Antipruritic Treatment Research Articles

#802 CENSUS-EU: a cross-sectional, study to assess the prevalence and burden of chronic kidney disease-associated pruritus in Europe

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common condition that can negatively affect patients’ health-related quality of life (HRQoL). Despite this, there has been a lack of clarity on its prevalence and impact, leading to increasing interest in and need for an accurate overview of its epidemiology. Here we present the interim analyses of the real-world study CENSUS-EU to estimate the prevalence of CKD-aP and its impact on patients’ HRQoL. Method CENSUS-EU is a retrospective, cross-sectional, multicentre study across seven countries in Europe. Eligible patients (aged ≥18 years and on dialysis for ≥3 months) consenting to participate were asked to complete five patient-reported outcome questionnaires, one on CKD-aP severity (the Worst Itching Intensity Numerical Rating Scale) and four on HRQoL, including the 5-D itch scale and the integrated palliative care outcome scale symptom list for end-stage renal disease (IPOS-Renal). Patients also completed a survey on the communication and management of their pruritus, including current anti-pruritic medication use. In addition, the medical records of patients were assessed to gather retrospective information on clinical dialysis characteristics, treatment patterns and healthcare resource utilisation. In this presentation of the interim data, we report the prevalence of pruritus and the distribution of severity subgroups, how pruritus severity affects the disability score from the 5-D itch (impact on sleep, leisure, errands, and work/school), and the sleep and depression scores from the IPOS-Renal questionnaire. Results The interim analysis included 1,482 patients, of which 59.9% were ≥65 years of age and 61.2% were male. Patient characteristics were balanced across severity subgroups. Overall prevalence of CKD-aP was 52.6% (95% confidence interval 50.02, 55.10); 21.5% of patients experienced mild pruritus, 17.5% moderate pruritus, and 13.5% severe pruritus (Fig. 1). As pruritus severity increased from no pruritus to severe pruritus, patients reported greater difficulty sleeping, as shown by increasing scores for question 2 of the IPOS-Renal questionnaire (Fig. 2A). Patients with more severe pruritus also reported feeling depressed more often than those with less severe or no pruritus (Fig. 2B). There were also increasing scores for the 5-D itch disability subscale (Fig. 2C). Patients with moderate or severe pruritus were also hospitalised more often than patients with mild or no pruritus (mean 1.7 and 1.9 hospitalisations per year, respectively). Overall, 17.9% of patients were receiving at least one ongoing anti-pruritic treatment, and the proportion of patients using at least one anti-pruritic treatment became greater with increasing itch intensity. Despite the impact of pruritus on HRQoL, 40.6% of patients with severe pruritus who had ever suffered from itch while on dialysis were not receiving anti-itch treatment. Conclusion The interim results of this cross-sectional study suggest that approximately 50% of patients on haemodialysis experience CKD-aP. The data reveal that as pruritus severity increases, the effect on sleep and depression scores becomes greater, potentially impacting more deeply on patients’ HRQoL.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Bacterial microbiota and proinflammatory cytokines in the anal sacs of treated and untreated atopic dogs: Comparison with a healthy control group.

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs.

Imiquimod-induced pruritus in female wild-type and knockin Wistar rats: underscoring behavioral scratching in a rat model for antipruritic treatments

ObjectivesAnimal models of skin disease are used to evaluate therapeutics to alleviate disease. One common clinical dermatological complaint is pruritus (itch), but there is a lack of standardization in the characterization of pre-clinical models and scratching behavior, a key itch endpoint, is often neglected. One such model is the widely used imiquimod (IMQ) mouse model of psoriasis. However, it lacks characterized behavioral attributes like scratching, nor has widely expanded to other species like rats.Given these important attributes, this study was designed to broaden the characterization beyond the expected IMQ-induced psoriasis-like skin inflammatory skin changes and to validate the role of a potential therapeutic agent for pruritus in our genetic rat model. The study included female Wistar rats and genetically modified knockin (humanized proteinase-activated receptor 2 (F2RL1) female rats, with the widely used C57BL/6 J mice as a methodology control for typical IMQ dosing.ResultsWe demonstrate that the IMQ model can be reproduced in rats, including their genetically modified derivatives, and how scratching can be used as a key behavioral endpoint. We systemically delivered an anti-PAR2 antibody (P24E1102) which reversed scratching bouts—validating this behavioral methodology and have shown its feasibility and value in identifying effective antipruritic drugs.

What's New in Cutaneous T-Cell Lymphoma-Associated Pruritus.

Cutaneous T-cell lymphomas are a heterogenous group of lymphomas that cause various skin manifestations. Severe pruritus occurs frequently in cutaneous T-cell lymphoma and negatively impacts patients' quality of life. The pathophysiology of cutaneous T-cell lymphoma-associated itch is complex and involves various immune cells, inflammatory cytokines, and neuroimmune interactions. Treating cutaneous T-cell lymphoma pruritus can be challenging, and there have been few randomized controlled studies evaluating the use of antipruritic treatments in these patients. Systemic therapies targeting the disease have also beenshown to have some antipruritic effects. Furthermore, although biologic therapy has revolutionized the treatment of other pruritic skin conditions, the use of biologics in cutaneous T-cell lymphoma remains controversial.

Evaluation of chronic pruritus and associated skin findings in patients with diabetes mellitus.

To explore the dermatological lesions associated with chronic pruritus in patients who were followed up at our clinic for type 1 and type 2 diabetes mellitus (DM). The study population consisted of 249 patients with DM, who presented to the endocrinology clinic at Ankara University Faculty of Medicine between January 2022, and March 2022, regardless of whether they had reported experiencing pruritus symptoms. The visual analog scale and 5-D itch scale were used to determine the severity of itching in patients. Dermatological examination findings were also evaluated. Of the 249 patients with DM, mean duration since diabetes was diagnosed was 12 ± 9.2 [median 10 (0.3-46)] years, and the mean HbA1c levels were 8.1% ± 2.1%. Pruritus was detected in 77 (30.9%) patients and the mean duration of diabetes diagnosis was 13.4 ± 9.7 years. Examination of the microvascular and macrovascular complications showed that the incidence of retinopathy, nephropathy, neuropathy and peripheral arterial disease was 31.2% (p = 0.003), 31.2% (p = 0.005), 66.2% (p < 0.001) and 10.4% (p = 0.038), respectively, in the group with pruritus. These incidences were significantly higher in the group with pruritus than in those without pruritus. Dermatological examination showed that the most common condition was xerosis (64%), followed by fungal skin infection (16%) and bullous pemphigoid (8%). No skin findings were noted in 7% of patients who complained of itching. Chronic pruritus may be associated with several factors such as poor glycemic control, high BMI and microvascular and macrovascular complications in patients with DM. Especially in patients with severe generalized pruritus who do not respond to standard antipruritic treatments, the use of DPP-4 inhibitors, a class of oral antidiabetic agents, should be questioned and all medications being used by the patient should be reviewed.

Mechanisms and treatment of opioid-induced pruritus: Peripheral and central pathways.

Pruritus (also known as itch) is defined as an unpleasant and irritating sensation of the skin that provokes an urge to scratch or rub. It is well known that opioid administration can cause pruritus, which is paradoxical as itch and pain share overlapping sensory pathways. Because opioids inhibit pain but can cause itching. Significant progress has been made to improve our understanding of the fundamental neurobiology of itch; however, much remains unknown about the mechanisms of opioid-induced pruritus. The prevention and treatment of opioid-induced pruritus remains a challenge in the field of pain management. The objective of this narrative review is to present and discuss the current body of literature and summarize the current understanding of the mechanisms underlying opioid-induced pruritus, and its relationship to analgesia, and possible treatment options. The incidence of opioid-induced pruritus differs with different opioids and routes of administration, and the various mechanisms can be broadly divided into peripheral and central. Especially central mechanisms are intricate, even at the level of the spinal dorsal horn. There is evidence that opioid receptor antagonists and mixed agonist and antagonists, especially μ-opioid antagonists and κ-opioid agonists, are effective in relieving opioid-induced pruritus. Various treatments have been used for opioid-induced pruritus; however, most of them are controversial and have conflicting results. The use of a multimodal analgesic treatment regimen combined with a mixed antagonist and κ agonists, especially μ-opioid antagonists, and κ-opioid agonists, seems to be the current best treatment modality for the management of opioid-induced pruritus and pain. Opioids remain the gold standard for the treatment of moderate to severe acute pain as well as cancer pain. It is well known that opioid-induced pruritus often does not respond to regular antipruritic treatment, thereby posing a challenge to clinicians in the field of pain management. We believe that our review makes a significant contribution to the literature, as studies on the mechanisms of opioid-induced pruritus and effective management strategies are crucial for the management of these patients.

#6113 SCRATCHING THE SURFACE? A LONGITUDINAL OBSERVATIONAL STUDY ON PRURITUS AND ITS CURRENT TREATMENT IN INCIDENT DIALYSIS PATIENTS

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in dialysis patients. It is associated with impaired health-related quality of life (HRQoL) and sleep disturbances. The pathophysiology remains unclear resulting in limited treatment options and lack of treatment guidelines. The exact course of CKD-aP after dialysis initiation has not been identified nor the state of current medical treatment. Therefore, the aim of this study was to assess presence and severity of CKD-aP during the first year of dialysis, and to assess how it is currently medically managed. Method Data were used from the ongoing multicentre, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). This study longitudinally compares HRQoL between different dialysis modalities. Incident dialysis patients (&amp;gt; 18 years) were included, if they completed a HRQoL questionnaire around initiation. Pruritus was assessed using the Dialysis Symptom Index (DSI), using a 5-point Likert scale. Medication data were retrieved from electronic patient files. Outcome parameters were prevalence, severity of pruritus and the use of antipruritic medication, both systemic and topical, all measured at dialysis initiation and after 3,6 and 12 months. The association between pruritus and treatment was studied using logistic regression analysis and adjusted for potential confounders. Results A total of 643 patients were included, 70.8% started with hemodialysis and 29.2% with peritoneal dialysis. The mean (SD) age was 64.0 years (13.8) and 68.3% were men. At dialysis initiation 53.5% of all patients suffered from pruritus with a fluctuation in prevalence following the first year of dialysis (Fig. 1). During the first year 35.7% of the patients had persistent itching, 35.5% had fluctuating itching and 28.8% never experienced itching. There was a small increase in number of patients without itching at 3 months followed by an increase in number of patients with ‘quite some itch’ to ‘severe itch’ over the next months (Fig. 2). At 6 months after start dialysis 10.8% of the dialysis patients received topical antipruritic treatment, 17.2% received systemic antipruritic treatment and 3.3% received both topical and systemic treatment. The majority of patients with topical antipruritic treatment received emollients (58.9%) followed by cutaneous steroids (37.6%). Systemic steroids were the most used systemic antipruritic treatment (58.7%), followed by antihistamines (20.4%) and gabapentoids (17.4%). Patients treated with topical agents at 6 months showed an odds ratio of 3.48 (95%CI: 1.11 – 10.91) on severe itching compared to patients without treatment. Furthermore, patients with systemic antipruritic treatment and with both systemic and topical treatment showed an odds ratio of 1.40 (95%CI: 0.48 – 4.03) and 1.52 (95%CI: 0.41 – 5.70) compared to patients without treatment respectively. Conclusion CKD-aP is highly prevalent in incident dialysis patients. The presence of CKD-aP is fluctuating during the first year of dialysis, with a third of patients experiencing intermittent itching. Starting dialysis may have a small beneficial effect on presence and severity of CKD-aP, but this is lost over time with moderate to severe CKD-aP increasing over the following months. Approximately a third of the patients received treatment for CKD-aP, predominantly as systemic treatment. The use of topical antipruritic treatment is associated with more severe CKD-aP at six months after start dialysis. These findings emphasize the need for further research on the pathophysiology and optimal treatment in dialysis patients.

#4400 QUALITY OF LIFE, PRURITUS BURDEN, AND TREATMENT SATISFACTION IN CHRONIC KIDNEY DISEASE PATIENTS IN GERMANY

Abstract Background and Aims Chronic kidney disease (CKD) and its related symptoms significantly impact patients’ health-related quality of life (HRQoL). CKD-associated pruritus (CDK-aP) often affects patients with advanced CKD, particularly those on renal replacement therapy, and remains mostly underrecognized by both patients and medical providers. To explore the current patients’ impairment of HRQoL due to CKD-aP, we conducted a quantitative survey amongst members of a CKD patient association in Germany. Methods Our questionnaire was distributed via the channels of the German National Kidney Patients Association (Bundesverband Niere e.V.) from mid-June to mid-September 2022. Responses of 569 CKD-patients of a total of roughly 16,000 members were analysed regarding their general health, HRQoL, and general treatment satisfaction using multiple choice questions. Pruritus burden was assessed with a 0-10 numeric rating scale. Results The demographic details are displayed in Figure 1. Among the surveyed CKD patients, 33% were transplanted, 39% on hemodialysis, and 7% on peritoneal dialysis. We could confirm that most CKD patients (92 %) suffered from comorbidities. Initially, 12% reported dermatological comorbidities but when asked specifically about pruritus, 62% reported this symptom which was also associated with worse HRQoL (Figure 2). However, only one third was receiving antipruritic treatment by a physician. Furthermore, patients who were able to fully or at least partially participate in their medical decisions showed higher satisfaction and higher HRQoL (86% vs. 65% vs. 43% satisfaction, depending on full/partial/no participation, respectively) yet the patients did not always perceive that shared-decision-making was possible. Patients also showed high interest in topics outside of their primary CKD treatment, such as overall symptom control and additional psychological measures. They reported higher HRQoL when these areas were addressed by the medical team (87% vs. 55% satisfaction). Conclusions Our survey results emphasize the persisting need for shared or co-creative exchange between patient and physician. Improving patient education and the caregiver's awareness of the burden of pruritus – one of the many CKD-related symptoms – could be a first step towards higher patient satisfaction and HRQoL and higher treatment rates. CKD-aP appears underreported by patients via unprovoked questioning and should be screened frequently.

Pruritus in cutaneous graft-versus-host disease: A systematic review.

Pruritus is a common symptom of cutaneous graft-versus-host disease (GVHD) following haematopoietic stem cell transplantation (HSCT). However, little is known about its prevalence, pathophysiology, perceptual characteristics, impact on quality of life and response to antipruritic therapies. The aim of this review was to determine the current knowledge on pruritus in cutaneous GVHD. The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Of the 338 studies screened, 13 were included. The prevalence of pruritus in cutaneous GVHD was reported in three studies, ranging from 37.0% to 63.8%. Only four trials used pruritus assessment tools. There was little or no information on the intensity of pruritus, its qualitative perception, the location of pruritus and the impact of pruritus on quality of life. Antipruritic treatments for GVHD-associated pruritus were mentioned in five studies (38.5%), including topical ointments (steroids, tacrolimus and calcipotriene), broadband UVB, systemic antihistamines and oral ursodeoxycholic acid. In conclusion, pruritus in cutaneous GVHD appears to be common, but very little is known about the pathophysiology, impact on quality of life and effective treatment options. Basic research and controlled clinical trials are warranted to improve knowledge and management of this important issue.

GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet are involved in itch processing in mice

Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear. In this study, chloroquine and histamine were utilized to induce acute itch models in mice. Neuronal activities in vLGN/IGL nucleus were evaluated with c-fos immunostaining as well as fiber photometry. Optogenetic manipulations were performed to activate or inhibit GABAergic neurons in the vLGN/IGL nucleus. Our results showed that the expressions of c-fos in vLGN/IGL were significantly increased upon both chloroquine- and histamine-induced acute itch stimuli. GABAergic neurons in vLGN/IGL were activated during histamine and chloroquine-induced scratching. Optogenetic activation of the vLGN/IGL GABAergic neurons exerts antipruritic effect, while inhibiting these neurons exerts pruritic effect. Our results provide evidence that GABAergic neurons in vLGN/IGL nucleus might play a crucial role in modulating itch, which may provide clue for application of bright light as an antipruritic treatment in clinic.

Dupilumab for Recurrent Prurigo Nodularis: A Case Report and Review of the Literature

Prurigo nodularis (PN) is a chronic inflammatory skin disease that affects the quality of life of patients and is classified in the ICD-10 as a group of chronic lichen simplex and itchy skin diseases (ICD-10/L28) with an incidence of approximately 36.7-148.53 per 100,000 people. The pathogenesis of PN is closely related to type 2 inflammatory response. There are no standardized treatment guidelines for this disease, and traditional anti-pruritic treatment regimens often fail to control the vicious pruritic-scratch cycle in PN and have a poor safety profile. Traditional treatment options for PN include oral antihistamines, thalidomide, and topical hormones, calcium phosphatase inhibitors, and other treatments. However, traditional treatment options often suffer from poor pruritus control and high side effects. A patient with prurigo nodularis was admitted to our hospital who responded poorly to routine topical glucocorticoids and other drug therapies and relapsed after discharge from treatment. After readmission, the patient was successfully treated with dupilumab, a biological agent targeting interleukin-4/13. The patient's rash was significantly flattened, and the pruritus NRS score was significantly decreased. In this case, successful treatment of refractory PN with dupilumab could provide new ideas for treatment.

Transient Receptor Potential Channels and Itch

Transient Receptor Potential (TRP) channels are multifunctional sensory molecules that are abundant in the skin and are involved in the sensory pathways of itch, pain, and inflammation. In this review article, we explore the complex physiology of different TRP channels, their role in modulating itch sensation, and their contributions to the pathophysiology of acute and chronic itch conditions. We also cover small molecule and topical TRP channel agents that are emerging as potential anti-pruritic treatments; some of which have shown great promise, with a few treatments advancing into clinical trials-namely, TRPV1, TRPV3, TRPA1, and TRPM8 targets. Lastly, we touch on possible ethnic differences in TRP channel genetic polymorphisms and how this may affect treatment response to TRP channel targets. Further controlled studies on the safety and efficacy of these emerging treatments is needed before clinical use.

Clinical Efficacy and Safety of Chinese Herbal Medicine in the Treatment of Uremic Pruritus: A Meta-Analysis of Randomized Controlled Trials.

Uremic pruritus is a disturbing and refractory symptom in patients with advanced chronic kidney disease. Chinese herbal medicine has been reported to alleviate uremic pruritus. To investigate the effects of Chinese herbal medicine, we conducted a systematic review and meta-analysis on patients with uremic pruritus. We searched databases (prior to 3 May 2022) for randomized controlled trials on the effects of Chinese herbal medicine in treating uremic pruritus. Our meta-analysis included 3311 patients from 50 randomized controlled trials. In patients with uremic pruritus, adjunctive Chinese herbal medicine significantly improved overall effectiveness (risk ratio 1.29, 95% CI 1.23 to 1.35), quality of life, renal function, reduced pruritus score, and inflammatory biomarkers compared to control groups with hemodialysis alone or with anti-pruritic treatments. Chinese herbal medicine treatment showed a time-dependent tendency in improving the visual analog scale of dialysis patients. Compared to control groups, no significantly higher risk of adverse events in patients taking Chinese herbal medicine (risk ratio 0.60, 95% CI 0.22 to 1.63). Chinese herbal medicine appears to be effective and safe in complementing the treatment of patients with uremic pruritus.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

33993 Oral difelikefalin improves itch and quality of life in subjects with itch-dominant atopic dermatitis: Subgroup analysis of a randomized, phase 2 study

Background: In atopic dermatitis (AD), pruritus and lesional severity are not well correlated. Patients with limited body surface area (BSA) involvement may have intense pruritus not fully addressed by available therapies. Itch-dominant AD impairs quality of life (QoL). We report efficacy of oral difelikefalin (DFK), a kappa-opioid receptor agonist, for pruritus, QoL, and sleep disturbance in subjects with BSA <10% receiving DFK 0.5 mg or placebo (PBO) for 12 weeks. Methods: Phase 2, randomized, PBO-controlled study (NCT04018027) in adults with AD (Investigator Global Assessment ≥2, BSA ≤30%) and moderate-to-severe pruritus (Itch Numerical Rating Scale [I-NRS] ≥5.0) inadequately controlled by topical therapy. Results: Subjects (DFK, n = 82; PBO, n = 79) had high disease burden (mean I-NRS, 7.7, 7.6, respectively; DLQI, 10.6, 12.0) despite limited Eczema Area and Severity Index (mean, 4.0, 3.7). At week 12, a significantly greater proportion of subjects receiving DFK achieved ≥4-point I-NRS improvement versus PBO (33% vs 19%; P < .05; OR = 2.1). Greater proportions of subjects receiving DFK achieved responses at week 12 on the Patient Global Impression of Change (“much improved” or “very much improved”: 50% vs 35%; OR = 1.8); Sleep NRS (≥3-point improvement: 57% vs 47%; OR = 1.5); and Dermatology Life Quality Index (≥4-point improvement: 62% vs 50%; OR = 1.6). Conclusion: Itch-dominant AD is associated with impaired QoL despite mild-to-moderate lesional severity, suggesting that itch reduction should be a primary treatment goal in these patients. DFK showed clinically meaningful improvements in itch intensity, sleep, and QoL and may address the unmet need for a safe, effective antipruritic treatment in itch-dominant AD.

The effects of oclacitinib treatment on antimicrobial usage in allergic dogs in primary practice: an Australia wide case-control study

BackgroundCanine allergic dermatitis is a common diagnosis in veterinary practices which can lead to secondary infections requiring treatment with antimicrobials. A previous study suggested that dogs treated with oclacitinib in an Australian referral hospital required fewer courses of antimicrobial therapy compared to dogs receiving other anti-pruritic treatments. This study aimed to quantify the effect of oclacitinib treatment on the use of antimicrobials and other therapies in general practice veterinary clinics across Australia. A retrospective case-controlled review of patient records was designed to investigate the number of courses of antimicrobials and other therapies in dogs that received oclacitinib (Apoquel®), compared with those who received an anti-pruritic treatment that was not oclacitinib.ResultsThe target population included canine patients with a presumptive diagnosis of allergic dermatitis presenting between 2008 and 2018 to general practices contributing to the VetCompass Australia database. Patient records of interest were identified using search terms relating to allergic dermatitis, resulting in over 700,000 observations. Multivariable logistic regression models were developed to determine whether cases were prescribed fewer antimicrobial courses than controls, after adjusting for the presence of concurrent skin infections or infectious agents in ears. Our results indicate that fewer antimicrobial courses were prescribed in the cases compared to the controls. After adjusting for the concurrent skin infections, there was a significant reduction in the use of cefovecin [OR:0.62(0.39–0.98), P = 0.043], chlorhexidine [OR:0.57(0.42–0.77), P < 0.001], neomycin [OR:0.4(0.28–0.56), P < 0.001] and amoxycillin clavulanic acid (AMC) [OR: 0.55(0.39–0.78), P = 0.001] in cases compared to controls.ConclusionThis study demonstrates a potential sparing effect of oclacitinib on the prescription of antimicrobials for the treatment of allergic skin diseases in dogs. This information may assist in the planning of treatment for canine allergic dermatitis, with consideration for antimicrobial stewardship.

Pruritus in Pregnancy.

Pruritus in pregnancy is a common and burdensome symptom that may be a first sign of a pregnancy-specific pruritic disease (atopic eruption of pregnancy, polymorphic eruption of pregnancy, pemphigoid gestationis, and intrahepatic cholestasis in pregnancy) or a dermatosis coinciding with pregnancy by chance. Despite its high prevalence, pruritus is often underrated by physicians, and data regarding the safety profiles of drugs for pruritus are very limited. In this review, we illustrate the epidemiology, possible pathophysiology, clinical characteristics, and diagnostic workup of various pregnancy-related diseases and discuss antipruritic treatments. The prevalence of pruritus in pregnancy demonstrates the importance of symptom recognition and the need for an holistic approach, taking into account both the potential benefits for the patient and the potential risks to the fetus.

Multilineage-differentiating stress-enduring cells alleviate atopic dermatitis-associated behaviors in mice

BackgroundPruritus is a recurring, long-lasting skin disease with few effective treatments. Many patients have unsatisfactory responses to currently available antipruritic treatments, and effective therapeutics are urgently needed to relieve symptoms. A previous study reported that mesenchymal stem cell (MSC)-mediated immune regulation could be used to treat skin inflammatory diseases. Multilineage-differentiating stress-enduring (Muse) cells are a new type of pluripotent stem cell that may also have the potential to treat inflammatory skin diseases.MethodsMuse cells were isolated from human bone marrow-derived MSCs (BMSCs) via the 8-h longterm trypsin incubation (LTT) method. Repeated use of 2,4-dinitrofluorobenzene (DNFB) induced atopic dermatitis (AD) in a mouse model. Immunofluorescence, behavior recording, and image analysis were used to evaluate the therapeutic effect of subcutaneous Muse cell injection. Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of inflammatory factors. In vitro, wound healing and cell proliferation experiments were used to examine the effect of Muse cell supernatant on keratinocytes.ResultsOur results showed that subcutaneous injection of Muse cells after AD model induction significantly alleviated scratching behavior in mice. The evaluation of dermatitis and photos of damaged skin on the back of the neck revealed that Muse cells reduced dermatitis, playing an active role in healing the damaged skin. The activation of spinal glial cells and scratching behavior were also reduced by Muse cell injection. In addition, we also showed that the expression levels of the inflammatory factors interleukin (IL)-6, IL-17α, and IL-33 in both the spinal cord and skin were suppressed by Muse cells. Furthermore, Muse cells not only exerted anti-inflammatory effects on lipopolysaccharide (LPS)-induced human HaCat cells but also promoted wound healing and keratinocyte proliferation.ConclusionsIn vivo, Muse cells could alleviate scratching symptoms, reduce epidermal inflammation, and promote wound healing. In vitro, Muse cells could also promote the migration and proliferation of keratinocytes. In summary, Muse cells may become a new therapeutic agent for the treatment of AD.