Chronic inducible urticaria (CIndU) is a group of skin disorders defined by recurrent itchy or burning wheals or angioedema that recur for more than six weeks with a specific triggering factor. This is different from chronic spontaneous urticaria which does not have a specific triggering factor. CIndU is subclassified in nine subtypes with each having its own specific trigger. These subtypes are further divided in physical urticarias (symptomatic dermographism, cold urticaria, delayed pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema) or non-physical urticarias, i.e., cholinergic urticaria, aquagenic urticaria, and contact urticaria. Symptomatic dermographism (SD) is the most prevalent subtype of the physical urticarias. Its prevalence in Western populations is estimated to be between 1-5%. Following SD, cold urticaria (ColdU) is the next most common form, its annual incidence is estimated to be 0.05%. In this study, patients with the ColdU and symptomatic SD subtypes will be enrolled. As of yet, disease diagnosis of SD and ColdU is mostly purely clinical (clinical picture + patients' history), as there is a lack of objective biomarkers. Currently only two objective tools are available for the diagnosis of SD and ColdU, which are the FricTest and Temptest (both provocation tests). In addition, there is a lack of objective biomarkers for the prediction of treatment response and for the monitoring of treatment effects, as this is nowadays only monitored by patient reported outcomes.
The objective of this study is to deep phenotype CIndU (subtype SD and ColdU) and detect novel biomarkers for diagnosis andtreatment response as well as establish methodologies for (non-) invasive monitoring of treatment effects in chronic inducible urticaria. For this purpose, a study with a multi-modal approach will be performed for in-depth characterization of SD and ColdU. The study willconsist of 2 parts: in part A the biology of disease will be investigated, and in part B the response of the biomarkers to real-world treatment with omalizumab will be monitored (part B). The former to characterize objectively measured disease characteristics and mechanisms underlying its development, the latter to monitor response of the disease and its characteristics to standard of care treatment once in four weeks. The study focusses on cellular, molecular, biophysical, imaging and microbiome analyses in comparisonwith chronic spontaneous urticaria (CSU) patients and matched healthy volunteers.
Study Type
OBSERVATIONAL
Enrollment
40
Centre for Human Drug Research
Leiden, South Holland, Netherlands
COMPLETEDErasmus Medical Center
Rotterdam, South Holland, Netherlands
RECRUITINGUniversity Medical Center Utrecht
Utrecht, Utrecht, Netherlands
RECRUITINGAbsolute eosiniphil count
cells/µL
Time frame: Baseline - day 99
IgG-anti-FcεRI
IU/mL
Time frame: Baseline - day 99
Absolute basophil count
cells/µL
Time frame: Baseline - day 99
C-reactive protein
mg/L
Time frame: baseline - day 99
D-dimer
µg/mL
Time frame: Baseline - day 99
Complement assessment
mg/dL
Time frame: Baseline - day 99
Total serum IgE
IU/mL
Time frame: Baseline - day 99
Basophil activcation test (BAT)
% activation or Stimulation index
Time frame: Baseline - day 99
Cytokine profile assessment
pg/mL
Time frame: Baseline - day 99
Tissue mass cytometry (CyTOF)
Skin punch biopsies (4mm) will be taken from (non-)lesional skin and healthy for tissue mass cytometry (CyTOF).
Time frame: Baseline - day 99
RNA-sequencing analysis
Skin punch biopsies (4mm) will be taken from (non-)lesional skin and healthy for RNA-sequencing analysis
Time frame: Baseline - day 99
Next-generation sequencing of skin swabs
The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.
Time frame: Baseline - day 99
Composition and diversity of faecal microbiota
Faecal samples will be collected to measure the composition and diversity of gut microbiota.
Time frame: Baseline - day 99
3D Multispectral imaging
The redness and superficial morphology of (non-)lesional skin sites and healthy skin will be determined using a 3D multispectral imaging system.
Time frame: Baseline - day 99
Laser Speckle Contrast Imaging (LSCI)
The cutaneous microcirculation of (non-)lesional skin sites and healthy skin will be monitored over a 40 second timespan with a laser speckle contrast imager.
Time frame: Baseline - day 99
2D photography
Standardized 2D clinical photographs will be taken of lesional and non-lesional skin, as well as healthy control skin, to build a longitudinal photo library for visual assessment of disease morphology and treatment response over time.
Time frame: Baseline - day 99
Urticaria Activity Score over 7 days (UAS7)
The Urticaria Activity Score over 7 days (UAS7) is a validated patient-reported outcome measure used to assess the severity and frequency of urticaria symptoms-specifically wheals (hives) and pruritus (itch)-over the previous week. Scores range from 0 to 42, with higher scores reflecting more severe disease activity. The UAS7 is applied exclusively in patients with chronic spontaneous urticaria (CSU) to monitor disease burden and evaluate treatment response.
Time frame: Baseline - day 99
Urticaria Control Test (UCT)
The Urticaria Control Test (UCT) is a validated patient-reported outcome measure used to assess disease control in patients with chronic spontaneous urticaria (CSU). The total UCT score ranges from 0 to 16, with higher scores indicating better disease control. This questionnaire is used exclusively in patients with CSU to monitor treatment response and disease management over time.
Time frame: Baseline - day 99
Dermatology Life Quality Index (DLQI)
The Dermatology Life Quality Index (DLQI) is a validated patient-reported outcome measure that assesses the impact of skin diseases on patients' quality of life over the previous week. The total DLQI score ranges from 0 to 30, with higher scores indicating greater impairment in quality of life. A score of 0 reflects no impact, whereas 30 represents the most severe impact on quality of life. The DLQI will be assessed in all patients across the included skin disease cohorts.
Time frame: Baseline - day 99
Symptomatic Dermographism Activity Score (SDAS)
The Symptomatic Dermographism Activity Score (SDAS) is a patient-reported outcome measure specifically designed to assess disease activity in individuals with symptomatic dermographism. Patients rate the severity of their symptoms, such as itching and whealing, over the previous 24 hours on a scale from 0 to 4, with higher scores indicating more severe symptoms. The SDAS will be assessed daily in patients with symptomatic dermographism throughout the study to monitor disease activity and treatment response.
Time frame: Baseline - day 99
Symptomatic Dermographism Quality of Life Questionnaire (SD-QoL)
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The Symptomatic Dermographism Quality of Life Questionnaire (SD-QoL) is a disease-specific, patient-reported outcome measure that evaluates the impact of symptomatic dermographism on patients' daily functioning and well-being. It covers domains such as symptoms, emotional burden, and social limitations, with higher scores indicating greater impairment in quality of life. The SD-QoL will be administered to all patients with symptomatic dermographism to assess the condition's impact over time and in response to treatment.
Time frame: Baseline - day 99
Cold Urticaria Activity Score (ColdUAS)
The Cold Urticaria Activity Score (ColdUAS) is a patient-reported outcome measure used to assess daily disease activity in individuals with cold urticaria. Patients rate the severity of their symptoms, such as itching, whealing, and swelling, over the previous 24 hours on a scale from 0 to 3 for each symptom, with higher scores reflecting greater disease activity. The ColdUAS will be completed daily by patients with cold urticaria throughout the study to monitor fluctuations in disease activity and evaluate treatment effects.
Time frame: Baseline - day 99
Cold Urticaria Quality of Life Questionnaire (ColdU-QoL)
The Cold Urticaria Quality of Life Questionnaire (ColdU-QoL) is a disease-specific, patient-reported outcome measure that assesses the impact of cold urticaria on various aspects of daily life, including symptoms, emotional well-being, and social and occupational functioning. Higher scores indicate greater impairment in quality of life. The ColdU-QoL will be administered to all patients with cold urticaria to evaluate the burden of disease and changes in quality of life over the course of treatment.
Time frame: Baseline - day 99
Activity Tracking Sleep
Subjects are requested to wear a smartwatch at all times which register sleep (hrs, minutes, seconds of rest)
Time frame: Baseline - day 99
Activity Tracking Steps
Subjects are requested to wear a smartwatch at all times which register steps (amount of steps taken)
Time frame: Baseline - day 99