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Selected articles

Cholinergic Urticaria: Subtype Classification and Clinical Approach

By New, Selected articles

Atsushi Fukunaga

Am J Clin Dermatol . 2022 Sep 15;1-14. doi: 10.1007/s40257-022-00728-6. Online ahead of print.

Cholinergic urticaria is a subtype of chronic inducible urticaria with painful wheals with surrounding erythema which occur after sweating. The objective of this review was to analyze different subtypes of cholinergic urticaria and its correlation to anhidrosis.

Recent publications were reviewed to update evidence on epidemiology, clinical features, diagnostic approaches, physiopathology subtype classification and therapeutic approaches of cholinergic urticaria.

When examining patients who present with symptoms similar to cholinergic urticaria, it is important to run a differential diagnosis to screen for a sweating dysfunction.

There are different mechanisms that contribute to the development of cholinergic urticaria, namely histamine, sweat allergy, cholinergic-related substances, poral occlusion and hypohidrosis/anhidrosis. These mechanisms are important to focus on the subtypes of cholinergic urticaria so that it can be managed and treated adequately, given the fact that this condition does not present in a homogeneous way.

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By New, Selected articles

Pavel Kolkhir

Nat Rev Dis Primers. 2022 Sep 15;8(1):61. doi: 10.1038/s41572-022-00389-z

Urticaria is a common and heterogeneous inflammatory skin disease that affect up to 20% of the world population. Its symptoms include wheals, angioedema or both which are due to the stimulation and degranulation of skin mast cells and release of histamine and other mediators. Acute urticaria accounts for the majority of cases can last up to 6 weeks and be related to infections or intake of drugs or food. Chronic urticaria may be spontaneous or inducible, can last more than 6 weeks and persist for more than one year in most patients. Patients with chronic urticaria are deeply affected in their daily activities and may suffer from psychiatric comorbidities. Chronic inducible urticaria has different subtypes and triggers that lead to different symptoms.

The mechanism of chronic spontaneous urticaria includes autoantibodies, complement and coagulation cascades. Its diagnosis includes differential testing to identify underlying causes or triggers.

Urticaria treatment first line uses second-generation H1 antihistamines, and omalizumab and cyclosporine in a second line. Other new approaches focus on targeting mediators, signalling pathways and receptors of mast cells and other immune cells.

There’s still some research needed to define disease endotypes and their biomarkers, identifying new treatment targets and developing improved therapies.

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Control of allergic rhinitis in four latin american countries: Rinola study

By New, Selected articles

Diana L Silva

Front Allergy . 2022 Aug 24;3:980515. doi: 10.3389/falgy.2022.980515. eCollection 2022

Up to 40% of people worldwide suffer from allergic rhinitis. Although there are clinical trials that describe its characteristics, there is a lack of real-world studies from Latin America. This manuscript describes a cross-sectional, descriptive, multicenter study that took place in 4 countries from Latin America (Colombia, Argentina, Cuba and Peru) and which included 412 patients diagnosed with allergic rhinitis between November 2017 and June 2020. Patients completed different assessment questionnaires and their sociodemographic and clinical data were collected.

This study included patients aged between 15 and 39 years old. Three quarters of the participants presented with nasal obstruction and 81% with persistent allergic rhinitis. 31% of them had associated asthma. Skin tests were positive in over 80% of the participants (81.3% were positive for Dermatophagoides farinae and 88.6% positive for Dermatophagoides pteronyssinus). All but one participant reported that allergic rhinitis affected their daily activities. Upon consultation, specialists started nasal corticosteroids in 72% of the patients, but only 17% patients were on immunotherapy. 60% of the patients were already on oral antihistamines only.

In conclusion, this study confirms that people with allergic rhinitis from Latin America have an impaired quality of life due to persistent disease. Dust mites are the main sensitizers.

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An evaluation of remission rates with first and second line treatments and indicators of antihistamine refractoriness in chronic urticaria

By New, Selected articles

Sinem Ayse Ornek

Int Immunopharmacol . 2022 Sep 15;112:109198. doi: 10.1016/j.intimp.2022.109198. Online ahead of print.

Chronic urticaria is a common condition characterized by recurrent pruritic wheals and/or angioedema for more than 6 weeks. As a first-line treatment, guidelines recommend standard doses of antihistamines and as second-line an increase in antihistamines’ dose. There is a lack of studies on remission rates with first and second-line treatments as well as indicators of antihistamine response. The aim of this study was to assess response rates to chronic urticaria first and second-line treatments and to identify characteristics of the patients that can help estimate treatment outcomes.

Different types of urticaria outcomes were retrospectively analyzed: 556 chronic spontaneous urticaria and 101 chronic inducible urticaria cases on at least 3 months of follow-up data.

Results have shown that a standard dose of 2nd generation antihistamines was proving efficacy in 43% of the patients. An additional 28.8% of patients were in remission with 2nd line treatments. Increasing antihistamine dose, combining two different 2nd generation antihistamines, combining 1st and 2nd generation antihistamines or combining leukotriene receptor antagonist offered remission in 38.3 %, 35.8 %, 37.5% and 25 % of patients who were given these treatments, respectively.

In conclusion, it is important to have a stepwise approach to managing chronic urticaria because the number of patients who respond to treatment increases with each step.

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Non-allergic Rhinitis, Allergic Rhinitis and Immunotherapy: Advances in the Last Decade

By New, Selected articles

Punita Ponda

J Allergy Clin Immunol Pract . 2022 Sep 21;S2213-2198(22)00945-X. doi: 10.1016/j.jaip.2022.09.010. Online ahead of print

Allergic and nonallergic rhinitis are two of the most common diseases seen by immunoallergologists. These conditions have a huge impact on daily life activities and represent an economic burden to health systems globally. Immunotherapy is currently a common practice to address individual triggers of allergic rhinitis.

This review makes an approach to the most recent advances in these conditions, from diagnosis to treatment, allergen immunotherapy and global and digital health strategies. In the past 10 years there was a great growing understanding on these conditions, helping optimize patient care and outcomes.

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New transcriptome and clinical findings of platelet-activating factor in chronic spontaneous urticaria: Pathogenic and treatment relevance

By Artículos seleccionados, Selected articles

Andrades E, Clarós M, Torres JV

Biofactors . 2022 Aug 4. doi: 10.1002/biof.1880. Online ahead of print.

Urticaria is characterized by transient wheal-and-flare skin reaction with pruritus. More than 5 million people suffer from persisting urticaria symptoms in Europe, causing a huge burden on patients and healthcare systems. The aim of this study was to evaluate the relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU).

Skin samples of 45 patients with moderate/severe CSU and 17 healthy controls were analyzed for the expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF-AH). Serum PAF and PAF-AH levels were assessed by ELISA and compared between patient and healthy controls and also between those refractory and non-refractory to 2nd-generation H1-antihistamines. PAFR mRNA expression was significantly higher in LS-CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, while it was largely present along the epidermis in LS-CSU samples. Endothelial cells showed PAFR expression exclusively in LS-CSU and NLS-CSU samples. PAFR expression was observed in the nerves of HC, LS-CSU, and NLS-CSU samples. Double PAFR/CD43 expression demonstrated that T-lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF-AH/PAF ratio was observed in 2nd-generation H1-antihistamines non-responders versus responders (6.1 vs. 12.6; p = 0.049).

In conclusion, this study corroborates that PAF is a mediator of wheal pathogenesis in CSU and suggests that PAF could be a potential biomarker of 2nd-generation H1-antihistamines refractoriness due to the significantly lower PAF-AH/PAF ratio in 2nd-generation H1-antihistamines non-responders vs responders.

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Acute Urticaria and Anaphylaxis: Differences and Similarities in Clinical Management

By Artículos seleccionados, Selected articles

Ensina LF, Min TK, Félix MMR, et al.

Front Allergy. 2022 Apr 15;3:840999. doi: 10.3389/falgy.2022.840999. eCollection 2022.

Acute urticaria is common and presents with wheals and/or angioedema. These symptoms are also frequent in anaphylaxis, a life-threatening reaction that must be immediately treated. In both conditions, mast cells have a central role in their mechanism of action. Although these similarities, the diagnostic approach is usually different, as it depends on the suspicious triggers, age of the patient and region where they’re based.

Anaphylaxis must be treated with adrenaline as first-line while urticaria flares can be treated with H1-antihistamines are the first choice.

The best approach to prevent anaphylaxis or acute urticaria episodes is to avoid the trigger that is responsible for the reaction, having in consideration that a solution may be desensitization to drugs and foods in selected patients to improve their quality of life.

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Academic productivity of young people with allergic rhinitis: A MASK-air® study

By Artículos seleccionados, Selected articles

Viera RJ, Pham-Thi N, Anto JM

J Allergy Clin Immunol Pract. 2022 Aug 20;S2213-2198(22)00820-0. doi: 10.1016/j.jaip.2022.08.015. Versión digital previa a la impresión.

Allergic rhinitis has a high prevalence, with more than 400 million affected globally. The aim of this study was to use real-world data to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale – VAS education – and the WPAI+CIQ:AS questionnaire), and to identify factors associated with the impact of allergic rhinitis on academic performance.

Data from 1970 users of the MASK-air® mHealth app between 13 and 29 years old was used. Researchers assessed the correlation between variables calculating the impact of allergies on academic performance (VAS education, WPAI+CIQ:AS impact of allergy symptoms on academic performance, and WPAI+CIQ:AS percentage of education hours lost due to allergies), and other variables. Furthermore, they have identified factors linked to the impact of allergic symptoms on academic productivity through statistical models.

VAS education was strongly correlated with the WPAI+CIQ:AS impact of allergy symptoms on academic productivity, VAS global allergy symptoms, and VAS nose. In multivariable regression models, immunotherapy showed a strong negative association with VAS education. Poor rhinitis control, measured by the combined symptom-medication score, was associated with worse VAS education, higher impact on academic productivity, and higher percentage of missed education hours due to allergy.

In conclusion, allergy symptoms and worse rhinitis control are correlated with worse academic productivity, while immunotherapy is linked to higher productivity.

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Current treatment strategies for seasonal allergic rhinitis: where are we heading?

By Artículos seleccionados, Selected articles

Ridolo E, Incorvaia C, Pucciarini F, et al.

Clin Mol Allergy. 2022 Aug 10;20(1):9. doi: 10.1186/s12948-022-00176-x.

Allergic rhinitis is caused by pollens and its symptoms include sneezing, nasal congestion, rhinorrhea, nasal itching and airflow obstruction. Allergic rhinitis diagnosis is usually made based on clinical history, skin prick tests and biomarkers measurement of specific IgE, but there is space for precision medicine to provide more accurate diagnostic tools.

The aim of this review was to describe the advances in the treatment of seasonal allergic rhinitis and evaluate the drugs to be used according to the grade of disease and the characteristics of the patients, and the role of allergen immunotherapy.

The experts concluded that treatment of allergic rhinitis includes various agents, depending on the severity of the disease. Allergen immunotherapy has high evidence of demonstrated efficacy demonstrated, and precision medicine is improving a lot the diagnosis of allergic rhinitis. Nevertheless, there is a long-term low adherence to allergen immunotherapy that needs to be resolved in the future.

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The ARIA approach of Value-Added Medicines: as-needed treatment in allergic rhinitis

By Artículos seleccionados, Selected articles

Bousquet J, Toumi M, Sousa-Pinto B, et al.

J Allergy Clin Immunol Pract . 2022 Aug 4;S2213-2198(22)00749-8. doi: 10.1016/j.jaip.2022.07.020. Online ahead of print.

Allergic rhinitis has a lifetime prevalence of up to 50% in some countries. This constitutes a high burden in social, school and work life. The aim of this report is to demonstrate that Value-Added Medicines such as the use of on-demand (PRN) nasal sprays may be enough to manage allergic rhinitis.

Value-Added Medicines consists of the research of existing medicines for new therapeutic purposes.

Current treatment for allergic rhinitis consists in continuous long-term treatments after clinical trials carried for at least 14 days with over 70% adherence. A new format to treat allergic rhinitis could be using on demand treatments according to symptoms, instead of the continuous treatment.

Real-world data found that 90% of the patients increase their medications to control symptoms during the pollen season, including oral H1-antihistamines, which is not in line with the recommendations.

As most patients who request for a primary care appointment have uncontrolled symptoms, they don’t follow the long-term prescription and self-medicate.

In conclusion, real-life data indicates that patients prefer on-demand treatment instead of continuous and this should be reflected in the upcoming orientations: individualized treatment according to symptom profile, severity, and duration, along with the patient’s preference for oral or intranasal administration.

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Update on pathomechanisms and treatments in allergic rhinitis

By Selected articles

Zhang Y, Lan F, Zhang L

Allergy. 2022 Jul 27. doi: 10.1111/all.15454. Online ahead of print.

Allergic rhinitis represents a worldwide health problem with increasing prevalence and relationship to a growing medical and socioeconomic burden. The objective of this review was to recognize immune cells such as type 2 innate lymphocytes (ILC2s), T helper (Th2) 2 cells, follicular helper T cells, follicular regulatory T cells, regulatory T cells, B cells, dendritic cells, and epithelial cells in allergic rhinitis pathogenesis.

It is important to have an in-depth understanding of the mechanisms of allergic rhinitis to help with the identification of biomarkers and eventually provide valued parameters o guide tailored targeted therapy. Allergen-specific immunotherapy is the only etiological treatment option for allergic rhinitis with evidence for effectiveness and that has been gaining increased attention. This immunotherapy recently demonstrated effectiveness and evidence in several randomized controlled trials and long-term real-life studies. The research of biologics as therapeutic options for allergic rhinitis has only involved anti-IgE and anti-type 2 inflammatory agents; nevertheless, the cost-effectiveness of these agents still needs to be explained.

During the COVID-19 pandemic, allergic rhinitis has not showed a risk factor for severity and mortality of COVID-19, however this needs to be confirmed in multi-centre, real-life studies worldwide.

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In silico Identification of Immune Cell-Types and Pathways Involved in Chronic Spontaneous Urticaria Connor Prosty

By Selected articles

Prosty C, Gabrielli S, Ben-Shoshan M, Le M, Giménez-Arnau AM, Litvinov IV, Lefrançois P, Netchiporouk E

Front Med (Lausanne). 2022 Jul 7;9:926753. doi: 10.3389/fmed.2022.926753. eCollection 2022.

Chronic spontaneous urticaria (CSU) is defined by the presence of wheals and/or angioedema that occur in the absence of specific external stimuli and persist for more than 6 weeks. Its immunopathogenesis is not yet fully understood, but there are new trends on dividing patients into auto allergic and autoimmune subtypes.

The aim of this study was to investigate immune cells and pathways of CSU through the reanalysis of available transcriptomic data.

Investigators obtained microarray data of CSU and healthy control skin and blood from the Gene Expression Omnibus. Differentially expressed genes were analyzed using ToppGene and KEGG and cell-type enrichment was determined by CIBERSORT and xCell and correlated with clinical characteristics.

Th2 (IL-4/13 signaling) and Th17-related (IL-17/23 signaling) patways were found to be upregulated in lesional samples. CIBERSORT analysis showed that non-lesional samples had increased regulatory T-cells and resting mast cells. The xCell analysis revealed no significant differences between samples, however, Th2 scores in both types of samples correlated positively with disease severity. There were few differentially expressed genes and pathways identified between CSU and healthy control blood samples.

These results revealed and supported the connection of Th2 and Th17-related genes and pathways in CSU. Th2 scores related to disease severity, where increased resting mast cell and Treg scores in non-lesional samples indicate local suppression of wheal formation. Furthermore, disease activity seemed to be restricted to the skin as there were limited findings from blood. More studies are needed to further support this information.

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Mechanism of Lower Airway Hyperresponsiveness Induced by Allergic Rhinitis Yiting Liu

By Artículos seleccionados, Selected articles

Liu Y, Sha J, Meng C, Zhu D

J Immunol Res. 2022 Jul 12;2022:4351345. doi: 10.1155/2022/4351345. eCollection 2022.

Allergic rhinitis affects up to 40% of adults and 25% of children globally, however its mechanisms are not yet well elucidated. The majority of people with allergic rhinitis also have lower airway hyperresponsiveness, and an allergic rhinitis occurrence can increase this hyperresponsiveness.

The aim of this review was to understand the mechanism of the effect of allergic rhinitis on the lower airways. The effects of allergic rhinitis on the lower airways were studied in terms of epidemiology, anatomy, pathophysiology, nasal function loss, inflammation drainage, nasobronchial reflex, and whole-body circulatory flow to elucidate the mechanisms involved and provide patterns for future diagnosis, treatment, and experiments.

Researchers concluded that these mechanisms cannot be explained by a single mechanism, but by an interaction of several ones. The hyperresponsiveness of the lower airway may be caused by the rhinopulmonary reflex, lower airway drainage of allergens and nasal obstruction. However, it may also be caused by circulating factors such as IL-5 that stimulate bone marrow cells to differentiate into eosinophils and for IL-4 and IL-13 to upregulate adhesion- and chemotaxis-related proteins. More studies are needed to design future diagnosis and treatment approaches.

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Urticaria in Pregnancy and Lactation

By Artículos seleccionados, Selected articles

Kocatürk E, Podder I, Zenclussen AC, Kasperska Zajac A, Elieh-Ali-Komi D, Church MK, Maurer M

Front Allergy. 2022 Jul 7;3:892673. doi: 10.3389/falgy.2022.892673. eCollection 2022.

More women than men suffer from chronic urticaria, and they are mostly affected in their reproductive age, including pregnancy. Sex hormones affect mast cell biology and the hormonal changes that occur in pregnancy modulate inflammatory conditions such as chronic urticaria.

Pregnancy-related changes in the immune system, involving local adaptation of innate and adaptive immune responses and skewing of adaptive immunity toward a Th2/Treg profile were found to be related to changes in inflammatory diseases. The PREG-CU study provided the first insights on the effect of pregnancy on chronic urticaria, the outcomes of pregnancy in pregnant women with chronic urticaria and safety of urticaria medications and revealed that chronic urticaria improves during pregnancy in half of pregnant women, whereas it worsens in one-third. Also, two of five pregnant women with chronic urticaria experience flare-ups during pregnancy.

The international EAACI/GALEN/EuroGuiDerm/APAAACI guideline for urticaria recommends the same management strategy in pregnant and lactating women with chronic urticaria: start with standard doses of second-generation (non-sedative) H1 antihistamines and increase the dose up to 4-folds in case of no response. Antihistamine-refractory patients should be given omalizumab.

The PREG-CU study assessed treatments and their outcomes during pregnancy: H1 antihistamines, montelukast, omalizumab, cyclosporine-A and systemic steroids, however there isn’t still enough information on the management of chronic urticaria during pregnancy.

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Usage patterns of oral H1-antihistamines in 10 European countries: A study using MASK-air® and Google Trends real-world data

By Artículos seleccionados, Selected articles

Vieira RJ, Sousa-Pinto B, Anto JM, Sheikh A, Klimek L, Zuberbier T, Fonseca JA, Bousquet J

World Allergy Organ J. 2022 Jun 24;15(7):100660. doi: 10.1016/j.waojou.2022.100660. eCollection 2022 Jul.

Real-world data may help provide important data on different conditions, namely allergic rhinitis. However, evaluating this information can represent a challenge, as results from internet users may be influenced by different factors, from the real epidemiology of the conditions being evaluated, but also by the attention they get in the media.

This study compared real-world data from MASK-air®, a mobile app for allergic rhinitis on the usage of oral H1-antihistamines from 2016 to 2020 in 10 European countries with Google Trends data on the relative volume of search for these antihistamines.

5 different oral H1-antihistamines were selected for each country and the investigators perceived a perfect agreement on the order of antihistamine use in MASK-air® and Google Trends in France, Germany, Sweden, and the United Kingdom. Different levels of agreement were observed in the remaining countries (Italy, Poland, Portugal, Spain, Switzerland, Netherlands). Sales data-wise, there was a consistency in data from Google Trends and MASK-air® in France, Germany and the United Kingdom.

In conclusion, these results suggest that the mobile app MASK-air® data may have a common trend in relation to other real-world data, however, more studies are needed.

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