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Selected articles

Anxiety and depression risk in patients with allergic rhinitis: a systematic review and meta-analysis

By | Artículos seleccionados, New, Selected articles

J. Rodrigues, F. Franco-Pego, B. Sousa-Pinto, J. Bousquet, K. Raemdonck, R. Va

Rhinology. 2021 Aug 1;59(4):360-373. doi: 10.4193/Rhin21.087.

More than 400 million people suffer from allergic rhinitis worldwide. In Europe, its prevalence is around 25%, higher in urban areas. Although allergic rhinitis is not a life-threatening condition, it affects health and well-being (disruption of sleeping patterns, cognitive and performance impairment, decreased quality of life, and work/school performance). It may also be associated with a higher risk for psychiatric diseases, such as depression and anxiety.

This systematic review and meta-analysis aimed to quantify the relationship between allergic rhinitis and depression and anxiety.

An electronic search for observational studies that evaluated the relationship between allergic rhinitis and depression and anxiety was conducted. The association was quantified by random-effects meta-analysis, with an estimation of the pooled odds ratio.

Twenty-four studies were included (23 evaluated depression and 11 anxiety). Of these, 12 have odds ratio values from multivariable regression models and were included.

Allergic rhinitis was associated with higher odds of depression and anxiety.

In conclusion, allergic rhinitis seems to be related to a high risk of depression and anxiety; however, more studies are needed.

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Autoimmune chronic spontaneous urticaria detection with IgG anti-TPO and total IgE

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Pavel Kolkhir, Elena Kovalkova, Anton Chernov, Inna Danilycheva, Karoline Krause, Merle Sauer, Andrey Shulzhenko, Daria Fomina, Marcus Maurer

J Allergy Clin Immunol Pract . 2021 Aug 4;S2213-2198(21)00884-9. doi: 10.1016/j.jaip.2021.07.043. Online ahead of print.

Common spontaneous urticaria (CSU) is a common skin condition driven by mast cells and characterized by the development of wheals, angioedema, or both for more than six weeks. Recently, studies have demonstrated the existence of two endotypes on the pathogenesis of CSU: type I (“autoallergic”) and type IIb autoimmune CSU.

Type IIb autoimmune CSU (aiCSU) is related to IgG, IgM, and IgA autoantibodies against the high affinity IgE receptor, FcɛRIα, activating skin mast cells. At least 8% of the CSU cases are aiCSU and represent a high disease burden (high disease activity, high rates of autoimmune comorbidity, and inadequate response to treatment). aiCSU can be challenging to diagnose because the existing tests (autologous serum skin test (ASST), autoantibody immunoassays, and basophil testing) are not usually available and have limitations. Also, aiCSU responds poorly to treatment.

This study aimed to evaluate how high anti-thyroid peroxidase (aTPO) and low IgE relate to aiCSU and treatment response.

A total of 1120 patient records were analyzed for demographic, clinical, laboratory parameters and treatment responses. Total IgE and aTPO were measured, and four markers were analyzed (ASST, basophil activation test (BAT), eosinophil, and basophil counts).

One of ten patients (n=123) had both high aTPO and low IgE, which was linked to higher age at CSU onset, female, angioedema, and shorter CSU duration. It was also related to positivity to aiCSU markers. A positive BAT was present in 44% of the patients with high aTPO and low IgE. These patients had low response rates to antihistamine treatment compared to the remaining patients.

In conclusion, a high aTPO and low IgE may constitute a valuable biomarker for diagnosing aiCSU in daily clinical practice.

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One hundred and ten years of Allergen Immunotherapy: A journey from empiric observation to evidence

By | Artículos seleccionados, New, Selected articles

Oliver Pfaar, Jean Bousquet, Stephen R. Durham, Jörg Kleine-Tebbe, Mark Larche, Graham C Roberts, Mohamed H Shamji, Roy Gerth Van Wijk

Allergy . 2021 Jul 27. doi: 10.1111/all.15023. Online ahead of print.

It was back in 1911 that Noon has first described the favorable effects of subcutaneous injections with grass pollen extract on himself. Since then, allergen immunotherapy (AIT) has evolved as the most important treatment for allergic patients. AIT constitutes the only disease-modifying treatment available, with consistent efficacy and safety. Worldwide regulatory authorities recognize AIT, which products are subject to thorough assessments before a market authorization is granted.

The disease-modifying effects of AIT are associated with immune modulation of the innate and adaptive immune responses. The recent advances in understanding

the mechanisms supporting AIT will enable the identification of immune monitoring biomarkers as well as biomarkers of efficacy and tolerance. Additionally, this knowledge will be helpful for the development of new therapeutic targets that can be used in conjunction with immunotherapy to shorten treatment duration and improve patient compliance and efficacy.

Recent regulations of allergen products by authorities have positively integrated scientific progress in modern allergology and clinical advances. Definitions of homologous allergen groups based on biological and molecular relationships, manufacturing, and quality aspects have been combined with a framework for the clinical development of allergen products.

Also, a list of in vivo diagnostic and AIT-products is still to be market authorized, including pollen, dust mites, pets, and venoms.

The delivery of cost-effective modern health care is exciting for allergic diseases. Novel solutions – based on mobile health devices- are required to support authorities, and they should promote change of health and care towards integrated care with organizational health literacy.

International guidelines describe and acknowledge the use of AIT.

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The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria

By | Artículos seleccionados, New, Selected articles

Yuhki Yanase, Shunsuke Takahagi, Koichiro Ozawa y Michihiro Hide

Cells. 2021 Jul 12;10(7):1759. doi: 10.3390/cells10071759.

Chronic spontaneous urticaria is a skin condition characterized by skin edema and itchy flares for more than six weeks. Inflammatory mediators, such as histamine, are released from skin mast cells and/or peripheral basophils at the cell level. It is known that the extrinsic coagulation cascade triggered by tissue (TF) and complement factors is based on the pathogenesis of chronic spontaneous urticaria (CSU).

This review aimed to give a detailed role of vascular endothelial cells, leukocytes, extrinsic coagulation factors, and complement components on TF-induced activation of skin mast cells and peripheral basophils to form edema.

The extrinsic coagulation system triggered by TF and activated coagulation factors has been suggested in urticaria’s pathogenesis. Some studies have reported its improvement with heparin or warfarin treatment.

The detailed role of vascular endothelial cells in plasma leakage, especially at local areas of the skin in CSU is unclear. In vitro studies revealed that vascular endothelial cells might have a role in the early stage of CSU pathogenesis, as human umbilical vein endothelial cells and human dermal microvascular endothelial cells express a large amount of TF on their surface in response to the combination of several molecules such as histamine. TF-expressing leucocytes can generate the extrinsic coagulation cascade and produce activated coagulation factors, followed by the induction of intercellular gap formation of human umbilical vein endothelial cells. TF expression on monocytes may be utilized as a marker for pathological conditions of CSU and a therapeutic target of severe and refractory CSU. Studies have also shown that complement factors, such as C5a are increased in people with CSU.

Medications that target the activated coagulation factors and/or complement components may constitute a new and effective treatment for severe and refractory urticaria, namely low-molecular-weight antagonists of C5a and targets of the TF-triggered extrinsic coagulation pathway – complement system – mast cell and/or basophil activation axis.

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Severity and duration of allergic conjunctivitis: are they associated with severity and duration of allergic rhinitis and asthma?

By | Artículos seleccionados, New, Selected articles

M C Sánchez-Hernández, M. T. Dordal, A. M. Navarro, I. Dávila, B. Fernández-Parra, C. Colás, C. Rondón, A. del Cuvillo, F. Vega, J. Montoro, M. Lluch-Bernal, V. Matheu, P. Campo, M. L. González, R. González-Pérez, A. Izquierdo-Domínguez, A. Puiggros, M. Velasco, A. Fernández-Palacín, A. Valero, SEAIC Rhinoconjunctivitis Committee 2014-2018

Eur Ann Allergy Clin Immunol. 2021 Jul 27. doi: 10.23822/EurAnnACI.1764-1489.231. Versión digital previa a la impresión.

Allergic conjunctivitis is a reaction of the conjunctiva of the eye due to IgE hypersensitivity. It is commonly associated with other allergic conditions, such as eczema, food allergy, but especially allergic rhinitis and asthma. Still, the relation between allergic conjunctivitis and allergic rhinitis and asthma needs to be understood.

This study aimed to classify allergic conjunctivitis in a patient population and evaluate the relationship between allergic conjunctivitis and asthma, using the Consensus Document for Allergic Conjunctivitis (DECA).

A total of 2914 participants of all ages who participated in the “Alergológica 2015” study were included. They were then divided into two age groups ≤14 and >14 years old. Of these, 965 participants were diagnosed with allergic conjunctivitis, classified by severe (1,8%), moderate (46,4%) or mild (51,8%), and as intermittent (51,6%) or persistent (48,4%). Allergic conjunctivitis was mainly associated with allergic rhinitis (88,4%), asthma (38,2%), food allergy (8,3%), and atopic dermatitis (3,5%). The duration and severity of allergic conjunctivitis were significantly related to allergic rhinitis for both age groups and asthma in adults.

In conclusion, the new DECA classification showed a direct relationship between allergic conjunctivitis, allergic rhinitis, and asthma, which suggests that it should be considered in the hypothesis of the one airway concept.

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The challenges of chronic urticaria part 2: Pharmacological treatment, chronic inducible urticaria, urticaria in special situations

By | New, Selected articles

Mario Sanchez-Borges, Ignacio J. Ansotegui, Ilaria Baiardini, Jonathan Bernstein, Giorgio Walter Canonica, Motohiro Ebisawa, Maximiliano Gomez, Sandra Nora Gonzalez-Diaz, Bryan Martin, Mario Morais-Almeida and Jose Antonio Ortega Martell

World Allergy Organ J . 2021 Jun 3;14(6):100546. doi: 10.1016/j.waojou.2021.100546. eCollection 2021 Jun.

Chronic spontaneous urticaria consists in the occurrence of wheals, angioedema, or both more than 6 weeks, and 1-2% of the population is affected. It is more prevalent in women and frequently compromises quality of life and the costs for national health systems can be considerable.

The World Allergy Organization (WAO) has reviewed a position paper published in 2012 regarding diagnosis and treatment of urticaria and angioedema. Since then, there have been advances in the knowledge of urticaria mechanism of action, and new treatments (biologics) have been released for severe refractory disease.

This is the second part of an update from the WAO, which intention is to provide an updated guidance for urticaria, especially in special situations such as childhood and pregnancy.

Second generation H1 antihistamines are recommended in major guidelines as the first line treatment for urticaria, as they are effective and safe. Some guidelines include first generation antihistamines for non responders. The dose can also be increased up to 4 times to improve efficacy (and without compromising safety). Combination of antihistamines does not seem to induce better effects, and patients who are refractory to antihistamines are candidates to omalizumab or cyclosporin-A. Omalizumab is the only biological approved for the treatment of antihistamine-refractory patients with moderate to severe urticaria. Cyclosporin-A is an immunosuppressing drug that inhibits T helper cells by blocking the production of inflammatory cytokines.

Special conditions associated with urticaria include autoinflammatory syndromes and various forms of urticarial vasculitis, which are treated with second generation antihistamines and systemic glucocorticoids, and alternatively immunomodulators and immunosuppressors.

 

Specialists are recommended to follow the guidelines, use validated PRO instruments and use effective and safe medications.

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The challenges of chronic urticaria part 1: Epidemiology, immunopathogenesis, comorbidities, quality of life, and management

By | Artículos seleccionados, Selected articles

Mario Sanchez-Borges, Ignacio J. Ansotegui, Ilaria Baiardini, Jonathan Bernstein, Giorgio Walter Canonica, Motohiro Ebisawa, Maximiliano Gomez, Sandra Nora Gonzalez-Diaz, Bryan Martin, Mario Morais-Almeida and Jose Antonio Ortega Martell World Allergy Organ J. 2021 Jun 1;14(6):100533. doi: 10.1016/j.waojou.2021.100533. eCollection 2021 Jun.

Chronic spontaneous urticaria consists in the occurrence of wheals, angioedema, or both more than 6 weeks, and 1-2% of the population is affected. It is more prevalent in women and frequently compromises quality of life and the costs for national health systems can be considerable.

The World Allergy Organization (WAO) has reviewed a position paper published in 2012 regarding diagnosis and treatment of urticaria and angioedema. Since then, there have been advances in the knowledge of urticaria mechanism of action, and new treatments (biologics) have been released for severe refractory disease. Urticaria pathological mechanisms include different cell types, mainly mast cells, basophils, eosinophils, T and B lymphocytes and epithelial and endothelial cells. The dysregulation of intracellular signaling pathways and autoimmune mechanisms have an important role in the activation of mast cells/basophils, which leads to the release of inflammatory mediators resulting in wheals and angioedema.

This is the first part of an update from the WAO, which intention is to provide an updated guidance for urticaria.

Biomarkers have been identified for the prognosis of chronic urticaria (total IgE, CRP, ASST, Anti-TPO, IL-17, IL-31, IL-33) and the assessment of the response of different therapies. Specialists are recommended to follow the guidelines, use validated PRO instruments and use effective and safe medications.

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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Future of Allergic Rhinitis Management

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Sophia Linton, Alyssa G. Burrows, Lubnaa Hossenbaccus, Anne K. Ellis

Ann Allergy Asthma Immunol . 2021 May 7;S1081-1206(21)00337-9. doi: 10.1016/j.anai.2021.04.029. Online ahead of print.

Allergic rhinitis is a chronic inflammatory condition that affects up to 30% of people in America. Immunoglobulin E-mediated hypersensitivity responses to allergens cause it. This review aimed to provide a complete, clinical assessment of therapeutic agents and practices to manage allergic rhinitis.

A systematic review of the literature was completed using PubMed, published abstracts and virtual presentations, and results published on clinicaltrials.gov. Manuscripts with trial results, case reports, case series, and clinical trial data were selected.

Social media, telemedicine, and mHealth demonstrated useful tools for integrated care for allergic rhinitis management, as they can connect allergologists and their patients. A multidisciplinary approach is positive for optimal control of allergic rhinitis. Pharmacotherapy is the standard of care for the management of allergic rhinitis (azelastine hydrochloride and fluticasone propionate, or a combination of both) and represents the future of allergic rhinitis care. Intralymphatic immunotherapy (ILIT) and peptide immunotherapy (PIT) are the most promising new allergen immunotherapy options, with better time and cost-effectiveness than subcutaneous immunotherapy and sublingual immunotherapy, with studies demonstrating positive results. Studies of targeted biologics for allergic rhinitis are ongoing.

Probiotics, in particular, Bifidobacterium spp may be beneficial for allergic rhinitis management and as an add-on to allergen immunotherapy (AIT).

In conclusion, being a chronic and often comorbid condition, allergic rhinitis requires integrated care for optimal management. New formulations and combinations of existing treatments are the most promising and deserve future research.

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covid and rinitis

How does allergic rhinitis impact the severity of COVID-19?: a case-control study

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Ali Guvey

Eur Arch Otorhinolaryngol . 2021 May 1;1-5. doi: 10.1007/s00405-021-06836-z. Online ahead of print.

 

SARS-CoV-2, which leads to coronavirus disease (COVID-19), is an exceptionally infectious disease which symptoms include fever, cough, fatigue, and dyspnea, and sometimes can be fatal in people with risk factors. Initially, some allergic diseases, including asthma, were defined as risk factors and poor outcomes. The objective of this study was to evaluate how allergic rhinitis affects the severity of COVID-19.

This was a case-control study conducted at Sakarya Educational and Research Hospital, Toyota Hospital, and Yenikent State Hospital between March 18, 2020, and August 30, 2020. It included 125 randomly selected patients previously diagnosed with allergic rhinitis before being diagnosed with COVID-19; and a control group of 125 patients without allergic rhinitis and diagnosed with COVID-19.

Patients were assessed regarding symptoms, lifestyle (smoke), comorbidities, and length of hospitalization.

The two groups did not have statistical differences in asymptomatic patients, smokers, hospitalization status, and length.

Two patients from each group went to an intensive care unit, and three patients died: one patient with allergic rhinitis and two from the control group.

In conclusion, allergic rhinitis did not impact the severity of COVID-19. However, more studies are needed with patients with allergic rhinitis and COVID-19.

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Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria

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Yue Zhang, Hanyi Zhang, Shengyi Du, Siyu Yan, Jinrong Zeng

Int Arch Allergy Immunol . 2021 Apr 29;1-15. doi: 10.1159/000515753. Online ahead of print.

Urticaria is a skin disease characterized by rapid onset of hives (superficial dermis edema, erythema, pruritus, or burning sensation), which can be worsened by angioedema (edema of the deep dermis, fat tissue, and gastrointestinal tract). It reduces the quality of life of people and can consist of recurrent attacks. It can be considered acute urticaria or chronic urticaria if it takes longer than six weeks.

Chronic spontaneous urticaria is the most common and can be induced by autoreactivity or other causes. The diagnosis of chronic urticaria is usually complex and requires the exclusion of recurrent angioedema or hereditary angioedema, so biomarkers are essential to diagnose urticaria patients.

Currently, the assessment of chronic urticaria activity depends on the Urticaria Activity Score (UAS), with few evaluation indicators. Consistent biomarkers are needed to assess urticaria.

This article summarizes advanced biomarkers and related pathogenic pathways recently discovered, such as the cell adhesion/chemotaxis pathway, interleukin (IL)-6/Janus tyrosine kinase/STAT pathway, IL-17/IL-23 pathway, basophil- and mast cell-related pathway, coagulation/fibrinolysis-related pathways, single-nucleotide polymorphism, and some other pathways.

This review aims to discover adequate biomarkers to assess disease activity, find novel therapeutic targets, and predict the patients’ response to therapeutic agents (table 1).

 

Table 1. Biomarkers uses in urticaria

 

IL-18BP

IL-6 IL-33

Dimeric TCTP

IL-17

CRP

Siglec-8 IL-23

D-dimer

BDNF

CD203c

5-HT transporter protein

Syk

Vitamin D3/VDBP SSA

CCL17

Substance P

PAF

Keratin86; desmocollin 1; lectin, galactoside-binding, soluble, 7; lactotransferrin; keratin, type II cytoskeletal 4; keratin 31; keratin 80; premature ovarian failure, 1B; plakophilin 1; defensin, alpha 3, and neutrophil-specific

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