Chronic urticaria, defined as having urticaria for over 6 weeks, is divided into two categories; namely, inducible urticaria and chronic spontaneous urticaria (CSU). Inducible urticarias have an initiating stimulus, often “physical”, and actually occur intermittently, but the total duration of symptoms can encompass many years. CSU is more typically chronic, has urticarial lesions most days of the week, has no exogenous cause, and from the patient’s point of view, does seem spontaneous. An algorithm for the diagnosis of CSU is shown in Fig. 1. Angioedema can accompany many inducible urticarias, but is more typically associated with CSU affecting face, extremities, genitalia, lips, tongue, and rarely pharynx, but not the larynx. Thus risk of asphyxiation is nil. The disorder is strongly associated with autoimmunity. The best studied (often referred to as type IIb autoimmunity) involves IgG antibody to the IgE receptor[1](#ref-0001) which cross-links unoccupied IgE receptors of mast cells and activates the cells to cause secretion of histamine, leucotrienes, cytokines, and chemokines. Complement is activated and release of C5a augments the mast cell secretion[2](#ref-0002). There is a second scenario in which patients have IgE antibody to a large variety of autoantigens[3](#ref-0003) including thyroperoxidase and interleukin 24, although which are pathogenic is not yet clear. This is often designated as type I autoimmunity or autoallergy. Clinically, other autoimmune disorders may be present. The most prominent is Hashimoto’s thyroiditis, but also type I diabetes and vitiligo. Antithyroid antibodies (i.e. IgG anti microsomal antigen and IgG antithyroglobulin) are seen in 25% of patients regardless of thyroid status. Total IgE is elevated within this population although much less so than in asthma or atopic dermatitis. Low or very low IgE levels may be seen and such patients are less responsive to omalizumab[4](#ref-0004).

Background: As the use of multiplex specific IgE (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. The objective of this study was to assess the clinical and technical performance of the ALEX platform (MacroArray Diagnostics), in comparison to the ImmunoCAP ISAC 112 microarray and the ImmunoCAP singleplex method (ThermoFisher Scientific) in the diagnosis of pollen (cypress, grass, olive), dust mite Dermatophagoides pteronyssinus, Alternaria alternata, fruit (apple, peach) and nut (walnut, hazelnut and peanut) allergy. Methods: We enrolled 153 allergic patients and 16 non-atopic controls. sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and inter-assay, inter-batch and inter-lab reproducibility. Results: When measured globally (detection by one or more allergen components), ALEX2 showed adequate sensitivity and specificity for most of the allergens studied, comparable in general to that of ISAC112 (except for olive pollen and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis showed comparable results for all techniques, except for Ole e 1 and Jug r 3 in both ISAC112 and ImmunoCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. Conclusions: ALEX2 shows sound technical performance, and adequate diagnostic capacity, comparable in general to that of ISAC112 and ImmunoCAP for some aeroallergens and plant-food allergies in Mediterranean patients.

Background: Chronic histaminergic angioedema (CHA) is defined as recurrent episodes of isolated angioedema (without hives) of unknown cause that respond to the same treatment as chronic spontaneous urticaria (CSU). Quality of life (QoL) studies have not been performed for CHA, except those carried out in the context of CSU associated with angioedema attacks (CSU-AE). Moreover, biomarkers for monitoring disease activity in CHA have not been identified. We aim to describe the burden of CHA and impact on patient QoL, compare the findings to those in CSU-AE patients, and investigate biomarker associations with disease severity and QoL parameters. Methods: We performed a prospective multicenter study that included 68 patients with CHA and 63 patients with CSU-AE. Demographic and clinical variables were collected. Validated patient-reported questionnaires were employed to analyze the quality of life and disease activity. Blood and serological parameters, including blood cell count, C-reactive protein, D-dimer and total IgE, were also analyzed. Results: Angioedema disease activity was significantly higher in CSU-AE patients (median AAS7, IQR: 1, [0–1]) than CHA patients (0, [0–1]; p= 0.022). A considerable impact on QoL was found in both groups, although significantly worse values were found for CSU-AE (median AEQoL, IQR: 37, [10–65]; p=0.005). CHA patients were older than CSU-AE patients, and female predominance was not observed. Conclusions: Angioedema severity and QoL impacts are significantly worse in CSU than in chronic histaminergic angioedema. Angioedema should be included in severity urticaria scores (UAS) as well as in specific quality of life urticaria scales.

Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. It has led to the development of nanomaterials, which behave very differently compared with materials with larger scales and can be applied in a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition, and functionalisation of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers, nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalisation with ligands, which provide the desired interaction with the immunological system. However, undesired issues related to their toxicity and hypersensitivity responses have impeded more rapid health applications. Through interactions with the immune system, some of these nanostructures show promising applications as vaccines and diagnostics tools. Dendrimeric Antigens, Nanoallergens, and nanoparticles are potential tools for the in vitro diagnosis of allergic reactions. Glycodendrimers, liposomes, polymers, and nanoparticles have shown interesting applications in immunotherapy. There are wide panels of structures accessible, and controlling their physico-chemical properties would allow the obtainment of safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment.