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urticaria archivos - Bilastina

Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens

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Mohamed H. Shamji, Janice A. Layhadi, Hanisah Sharif, Martin Penagos, Stephen R. Durham

J Allergy Clin Immunol Pract. 2021 Mar 27:S2213-2198(21)00363-9. doi: 10.1016/j.jaip.2021.03.029.

Patients with IgE-mediated rhinoconjunctivitis and/or bronchial asthma who do not respond to symptomatic treatment or have severe side effects are often recommended allergen immunotherapy. Prolonged treatment has shown long-term benefits in patients with moderate to severe allergic rhinitis. The long-term efficacy from allergen immunotherapy represents a decrease in IgE activation of mast cells and tissue eosinophilia, which is accompanied by early induction of regulatory T cells, immune deviation in favor of TH1 responses, and induction of local and systemic IgG and IgA antibodies. These antibodies, whose primary function is to be protective, can prevent the formation of allergen-IgE complex and subsequent activation of the mast cells and TH2 facilitated by IgE.

Some studies demonstrate the importance of innate responses mediated by type 2 dendritic cells and innate lymphoid cells in allergic inflammation. Type 2 dendritic cells and lymphoid cells are regulated by cytokines derived from the respiratory epithelium. New subsets of regulatory cells induced by immunotherapy include:

  • IL-35-producing regulatory T cells,
  • Regulatory B cells,
  • A subset of T follicular regulatory cells, and
  • IL-10-producing group 2 innate lymphoid cells.

These regulatory cells may represent biomarkers that will predict the clinical response to immunotherapy and evaluate the efficacy, safety, and long-term tolerance.

More studies are required to identify candidate biomarkers as a routine immune-monitoring tool for assessing allergen immunotherapy response.

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Chronic Spontaneous Urticaria

The Pathogenesis of Chronic Spontaneous Urticaria: The Role of Infiltrating Cells

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Ana M. Giménez-Arnau, Laurence DeMontojoye, Riccardo Asero, Massimo Cugno, Kanokvalai Kulthanan, Yuhki Yanase, Michihiro Hide, Allen P. Kaplan

J Allergy Clin Immunol Pract. 2021 Apr 3:S2213-2198(21)00374-3. doi: 10.1016/j.jaip.2021.03.033. Epub ahead of print.

In chronic spontaneous urticaria, cutaneous mast cells are activated to initiate the process. There are different triggers, including the hypothesis that it is an autoimmune disease not driven by exposure to an exogenous agent.

It is characterized by a perivascular non-necrotizing cellular infiltrate around small venules of the skin. These infiltrates include CD4+ lymphocytes, Th2 and Th1 subtypes, Th17 cell-derived cytokines, neutrophils, eosinophils, basophils and monocytes, which contribute to the pathogenesis and responsiveness to steroid

This review focuses on each cell’s contribution to the inflammatory response and a view toward developing therapeutic options.

Immunohistochemistry can help reveal the function of each cell within the perivenular infiltrate. Rituximab efficacy is probably due to the prevention of autoantibody synthesis. Corticosteroids inhibit the function of T lymphocytes and eosinophils and prevent egress of most cell types from the bloodstream into tissues.

In the future, there may be studies that include drugs with increasing specificity in the course of urticaria, such as secukinumab (targets IL-17), dupilumab (targets TH-2 dependent cytokines, IL-4 and IL-3), mepolizumab, reslizumab and benralizumab (target TH2 and eosinophil-dependent cytokines), avdoralimab (complement C5a receptor) and lirentelimab (targets Siglec-8 on the surface of mast cells and eosinophils).

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Biologics for the Use in Chronic Spontaneous Urticaria: When and Which

By | Artículos seleccionados, Selected articles

Marcus Maurer, David A. Khan, Daniel Elieh Ali Komi, Allen P. Kaplan

J Allergy Clin Immunol Pract . 2021 Mar;9(3):1067-1078. doi: 10.1016/j.jaip.2020.11.043.

Urticaria treatment has evolved a lot during the past decade. Current guidelines for the treatment of chronic spontaneous urticaria recommend the use of omalizumab, an IgE-targeted biologic. IgE has high-affinity to the receptor FcεRI, and degranulate skin mast cells, which are responsible for the development of signs and symptoms of urticaria, itchy wheals and angioedema. This study aims to review the existing understanding of the pathogenesis of chronic urticaria and its autoimmune endotypes.

Omalizumab is the only licensed biologic for use in chronic urticaria from 12 years old age. It is recommended as the third step of the therapy in patients who have failed standard or high-dose second-generation antihistamines and is generally well tolerated. Omalizumab has multiple potential mechanisms of action in chronic urticaria, with effects on mast cells and basophils, reducing mediators’ release and decreasing FcεRI expression. It has been approved for chronic urticaria at doses of 150 or 300 mg every 4 weeks. Poor responders may benefit from shortening the dosing interval to every 2 or 3 weeks or by adjunctive therapy with cyclosporine 3 mg/kg/day for 4 months each.

Some other biologic drugs used as off-label in chronic urticaria include dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. New biologics under development aim to reduce mast cell activation by blocking activating pathways or engaging inhibitory receptors or mast cell numbers. These include ligelizumab and GI-301, avdoralimab, tezepelumab, lirentelimab, LY3454738, and CDX-0159 at different stages of development.

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Differences in gut microbiota between allergic rhinitis, atopic dermatitis, and skin urticaria: A pilot study

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Yu-Jih Su, Sheng-Dean Luo, Chung-Yuan, Ho-Chang Kuo

Medicine (Baltimore) . 2021 Mar 5;100(9):e25091. doi: 10.1097/MD.0000000000025091.

Allergic rhinitis and urticaria prevalence are increasing. The intestinal flora or microbiota may influence their pathogeneses. This study aimed to compare differences between the gut microbiota of people with atopic dermatitis, allergic rhinitis, and chronic urticaria.

The study included 19 participants with eczema, nine with urticaria, and 11 with allergic rhinitis. The microbiota was compared by examining participants’ fecal samples using 16S ribosomal ribonucleic acid amplicon sequencing and bioinformatics and statistical analysis.

All three groups of patients had similar clinical data. The microbiota was substantially different between participants with atopic dermatitis, allergic rhinitis, and chronic urticaria, demonstrating gut-skin and gut-nose axes. Bacteroidales species were found in skin allergies more than in allergic rhinitis. This may represent a link between gut flora and skin allergy because gut flora colonies differ significantly between them.

In conclusion, different conditions have heterogeneous microbiota. Bacteroidales species could represent a link between gut flora and skin allergy, with Bacteroids Plebeius DSM 17135 being significantly associated with urticaria. Ruminococcaceae is also associated with allergic diseases.

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Exaggerated neurophysiological responses to stressor in patients with chronic spontaneous urticaria

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Engel-Yeger B, Maurer M, Hawro T, Zubedat S, Avital A, Kessel A

Clin Exp Allergy. 2021 Feb 22. doi: 10.1111/cea.13854. Versión digital previa a la impresión.

Chronic spontaneous urticaria impacts the quality of life and emotional well-being of people suffering from it. People with chronic spontaneous urticaria have increased emotional distress, anxiety, depression, somatoform disorders, and stress, which correlates with the activity of urticaria.

People with chronic spontaneous urticaria may be more susceptible to stressors and thus have increased stress responses. Stress responses may lead to the secretion of neuropeptides from sensory skin nerves, interacting with mast cells and releasing histamine, causing chronic spontaneous urticaria attacks.

This study compared the stress responses to acoustic startle and stress levels between 47 people with chronic spontaneous urticaria and 56 healthy volunteers. Stress levels were evaluated with the Perceived Stress Scale.

The stressor exposure session was three minutes long. Participants were exposed to 40 randomly spaced auditory startle stimuli. Responses to the stimuli were measured by electromyography assessment of the contraction amplitude of the orbicularis oculi muscle for each startle stimulus and the number of eye blinks.

People with chronic spontaneous urticaria had stronger responses to acoustic startles with high mean electromyography values and a higher number of eye blinks than healthy volunteers. People with urticaria also had longer stress responses and stress levels, as assessed by the Perceived Stress Scale.

In conclusion, people with urticaria have increased stress responses using objective and subjective measures. Underlying neuroimmune mechanisms should be studied further, as it is possible that stress predisposes to chronic spontaneous urticaria and that chronic spontaneous urticaria increases stress, forming a disease amplification loop.

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Predictors of treatment response in chronic spontaneous urticaria

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Jie Shen Fok, Pavel Kolkhir, Martin K. Church, Marcus Ma

Allergy . 2021 Feb 4. doi: 10.1111/all.14757. Online ahead of print.

Chronic spontaneous urticaria consists of wheals, angioedema, or both for more than six weeks. Patients with chronic urticaria have an impaired quality of life that impacts their relationships, work, and sleep. Existing treatment guidelines recommend a treatment escalation from second-generation H1-antihistamines to omalizumab and cyclosporine until complete response.

This review aimed to evaluate the predictors of response and nonresponse to these treatments in chronic spontaneous urticaria.

A systematic search was executed using the PubMed/MEDLINE database, and 73 studies were included. Different levels of evidence were categorized as strong (robust predictors), weak (emerging predictors), or not associated.

High disease activity, high C-reactive protein levels, and D-dimer are robust predictors of a poor or no response to H1-antihistamines. Low serum levels of total IgE may predict omalizumab response. Cyclosporine response may be predicted by a positive basophil histamine release assay, while low total IgE is an emerging predictor.

In conclusion, there are clinical and biochemical predictors of nonresponse to H1-antihistamines and omalizumab, as well as predictors of response to cyclosporine. These predictors can help specialists counsel patients and prioritize patients at risk of nonresponse to be assessed and switched to more effective treatments.

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The usage, quality and relevance of information and communications technologies in patients with chronic urticaria:

The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study

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Marcus Maurera, et al.

World Allergy Organ J . 2020 Oct 30;13(11):100475. doi:10.1016/j.waojou.2020.100475. eCollection 2020 Nov.

Chronic urticaria is characterized by itchy wheals, angioedema, or both for six weeks or more. It impacts patients’ physical and emotional quality of life. People with chronic urticaria and other chronic conditions are information seekers from information and communications technologies (ICTs). This study aimed to evaluate the frequency of use and preference of ICTs from chronic urticaria patients.

This was a cross-sectional study that included 1800 patients with chronic spontaneous urticaria or chronic inducible urticaria, over 12 years old, recruited from primary healthcare centers, university hospitals, or specialized clinics UCARE (Urticaria Centers of Reference and Excellence) in 16 countries. Patients were requested to complete a 23-item questionnaire with questions about the use of ICT, including the type, frequency, preference, and quality. Answers were registered in a database. ICTs were then categorized into three groups: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, blogs or forums; and many-to-many: Instagram, Twitter, Facebook, and LinkedIn.

Globally, most chronic urticaria had access to ICT platforms (99.6%) and internet access (96.7%). One-to-one ICT platforms were used most often (85.4%), followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The use of ICT platforms increased with patient education. One-to-many was preferred for general health information and chronic urticaria information. For chronic urticaria specific information, 3 in every 4 patients used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in five patients didn’t use any form of ICT. The quality of information was rated as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) compared to other categories.

In conclusion, the use of information and communications technologies for health and urticaria specific information is very high in all countries, with web browsers being the preferred platform.

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Cold urticaria what we know and what we do not know

Cold urticaria what we know and what we do not know

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Natalya Maltseva, et al.

Allergy . 2020 Nov 28. doi: 10.1111/all.14674. Online ahead of print.

Cold urticaria is a subtype of chronic inducible urticaria, characterized by wheals and/or angioedema that occur after cold exposure. It constitutes a challenging clinical problem due to the risk of cold-induced anaphylaxis, its long duration, and diagnostic difficulties with atypical cold urticaria. The classification of cold urticaria includes typical and atypical subtypes. Recent studies and guidelines have progressed its understanding and management.

It is thought to involve the formation of autoallergens and IgE to these autoallergens induced by cold, which provoke a release of mediators from skin mast cells.

It is known that cold-induced wheals develop on rewarming and resolve within an hour and that anaphylaxis can occur. Its diagnosis is based on the patient’s history and cold stimulation testing. Other tests include searching for underlying infections, to be done if the patient has a relevant record. The management of cold urticaria includes avoiding cold, using nonsedating antihistamines, and, if needed, omalizumab.

Questions unanswered include cold urticaria epidemiology, underlying pathomechanisms, clinical heterogeneity, and treatment outcomes.

An international multicenter observational prospective study COLD-CE is being conducted to globally improve the understanding of cold urticaria and cold anaphylaxis, with their pathophysiology representing a research priority. Oropharyngeal angioedema and/or cold anaphylaxis in cold urticaria require further studies of innovative agents. The use of genomic, postgenomic, and machine learning approaches is the next frontier in research leading to novel therapeutic targets.

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urticaria y antihistaminicos H1

Current and emerging pharmacotherapy for chronic spontaneous urticaria: a focus on nonbiological therapeutics

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Kam Lun Hon, Joyce T. S. Li, Alexander K.C. Leung, Vivian Lee

Expert Opin Pharmacother. 2020 Sep 29. doi: 10.1080/14656566.2020.1829593. Online ahead of print.

Urticaria is characterized by pruritic wheals of the skin’s superficial layers, which occurs for six weeks or longer, with no apparent cause. It is a condition that reduces the quality of life of the patient and may have a significant economic and social burden. The objective of this revision was to review the guidelines for urticaria management.

According to the joint initiative of the EU-founded network of excellence, the Global Allergy and Asthma European Network, the European Academy of Allergology and Clinical Immunology, the World Allergy Organization, and the European Dermatology Forum, management of urticaria should be done in a stepwise manner. Second-generation H1-antihistamines are considered first-line treatment. Whenever symptoms are not adequately controlled, treatment should follow the algorithm. This algorithm includes an increase of the dose of second-generation H1-antihistamines, alongside first-generation H1-antihistamines, H2 antagonists, omalizumab, ciclosporin A, or short-term corticosteroids if needed. New treatments on development include spleen tyrosine kinase inhibitor, Bruton tyrosine kinase inhibitor, prostaglandin D2 receptor inhibitor, H4-antihistamines, and biologics. Alternative agents include leukotriene receptor antagonists, anticoagulant and antifibrinolytic agents, antidepressants, vitamin D, and other anti-inflammatory or immune-suppressing agents.

According to the authors, second-generation H1-antihistamines should always be considered the first-line therapeutic option for urticaria management. For those who do not respond to a higher dose of H1-antihistamines, guidelines recommend adding omalizumab. Well-designed trials are required to draw clear conclusions.

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urticaria and covid

Management of urticaria in COVID-19 patients: A systematic review

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Eyad Abuelgasim, Ann Christine Modaragamage Dona, Rajan Singh Sondh, Amer Harky

Dermatol Ther. 2020 Sep 28;e14328. doi: 10.1111/dth.14328. Online ahead of print.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), has resulted in an increased healthcare burden, with different symptoms manifesting in other patients. The evidence of skin manifestations similar to urticaria is also growing. The objective of this systematic revision was to review the current literature on urticaria in COVID-19 patients.

According to PRISMA guidelines, investigators carried out an extensive literature search in Medline, EMBASE, Scopus, Cochrane, and Google Scholar, using “COVID-19”, “Coronavirus”, “SARS-CoV-2”, “urticaria”, “angioedema” and “skin rash” until August 2020. Articles related to urticaria and/or angioedema due to COVID-19 and its management and outcome were included.

From the 169 articles returned by the search, 25 of them met the inclusion criteria. These articles were case reports, which related 26 patients infected with SARS-CoV-2 with symptoms such as urticaria and/or angioedema. Most patients (69%, n = 16) were over 50 years old. Treatment with antihistamines and/or steroids resolved the symptoms in different time frames, from less than 24 hours to up to 2 weeks. There was no report of recurrent cases of urticaria or non-responsiveness to treatment.

Patients infected with SARS-CoV-2 who develop urticaria symptoms should be managed with antihistamines. The use of a low prednisolone dose should be evaluated according to each patient in the shortest duration possible until symptoms are controlled.

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Cansancio, urticaria y mujeres

Fatigue is Common and Predicted by Female Gender and Sleep Disturbance in Patients with Chronic Spontaneous Urticaria

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Kemal Erol, Sule Ketenci Ertas, Ragıp Ertas

J Allergy Clin Immunol Pract . 2020 Aug 25;S2213-2198(20)30836-9. doi: 10.1016/j.jaip.2020.08.020. Online ahead of print.

Chronic spontaneous urticaria is a chronic disease characterized by wheals and pruritus and/or angioedema. Most urticaria patients are women who have their quality of life reduced due to the impact of the disease on daily life and sleep quality. Fatigue is a common symptom in urticaria. This study’s objective was to assess fatigue and how it affects people with chronic spontaneous urticaria compared to healthy people.

This study included 103 patients with chronic spontaneous urticaria and 35 age and gender-matched healthy controls. They were assessed for fatigue with the Fatigue Severity Scale (FSS) and VAS-Fatigue. Duration, activity, and control of disease, as well as anxiety, depression, and quality of life, were also evaluated.

No significant associations were seen in disease activity, disease control scores, FSS, positivity for anti-nuclear antibodies, and IgE levels between fatigued and non-fatigued patients with urticaria. Fatigued patients had significantly higher CRP levels (p=0,009). Also of note was the significant correlation between total FSS score and chronic urticaria quality of life in patients with chronic spontaneous urticaria, where women with urticaria and with disturbed sleep complained of fatigue.

Women with chronic spontaneous urticaria commonly experience fatigue, which is an important symptom that negatively affects their quality of life.

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Urticaria (angioedema) and COVID- 19 infection

Urticaria (angioedema) and COVID- 19 infection

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Mojgan Najafzadeh, Fanila Shahzad, Nader Ghaderi, Kaveh Ansari, Badie Jacob, Andrew Wright

J Eur Acad Dermatol Venereol . 2020 Jun 11;10.1111/jdv.16721. doi:10.1111/jdv.16721. Online ahead of print.

The relationship between urticaria and COVID-19 infection has rarely been reported, however, it has been reported that in addition to the conventional respiratory symptoms, some COVID-19 patients also have skin manifestations, such as urticaria and angioedema.

This is a case study of an elderly man who first presented with generalised pruritic hives with a diameter of 1,5 to 8,0 cm, general malaise, fatigue, temperature and sore throat. He was negative for parasitic and bacterial infections, however presented low white blood cells and lymphopenia. The CT chest showed pneumonia with bilateral and subpleural areas of ground-glass opacification, consolidation affecting the lower lobes, thus confirming the diagnosis of COVID-19.

Although the relationship between urticaria and infection has rarely been reported, literature suggests that urticaria and angioedema can be induced by viral and bacterial infections. Urticaria has been associated before with Cytomegalovirus, Herpesvirus and Epstein-Barr virus. It was also found that once the viral infection was controlled, urticaria manifestations cleared up.

One study with 88 COVID-19 patients that analysed the cutaneous involvement found that 20,4 % presented with cutaneous manifestation, 8 of them developed it at disease onset, while 10 of the, developed it after hospitalisation. The cutaneous manifestations were erythematous rash, widespread urticaria and chickenpox-like vesicles.

Urticarial skin manifestations may be used as a possible diagnostic indicator in early COVID-19 stages.

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urticaria angioedema hipersensibilidad

IgM and IgA in Addition to IgG Autoantibodies against FcεRIα Are Frequent and Associated with Disease Markers of Chronic Spontaneous Urticarial

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Altrichter S, Zampeli V, Ellrich A, Zhang K, Church MK, Maurer M.

Allergy. 2020 May 23. doi: 10.1111/all.14412. Online ahead of print.

Chronic spontaneous urticaria (CSU) is a mast cell–driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. IgG-autoantibodies against the high affinity IgE-receptor, FcεRIα, contribute to the pathogenesis of autoimmune chronic spontaneous urticaria.

The objective of this study was to develop an ELISA to assess serum levels of IgG, IgM and IgA autoantibodies against FcεRIα and to explore if their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST).

Serum samples of 35 people with CSU and 52 healthy controls were tested using an ELISA for IgG, IgM and IgA autoantibodies to FcεRIα. 24 % of CSU patients had high serum levels of IgG-anti-FcεRIα compared to 6 % in healthy controls. IgM and IgA levels were positive for more than half of people with CSU, compared to 5 % in healthy controls. Elevated IgM, but not IgG nor IgA autoantibodies, were significantly more common in ASST-positive CSU patients (72 %) compared with ASST-negative patients (33 %). Also, elevated levels of IgM-anti-FcεRIα, but not of IgG or IgA against FcεRIα, were linked to low blood basophil and eosinophil counts.

In conclusion, people with CSU have increased serum levels of IgM-anti-FcεRIα which may relate to characteristics of autoimmune CSU.

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Nivel de dímero D en plasma

Efficacy and Safety of Active Vitamin D Supplementation in Chronic Spontaneous Urticaria Patients.

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Ahmed Mohamed A, Hussein MS, Salah EM, Eldemery A, Darwish MM, Ghaith DM, Attala RA, El Borolossy R.

J Dermatolog Treat. 2020 Apr 29:1-22. doi: 10.1080/09546634.2020.1762838. [Epub ahead of print]

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.

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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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