urticaria

Acute urticaria is common and presents with wheals and/or angioedema. These symptoms are also frequent in anaphylaxis, a life-threatening reaction that must be immediately treated. In both conditions, mast cells have a central role in their mechanism of action. Although these similarities, the diagnostic approach is usually different, as it depends on the suspicious triggers, age of the patient and region where they’re based.

Anaphylaxis must be treated with adrenaline as first-line while urticaria flares can be treated with H1-antihistamines are the first choice.

The best approach to prevent anaphylaxis or acute urticaria episodes is to avoid the trigger that is responsible for the reaction, having in consideration that a solution may be desensitization to drugs and foods in selected patients to improve their quality of life.

There are some arguments on whether neutrophilic urticaria (NU) is distinct from chronic spontaneous urticaria (CSU), although with no consensus. This study aimed to compare clinical, biological, and histological characteristics and therapeutic responses between NU and CSU.

This was an observational, retrospective study that included adults with chronic urticarial rash who had undergone a skin biopsy. One dermatologist and one cytopathologist blindly and independently reviewed the biopsies [cytology counting technique for a precise proportion of neutrophilic/eosinophilic polynuclear cells (PNN/PNEo)]. NU was defined by an inflammatory dermal infiltrate composed of at least 60% PNN, without leukocytoclasia/vasculitis.

Forty-four patients were included, and their biopsies were classified into two groups: NU (n=28) and CSU (n=16). From the bibliography, there are no characteristics related to PNN at histology, but an increase in erythrocyte sedimentation rate in the NU group (p=0.03). Colchicine also showed to be more effective in cases of significant neutrophilic infiltrate: 42.85% effectiveness in NU group versus 6.25% in CSU group.

Two other findings were a statistically associated relation with neutrophilic venulitis (p=0.04) (corresponding to an intraparietal aggregation of PNN without vasculitis) and a basophilic interstitial flame figure corresponding to degranulation of the PNN cytoplasm and exclusively associated with NU (p=0.04).

A diagnostic score was established using strict quantitative histological criteria (intensity of neutrophilic infiltrate, the existence of neutrophilic venulitis, basophilic flame figures, and intense leukocytoclasia), which allows the classification of urticarial eruptions into NU or UCS.

This score will allow diagnosis and homogenization of NU patients (it correctly classified 40 of the 44 patients from the study).

In conclusion, NU is an independent entity as some histological images were significantly (neutrophilic venulitis) or exclusively (basophilic flame figure) associated with an intense neutrophilic infiltrate. A prospective study is needed to validate this new score.

Chronic spontaneous urticaria (CSU) is a common condition in adults and children, impacting the quality of life. Recent studies characterized chronic spontaneous urticaria as an autoantibody-driven condition, with mast cells and basophils being activated through two distinct pathways: type I autoimmune CSU, where IgE autoantibodies are cross-linked by self-antigens; and type IIb autoimmune CSU, where IgG and IgM autoantibodies are directed against IgE receptors on the surface of mast cells and basophils. Basophil testing is the most effective way to diagnose type IIb autoimmune CSU: a positive basophil test correlates to long disease duration, higher disease activity, poor response to antihistamines and omalizumab, and a better response to cyclosporine and fenebrutinib.

The objective of this study was to identify features of basophil test-positive patients.

This was a cross-sectional study that included 85 participants with CSU. They were tested for basophils with the basophil-activation test (BAT), the basophil histamine release assay (BHRA), and data were statistically analyzed.

Of all the participants, 44% tested positive with the BAST, and 28% tested positive with BHRA. These participants had higher activity and impact of disease, less disease control, and lower total serum IgE. In contrast, they had a higher rate of positive autologous serum skin test (ASST), angioedema, nocturnal symptoms, symptoms more than five days/week, and thyroid autoantibodies. The ASST was a good predictor of a positive basophil test when combined with angioedema, thyroid autoantibodies, and low IgE.

This study showed that a positive basophil test is related to known characteristics of type II autoimmune CSU, allowing a better approach to these patients’ condition management.

Chronic urticaria is a condition driven by mast cells, with an average lifetime prevalence of 1.4%. Chronic spontaneous urticaria is a common type of chronic urticaria that impacts quality of life and has a high economic and social burden. Chronic spontaneous urticaria is treated with oral second-generation antihistamines, however only half of the patients respond to up to quadruple doses of these antihistamines. It is known that gut microbiota can affect their efficacy. The objective of this study was to explore the relationship between gut microbiota and the efficacy of antihistamines in people with chronic spontaneous urticaria.

The gut microbiota of fecal samples from 15 responders to antihistamine monotherapy and 15 non-responders was assessed by 16S rDNA sequencing, and the differential bacterial species between them were confirmed by quantitative polymerase chain reaction (qPCR). Samples from 30 responders and 30 non-responders were used to confirm the differential bacterial species by qPCR.

The main difference between responders and non-responders was the presence of Lachnospiraceae and its subordinate taxa. The quantity of Lachnospira was higher in responders than non-responders.

In conclusion, the presence of Lachnospira has shown to have a moderate diagnostic value in assessing the efficacy of chronic urticaria with antihistamines.

Urticaria is a mast-cell-driven condition with symptoms such as wheals, angioedema, or both. Chronic spontaneous urticaria and chronic inducible urticaria reduce the quality of life, affecting performance at school and work.

This document is an update and revision of the international guideline for urticaria, from a consensus conference held on the 3^rd of December of 2020. It covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

The objective of this guideline is to facilitate a definition and classification of urticaria, helping with data interpretation from different centers and areas of the world.

The table below summarizes the guideline.

*≥90% agreement

**>75% agreement

***≥70% agreement

Chronic spontaneous urticaria is an autoimmune condition for, at least, 50% of the cases, and sometimes it is associated with other autoimmune diseases such as thyroid autoimmunity and systemic lupus erythematosus. They have an increased prevalence of autoreactive T-cell responses to FceRI and serum anti-thyroid antibodies. There are still a lot of unclear aspects to be determined, namely how long CSU will last. Most patients with chronic spontaneous urticaria are concerned about the probability of recurrence and wish for the existence of clinical or laboratory markers. The aim of this study was to understand the prevalence and characteristics of the recurrence of chronic spontaneous urticaria to prevent stressful comorbidities.

The study included 180 regular patients from the local registry. Chronic spontaneous urticaria lasted more than 5 years in 47 (26%) patients and was resolved during the first year in 23 (13%) patients. 21% of the patients reported recurrence of chronic spontaneous urticaria after a full remission between 1 and 10 years (mean 2.9 years).

In the search for predictive clinical or laboratory markers, the main differences found are registered in the table below.

In conclusion, the prevalence of chronic spontaneous urticaria after a full remission is significantly higher in patients with bronchial asthma, increased levels of total IgE and autoimmunity. More studies are needed to support these findings.

Chronic spontaneous urticaria consists in the occurrence of wheals, angioedema, or both more than 6 weeks, and 1-2% of the population is affected. It is more prevalent in women and frequently compromises quality of life and the costs for national health systems can be considerable.

The World Allergy Organization (WAO) has reviewed a position paper published in 2012 regarding diagnosis and treatment of urticaria and angioedema. Since then, there have been advances in the knowledge of urticaria mechanism of action, and new treatments (biologics) have been released for severe refractory disease. Urticaria pathological mechanisms include different cell types, mainly mast cells, basophils, eosinophils, T and B lymphocytes and epithelial and endothelial cells. The dysregulation of intracellular signaling pathways and autoimmune mechanisms have an important role in the activation of mast cells/basophils, which leads to the release of inflammatory mediators resulting in wheals and angioedema.

This is the first part of an update from the WAO, which intention is to provide an updated guidance for urticaria.

Biomarkers have been identified for the prognosis of chronic urticaria (total IgE, CRP, ASST, Anti-TPO, IL-17, IL-31, IL-33) and the assessment of the response of different therapies. Specialists are recommended to follow the guidelines, use validated PRO instruments and use effective and safe medications.