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urticaria

urticaria and covid

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

By Artículos seleccionados, Selected articles

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

By Artículos seleccionados, Selected articles

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.

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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

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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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Diagnosis and treatment of urticaria in primary care

Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020.

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Maurer M, Eyerich K, Eyerich S, Ferrer M, Gutermuth J, Hartmann K, Jakob T, Kapp A, Kolkhir P, Larenas-Linnemann D, Park HS, Pejler G, Sánchez-Borges M, Schäkel K, Simon D, Simon HU, Weller K, Zuberbier T, Metz M.

Int Arch Allergy Immunol. 2020 Mar 30:1-13. doi: 10.1159/000507218. [Epub ahead of print] Review.

Chronic urticaria is a heterogeneous persistent, severely debilitating and often poorly controlled disease. Recent studies have shown that the prevalence of CU and its sub forms may be more heterogeneous than previously thought.

This update on chronic urticaria focuses on its prevalence and pathogenesis, the expanding spectrum of patient-reported outcome measures for assessing disease activity, impact and control, as well as future treatment options.

Chronic urticaria is a mast cell-driven disease which presents with transient wheals (hives), angioedema, or both, without any definite triggers and reoccurrence of signs and symptoms for more than six weeks. It is common in both children and adults; its prevalence is increasing with substantial differences across geographical regions.

The objective of treatment in chronic urticaria is complete disease control with absence of signs and symptoms, as well as normalization of quality of life. Specialists can monitor by using sets of patient-reported outcome measures. Antihistamines and omalizumab are the only currently licensed treatments for chronic urticaria. Some inhibit the effects of signals that drive mast cells activation and accumulation, others inhibit intracellular pathways of mast cells activation and degranulation, or silence mast cells by binding to inhibitory receptors.

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enfermedades de la piel

The role of eosinophils in chronic spontaneous urticaria

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Altrichter S, Frischbutter S, Fok JS, Kolkhir P, Jiao Q, Skov PS, Metz M, Church MK, Maurer M.

J Allergy Clin Immunol. 2020 Mar 26. pii: S0091-6749(20)30406-1. doi: 10.1016/j.jaci.2020.03.005. [Epub ahead of print]

Chronic spontaneous urticaria is a mast-cell driven skin disease characterized by the recurrence of transient wheals, angioedema or both for more than 6 weeks. Recent studies have suggested that eosinophils may also have a major role in symptomatology. In urticaria, it is usually observed a peripheral blood eosinopenia, opposed to other allergic and inflammatory conditions. Histological studies have shown the presence of eosinophils and eosinophil granules in urticaria lesions. They may enhance urticaria in three ways: first, eosinophil-derived stem cell factor (SCF) promotes the recruitment and local maturation of mast cells in the tissues. Second, eosinophil proteins, such as major basic protein, eosinophil cationic protein and eosinophil peroxidase can provoke mast cell degranulation. And third, activated eosinophils also express tissue factor, the main initiator of the coagulation cascade leading to thrombin formation. Eosinophil infiltration may contribute to tissue edema of skin in urticaria but can also, together with increased mast cells, prime the skin for further healing.

Treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL5 humanized antibodies mepolizumab, reslizumab and benralizumab, have shown to reduce chronic spontaneous urticaria.

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Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria.

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Asero R, Marzano AV, Ferrucci S, Lorini M, Carbonelli V, Cugno M.

Clin Exp Immunol. 2020 Mar 2. doi: 10.1111/cei.13428. [Epub ahead of print]

Chronic spontaneous urticaria (CSU) is the recurrent manifestation of wheals sometimes associated with angioedema for more than 6 weeks. It is a usual and potentially disabling disease. Its pathogenesis shows a complex and unclear connection between immunoglobulin G (IgG) and immunoglobulin E (IgE)-mediated autoimmunity, which leads to mast cell and basophil degranulation and formation of wheals.

The aim of this study was to assess the IgG and IgE reactivity to autoantigens in people with chronic spontaneous urticaria and to evaluate its effects on response to the anti-IgE monoclonal antibody omalizumab.

The study included 20 participants who underwent omalizumab treatment (300 g /month). Urticaria activity score 7 (UAS7) was registered at baseline and 1, 3 and 4 months after treatment initiation to categorize early-, late- or non-responders. At baseline, sera from the 20 participants and 20 controls were tested for IgE and IgG autoantibodies to high- and low-affinity IgE receptors, tissue factor and thyroglobulin by ELISA. Antibody levels were compared with those of controls and analysed according to response.

There were 18 omalizumab responders (11 early and 7 late) and 2 non-responders. More than half of the participants had contemporary IgE and IgG to at least one of the four autoantigens. Late responders had higher levels of anti-TF IgG and IgE. 25% of the participants had levels of anti-high and low affinity IgE receptors (anti-FcεRI IgE), which suggests that it could be a novel auto-allergen in chronic spontaneous urticaria.

In conclusion, autoimmune responses sustained by both IgE and IgG antibody classes were detected in more than half of the participants with chronic spontaneous urticaria. Such autoimmune responses may co-exist and possibly influence the clinical response to anti-IgE therapy, especially in late responders to omalizumab.

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Identification of antigenic epitopes of thyroperoxidase, thyroglobulin and interleukin-24. Exploration of cross-reactivity with environmental allergens and possible role in urticaria and hypothyroidism.

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Sánchez A, Cardona R, Munera M, Sánchez J.

Immunol Lett. 2020 Apr;220:71-78. doi: 10.1016/j.imlet.2020.02.003. Epub 2020 Feb 3.

Chronic spontaneous urticaria is characterized by hives and angioedema that significantly affects quality of life. People with urticaria have higher self-reactive autoantibodies IgE and IgG than healthy people. Other proteins implicated in the pathogenesis of urticaria include thyroperoxidase (TPO), interleukin 24 (IL24) and thyroglobulin (Tg). The reason why these proteins are recognized by specific autoantibodies in people with urticaria is unknown.

The aim of this study was to compare the sequences of TPO, Tg and IL24 with some prevalent allergens through in silico analysis.

The amino acid sequences of IL24, TPO and Tg were compared between them and with 22 environmental allergens. To explore the degree of protein identity and cover, researchers carried out phylogenetic studies and multiple pairing. Proteins without 3D structure reported in the database were modelled and compared by homology. Residues conserved and accessible to the solvent were located in the 3D model to identify possible areas of cross-reactivity and antigen binding.

Five epitopes for TPO, six for IL24 and six for Tg were predicted with the 3D model built. The amino acid sequences of allergens from different sources (Dermatophagoides pteronyssinus, Blomia tropicalis, Betula verrucosa, Cynodon dactylon, Aspergillus fumigatus, Canis domesticus, Felis domesticus) were also compared with the human proteins. The cover and alignments between allergens and human proteins were low.

In conclusion, there are possible linear and conformational epitopes of TPo, Tg and IL24 that can be the target of IgE and IgG binding in patients with urticaria. These epitopes aren’t found in common allergens, which indicates that autoreactivity to the human proteins is not through cross-reactivity.

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Urticaria

Clinically significant differences in patient-reported outcomes evaluations in chronic spontaneous urticaria.

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Baiardini I, Canonica GW, La Grutta S, Braido F.

Curr Opin Allergy Clin Immunol. 2020 Feb 18. doi: 10.1097/ACI.0000000000000636. [Epub ahead of print]

Chronic spontaneous urticaria is a common skin disorder that affects up to 1% of the world population, with more women affected. Its symptoms include repeated occurrence of itchy wheals, angioedema or both, for over 6 weeks. The objective of this review was to highlight the conceptual and practical knowledge for interpreting score changes in patient-reported outcomes (PROs) that have been validated for chronic spontaneous urticaria.

Guidelines recommend assessing PROs as Health-Related Quality of Life, disease activity and disease control to detect the impact of urticaria and the overall treatment effect. In order to have this, it is fundamental to determine the minimal important difference (MID) to evaluate if changes in questionnaire scores represent a perceived improvement or deterioration for patients. MID are collected into two categories, distribution-based and anchor-based.

For most chronic spontaneous urticaria questionnaires, a MID has been defined according to the results of various approaches. The majority of studies analysed in this review used anchor-based methods. The available information regarding MIDs across validated tools for people with chronic spontaneous urticaria helps to interpret measurement scores and allows the implementation of PROs in routine practices.

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optimizacion evaluacion urticaria

Optimizing Value in the Evaluation of Chronic Spontaneous Urticaria: A Cost-effectiveness Analysis

By Artículos seleccionados, Selected articles

Shaker M, Oppenheimer J, Wallace D, Lang DM, Rambasek T, Dykewicz M, Greenhawt M.

J Allergy Clin Immunol Pract. 2019 Nov 18. pii: S2213-2198(19)30938-9. doi: 10.1016/j.jaip.2019.11.004. [Epub ahead of print]

Chronic spontaneous urticaria can occur in both children and adults, however it is more common in adults, affecting approximately 1% of the population. It usually has an impact in quality of life, sleep and anxiety.

The aim of this study was to assess the cost-effectiveness of routine laboratory testing for secondary causes of chronic spontaneous urticaria.

Patients with more than 20 years old, over a 10-year time horizon, were randomized to receive screening laboratory testing or a no-testing approach. Laboratory results were derived from previously published retrospective studies of patients with chronic spontaneous urticaria. Cost-effectiveness was evaluated at a Willingness to Pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY) using the incremental cost-effectiveness ratio (ICER) in people with untreated urticaria, and patients treated with antihistamines, cyclosporine, or omalizumab.

Average laboratory costs per simulated urticaria patient were $572.97, with only 0.16% (SD, 3.99%) of tests resulting in improved clinical outcomes. Testing costs per laboratory-associated positive outcome were $358,052 (no therapy), $357,576 (antihistamine therapy), $354,115 (cyclosporine), and $262,121 (omalizumab). Screening tests were not cost effective, with ICERs of $856,905 (no therapy), $855,764 (antihistamine therapy), $847,483 (cyclosporine), and $627,318 (omalizumab). In the omalizumab-treated subgroup, testing could be cost-effective below $220 or if it resulted in a 0.73% rate of CSU resolution. From a simulated US population perspective, nation-wide screening costs could reach $941,750,741 – $1,833,501,483.

This study concluded that the likelihood of clinical improvement from laboratory testing is very low, and that testing is not cost-effective in people with urticaria. Therefore, it is not recommended to routinely perform laboratory testing in urticaria patients with normal clinical and physical evaluations.

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urticaria angioedema hipersensibilidad

Urticaria, angioedema, and type I hypersensitivity reactions associated with fibrinolytic agents

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Duangmee K, Boonmuang P, Santimaleeworagun W, Prasitdumrong H.

Several clinical trials of fibrinolytic agents have reported the occurrence of allergic reactions, in addition to hemorrhage. These reactions might worsen patient outcomes, especially by causing life-threatening type I hypersensitivity reactions, including anaphylaxis; however, there is a scarcity of data in this regard. This study described and characterized patients with urticaria, angioedema and type I hypersensitivity reactions caused by fibrinolytic agents.

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urticaria cronica grave

Severe CSU and activation of the coagulation/fibrinolysis system: clinical aspects

By Selected articles

Asero R.

Eur Ann Allergy Clin Immunol. 2019 Oct 8. doi: 10.23822/EurAnnACI.1764-1489.109. [Epub ahead of print]

This study aimed at comparing patients with severe urticaria and not showing elevated D-dimer plasma levels. It was a real life, cross-sectional study that included 132 adult urticaria patients and results showed identical numbers of patients with elevated and normal D-dimer plasma levels.

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