Evaluation of New Markers in Type 3 Angioedema

Study Overview
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Brief Summary
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Angioedema is a common condition, with multiple etiologies. Type 3 angioedema is caused by an increase in kininogenase activity responsible for an increased production of bradykinin. In some cases, it may be associated with clotting factor 12 mutations. However, other genetic abnormalities remain to be identified. Clinically, this angioedema type 3 is similar to types 1 and 2. The patient's vital prognosis is good if the diagnosis is made and if they have access to the appropriate treatment. Otherwise a significant morbidity is associated with it, hence the importance of being able to define a diagnostic marker. Videocapillaroscopy might be able to highlight abnormalities in the microcirculation of patients with a clinical display of angioedema. The purpose of this study is to highlight markers allowing to make an early diagnosis of angioedema. Functional analysis of factor XII in patients with symptoms of angioedema may be an interesting marker for diagnosis. Microcirculation abnormalities will also be evaluated by videocapillaroscopy, which may be another indicator of the disease.

Official Title
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Evaluation of New Markers (FXII and Videocapillaroscopy) in Type 3 Angioedema

Conditions
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Angio Edema

Intervention / Treatment
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* Diagnostic Test: Factor XII dosage
* Genetic: p.Thr328Lys mutation detection
* Diagnostic Test: Videocapillaroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Population of patients treated within the CHU Brugmann Hospital for an angioedema (and control group of healthy individuals) Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Type III angioedema<br>White angioedema. Positive for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC. | Diagnostic Test: Factor XII dosage<br>* Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.<br>Genetic: p.Thr328Lys mutation detection<br>* Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.<br>Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|
| Experimental: Idiopathic angioedema<br>White angioedema. Negative for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC. | Diagnostic Test: Factor XII dosage<br>* Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.<br>Genetic: p.Thr328Lys mutation detection<br>* Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.<br>Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|
| Experimental: Type I or II angioedema<br>White angioedema. Negative for Factor XII mutation. C1-inhibitors anomaly. Not caused by IEC. | Diagnostic Test: Factor XII dosage<br>* Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.<br>Genetic: p.Thr328Lys mutation detection<br>* Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.<br>Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|
| Experimental: Post IEC (conversion enzyme inhibitors) angioedema<br>White angioedema. Negative for Factor XII mutation. No C1-inhibitors anomaly. Caused by IEC. | Diagnostic Test: Factor XII dosage<br>* Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.<br>Genetic: p.Thr328Lys mutation detection<br>* Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.<br>Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|
| Experimental: Histaminic angioedema<br>Red angioedema.Negative for Factor XII mutation. No C1-inhibitors anomaly. Not caused by IEC. | Diagnostic Test: Factor XII dosage<br>* Factor XII (FXII, Hageman factor) will be measured in plasma. It is converted to FXIIa by an activator. The FXIIa protease cleaves a chromogenic substrate and releases p-nitroaniline (pNA), which can be measured photometrically.<br>Genetic: p.Thr328Lys mutation detection<br>* Sequencing of exon 9 of franking introns of FXII, for identification of the p.Thr328Lys mutation.<br>Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|
| Other: Control<br>Healthy individuals, no angioedema. | Diagnostic Test: Videocapillaroscopy<br>* It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of Factor XII | Plasma concentration of Factor XII | 24 hours | 
| Presence of p.Thr328Lys mutation | Genetic analysis : sequencing of the Factor VII gene. Presence/Absence of the p.Thr328Lys mutation (single nucleotide variation inducing a missense variant). | 24 hours | 
| Videocapillaroscopy result | It is an optical method to visualize the most superficial part of the cutaneous microcirculatory network. It provides morphological information.The result will be classified as 'normal' or 'abnormal' by the videocapillaroscopy specialist. | 24 hours |