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Chronic Pruritus in Multiple Sclerosis and Clinical Correlates.

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

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English Version of Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021.

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

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Efficacy and safety of dupilumab in pediatric patients with moderate to severe atopic dermatitis: a real-world study.

Dupilumab is the first human monoclonal antibody that treats atopic dermatitis (AD) by blocking interleukin 4 (IL-4) and interleukin 13 (IL-13), which can suppress the Th2 inflammatory reaction. Effective treatments for pediatric AD patients are limited; therefore, we aimed to assess the efficacy and safety of dupilumab in pediatric AD patients. Fifteen pediatric patients diagnosed with moderate to severe AD and treated with dupilumab were enrolled in this study. SPSS was used to analyze data and obtain the average values of Eczema Area and Severity Index (EASI), SCORing AD (SCORAD), and Children's Dermatology Life Quality Index (CDLQI). GRAPHPAD was used to analyze and plot the statistics. The average EASI values were 19.23 ± 3.03 and 1.69 ± 0.54 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average SCORAD values were 43.27 ± 4.63 and 6.13 ± 1.41 at baseline and at following up for 6 months after standardized treatment protocol, respectively. The average CDLQI value at baseline was 13.53 ± 2.88 and following up for 6 months after standardized treatment protocol was 1.60 ± 0.63. The most frequent adverse event was conjunctivitis. No serious adverse events occurred during the treatment period. Dupilumab could reduce symptoms and improve pruritus in pediatric AD patients, and the frequent adverse events were reversible. It has a definite therapeutic effect on AD; nevertheless, further studies should be conducted to obtain information on its the long-term efficacy and safety.

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Psychological Therapies and Mind-Body Techniques in the Management of Dermatologic Diseases: A Systematic Review.

There is a clear link between skin disease and psychological factors and this relationship works both ways: skin diseases can cause psychological distress and psychological issues can worsen skin disease. There are a number of therapies that approach this problem from the psychological side and may be useful, especially as adjunctive therapies in select patients.

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Difelikefalin: A New κ-Opioid Receptor Agonist for the Treatment of Hemodialysis-Dependent Chronic Kidney Disease-Associated Pruritus.

To review data for difelikefalin (Korsuva) intravenous solution for management of moderate-to-severe pruritus in hemodialysis (HD) patients.

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Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program.

We report a pooled safety analysis of intravenous difelikefalin in participants with moderate to severe chronic kidney disease-associated pruritus (CKD-aP) treated by hemodialysis in 4 phase 3 clinical studies.

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Onset of Plaque Psoriasis Treatment Responses With Anti-IL-17/IL-23 Biologic Therapies.

The impact of psoriasis on quality of life arises from both physical symptoms, such as pain and pruritus, and the psychosocial effects of the often highly visible lesions. For patients with moderate-to-severe psoriasis seeking amelioration of these symptoms, time to onset of treatment response is an important consideration when determining an appropriate therapeutic approach with their healthcare provider.

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Psoriasis of the external auditory canal: prevalence, clinical features and impact on quality of life.

Psoriasis of the external auditory canal (PsEAC) is often under-recognized. The aims of this study were to assess the prevalence of PsEAC, its association with a particular psoriasis subtype and its impact on quality of life (QoL). A prospective study was carried out in two Spanish university hospitals, enrolling consecutive patients who attended a consultation for psoriasis. The clinical features of psoriasis and PsEAC were recorded and the Dermatology Life Quality Index (DLQI) and Itch Numerical Rating Scale (Itch-NRS) were distributed to patients. Overall, 188 of 1000 patients (18.8%) included in the study had PsEAC, which was associated with severity of psoriasis, presence of inverse psoriasis and involvement of the scalp, nails and genitals, but not with obesity or psoriatic arthritis. PsEAC was the main reason for consultation in 27 patients, with itching being the main symptom. In this study, PsEAC had a prevalence of 18.8%. The occurrence of PsEAC was associated with poorer QoL, as measured by DLQI and Itch-NRS.

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Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing.

Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.

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Activation of serotonin receptor 2 by glucosylsphingosine can be enhanced by TRPA1 but not TRPV1: Implication of a novel glucosylsphingosine-mediated itch pathway.

Glucosylsphingosine (GS) is an endogenous sphingolipid that specifically accumulates in the skin of patients with atopic dermatitis (AD). Notably, it was recently found that GS can induce itch sensation by activating serotonin receptor 2A and TRPV4 ion channels. However, it is still uncertain whether other molecules are involved in GS-induced itch sensation. Therefore, by using the calcium imaging technique, we investigated whether serotonin receptor 2 – specifically 2A and 2B – can interact with TRPV1 and TRPA1, because these are representative ion channels in the transmission of itch. As a result, it was found that GS did not activate TRPV1 or TRPA1 per se. Moreover, cells expressing both serotonin receptor 2 and TRPV1 did not show any changes in calcium responses. However, enhanced calcium responses were observed in cells expressing serotonin receptor 2 and TRPA1, suggesting a possible interaction between these two molecules. Similar synergistic effects were also observed in cells expressing serotonin receptor 2 and TRPA1, but not TRPV1. Furthermore, a phospholipase C inhibitor (U73122) and a store-operated calcium entry blocker (SKF96365) significantly reduced GS-induced responses in cells expressing both serotonin receptor 2 and TRPA1, but not with pre-treatment with a Gβγ-complex blocker (gallein). Therefore, we propose a putative novel pathway for GS-induced itch sensation, such that serotonin receptor 2 could be coupled to TRPA1 but not TRPV1 in sensory neurons.

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