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Monthly Archives

July 2021

Cold Agglutinins and Cryoglobulins Associate with Clinical and Laboratory Parameters of Cold Urticaria

By Selected articles

Mojca Bizjak, Mitja Kosnik, Dorothea Terhorst-Molawi, Dejan Dinevski, Marcus Maurer

Front Immunol. 2021 Apr 29;12:665491. doi: 10.3389/fimmu.2021.665491. eCollection 2021

Cold urticaria is a condition characterized by wheals and/or angioedema in response to cold. It is usually diagnosed after provocation testing, and trigger thresholds measure its activity. Just as “common” urticaria, cold urticaria is also a mast-cell driven condition, where cold is an activating signal which causes a release of histamine from dermal mast cells. Cold agglutinins and cryoglobulins were designated as elements related to cold urticaria. The objective of this study was to understand the impact of cold agglutinins and cryoglobulins on the molecular level and evaluate strategies for cold urticaria.

This was a single-center prospective cohort study that included 35 participants with cold urticaria. They were analyzed for cold agglutinins and cryoglobulin, demographics, history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels.

Sixteen (46%) of the 35 participants tested positive for cold agglutinin, and 9 (27%) of 33 tested participants had a positive cryoglobulin test. There was no gender association for cryoglobulin. However, a positive cold agglutinin was mainly in female participants. Also, a positive cold agglutinin test showed a higher rate of reactions triggered by cold ambient air, immersion in cold water, and aggravated by summer humidity. These participants also had more angioedema triggered by cold foods or drinks.

Cold agglutinin serum levels correlated with erythrocyte and monocyte counts. Cryoglobulin concentrations associated with basal serum tryptase levels and cold urticaria duration.

In conclusion, this study suggests that cold agglutinins and cryoglobulins are related to the course and pathogenesis of cold urticaria. More studies are encouraged to explore mechanisms of action, treatment, and use as biomarkers.

This document is only available for registered healthcare professionals


Effects of Serum Vitamin D Levels and Vitamin D Supplementation on Urticaria: A Systematic Review and Meta-Analysis

By Selected articles

Yajia Li, Ziqin Cao, Jia Guo, Qiangxiang Li, Juan Su

Int J Environ Res Public Health. 2021 May 5;18(9):4911. doi: 10.3390/ijerph18094911.

Urticaria is characterized by itchy wheals and/or angioedema. It is a common condition with an impact on the quality of life driven by mast cells. Numerous studies have demonstrated that serum levels of 25-hydroxyvitamin D can impact urticaria. However, the relation between vitamin D and urticaria is not well recognized. The objective of this study was to systematically synthesize the associations of vitamin D and urticaria published until March 2021.

A systematic search was done in PubMed, EMBASE, Web of Science, and Cochrane. Observational studies with the comparisons of vitamin D and people with urticaria and clinical studies were included.

A meta-analysis of 17 studies of urticaria patients compared to controls demonstrated a mean difference of -9.35 ng/mL in vitamin D, which complied with the association of urticaria with a deficiency in vitamin D. Studies with supplementation of vitamin D also demonstrated a significant reduction in clinical urticarial score in people supplemented with vitamin D.

In conclusion, people with urticaria may have a lower level of serum vitamin D, and vitamin D supplementation may reduce urticaria symptoms and exacerbations and improve quality of life due to vitamin D immunomodulatory and anti-inflammatory properties. However, more studies are needed to assess the clinical benefits and mechanisms of action of vitamin D in urticaria.

This document is only available for registered healthcare professionals


Could Histamine H1 Receptor Antagonists Be Used for Treating COVID-19?

By Selected articles

Changbo Qu, Gwenny M. Fuhler, Yihang Pan

Int J Mol Sci . 2021 May 26;22(11):5672. doi: 10.3390/ijms22115672.

The pandemic of COVID-19, caused by SARS-CoV-2, has led to extensive and long-term health issues in those affected by the disease. It is essential to identify new treatments for COVID-19 infection with a better outcome too. The objective of this review is to summarize the use of H1 receptor antagonists in SARS-CoV-2 infection.

One of the common characteristics of severe COVID-19 is unbalanced lung inflammation. Reducing lung inflammation can help improve COVID-19 clinical manifestations. H1 receptor antagonists may inhibit SARS-CoV-2 either via the H1 receptor or via the ACE2 receptor. The virus spike proteins interact with both cellular heparan sulfate and ACE2 through its receptor-binding domain, and H1-antihistamines may disrupt the interaction between heparan sulfate and spike protein, inhibiting the virus entry in the cell.

New-generation H1 receptor antagonists, such as loratadine and desloratadine, may help inhibit SARS-CoV-2 infection by reducing lung inflammation induced by histamine, as well as other inflammatory activities. These antihistamines have also been shown to exert antiviral effects when blocking H1 receptors and, therefore, to affect SARS-CoV-2 replication via the mediation of metabolism and immune responses.

In conclusion, H1 receptor antagonists are relatively inexpensive drugs, ready to use and with the capacity to improve patient outcomes due to their role in reducing inflammation and antiviral effects. They may also be attractive prophylactic candidates for lowering the risk of SARS-CoV-2 infection in the general population.

This document is only available for registered healthcare professionals


Triggers of Exacerbation in Chronic Urticaria and Recurrent Angioedema-Prevalence and Relevance

By Selected articles

Anete Sevciovic Grumach, Petra Staubach-Renz, Ricardo Cardona Villa, Susana Diez-Zuluaga, Imke Reese, William R. Lumry

J Allergy Clin Immunol Pract . 2021 Jun;9(6):2160-2168. doi: 10.1016/j.jaip.2021.04.023


The causes of urticaria vary with patients, with hives mainly characterizing most of them. Urticaria can be classified as acute or chronic according to its duration. Most patients have triggers that cause exacerbations, which should be avoided to help control the disease. This review aims to describe the factors that may trigger chronic urticaria and angioedema, highlighting its mechanisms.

The major drug groups that may trigger urticaria include nonsteroidal anti-inflammatory drugs, antibiotics (especially beta-lactams), vaccines, bupropion, antidepressants, antihypertensives, H2 antihistamines, antifungals, and H1 antihistamines. Other drugs that decrease the degradation of bradykinin (from the mast cell degranulation cascade) lead to angioedema and include angiotensin-converting enzyme inhibitors, neutral endopeptidase, and dipeptidyl peptidase-4 inhibitors, resulting in the accumulation of bradykinin, followed by localized vasodilation and then angioedema.

Food and food components may also trigger urticaria or angioedema, such as food additives and naturally occurring substances (biogenic amines and aromatic compounds).

Other triggers of angioedema without urticaria include emotional distress, physical exertion, mechanical trauma, infection, menstruation, pregnancy, medical procedures, weather changes, alcohol ingestion, and some medicinal products.

In conclusion, patients with urticaria or angioedema must know trigger factors to introduce changes in their lifestyle and an individualized approach to treatment.

This document is only available for registered healthcare professionals


Effects of pregnancy on chronic urticaria: Results of the PREG-CU UCARE study

By Selected articles

Emek Kocatürk, et al.

Allergy. 2021 May 22. doi: 10.1111/all.14950. Online ahead of print.

Chronic urticaria is an inflammatory condition characterized by wheals, angioedema, or both for more than six weeks. Women are more affected, and it is thought that sex hormones have a modulation capacity in women with urticaria. The objective of this study was to assess the evolution and characteristics of chronic urticaria during pregnancy.

PREG-CU was an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network that included 288 women with chronic urticaria who became pregnant within the last three years and completed a 47-item questionnaire.

A total of 288 pregnancies of 288 women with chronic urticaria from 13 countries were analyzed. Half of the women reported their chronic urticaria had improved, 29% reported worsening, and 20% didn’t notice changes. Urticaria exacerbations happened mainly in the first or third trimester (22,8% and 27,6%, respectively). The risk factors were: mild disease and no angioedema before pregnancy, no treatment before pregnancy, exacerbation in a previous pregnancy, treatment during pregnancy, and stress. After giving birth, 44% of the women reported no changes in the disease, 37% reported worsening, and 18% improved.

In conclusion, pregnancy impacts the course of urticaria, and counsel and management should be done on a one-to-one basis. More prospective studies are needed to assess the importance and reliability of urticaria risk factors during pregnancy.

This document is only available for registered healthcare professionals

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