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Artículos seleccionados

Prevalence, Management, and Anaphylaxis Risk of Cold Urticaria: A Systematic Review and Meta-Analysis

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Connor Prosty, Sofianne Gabrielli, Michelle Le, Luis F. Ensina, Xun Zhang, Elena Netchiporouk and Moshe Ben-Shoshan.

J Allergy Clin Immunol Pract . 2021 Oct 18;S2213-2198(21)01129-6. doi: 10.1016/j.jaip.2021.10.012. Online ahead of print.

Chronic spontaneous urticaria can be caused by specific triggers, namely cold, exercise or heat. Chronic inducible urticaria (CIndU) can coexist with chronic spontaneous urticaria and is defined as a particular trigger that provokes the symptoms. Cold inducible urticaria is one example of physical urticaria caused by exposure to cold air, liquids, or objects and is associated with significant morbidity and risk for anaphylaxis.

The objective of this study was to evaluate the prevalence of cold urticaria among cases of chronic urticaria and chronic inducible urticaria, evaluate its management, and determine the rate of associate anaphylaxis.

The investigators did bibliographic research in PubMed and EMBASE for papers on cold urticaria and/or chronic inducible urticaria in the past ten years. An analysis was made to determine the prevalence of cold urticaria among CIndU and chronic urticaria cases, its management with H1-antihistamines and omalizumab, and the rate of associated anaphylaxis.

The research identified 22 studies, of which 14 were included in the meta-analysis. The pooled prevalence of cold urticaria among patients with chronic urticaria and CIndU was, respectively, 7.62% [CI95%; 3.45%-15.99%; I2=98%] and 26.10% [CI95%; 14.17%-43.05%; I2=97%]. 95.67% of the cases of cold urticaria were managed by H1-antihistamines [CI95%; 92.47%-97.54%; I2=38%], and by omalizumab in 5.85% of the cases [CI95%; 2.55%-13.22%; I2=83%]. The pooled prevalence of anaphylaxis was 21.49% [CI95%; 15.79%-28.54%; I2=69%].

In conclusion, cold urticaria is common in cases of chronic urticaria and CIndU and frequently triggers anaphylaxis. H1-antihistamines are commonly used for its management, followed by omalizumab.

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Metabolomics Reveals Process of Allergic Rhinitis Patients with Single- and Double-Species Mite Subcutaneous Immunotherapy

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Zheng, P., Yan, G., Zhang, Y., Huang, H., Luo, W., Xue, M., Li, N., Wu, J. L., & Sun, B.

Metabolites . 2021 Sep 9;11(9):613. doi: 10.3390/metabo11090613.

Allergic rhinitis is also known as anaphylactic rhinitis and includes infectious inflammatory conditions of the nasal mucosa triggered by exposure to atopic allergens. House dust mites are the most common allergens in patients with rhinitis. Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic rhinitis, but there is a lack of knowledge in relation to AIT with single or mixed allergens. The aim of this study was to assess and compare the clinical efficacy of single-mite subcutaneous immunotherapy or double-mite subcutaneous immunotherapy using the visual analogue scale (VAS) score and rhinoconjunctivitis quality of life questionnaire score to evaluate and compare its clinical efficacy.

Patients with allergic rhinitis caused by Dermatophagoides pternussinus and Dermatophagoides farinae received a single-mite and double-mite subcutaneous immunotherapy, respectively.

There was no significant difference in efficacy between treatments. A total of 57 metabolites were identified, among which down-stream metabolites (5(S)-HETE (Hydroxyeicosatetraenoic acid), 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11-hydro TXB2) in the ω-6-related arachidonic acid and linoleic acid pathway showed significant differences after approximately one year of treatment with single-mite or double-mite subcutaneous immunotherapy, and the changes of the above serum metabolic components were correlated with the magnitude of rhinoconjunctivitis quality of life questionnaire improvement, respectively.

The major difference found was with 11(S)-HETE, which decreased more with single-mite immunotherapy, having the possibility to be used as a biomarker to distinguish the two treatments.

In conclusion, both treatments showed therapeutic effects on patients with allergic rhinitis, with no differences in efficacy. The production of different inflammation-related metabolites can lead to potential biomarkers.

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Lachnospira is a signature of antihistamine efficacy in chronic spontaneous urticaria

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Liu, R., Peng, C., Jing, D., Xiao, Y., Zhu, W., Zhao, S., Zhang, J., Chen, X., & Li, J.

Exp Dermatol. 2021 Sep 24. doi: 10.1111/exd.14460. Online ahead of print.

Chronic urticaria is a condition driven by mast cells, with an average lifetime prevalence of 1.4%. Chronic spontaneous urticaria is a common type of chronic urticaria that impacts quality of life and has a high economic and social burden. Chronic spontaneous urticaria is treated with oral second-generation antihistamines, however only half of the patients respond to up to quadruple doses of these antihistamines. It is known that gut microbiota can affect their efficacy. The objective of this study was to explore the relationship between gut microbiota and the efficacy of antihistamines in people with chronic spontaneous urticaria.

The gut microbiota of fecal samples from 15 responders to antihistamine monotherapy and 15 non-responders was assessed by 16S rDNA sequencing, and the differential bacterial species between them were confirmed by quantitative polymerase chain reaction (qPCR). Samples from 30 responders and 30 non-responders were used to confirm the differential bacterial species by qPCR.

The main difference between responders and non-responders was the presence of Lachnospiraceae and its subordinate taxa. The quantity of Lachnospira was higher in responders than non-responders.

In conclusion, the presence of Lachnospira has shown to have a moderate diagnostic value in assessing the efficacy of chronic urticaria with antihistamines.

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The International EAACI/GA²LEN/EuroGuiDerm/APAAACI Guideline for the Definition, Classification, Diagnosis and Management of Urticaria

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Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al.

Allergy . 2021 Sep 18. doi: 10.1111/all.15090. Online ahead of print.

Urticaria is a mast-cell-driven condition with symptoms such as wheals, angioedema, or both. Chronic spontaneous urticaria and chronic inducible urticaria reduce the quality of life, affecting performance at school and work.

This document is an update and revision of the international guideline for urticaria, from a consensus conference held on the 3rd of December of 2020. It covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

The objective of this guideline is to facilitate a definition and classification of urticaria, helping with data interpretation from different centers and areas of the world.

The table below summarizes the guideline.

How should urticaria be classified?

We recommend that urticaria is classified based on its duration as acute (<= 6 weeks) or chronic (> 6 weeks).

­­↑ ↑

Strong consensus*

Expert consensus

We recommend that urticaria is classified as spontaneous (no definite eliciting factor involved) or inducible (specific definite factor involved).

­­↑ ↑

Strong consensus*

Expert consensus

Should we maintain the current guideline classification of chronic urticaria?

We recommend that the current guideline classification of chronic urticaria should be maintained.

­­↑ ↑

Strong consensus*

Expert consensus

Should routine diagnostic measures be performed in acute urticaria?

We recommend against any routine diagnostic measures in acute spontaneous urticaria.

↓ ↓

Strong consensus*

Expert consensus

Should differential diagnoses be considered in patients with chronic spontaneous urticaria?

We recommend that differential diagnoses be considered in all patients with signs or symptoms suggestive of chronic urticaria based on the guideline algorithm.

­­↑ ↑

Strong consensus*

Expert consensus

What routine diagnostic measures should be performed in chronic spontaneous urticaria?

We recommend limited investigations. Basic tests include differential blood count, CRP and/or ESR, and in specialized care total IgE and IgG anti-TPO, and more biomarkers as appropriate.

We recommend performing further diagnostic measures based on the patient history and examination, especially in patients with long standing and/or uncontrolled disease.

↑ ↑­­

Consensus**

Expert consensus

Should routine diagnostic measures be performed in inducible urticaria?

We recommend using provocation testing to diagnose chronic inducible urticaria.

We recommend using provocation threshold measurements and the UCT to measure disease activity and control in patients with chronic inducible urticaria, respectively.

­­↑ ↑

Strong consensus*

Expert consensus

Should patients with chronic urticaria be assessed for disease activity, impact, and control?

We recommend that patients with CU be assessed for disease activity, impact, and control at every visit.

­­↑ ↑

Strong consensus*

Expert consensus

Which instruments should be used to assess and monitor disease activity in chronic spontaneous urticaria patients?

We recommend the use of the urticaria activity score, UAS7, and/or of the angioedema activity score, AAS, for assessing disease activity in patients with chronic spontaneous urticaria.

­­↑ ↑

Strong consensus*

Expert consensus

Which instruments should be used to assess and monitor quality of life impairment in chronic spontaneous urticaria patients?

We recommend the use of the chronic urticaria quality of life questionnaire, CU-Q2oL, and the angioedema quality of life questionnaire, AE-QoL, for assessing quality of life impairment in patients with chronic spontaneous urticaria.

­­↑ ↑

Strong consensus*

Expert consensus

Which instruments should be used to assess and monitor disease control in chronic spontaneous urticaria patients?

We recommend the use of the urticaria control test, UCT, and/or the angioedema control test, AECT, for assessing disease control in patients with CSU.

­­↑ ↑

Strong consensus*

Expert consensus

Should treatment aim at complete symptom control in urticaria?

We recommend aiming at complete symptom control in urticaria, considering as much as possible the safety and the quality of life of each individual patient.

­­↑ ↑

Strong consensus*

Expert consensus

Should patients with chronic spontaneous urticaria be advised to discontinue medication that is suspected to worsen the disease?

We recommend advising patients with chronic spontaneous urticaria to discontinue medication that is suspected to worsen the disease, e.g. NSAIDs.

­­↑ ↑

Strong consensus*

Expert consensus

Should modern 2nd generation H1-antihistamines be used as first-line treatment of urticaria?

We recommend a 2nd generation H1-antihistamine as first-line treatment for all types of urticaria.

­­↑ ↑

Strong consensus*

Evidence and consensus-based

Is an increase in the dose to up to four-fold of modern 2nd generation H1-antihistamines useful and to be preferred over other treatments in urticaria?

We recommend updosing of a 2nd generation H1-antihistamine up to 4-fold in patients with chronic urticaria unresponsive to a standard-dosed 2nd generation H1-antihistamines as second line treatment before other treatments are considered.

­­↑ ↑

Strong consensus*

Evidence and consensus-based

Should modern 2nd generation H1-antihistamines be taken regularly or as needed?

We suggest 2nd generation H1-antihistamines to be taken regularly for the treatment of patients with chronic urticaria.

­↑

Strong consensus*

Evidence and consensus-based

Should different 2nd generation H1-antihistamines be used at the same time?

We suggest against using different H1-antihistamines at the same time.

Consensus***

Evidence and consensus-based

If there is no improvement, should higher than fourfold doses of 2nd generation H1-antihistamines be used?

We recommend against using higher than 4-fold standard dosed H1-antihistamines in chronic urticaria

 ↓ ↓

Strong consensus*

Evidence and consensus-based

Is omalizumab useful as add-on treatment in patients unresponsive to high doses of H1-antihistamines?

We recommend adding on omalizumab* for the treatment of patients with CU unresponsive to high dose 2nd generation H1-antihistamines.

*currently licensed for chronic spontaneous urticaria

­­↑ ↑

Strong consensus*

Evidence and consensus-based

Is ciclosporin useful as add-on treatment in patients unresponsive to high doses of H1-antihistamine?

We suggest using ciclosporin for the treatment of patients with CU unresponsive to high dose of 2nd generation H1-antihistamine and omalizumab.

­↑

Strong consensus*

Evidence and consensus-based

Should oral corticosteroids be used as add-on treatment in the treatment of urticaria?

We recommend against the long-term use of systemic glucocorticosteroids in CU.

↓ ↓

Strong consensus*

Evidence and consensus-based

We suggest considering a short course of rescue systemic glucocorticosteroids in patients with an acute exacerbation of CU.

­ ↑

Strong consensus*

Evidence and consensus-based

Are H2-antihistamines useful as add-on treatment in patients unresponsive to low or high doses of H1-antihistamines?

We cannot make a recommendation for or against the combined use of H1- and H2-antihistamines in patients with chronic urticaria.

0

Strong consensus*

Expert consensus

Could any other treatment options be recommended for the treatment of urticaria?

We cannot make a recommendation with respect to further treatment options as standard therapies, but these may be considered in special cases, which also include those where financial or legal limitations for the recommended algorithm treatment exist.

0

Strong consensus*

Expert consensus

Should the same treatment algorithm be used in children?
We suggest using the same treatment algorithm with caution (e.g. weight adjusted dosage) in children with chronic urticaria

­ ↑

Strong consensus*

Expert consensus

Should the same treatment algorithm be used in pregnant women and during lactation?
We suggest using the same treatment algorithm with caution both in pregnant and lactating women after risk-benefit assessment. Drugs contraindicated or not suitable in pregnancy should not be used

­ ↑

Strong consensus*

Expert consensus

*≥90% agreement

**>75% agreement

***≥70% agreement

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Predictive features associated with chronic spontaneous urticaria recurrence

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Elias Toubi, Zahava Vadasz

J Dermatol . 2021 Sep 14. doi: 10.1111/1346-8138.16119. Online ahead of print.

Chronic spontaneous urticaria is an autoimmune condition for, at least, 50% of the cases, and sometimes it is associated with other autoimmune diseases such as thyroid autoimmunity and systemic lupus erythematosus. They have an increased prevalence of autoreactive T-cell responses to FceRI and serum anti-thyroid antibodies. There are still a lot of unclear aspects to be determined, namely how long CSU will last. Most patients with chronic spontaneous urticaria are concerned about the probability of recurrence and wish for the existence of clinical or laboratory markers. The aim of this study was to understand the prevalence and characteristics of the recurrence of chronic spontaneous urticaria to prevent stressful comorbidities.

The study included 180 regular patients from the local registry. Chronic spontaneous urticaria lasted more than 5 years in 47 (26%) patients and was resolved during the first year in 23 (13%) patients. 21% of the patients reported recurrence of chronic spontaneous urticaria after a full remission between 1 and 10 years (mean 2.9 years).

In the search for predictive clinical or laboratory markers, the main differences found are registered in the table below.

Recurrent urticaria

General urticaria

P value

Bronchial asthma

10/25 (40%) 45/180 (25%)

p=0.049

Total immunoglobulin E

10/25 (40%) 34/150 (23%)

p=0.04

Anti-thyroid peroxidase antibodies

11/25 (44%) 32/160 (20%)

p=0.003

In conclusion, the prevalence of chronic spontaneous urticaria after a full remission is significantly higher in patients with bronchial asthma, increased levels of total IgE and autoimmunity. More studies are needed to support these findings.

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The effect of face mask usage on the allergic rhinitis symptoms in patients with pollen allergy during the covid-19 pandemic

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Mengi E, Kara CO, Alptürk U, Topuz B

Am J Otolaryngol . 2021 Sep 10;43(1):103206. doi: 10.1016/j.amjoto.2021.103206. Online ahead of print.

Allergic rhinitis is an inflammation of the nasal mucosa mediated by IgE. It is characterized by nasal discharge, nasal obstruction, nasal itching, and sneezing. Allergic rhinitis prevalence has been increasing worldwide and it is believed that it affects up to 40% of the population. The objective of this study was to assess the use of face masks on allergic rhinitis symptomatology in people allergic to pollen and who were using face masks during the COVID-19 pandemic.

A total of 50 participants answered over the telephone a 15-item questionnaire which was developed by a team of allergic rhinitis experts. Participants were selected from those who had had allergy tests between 2013 and 2019.

The mean age of the participants was 34.34±9.41 years old and 60% were female. The number of participants who defined their nasal symptoms as severe-moderate in the pre-pandemic was higher (46 participants) than the number of participants with severe-moderate symptoms during the pandemic (28 participants). Patients who used mask had a statistically significant decrease in nasal and ocular symptoms (p<0,001), in sneezing (p=0,029) and nasal discharge (p=0,039).

In conclusion, the use of face mask reduced allergic rhinitis symptoms in people with pollen allergy, which supports the use of face masks for people with allergic rhinitis.

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Allergic rhinitis and COVID-19: friends or foes?

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F Gani

Eur Ann Allergy Clin Immunol . 2021 Sep 10. doi: 10.23822/EurAnnACI.1764-1489.234. Online ahead of print.

Allergic rhinitis is a usual condition that affects around 40% of the world population. During the COVID-19 pandemic, there was an increase in observational studies on the effect of asthma and chronic obstructive pulmonary disease and the risk of developing COVID-19. Still, there were no studies on allergic rhinitis and COVID-19.

This review aimed at assessing the risk of patients with allergic rhinitis developing worse COVID-19 outcomes. It also evaluated if COVID-19 can influence allergic rhinitis symptoms and influence the psychological conditions of pediatric and adult patients with allergic rhinitis.

The authors performed a comprehensive review of the literature. It included a set of different keywords, such as allergic rhinitis, rhinitis, allergy, atopy, COVID-19, and SARS-CoV-2.

From the articles selected, allergic rhinitis patients, appear to be protected from COVID-19 infection. However, there is not enough data on the influence of allergic rhinitis and the severity of COVID-19 disease; there is some information that being an allergic rhinitis patient does not increase the risk of a poor prognosis SARS-CoV-2 infection. The authors suggest that patients with allergic rhinitis follow their treatment accordingly, especially while the COVID-19 pandemic persists.

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Advances and highlights in allergic rhinitis

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Yuan Zhang, Feng Lan, Luo Zhang

Allergy . 2021 Aug 11. doi: 10.1111/all.15044. Online ahead of print.

Allergic rhinitis incidence has been growing in the past years, representing a medical and economic burden worldwide. This review describes the main findings with regards to allergic rhinitis for the past two years, including risk factors for the growing prevalence of allergic rhinitis, its strategy for the diagnosis, immunological mechanisms underlying the condition, and therapies used during the COVID-19 pandemic. It also aims at describing future perspectives.

Some of the most critical risk factors for allergic rhinitis are environmental exposures, climate changes, and lifestyle. There is an essential need to understand the connection between environmental exposures and health to design risk profiles instead of using single predictors and help eliminate adverse health outcomes in these conditions.

A newly defined allergic rhinitis phenotype, dual allergic rhinitis, includes perennial and seasonal related nasal symptoms but is more connected to seasonal allergic allergens. This indicates that it is crucial to assess inflammation at the local sites.

The authors suggest a combination of precise diagnosis in local sites and territories and traditional diagnostic methods to improve the precision medicine-based approach to managing allergic rhinitis.

In conclusion, further understanding of changes in cell profiles after treatment is needed. Apart from the usual treatments for allergic rhinitis during the current pandemic, social distancing, washing hands, and disinfection are also great aids in managing patients with allergic rhinitis.

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Association of severity of allergic rhinitis with neutrophil-to-lymphocyte, eosinophil-to-neutrophil, and eosinophil-to-lymphocyte ratios in adults

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Aydin Kant, Kadriye Terzioğlu

Allergol Immunopathol (Madr). 2021 Sep 1;49(5):94-99. doi: 10.15586/aei.v49i5.204. eCollection 2021.

Allergic rhinitis is an immunoglobulin E-mediated disorder of the nasal mucosa, with symptoms such as recurrent sneezing, rhinorrhea, and nasal congestion. People with allergic rhinitis suffer from sleep disturbances, emotional distress, and impaired social activity, which results in a reduced quality of life. This study aimed to assess the practicality of inflammatory parameters of neutrophil-to-lymphocyte ratio (NLR), eosinophil-to-neutrophil ratio (ENR), and eosinophil-to-lymphocyte ratio (ELR) as markers used to distinguish between intermittent and persistent allergic rhinitis.

This double-center, retrospective study included 205 patients with allergic rhinitis and 49 healthy individuals who acted as a control group. Patients with active infection were excluded. NLR, ENR, and ELR were calculated using the results from the participants’ complete blood count. A statistical analysis was also performed.

The participants with allergic rhinitis had significantly higher levels of absolute eosinophils, ENR, and ELR, and also lower levels of NLR when compared to healthy controls. A total of 80% of participants with persistent allergic rhinitis had significantly higher levels of absolute eosinophils, ENR, and ELR and significantly lower levels of NLR than patients with intermittent allergic rhinitis.

In conclusion, allergic rhinitis severity is classified according to the patient’s anamnesis, with serum eosinophil levels and the proportions of ENR and ELR in patients with persistent allergic rhinitis, highlighting the severity of the disease.

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Meta-analyses of the efficacy of pharmacotherapies and sublingual allergy immunotherapy tablets for allergic rhinitis in adults and children

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Eli O. Meltzer, Dana Wallace, Howard S. Friedman, Prakash Navaratnam, Erin P. Scott, Hendrik Nolte

Rhinology . 2021 Aug 31. doi: 10.4193/Rhin21.054. Online ahead of print.

Allergic rhinitis impacts the quality of life of people who suffer from it, such as sleep impairment and reduction in work and school productivity. Current treatment options for seasonal and perennial allergic rhinitis include pharmacotherapy and immunotherapy. These meta-analysis aimed to assess the efficacy of pharmacotherapies and sublingual immunotherapy tablets (SLIT) versus placebo on people with nasal symptoms associated with both types of allergic rhinitis.

A systematic search identified randomized, double-blind, placebo-controlled trials with these comparisons. The primary outcome was the mean numerical difference in total nasal symptom score (TNSS) between active treatment and placebo at the end of the assessment timeline. A meta-analysis estimated the mean difference for each group of medication weighted by the inverse of the trial variance.

Most pharmacotherapy trials did not allow rescue symptom-relieving medicines but were allowed in sublingual immunotherapy tablets. The following table includes total nasal symptom scores for children and adults with allergic rhinitis.

 

Seasonal allergic rhinitis TNSS mean numerical difference (95%CI) vs. placebo

Perennial allergic rhinitis TNSS mean numerical difference (95%CI) vs. placebo

Intranasal corticosteroids 1.38 (1.18-1.58) 0.82 (0.66-0.97)
Combination intranasal antihistamines+corticosteroids 1.34 (1.15-1.54)
Intranasal antihistamines 0.72 (0.56-0.89)
Oral antihistamine 0.62 (0.35-0.90) 0.27 (0.11-0.42)
SLIT tablets 0.57 (0.41-0.73) 0.65 (0.42-0.88)
Montelukast 0.48 (0,36-0,60)

 

In conclusion, all treatments significantly improved nasal symptoms when compared with placebo. SLIT-tablets improved TNSS, even using rescue symptom-relieving pharmacotherapy. However, since trials have considerable heterogeneity, it is difficult to compare treatment effects among treatment classes.

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

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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

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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

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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?

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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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