Single-cell profiling of prurigo nodularis demonstrates immune-stromal crosstalk driving profibrotic responses and reversal with nemolizumab.

BACKGROUND: Prurigo nodularis (PN) is a chronic neuroimmune skin disease characterized by bilaterally distributed pruritic hyperkeratotic nodules on extremities and trunk. Neuroimmune dysregulation and chronic scratching are believed to both induce and maintain the characteristic lesions. OBJECTIVES: This study sought to provide a comprehensive view of the molecular pathogenesis of PN at the single-cell level to identify and outline key pathologic processes and the cell types involved. Features that distinguish PN skin from the skin of patients with atopic dermatitis were of particular interest. We further aimed to determine the impact of the IL31RA antagonist, nemolizumab, and its specificity at the single-cell level. METHODS: Single-cell RNA-sequencing of skin from 15 healthy donors and nonlesional and lesional skin from 6 patients each with PN and atopic dermatitis, combined with spatial-sequencing using the 10x Visium platform. Integration with bulk RNA-sequencing data from patients treated with nemolizumab. RESULTS: This study demonstrates that PN is an inflammatory skin disease characterized by both keratinocyte proliferation and activation of profibrotic responses. This study also demonstrates that the COL11A1+ fibroblast subset is a major contributor to fibrosis and is predominantly found in the papillary dermis of PN skin. Activation of fibrotic responses is the main distinguishing feature between PN and atopic dermatitis skin. This study further shows the broad effect of nemolizumab on PN cell types, with a prominent effect driving COL11A1+ fibroblast and keratinocyte responses toward normal. CONCLUSIONS: This study provides a high-resolution characterization of the cell types and cellular processes activated in PN skin, establishing PN as a chronic fibrotic inflammatory skin disease. It further demonstrates the broad effect of nemolizumab on pathological processes in PN skin.

The relationship between acrochordons, obesity, and metabolic syndrome in the pediatric population: A retrospective cohort study.

BACKGROUND: Acrochordons or skin tags are common benign skin growths. Several studies explored the relationship between obesity and metabolic syndrome in adults but remains unexplored in children. METHODS: This was a single-center retrospective cohort study of outpatient dermatology patients between 1 January 2000 to 1 January 2021. Children under 18 years old diagnosed with acrochordons using diagnostic codes International Classification of Diseases, 10th Revision (ICD-10) L91.8 and 9th Revision (ICD-9) 701.8 were included. We collected patient demographics, past medical history, laboratory values, vital signs, and physical exam. Body mass index (BMI) was calculated and stratified into categories based on the Center for Disease Control's BMI-for-Age Growth Charts. Metabolic syndrome was diagnosed when three of the five criteria were met. Data were propensity-matched and compared with NHANES (National Health and Nutrition Examination Survey), which offered a generalizable sample to the US population. RESULTS: Fifty-five patients under 18 years old with a diagnosis of acrochordons were mostly Caucasian (76%) and female (64%). The mean BMI was 27.3, with 49.5% categorized as obese and 20% as overweight. The mean age of diagnosis was 10.1 years. Acrochordon predominantly appeared in the axilla. In our cohort, three patients (5.5%) met the criteria for metabolic syndrome. The prevalence of obesity (42% vs. 21%), type 2 diabetes mellitus (4.8% vs. 0.6%), hyperlipidemia (8.1% vs. 0%), and hypertension (1.6% vs. 0%) was greater in our cohort compared with NHANES. CONCLUSIONS: Like the adult population, acrochordons may serve as marker for metabolic disease in the pediatric population.

Positive Perceptions Towards Virtual Didactics During The COVID-19 Pandemic: A Survey Assessment of Dermatology Residents.

BACKGROUND: During the COVID-19 pandemic, resident didactics at many institutions, including ours, were transitioned from in-person to virtual. OBJECTIVES: We aimed to assess dermatology residents' satisfaction, impression of effectiveness, and preference for virtual didactics, and factors correlating with these sentiments. METHODS: Questionnaire administered to dermatology residents at our institution 3-6 months following transition to virtual didactics. RESULTS: Response rate was 26/31 residents (83.9%), with 20/26 (76.9%) expressing satisfaction, 15/26 (57.7%) effectiveness, and 12/26 (46.2%) preference towards virtual didactics. Factors associated with satisfaction included feeling that virtual didactics positively impacted learning retention, represented time well spent, and utilized high-quality images. Perception of effectiveness correlated with using high-quality images, baseline preference for online instruction, and feeling engaged. Factors associated with preference for virtual didactics included having opportunities for critical thinking, using high-quality images, and utilizing images applicable to teledermatology care. Advantages to virtual didactics included convenience, decreased commuting, and easily hosting guest lecturers. Disadvantages included distractions/decreased focus, reduced social interaction, and difficulty with communication. CONCLUSIONS: Residents expressed satisfaction, effectiveness, and some preference towards virtual didactics, which correlated with numerous factors. Our findings suggest that it is reasonable to maintain a virtual didactic component as part of dermatology resident education. Furthermore, our data provide insights into strategies that residency program directors and educators may consider when/if integrating virtual didactics into future educational curricula.

Relationship between somatic symptoms with menstruation and intention to leave work among university hospital nurses in Japan: a cross-sectional study.

PURPOSE: This study investigated the association between menstrual symptoms and the intention to leave work among female nurses in Japan. METHODS: This cross-sectional study investigated female nurses (n = 317) at two university hospitals. The items measured were their characteristics (e.g., age, body mass index), "intention to leave" work, somatic symptoms related with menstruation, self-reported menstrual characteristics (e.g., pain), physical workloads (e.g., working hours and night shifts) and psychological workloads, measured with the Copenhagen Burnout Inventory (CBI), and the Job Content Questionnaire (JCQ). Participants with at least four somatic symptoms (e.g., cold, fatigue) which are present during their menstrual cycles were considered to have "somatic symptoms associated with menstruation." We also measured serum ovarian and gonadotropin-releasing hormones. RESULTS: Approximately 40% of women answered "intention to leave" work, and 17% had "somatic symptoms associated with menstruation." Multiple logistic regression analysis suggested that nurses reporting "somatic symptoms associated with menstruation" were more likely to have "intention to leave" work: the adjusted odds ratios (AOR, 95% confidence interval [CI]) were 2.15 (1.12-4.11) in the personal-burnout model, 2.23 (1.16-4.31) in the work-related burnout model, 2.91 (1.52-5.56) in the client-related burnout model; 2.96 (1.50-5.82) in the JCQ model. There was no association between serum and gonadotropin hormones and the intention to leave. CONCLUSION: Somatic symptoms with menstruation were associated with intention to leave work among female Japanese nurses. Intervention for somatic symptoms with menstruation might support nurses to continue work.

Pigmented Purpuric Dermatosis of the Hand: Clinicopathologic Analysis of Six Cases With Review of the Literature.

ABSTRACT: Pigmented purpuric dermatosis (PPD) is a group of skin disorders characterized by red, brown, or golden macules and patches with cayenne pepper-like spots. Classic histopathologic features include a perivascular lymphocytic infiltrate with associated erythrocyte extravasation and hemosiderin deposition. Although PPD most commonly affects the lower extremities, upper extremity involvement has been infrequently reported. Cases involving the hands are particularly rare. We present 6 new cases of PPD involving the hand and review 17 previously reported cases in the literature. All cases in our series were unilateral and localized to the dorsum of the hand. PPD was considered clinically in only 2 of these cases. Histopathologic examination revealed hallmark features of PPD, namely a superficial perivascular lymphocytic infiltrate and extravasated erythrocytes. Previous reports of PPD involving the hand described concurrent involvement of other anatomic sites in most cases; only 4 cases (24%) were confined to the hands. Histopathologic descriptions of these reported cases were compatible with PPD. In sum, our series describes a unique and rare clinical presentation of PPD confined to the unilateral dorsal hand. Because of the unusual presentation, biopsy is often required for accurate diagnosis.

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer.

BACKGROUND: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. OBJECTIVE: Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. METHODS: We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. RESULTS: We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. CONCLUSION: Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.

Dermatology residency preparation curriculum: a model for initiating new residents into dermatology clinical care.

Entering dermatology residency is an immersive experience requiring new specialty-specific skills. There is no standard Accreditation Council for Graduate Medical Education (ACGME) protocol for orienting new dermatology residents. We aimed to design, develop, and evaluate a curriculum for incoming first-year dermatology residents focusing on practical introduction to dermatologic clinical care emphasizing ACGME dermatology milestones. A concentrated 8-hour residency preparation course for first-year dermatology residents was designed and developed by faculty. The course encompassed clinical competencies, procedural techniques, and professionalism and collegiality principles. Teaching methods included lectures, video demonstrations, simulated patient experiences, and one-on-one practical instruction. Surveys were distributed before, immediately after, and 6-months following the course from 2016-2018 to assess participants' skill-based confidence level and perceived usefulness of the course. A total of 24 first-year dermatology residents participated in the residency preparation course over 3 years from 2016-2018. Residents' confidence levels in performing dermatology-specific skills immediately increased following the course and continued to increase 6 months into training. The majority of first-year residents "agreed" or "strongly agreed" that the course was helpful for improving clinical competence. Our residency preparation course increased first-year residents' confidence and perceived competence in performing clinical skills related to ACGME dermatology milestones.

Is Morgellons an organic disease? structural and functional abnormalities implicated in the pathophysiology of delusional infestation.

Little is known about the pathophysiology of delusional infestation (DI), a psychodermatologic condition in which patients have a fixed, false belief of being infested with parasites or inanimate material in their skin, despite lack of objective evidence. Because some delusional states, such as schizophrenia and psychotic state in bipolar disorder have been found to be associated with brain structural and functional abnormalities, a literature review was conducted to summarize available data on structural and functional abnormalities that are found to be associated with DI. A review of the literature found cases of brain imaging studies in patients with primary DI, as well as patients with secondary DI. Accumulating evidence from the studies reviewed suggests that dysfunction of the fronto-striato-thalamo-parietal network may explain how delusions manifest in DI and suggest that DI has an organic etiology. Abnormalities in the striato-thalamo-parietal network may cause false sensations of infestation through dysfunction in visuo-tactile regulation, whereas abnormalities in the frontal region may impair judgement. Delusional infestation patients also exhibit increased activation of brain structures implicated in itch processing. Furthermore, patients at high risk for cerebrovascular disease who present with secondary DI may benefit from brain imaging studies to rule out brain ischemic insult.

Influence of diet on the gut microbiome and implications for human health.

Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.

Update on the Systemic Risks of Superpotent Topical Steroids.

INTRODUCTION: The potential for systemic effects due to percutaneous absorption of superpotent topical steroids has been a longstanding concern. The Food and Drug Administration currently recommends limiting the use of superpotent topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the formulation, which is mostly based on the exact duration with which phase 3 clinical trials were allowed to be conducted per the FDA. This article reviews all published clinical incidence of adrenal adverse effects in the medical literature, specifically Cushing's syndrome (CS) and pathologic adrenal suppression (PAAS), to try to ascertain a more realistic limit for the safe use of superpotent topical steroids as it pertains to its potential systemic effects.

METHODS: Literature search was conducted using PubMed. Only cases of CS and PAAS secondary to the use of Class I superpotent topical steroids were included. Pediatric cases and full articles unavailable in English were excluded.

RESULTS: There were a total of 14 cases of CS and 5 cases of subsequent PAAS found in the current literature.

DISCUSSION: From our review of these cases, if the amount used per week is within FDA guidelines, it appears that patients needed to use superpotent topical steroids for far greater than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict occurrence of PAAS, but in all cases CS appeared to be a prerequisite for developing PAAS. All cases of CS and all but one case of PAAS were reversible. If excessive amount of greater than 50g per week is avoided, it appears that superpotent topical steroids may be safe to use consecutively for months, perhaps even years, without causing systemic effects.

J Drugs Dermatol. 2017;16(7):643-648.

Use of an oral phosphodiesterase-4 inhibitor (apremilast) for the treatment of chronic, severe atopic dermatitis: a case report.

Atopic dermatitis (AD) is a common inflammatory dermatosis characterized by pruritus, erythema, induration, and lichenification. Current treatment options for generalized atopic dermatitis are limited and have potentially serious adverse effects, especially in patients with severe, chronic AD who frequently require systemic anti-inflammatory agents. Apremilast, an oral phosphodiesterase-4 inhibitor, was FDA approved in September 2014 for the treatment of moderate-to-severe plaque psoriasis. However, its upstream anti-inflammatory effects, ease of use as an oral agent, and mild side-effect profile make it an interesting treatment option for AD as well. Herein, we present a patient with a life-long history of AD recalcitrant to topical steroids and cyclosporine who attained subjective and objective improvement in pruritus and erythema after 10-week treatment with apremilast.

Anti-IL-17 Agents for Psoriasis: A Review of Phase III Data.

BACKGROUND: Studies investigating the molecular basis of psoriasis have established the central roles of TNFa, interleukin (IL)-12, IL-22 and IL-23, and now there is increasing evidence that IL-17 plays a vital role in the complex pathophysiology of this disease. Preclinical and phase II studies of medications targeting IL-17 and its receptor have thus far proved to be promising. METHODS: We reviewed the results of the phase III clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS: By week 12, the proportion of patients reaching a 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) was comparable between the different agents (secukinumab 83%, ixekizumab 89%, and brodalumab 85%). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. CONCLUSION: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis treatment.

Phototherapy for the treatment of prurigo nodularis: a review.

BACKGROUND/PURPOSE: Review the available literature on phototherapy for treatment of prurigo nodularis (PN). METHODS: Literature search was conducted on MEDLINE. RESULTS:  6 prospective trials, 2 retrospective studies, and 3 case series were found investigating efficacy and safety of phototherapy for treatment of PN. CONCLUSION: Although large randomized clinical trials are necessary, phototherapy appears to be a safe and efficacious treatment for PN, alone and in combination with other common treatment modalities for PN.

Uremic pruritus treated successfully with the Goeckerman Program.

Uremic pruritus (UP) is a common condition among patients with chronic kidney disease (CKD) on hemodialysis (HD). We report 19 a case of severe UP recalcitrant to conventional therapy including topical corticosteroids, anti-histamines, and phototherapy, 20 which was treated successfully with the Goeckerman regimen consisting of topical coal tar, topical corticosteroids, and broadband 21 UVB (BB-UVB). Little is known about the pathophysiology of UP, and there is currently no consensus or evidence-based 22 treatments for UP. Although further studies are necessary, Goeckerman therapy may be a promising treatment option when 23 available for severe UP intractable to conventional therapies.

Narrowband UVB-induced iatrogenic polymorphous light eruption: a case and suggestions to overcome this rare complication.

Polymorphous light eruption (PMLE) is the most common photodermatosis characterized by pruritic papules and papulovesicles, which appear hours to days following ultraviolet (UV) exposure. Herein, the authors report successful treatment of generalized plaque psoriasis with Goeckerman regimen in a patient despite new onset iatrogenic PMLE following narrowband (NB) UVB therapy. Although further studies are necessary, this case suggests that the co-existence of psoriasis and PMLE should not prevent the use of phototherapy; phototherapy, especially as part of the Goeckerman regimen, remains a valuable treatment option for psoriasis in patients with PMLE.

Peritransplant absolute lymphocyte count as a predictive factor for advanced recurrence of hepatitis C after liver transplantation.

UNLABELLED: Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). The aim of this study was to investigate the impact of peritransplant ALC on HCV recurrence following LT. A total of 289 LT patients between 2005 and 2011 were evaluated. Peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence based on METAVIR fibrosis score. When stratifying patients according to pre- and post-LT ALC (<500/µL versus 500-1,000/µL versus >1,000/µL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). Multivariate Cox regression analysis showed posttransplant ALC at 1 month remained an independent predictive factor for recurrence (P = 0.02, hazard ratio [HR] = 2.47 for <500/µL). When peritransplant ALC was persistently low (<500/µL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years) (P = 0.02, HR = 3.16). Furthermore, severe pretransplant lymphopenia (<500/µL) was an independent prognostic factor for overall survival (P = 0.01, HR = 3.01). The use of rabbit anti-thymocyte globulin induction (RATG) had a remarkable protective effect on HCV recurrence (P = 0.02, HR = 0.6) despite its potential to induce lymphopenia. Subgroup analysis indicated that negative effects of posttransplant lymphopenia at 1 month (<1,000/µL) were significant regardless of RATG use and the protective effects of RATG were independent of posttransplant lymphopenia. CONCLUSION: Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC.

An analysis of 72% chromated glycerin used for sclerotherapy: sterility, potency, and cost after extended shelf life.

BACKGROUND: Sclerotherapy is the treatment of reticular veins and telangiectasias of the lower extremities. Sclerosants destroy endothelial tissue and expose subendothelial collagen fibers, which lead to subsequent fibrosis of vessels, thus preventing recanalization. There are several available sclerosants including sodium tetradecyl sulfate (STS), polidocanol (POL), and chromated glycerin (CG) with varying efficacy, potency, side effect profile, and cost. OBJECTIVE: To identify the possible bacterial contamination and potency of CG beyond the current recommended shelf life of 3 months and to prove if CG is as cost effective as other available sclerosants. METHODS: Samples of 72% CG underwent bacterial endotoxin, sterility, and potency analysis at Days 0, 24, and 183. In addition, cost comparison was performed with other commercially available sclerosants including STS and POL. RESULTS: No samples of CG showed any bacterial contamination. All aliquots of glycerin remained sterile at Day 14. Potency at Day 24 was 99.2%, which was the same at Day 183. Cost comparison with other sclerosants revealed that CG is lower cost per milliliter than STS and POL. CONCLUSION: Seventy-two percent CG has no contamination and maintains its reported potency up to 6 months while comparable with the cost of other commercially available sclerosants.

Comparison of photodermatoses in African-Americans and Caucasians: a follow-up study.

BACKGROUND/PURPOSE: Only a few studies have compared frequencies of photodermatoses among different races and skin types. This is an extension of a study performed by Kerr and Lim and evaluates the frequency of photodermatoses in African-Americans compared with Caucasians in the same institution during an 8-year period. METHODS: Retrospective chart review was performed, including dermatology clinic charts from October 2004 to August 2012 with International Classification of Diseases, Ninth Revision diagnostic codes related to photodermatoses. RESULTS: We identified 229 patients with photodermatoses. Of these, 138 (46.6%) were African-American and 63 (42.2%) were Caucasian. Statistically significant differences in the distribution of photodermatoses in African-Americans and Caucasians, respectively, were as follows: phototoxic drug eruption (0.7% and 15.9%, P < 0.0001), phytophotodermatitis (0% and 6.3%, P = 0.009), polymorphous light eruption (PMLE) (86.2% and 54%, P < 0.0001) and porphyrias (0% and 7.9%, P = 0.003). CONCLUSION: Combined with data from Kerr and Lim, this is the largest study of photodermatoses in African-Americans to date. Congruent to former studies, photodermatoses do occur regularly in dark-skinned individuals. Overall, the frequency of photodermatoses in African-Americans and Caucasians are similar; however, PMLE occurs more commonly in African-Americans, and porphyias and phototoxicity occur more commonly in Caucasians.

Clinical skills development in student-run free clinic volunteers: a multi-trait, multi-measure study.

BACKGROUND: At Wayne State University School of Medicine (WSU SOM), the Robert R. Frank Student Run Free Clinic (SRFC) is one place preclinical students can gain clinical experience. There have been no published studies to date measuring the impact of student-run free clinic (SRFC) volunteerism on clinical skills development in preclinical medical students. METHODS: Surveys were given to first year medical students at WSU SOM at the beginning and end of Year 1 to assess perception of clinical skills, including self-confidence, self-reflection, and professionalism. Scores of the Year 1 Objective Structured Clinical Exam (OSCE) were compared between SRFC volunteers and non-volunteers. RESULTS: There were a total of 206 (68.2%) and 80 (26.5%) survey responses at the beginning and end of Year 1, respectively. Of the 80 students, 31 (38.7%) volunteered at SRFC during Year 1. Statistically significant differences were found between time points in self-confidence (p < 0.001) in both groups. When looking at self-confidence in skills pertaining to SRFC, the difference between groups was statistically significant (p = 0.032) at both time points. A total of 302 students participated in the Year 1 OSCE, 27 (9%) of which were SRFC volunteers. No statistically significant differences were found between groups for mean score (p = 0.888) and established level of rapport (p = 0.394). CONCLUSIONS: While this study indicated no significant differences in clinical skills in students who volunteer at the SRFC, it is a first step in attempting to measure clinical skill development outside of the structured medical school setting. The findings lend themselves to development of research designs, clinical surveys, and future studies to measure the impact of clinical volunteer opportunities on clinical skills development in future physicians.