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Selected articles

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

By | Artículos seleccionados, New, 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

By | Artículos seleccionados, New, 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.

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

By | Artículos seleccionados, New, 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.

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

By | Artículos seleccionados, New, 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.

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

By | Artículos seleccionados, New, 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.

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Future of Allergic Rhinitis Management

By | Selected articles

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

By | Selected articles

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

By | Selected articles

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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The Diagnostic Workup in Chronic Spontaneous Urticaria-What to Test and Why

By | Selected articles

Martin Metz

J Allergy Clin Immunol Pract . 2021 Apr 20;S2213-2198(21)00435-9. doi: 10.1016/j.jaip.2021.03.049. Online ahead of print.

Chronic spontaneous urticaria (CSU) consists of wheals, angioedema, or both for longer than six weeks. Guidelines have limited procedures during the routine workup; however, some patients might need additional investigations. The objective of this article is to propose recommendations for the diagnostic and evaluation of some urticaria patients.

An extensive literature search was performed to identify important questions that should define diagnostic procedures based on expert consensus and published evidence.

The authors proposed seven questions for all chronic spontaneous urticaria patients: Confirm (rule out a differential diagnosis); Cause (look for indications of CSU); Cofactors (identify potential triggers, aggravators); Comorbidities (check for chronic inducible urticaria, autoimmunity, and mental health); Consequences (identify problems with sleep, distress, sexual health, work, and social performance); Components (assess potential biomarkers or predictors of treatment response); Course (monitor CSU activity, impact, and control).

Also, a complete medical history should be conducted in the assessment of the patient. CSU should be confirmed in all patients through a differential diagnosis, including blood testing for CRP and/or erythrocyte sedimentation rate and complete blood count with differential.

In conclusion, based on the answers, a decision for or against more diagnostic tests should be conducted by the specialist to prevent unnecessary and expensive testing and increase treatment effectiveness.

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Heterogeneity of the pharmacologic treatment of allergic rhinitis in Europe based on MIDAS and OTCims platforms

By | Selected articles

Jean Bousquet

Clin Exp Allergy . 2021 Apr 20. doi: 10.1111/cea.13884. Online ahead of print.

Allergic rhinitis is a prevalent chronic condition. There are different treatments across countries in Europe that depend on the cost and sales too. The objective of this study was to evaluate practices in Europe to implement the Good Practice of DG Santé (MASK-air). A secondary purpose included understanding the differences and propose improvement strategies.

This study consisted of analyzing a pharmaco-epidemiological database to evaluate prescribed allergic rhinitis treatment from 2016 to 2018 in the five principal markets in the EU (France, Germany, Italy, Poland, and Spain). To gather this information, the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics, and Services) and for OTC medicines (OTC International Market Tracking—OTCims) were used.

The analyses excluded intranasal decongestants as they are seldom prescribed for allergic rhinitis. France leads concerning the other countries in costs and Standard Units (SU). All other countries are similar in respect to SU. However, Poland’s costs are lower than the remaining. The use of medication is very different, though: in 2018, intranasal corticosteroid was the first treatment in Poland (70,0%), France (51,3%), Spain (51,1%), and Germany (50,3%). Systemic antihistamines were more sold in Italy (41,4%), followed by 30,1% of intranasal corticosteroids. In 2016 and 2017, the results were similar.

This study represents an excellent interest in assessing the differences in allergic rhinitis treatment in Europe and can be a start for future studies of treatment trends.

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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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B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated

By | Selected articles

Harsha H Kariyawasam & Louisa K James

Expert Rev Clin Immunol. 2021 Apr 1:1-15. doi: 10.1080/1744666X.2021.1905527. Epub ahead of print.

Allergic rhinitis and chronic rhinosinusitis with nasal polips (CRSwP) are upper airway immunological conditions with complex mechanisms of action. Airway local mucosal B cells are drivers for the conditions, with B cells migrating into the airway mucosa when there is an airway injury.

B-cells are very important in the defense, tissue surveillance, and immune modulation of the upper airways. Allergic rhinitis and CRSwP are two of the upper airway conditions that can be identified as expressing B-cells or dysregulating their function within T2-high mucosal inflammatory states. B cells can drive T2 inflammatory states via functional antibody production and also through interactions with commensal microbes and other recruited inflammatory cells such as Th2 cells and eosinophils, leading to immune amplification and dysregulation.

This review aimed to report the existing knowledge of the key role of B cells in allergic inflammatory upper airway disease and highlight the need for more focus on human B-cell-directed disease-context-specific upper airway studies.

The authors concluded that there is a lack of studies concerning the role of B-cell overexpression and dysfunction, especially those which relate sinonasal infection and mucosal inflammation. It is important to understand how respiratory inflammation, together with augmented or impaired B-cell function, increases and dysregulates immune signaling pathways in allergic rhinitis and CRSwP to develop novel B-cell disease-specific therapeutic interventions with molecular manipulation.

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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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Use of H-1 Antihistamine in Dermatology: More than Itch and Urticaria Control: A Systematic Review

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Chang-Yu Hsieh, Tsen-Fang Tsai

Dermatol Ther (Heidelb). 2021 Apr 12. doi: 10.1007/s13555-021-00524-w. Epub ahead of print.

H1-antihistamines are known for their effects in suppression of pruritus, especially in urticaria. However, there are many other dermatological uses of H1-antihistamines, such as scarring and nonscarring alopecia, acne, Darier disease, eosinophilic dermatoses, paraneoplastic dermatoses, psoriasis, lichen nitidus, radiation dermatitis, skin dysesthesia, and cutaneous malignancies.

This review includes a literature search on articles that report the use of H1-antihistamines.

It is the modulation of the immune system, inflammatory cytokines, and mast cells that explain why H1-antihistamines are effective in some autoimmune conditions, such as Kaposi sarcoma, melanoma, and alopecia areata. Some eosinophilic dermatosis may be relieved with the use of cetirizine and bilastine due to their effects on the chemotaxis of eosinophils. Hydroxyzine, together with GABA receptor agonists, may have an effect on cutaneous dysesthesia. A combination of antihistamines with isotretinoin helps control acne better, probably due to the inhibition of the production of sebum. The reversing vascular effect of histamine seems to be of interest for erythema, edema, and pain control in radiation dermatitis and erythromelalgia.

New properties of antihistamines have also been studied in vitro: antibacterial activity, antiangiogenesis, and antifibrosis.

H1-antihistamines may improve symptoms of some conditions when used alone or in combination with other treatments; however, this evidence is still limited. More studies are needed to assess the efficacy and dosage of H1-antihistamines in other dermatological conditions.

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Systematic review of measures of disease severity in rhinitis

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Andraia R. Li, Kathy Zhang, Priyanka D. Reddy, Shaun A. Nguyen, Amar Miglani, Jacob Fried, Mariam I. Nguyen, Rodney J. Schlosser

Int Forum Allergy Rhinol. 2021 Mar 27. doi: 10.1002/alr.22794. Epub ahead of print.

Rhinitis is an inflammation of the nasal mucosa with itching, sneezing, rhinorrhea, and congestion. It may be classified into allergic rhinitis and nonallergic rhinitis. The ARIA (allergic rhinitis and its impact on asthma) guidelines categorize allergic rhinitis upon intermittent or persistent timing of symptoms and mild, moderate or severe. The objective of this review was to assess if patient-reported outcome measures (PROMs) and clinical physiological measures vary, and which factors impact rhinitis.

A systematic search identified allergic rhinitis and nonallergic rhinitis that reported Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), total nasal symptom score (TNSS), or visual analog scale (VAS) scores, and physiologic measures (peak nasal inspiratory flow and nasal airflow). The relationship between PROMs, physiologic measures, and associated factors was statistically evaluated.

The review included 171 studies, which reflected 33843 patients. Patients with allergic rhinitis had more severe symptoms than nonallergic rhinitis ones. There was no significant correlation between PROMs and demographic factors, comorbidities, or physiologic measures. Statistical analysis identified a correlation between the worse quality of life and shorter disease duration.

In conclusion, patients with rhinitis have a more severe impact in their quality of life in the presence of allergy with variable impact upon specific symptom subdomains. PROMs did not show a correlation with demographic factors, comorbidities, or physiologic measures of nasal airflow.

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