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Monthly Archives

March 2021

Expert consensus on practical aspects in the treatment of chronic urticaria

By Selected articles

Andrea Bauer, et al.

Allergo J Int . 2021 Feb 24;1-12. doi: 10.1007/s40629-021-00162-w. Online ahead of print.

Chronic urticaria is a frequent disease and represents a large burden for many patients because symptoms are often not adequately controlled. Evidence-based diagnosis and treatment of urticaria are part of the existing guidelines. However, these do not address some questions from everyday clinical practice. This study aimed to summarize the results from a digital meeting held in May 2020, where specialists discussed the practical aspects of chronic urticaria to formulate supporting aids for everyday clinical treatment.

It is known that the diagnosis of chronic urticaria is prompt by a physical examination, anamnesis, and laboratory testing, and treatment should be performed similarly, whether there are wheals, angioedema, or both. A second-generation non-sedating H1 antihistamine is the first treatment of choice. If urticaria doesn’t clear in two to four weeks, a higher dosage is recommended. If there is no improvement after two to four weeks, additional treatment with approved IgE antibodies, such as omalizumab should be administered.

When there is no therapeutic success after six months of treatment with omalizumab, it is recommended an off-label treatment with cyclosporin A in addition to existing therapy with H1 antihistamines. In case of acute exacerbations, oral-systemic glucocorticoids can be given up to 10 days to decrease duration and activity.

In conclusion, these recommendations add on to the existing treatment guidelines and support clinical practice with people with chronic urticaria, with the objective to help them live with no symptoms and a better quality of life, ensuring that the treating physician provides good documentation and education to the patient about off-label use of drugs.

This document is only available for registered healthcare professionals


Exaggerated neurophysiological responses to stressor in patients with chronic spontaneous urticaria

By Selected articles

Engel-Yeger B, Maurer M, Hawro T, Zubedat S, Avital A, Kessel A

Clin Exp Allergy. 2021 Feb 22. doi: 10.1111/cea.13854. Versión digital previa a la impresión.

Chronic spontaneous urticaria impacts the quality of life and emotional well-being of people suffering from it. People with chronic spontaneous urticaria have increased emotional distress, anxiety, depression, somatoform disorders, and stress, which correlates with the activity of urticaria.

People with chronic spontaneous urticaria may be more susceptible to stressors and thus have increased stress responses. Stress responses may lead to the secretion of neuropeptides from sensory skin nerves, interacting with mast cells and releasing histamine, causing chronic spontaneous urticaria attacks.

This study compared the stress responses to acoustic startle and stress levels between 47 people with chronic spontaneous urticaria and 56 healthy volunteers. Stress levels were evaluated with the Perceived Stress Scale.

The stressor exposure session was three minutes long. Participants were exposed to 40 randomly spaced auditory startle stimuli. Responses to the stimuli were measured by electromyography assessment of the contraction amplitude of the orbicularis oculi muscle for each startle stimulus and the number of eye blinks.

People with chronic spontaneous urticaria had stronger responses to acoustic startles with high mean electromyography values and a higher number of eye blinks than healthy volunteers. People with urticaria also had longer stress responses and stress levels, as assessed by the Perceived Stress Scale.

In conclusion, people with urticaria have increased stress responses using objective and subjective measures. Underlying neuroimmune mechanisms should be studied further, as it is possible that stress predisposes to chronic spontaneous urticaria and that chronic spontaneous urticaria increases stress, forming a disease amplification loop.

This document is only available for registered healthcare professionals


Antihistamine and cationic amphiphilic drugs, old molecules as new tools against the COVID-19?

By Selected articles

Clara Gitahy Falcao Faria, eta al.

Med Hypotheses . 2021 Jan 24;148:110508. doi: 10.1016/j.mehy.2021.110508. Online ahead of print.

Some studies demonstrate that psychoactive drugs may protect from SARS-CoV-2 infection. H1 antihistamines and cationic amphiphilic drugs (CAD) have been identified as potentially effective against coronavirus. CAD lead to intracellular trafficking disturbances, which disrupt viral entry and replication.

Many antihistamines are also CAD, acting on both virus entry and exerting a negative regulation on IL-6 release from human lung macrophages, which are secreted in great amounts during the cytokine-storm of COVID-19.

H1 antihistamines in general and phenothiazines and derivates, in particular, can represent a useful strategy against SARS-CoV-2 at different stages, from the prophylaxis to complications’ prevention. Also, a sample of 219000 health records demonstrated that three antihistamines (azelastine, diphenhydramine, and hydroxyzine) were associated with reduced incidence of SARS-CoV-2 in people older than 61.

Although more recent studies suggest that a psychiatric disorder can increase the risk of COVID-19 or developing a severe form, the authors came to the assumption that mental health patients, once hospitalized due to COVID-19, have their risk increased due to the possible reduction or interruption of medications with a potential effect against SARS-CoV-2.

In conclusion, the best tolerated drugs with few side effects can become prophylactic candidates to reduce the risk of infection by SARS-CoV-2 in the general population. However, the benefit-risk should always be assessed.

This document is only available for registered healthcare professionals


Predictors of treatment response in chronic spontaneous urticaria

By Selected articles

Jie Shen Fok, Pavel Kolkhir, Martin K. Church, Marcus Ma

Allergy . 2021 Feb 4. doi: 10.1111/all.14757. Online ahead of print.

Chronic spontaneous urticaria consists of wheals, angioedema, or both for more than six weeks. Patients with chronic urticaria have an impaired quality of life that impacts their relationships, work, and sleep. Existing treatment guidelines recommend a treatment escalation from second-generation H1-antihistamines to omalizumab and cyclosporine until complete response.

This review aimed to evaluate the predictors of response and nonresponse to these treatments in chronic spontaneous urticaria.

A systematic search was executed using the PubMed/MEDLINE database, and 73 studies were included. Different levels of evidence were categorized as strong (robust predictors), weak (emerging predictors), or not associated.

High disease activity, high C-reactive protein levels, and D-dimer are robust predictors of a poor or no response to H1-antihistamines. Low serum levels of total IgE may predict omalizumab response. Cyclosporine response may be predicted by a positive basophil histamine release assay, while low total IgE is an emerging predictor.

In conclusion, there are clinical and biochemical predictors of nonresponse to H1-antihistamines and omalizumab, as well as predictors of response to cyclosporine. These predictors can help specialists counsel patients and prioritize patients at risk of nonresponse to be assessed and switched to more effective treatments.

This document is only available for registered healthcare professionals


Repositioning of histamine H1 receptor antagonist: Doxepin inhibits viropexis of SARS-CoV-2 Spike pseudovirus by blocking ACE2

By Selected articles

Shuai Ge, Xiangjun Wang, Yajing Hou, Yuexin Lv, Cheng Wang, Huaizhen He

Eur J Pharmacol . 2021 Jan 23;896:173897. doi: 10.1016/j.ejphar.2021.173897. Online ahead of print.

The spread of the coronavirus SARS-CoV-2 has continuously threatened our global health since the end of 2019. There is an urgent need for effective drugs and vaccines to fight the COVID-19; however, this may take longer than expected. One of the feasible strategies to combat this situation is to repurpose existing drugs, shorten the development time, and fight this virus outbreak.

It has been shown that histamine H1 receptor antagonists (H1-antihistamines) have broad-spectrum antiviral effects.

This study’s objective was to screen potential drugs among histamine H1 receptors that may have the capacity to inhibit the infection by the SARS-CoV-2 virus.

Five FDA-approved H1-antihistamines were found to have bioaffinity to angiotensin-converting enzyme 2 (ACE2), based on the model of ACE2 overexpressing HEK293T cell membrane chromatography.

Afterward, the interaction between these drugs and ACE2 was determined by frontal analysis and surface plasmon resonance (SPR), which also consistently demonstrated that these hits bind to ACE2 at micromolar levels of affinity.

A pseudovirus assay has helped identify that doxepin could inhibit SARS-CoV-2 spike pseudovirus from entering the ACE2-expressing cell, reducing the infection rate to 25,8%.

Doxepin may be a viable drug candidate for clinical trials to fight COVID-19. It is now recommended to compare these results with in vivo results and provide evidence for clinical trials’ final attempt. (215 words)

This document is only available for registered healthcare professionals

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