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The Role of BTK Inhibition in CSU

Video content above is prompted by the following:

We previously discussed the role that BTK plays in mediating mast cell degranulation. Why does this make BTK an ideal target for CSU treatment?

Videos

Bruton's tyrosine kinase (BTK) is integral in the signaling pathways that lead to mast cell degranulation, a key process in chronic spontaneous urticaria (CSU). Targeting BTK can potentially inhibit this degranulation, reducing the release of histamines and other inflammatory mediators responsible for CSU symptoms. By focusing on BTK, treatments can more precisely modulate the immune response, offering a targeted therapeutic approach. This specificity may lead to improved efficacy and reduced side effects compared to broader immunosuppressive therapies.

Panelists discuss how Bruton tyrosine kinase’s (BTK) role in mediating mast cell degranulation makes it an ideal target for chronic spontaneous urticaria (CSU) treatment, as inhibiting BTK could effectively reduce histamine release and its associated symptoms.

Novel Therapeutics in Development for CSU

Can you describe what you see as the current and future role of advanced treatments such as biologics and BTK inhibitors in CSU management?

What gap currently exists in transitioning from antihistamine cycling to a biologic?

Steroids are often employed in the management of chronic spontaneous urticaria (CSU) to provide rapid relief from severe symptoms. However, their use is typically limited to short-term interventions due to potential adverse effects associated with long-term systemic steroid use. Practitioners should exercise caution, considering the risk of side effects such as osteoporosis, hypertension, and glucose intolerance. It is crucial to balance the benefits of symptom control with the potential for harm, and to explore alternative therapies for long-term management to minimize reliance on systemic steroids.

Panelists discuss how the integration of advanced treatments such as biologics and Bruton tyrosine kinase (BTK) inhibitors can bridge the gap in managing chronic spontaneous urticaria (CSU) for patients unresponsive to antihistamines.

Chelsie Derman is an assistant editor for 

who covers psychiatry, sleep medicine, and geriatrics. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

New data demonstrates that patients with violence in 

 had lower gray matter volume in the left frontal pole and greater thyroid-stimulating hormone (TSH) levels than patients who were not exhibiting violence.

Frontal lobe gray matter changes are linked to violence in schizophrenia.

However, not a lot is known about the relationship between thyroid dysfunction and frontal lobe gray matter volume, so investigators sought to assess whether TSH was associated with frontal lobe gray matter volume in male patients with violent schizophrenia.

“To the best of our knowledge, this is the first study to investigate the relationship between thyroid hormone levels and frontal lobe [gray matter volume] associated with violence in male patients with [violence in schizophrenia],” wrote investigators, led by Tao Yu, from Anhui Mental Health Center at Hefei Fourth People's Hospital in People's Republic of China.

The study included 29 male patients with violent schizophrenia and 26 without violence who were enrolled in a general psychiatry ward at the Hefei Fourth People’s Hospital in Anhui from December 2021 to March 2022. Violent behavior was defined as aggression toward objects, oneself, and others. Patients were included if they were male, right-handed, did not drink or smoke, and had no neurological diseases; they were excluded if they had substance dependence, history of severe head trauma, mental retardation, and MRI contraindications.

As part of their regular treatment regimen, participants took risperidone (n = 19), paliperidone (n = 8), olanzapine (n = 11), sulfamethoxide (n = 8), clozapine (n = 16), ziprasidone (n = 5) piropilone (n = 5) aripiprazole (n = 3), quetiapine (n = 2), and perphenazine (n = 2). The antipsychotics used were switched to the equivalent chlorpromazine.

Twenty-four hours after admission, patients with violence had their aggression evaluated with the 5-point Modified Overt Aggression Scale, which contained 4 subscales: verbal aggression, aggression against objects, physical aggression against oneself, and physical aggression against others. Participants also had a fasting venous blood sample collected on the morning of the second day of admission so investigators could analyze the concentrations of triiodothyronine (T3), thyroxine (T4), TSH, free triiodothyronine (fT3), and free thyroxine (fT4). Moreover, participants underwent structural resonance imaging (sMRI).

The study discovered significant differences in age and total brain volume between patients with and without violence. For patients with violence, the older they were, the lower total brain volume they had. The research did not find differences between the dosage of chlorpromazine in patients with and without violence.

Investigators saw patients with violence had greater TSH levels than patients without violence.

“[This suggests] that alterations in TSH levels may be involved in [violence in schizophrenia] through changing the frontal pole [gray matter volume],” investigators wrote. “The underlying mechanisms might be that the normal levels of TSH are crucial to the regulation of neuronal differentiation and synaptic plasticity.”

The frontal lobe controls cognitive functions, such as decision-making and problem-solving. When gray matter volume becomes abnormal, individuals experience persecutory delusions that are closely associated with violence.

Investigators wrote high TSH levels might be harmful to the brain structure, resulting in lower levels of T3 and T4 in the brain which are closely related to neurotransmitter release, protein synthesis, and gene transportation. They theorized an inadequate amount of T3 and T4 could impact the gray matter volume in the frontal lobe, although the study found T3, T4, fT3, and fT4 did not differ between patients with and without violence.

Additionally, patients with violence had reduced gray matter volume in the left frontal pole role, compared with those without violence. Even after controlling for total brain volume and age, the reduced gray matter volume in the left frontal pole was still linked to violence in schizophrenia.

“These findings provide valuable insights into the important role of reduced frontal [gray matter volume] in violence among patients with schizophrenia,” investigators wrote. “Additionally, the practical implications are that several potential factors that may lead to increased levels of TSH associated with violence in schizophrenia should be heeded to reduce the risk of violence in schizophrenia. Therefore, alterations in thyroid hormone levels in [violence in schizophrenia] patients should be emphasized.”

Yu T, Pei W, Zhang X, Deng C. Associations Between Thyroid Hormones Levels and Gray Matter Volume of Frontal Lobe Involved into Violence in Male Schizophrenia Patients. Neuropsychiatr Dis Treat. 2024 Nov 18;20:2169-2175. doi: 10.2147/NDT.S481875. PMID: 39583013; PMCID: PMC11583757.

Gou N, Lu J, Zhang S, Liang X, Guo H, Sun Q, Zhou J, Wang X. Structural Deficits in the Frontotemporal Network Associated With Psychopathic Traits in Violent Offenders With Schizophrenia. Front Psychiatry. 2022 Apr 12;13:846838. doi: 10.3389/fpsyt.2022.846838. PMID: 35492688; PMCID: PMC9039223.


Articles

New research highlights a correlation between violence in schizophrenia and reduced gray matter volume in the left frontal pole, alongside elevated thyroid-stimulating hormone (TSH) levels. The study, involving male patients with violent schizophrenia, suggests that TSH alterations may influence frontal lobe gray matter volume, potentially affecting cognitive functions and contributing to violent behavior. Despite no differences in T3, T4, fT3, and fT4 levels between violent and non-violent patients, the findings underscore the importance of monitoring TSH levels to mitigate violence risk in schizophrenia.

A study found patients with schizophrenia exhibiting violence, vs. those who don’t, have less gray matter volume in the frontal lobe and greater thyroid-stimulating hormone levels.

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Schizophrenia with Violence Linked to Reduced Left Frontal Gray Matter, Higher TSH

Patient Education Tips for CSU and Final Thoughts

Can you describe the importance of patient education and shared decision-making when selecting an appropriate therapy?

What are the unmet needs in CSU management? How is the field evolving?

What advice do you have for allergists for managing CSU based on your experience and the data available?

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Patient education and shared decision-making are crucial in selecting appropriate therapies, as they empower patients and ensure treatment plans align with their values and preferences. In chronic spontaneous urticaria (CSU) management, unmet needs include more effective treatments and better understanding of disease mechanisms. The field is evolving with advancements in biologics and personalized medicine approaches. Allergists should stay informed about emerging therapies, engage patients in discussions about treatment options, and tailor management strategies to individual patient needs and responses, leveraging the latest data and clinical experience.

Panelists discuss the importance of patient education and shared decision-making in selecting appropriate therapies for chronic spontaneous urticaria (CSU), addressing unmet needs in CSU management and the evolving nature of the field, while also offering practical advice for allergists based on their experiences and available data.

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American Association for the Study of Liver Diseases (AASLD)

 released a pair of practice guidelines for the use of blood- and imaging-based noninvasive assessment of fibrosis and steatosis, both intended for adult and pediatric healthcare providers who see patients with chronic liver disease.

Test your knowledge of the 2024 AASLD Practice Guidelines on imaging-based and blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis with this HCPLive Clinical Quiz!

Eliminate the need for imaging modalities

Sterling RK, Duarte-Rojo A, Patel K, et al. AASLD Practice Guideline on imaging-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. 

Sterling RK, Patel K, Duarte-Rojo A, et al. AASLD Practice Guideline on blood-based noninvasive liver disease assessment of hepatic fibrosis and steatosis. 

Early detection of moderate-to-advanced fibrosis is crucial for better outcomes in chronic liver disease patients. While liver biopsy is the traditional "gold standard" for assessing fibrosis and steatosis, its limitations include cost, invasiveness, and potential complications. This highlights the need for noninvasive alternatives. In 2024, the American Association for the Study of Liver Diseases (AASLD) introduced practice guidelines for noninvasive blood- and imaging-based assessments of fibrosis and steatosis, targeting both adult and pediatric healthcare providers managing chronic liver disease patients.

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The Role of BTK Inhibition in CSU

Novel Therapeutics in Development for CSU

Schizophrenia with Violence Linked to Reduced Left Frontal Gray Matter, Higher TSH

Patient Education Tips for CSU and Final Thoughts

Clinical Quiz: AASLD Guidelines for Noninvasive Testing in Chronic Liver Disease