RESUMEN
Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.
Asunto(s)
Urticaria Crónica , Omalizumab , Humanos , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/diagnóstico , Omalizumab/uso terapéutico , Omalizumab/administración & dosificación , Antagonistas de los Receptores Histamínicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/uso terapéutico , Ciclosporina/uso terapéutico , Ciclosporina/administración & dosificación , Urticaria/tratamiento farmacológico , Urticaria/diagnósticoRESUMEN
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.
Asunto(s)
Antialérgicos , Urticaria Crónica , Omalizumab , Humanos , Omalizumab/uso terapéutico , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/inmunología , Urticaria Crónica/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antialérgicos/uso terapéutico , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/efectos de los fármacos , Anciano , Inmunofenotipificación , Resultado del Tratamiento , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/efectos de los fármacos , Adulto JovenRESUMEN
Chronic spontaneous urticaria (CSU) is associated with skin mast cell activation, and its triggering mechanisms are not completely elucidated. Evidence suggests an autoimmune component of CSU. Our aim was to assess the usefulness of an autoimmune mast cell activation test (aiMAT) for diagnosing and differentiating CSU into different subtypes. We enrolled 43 patients with active, uncontrolled CSU before starting treatment with omalizumab and 15 controls. Patients were evaluated based on omalizumab response. aiMATs were performed using non-IgE-sensitized (NS) or myeloma IgE-sensitized (S) LAD2 cells, which were then stimulated with CSU/control sera (25 µL and 10 µL). The expression of CD63 was assessed with flow cytometry. CD63 response on NS-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.0007) and with 10 µL CSU/control sera (p = 0.0001). The ROC curve analysis demonstrated an area under the curve (AUC) of 0.82. The cutoff for autoimmune-non-IgE-sensitized-MAT was 40.3% CD63+ LAD2, which resulted in 73.3% sensitivity and 81.4% specificity. CD63 response on S-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.03). The ROC curve analysis demonstrated an AUC of 0.66. The cutoff for the autoimmune-myeloma IgE-sensitized-MAT was 58.4% CD63+ cells, which resulted in 62.8% sensitivity and 66.7% specificity. Overall, 36 out of 43 (84%) patients responded to omalizumab, and 7 (16%) were nonresponders. We found no differences between LAD2 CD63 response and response to omalizumab. In conclusion, aiMAT could represent a new diagnostic tool in CSU. Additional studies are needed to evaluate the potential benefits during omalizumab therapy.
Asunto(s)
Urticaria Crónica , Mastocitos , Tetraspanina 30 , Humanos , Urticaria Crónica/diagnóstico , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/inmunología , Urticaria Crónica/sangre , Femenino , Mastocitos/inmunología , Mastocitos/metabolismo , Masculino , Persona de Mediana Edad , Adulto , Tetraspanina 30/metabolismo , Omalizumab/uso terapéutico , Anciano , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Curva ROC , Estudios de Casos y ControlesRESUMEN
Contexto: Urticária crônica caracteriza-se pela presença de urticas e/ou angioedema, com tempo de evolução superior a 6 semanas. Classifica- se em urticária crônica espontânea (UCE), com causas conhecidas ou não conhecidas e urticária crônica induzida (UCI). Objetivo: Esta revisão de UCE visa abordar os aspectos clínico-laboratoriais e indicações terapêuticas, de acordo com as diretrizes brasileira e internacional. Métodos: para esta revisão de UCE foi realizada pesquisa nas bases de dados PubMed, Embase, Google Acadêmico e Web of Science. Resultados: Foram incluídos artigos em inglês publicados entre 2018 e 2024, de acordo com sua relevância. Discussão: A patogênese da UCE engloba mecanismos imunológicos do tipo I e IIb. O diagnóstico da afecção é clínico, podendo ser realizados exames laboratoriais complementares, incluindo hemograma, VHS, D-dímero, PCR, anticorpos anti-peroxidase tireoidiana e IgE total. O diagnóstico diferencial da UCE apresenta diversas condições clínicas com morfologia semelhante à UCE. O tratamento indicado da UCE envolve medidas como suspensão de eventuais fatores desencadeantes e abordagem farmacológica, com utilização de anti-histamínicos não-sedantes, omalizumabe e uso eventual de ciclosporina. Conclusões: O impacto da UCE para os pacientes e para o sistema de saúde é de extrema relevância e avanços nas pesquisas permitirão um tratamento individualizado, com melhores perspectivas em relação à terapêutica e qualidade de vida dos pacientes.
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Urticaria Crónica , Urticaria Crónica InducibleRESUMEN
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.
Asunto(s)
Urticaria Crónica , Cilostazol , Dipiridamol , Quimioterapia Combinada , Productos de Degradación de Fibrina-Fibrinógeno , Loratadina , Inhibidores de Agregación Plaquetaria , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Urticaria Crónica/tratamiento farmacológico , Cilostazol/administración & dosificación , Cilostazol/uso terapéutico , Dipiridamol/administración & dosificación , Dipiridamol/uso terapéutico , Método Doble Ciego , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Antagonistas de los Receptores Histamínicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/uso terapéutico , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Loratadina/análogos & derivados , Inhibidores de Agregación Plaquetaria/administración & dosificación , Calidad de Vida , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéutico , Resultado del TratamientoAsunto(s)
Enfermedades Cardiovasculares , Urticaria Crónica , Humanos , Estudios de Casos y Controles , Urticaria Crónica/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Factores de RiesgoRESUMEN
Chronic spontaneous urticaria (CSU) significantly impacts the quality of life of affected individuals. This study aimed to elucidate the epidemiological and clinical profiles of adult CSU patients in Latvia. Patient interviews and electronic medical records from two study centres in Riga, Latvia, were reviewed. PROMs, including UCT, UAS7, USS, and CU-Q2oL, were used to assess disease control, activity, severity, and quality of life. Statistical analysis was performed using Jamovi v. 2.3.28 and IBM SPSS v. 29.0.0.0. The cohort included 140 CSU patients (76.4% female; mean age 41.3 ± 14.9 years), mostly urban residents (87.1%) and non-smokers (53.6%). Urticaria with angioedema occurred in 52.1% and isolated urticaria in 47.9%, with 40% experiencing CSU for 1-5 years. Accompanying symptoms were reported by 63% and triggers by 72.9%. Allergy history and autoimmune disease diagnosis were noted in 49.3% and 29.3%. Treatment mainly involved second-generation antihistamines (85.7%) and omalizumab (17.9%). Mean scores for USS, UCT, and UAS7 were 28.8 (SD: 17.8), 8.2 (SD: 3.7), and 17.2 (SD: 14.1). UAS7 indicated severe CSU in 28.6%, and UCT suggested poorly controlled disease in 77.9%. CU-Q2oL total scores revealed mental status as the most affected domain (mean score: 51.7, SD: 28.7), with a significant association between accompanying symptoms and questionnaire scores. This study provides insights into the demographic and clinical aspects of CSU patients in Latvia, highlighting areas for potential improvement in patient care and emphasizing the need for further investigation into treatment outcomes and patient quality of life.
Asunto(s)
Urticaria Crónica , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Femenino , Letonia/epidemiología , Masculino , Adulto , Urticaria Crónica/epidemiología , Persona de Mediana Edad , Omalizumab/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico , Angioedema/epidemiología , Antialérgicos/uso terapéutico , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Adulto JovenRESUMEN
Background: The proximity of activated T cells and mast cells in the lesional skin of patients with chronic spontaneous urticaria (CSU) is held to contribute to the development of wheals and angioedema. In a previous study, we demonstrated that increased IL-17 expression in T cells and mast cells in skin lesions of patients with CSU is associated with T/mast cell proximity, but the mechanisms that drive T cell/mast cell co-localization remain unknown. Objectives: To assess if chemokines expressed in lesional CSU skin contribute to T cell/mast cell proximity. Patients and methods: Biopsies from lesional CSU skin were compared to biopsies from healthy skin for expression of CCR5 and its ligand CCL3 by CD4+ T cells and mast cells, respectively. Results: Numbers of CCR5-positive CD4+ T cells in lesional CSU skin were significantly increased as compared to healthy normal skin (p < 0.0001). The number of mast cells expressing CCL3 (ligand for CCR5) in CSU skin was also increased (p < 0.0002) and significant association with T-cell close proximity (p < 0.0001) is noticed. Conclusions: The close proximity of T cells and mast cells in the skin of severe CSU may be driven, at least in part by increased CCR5 and CCL3 expression. Therapies that target CCL3 interaction with CCR5 should be assessed for their effects in CSU.
Asunto(s)
Linfocitos T CD4-Positivos , Quimiocina CCL3 , Urticaria Crónica , Mastocitos , Receptores CCR5 , Piel , Humanos , Mastocitos/inmunología , Mastocitos/metabolismo , Piel/inmunología , Piel/patología , Piel/metabolismo , Urticaria Crónica/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Quimiocina CCL3/metabolismo , Adulto , Masculino , Receptores CCR5/metabolismo , Femenino , Persona de Mediana Edad , BiopsiaRESUMEN
PURPOSE OF REVIEW: To resume the current literature about vaccination and the onset of chronic urticaria. RECENT FINDINGS: The recent large-scale vaccination against SARS-CoV-2 targeting elderly, adult and children, has highlighted how vaccines can trigger onset or exacerbation of chronic urticaria. SUMMARY: COVID-19 vaccines may act as triggers in the development of chronic spontaneous urticaria. More data regarding the other vaccines are necessary to evaluate a similar potential role. Proper education of patients with vaccine-induced chronic urticaria is essential to avoid vaccination hesitancy.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Urticaria Crónica , Vacunación , Adulto , Anciano , Niño , Humanos , Urticaria Crónica/inducido químicamente , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunación/efectos adversosRESUMEN
BACKGROUND: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. METHODS: We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. RESULTS: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. CONCLUSION: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.
Asunto(s)
Antialérgicos , Urticaria Crónica , Omalizumab , Humanos , Omalizumab/uso terapéutico , Omalizumab/administración & dosificación , Femenino , Masculino , Urticaria Crónica/tratamiento farmacológico , Estudios Prospectivos , Persona de Mediana Edad , Antialérgicos/uso terapéutico , Antialérgicos/administración & dosificación , Adulto , Resultado del Tratamiento , Anciano , PronósticoRESUMEN
PURPOSE: Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab. RESULTS: The model equation for the CFB-UAS7 was established as E = -Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max , ET 50 , b 0 , and b 1 were -1.16, 1.26 weeks, -9.90, and -0.0361 mg-1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were -16.0 (95% CI, -17.2 to -14.8) and -21.7 (95% CI, -22.9 to -20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were -19.4 (95% CI, -20.7 to -18.1) and -19.3 (95% CI, -20.6 to -18.0), respectively. In the PEARL-2 trial, these values were -19.2 (95% CI, -20.5 to -17.9) and -20.3 (95% CI, -21.6 to -19.0), respectively. CONCLUSION: Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab.
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Antialérgicos , Urticaria Crónica , Relación Dosis-Respuesta a Droga , Omalizumab , Omalizumab/administración & dosificación , Omalizumab/uso terapéutico , Humanos , Urticaria Crónica/tratamiento farmacológico , Antialérgicos/administración & dosificación , Antialérgicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento , Modelos BiológicosRESUMEN
BACKGROUND: Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. OBJECTIVES: To characterize the role and relevance of Gal-9 in the pathogenesis of CSU. METHODS: We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils. RESULTS: Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells. CONCLUSION: Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.
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Antialérgicos , Basófilos , Biomarcadores , Urticaria Crónica , Eosinófilos , Galectinas , Omalizumab , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antialérgicos/uso terapéutico , Antialérgicos/farmacología , Basófilos/metabolismo , Basófilos/inmunología , Estudios de Casos y Controles , Urticaria Crónica/tratamiento farmacológico , Eosinófilos/metabolismo , Eosinófilos/inmunología , Galectinas/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Omalizumab/uso terapéutico , Omalizumab/farmacología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Chronic spontaneous urticaria (CSU) involves recurrent, pruritic wheals lasting more than 6 weeks in response to various etiologies, including unknown causality. Though most cutaneous reactions to the COVID-19 vaccine series are self-limited and of short duration, more complex presentations including chronic spontaneous urticaria have been described. To the best of our knowledge, this is the first report of chronic spontaneous urticaria following heterologous mRNA COVID-19 booster vaccination that includes vaccination with both forms of the mRNA vaccine. Our patient received Pfizer-BioNTech for the primary series and Moderna for the booster. After failing several therapies, our patient's urticaria was refractory even to omalizumab. The source for chronic spontaneous urticaria development in our patient may be related to the unique humoral response elicited by receipt of a different mRNA vaccine manufacturer.
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Vacunas contra la COVID-19 , Urticaria Crónica , Inmunización Secundaria , Humanos , Vacunas contra la COVID-19/efectos adversos , Inmunización Secundaria/efectos adversos , Vacuna BNT162/efectos adversos , Femenino , Omalizumab/uso terapéutico , COVID-19/prevención & control , COVID-19/complicaciones , Persona de Mediana Edad , Masculino , AdultoRESUMEN
Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.
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Antialérgicos , Urticaria Crónica , Inmunoglobulina E , Omalizumab , Humanos , Omalizumab/uso terapéutico , Urticaria Crónica/tratamiento farmacológico , Femenino , Masculino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Antialérgicos/uso terapéutico , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Resultado del Tratamiento , Eosinófilos/inmunología , Recuento de Leucocitos , Anciano , Adulto JovenAsunto(s)
Antialérgicos , Urticaria Crónica , Metaloproteinasa 9 de la Matriz , Omalizumab , Humanos , Omalizumab/uso terapéutico , Urticaria Crónica/tratamiento farmacológico , Metaloproteinasa 9 de la Matriz/metabolismo , Antialérgicos/uso terapéutico , Quimiocinas CC/metabolismo , Colágeno/metabolismo , Femenino , Masculino , Resultado del TratamientoRESUMEN
Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There is an unmet need to develop therapies that target disease-driving pathways upstream of mast cell activation to inhibit or delay the progression of CSU and associated comorbidities. Here, we aim to define disease modification due to a treatment intervention and criteria that disease-modifying treatments (DMTs) must meet in CSU. We have defined disease modification in CSU as a favorable treatment-induced change in the underlying pathophysiology and, therefore, the disease course, which is clinically beneficial and enduring. A DMT must fulfil the following criteria: (1) prevents or delays the progression of CSU, (2) induces long-term, therapy-free clinical remission, which is the sustained absence of CSU signs and symptoms without the need for treatment, and (3) affects the underlying mechanism of CSU, as demonstrated by an effect on disease-driving signals and/or a biomarker. DMTs in CSU should slow disease progression, achieve long-lasting disease remission, target disease-driving mechanisms, reduce mast cell-activating IgE autoantibodies, target cytokine profile polarization, and normalize the gut microbiome and barrier. Treating CSU at the immune system level could provide valuable alternatives to pharmacotherapy in CSU management. Specific DMTs in CSU are yet to be developed, but some show potential benefits, such as inhibitors of Bruton's Tyrosine Kinase, IL-4 and IL-13. Future therapies could prevent CSU signs and symptoms, achieve long-term clinical benefits after discontinuing treatment, and prevent associated concomitant disorders.
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Urticaria Crónica , Humanos , Urticaria Crónica/tratamiento farmacológico , Urticaria Crónica/etiología , Manejo de la Enfermedad , Mastocitos/inmunología , Mastocitos/metabolismo , Resultado del Tratamiento , Progresión de la EnfermedadRESUMEN
The immunological pathogenesis of atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) has not been fully elucidated yet. The aim of our research was to assess the serum concentration of interleukin-5 receptor (IL-5R) in relation to the disease activity and pruritus intensity in adult patients with AD and CSU. This pilot study included 45 participants (15 patients with AD, 15 patients with CSU, and 15 healthy controls). Blood samples were taken to examine the serum levels of IL-5R using the enzyme-linked immunosorbent assay (ELISA) test. The Scoring Atopic Dermatitis (SCORAD) index, the Urticaria Activity Score (UAS7), and the Visual Analogue Scale (VAS) were used to assess the disease activity and the pruritus intensity, respectively. Obtained results revealed that the IL-5R concentration was significantly higher in patients with CSU than in patients with AD and in the controls (p = 0.038). There was a positive correlation between the IL-5R level and the SCORAD index in patients with AD (r = -0.9, p = 0.047), which was not found for the CSU activity by UAS7 and with the pruritus severity by VAS in both examined groups of patients. Our findings underscore higher serum levels of IL-5R among CSU and AD patients, which may highlight its functional role in the pathogenesis of these diseases. In contrast, IL-5R might not be fully useful in reflecting the severity of symptoms. Although our results are promising, this study should be conducted on a larger cohort of patients.
Asunto(s)
Urticaria Crónica , Dermatitis Atópica , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/sangre , Femenino , Masculino , Adulto , Urticaria Crónica/sangre , Persona de Mediana Edad , Prurito/sangre , Proyectos Piloto , Biomarcadores/sangre , Estudios de Casos y Controles , Receptores de Interleucina-5/sangre , Adulto Joven , Subunidad alfa del Receptor de Interleucina-5RESUMEN
Background: Sleep can be affected in patients with chronic spontaneous urticaria (CSU). The mechanisms of sleep regulation remain poorly understood. Orexin-A, a neuroexcitatory peptide, plays a role in coordinating sleep-wake states. Ghrelin and leptin are involved in sleep regulation through the orexin system. Objective: The effects of orexin-A, ghrelin, and leptin on sleep quality in patients with CSU have not been investigated. We aimed to determine the effects of CSU on sleep quality and the association between serum orexin-A, ghrelin, and leptin levels, and sleep quality in patients with CSU. Methods: Thirty-three patients with CSU and 34 sex- and age-matched controls were included in the study. Serum orexin-A, leptin, and ghrelin levels, and the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores were measured in patients with CSU and in the controls; also used were the chronic urticaria quality-of-life questionnaire score and the urticaria activity score used for 7 consecutive days. Results: Median (minimum-maximum) orexin-A, leptin, and ghrelin levels in patients were 385 pg/mL (90-495 pg/mL), 3.1 ng/mL (0-21.2 ng/mL), and 701.8 pg/mL (101.9-827.7 pg/mL), respectively. Median serum orexin-A and leptin levels were higher in the patients compared with the controls (p < 0.001 and p = 0.012, respectively), whereas the median serum ghrelin levels were similar to the controls (p = 0.616). The serum orexin-A level was positively correlated with ghrelin (r = 0.298, p = 0.014), PSQI sleep quality (r = 0.356, p = 0.003), and ESS (r = 0.357, p = 0.003). Conclusion: Serum orexin-A is associated with sleep quality in patients with CSU. Further studies are needed to elucidate the role of ghrelin and leptin on sleep quality in patients with CSU.