Chronic Urticaria in Children: A Single-Center Retrospective Study From Turkey.

The studies on childhood chronic urticaria (CU) are limited. We aimed to investigate the epidemiological and etiological factors of children with CU. Demographic characteristics, laboratory findings, and etiological factors of patients diagnosed with CU younger than the age of 18 were retrospectively evaluated. Of the 124 participants, 68 (54.8%) were aged 12 and older. Angioedema accompanied 18.5% of the patients. Chronic spontaneous urticaria (CSU) was found in 75%, while 24.2% had chronic inducible urticaria. Symptomatic dermographism (16.1%) was the most common among chronic inducible urticaria, followed by cholinergic urticaria (4.8%). No etiological factor could be detected in 56.5% of the children. Infections (29.8%) were the most common etiological factor, followed by drugs (8%). Dental problems (16.9%) were the primary infections associated with CU. Chronic urticaria prevalence in children increased with age, with CSU being the most common type. Infections played a significant role in childhood CU.

[Chronic urticaria as an atypical reaction after a vespid bite]. / Urticaria crónica como reacción atípica luego de la picadura de véspidos.

BACKGROUND: Hymenoptera stings can produce IgE-mediated reactions, toxic reactions, or atypical reactions, which are rare. Cold urticaria has been described among the cutaneous manifestations in the atypical ones, but there is only one case of chronic urticaria. CASE REPORT: A 56-year-old female patient experienced palmoplantar pruritus and generalized urticaria 60 minutes after two vespid stings, requiring medical assistance and several cycles of home treatment with oral antihistamines and corticosteroids for resolution in 12 weeks. Allergological studies showed normal tryptase and primary sensitization to Polistes dominula venom. Given the patient's profession, venom immunotherapy was started with Polistes dominula 100% without recurrence of urticaria after its administration. CONCLUSIONS: We present a case of IgE-mediated systemic reaction followed by self-limited chronic urticaria, related chronologically to the same vespid sting trigger.

ANTECEDENTES: La picadura de himenópteros puede producir reacciones mediadas por IgE, reacciones tóxicas o reacciones atípicas poco frecuentes. Dentro de las manifestaciones cutáneas por reacciones atípicas se incluye urticaria por frío, y sólo existe un informe de caso de urticaria crónica. REPORTE DE CASO: Paciente femenina de 56 años, quien 60 minutos después de recibir dos picaduras de véspidos manifestó prurito palmoplantar y urticaria generalizada, precisando asistencia sanitaria y varios ciclos de tratamiento domiciliario con antihistamínicos y corticosteroides por vía oral, con curación completa luego de 12 semanas. El estudio alergológico reportó: concentración de triptasa normal y sensibilización primaria al veneno de Polistes dominula. Debido a la profesión de la paciente se inició inmunoterapia con veneno de Polistes dominula al 100%, sin recurrencia de la urticaria después de la administración. CONCLUSIÓN: El caso aquí expuesto combina una reacción sistémica mediada por IgE seguida de urticaria crónica, de curso autolimitado, cronológicamente relacionada con el mismo desencadenante (picadura de véspidos).

Clinical and Immunological Features of Bronchial Asthma Comorbid Chronic Urticaria: A Retrospective Study.

INTRODUCTION: Asthma and chronic urticaria (CU) are two high prevalent diseases and often coexist. The underlying relationship and potential immunological mechanism between the two diseases are still unclear. The objective of this study was to investigate the clinical and immunological feature of asthma comorbid with CU. METHODS: A retrospective study was conducted. Fifty patients with asthma comorbid CU, 50 patients with asthma, and 50 patients with CU alone were included. Age and sex of the patients enrolled were matched. Data of demographic characteristics, clinical manifestations including disease severity (frequency of symptoms, age of onset, disease duration, symptom score, complication with allergic rhinitis) as well as serum immunological index including total IgE (tIgE), allergen-specific IgE (sIgE), and food-specific IgG4 (FS-IgG4), were collected and analyzed. RESULTS: No significant differences in the frequency of symptoms, age of onset, and disease duration were found among the three groups. The score of asthma control test (ACT) in patients with asthma comorbid CU was significantly lower than that of asthma (p = 0.005); however, compared with patients with CU, the 7-day urticaria activity score (UAS7) of patients with asthma comorbid CU did not show obvious differences. Immunological index showed that the positive rates of tIgE, house dust mite (HDM)-sIgE, and FS-IgG4 were different among the three groups (p < 0.05). Patients with asthma comorbid CU had the highest rate of positive tIgE, moderate and severe positive sIgE to HDM. Egg-specific IgG4 (egg-sIgG4) had the highest positive rate in all groups. Patients of asthma comorbid CU obtained the highest rate of severe positive of egg-sIgG4. CONCLUSION: Our results demonstrated that patients with asthma comorbid CU have lower control level of asthma symptoms, higher tIgE and HDM-sIgE level, and highest rate of severe positive egg-sIgG4. These results indicate that comorbidity of CU in asthma obviously increases the severity of allergens.

Peripheral blood T-cell modulation by omalizumab in chronic urticaria patients.

Background: Chronic spontaneous urticaria (CSU) is a highly prevalent and difficult to manage cutaneous disease characterized by the presence of recurrent urticaria, angioedema, or both, for a period of 6 weeks or longer. One of the biological treatments used for patients with CSU with an autoimmune background and bad control of the disease is omalizumab, an anti-IgE monoclonal antibody. The understanding of the mechanism of action of this biological drug in CSU along with the identification of potential biomarkers of clinical response can be helpful in the personalized management of the disease. Objective: The purpose of this study was to analyze the effect of omalizumab on peripheral blood lymphocyte subpopulations in patients with CSU in order to identify potential biomarkers of treatment response. Methods: We analyzed 71 patients with CSU [33 under omalizumab and 38 under non-immunomodulatory drugs (treated with antihistamines; NID)] and 50 healthy controls. An exhaustive immunophenotyping of whole blood T-cell subpopulations, including naïve, central memory, effector memory, effector cells, Th1, Th2, and Th17 was performed by multiparametric flow cytometry. Moreover, in CSU patients, we analyzed markers of inflammation (ESR, DD, CRP), atopy (prick test, IgE quantification), and autoimmunity (anti-thyroid antibodies and indirect basophil activation test).To evaluate the clinical activity, the Urticaria Activity Score 7 (UAS 7) test was used. Results: In patients with CSU under treatment with omalizumab, there was a significant decrease in the percentage of naïve and an increase in the percentage of central memory CD4 T cells as well as a decrease in the percentage of naïve and increase in the percentage of effector CD8 T-cell subsets. Moreover, patients under treatment with omalizumab had higher percentages of Th1 and Th2 cells than patients under treatment with NID. Conclusion: The immune monitoring of T-cell subpopulations in patients with CSU starting omalizumab, may be a useful strategy to analyze treatment response in the clinical practice.

Combining dipyridamole and cilostazol with up-dosing antihistamines improves outcomes in chronic spontaneous urticaria with high D-dimer levels: A randomized controlled trial.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

The potential of Bruton's tyrosine kinase (BTK) inhibitors in the pharmacotherapeutic management of immune and dermatological disease.

INTRODUCTION: The review article explores the evolving role of Bruton's tyrosine kinase (BTK) inhibitors in immune-mediated dermatological conditions, addressing significant gaps in current treatment approaches. AREAS COVERED: The review comprehensively discusses the mechanisms of action of BTK inhibitors, including irreversible and reversible inhibitors. Clinical applications of BTK inhibitors in dermatological diseases such as pemphigus, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), and atopic dermatitis are explored, highlighting recent advancements and ongoing clinical trials. Potential advantages of BTK inhibitors over existing therapies and challenges in translating preclinical findings to clinical outcomes are discussed. EXPERT OPINION/COMMENTARY: BTK inhibitors represent a promising therapeutic avenue for immune-mediated dermatological conditions, offering oral administration, targeted pathway inhibition, and a favorable safety profile compared to biologic therapies. Ongoing research and clinical trials hold the potential to address unmet needs and reshape the therapeutic landscape in dermatology.

Our manuscript explores how a new class of medications called Bruton tyrosine kinase (BTK) inhibitors could revolutionize the treatment of skin conditions caused by the immune system. These conditions, like chronic spontaneous urticaria (CSU), pemphigus, and systemic lupus erythematosus (SLE), often lack effective treatments. BTK inhibitors work by targeting specific pathways in the immune system, offering hope for patients with these challenging conditions.We reviewed clinical trials and research studies to understand how BTK inhibitors could benefit patients. One significant advantage of BTK inhibitors is their ability to provide targeted therapy, meaning they can specifically block the faulty immune responses driving these conditions without affecting the entire immune system. This targeted approach could lead to fewer side effects compared to current treatments, such as corticosteroids or immunosuppressants, which can have widespread effects on the body.Overall, BTK inhibitors represent a promising new approach to treating immune-mediated skin conditions. With further research and development, they could offer safer and more effective alternatives to current treatments, improving the lives of patients worldwide.

Validation and correlations of the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT) in Chinese patients with angioedema.

Background: The impact of recurrent angioedema can be severely debilitating and remains difficult to quantify. Several standardized patient-reported outcome measures (PROMs), including the Angioedema Activity Score (AAS), Angioedema Quality of Life (AE-QoL) questionnaire, and Angioedema Control Test (AECT), have been developed and translated into different languages. However, these PROMs have yet to be validated in Chinese individuals, and their correlations in the Chinese population remain unknown. Objective: Our aim was to validate the Chinese versions of the AAS, AE-QoL questionnaire, and AECT and assess their intercorrelations. Methods: A prospective cohort of 118 Chinese patients with recurrent angioedema at the Angioedema and Urticaria Centre of Reference and Excellence in Hong Kong completed the traditional Chinese versions of the AAS, AE-QoL questionnaire, and AECT. We analyzed the reliability and validity of these PROMs and their correlations with each other as well as with generic PROMs. Results: The Chinese AAS, AE-QoL questionnaire, and AECT demonstrated excellent internal consistency (Cronbach α = 0.920, 0.976, and 0.832, respectively; McDonald ω = 0.972, 0.977, and 0.901, respectively). Confirmatory factor analysis for the AE-QoL questionnaire showed an acceptable fit with the 4-dimensional model (comparative fit index = 0.869; Tucker-Lewis index = 0.842). The AECT showed significant correlations with both the AAS and AE-QoL questionnaire (ρ = -0.750 and -0.456 respectively [both P < .05]). The AE-QoL questionnaire was moderately correlated with certain domains of generic PROMs such as the Work Productivity and Activity Impairment Questionnaire: General Health, version 2.0, and the Short Form 12-Item Health Survey, version 2 (all ρ < 0.60). Conclusion: The Chinese AE-QoL questionnaire, AAS, and AECT are valid and reliable tools for use with Chinese patients. More validated tools should be made available to improve patient care and research for all patients with angioedema globally.

Integrating network toxicology and molecular docking to explore the toxicity of the environmental pollutant butyl hydroxyanisole: An example of induction of chronic urticaria.

The study aimed to comprehensively investigate environmental pollutants' potential toxicity and underlying molecular mechanisms, focusing on chronic urticaria (CU) induced by butylated hydroxyanisole (BHA) exposure, further drawing public awareness regarding the potential risks of environmental pollutants, applying ChEMBL, STITCH, and SwissTargetPrediction databases to predict the targets of BHA, CTD, GeneCards, and OMIM databases to collect the relevant targets of CU. Ultimately, we identified 81 potential targets of BHA-induced CU and extracted 31 core targets, including TNF, SRC, CASP3, BCL2, IL2, and MMP9. GO and KEGG enrichment analyses revealed that these core targets were predominantly involved in cancer signaling, estrogen and endocrine resistance pathways. Furthermore, molecular docking confirmed the ability of BHA to bind with core targets. The onset and development of CU may result from BHA by affecting multiple immune signaling pathways. Our study elucidated the molecular mechanisms of BHA toxicity and its role in CU induction, providing the basis for preventing and treating chronic urticaria associated with environmental BHA exposure.

Adrenergic Urticaria: An Updated Review.

It can be difficult to delineate the cause of urticarial eruptions, and in chronic cases, it can be a challenging condition to effectively treat. Several forms of urticarial eruptions are well documented and established. Our review focuses on a form of urticaria that is less commonly reported: adrenergic urticaria. In this review, we aim to consolidate the literature in the hopes that this urticarial subtype is considered in urticarial differentials, as well as highlight potential gaps in the research and future directions in treatment options.

Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches.

Chronic urticaria (CU) is a prevalent skin disorder greatly impacting the patients' life quality, in which immune dysregulation mediated by gut microbiome plays a significant role. Several studies have found the gut dysbiosis exists in patients with CU. In addition, infection may also be one of the causes of CU. The primary treatment currently used for CU is the second-generation non-sedating H1-antihistamines (nsAH). However, there are some limitations in current therapies. Based on the latest evidence, this review provides an updated overview of how the gut dysbiosis influences CU development, explores potential therapeutic approaches based on the gut microbiota and summarizes the interaction between gut microbiota and current treatment.

Knockdown of miR-155 alleviates skin damage in rats with chronic spontaneous urticaria by modulating the JAK/STAT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). METHODS: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. RESULTS: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. CONCLUSION: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

Chronic urticaria associated with Blastocystis hominis infection.

Urticaria is a skin rash with several etiologic factors, including infectious agents. Blastocystis hominis is an intestinal protozoan parasite that has been linked to urticaria and skin lesions. The aim of this work was to investigate the association between B. hominis infection and chronic urticaria. In a case-control study, stool samples were obtained from 94 patients with chronic urticaria as case group and 285 healthy individuals as control group. Urticaria activity score 7 (UAS7) was used to score the severity of urticaria, classified as mild, moderate and intense. All stool samples underwent routine stool examinations, as well as polymerase chain reaction (PCR) for the detection of B. hominis. Molecular detection was carried out using the small subunit ribosomal RNA (SSU-rRNA) gene and the parasite subtypes were determined by sequencing. The rate of B. hominis infection was 21.3% (20 out of 94) and 17.2% (49 out of 285) between the case and control groups, respectively (p = 0.463). Three subtypes of B. hominis, including ST-1, ST-2 and ST-3, were detected in the case and control groups (ST-1 = 30% vs. 8.3%, ST-2 = 40% vs. 25% and ST-3 = 30% vs. 66.6% in the case and control group, respectively), which was statistically significant (p = 0.00001). However, no statistical differences were found between the severity of the urticaria and the B. hominis subtypes (p = 0.533). This study revealed a higher prevalence (but not significant) of B. hominis infection among patients with urticaria than healthy individuals. However, the results did not find a significant association between the subtypes of B. hominis and the severity of urticaria.

Leukotriene receptor antagonists as add-on therapy to antihistamines for urticaria: Systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

Quality of Life and Perceived Stress in Chronic Spontaneous Urticaria: Counting the Burden.

Background: Chronic spontaneous urticaria (CSU) is a dermatosis with a significant psychological component. Only a few studies have assessed the quality of life (QoL) and perceived stress in CSU patients. Objectives: To evaluate the QoL and perceived stress in patients with CSU. Materials and Methods: A cross-sectional study was done on 54 patients of CSU attending the Urticaria clinic of the Dermatology department in a tertiary care postgraduate teaching hospital in North Kerala. QoL in chronic urticaria was assessed using the Chronic Urticaria-Quality of Life (CU-QoL) questionnaire and perceived stress was assessed using the Perceived Stress Scale (PSS). Results: The mean scores of CU-QoL and PSS were 55.78 and 16.31, respectively. Out of 54 patients, 26 (48.1%) had mild impairment, 26 (48.1%) had moderate impairment, and 2 (3.7%) had severe impairment of QoL. Low stress was seen in 20 (37%) patients, moderate stress in 28 (51.9%), and six (11.1%) patients had high stress. Conclusion: This study shows that more than half of the patients with CSU had moderate to severe impairment of QoL and had moderate to severe stress.

Chronic Inducible Urticaria.

Chronic inducible urticaria (CIndU) is characterized by the appearance of hives (urticaria) and/or angioedema in response to specific triggers or stimuli. For accurate diagnosis, anamnesis-driven specific, and if available, standardized trigger testings, as well as patient reported outcomes, should be applied. The currently recommended treatment algorithm is the same as for chronic spontaneous urticaria but is largely off-label for CIndU. New, and possibly more disease-specific, treatment options are needed for CIndU patients, who are often severely impacted by their disease. Several clinical trials are currently ongoing.

Chronic Spontaneous Urticaria: Etiology and Pathogenesis.

Urticaria, also known as hives, is a common condition thought to affect up to 20% of individuals worldwide in their lifetime. This skin condition is characterized by the appearance of pruritic, erythematous papules or plaques with superficial swelling of the dermis. The major complaint is the symptom of pruritus. Angioedema, which involves a deeper swelling of dermal or mucosal tissues, may accompany urticaria. Urticaria can be classified by both time course of symptoms and the underlying etiology.

Emerging Therapeutics in Chronic Urticaria.

Chronic urticaria (CU) is a common and long-lasting mast cell-mediated skin disease associated with psychiatric and autoimmune comorbidities, high economic costs, and considerable impact on quality of life. Available therapies show limited efficacy in many CU patients, which may be related to distinct underlying pathophysiology. Targeted and disease-modifying treatments with higher and broader efficacy are needed and are under development for CU. These novel drugs, small molecules, and monoclonal antibodies target mast cells and their receptors, signaling pathways, or mediators and other immune cells. In this article, the authors focus on the most promising emerging therapeutics in advanced development and discuss their potential place in future management of CU.