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chronic urticaria

Urticaria.

By New, Selected articles

Pavel Kolkhir

Nat Rev Dis Primers. 2022 Sep 15;8(1):61. doi: 10.1038/s41572-022-00389-z

Urticaria is a common and heterogeneous inflammatory skin disease that affect up to 20% of the world population. Its symptoms include wheals, angioedema or both which are due to the stimulation and degranulation of skin mast cells and release of histamine and other mediators. Acute urticaria accounts for the majority of cases can last up to 6 weeks and be related to infections or intake of drugs or food. Chronic urticaria may be spontaneous or inducible, can last more than 6 weeks and persist for more than one year in most patients. Patients with chronic urticaria are deeply affected in their daily activities and may suffer from psychiatric comorbidities. Chronic inducible urticaria has different subtypes and triggers that lead to different symptoms.

The mechanism of chronic spontaneous urticaria includes autoantibodies, complement and coagulation cascades. Its diagnosis includes differential testing to identify underlying causes or triggers.

Urticaria treatment first line uses second-generation H1 antihistamines, and omalizumab and cyclosporine in a second line. Other new approaches focus on targeting mediators, signalling pathways and receptors of mast cells and other immune cells.

There’s still some research needed to define disease endotypes and their biomarkers, identifying new treatment targets and developing improved therapies.

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New transcriptome and clinical findings of platelet-activating factor in chronic spontaneous urticaria: Pathogenic and treatment relevance

By Artículos seleccionados, Selected articles

Andrades E, Clarós M, Torres JV

Biofactors . 2022 Aug 4. doi: 10.1002/biof.1880. Online ahead of print.

Urticaria is characterized by transient wheal-and-flare skin reaction with pruritus. More than 5 million people suffer from persisting urticaria symptoms in Europe, causing a huge burden on patients and healthcare systems. The aim of this study was to evaluate the relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU).

Skin samples of 45 patients with moderate/severe CSU and 17 healthy controls were analyzed for the expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH). Serum PAF and PAF-AH levels were assessed by ELISA and compared between patient and healthy controls and also between those refractory and non-refractory to 2nd-generation H1-antihistamines. PAFR mRNA expression was significantly higher in LS-CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, while it was largely present along the epidermis in LS-CSU samples. Endothelial cells showed PAFR expression exclusively in LS-CSU and NLS-CSU samples. PAFR expression was observed in the nerves of HC, LS-CSU, and NLS-CSU samples. Double PAFR/CD43 expression demonstrated that T-lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF-AH/PAF ratio was observed in 2nd-generation H1-antihistamines non-responders versus responders (6.1 vs. 12.6; p = 0.049).

In conclusion, this study corroborates that PAF is a mediator of wheal pathogenesis in CSU and suggests that PAF could be a potential biomarker of 2nd-generation H1-antihistamines refractoriness due to the significantly lower PAF-AH/PAF ratio in 2nd-generation H1-antihistamines non-responders vs responders.

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Urticaria (angioedema) and COVID- 19 infection

Chronic Urticaria: The Need for Improved Definition

By Artículos seleccionados, Selected articles

Gómez RM, Bernstein JA, Ansotegui I, Maurer M

Front Allergy. 2022 Jun 9;3:905677. doi: 10.3389/falgy.2022.905677. PMID: 35769560; PMCID: PMC9234868.

Chronic urticaria is usually diagnosed after daily or almost daily presence of symptoms for more than 6 weeks. Urticaria symptoms include pruritic wheals or hives, accompanied by angioedema in 40% of cases. Up to 20% of patients have isolated angioedema. Chronic urticaria represents a significant burden which has been extensively reported with numerous validated patient-reported outcome measures that represent a significant impact on several aspects of life ranging from physical discomfort to personal mood changes (anxiety and depression) which frequently interferes with interpersonal relationships, daily activities including work and school. It is not a surprise that management of chronic urticaria is related to substantial

costs to health care systems due to recurrent medical visits and treatments. Consequently, it is crucial to generate awareness among healthcare payors and other stakeholders on the prevalence of chronic urticaria and its impact on quality of life and on the economic burden it has on society. There is no consensus on diagnostic and management criteria for CU, which makes this task more challenging.

In conclusion, the health and economic burden of chronic urticaria is significant and should not be underestimated. The significant impact of this condition requires that physicians and other health care providers understand how to properly identify and manage this condition.

An expert consensus on diagnostic and management criteria for chronic urticaria is needed.

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skin microdyalisis

Chronic urticaria in the real-life clinical practice setting in the UK: results from the non-interventional multicentre AWARE study.

By Selected articles

Savic S, Leeman L, El-Shanawany T, Ellis R, Gach JE, Marinho S, Wahie S, Sargur R, Bewley AP, Nakonechna A, Randall R, Fragkas N, Somenzi O, Marsland A.

Clin Exp Dermatol. 2020 Apr 4. doi: 10.1111/ced.14230. [Epub ahead of print]

Chronic urticaria is a group of skin conditions that include chronic spontaneous urticaria and chronic inducible urticaria. Symptoms include itchy wheals and/or angioedema for a period longer than 6 weeks. The objective of this study was to provide information demonstrating the real-life burden of chronic urticaria in the UK.

The non-interventional AWARE study (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) collected data from a representative sample of chronic urticaria patients worldwide. A subset of UK patients aged 18-75 diagnosed with H1-antihistamine-refractory chronic spontaneous urticaria was analysed.

Baseline analysis included 252 UK patients, mostly female (77,8%) with moderate-to-severe disease activity and a spontaneous component to their chronic urticaria. Comorbidities included depression/anxiety (24,6%), asthma (23,8%) and allergic rhinitis (12,7%). 57,9% of the patients had undergone a treatment. Their mean Dermatology Life Quality Index score was 9,5 with report of reduction in work productivity and activity. These patients referred a high need to use healthcare resources. Chronic spontaneous urticaria severity was linked to gender, obesity, anxiety and diagnosis.

Only 28,5% of UK patients completed all nine study visits, which limits analysis of long-term treatment patterns and disease impact. Chronic urticaria patients reported high rates of healthcare resource use and impairment in quality of life, work productivity and activity at baseline, which highlights the need to ensure appropriate management to optimise patient quality of life and reduce the socioeconomic burden of chronic urticaria in the UK.

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Urticaria cronica angioedema

Urticaria and Angioedema Across the Ages

By Selected articles

Saini S, Shams M, Bernstein JA, Maurer M.

J Allergy Clin Immunol Pract. 2020 Apr 13. pii: S2213-2198(20)30329-9. doi: 10.1016/j.jaip.2020.03.030. [Epub ahead of print]

Chronic urticaria symptoms include itchy wheals, angioedema, or both, caused by the release of histamine, prostaglandin metabolites, leukotrienes, platelet activating factor and other proinflammatory mediators, which in turn lead to vasodilation and extravasation, sensory nerve activation and cellular infiltration.

Chronic urticaria is a common clinical condition that impairs quality of life of people and represent an important health burden. International Consensus guidelines have been published that recommend the use of standard terminology and definitions for different types of chronic urticaria, such as chronic spontaneous urticaria and chronic inducible urticaria. However, there is a lack in the understanding of mechanistic pathways and treatment in some more vulnerable populations, such as children, elderly people and pregnant or lactating women.

40-50% of the patients are effectively treated with monotherapy with a non-sedating H1-antihistamine or 2-4 times the recommended dose of a non-sedating H1-antihistamine. Biologics like omalizumab or immunosuppressants such as cyclosporin are used when patients fail to respond to simpler treatments. There is evidence that omalizumab can be safely used in the vulnerable populations, however cyclosporin has a greater toxicity and is not appropriate in these populations.

Additional therapies for vulnerable chronic urticaria patients are needed.

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Current and Emerging Treatments for Chronic Spontaneous Urticaria

By Selected articles

Johal KJ, Saini SS.

(2019) Ann Allergy Asthma Immunol. 2019 Sep 5. pii: S1081-1206(19)31054-3. doi: 10.1016/j.anai.2019.08.465. [Epub ahead of print] Review.

This is a review of published literature on current and new treatments for chronic spontaneous urticaria.

Chronic spontaneous urticaria is defined as the spontaneous appearance of wheals, angioedema or both for at least 6 weeks due to unknown causes. The management of chronic urticaria frequently overlap with chronic spontaneous urticaria, with the primary aim of the treatment being to eliminate symptoms. Current guidelines recommend H1-antihistamines (up to 4 times the upper limit of normal dosing) with the possible use of an LTRA, H2-antihistamines or alternative ones prior to omalizumab.

A PubMed search was performed to include relevant articles, including studies if they provided information related to the current understanding of the pathophysiology and management of chronic spontaneous urticaria, as well as potential novel therapeutics.

Current treatments include antihistamines, leukotriene receptor antagonists, omalizumab and immunosuppressants. New therapeutics under investigation include new IgG1 and anti-IgE monoclonal antibody with higher affinity for IgE than omalizumab (ligelizumab), targets of receptors regulating inflammatory cell chemotaxis, such as CRTH2/DP2 antagonists (AZD1981), Btk inhibitors (fenebrutinib), anti-siglec-8 monoclonal antibody (AK002) are thought to lead to apoptosis of eosinophils and anti-mediator effects on mast cells, topical syk inhibitors (GSK2646264) and designed ankyrin repeat proteins (DARPins).

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Alergenos farmacoterapia e inmunologia

Psychiatric comorbidity in chronic urticaria patients: a systematic review and meta‑analysis

By Selected articles

Gerasimos N. Konstantinou and George N. Konstantinou

(2019) Clin Transl Allergy

Chronic urticaria may affect the quality of life, namely in respect to an increase of psychiatric disorders.

This study aimed at evaluating the published evidence of psychiatric disorders that may coexist with chronic urticaria and the effect of psychiatric treatments on people with urticaria.

A systematic literature search for studies that investigated the existence of psychiatric comorbidity in patients with chronic urticaria was conducted, and twenty-five studies that met all the criteria were identified. Studies to be included in the study had to possess the following features: distinction between chronic urticaria and allergic conditions, direct collection of diagnostic psychiatric data by using clinical interview and standardized questionnaires, International Classification of Disorders criteria or the Diagnostic and Statistical Manual of Mental Disorders criteria for the diagnosis of mental disorders and manuscripts written or publish in English.

Analysis of the included studies showed that almost one out of three patients with chronic urticaria have at least one underlying psychiatric disorder. However, no studies clarified if the psychiatric disorder pre-existed at chronic urticaria onset and no association between chronic urticaria severity and duration and psychological functioning. Only a case report and two case series referred to the psychiatric disorder treatment as improving of urticaria.

This study shows the importance of a multidisciplinary approach involving recognition and management of any psychiatric disorder in addition to urticaria treatment.

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Terapia de sangrado

New treatments for chronic urticaria

By Selected articles

Pavel Kolkhir, Sabine Altrichter, Melba Munoz, Tomasz Hawro, Marcus Maurer,

(2019) Annals of Allergy, Asthma and Immunology

Current international guideline classifies chronic urticaria as inducible or spontaneous, whether there is a defined trigger sign or not. However chronic urticaria is unpredictable in its course and duration and persists for several years in many patients.

Antihistamines and omalizumab are the most common treatments for chronic urticaria.

This study reviewed the off and beyond label use of licensed drugs, novel treatments under development and promising new targets.

A search was performed and some of the key messages include that omalizumab should be explored in chronic inducible urticaria, in children with chronic spontaneous urticaria and at higher doses. Off label treatments, such as dupilumab, reslizumab, mepolizumab and benralizumab are showing effectiveness in chronic urticaria. Ongoing clinical trials include more monoclonal antibodies, ligelizumab and UB-221. Other promising treatments under development for chronic urticaria include a CRTh2 antagonist, a monoclonal antibody to Siglec-8, bruton’s tyrosine kinase inhibitors, a Syk inhibitor and dupilumab.

New pathogenically important targets for chronic urticaria include Mas-related G-protein coupled receptor X2, the H4 receptor, C5a and its receptor, and other inhibitory mast cell receptors.

The ultimate goal remains the development of treatments that can prevent chronic urticaria, alter its course and cure it.

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Efficacy and safety of bilastine in reducing pruritus in patients with chronic spontaneous urticaria and other skin diseases: an exploratory study

Efficacy and safety of bilastine in reducing pruritus in patients with chronic spontaneous urticaria and other skin diseases: an exploratory study

By Eprint

Esther Serra, Cristina Campo, Zoltan Novak, Bernadetta Majorek-Olechowska, Grazyna Pulka, Aintzane García-Bea and Luis Labeaga

Pruritus is a common symptom associated with different skin diseases, including urticaria, atopic dermatitis, eczema and prurigo. Pruritus may have a significant impact on the quality of life and psychosocial wellbeing of patients with skin urticaria. Bilastine is a H1-antihistamine with demonstrable efficacy for the symptomatic treatment of chronic spontaneous urticaria.

 

A phase IV, multicentre, open-label, exploratory study to evaluate the efficacy and safety of bilastine in reducing pruritus in patients with chronic spontaneous urticaria and other skin diseases was conducted at 10 European Centres.

 

115 patients between 18 and 74 years diagnosed with chronic spontaneous urticaria, eczema/dermatitis, prurigo or cutaneous pruritus who had not responded to placebo during a run-in period of 7-14 days and with, at least 4 points for the sum of itch score during the last 3 days of the run-in period were included. Patients received bilastine 20 mg once daily for 8 weeks and non-responders (<30% improvement in pruritus score at week 2), received 40 mg daily from week 2.

 

Bilastine reduced the mean change in weekly pruritus severity score from baseline to week 8 (primary endpoint) (overall and by disease group). Up dosed non-responders (n = 31) improved weekly pruritus severity scores from baseline to week 8. Bilastine improved the Dermatology Life Quality Index at weeks 4 and 8 (p < 0,001) in all disease groups, and the 7-day Urticaria Activity Score in CSU patients (p <0 ,001).

 

In conclusion, bilastine has demonstrated efficacy for the relief of pruritus associated with urticaria and other skin diseases in adults, with a very good safety profile. Also, bilastine up dosing to 40mg (double dose), for patients who did not achieve a significant improvement after 2 weeks of treatment, was efficacious without any safety concerns.

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La urticaria crónica (CUR) contribuye a la comprensión y el conocimiento de la enfermedad en la región.

Latin American chronic urticaria registry (CUR) contribution to the understanding and knowledge of the disease in the region

By Selected articles

Gómez RM, Jares E, Borges MS, Baiardini I, Canonica GW, Passalacqua G, Kaplan A, Latour P, Costa E, Dias G, Lavrut J; SLAAI CUR group.

Chronic urticaria (CU) has a widespread spectrum on causal or exacerbating factors, clinical manifestations, therapeutic response and quality of life affectation. Registries are useful tools in several real-life diagnosis and management approach.We aimed to evaluate the characteristics of CU patients living in Latin America through an original cross-sectional registry with data entered by regional allergologists.

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Diagnosis and treatment of urticaria in primary care

Diagnosis and treatment of urticaria in primary care

By Selected articles

Kayiran MA, Akdeniz N.

Urticaria, also known as hives among people, is a very common disease characterized by erythematous, edematous, itchy, and transient plaques that involve skin and mucous membranes. It is classified as acute spontaneous urticaria, chronic spontaneous urticaria, chronic inducible urticaria, and episodic chronic urticaria. Many factors such as infections, medicines, food, psychogenic factors, and respiratory allergens are accused of etiology, but sometimes, it is idiopathic. Clinical presentation involves red, swelling, and itchy plaques. The lesions usually resolve spontaneously within 2-3 h without a trace.

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Treatment of urticaria: a clinical and mechanistic approach

Treatment of urticaria: a clinical and mechanistic approach

By Selected articles

Kaplan AP.

Urticaria can be divided into three general subtypes. Acute urticaria is defined as urticaria of relatively short duration that can be as brief as a day or two or can last up to 6 weeks. “Physical urticarias or inducible urticarias” consist of cold urticaria, cholinergic urticaria, and dermatographism as the most common, plus solar urticaria, local heat urticaria, aquagenic urticaria, vibratory urticaria/angioedema, and delayed pressure urticaria. The third subtype is chronic spontaneous urticaria (CSU) where the urticaria is present for over a minimum of 6 weeks up to many years.

Antihistamines are effective in about 50% of patients with CSU by interacting with the H1 receptor rendering it unresponsive to histamines. Omalizumab is effective in 65–80% of antihistamine-resistant patients and acts by binding IgE, thereby eliminating IgE directed to an autoantigen, downregulating IgE receptors, so that antireceptor antibodies are blocked, and ultimately leading to unresponsiveness of cutaneous mast cells and basophils. The addition of omalizumab represents a major advance because of its efficacy, easy utility, and favourable side-effect profile. Cyclosporine inhibits not only T cells but also histamine release from basophils and mast cells, has a success rate of about 70%, and is recommended third-line with care directed to potential side effects affecting blood pressure and renal function.

In conclusion, the use of antihistamines in high dosage (at least four times a day) is effective in close to half the patients with chronic spontaneous urticaria. For antihistamine resistance, the use of omalizumab has revolutionized therapy of antihistamine-resistant cases because of its efficacy and excellent side-effect profile. If the response is insufficient, cyclosporine is the next choice. Patients should be monitored regarding any adverse effects on blood pressure or renal function. All these are far safer than extended use of corticosteroid.

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Urticaria crónica

Systematic reviews of pharmacological and nonpharmacological treatments for patients with chronic urticaria: An umbrella systematic review

By Selected articles

Shi Y, Zhou S, Zheng Q, Huang Y, Hao P, Xu M, Zhang L, Xiao X, Zheng H, Li Y.

A wide range of pharmacological and nonpharmacological interventions for chronic urticaria (CU) have been evaluated in systematic reviews (SRs). We conducted an umbrella review of SRs of the effectiveness and safety of pharmacological and nonpharmacological interventions for CU.

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Terapia de sangrado

Bloodletting Therapy for Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis

By Selected articles

Yao Q, Zhang X, Mu Y, Liu Y, An Y, Zhao B.

Many trials have reported that bloodletting therapy is effective when treating chronic urticaria. There are currently no systematic reviews of bloodletting therapy for chronic urticaria.

Bloodletting therapy might be an effective and safe treatment for chronic urticaria, but the evidence is scarce. More high quality trials are needed in the future.

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Urticaria cronica angioedema

Cost-Utility of Routine Testing in Chronic Urticaria/Angioedema: A Cohort Study

By Selected articles

Carrillo-Martin I, Dudgeon MG, Chamorro-Pareja N, Haehn DA, Rivera-Valenzuela MG, Spaulding AC, Heckman MG, Diehl NN, Irizarry-Alvarado JM, Helmi H, Gonzalez-Estrada A

Chronic urticaria/angioedema (CUA) guidelines recommend limiting tests to diagnose and assess prognosis, activity, and severity. Routine testing in CUA might substantially increase cost of disease without benefiting outcome.

In CUA, tests rarely uncover underlying conditions or lead to changes in management and outcome, but they substantially increase the costs generated by the disease. Adherence to current recommendations to limit testing might help in reducing the financial burden of CUA and improve delivery of care.

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