Treating Chronic Pruritus: Are We at the Threshold of a Breakthrough?

Chronic pruritis, characterized by persistent itchiness lasting more than six weeks, affects up to 15% of the population, significantly impairing quality of life. Despite its prevalence and impact, there is an absence of FDA-approved medications specifically for the treatment of chronic pruritus, highlighting a significant unmet need in dermatology. Advancements in dermatologic medications, however, including the development of biologics and Janus kinase (JAK) inhibitors, signal potential breakthroughs in pruritus management through a radically different mechanism of action that focuses on their effect on the nervous system. Currently, the most commonly utilized treatments for pruritis are sedating antihistamines, which have been largely ineffective for non-histamine-induced itch, underscoring the necessity for novel approaches. This editorial reviews key studies and clinical trials with a particular focus on cases of prurigo nodularis, where itch serves as the primary pathology rather than just a symptom. The effectiveness of dupilumab in phase III trials for treating prurigo nodularis, independent of its effects on dermatitis or atopic background, alongside the success of JAK inhibitors in managing chronic idiopathic pruritus, indicates a shift towards therapies that directly and specifically target itch nerve pathways instead of indirectly via immune system modulation or sedation. These developments suggest that significant progress may be on the horizon for treating chronic itch, providing hope for those suffering from pruritis, the number one cause of misery in dermatology.

Cellular indexing of transcriptomes and epitopes (CITE-Seq) in hidradenitis suppurativa identifies dysregulated cell types in peripheral blood and facilitates diagnosis via machine learning.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and scarring, predominantly affecting intertriginous regions and it is often underdiagnosed. This study aimed to utilize single cell RNA and cell-surface protein sequencing (CITE-Seq) to delineate the immune composition of circulating cells in Hidradenitis suppurativa (HS) peripheral blood compared to healthy controls. CITE-Seq was used to analyze the gene and protein expression profiles of peripheral blood mononuclear cells (PBMCs) from 9 HS and 29 healthy controls. The study identified significant differences cell composition between HS patients and healthy controls, including increased proportions of CD14+ and CD16+ monocytes, cDC2, plasmablasts, and proliferating CD4+ T cells in HS patients. Differential expression analysis revealed upregulation of inflammatory markers such as TNF, IL1B, and NF-κB in monocytes, as well as chemokines and cell adhesion molecules involved in immune cell recruitment and tissue infiltration. Pathway enrichment analysis highlighted the involvement of IL-17, IL-26 and TNF signaling pathways in HS pathogenesis. Machine learning identified key markers for diagnostics and therapeutic development. The findings also support the potential for machine learning models to aid in the diagnosis of HS based on immune cell markers. These insights may inform future therapeutic strategies targeting specific immune pathways in HS.

Advancing Psoriasis Care through Artificial Intelligence: A Comprehensive Review.

Purpose of Review: Machine learning (ML), a subset of artificial intelligence (AI), has been vital in advancing tasks such as image classification and speech recognition. Its integration into clinical medicine, particularly dermatology, offers a significant leap in healthcare delivery. Recent Findings: This review examines the impact of ML on psoriasis-a condition heavily reliant on visual assessments for diagnosis and treatment. The review highlights five areas where ML is reshaping psoriasis care: diagnosis of psoriasis through clinical and dermoscopic images, skin severity quantification, psoriasis biomarker identification, precision medicine enhancement, and AI-driven education strategies. These advancements promise to improve patient outcomes, especially in regions lacking specialist care. However, the success of AI in dermatology hinges on dermatologists' oversight to ensure that ML's potential is fully realized in patient care, preserving the essential human element in medicine. Summary: This collaboration between AI and human expertise could define the future of dermatological treatments, making personalized care more accessible and precise.

Adapting the Goeckerman Regimen for Psoriasis Treatment in Kenya: A Case Study of Successful Management in a Resource-Limited Setting.

Introduction:  Goeckerman therapy, which combines ultraviolet B (UVB) light with crude coal tar (CCT), remains highly effective for moderate-to-severe psoriasis. While it is rarely still used in the USA as effective biotherapeutics have become more readily available, it offers an alternative therapy in developing countries with limited access to newer medications. Moi Teaching & Referral Hospital (MTRH) in Eldoret, Kenya, in collaboration with UCSF, developed a modified Goeckerman regimen suitable for local healthcare needs, condensing the treatment into an intensive two-week program. Case Report:  A 55-year-old female with erythrodermic psoriasis traveled 350 kilometers to MTRH. After the diagnosis was confirmed, she underwent a nine-day inpatient treatment with narrow-band UVB phototherapy and topical medications under occlusion as a modified Goeckerman regimen. Response to Treatment:  Significant improvement was observed within three days, with full recovery in ten days. Follow-up one month later showed no active lesions, and her psoriasis remained controlled for four months with topical treatments. Conclusion:  The modified Goeckerman regimen at MTRH, in collaboration with UCSF, effectively treated severe psoriasis in a challenging healthcare context. This case highlights the potential for adapting established treatments to improve patient outcomes in developing countries with limited access to systemic therapies.

A partitioned polygenic risk score reveals distinct contributions to psoriasis clinical phenotypes across a multi-ethnic cohort.

Psoriasis is a chronic, immune-mediated inflammatory skin disease associated with a polygenic mode of inheritance. There are few studies that explore the association of a psoriasis Polygenic Risk Score (PRS) with patient clinical characteristics, and to our knowledge there are no studies examining psoriasis PRS associations across different ethnicities. In this study, we used a multi-racial psoriasis cohort to investigate PRS associations with clinical phenotypes including age of onset, psoriatic arthritis, other comorbidities, psoriasis body location, psoriasis subtype, environmental triggers, and response to therapies. We collected patient data and Affymetrix genome-wide SNP data from a cohort of 607 psoriasis patients and calculated an 88-loci PRS (PRS-ALL), also partitioned between genetic loci within the HLA region (PRS-HLA; 11 SNPS) and loci outside the HLA region (PRS-NoHLA; 77 SNPS). We used t-test and logistic regression to analyze the association of PRS with clinical phenotypes. We found that PRS-HLA and PRS-noHLA had differing effects on psoriasis age of onset, psoriatic arthritis, psoriasis located on the ears, genitals, nails, soles of feet, skin folds, and palms, skin injury as an environmental trigger, cardiovascular comorbidities, and response to phototherapy. In some cases these PRS associations were ethnicity specific. Overall, these results show that the genetic basis for clinical manifestations of psoriasis are driven by distinct HLA and non-HLA effects, and that these PRS associations can be dependent on ethnicity.

Commercial Diagnostics and Emerging Precision Medicine Technologies in Psoriasis and Atopic Dermatitis.

While psoriasis and atopic dermatitis (AD) are two common dermatological conditions, their diagnosis and therapeutic decision-making pathways are often complex. As a result, there has been increased focus on the development of precision medicine approaches for psoriasis and AD. Two companies at the forefront of dermatology precision medicine research are Mindera Health and Castle Biosciences. Here, we review the technologies developed by these two companies using a dermal diagnostic patch and superficial skin scrapings, respectively, their research published to date, and their future research goals. Research from both companies shows promise in predicting the response of inflammatory skin disease to biologics using minimally invasive techniques. However, challenges to adoption include insurance coverage and patient trust in the technologies. While there are several differences between Mindera Health and Castle Biosciences, they have a shared goal of utilizing minimally invasive technologies to sample skin and predict response to biologic treatments using a panel of optimized biomarkers.

The Mediterranean Diet as a Potential Solution to the Gut Microbiome Dysbiosis in Psoriasis Patients.

Background: Adherence to a Mediterranean Diet (MeD) has been associated with lower disease severity in patients with psoriasis. However, the mechanism behind how this diet may lead to disease modification remain understudied. Recent studies have revealed dysbiosis of the gut microbiome in patients with psoriasis suggestive of inflammation and altered immune regulation. Diet affects the gut microbiome and this review aims to evaluate whether correcting this dysbiosis may be one theoretical mechanism by which the MeD may be associated with lower psoriasis severity. Methods: A literature search of the PubMed database was conducted for the terms 1) 'psoriasis' and 'microbiome' or 'microbiota,' and 2) 'Mediterranean diet' and 'microbiome' or 'microbiota' with manual screening for relevant articles. In total, we identified 9 relevant primary research studies investigating the gut microbiome in patients with psoriasis and 16 relevant primary research studies investigating changes in the microbiota for those consuming a MeD. Results: Though varying in exact levels of certain bacteria, studies analyzing the microbiome in psoriasis revealed dysbiosis. Those analyzing the effect of the Mediterranean diet on the microbiome revealed beneficial changes, including alleviating some of the same alterations seen in the microbiome of those with psoriasis. Conclusion: Microbiota change is a possible mechanism why the MeD has previously been associated with lower psoriasis severity.

Psoriasis and Sleep Disturbance: A US Population-Based Study Using the NHANES Database.

INTRODUCTION: Psoriasis, a chronic inflammatory skin condition, affects approximately 3.0% of the US population, with patients often experiencing significant sleep disturbances. These disturbances include a higher prevalence of conditions such as obstructive sleep apnea, restless leg syndrome, and insomnia. Given the additional risks for cardiovascular disease, metabolic disorders, and depression linked to both poor sleep and psoriasis, addressing sleep issues in this patient group is critical. METHODS: The study utilized National Health and Nutrition Examination Survey (NHANES) data, focusing on individuals aged ≥ 20 years who provided information on psoriasis status and sleep. Multistage stratified survey methodology was applied, with multivariable logistic regression models used to examine the association between psoriasis and sleep issues, adjusting for factors such as age, gender, and health history. RESULTS: Psoriasis diagnosis was significantly associated with trouble sleeping (adjusted odds ratio [aOR] 1.88; 95% confidence interval [CI] 1.44-2.45). There was no significant association between psoriasis and sleep quantity. Older age, female gender, and a history of sleep disorders were predictors of trouble sleeping among psoriasis patients. CONCLUSIONS: Psoriasis is significantly associated with sleep disturbances, independent of sleep duration. This underscores the need for clinical screening focusing on sleep quality rather than quantity in psoriasis patients to effectively identify and treat sleep-related comorbidities. Further research using objective sleep measures is warranted to guide clinical management and improve patient quality of life.

The Role of Genetics on Psoriasis Susceptibility, Comorbidities, and Treatment Response.

This review highlights advances made in psoriasis genetics, including findings from genome-wide association studies, exome-sequencing studies, and copy number variant studies. The impact of genetic variants on various comorbidities and therapeutic responses is discussed.

The Influence of COVID-19 on Patient Mobilization and Injury Attributes in the ICU: A Retrospective Analysis of a Level II Trauma Center.

The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of trauma patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n = 378) and after (n = 499) 1 April 2020 when Georgia's COVID-19 shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after-COVID patients examined the extent to which mobilization (n = 328) or lack of mobilization (n = 171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. The after-COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before-COVID patients. After-COVID patients also had a greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or days to mobilization. Within the after-COVID cohort, those who were mobilized were older, had greater Glasgow Coma Scale scores, had longer total hospital days, and had a lesser mortality rate, and a higher proportion were female. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.

Risk of Cutaneous T Cell Lymphoma with Psoriasis Biologic Therapies.

BACKGROUND: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. METHODS: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. RESULTS: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. CONCLUSION: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use.

#PRS: A Study of Plastic Surgery Trends With the Rise of Instagram.

Background: Instagram (Menlo Park, CA) has become a popular means of advertisement for aesthetic surgery procedures, influencing patients' likelihood of undergoing a procedure. In this study, the authors aim to explore public interest in aesthetic procedures before and after the Instagram platform started gaining in popularity through Google Trends (Google, Mountain View, CA), a platform with previously demonstrated utility for tracking interest in surgical procedures. Objectives: The authors hypothesize that as a result of increased medical marketing on Instagram, there is an increase in public interest in elective procedures of plastic surgery. Methods: Trends in the United States for given search terms and volumes were gathered through Google Trends between April 2004 and January 2022. Search terms included popular aesthetic procedures based on the 2020 Aesthetic Plastic Surgery National Data Bank Statistics. The search volumes were normalized, and a bivariate regression analysis of panel data was then applied to the aggregate trendlines to determine whether a statistically significant change in search volume occurred following the increase in user traffic of the Instagram platform. Results: The authors found significant variations in search volume for plastic surgery procedures before and after April 2012. Blepharoplasty, Botox, brachioplasty, breast implant removal, breast reduction, brow lift, butt lift, hair transplantation, lip augmentation, male breast surgery, mastopexy, mentoplasty, otoplasty, platysmaplasty, rhinoplasty, and thighplasty (P < .000) had statistically significant increases in search volume, whereas buccal fat removal (P = .003) had a statistically significant decrease in search volume after April 2012. Conclusions: The authors observed a significant increase in public interest in both surgical and nonsurgical aesthetic procedures after Instagram gained popularity in the April of 2012.