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Chronic Spontaneous Urticaria archivos - Bilastina

Positive effect of Helicobacter pylori treatment on outcome of patients with chronic spontaneous urticaria

By | Artículos seleccionados, Selected articles

Mohammed Elhendawy, Maha Hagras, Shaimaa Soliman, Engi Seif Shaker

Am J Clin Pathol. 2020 Sep 17;aqaa134. doi: 10.1093/ajcp/aqaa134. Online ahead of print.

People with chronic urticaria have chronic hives, itching, and wheels that come and go for long periods. Chronic spontaneous urticaria represents 80 – 90 % of chronic urticaria cases, and the release of histamine and other inflammatory mediators from mast cells and basophils may be immunoglobulin E (IgE)–mediated or non-IgE-mediated. Helicobacter pylori is a gram-negative bacterium with a high prevalence worldwide, and that persistently colonizes the stomach. Its presence is associated with an increased risk of peptic ulcer and gastric cancer. The association between Helicobacter pylori and chronic spontaneous urticaria is controversial. This study’s objective was to assess the relationship between Helicobacter pylori eradication therapy and chronic spontaneous urticaria remission.

This was a randomized, double-blind, placebo-controlled pilot study that included 72 patients with urticaria. From these, 27 were positive for Helicobacter pylori stool antigen and PCR in gastric biopsy and were randomly assigned to receive anti-Helicobacter pylori treatment or placebo.

Participants with Helicobacter pylori had significantly lower hemoglobin concentrations with microcytic hypochromic anemia and a significantly higher occurrence of dyspepsia symptoms. All Helicobacter pylori patients (except 2) had significant improvement of the urticaria itching and red wheals after two weeks of therapy compared to placebo.

This study showed an association between chronic spontaneous urticaria and the presence of Helicobacter pylori in the gastric tissue. Patients with urticaria who do not respond to usual chronic urticaria treatment should be tested for Helicobacter pylori as therapy of Helicobacter pylori showed to improve the symptoms of chronic spontaneous urticaria.

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Urticaria Crónica Espontánea

Targeted Therapy for Chronic Spontaneous Urticaria: Rationale and Recent Progress

By | Artículos seleccionados, Selected articles

Ana M. Giménez‑Arnau, Andaç Salman

Drugs . 2020 Aug 28. doi: 10.1007/s40265-020-01387-9. Online ahead of print.

Chronic spontaneous urticaria is characterized by wheals, angioedema, or both for at least 6 weeks and can last for a long time, up to 5 years. The effects of chronic spontaneous urticaria on quality of life are comparable to psoriasis, atopic dermatitis, or even ischemic heart disease.

Antihistamines continue to be the first choice for treatment of urticaria, however rates of response are low (ranging from 38.6% in standard doses to 63.2% in higher doses), some patients don’t experience a complete of symptoms. The use of omalizumab has shown a major advance in treating patients with chronic spontaneous urticaria, however, there is a subgroup of patients who have a partial or even lack of response to omalizumab.

Some of the upcoming targeted therapies for chronic spontaneous urticaria include:

  1. anti-IgE antibodies, such as ligelizumab, a monoclonal antibody directed against the Cε3 domain of IgE and which has shown a six- to ninefold greater potency in vivo compared to omalizumab; UB-221, another monoclonal antibody against IgE with up to eightfold greater affinity for free IgE, compared to omalizumab; quilizumab, a humanized monoclonal antibody directed against membrane-bound IgE.
  2. Anti-Siglec-8. Siglecs are a transmembrane family with regulatory effects on intercellular and intracellular signaling, with Siglec-8 having expression on eosinophils and mast cells.
  3. Bruton’s Tyrosine Kinase (BTK) inhibitors. BTK is a tyrosine kinase expressed in hematopoietic cells, including macrophages, mast cells and basophils. BTK inhibitors are used to treat different malignancies of B-cell origin. Ibrutinib, dasatinib, AVL-292 and CNX-774 effectively suppressed IgE-induced activation and histamine release from basophils and mast cells.
  4. Chemoattractant receptor-homologous molecule expresses on Th2 (CRTH2) inhibitors; Spleen Tyrosine Kinase (SYK) inhibitors; Anti-CD20; Anti-IL-1; Anti-IL-4/13; and Anti-IL-5.

The future treatment of chronic urticaria will probably change once potential new treatments are completely developed.

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Clinical Control of CSU with Antihistamines Allows for Tolerance of NSAID-Exacerbated Cutaneous Disease

By | Selected articles

Jorge Sánchez

J Allergy Clin Immunol Pract . 2020 Jul 14;S2213-2198(20)30700-5. doi: 10.1016/j.jaip.2020.06.057. Online ahead of print.

A great number of patients with chronic spontaneous urticaria experience exacerbations after treatment with non-steroidal anti-inflammatory drug (NSAID). Although international guidelines suggest that people with urticaria avoid NSAIDs, this is sometimes difficult. Some case reports recommend that H1-antihistamines can help prevent these exacerbations.

The objective of this study was to evaluate if H1-antihistamines can help prevent NSAID-exacerbated reactions in people with chronic spontaneous urticaria.

This was a cross-over, multi-center, and ambispective study in 3 centers in Medellín, Colombia that included 121 participants with chronic spontaneous urticaria and a history of NSAIDs exacerbations. A diagnostic challenge test without the use of antihistamines and a challenge test using antihistamines were performed using the NSAID reported in the medical record. The order in which test were performed in each participant was determined by the investigator: participants with a positive first diagnostic challenge, were subject to a second challenge using H1-antihistamines, those with a negative first challenge using H1-antihistamines, were subject to a second one without the use of H1-antihistamines, and those with a negative first diagnostic challenge or a positive first challenge using H1-antihistamines, did not undergo a second challenge. Some patients were subject to an alternative NSAID before the diagnostic challenge test or the challenge test using H1-antihistamines.

The diagnostic challenge test retrieved 96 participants testing positive, with 75 % (72 participants) tolerating the NSAID involved in the reaction when they added H1-antihistamines.

In conclusion, although NSAID may represent some restrictions for people with chronic spontaneous urticaria, the use of H1-antihistamines can help control further urticaria exacerbations due to NSAID treatment.

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Characteristics and determinants of patient burden and needs in the treatment of chronic spontaneous urticaria

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Rachel Sommer, Neuza da Silva, Anna Langenbruch, Marcus Maurer, Petra Staubach-Renz, Matthias Augustin

Eur J Dermatol. 2020 Jun 1;30(3):259-266. doi: 10.1684/ejd.2020.3763

About 1 % of the population suffers from chronic spontaneous urticaria. The highest incidence is between 30 and 40 years of age, with women being most affected. The objective of this study was to characterise the specific needs and treatment objectives in chronic spontaneous urticaria from the view of the patient.

This was a cross-sectional study that included 103 participants from 4 German outpatient dermatology clinics. The validated Patient Needs Questionnaire (PNQ) for chronic spontaneous urticaria was used to determine patient needs and potential treatment objectives. To determine the relationship between patient needs and disease burden, different scales were used: disease-specific (CU-Q2oL), skin-generic (DLQI) and health generic (EQ VAS).

Most participants were female (71,4 %), with a mean age of 43,92 ± 14,96 years. The most important treatment objective was the absence of visible skin lesions (92,3 % considered important/ very important), then to be free of itching (91,5 %) and lately the desire to be healed of all skin defects (89,5 %). All other 26 items analysed, were considered to be quite important/ very important by, at least, 30 % of the participants. In relation to patient specific needs, this were related to gender and duration of disease.

In conclusion, these data show that people with chronic spontaneous urticaria have an individual broad range of needs, enabling specialists to adapt treatment to their needs. Innovative treatments may also help increase overall benefits. Independently of the treatment, the decision should be shared to help a better management of the condition.

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Effectiveness, safety and tolerability of Bilastine 20 mg versus Levocetirizine 5 mg for the treatment of chronic spontaneous urticaria: a double-blind, parallel group, randomized controlled trial

By | Articles about Bilastine

Indrashis Podder, Anupam Das, Shouvik Ghosh, Debalina Biswas, Sujata Sengupta, Satyendra Nath Chowdhury

Dermatol Ther. 2020 Jul 2;e13946. doi: 10.1111/dth.13946. Online ahead of print.

Chronic urticaria is characterized by wheals with or without angioedema for, at least, 6 weeks. It is a debilitating condition that affects people’s quality of life. Bilastine is a novel non-sedative H1 antihistamine approved for symptomatic treatment of allergic rhinoconjunctivitis and urticaria in patients older than 12 years old.

The objective of this study was to compare the effectiveness, safety and tolerability of bilastine 20 mg with levocetirizine 5 mg in moderate-to-severe chronic spontaneous urticaria.

This was a double-blind, randomized, controlled study with two arms: bilastine 20 mg once daily (31 participants) and levocetirizine 5 mg once daily (27 participants) for 42 days. The severity of urticaria, global urticaria-induced discomfort and quality of life were evaluated with UAS7 (urticaria activity score), VAS (visual analogue scale) and DLQI (dermatology life quality index) at baseline and follow-up visits.

Primary objective was to assess the variation of the UAS7, and secondary objectives assessed changes in DLQI and VAS. Safety, tolerability and compliance were evaluated by analysis of drug-related adverse events, biochemical investigations and electrocardiogram.

Both bilastine and levocetirizine improved UAS7, DLQI and VAS at the end of treatment. Also, all parameters showed greater improvement with bilastine, but only the UAS7 revealed a significant reduction (p = 0,03). Sedation was also significantly less with bilastine (p = 0,04). Both treatments improved UAS7 and VAS significantly from day 14. No serious adverse effects were registered.

In conclusion, bilastine demonstrated a better efficacy and less sedation for chronic spontaneous urticaria when compared to levocetirizine, however similar effect on quality of life.

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Eosinopenia, in chronic spontaneous urticaria, is associated with high disease activity, autoimmunity and poor response to treatment

By | Selected articles

Pavel Kolkhir, Martin K. Church, Sabine Altrichter, Per Stahl Skov, Tomasz Hawro, Stefan Frischbutter, Martin Metz, Marcus Maurer.

(2019) The Journal of Allergy and Clinical Immunology: In Practice

Chronic spontaneous urticaria is characterized by the degranulation of skin mast cells and the influx of basophils and eosinophils to affected skin sites. Blood basopenia has been linked to severe antihistamine-resistant urticaria and type IIb autoimmunity, whereas the role of eosinophils in chronic spontaneous urticaria is largely unknown.

This study analysed the prevalence, role and relevance of eosinopenia of 1613 patients with chronic spontaneous urticaria from two centres. Peripheral blood eosinophil and basophil counts were analysed, and patient files were screened for clinical characteristics, results of laboratory tests, the autologous serum skin test, the serum-induced basophil-histamine release assay, and response to second generation H1-antihistamines and omalizumab.

Ten percent of the patients analysed had eosinopenia. This was also associated with being female, high disease activity, autologous serum skin test and basophil-histamine release assay positivity, low total IgE and high levels of C-reative protein and IgG-anti-TPO. Non-responders to treatment had even lower eosinophils compared to responders. Blood eosinophil counts correlated with basophil counts and 81% of patients with undetectable eosinophils had basopenia.

Investigators concluded that the combination of eosinopenia and basopenia is a better predictor of non-response to sgAHs than eosinopenia alone and that eosinopenia in patients with chronic spontaneous urticaria is associated with type IIb autoimmunity, high disease activity and poor response to treatment. This makes eosinophils as excellent biomarkers for the management of people with chronic urticaria.

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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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Spontaneous Urticaria

Immunological effects and potential mechanisms of action of autologous serum therapy in chronic spontaneous urticaria

By | Selected articles

Yu L, Buttgereit T, Stahl Skov P, Schmetzer O, Scheffel J, Kocatürk E, Zawar V, Magerl M, Maurer M.

The findings of this study suggest that the immunological effects of autologous serum therapy include a reduction of IgE-anti-IL24 autoantibodies, which may contribute to the pathogenesis of spontaneous chronic urticaria (CSU).

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Bilastina y anticuerpos anti-

The real-life effectiveness and safety of omalizumab updosing in patients with chronic spontaneous urticaria

By | Articles about Bilastine

Andac Salman and Elif Comert

(2019) Journal of Cutaneous Medicine and Surgery

A retrospective cohort study was conducted to investigate the effectiveness and safety of 450 mg of omalizumab in chronic spontaneous urticaria.

Omalizumab is a third-line treatment for chronic spontaneous urticaria, however there are not enough studies regarding its use in patients that are unresponsive to regular doses of omalizumab.

A total of 72 patients were included, according to their Urticaria Activity Score over 7 days and the Urticaria Control Test and divided in two groups. Group 1 (n=59) included those showing a complete response to omalizumab 300 mg and group 2 (n=13) included those who received at least 3 doses of omalizumab 450 mg between 2016 and 2018.

The mean Urticaria Activity Score over 7 days decreased from 18,6 to 5,1 and the mean Urticaria Control Test score increase from 8,6 to 12 in group 2 participants after a mean 4,3 courses of omalizumab 450 mg. Of all 13 participants from group 2, 6 of them had a complete response, and 3 a good disease control. Those whose response to treatment was lower had low baseline total IgE levels (<43 IU/mL).

In conclusion, this team demonstrated that higher doses of omalizumab are effective and safe in patients with chronic spontaneous urticaria that is unresponsive to omalizumab 300 mg. Also, they predict that lower baseline total IgE levels might be related to a nonresponse to omalizumab and the need for higher doses.

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Urticaria Espontánea Crónica

Tumor necrosis factor-alpha and Fas/Fas ligand signaling pathways in chronic spontaneous urticaria

By | Selected articles
Grzanka R, Damasiewicz-Bodzek A, Kasperska-Zajac A.

Tumor necrosis factor-alpha (TNF-a) is a key inflammatory and apoptotic mediator in urticaria. However, its role is still unclear in the apoptosis-inducing pathways in chronic spontaneous urticaria.

A group of people with chronic spontaneous urticaria and healthy people had their circulating concentrations of TNF-a, soluble TNF-a receptor types 1 and 2 and soluble Fas and Fas Ligand measured using enzyme-linked immunosorbent assay.

TNF-a and soluble TNF-a receptor types 1 and 2 concentrations were significantly higher in people with moderate-to-severe chronic spontaneous urticaria than healthy people. No significant differences were found between people with mild urticaria and healthy people. There were no differences observed in Fas and Fas Ligand concentrations in all participants.

In conclusion, chronic spontaneous urticaria is associated with the activation of the TNF-a/receptors signalling pathway marked by increased circulating concentrations of TNF-a and soluble TNF-a receptor types 1 and 2. In contrast, the circulating soluble Fas/Fas Ligand system is not up-regulated in chronic urticaria and does not seem to be an useful marker for the disease.

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