Hepatitis C virus RNA functionally sequesters miR-122.

Hepatitis C virus (HCV) uniquely requires the liver-specific microRNA-122 for replication, yet global effects on endogenous miRNA targets during infection are unexplored. Here, high-throughput sequencing and crosslinking immunoprecipitation (HITS-CLIP) experiments of human Argonaute (AGO) during HCV infection showed robust AGO binding on the HCV 5'UTR at known and predicted miR-122 sites. On the human transcriptome, we observed reduced AGO binding and functional mRNA de-repression of miR-122 targets during virus infection. This miR-122 "sponge" effect was relieved and redirected to miR-15 targets by swapping the miRNA tropism of the virus. Single-cell expression data from reporters containing miR-122 sites showed significant de-repression during HCV infection depending on expression level and site number. We describe a quantitative mathematical model of HCV-induced miR-122 sequestration and propose that such miR-122 inhibition by HCV RNA may result in global de-repression of host miR-122 targets, providing an environment fertile for the long-term oncogenic potential of HCV.

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

From traditional to targeted: the changing trajectory of therapies in dermatomyositis.

PURPOSE OF REVIEW: New breakthroughs in our understanding of dermatomyositis (DM) have spawned the recent development of novel agents that specifically target key drivers in DM immunopathogenesis. This review aims to provide a comprehensive overview of new and forthcoming therapies for DM and to highlight their mechanisms of action, best evidence to date, and potential impact on disease management. RECENT FINDINGS: Strategies that either counteract dysregulated interferon signaling [via the inhibition of interferon ß, the type I interferon receptor subunit 1 (IFNAR1), or janus kinase (JAK)-signal transducer and activator of transcription (STAT) transduction] or induce durable autoreactive B cell depletion through chimeric antigen receptor (CAR) T-cell therapy appear to hold the most promise for sustained remission in DM. SUMMARY: The trajectory of DM treatments is rapidly evolving, fueled by the unparalleled insights provided by multiomic studies and big data analysis pipelines. Targeted therapies that maximize both efficacy and safety have the potential to complement or replace traditional immunosuppressives and revolutionize the approach to the management of DM.

Pediatric consultative dermatology: A survey of the Society for Pediatric Dermatology workforce reveals shortcomings in existing practice models of pediatric dermatology consult services in the United States.

The rate of pediatric hospitalization for cutaneous pathology has been increasing in recent years, often requiring the expertise of consulting pediatric dermatologists; however, the infrastructure of inpatient pediatric dermatology consultative services remains poorly characterized. We sought to assess the structure, consult volume, physician compensation, and utilization of teledermatology in pediatric dermatology inpatient services to better understand the current care model. Our survey of 118 pediatric dermatologists revealed that 89% of respondents see between 1 and 10 new consults per week, 39% perform all inpatient consults including evening and weekends without assistance from other providers, 71% do not have protected time during the week to provide inpatient consultations, and only 10% receive financial compensation via stipend. By highlighting both the high demand for pediatric consultative dermatology as well as the significant burden placed on these providers by existing practice models, we hope to encourage a reappraisal of the current infrastructure of pediatric inpatient dermatology to increase structural and financial support for this vital service.

Pediatric cutaneous Crohn disease: A case series of 89 patients and review.

BACKGROUND: Cutaneous (or "Metastatic") Crohn disease (CCD) is a rare and underrecognized disease characterized by cutaneous granulomatous inflammation. We describe patient demographics, clinical characteristics, histology, and treatment of 89 pediatric cases of CCD, including 78 previously reported and 11 new cases seen at four academic institutions. We emphasize the efficacy of biologic mono- and dual therapy. METHODS: PubMed identified cases using keywords including "metastatic Crohn disease" and "cutaneous Crohn disease". Patients were identified by retrospective review of the electronic health record including histopathologic diagnosis consistent with CCD. Chart review collected demographic, clinical, and histologic data. RESULTS: Most pediatric patients with CCD are male 55% (49/89), present with edema (73/89, 82%) and erythema (47/89, 53%) of the genitals (33/49, 67%), and have intestinal Crohn disease (69/89, 78%). Oral corticosteroids (53/75, 71%) and metronidazole (29/75, 39%) are the most frequently prescribed medications. Of the 17 patients treated with tumor necrosis factor (TNF)-blockade, 94% (16/17) had partial or total clearance. Ustekinumab resulted in clearance of cutaneous disease in two patients (2/3, 67%) and partial clearance in one patient (1/3, 33%). Two cases achieved total clearance with the use of dual biologic therapy defined as the use of two biologic therapies with differing mechanisms of action or the use of a biologic therapy and small molecule inhibitor. CONCLUSIONS: TNF blockade is an effective treatment for pediatric CCD, and interleukin-12/23 inhibitors may be similarly effective. Consideration of dual biologic therapy may be useful in pediatric patients requiring discordant therapies for their intestinal and cutaneous CD.

A narrative review of therapies for scalp dermatomyositis.

Cutaneous involvement of the scalp is a common manifestation of dermatomyositis (DM), occurring in up to 82% of adults with DM. Scalp DM predominantly affects women and is characterized by dermatitis, alopecia, pruritus, and/or burning. While cutaneous DM negatively impacts quality-of-life, scalp symptoms in particular are often severe, debilitating, and recalcitrant to standard DM therapies. Currently, there is a paucity of guidelines to inform management of scalp symptoms in patients with cutaneous DM. In this narrative review, we summarize the treatments utilized to manage scalp DM and highlight potential areas for future research. We identified eight studies that reported on 27 treatments focused on cutaneous DM and described outcomes on scalp symptoms. A majority of the treatments were standard therapies for cutaneous DM and resulted in no or minimal improvement in scalp symptoms. Five therapies did result in complete resolution of scalp symptoms and were recommended as potential areas of future research. These included low-dose naltrexone and platelet-rich plasma, as well as two frequent and one less common therapy for cutaneous DM respectively: intravenous immunoglobulin, rituximab, and apremilast. Though the literature was not systematically assessed in this review, these findings illustrate not only that strategies for refractory scalp DM are lacking, but also that those demonstrating potential efficacy are limited by low levels of evidence. Additional studies, especially randomized controlled trials, are needed to better inform management of scalp DM.

Safety Profile of Combined Same-Day Treatment for Botulinum Toxin With Full Face Nonablative Fractionated Laser Resurfacing.

BACKGROUND: Spread of botulinum toxin outside the treated muscle is a concern, when energy-based device treatment is performed on the same day as toxin injection. OBJECTIVE: We assessed the frequency of eyelid ptosis after the glabella/periorbital botulinum toxin injection and nonablative fractionated laser performed at the same session. METHODS AND MATERIALS: This single-center, retrospective study identified treatments consisting of glabella and/or periorbital botulinum toxin injection and nonablative fractionated laser treatment to full face from 2017 to 2019 and eyelid ptosis determined by documentation of the complication at a follow-up encounter, or prescription of apraclonidine. RESULTS: Six hundred sixteen treatments of glabella/periorbital botulinum toxin injection and full-face nonablative fractionated laser on the same day on 393 individuals were identified. Five hundred eighty treatments (94%) included botulinum toxin injected in the glabella, 541 (88%) in the periorbital areas, and 508 (82%) in the forehead. Nonablative fractionated lasers used to treat the cohort were a 1,927-nm thulium and a 1,550-nm er:glass laser. Eyelid ptosis complication was documented in one case (0.2%) following the combined laser and toxin treatment. CONCLUSION: The risk of spread of glabella/periorbital botulinum toxin to an unintended muscle was minimal in the setting of the concomitant full-face nonablative fractionated laser.

Hair Care Professionals as Community Health Partners in Detection and Management of Alopecia: A Pilot Survey Study.

BACKGROUND: Alopecia is one of the most common diagnoses encountered by dermatologists; despite this, patients with hair loss often seek help from hair stylists prior to seeing a physician. OBJECTIVE: The purpose of this pilot survey study was to investigate hair stylists as hair loss community health partners and identify how dermatologists can potentially play a key role in cosmetology education. STUDY-DESIGN: Twenty-four New York City hair stylists completed a novel 23-item survey via email. RESULTS: When encountering hair loss in clients, stylists not formally educated about alopecia reported initially recommending their clients see a dermatologist, while those who were taught on the subject reported first recommending over the counter products as treatment. Hair stylists with alopecia training were equally as likely as those without alopecia training to believe hair styling practices do not contribute to hair loss. CONCLUSION: Our data support the need for integrated dermatologic training in cosmetology schools, particularly in the area of hair loss, with combined support of established hair instructors and dermatologists. Developing a brief curriculum regarding the fundamentals of alopecia etiology, diagnostics and therapeutics could equip hair stylists with useful evidence-based information they can use to help their clientele prevent and detect early stages of hair loss. By doing so, we can increase accessibility to quality hair care in the community and therefore streamline the process of alopecia patients getting the medical care they need. J Drugs Dermatol. 2021;20(8): 908-910. doi:10.36849/JDD.5643.

COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients.

Early in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects.

Two-Stage Syphilis Testing.

A 54-year-old woman presented with erythematous annular and indurated plaques on her face, trunk, and extremities and had false-positive syphilis test results during 2 pregnancies 25 and 22 years prior. What would you do next?