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: Quality of Life and Economic Impacts.

This study focuses on quality of life (QoL) assessment in chronic urticaria, delving into tools, disease-specific measures, and its profound impact. With expanding therapeutic options, understanding QoL becomes crucial. QoL measures often involve comparisons of patient-reported outcomes in addition to quantitative measures of disease control. Emerging tools include the Urticaria Activity and Impact Measure, which may provide a balanced evaluation. In addition to discussions of the various QoL measures, the psychological impact of chronic urticaria are highlighted, covering emotional burden, stress, and psychiatric comorbidities. Finally, the economic impacts reveal escalating health care costs and cost-effectiveness considerations of therapies like omalizumab.

Chronic Urticaria in Special Populations: Pediatric, Pregnancy, and the Elderly.

Chronic urticaria is an inflammatory skin disorder defined by the presence of evanescent erythematous pruritic wheals, angioedema, or both. While treatment guidelines are continuing to become more clearly defined, there is still a gap in the medical literature surrounding chronic spontaneous urticaria (CSU) treatment in vulnerable populations such as children (aged 0-18 years), pregnant women, and the elderly (aged >65 years). The purpose of this review is to provide an update on CSU in each of these special population categories by defining prevalence, identifying diagnostic considerations, and exploring current and future management options.

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.

Chronic Spontaneous Urticaria: An Update on the Evaluation and Management.

Chronic spontaneous urticaria (CSU) affects 0.5% to 1% of the general population and is often managed by allergy and immunology specialists. Guidelines have evolved over the past several decades with an emphasis on decreasing extensive screening laboratory testing as they are of low-yield and cost-ineffective. The utility of biomarkers remains under investigation but total immunoglobulin E may be helpful in determining specific endotypes and response to omalizumab. Antihistamines and omalizumab remain the primary therapeutic options for CSU, but an expanding body of evidence supports the use of immunosuppressants and anti-inflammatory medications in refractory cases.

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.

Is It Possible to Use Inflammatory Markers as Potential Biomarkers for Chronic Urticaria?

Background: This study aimed to determine whether the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) at admission affect the transition of pediatric patients diagnosed with acute spontaneous urticaria to chronic urticaria. Methods: This study included 390 patients who presented to the Department of Pediatrics at Akdeniz University Hospital with acute spontaneous urticaria between January 2020 and December 2022. A statistical comparison was made between the hematological parameters of patients who developed chronic urticaria and those who did not. Neutrophil, lymphocyte, and platelet counts, as well as NLR, PLR, and SII ratios, were used for the comparison. Results: It was observed that acute urticaria progressed to chronic urticaria in 5.8% (n = 23) of the patients. No significant differences in lymphocyte, hemoglobin, and platelet counts were observed between the group progressing to chronic urticaria and the control group (P > 0.05). However, the chronic urticaria group had higher leukocyte and absolute neutrophil counts (P = 0.009 and P < 0.001, respectively). In addition, the NLR was significantly higher in the chronic urticaria group (P = 0.029), whereas no statistically significant difference was observed in the PLR (P = 0.180). The chronic urticaria group had a significantly higher SII than the control group (P = 0.011). Conclusion: Hematological parameters, particularly NLR and SII, may be useful indicators of the transition from acute to chronic urticaria in pediatric patients. The early identification of these markers could help monitor patients and guide treatment decisions. Further comprehensive studies are required to validate these findings.

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.

Increased Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Chronic and Severe Urticaria.

Chronic spontaneous urticaria (CSU) is a disturbing skin condition often severely detrimental to quality of life. Haematological markers of inflammation such as neutrophil-to-lymphocyte and platelet-to-lymphocyte may be used in the assessment of inflammatory skin diseases. Their usefulness in urticaria is unknown. Neutrophil- to-lymphocyte, platelet-to-lymphocyte, and total serum IgE were investigated in urticaria patients: acute spontaneous urticaria (ASU) versus CSU, children versus adults with CSU, and patients with mild-to-moderate versus severe CSU. This retrospective cohort study included patients of all ages diagnosed with urticaria between 2005 and 2020 and blood counts within 30 days of diagnosis. Patients with comorbidities influencing blood cells (infection, surgery, malignancy) were excluded. Neutrophil-to-lymphocyte and platelet-to-lymphocyte were evaluated in patients with ASU vs CSU and mild-to-moderate CSU vs severe CSU (defined by the use of systemic medications or hospitalizations). A total of 13,541 urticaria patients were included in the study. CSU patients (n = 5,021) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte, as well as serum IgE levels compared with ASU patients (n = 8,520). Adults had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte than children. Severely affected patients (n = 53) had higher neutrophil-to-lymphocyte and platelet-to-lymphocyte compared with mild-to-moderately affected patients (n = 4,968). Patients with higher neutrophil-to-lymphocyte and platelet-to-lymphocyte had higher odds of having CSU rather than ASU and severe urticaria rather mild-to-moderate. In conclusion, neutrophil-to-lymphocyte and platelet-to-lymphocyte are simple and available markers that can be used to predict and assess severe and chronic urticaria.

PD-BAT: A novel approach of pooling basophil donors for expansion of commercial laboratory testing of Chronic Spontaneous Urticaria.

The type II autoimmune subtype of Chronic Spontaneous Urticaria (CSU) is characterized by the presence of IgG autoantibodies targeting IgE or the IgE high-affinity receptor (FcεRI) on mast cells and basophils. In evaluation of CSU patients, indirect basophil activation testing (BAT), has been utilized, involving the mixing of patient serum with heterologous peripheral blood donors, followed by flow cytometric assessment of basophil markers. However, the reliability of the indirect BAT results hinges on the quality of the donor basophils utilized. In this study, we introduce an innovative approach where multiple potential basophil donors undergo rigorous BAT characterization alongside control samples. By selecting and pooling donors with optimal performance, we significantly enhance the inter-assay reproducibility of the indirect BAT test.

[The disease under chronic urticaria: beyond itching]. / La enfermedad crónica bajo la urticaria: más allá del prurito.

BACKGROUND: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. CASE REPORT: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. CONCLUSION: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential.

ANTECEDENTES: Los exantemas cutáneos eritemato-papulares de breve duración sugieren el diagnóstico clínico de urticaria; no obstante, puede tratarse de otro tipo de dermatitis, y para establecer el diagnóstico deben llevarse a cabo exploraciones complementarias. REPORTE DE CASO: Paciente femenina de 53 años, diagnosticada en 2016 con linfoma difuso de células B grandes, en remisión completa. Desde el 2010 manifestó episodios de lesiones eritemato-papulosas, de 24-36 horas de duración. Recibió antihistamínicos, corticoides y omalizumab sin mejoría clínica. La determinación de ANA resultó positiva (1/320), con patrón mitótico nuclear. La biopsia cutánea fue compatible con dermatitis herpetiforme. El estudio de anticuerpos de celiaquía y locus mostró positividad para HLA-DQ2 y DQ2.5 con heterocigosis. Se estableció el diagnosticó de dermatitis herpetiforme. El tratamiento consistió en dieta exenta de gluten y prescripción de dapsona, con resultados satisfactorios. CONCLUSIÓN: Es importante establecer el diagnóstico diferencial de pacientes con urticaria crónica que no responden al tratamiento de referencia, además de efectuar el examen clínico y la exploración física exhaustivos antes de iniciar el protocolo, y apoyarse de un equipo multidisciplinario para establecer el diagnóstico certero y tratamiento adecuado. Debido a los efectos secundarios de la dapsona, es imprescindible el seguimiento posterior de los pacientes.

Impact of Chronic Spontaneous or Inducible Urticaria on Occupational Activity.

The impact of chronic urticaria on work has been scarcely reported, whereas its peak incidence is between the ages of 20 and 40. The aim of this study was to assess the occupational impact of chronic urticaria and its treatment, by combining objective and patient-reported data. A monocentric observational study was performed using questionnaires over a 1-year period from 2021 to 2022 in chronic urticaria patients who were in a period of professional activity and agreed to participate. Of the 88 patients included, 55.7% assessed the occupational impact of their chronic urticaria as significant, and even more severe when chronic urticaria was poorly controlled. Some 86% of patients had symptoms at work, in a third of cases aggravated by work. However, occupational physical factors were not associated with an aggravation of inducible chronic urticaria. A total of 20% reported treatment-related adverse effects affecting their work. Despite low absenteeism, presenteeism and reduced productivity were important (> 20%). Six patients (6.8%) had difficulties keeping their work. For 72.7% of the patients, the occupational physician was not informed. The occupational impact of chronic urticaria should be discussed during consultations, particularly when it is insufficiently controlled. The occupational physician should be informed in order to support patients' professional project.

Intersecting pathways: evaluating inflammatory markers and metabolism in chronic spontaneous urticaria with a multi-marker approach.

BACKGROUND: Chronic spontaneous urticaria (CSU) is an inflammatory skin disease with intricate mechanisms. This study comprehensively assessed markers from diverse metabolic pathways, including novel inflammatory indicators, to evaluate their potential for diagnosing and monitoring CSU. MATERIALS AND METHODS: In the study involving 90 CSU patients and 90 healthy controls, the levels of albumin, high-density lipoprotein (HDL), fibrinogen, uric acid, D-dimer, C-reactive protein (CRP), and white blood cells (WBC) values were analyzed. The D-dimer/albumin ratio (DAR), fibrinogen/albumin ratio (FAR), and uric acid/HDL ratio (UHR), considered novel inflammatory markers, were calculated. The Urticaria Activity Score 7 (UAS7) was also calculated. Pearson chi-squared test, Mann-Whitney U test, Spearman correlation coefficient, and univariate logistic regression analysis were employed for data analysis. RESULTS: In the patient group, significant elevations were observed in DAR, FAR, fibrinogen, CRP, D-dimer, and UHR values. Additionally, albumin, HDL, and uric acid values exhibited significant decreases. HDL and albumin provided the most accurate results in the univariate logistic regression analysis. CRP had less accuracy, FAR exhibited greater accuracy than fibrinogen, and DAR demonstrated higher accuracy than D-dimer. There was no statistically significant correlation between the UAS7 and parameters. The considerable correlation of CRP with other parameters, except D-dimer, was also remarkable. CONCLUSIONS: Indicators from diverse metabolic pathways, including albumin, HDL, uric acid, fibrinogen, D-dimer, and CRP, can be valuable in assessing CSU. In particular, FAR and DAR are emerging as potential markers to consider in the assessment of CSU.

[Recognition and management of relevant comorbidities in chronic spontaneous urticaria]. / Erkennen und Management relevanter Komorbiditäten bei chronischer spontaner Urtikaria.

Various mechanisms contributing to the activity of chronic spontaneous urticaria (CU) have been postulated. Associated comorbidities are increasingly leading to the discovery of further signaling pathways which may support the activity of chronic urticaria or contribute to low-grade systemic inflammation. Moreover psychoimmunological factors may also be involved. The aim of this work is to improve the clinical care of patients with CU by increasing knowledge regarding optional influencing factors due to comorbidities and to possibly influence disease activity. Chronic urticaria due to autoimmune mechanisms may dispose to other autoimmune diseases, especially autoimmune thyroiditis, which can trigger chronic disease. Association of CU with metabolic syndrome has received little attention to date. Obesity may contribute to low-grade systemic inflammation by cytokine-secreting adipose tissue and hence to mediator-release of mast cells. Furthermore, neuroimmunological pathways, especially increased release of substance P, an activating ligand of Mas-related G protein-coupled receptor X2 (MRGPX2) on mast cells, should be addressed when optimizing therapy.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

A Case-Control Study Comparing the General Characteristics of Patients with Symptomatic Dermographism and Chronic Spontaneous Urticaria: Is Atopy a Risk Factor for Symptomatic Dermographism?

INTRODUCTION: Symptomatic dermographism (SDerm) is the most common chronic inducible urticaria (CIndU) subtype. There is still limited information in the literature about clinical features, triggering factors, and accompanying comorbidities of SDerm. The aim of this study was to compare the clinical features and laboratory data of patients with SDerm and chronic spontaneous urticaria (CSU). METHODS: The clinical features and laboratory data of patients with SDerm and CSU were compared retrospectively. The laboratory data and general characteristic features of the patients were obtained from the medical records. RESULTS: The study included a total of 361 patients (CSU: 220, SDerm: 141). The rates of asthma (odds ratio [OR]: 1.79, p = 0.036), allergic rhinitis (OR: 6.03, p < 0.001), and thyroid disease (OR: 1.78, p = 0.039) were higher in patients with SDerm. The disease duration (median 12 months, p < 0.001) and regular antihistamine use (OR: 0.31, p < 0.001) were lower in patients with SDerm. Total IgE level (median: 193, p < 0.001), thyroid antibody positivity (OR: 1.93, p = 0.039), and atopy (OR: 8.81, p < 0.001) were higher in patients with SDerm. Dermatophagoides pteronyssinus (OR: 17.72, p < 0.001), Dermatophagoides farinae (OR: 17.20, p < 0.001), grass pollen (OR: 2.50, p < 0.026), cat epithelium (OR: 3.68, p < 0.023), and cockroach (OR: 4.93, p < 0.009) allergen positivity rates were higher in patients with SDerm. CONCLUSION: Atopic diseases such as asthma and allergic rhinitis and the sensitization rate to aeroallergens seem to be higher in patients with SDerm than in patients with CSU. The results of this study should be supported by multicenter studies of patients from different geographical regions.

[Practical update for the diagnosis and treatment of chronic urticaria]. / Actualización práctica de diagnóstico y tratamiento de la urticaria crónica.

Urticaria is a distinctive pattern of inflammatory response of the skin and/or mucous membranes characterized by the sudden appearance of vanishing wheals, angioedema, or both, associated with pruritus. Acute forms are frequent and limited to outbreaks of less than 6 weeks; while the chronic ones have a prevalence of less than 1%, longer duration and can be spontaneous or inducible. The etiopathogenic mechanisms involved in this disease include autoallergy, autoimmunity, and inflammation with cell activation, mainly of the mast cell, leading to its degranulation with the release of vasoactive mediators. Along its approach, diagnostic confirmation, search for indicators of its etiopathogenesis, detection of cofactors that can modulate its activity, recognition of comorbidities, evaluation of possible biomarkers and the assessment of disease activity, impact and control are essential. The pharmacological management aims to control the symptoms, until the urticaria, which is self-resolving, is gone. This is described in a stepwise fashion with increasing complexity.

La urticaria es un patrón distintivo de respuesta inflamatoria de piel y/o mucosas caracterizada por la aparición súbita de ronchas evanescentes, angioedema o ambos, asociados a prurito. Las formas agudas son frecuentes y se limitan a brotes de menos de 6 semanas; mientras que las crónicas tienen una prevalencia menor al 1%, mayor duración y pueden ser espontáneas o inducibles. Los mecanismos etiopatogénicos involucrados en esta enfermedad incluyen la autoalergia, la autoinmunidad y la inflamación con la activación celular, principalmente del mastocito, lo que lleva a su degranulación con liberación de mediadores vasoactivos. En su abordaje son fundamentales la confirmación diagnóstica; la búsqueda de indicadores de su etiopatogenia; la detección de cofactores que pueden modular su actividad; el reconocimiento de comorbilidades; la evaluación de posibles biomarcadores y, el impacto en la calidad de vida, el registro de la actividad y el control de la enfermedad. El manejo farmacológico tiene por objetivo controlar los síntomas, mientras la urticaria resuelve de forma espontánea. Este se describe de forma escalonada con una complejidad creciente.