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There is an unmet need for psychometrically sound instruments to measure pruritus associated with prurigo nodularis (PN).
Learn More >Chronic pruritus has considerable implications for quality of life (QoL). However, its impact on health-related QoL and economic burden is not fully characterized. We administered a cross-sectional survey of 132 patients with chronic pruritus using the Health Utilities Index Mark 3 (HUI3) instrument. Normative data from healthy adults (n=4,187) were obtained from the Joint Canada/U.S. Survey of Health. Quality-adjusted life-year (QALY) loss and economic costs were estimated based on HUI3 scores of chronic pruritus patients vs. controls. Patients with chronic pruritus had lower overall health performance compared to the control (0.56±0.03 vs. 0.86±0.003, p<0.001). In multivariable regression, chronic pruritus was associated with worse overall health performance (coefficient -0.30, 95% CI [-0.33 to -0.27]), most accentuated in the domains of pain (coefficient -0.24, [-0.28 to -0.21]) and emotion (coefficient -0.11, [-0.13 to -0.10]). The reduced HUI3 score correlated to 5.5 average lifetime QALYs lost per patient. Using conservative estimates for willingness-to-pay, the QALY loss translated to an individual lifetime economic burden of $274,921 and a societal burden of $88.8 billion. Chronic pruritus is associated with significant QoL impairment. The economic burden of chronic pruritus highlights the necessity of further research into management options.
Learn More >Psoriasis (PS) is a chronic inflammatory skin disease accompanied by reduced quality of life. Mindfulness is the ability to focus on the present moment without evaluation. Findings on the effects of 8-week mindfulness trainings in patients with PS reveal positive effects on the severity of the disease and quality of life. However, it remained unclear what distinguishes patients with PS interested in psychological interventions from those without interest and whether also a shorter, namely 2-week mindfulness-based intervention is beneficial in this patient group. This will be investigated with this study.
Learn More >Recent advances in our understanding of the pathophysiology of atopic dermatitis (AD) have revealed that skin microbiome dysbiosis plays an important role in the disease. In this review, we describe how changes in the structure and function of the microbiome are involved in the pathogenesis of AD. We highlight recent data showing that differential changes in microbial diversity, both within and across communities from different body habitats (including the skin, gut, and oral mucosa), are associated with the development and severity of AD. We also describe recent evidence demonstrating that the metabolic activity of the skin microbiome can act as a regulator of inflammation, with alterations in the level of a skin microbiome-derived tryptophan metabolite, indole-3-aldehyde (IAId), being shown to play a role in AD. The various mechanisms by which interactions between the microbiome and components of the non-histaminergic pathway result in itch in AD are also discussed.
Learn More >Innocuous mechanical stimuli, such as rubbing or stroking the skin, relieve itch through the activation of low-threshold mechanoreceptors (LTMRs). However, the mechanisms behind this inhibition remain unknown. We presently investigated whether stroking the skin reduces the responses of superficial dorsal horn neurons to pruritogens in male C57BL/6J mice. Single-unit recordings revealed that neuronal responses to chloroquine were enhanced during skin stroking, and this was followed by suppression of firing below baseline levels after the termination of stroking. Most of these neurons additionally responded to capsaicin. Stroking did not suppress neuronal responses to capsaicin, indicating state-dependent inhibition. Vesicular glutamate transporter 3 (VGLUT3)-lineage sensory nerves compose a subset of LTMRs. Stroking-related inhibition of neuronal responses to chloroquine was diminished by optogenetic inhibition of VGLUT3-lineage sensory nerves in male and female / mice. Conversely, in male and female mice, optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited firing responses of spinal neurons to pruritogens after the termination of stimulation. This inhibition was nearly abolished by spinal delivery of the κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride, but not the neuropeptide Y receptor Y1 antagonist BMS193885. Optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited pruritogen-evoked scratching without affecting mechanical and thermal pain behaviors. Therefore, VGLUT3-lineage sensory nerves appear to mediate inhibition of itch by tactile stimuli.Rubbing or stroking the skin is known to relieve itch. We investigated the mechanisms behind touch-evoked inhibition of itch in mice. Stroking the skin reduced the activity of itch-responsive spinal neurons. Optogenetic inhibition of VGLUT3-lineage sensory nerves diminished stroking-evoked inhibition, and optogenetic stimulation of VGLUT3-lineage nerves inhibited pruritogen-evoked firing. Together, our results provide a mechanistic understanding of touch-evoked inhibition of itch.
Learn More >Dupilumab has demonstrated efficacy and acceptable safety in adults and children (aged 6-17 years) with moderate-to-severe atopic dermatitis (AD), but effective systemic therapy with a favorable risk-benefit profile in younger children remains a significant unmet need.
Learn More >Itch is a cardinal feature of pediatric disorders and can impair quality of life. However, few studies have addressed symptoms and impacts of itch in pediatric patients.
Learn More >Chronic pruritus is one dermatologic manifestation of an underlying substance use disorder. Recent literature has uncovered similarities between the general neurological mechanisms of addiction and chronic itch, largely involving activation of the dopaminergic reward circuits within the brain and imbalances between opioid mu- and kappa-opioid receptor activation. It is likely that use of specific drugs, like central nervous system (CNS) stimulants and opioids, results in further activation and imbalances within these pathways, perpetuating both addiction and pruritus simultaneously. Opioid users often present to dermatology clinics with a generalized pruritus, while individuals using CNS stimulants like cocaine and methylenedioxymetamphetamine (MDMA), as well as legally prescribed drugs like treatments for ADHD, frequently complain of crawling, delusional infestation-like sensations underneath the skin. Because of these overlapping mechanisms and similar clinical presentations to many other chronically itchy conditions, it is necessary for dermatologists to consider and investigate an underlying substance use disorder in order to effectively treat these patients.
Learn More >DNA methylation is an epigenetic modification that regulates gene transcription. DNA methyltransferase 1 (DNMT1) plays an important role in DNA methylation. However, the involvement of DNMT1 and DNA methylation in the pathogenesis of atopic dermatitis (AD) remains unclear. In this study, microarray analysis revealed that peripheral blood mononuclear cells of AD patients with low DNMT1 expression (DNMT1-low) highly expressed dendritic cell (DC) activation-related genes. Also, DNMT1-low AD patients exhibited a higher itch score compared to AD patients with high DNMT1 expression (DNMT1-high). By using an AD-like mouse model induced by the application of Dermatophagoides farinae body ointment, we found that Dnmt1 expression was decreased, while the expression of C-C chemokine receptor type 7 (Ccr7) was upregulated in mouse skin DCs. Furthermore, mice exposed to social defeat stress exhibited Dnmt1 downregulation and Ccr7 upregulation in skin DCs. Additionally, dermatitis and itch-related scratching behavior were exacerbated in AD mice exposed to stress. The relationship between low DNMT1 and itch induction was found in both human AD patients and AD mice. In mouse bone marrow-derived DCs, Ccr7 expression was inhibited by 5-aza-2-deoxycytidine, a methylation inhibitor. Furthermore, in mouse skin DCs, methylation of CpG sites in Ccr7 was modified by either AD induction or social defeat stress. Collectively, these findings suggest that social defeat stress exacerbates AD pathology through Dnmt1 downregulation and Ccr7 upregulation in mouse skin DCs. The data also suggest a role of DNMT1 downregulation in the exacerbation of AD pathology.
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