May 2020

Chronic spontaneous urticaria is one of the most common cutaneous disorders, characterized by the recurrence of transient wheals, angioedema or both for more than 6 weeks. Vitamin D has a main role in bone homeostasis, but also has immunomodulatory action in innate and adaptive immunity. Some studies have shown that vitamin D plays also a role in the improvement of clinical symptoms of chronic urticaria.

The aim of this study was to assess the association between serum levels of vitamin D and chronic spontaneous urticaria and to evaluate its efficacy and safety.

The study included 77 participants with chronic spontaneous urticaria and 67 healthy controls. They were randomized to receive 0,25 ug of alfacalcidol daily or placebo for 12 weeks.

Participants with chronic spontaneous urticaria had a significantly lower serum vitamin D than healthy controls at the beginning of the study. 12 weeks after administration of alfacalcidol, participants with chronic spontaneous urticaria showed a significant higher level of serum vitamin D compared to placebo. Additionally, mean serum level of IL6, CRP and TNFa significantly also decreased in these participants.

Although vitamin D deficiency is more common in people with chronic spontaneous urticaria, supplementation with alfacalcidol may have a beneficial role as add-on therapy of chronic spontaneous urticaria with no relevant side effects.

Chronic urticaria is a heterogeneous persistent, severely debilitating and often poorly controlled disease. Recent studies have shown that the prevalence of CU and its sub forms may be more heterogeneous than previously thought.

This update on chronic urticaria focuses on its prevalence and pathogenesis, the expanding spectrum of patient-reported outcome measures for assessing disease activity, impact and control, as well as future treatment options.

Chronic urticaria is a mast cell-driven disease which presents with transient wheals (hives), angioedema, or both, without any definite triggers and reoccurrence of signs and symptoms for more than six weeks. It is common in both children and adults; its prevalence is increasing with substantial differences across geographical regions.

The objective of treatment in chronic urticaria is complete disease control with absence of signs and symptoms, as well as normalization of quality of life. Specialists can monitor by using sets of patient-reported outcome measures. Antihistamines and omalizumab are the only currently licensed treatments for chronic urticaria. Some inhibit the effects of signals that drive mast cells activation and accumulation, others inhibit intracellular pathways of mast cells activation and degranulation, or silence mast cells by binding to inhibitory receptors.

Chronic spontaneous urticaria is a mast-cell driven skin disease characterized by the recurrence of transient wheals, angioedema or both for more than 6 weeks. Recent studies have suggested that eosinophils may also have a major role in symptomatology. In urticaria, it is usually observed a peripheral blood eosinopenia, opposed to other allergic and inflammatory conditions. Histological studies have shown the presence of eosinophils and eosinophil granules in urticaria lesions. They may enhance urticaria in three ways: first, eosinophil-derived stem cell factor (SCF) promotes the recruitment and local maturation of mast cells in the tissues. Second, eosinophil proteins, such as major basic protein, eosinophil cationic protein and eosinophil peroxidase can provoke mast cell degranulation. And third, activated eosinophils also express tissue factor, the main initiator of the coagulation cascade leading to thrombin formation. Eosinophil infiltration may contribute to tissue edema of skin in urticaria but can also, together with increased mast cells, prime the skin for further healing.

Treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL5 humanized antibodies mepolizumab, reslizumab and benralizumab, have shown to reduce chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is the recurrent manifestation of wheals sometimes associated with angioedema for more than 6 weeks. It is a usual and potentially disabling disease. Its pathogenesis shows a complex and unclear connection between immunoglobulin G (IgG) and immunoglobulin E (IgE)-mediated autoimmunity, which leads to mast cell and basophil degranulation and formation of wheals.

The aim of this study was to assess the IgG and IgE reactivity to autoantigens in people with chronic spontaneous urticaria and to evaluate its effects on response to the anti-IgE monoclonal antibody omalizumab.

The study included 20 participants who underwent omalizumab treatment (300 g /month). Urticaria activity score 7 (UAS7) was registered at baseline and 1, 3 and 4 months after treatment initiation to categorize early-, late- or non-responders. At baseline, sera from the 20 participants and 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors, tissue factor and thyroglobulin by ELISA. Antibody levels were compared with those of controls and analysed according to response.

There were 18 omalizumab responders (11 early and 7 late) and 2 non-responders. More than half of the participants had contemporary IgE and IgG to at least one of the four autoantigens. Late responders had higher levels of anti-TF IgG and IgE. 25% of the participants had levels of anti-high and low affinity IgE receptors (anti-FcεRI IgE), which suggests that it could be a novel auto-allergen in chronic spontaneous urticaria.

In conclusion, autoimmune responses sustained by both IgE and IgG antibody classes were detected in more than half of the participants with chronic spontaneous urticaria. Such autoimmune responses may co-exist and possibly influence the clinical response to anti-IgE therapy, especially in late responders to omalizumab.

Chronic spontaneous urticaria is characterized by hives and angioedema that significantly affects quality of life. People with urticaria have higher self-reactive autoantibodies IgE and IgG than healthy people. Other proteins implicated in the pathogenesis of urticaria include thyroperoxidase (TPO), interleukin 24 (IL24) and thyroglobulin (Tg). The reason why these proteins are recognized by specific autoantibodies in people with urticaria is unknown.

The aim of this study was to compare the sequences of TPO, Tg and IL24 with some prevalent allergens through in silico analysis.

The amino acid sequences of IL24, TPO and Tg were compared between them and with 22 environmental allergens. To explore the degree of protein identity and cover, researchers carried out phylogenetic studies and multiple pairing. Proteins without 3D structure reported in the database were modelled and compared by homology. Residues conserved and accessible to the solvent were located in the 3D model to identify possible areas of cross-reactivity and antigen binding.

Five epitopes for TPO, six for IL24 and six for Tg were predicted with the 3D model built. The amino acid sequences of allergens from different sources (Dermatophagoides pteronyssinus, Blomia tropicalis, Betula verrucosa, Cynodon dactylon, Aspergillus fumigatus, Canis domesticus, Felis domesticus) were also compared with the human proteins. The cover and alignments between allergens and human proteins were low.

In conclusion, there are possible linear and conformational epitopes of TPo, Tg and IL24 that can be the target of IgE and IgG binding in patients with urticaria. These epitopes aren’t found in common allergens, which indicates that autoreactivity to the human proteins is not through cross-reactivity.

Chronic spontaneous urticaria is a common skin disorder that affects up to 1% of the world population, with more women affected. Its symptoms include repeated occurrence of itchy wheals, angioedema or both, for over 6 weeks. The objective of this review was to highlight the conceptual and practical knowledge for interpreting score changes in patient-reported outcomes (PROs) that have been validated for chronic spontaneous urticaria.

Guidelines recommend assessing PROs as Health-Related Quality of Life, disease activity and disease control to detect the impact of urticaria and the overall treatment effect. In order to have this, it is fundamental to determine the minimal important difference (MID) to evaluate if changes in questionnaire scores represent a perceived improvement or deterioration for patients. MID are collected into two categories, distribution-based and anchor-based.

For most chronic spontaneous urticaria questionnaires, a MID has been defined according to the results of various approaches. The majority of studies analysed in this review used anchor-based methods. The available information regarding MIDs across validated tools for people with chronic spontaneous urticaria helps to interpret measurement scores and allows the implementation of PROs in routine practices.