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Clinical and histological characteristics during chronic urticaria with dermal neutrophilic infiltrate: Proposal of a diagnostic score

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A Brehon, P Moguelet, V Seta, E Amsler, A Fajac, A Barbaud, A Soria, JB Monfort

J Eur Acad Dermatol Venereol . 2021 Nov 6. doi: 10.1111/jdv.17788. Online ahead of print.

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.

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Impact of Allergic Rhinitis and Asthma on COVID-19 Infection, Hospitalization and Mortality

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Jianjun Ren, et al.

J Allergy Clin Immunol Pract . 2021 Oct 30;S2213-2198(21)01202-2. doi: 10.1016/j.jaip.2021.10.049. Online ahead of print.

The COVID-19 pandemic has impacted worldwide health. Underlying diseases have been shown to affect the prevalence and outcomes of COVID-19. Allergic rhinitis and asthma can increase the susceptibility and severity of COVID-19, but it is not known to which extension. This study aimed to study the role of allergic rhinitis and/or asthma in COVID-19 infection, severity, and mortality and evaluate whether its long-term medication can affect COVID-19 outcomes.

A total of 70,557 persons who had a SARS-CoV-2 test between March 16 and December 31, 2020, in the UK Biobank were analyzed. The rate of COVID-19 infection, hospitalization, and mortality concerning existing allergic rhinitis and/or asthma were statistically analyzed, together with the impact of long-term medications and the risk of hospitalization and death due to COVID-19 infection.

People with allergic rhinitis had lower positive rates of SARS-CoV-2 tests (RR:0.75; 95%CI, 0.69-0.81, p<0.001), with men having a lower susceptibility (RR:0.74; 95%CI, 0.65-0.85, p<0.001) than women (RR:0.8; 95%CI, 0.72-0.9, p<0.001). People with asthma had comparable results if they were <65 years-old (RR:0.93; 95%CI, 0.86-1, p=0.044). People with asthma who tested positive for SARS-CoV-2 had a higher risk of hospitalization (RR:1.42; 95%CI, 1.32-1.54, p<0.001). COVID-19 mortality was not impacted by allergic rhinitis or asthma. There was no relation between COVID-19 infection and severity and conventional medications for allergic rhinitis and/or asthma.

In conclusion, allergic rhinitis and asthma (<65 years old) may be a protective factor against COVID-19 infection, with asthma increasing the risk of hospitalization.

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What Basophil Testing Tells Us About CSU Patients – Results of the CORSA Study

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João Marcelino, et al.

Front Immunol. 2021 Sep 28;12:742470. doi: 10.3389/fimmu.2021.742470. eCollection 2021

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.

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Prevalence, Management, and Anaphylaxis Risk of Cold Urticaria: A Systematic Review and Meta-Analysis

By | Artículos seleccionados, New, Selected articles

Connor Prosty, Sofianne Gabrielli, Michelle Le, Luis F. Ensina, Xun Zhang, Elena Netchiporouk and Moshe Ben-Shoshan.

J Allergy Clin Immunol Pract . 2021 Oct 18;S2213-2198(21)01129-6. doi: 10.1016/j.jaip.2021.10.012. Online ahead of print.

Chronic spontaneous urticaria can be caused by specific triggers, namely cold, exercise or heat. Chronic inducible urticaria (CIndU) can coexist with chronic spontaneous urticaria and is defined as a particular trigger that provokes the symptoms. Cold inducible urticaria is one example of physical urticaria caused by exposure to cold air, liquids, or objects and is associated with significant morbidity and risk for anaphylaxis.

The objective of this study was to evaluate the prevalence of cold urticaria among cases of chronic urticaria and chronic inducible urticaria, evaluate its management, and determine the rate of associate anaphylaxis.

The investigators did bibliographic research in PubMed and EMBASE for papers on cold urticaria and/or chronic inducible urticaria in the past ten years. An analysis was made to determine the prevalence of cold urticaria among CIndU and chronic urticaria cases, its management with H1-antihistamines and omalizumab, and the rate of associated anaphylaxis.

The research identified 22 studies, of which 14 were included in the meta-analysis. The pooled prevalence of cold urticaria among patients with chronic urticaria and CIndU was, respectively, 7.62% [CI95%; 3.45%-15.99%; I2=98%] and 26.10% [CI95%; 14.17%-43.05%; I2=97%]. 95.67% of the cases of cold urticaria were managed by H1-antihistamines [CI95%; 92.47%-97.54%; I2=38%], and by omalizumab in 5.85% of the cases [CI95%; 2.55%-13.22%; I2=83%]. The pooled prevalence of anaphylaxis was 21.49% [CI95%; 15.79%-28.54%; I2=69%].

In conclusion, cold urticaria is common in cases of chronic urticaria and CIndU and frequently triggers anaphylaxis. H1-antihistamines are commonly used for its management, followed by omalizumab.

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Particulate Matter Exposure and Allergic Rhinitis: The Role of Plasmatic Extracellular Vesicles and Bacterial Nasal Microbiome

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Jacopo Mariani, Simona Iodice, Laura Cantone, Giulia Solazzo, Paolo Marraccini, Emanuele Conforti, Pallav A. Bulsara, Maria Stella Lombardi, Robert P. Howlin, Valentina Bollati and Luca Ferrari

Int J Environ Res Public Health. 2021 Oct 12;18(20):10689. doi: 10.3390/ijerph182010689.

Particulate matter (PM) exposure is known to worsen respiratory conditions, namely allergic rhinitis. Allergic rhinitis prevalence is rising, affecting the quality of life. The objective of this study was to investigate the molecular mechanisms beneath the triggering of nasal and systemic inflammation by particulate matter, specifically the release of plasmatic extracellular vesicles and the relation between the host and nasal microbiome.

The study included 26 participants with allergic rhinitis and 24 matched healthy participants, whose reaction to PM10 and PM25 exposure was assessed on the bacteria-derived-extracellular vesicles portion (bEV) and the host-derived-extracellular vesicles (hEV), and also on the bacterial nasal microbiome (bNM). The function of bNM as a modifier of PM effects on the extracellular vesicles signaling network in the context of allergic rhinitis was also evaluated.

This study has shown an association between particulate matter exposure in participants with allergic rhinitis, both in the context of bNM composition and plasmatic extracellular vesicles release, affecting in different ways the release of extracellular vesicles and the composition of bNM. More studies are needed to better understand the link between particulate matter exposure and bNM modulation and plasmatic extracellular vesicles release and characterize the different responses observed in participants after particulate matter exposure.

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The challenges of chronic urticaria part 2: Pharmacological treatment, chronic inducible urticaria, urticaria in special situations

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Mario Sanchez-Borges, Ignacio J. Ansotegui, Ilaria Baiardini, Jonathan Bernstein, Giorgio Walter Canonica, Motohiro Ebisawa, Maximiliano Gomez, Sandra Nora Gonzalez-Diaz, Bryan Martin, Mario Morais-Almeida and Jose Antonio Ortega Martell

World Allergy Organ J . 2021 Jun 3;14(6):100546. doi: 10.1016/j.waojou.2021.100546. eCollection 2021 Jun.

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.

This is the second part of an update from the WAO, which intention is to provide an updated guidance for urticaria, especially in special situations such as childhood and pregnancy.

Second generation H1 antihistamines are recommended in major guidelines as the first line treatment for urticaria, as they are effective and safe. Some guidelines include first generation antihistamines for non responders. The dose can also be increased up to 4 times to improve efficacy (and without compromising safety). Combination of antihistamines does not seem to induce better effects, and patients who are refractory to antihistamines are candidates to omalizumab or cyclosporin-A. Omalizumab is the only biological approved for the treatment of antihistamine-refractory patients with moderate to severe urticaria. Cyclosporin-A is an immunosuppressing drug that inhibits T helper cells by blocking the production of inflammatory cytokines.

Special conditions associated with urticaria include autoinflammatory syndromes and various forms of urticarial vasculitis, which are treated with second generation antihistamines and systemic glucocorticoids, and alternatively immunomodulators and immunosuppressors.

 

Specialists are recommended to follow the guidelines, use validated PRO instruments and use effective and safe medications.

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Real-Life Experience of Efficacy and Safety of Bilastine in the Refractory Cases of Chronic Spontaneous Urticaria and its Effect on the Quality of Life of Patients

By | Articles about Bilastine, New

Abhishek De, Kiran Godse, Dhiraj Dhoot, and Aarti Sarda

Indian J Dermatol . Mar-Apr 2021;66(2):159-164. doi: 10.4103/ijd.IJD_771_20.

Chronic spontaneous urticaria is a skin condition with wheals and angioedema, for more than six weeks. Second-generation H1-antihistamines are the first line treatment for these allergic conditions, namely bilastine. The aim of this study was to assess long-term efficacy and tolerability of bilastine in patients with chronic spontaneous urticaria in India.

This was a retrospective analysis that identified patients with urticaria who were prescribe bilastine between May, 1, 2019 to March, 20, 2020 from analysis of electronic medical records. Patients with unsatisfactory response to previous treatment were also included. Unsatisfactory treatment was assessed as per Urticaria Activity Score 7 (UAS7). The efficacy of the treatment was evaluated by revising their UAS7 score ate weeks 4, 8, 12, 16, 20. DLQI was also evaluated and compared at baseline and week 24.

The study included 49 patients. At 24 weeks, 51% of them had achieved treatment response (UAS = 0) and the remaining 49% had a well-controlled urticaria (UAS <6). At 24 weeks, mean UAS7 was statistically significant compared to baseline values (1,35 ± 1,61 vs. 20,2 ± 5,73), and mean DLQI score also decreased to 1,63 ± 1,18, compared to 8,39 ± 2,49 at baseline.

In conclusion, this study demonstrated that patients who usually had an inadequate response with commonly used antihistamines, when switched to bilastine had their quality of life and symptoms improved.

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Application of a dual mechanistic approach to support bilastine dose selection for older adults

By | Articles about Bilastine, New

Chaejin Kim, Valentina Lo Re, Monica Rodriguez, John C Lukas, Nerea Leal, Cristina Campo, Aintzane Garcia-Bea, Elena Suarez, Stephan Schmidt, Valvanera Vozmediano

CPT Pharmacometrics Syst Pharmacol . 2021 Jun 22. doi: 10.1002/psp4.12671. Online ahead of print.

Bilastine is a second-generation H1-selective antihistamine for the treatment of allergic conditions in adults and children. It has a rapid onset and a long duration of action. Its pharmacokinetic and pharmacodynamic properties are favorable for all ages, although there’s a lack of studies in older adults, who are heterogenous in different aspects, namely age, comorbidities and comedication.

The aim of this study was to assess the recommendation of the dose of bilastine in older adults.

This was done by integration of bilastine in vitro and in vivo physicochemical data from young adults and studying the effect of aging with two different approaches: a physiologically based pharmacokinetic (PBPK) model and a semi-mechanistic population pharmacokinetic model (Senescence). The PBPK model used intestinal apical efflux and basolateral influx transporters to capture the results from young adults after single IV (10 mg) and 20 mg oral doses, which supports the hypothesis of gut transporters involvement on secretion. The Senescence model was developed from a published PopPK model adding up declining functions on different physiological systems and body composition changes with age.

Both models were then qualified using data from 16 older adults, mean age 68,7 years. The PBPK model was also used to assess the dose in older people (80 years old).

Both models showed that a daily dose of 20 mg is safe and effective in older people, supporting the existing information in this age group.

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