Delayed Pressure Urticaria: Clinical and Diagnostic Features and Response to Omalizumab.

BACKGROUND: Delayed pressure urticaria (DPU) is a rare form of chronic inducible urticaria (CIndU) when it manifests alone. Treatment of DPU is disappointing owing to the lack of response to antihistamines, even when up-dosing. In addition, the absence of randomized clinical trials and the low number of patients included in the studies mean that there is little scientific evidence for the validity of omalizumab in DPU. OBJECTIVE: Objectives of the study were to perform a real-world study of the effectiveness and safety of omalizumab in DPU patients without chronic spontaneous urticaria or other forms of CIndU and to describe their clinical and diagnostic features. METHOD: We performed an ambispective observational study of 14 patients with DPU who did not respond to 2 or more second-generation H1-antihistamines in an up-dosing regimen and/or corticosteroids, montelukast, or cyclosporine. Treatment was initiated with omalizumab 300 mg every 4 weeks. We recorded the following: age, time to diagnosis, previous treatment, diagnostic testing (mean time threshold after removing the stimulus and duration of the lesions), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D dimer, total IgE, antithyroid peroxidase (anti-TPO) antibodies, and the Urticaria Control Test (UCT) score before and after the first dose. We evaluated the efficacy of omalizumab according to the Urticaria Control Test score. We analyzed the time to complete or satisfactory response after the first dose (superfast) and its adverse effects. RESULTS: Women accounted for 64.28% patients. The mean age at diagnosis was 43.64 (±13.78) years. The time to diagnosis was 4.53 (±5.54) years. The mean time threshold after removing the stimulus was 4.18 h (±2.75). The mean duration of lesions after testing was 32.42 (±13.8) hours. High ERS values (>20.0 mm/h) were detected in 50% of patients. CRP was >0.5 mg/dL in 42.85% and D dimer levels were high (>500.0 ng/mL) in 3/10 patients. Anti-TPO level was normal in 100% of patients. Total IgE was >100 IU/mL in 6/8 patients. Medium UCT levels before treatment with omalizumab were 3.07 (±2.40), reaching 15.28/16 (±1.72) after the first dose of omalizumab. All 14 patients responded superfast, and none experienced an adverse reaction. CONCLUSIONS: Despite the limitation of a low sample size in this real-life study, our findings suggest that omalizumab is a rapid, effective, and safe treatment for patients with DPU refractory to antihistamines in an up-dosing regimen. We recommend omalizumab for patients who do not respond to up-dosing antihistamines and montelukast.

[Inflammation and remodeling of the distal airways: studies in humans and experimental models]. / Inflamación y remodelación de la vía aérea pequeña: estudios en humanos y modelos experimentales.

Asthma is characterized by inflammation and remodeling of the airways, giving rise to airway obstruction and symptoms of wheezing, chest tightness, cough and dyspnea. Most of these observations arise from the study of samples obtained from the central airways by distinct methods. However, it is currently accepted that this inflammatory process occurs not only in the central airway but also in the small airway and even in the pulmonary parenchyma of all asthmatic patients, even those with mild asthma. CD4+ lymphocytes, activated eosinophils and IL-5 mRNA expression are present in a greater quantity in the small airways. Also present is remodeling, with an increase in submucosal thickness, the muscular layer and adventitia. This inflammatory process causes a disconnection between the pulmonary parenchyma and the airway, giving rise to obstruction of the small airway, which is currently considered to be predominant in asthmatic patients. Likewise, studies of experimental asthma in animals support the substantial role of the distal airway. Recognition that asthma affects the entire airway could be clinically important and lead to the distal lung being considered as a target in any effective therapeutic strategy. However, longitudinal studies are required to evaluate the impact of distal airway inflammation and its treatment in asthma.

Inflamación y remodelación de la vía aérea pequeña: estudios en humanos y modelos experimentales / Inflammation and remodeling of the distal airways: studies in humans and experimental models

El asma se caracteriza por inflamación y remodelación de la vía aérea, que da lugar a la obstrucción de ésta ysíntomas de sibilancias, opresión torácica, tos y disnea. La mayoría de estas observaciones surgen del estudiode muestras obtenidas de las vías aéreas centrales por distintos métodos, pero hoy en día se acepta que esteproceso inflamatorio ocurre no sólo en la vía aérea central, sino también en la vía aérea pequeña (VAP) e inclusoen el parénquima pulmonar de todos los pacientes asmáticos, incluso en aquellos con asma leve. Loslinfocitos CD4+, eosinófilos activados, y la expresión de ARNm para interleucina 5 están presentes en mayorcantidad en la VAP. También existe remodelación, con incremento del grosor de la submucosa, capa musculary adventicia. Este proceso inflamatorio causa un desacoplamiento entre el parénquima pulmonar y la víaaérea, dando lugar a una obstrucción de la pequeña vía aérea que hoy en día se considera como predominanteen pacientes asmáticos. Los estudios de asma experimental en animales apoyan asimismo una relevanteparticipación de la vía aérea distal. El reconocimiento del asma como una enfermedad que afecta a toda la víaaérea puede tener importancia clínica y obliga a considerar al pulmón distal como diana de cualquier estrategiaterapéutica para un tratamiento efectivo de la enfermedad, aunque faltan estudios longitudinales queayuden a valorar el impacto de la inflamación de la VAP y de su tratamiento en el asma(AU)

Asthma is characterized by inflammation and remodeling of the airways, giving rise to airway obstructionand symptoms of wheezing, chest tightness, cough and dyspnea. Most of these observations arise from thestudy of samples obtained from the central airways by distinct methods. However, it is currently acceptedthat this inflammatory process occurs not only in the central airway but also in the small airway and even inthe pulmonary parenchyma of all asthmatic patients, even those with mild asthma. CD4+ lymphocytes,activated eosinophils and IL-5 mRNA expression are present in a greater quantity in the small airways. Alsopresent is remodeling, with an increase in submucosal thickness, the muscular layer and adventitia. Thisinflammatory process causes a disconnection between the pulmonary parenchyma and the airway, givingrise to obstruction of the small airway, which is currently considered to be predominant in asthmatic patients.Likewise, studies of experimental asthma in animals support the substantial role of the distal airway.Recognition that asthma affects the entire airway could be clinically important and lead to the distal lungbeing considered as a target in any effective therapeutic strategy. However, longitudinal studies are requiredto evaluate the impact of distal airway inflammation and its treatment in asthma(AU)