-cytokine therapies, and mast cell depletion. This Therapeutics article focuses on the evidence for these novel drugs and their role in addressing an unmet need for personalised management of patients with chronic urticaria.

Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study.

Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13-8.04; p = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49-4.34; p < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21-4.41; p = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82-33.7; p < 0.001). Kaplan-Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.

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.

Long-term efficacy and safety of nonablative monopolar radiofrequency in the treatment of moderate to severe acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is a prevalent skin condition known for its potential to cause scarring and psychological distress, often leading to diminished self-esteem. While topical and oral treatments are commonly prescribed, some patients experience treatment failure, adverse effects, or contraindications to conventional therapies. In response to these challenges, laser and energy-based device therapies have emerged as promising alternatives for individuals who fall into these categories, showing considerable potential in the treatment of AV. OBJECTIVE: This study aimed to evaluate the long-term efficacy and safety of a nonablative monopolar radiofrequency (NMRF) in treatment of moderate to severe AV. METHODS: Twenty-four patients with moderate to severe AV underwent a series of two NMRF treatment sessions, spaced 4 weeks apart. To evaluate treatment outcomes, live in-person lesion counts and measurements of pore size and volume, and sebum production were quantified using Antera® 3D imaging system, and Sebumeter®, respectively. Patients' self-assessment data regarding degree of improvement and facial oiliness were gathered. Dermatology life quality index (DLQI) questionnaire was utilized to assess the impact of AV on their quality of life. All objective and subjective evaluations were conducted at the baseline, 1 month after the first treatment, and during follow-up visits 1, 3, and 6 months after the last treatment sessions. Adverse effects were also recorded during each visit. RESULTS: Twenty out of the 24 subjects completed the study protocol. The mean inflammatory lesion counts significantly reduced by 42.86% and 45.71% from the baseline at 3 (p = 0.027) and 6 months (p = 0.032) after the second treatment. Sebum excretion likewise significantly decreased from baseline by 11.62% (p = 0.012), 13.37% (p < 0.001), and 21.51% (p = 0.004), 1 month after the first treatment, 1 and 6 months after the second treatment, respectively. The pore volume continued to decrease by 35% (p = 0.003) and 41.5% (p < 0.001) at 1 and 6 months following the final treatment, respectively. The DLQI significantly decreased from 10.00 (interquartile range [IQR]: 6.50-15.00) to 2.00 (IQR: 1.00-4.75), corresponding to 80% improvement of the index, 1 month after the last treatment and was sustained up to the last follow-up visit. Patients' self-assessments on degree of improvement and facial oiliness also significantly improved following NMRF treatments. The treatments were well-tolerated without significant adverse effects. CONCLUSION: NMRF appears to be an effective and safe treatment for inflammatory AV, with therapeutic outcomes persisting up to 6 months after two treatment sessions.

Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores.

BACKGROUND: Baricitinib treatment in adults with moderate-to-severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest. OBJECTIVES: In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials. METHODS: We analysed the percent change from baseline in individual EASI subscores from three phase-III, double-blind, 16-week trials of baricitinib in monotherapy (BREEZE-AD1/BREEZE-AD2) and TCS combination therapy (BREEZE-AD7) cohorts via mixed model repeated measures (MMRM). RESULTS: Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near-maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy. CONCLUSIONS: Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch-scratch cycle.

Comparative analyses of various IgE-mediated and non-IgE-mediated inducers of mast cell degranulation for in vitro study.

In vitro investigations of mast cell (MC) degranulation are essential for studying many diseases, particularly allergy and urticaria. Many MC-degranulation inducers are currently available. However, there is no previous systematic comparative analysis of these available inducers in term of their efficacies to induce MC degranulation. Herein, we performed systematic comparisons of efficacies of five well-known and commonly used MC-degranulation inducers. RBL-2H3 cells were sensitized with 50 ng/ml anti-DNP IgE or biotinylated IgE followed by stimulation with 100 ng/ml DNP-BSA or streptavidin, respectively. For non-IgE-mediated inducers, the cells were treated with 5 µg/ml substance P, compound 48/80, or A23187. At 15-, 30-, 45- and 60-min post-induction, several common MC-degranulation markers (including intracellular [Ca2+], ß-hexosaminidase release, tryptase expression by immunofluorescence staining, cellular tryptase level by immunoblotting, secretory tryptase level by immunoblotting, CD63 expression by immunofluorescence staining, and CD63 expression by flow cytometry) were evaluated. The data showed that all these markers significantly increased after activation by all inducers. Among them, A23187 provided the greatest degrees of increases in intracellular [Ca2+] and ß-hexosaminidase release at all time-points and upregulation of CD63 at one time-point. These data indicate that all these IgE-mediated (anti-DNP IgE/DNP-BSA and biotinylated IgE/streptavidin) and non-IgE-mediated (substance P, compound 48/80, and A23187) inducers effectively induce MC degranulation, while A23187 seems to be the most effective inducer for MC degranulation.

Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials.

BACKGROUND: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. METHODS: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. FINDINGS: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, -8·0 (95% CI -10·6 to -5·4; PEARL-1), -10·0 (-12·6 to -7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (-1·2 to 2·5; PEARL-1), 0·4 (-1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo -8·0 (-10·5 to -5·4; PEARL-1), -11·1 (-13·7 to -8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (-1·1 to 2·5; PEARL-1), -0·7 (-2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. INTERPRETATION: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. FUNDING: Novartis Pharma.

Unveiling the role of neutrophils in chronic spontaneous urticaria: Beyond mast cells.

Mast cells and eosinophils are considered pivotal contributors to the pathogenesis of chronic spontaneous urticaria (CSU). However, emerging evidence suggests that neutrophils also play a central role. Cutaneous mast cells and macrophages orchestrate the recruitment of neutrophils through the regulation and activation of diverse processes, including heightened local vascular permeability and chemokine release. Studies have demonstrated increased activation and elevated levels of neutrophil-related cytokines in CSU patients. Moreover, neutrophils have been proposed as antigen-presenting cells during the late-phase reaction of immunoglobulin E-mediated allergy and have been associated with the expression of calcitonin gene-related protein and vascular endothelial growth factor in CSU. Histopathological analysis of lesional skin in CSU patients revealed significantly higher eosinophil and neutrophil counts than unaffected skin. However, the extent of neutrophil infiltration in the skin does not appear to correlate with the number of neutrophils in peripheral blood. The utility of the neutrophil-lymphocyte ratio as a marker for disease activity or remission in CSU remains inconclusive. Neutrophil-targeted therapy may confer benefits for CSU patients who exhibit resistance to antihistamines. Omalizumab has demonstrated its ability to reduce neutrophil counts, the neutrophil-lymphocyte ratio, and the neutrophil-monocyte ratio in peripheral blood. While dapsone and colchicine are recommended as alternative treatment options for CSU, their evidential support from published studies remains limited. Inhibitors targeting interleukin-1 and neutrophil-related cytokines have been proposed as potential therapeutic interventions for patients exhibiting neutrophil predominance. Further research is warranted to gain deeper insights into the involvement of neutrophils in CSU and to explore potential therapeutic interventions.

Patients With Chronic Spontaneous Urticaria Who Have Wheals, Angioedema, or Both, Differ Demographically, Clinically, and in Response to Treatment-Results From CURE.

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 H1-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.

Blue Wheals and Blue Angioedema Induced by Blue Dyes: A Systematic Review.

BACKGROUND: Blue wheals and blue angioedema, the adverse reactions to blue dye injections with or without anaphylaxis, are poorly defined. OBJECTIVE: The objective is to review the characteristics (ie, sex and age at onset, interval between blue dye injection and symptom onset, clinical manifestations, duration of blue wheals or angioedema), natural courses, and treatments of blue dye adverse reactions. METHODS: A review of the articles published through July 2021 was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. RESULTS: Across 523 patients (175 studies) with any adverse reactions to blue dye injections, wheals, angioedema, or both occurred in 193 patients (36.9%). Of these 193 patients, 68 patients (35.2%) developed blue wheals or angioedema, 118 (61.1%) had ordinary wheals or angioedema (nonbluish), and 7 had both (3.6%). We reviewed 169 patients with available data (99 with ordinary lesions and 70 with blue lesions). Patent blue violet had the highest rate of inducing blue wheals or angioedema (odds ratio 4.9). Almost half of the patients with blue wheals or angioedema developed systemic symptoms; and of those with systemic symptoms, all except 1 progressed to anaphylaxis. On-demand treatments with antihistamines, corticosteroids, and epinephrine were commonly used and effective. CONCLUSIONS: Using blue dyes can lead to blue wheals or angioedema and systemic reactions. In patients with a history of a severe allergic reaction to a blue dye, repeat administration of a blue dye should be used only after carefully weighing all the risks and benefits.

Potential Therapeutic Approaches for Chronic Urticaria: Beyond H1-Antihistamines and Biologics.

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.

Epidemiology of adult patients with atopic dermatitis in AWARE 1: A second international survey.

Background: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults. Objective: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia. Methods: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA). Results: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China - 10.8% Turkey) relative to PO-SCORAD (range 13.4% China - 41.6% KSA) and POEM (range 5.1% China - 16.6% Israel). Conclusions: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood-there is disease persistence and chronicity in adults.

Prevalence of concomitant angioedema in chronic spontaneous urticaria: A systematic review and meta-analysis.

BACKGROUND: Angioedema (AE) is a condition associated with considerable morbidity and mortality that can significantly affect quality of life. AE often occurs in patients with CSU although the true prevalence remains unknown. Therefore, we conducted this systematic review and meta-analysis to summarize the available data. OBJECTIVE: This study is conducted with the aim of retrieving data from all published studies and create the pooled prevalence of AE in CSU patients. METHODS: Narrative reviews of AE and CSU, a systematic review, and a meta-analysis were conducted. The Ovid Medline and Embase databases were systematically searched per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Studies were eligible if they were in English and measured the prevalence of AE in CSU in adults or children. Two reviewers independently extracted data and appraised each study's quality. Estimated prevalence and 95% confidence interval (CI) values were pooled using random-effects meta-analysis. RESULTS: Seventeen studies from 16 countries were included. The pooled prevalence of AE in patients with CSU was 36.5% (95%CI, 30.9-42.5%; I2 = 96%). The pooled estimated prevalence of AE in patients with CSU was 44.0% (95%CI, 34.1-54.5%) in Europe, 44.5% (95%CI, 28.5-61.8%), America, and 29.4% (95%CI, 24.7-34.7%) in Asia. CONCLUSIONS: Our systematic review and meta?analysis showed that AE affects over one-third of CSU patients, although the prevalence from individual study varied considerably, ranging from 5 to 67 percent. Subgroup-analysis found that AE is more prevalent in Europe and America than in Asia.

Food-Dependent Exercise-Induced Wheals/Angioedema, Anaphylaxis, or Both: A Systematic Review of Phenotypes.

BACKGROUND: Food-dependent exercise-induced allergic reactions can manifest with wheals, angioedema, and anaphylaxis, alone or in combination. OBJECTIVE: To systematically review the clinical manifestation, culprit foods and exercise, augmenting factors, comorbidities, and treatment options of each phenotype. METHODS: Using predefined search terms, we assessed and analyzed the relevant literature until June 2021. Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were applied to this systematic review. RESULTS: A total of 231 studies with 722 patients were included. The most common phenotype was anaphylaxis with wheals, angioedema, or both, reported in 80% of patients. This was associated with a higher number of anaphylactic episodes, augmenting factors, and use of on-demand antihistamine compared with the least common phenotype, anaphylaxis without wheals or angioedema, reported in 4% of patients. Anaphylaxis with wheals/angioedema was also associated with distinct characteristics compared with stand-alone wheals, angioedema, or both, in 17% of patients. Patients with anaphylaxis were older at the time of disease onset, less often had a history of atopy, showed more positive results in response to food and exercise provocation tests, had a more restricted spectrum of culprit foods, and more often used on-demand epinephrine. CONCLUSIONS: The three phenotypes of allergic reactions to food and exercise differ in clinical characteristics, triggers, and response to treatment. Knowledge of these differences may help with patient education and counseling as well as disease management.