Original Research, Human Studies, Itch

Psoriasis impacts various aspects of patients' health-related quality of life and is associated with sleep problems. However, research discussing the associations between interleukin-17 blockage therapies and sleep problems in patients with psoriasis is insufficient. We aimed to assess the effectiveness of brodalumab in alleviating sleep problems in real-life patients with plaque psoriasis. This analysis was part of the single-arm, open-label, multicenter, prospective, cohort study, ProLOGUE (study period October 2017-March 2020), which involved Japanese patients with plaque psoriasis. Assessments included correlation of Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R) scores (Sleep Problems Index-II [SPI-II] and MOS Sleep-R subscale scores) with multiple patient-reported outcome scores and the Psoriasis Area and Severity Index (PASI) at baseline. Additionally, change from baseline in MOS Sleep-R scores was assessed at weeks 12 and 48 of brodalumab treatment. Seventy-three patients were enrolled (male 82.2%, median age 54.0 years). At baseline, the SPI-II score correlated with the Patient Health Questionnaire-8 score (Spearman correlation coefficient [ρ] = -0.474) and weakly correlated with the Itch Numeric Rating Scale (NRS; ρ = -0.366), Skin Pain NRS (ρ = -0.275), and all Treatment Satisfaction Questionnaire for Medication-9 domain scores (ρ = 0.270, ρ = 0.303, and ρ = 0.322 for effectiveness, convenience, and global satisfaction, respectively) but did not correlate with the PASI score. The SPI-II score and MOS Sleep-R subscale scores, except the Snoring score (p = 0.0319), did not significantly change from baseline to week 12 of brodalumab treatment. In conclusion, treatment with brodalumab did not improve overall sleep problems in real-life patients with plaque psoriasis, suggesting that sleep problems require attention in daily clinical practice (Japan Registry of Clinical Trials identifier, jRCTs031180037).

To date, little is known about the prevalence of itch in multiple sclerosis (MS) and its characteristics.

Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized.

Chronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR sensory neurons responded to Serpin E1, resulting in enrichment of numerous itch- and inflammation-related genes and their protein release. PLAUR resides in TLR2 neurons and Serpin E1 stimulus led to transcriptional upregulation of TLR2 and its co-signaling proteins. Agonists of TLR2 propagated itch-related gene transcription including BNP, OSM, and PAR2. OSM induced acute itch in mice and promoted G-CSF and IL-8 release from human keratinocytes. Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.

Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment options are limited.

Chronic itch can severely affect quality of life. Patients report that their chronic itch can be exacerbated by exposure to warm conditions ("warmth hyperknesis"). The aim of this mechanistic study was to investigate the effect of mild heating of the skin in humans on various experimental models of itch. A total of 18 healthy subjects were recruited to the study. Itch was provoked by histamine, serotonin, or cowhage in 3 different sessions. The provoked area was heated with an infrared lamp, and the skin temperature was either not altered, or was increased by 4°C or 7°C. Subsequent to induction of itch, the itch intensity was recorded for 10 min while the skin was heated continuously throughout the entire period of itch induction. Heating the skin resulted in a significant increase in itch intensity when provoked by histamine or serotonin. It is possible that thermoception and pruriception interact and selectively produce a higher itch intensity in histaminergic and serotoninergic itch.

Patients with psoriasis have an impaired quality of life and higher use of analgesics than the general population. Whether such use is due to skin pain or a consequence of joint pain resulting from psoriatic arthritis (PsA) is unclear.

Itch severity in chronic itch patients is influenced by mental state. However, the brain network mediating this nuisance relationship remains unknown. The medial parietal cortex (MPC) is a key hub of the default mode network (DMN) that regulates the mental state and also a brain region selective for itch (i.e., itch, but not pain, activates the MPC). Moreover, antidepressants are used in the treatment of chronic itch and are well known to alter activity in DMN.