NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.

Pediatric hidradenitis suppurativa publication trends: 2012 to 2022.

There is a paucity of bibliometric data on pediatric-focused hidradenitis suppurativa (HS) publications. To better characterize research trends in pediatric HS and gaps in literature, we systematically searched PubMed between 2012 and 2022 for publications on pediatric HS and collected data on study design, topic, country, and level of evidence. Of 109 articles that met inclusion criteria, less than half (44/109, 40.4%) were high level of evidence studies; the most common study types were case reports/series (41/109, 37.6%) and cross-sectional studies (25/109, 22.9%), and the most common study topics were HS treatments (44/109, 40.4%), comorbidities (20/109, 18.3%), and clinical presentation (14/109, 12.8%). Although there has been expansion of the pediatric HS literature in recent years, our study highlights the need for larger prospective studies and trials to improve our ability to optimally manage pediatric HS patients and identify predictors of disease progression and treatment response.

N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake.

N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity.

Patient Perspectives on Hidradenitis Suppurativa and Infertility: A Survey Study.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition which predominantly affects women of childbearing age in the USA. There is a lack of research on the association between HS and fertility. OBJECTIVES: The aim of this study was to understand the perspectives of females with HS regarding the impact of their disease on reproductive health, the impact of fertility treatments on HS, and the impact of HS treatments on fertility. METHODS: An anonymous, online survey was disseminated through HS support groups from June to July 2022. Respondents aged 18-50 who were assigned female sex at birth were eligible for participation. Comparative statistics were performed using t tests/χ2 tests to assess associations between respondents' demographics and survey responses. RESULTS: Among the 312 respondents (80.8% White, mean age 35.7 ± 7.4 [range 18-50]), two-thirds of respondents (66.6%, 207/311) had been pregnant before and 79.5% (248/312) had ever tried to conceive. 41.5% (103/248) had unsuccessfully tried to conceive for 12 months or more. Of the 59 respondents who had never attempted to conceive, 39% reported that HS had impacted this decision. Amongst respondents who experienced fertility challenges but did not pursue fertility treatments, top barriers to fertility treatments include concerns about financial support/insurance coverage (47.5%, 29/61) and fertility treatments worsening HS (21.3%, 13/61). Most respondents who used fertility treatments reported either no change (73.7%, 28/38 or 77.8%, 14/18) or improvement (15.8%, 6/38 or 11.1%, 2/18) in their HS symptoms with oral or injectable medications. Respondents were most concerned about the effects of oral antibiotics (44.9%, 140/312), followed by hormonal medications (38.8%, 121/312) and biologics (35.9%, 112/312) on fertility. CONCLUSION: Females with HS reported high rates of infertility compared to the general population. The majority reported no change in HS symptoms with fertility treatments, and clinicians can use this finding to help counsel patients during family planning discussions. Further research in the field of HS and fertility is needed.

Hormonal Treatments in Hidradenitis Suppurativa: A Systematic Review.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition characterized by recurrent abscesses, nodules, and sinus tracts. Hormones are thought to play an important role in HS pathophysiology, but there is a lack of an updated review on hormonal treatments in HS.  Objective: Perform a systematic review of the literature on hormonal treatments in patients with HS.  Methods: In April 2022, MEDLINE and EMBASE databases were searched for articles on hormonal treatments in HS. Non-English, duplicate, and irrelevant results were excluded. Data extraction was performed by two reviewers.  Results: From 1952 to 2022, 30 articles (634 patients) met the inclusion criteria. Anti-androgen treatments discussed include finasteride (n=8), spironolactone (n=7), cyproterone acetate (CPA) (n=5), flutamide (n=1), leuprolide (n=1), and buserelin acetate (n=1). Metabolic treatments reported include metformin (n=8) and liraglutide (n=2). Three articles on hormonal contraceptives and 2 articles on testosterone were included. Of the articles which reported response rates, 62.8% (27/43) of patients improved with finasteride, 53.3% (32/60) with CPA mono/combination therapy, 50.5% (51/101) with spironolactone, and 46.0% (74/161) with metformin. Improvement in HS was also noted in case reports of patients treated with buserelin acetate, leuprolide, flutamide, and liraglutide.    Conclusions: Hormonal treatments for HS, especially finasteride, spironolactone, and metformin, are efficacious and safe; but large-scale randomized controlled trials are needed to determine the patient populations which would benefit from these therapies. Masson R, Shih T, Jeong C, et al. Hormonal treatments in hidradenitis suppurativa: a systematic review. J Drugs Dermatol. 2023;22(8):785-794. doi:10.36849/JDD.7325.

Efficacy of procedural treatments for pediatric hidradenitis suppurativa: A systematic review.

Hidradenitis suppurativa (HS) is a painful, inflammatory skin disease that has historically been understudied in the pediatric population. Procedural interventions, such as surgical excisions, skin grafts, and lasers, are important for comprehensive HS disease management. However, there is a lack of data on procedural treatments for HS in pediatric patients. The purpose of this study was to conduct a systematic review of the literature on the efficacy and safety of procedural treatments for HS in pediatric patients. In April 2022, MEDLINE and EMBASE databases were searched for articles on the efficacy of procedural treatments for HS in patients <18 years of age. Two independent reviewers extracted data from relevant studies. From 1974 to 2021, 23 articles with 81 patients were identified. Patients' Hurley stages included stage I (9.1%, 1/11), II (36.4%, 4/11), and III (54.5%, 6/11). The most extensively studied procedural interventions include negative pressure wound therapy (n = 30), surgical excision with skin graft/flap (n = 19), and endoscopic electrode or laser treatment (n = 11). In all, promising response rates for procedural management strategies were observed in the literature but the findings were largely based on case reports/series. Randomized controlled trials (RCTs), especially those geared toward minimally invasive procedural treatments, are needed to help guide clinicians on the most efficacious treatment modalities for pediatric patients with HS.

Efficacy of medical treatments for pediatric hidradenitis suppurativa: A systematic review.

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition that has been insufficiently studied in the pediatric population. Timely and effective medical treatments may improve quality of life, mitigate disease burden, and prevent the need for invasive procedural interventions such as surgical excisions. However, there is a paucity of research on the efficacy of medical management strategies for HS in children and adolescents. The aim of this study was to perform a systematic review of the literature on the efficacy and safety of medical treatments for HS in patients <18 years of age. In April 2022, MEDLINE and EMBASE databases were searched for articles on the efficacy of medical treatments for HS in the pediatric population. Between 1984 and 2022, 35 articles (101 patients) met the inclusion criteria. Most patients had Hurley Stage II disease (46.7%, 35/75) followed by Stage I (36%, 27/75), and Stage III (17.3%, 13/75). 100% (23/23) of patients responded to antibiotics, 100% (8/8) to finasteride, 93.9% (31/33) to biologics, 80% (4/5) to oral retinoids, and 50% (6/12) to metformin. Overall, this study demonstrates that medical treatment regimens can improve HS symptoms in pediatric patients, but the extent of improvement is unclear, and the results were largely based on case reports or case series. Prospective studies are warranted to better understand the efficacy and safety of medical treatments for pediatric HS. Clinical trials of HS therapies need to be inclusive of pediatric patients to help define the optimal timing of treatment initiation and guide patient selection.

Active learning narrows achievement gaps for underrepresented students in undergraduate science, technology, engineering, and math.

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

Geospatial analysis of access to dermatology care in Los Angeles County: a cross sectional study.

Geographic maldistribution of dermatologists contributes to disparities in access to dermatologic care. We aimed to investigate the geographic distribution of, and differences in wait times for medical dermatology services in Los Angeles County (LAC). We placed phone calls to 251 dermatology practices in LAC to ask for a new patient appointment for a changing mole. We found West LAC (Service Planning Area [SPA] 5) had the highest number of dermatologists and South LAC (SPA 6) had the lowest (26.1 versus 0 per 100,000 residents, P=0.01). Service Planning Area 6 has a higher non-White, uninsured, and impoverished population than SPA 5. Dermatology appointment wait times and Medicaid acceptance varied between SPAs but was not statistically significant (P=0.37 and P=0.20, respectively). Medicaid-accepting practices had a significantly longer mean wait time for an appointment than practices that did not accept Medicaid (26.1 versus 15.1 days, P=0.003). Regions with predominantly non-White, Spanish-speaking, and medically underinsured residents were found to be disproportionately lacking in dermatologists across LAC, which may contribute to impaired access to dermatology services in LAC.

Aryl hydrocarbon receptor/nuclear factor E2-related factor 2 (AHR/NRF2) signalling: A novel therapeutic target for atopic dermatitis.

Aryl hydrocarbon receptor (AHR)/nuclear factor-erythroid 2-related factor 2 (NRF2) modulation is emerging as novel targets in the treatment of atopic dermatitis and other inflammatory skin disorders. Agonist activation of this pathway has downstream effects on epidermal barrier function, immunomodulation, oxidative stress reduction and cutaneous microbiome modulation. Tapinarof, a dual agonist of the AHR/NRF2 signalling pathway, has shown promise in phase 2 trials for atopic dermatitis. In this review, we summarize current knowledge of the AHR/NRF2 pathway and implications in skin disease process. We also review the therapeutic potential of current AHR agonists and propose future directions to address knowledge gaps.

Adverse pregnancy and maternal outcomes in women with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) disproportionately affects women of childbearing age. However, pregnancy and maternal outcomes for women with HS are unknown. OBJECTIVE: To compare risk of adverse pregnancy and maternal outcomes among women with and without HS and to evaluate the influence of comorbid conditions. METHODS: Retrospective cohort analysis between January 1, 2011, and September 30, 2015. RESULTS: Compared to control pregnancies (n = 64,218), HS pregnancies (n = 1862) had a higher risk of spontaneous abortion (15.5% vs 11.3%), preterm birth (9.1% vs 6.7%), gestational diabetes mellitus (11.6% vs 8.4%), gestational hypertension (6.1% vs 4.4%), preeclampsia (6.6% vs 3.8%), and cesarean section (32.4% vs 27.1%). Relative risk of some pregnancy and maternal outcomes were attenuated after comorbidity adjustment. In the fully adjusted model, HS pregnancies were independently associated with spontaneous abortion (odds ratio, 1.20; 95% CI, 1.04-1.38), gestational diabetes mellitus (odds ratio, 1.26; 95% CI, 1.07-1.48), and cesarean section (odds ratio, 1.09; 95% CI, 1.004-1.17). LIMITATIONS: We could not evaluate potential influences of disease duration, activity, or severity. Newborn outcomes could not be evaluated. CONCLUSION: HS appears to be an independent risk factor for adverse pregnancy and maternal outcomes. This risk is influenced by comorbidities that may be modifiable with early identification and management.

Hyperhidrosis treatments in hidradenitis suppurativa: A systematic review.

Hyperhidrosis impairs quality of life (QOL) in hidradenitis suppurativa (HS) patients and may exacerbate HS. However, there is limited literature on whether hyperhidrosis treatments improve HS disease. To systematically review literature on efficacy and tolerability of hyperhidrosis treatments in HS patients. In May 2021, MEDLINE and EMBASE databases were systematically searched by two reviewers per PRISMA guidelines for articles on hyperhidrosis and HS. Sixteen articles met inclusion criteria (2 randomized controlled trials [RCTs], one case-control study, three cross-sectional studies, 10 case-studies/series), encompassing 252 HS patients across studies. They examined botulinum toxin A (BTX-A) (n = 6) and B (BTX-B) (n = 1), suction-curettage (n = 1), diode laser (n = 1), and microwave-based energy device (MED) (n = 3). Overall, BTX treatments improve HS severity, QOL, hyperhidrosis, and were well-tolerated. Suction-curettage did not improve disease. One HS patient tolerated diode laser well, with improvement in sweating and HS. One RCT studying MED was discontinued due to adverse events. Two studies reported MED-induced HS. BTX was overall helpful in HS patients, including in patients without concomitant hyperhidrosis. However, more prospective studies are needed to examine its utility in HS. There is potential harm of MEDs in HS. Most studies examining hyperhidrosis treatments in HS patients are low level of evidence. Larger RCTs should examine the efficacy and tolerability of hyperhidrosis treatments in HS.

Intralesional biologics for inflammatory dermatoses: A systematic review.

Biologic medications are systemic therapeutic options for inflammatory dermatoses. Local forms of administration are less well-studied. To provide a summary of intralesional (IL) administration of biologics for various non-malignant inflammatory dermatologic conditions reported in the literature. A systematic review was performed in the PubMed and Embase databases from 2000 to 2020. Inclusion criteria included the local use of biologic medications for non-malignant cutaneous conditions. Quality was assessed with the modified Oxford Centre for Evidence-Based Medicine ratings. A total of 19 articles describing the use of 5 biologic medications in 9 dermatologic conditions were identified, comprising 172 patients. Conditions successfully treated with intralesional biologics included pemphigus vulgaris (rituximab), granuloma faciale (rituximab), perianal Crohn's disease (infliximab), lichen sclerosus (adalimumab), and necrobiosis lipoidica (etanercept and infliximab). Intralesional etanercept reduced pruritus associated with keloids. A case report of the use of infliximab for pyoderma gangrenosum did not demonstrate any efficacy. There was no consistent effect noted with treatments for sarcoidosis (infliximab) or cutaneous lymphoid hyperplasia (rituximab). Local administration of biologic medications may offer an additional method of treating refractory inflammatory dermatoses, but further study is needed to develop standardized dosing protocols, clarify efficacy rates, and identify optimal treatment candidates.

Infliximab in hidradenitis suppurativa: A systematic review and meta-analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory often recalcitrant to treatment. There is a lack of an updated systematic data review for infliximab use in HS. We conducted a systematic review and meta-analysis of literature on infliximab in HS. This study was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was pre-registered on PROSPERO (CRD42021283596). In 9/2021, MEDLINE and EMBASE were systematically searched for articles on infliximab in HS. Non-English, duplicate, and studies with <5 HS patients were excluded. Study quality was assessed utilizing Cochrane Risk of Bias for prospective trials and Newcastle-Ottawa Scale for cohort studies. Random effects meta-analytical model, Cochran's Q statistic, and I squared index were performed. Nineteen articles (314 patients) met inclusion criteria (six prospective, 13 retrospective studies). All patients with HS severity data available (n = 299) had moderate-to-severe disease. Outcome measures used for meta-analysis of the pooled response rate were largely based on clinician reported outcomes (16 studies). One utilized both clinician and patient assessment. Two utilized patient-reported response alone. The pooled response rate of HS patients to infliximab was 83% (95% CI, 0.71-0.91). The most common adverse events (AEs) included non-serious infections (13.2%) and infusion reaction (2.9%). The rate of serious AEs was 2.9%. Study limitations include the small number of prospective studies and heterogeneity between studies. Overall, infliximab is an effective treatment for moderate-to-severe HS. Efficacy of infliximab in HS should be compared to other biologics in larger, randomized controlled trials.

Impact of Pregnancy on Hidradenitis Suppurativa Disease Course: A Systematic Review and Meta-Analysis.

BACKGROUND: Hormones are thought to play a role in hidradenitis suppurativa (HS). However, data on the HS disease course during pregnancy and the postpartum period has not been well established. The objective of this study is to analyze the available literature to determine HS disease activity during pregnancy and the postpartum period. METHODS: The PubMed and Embase databases were systematically searched for relevant articles from database inception until November 22, 2020. The inclusion criteria were a study population with the diagnosis of HS and discussion of pregnancy impact on the HS disease course or postpartum flare. Study characteristics, patient demographics, HS severity, and HS disease course during pregnancy and the postpartum period were extracted by 2 independent reviewers. The quality of included studies was assessed using the Newcastle-Ottawa Scale for observational studies. Heterogeneity was assessed using Cochran's Q statistic and I2 index. The random-effects meta-analytical model was used. The primary study outcome was the pooled odds ratio of improvement or of worsening of HS disease activity during pregnancy. RESULTS: The systematic search identified 8 studies for analysis. There was a total of 672 cases for which data on the patient-reported HS disease course during pregnancy were available, and 164 cases for which data on patient-reported postpartum flare were available. In the meta-analyses, the rate of HS disease improvement was 24% (95% CI 0.13-0.40) and the rate of HS disease worsening was 20% (95% CI 0.11-0.34). Sixty percent (99/164) of patients experienced a postpartum flare. CONCLUSION: While about a quarter of women will experience an improvement in HS during pregnancy, the majority will have a stable or worsened disease course, and over half of patients will experience a postpartum flare. Close monitoring of HS patients is needed during pregnancy and postpartum periods, as patients may need continued, or even escalated, disease management.

Bibliometric analysis of the 50 most cited publications in atopic dermatitis.

Atopic dermatitis (AD) affects up to 20% of children worldwide. We identified the top 50 cited AD articles in the last seven decades and examined their characteristics. The majority were discussing the pathogenesis of AD and have paved the way for discovering targeted immunomodulatory treatments. A lack of geographic diversity was noted, thus encouraging more countries to be involved in AD research can further progress the future of AD management.

Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes.

Atopic dermatitis (AD) is a common inflammatory dermatosis that has multiple contributing factors including genetic, immunologic and environmental. Staphylococcus aureus (SA) has long been associated with exacerbation of AD. SA produces many virulence factors that interact with the human skin and immune system. These superantigens and toxins have been shown to contribute to adhesion, inflammation and skin barrier destruction. Recent advances in genome sequencing techniques have led to a broadened understanding of the multiple ways SA interacts with the cutaneous environment in AD hosts. For example, temporal shifts in the microbiome, specifically in clonal complexes of SA, have been identified during AD flares and remission. Herein, we review mechanisms of interaction between the cutaneous microbiome and SA and highlight known differences in SA clonal complexes that contribute to AD pathogenesis. Detailed knowledge of the genetic strains of SA and cutaneous dysbiosis is becoming increasingly relevant in paving the way for microbiome-modulating and precision therapies for AD.

Diagnosis and management of hidradenitis suppurativa in women.

Hidradenitis suppurativa is a chronic inflammatory disease that disproportionately affects women of childbearing age. Hidradenitis suppurativa is characterized by painful nodules, abscesses, draining dermal tunnels, and scarring with a predilection for intertriginous sites, such as the axilla, groin, and breast regions. Delay in diagnosis and treatment of hidradenitis suppurativa often results in long-term sequelae leading to significant morbidity, and rarely mortality, in these patients. This clinical opinion suggests that obstetrician-gynecologists are uniquely poised to recognize early signs of hidradenitis suppurativa during routine well-woman examinations and initiate treatment or referral to dermatology. Herein, we provide clinical pearls for obstetrician-gynecologists caring for female patients with hidradenitis suppurativa, including strategies for comprehensive management and recommendations to improve the comfort of patients with hidradenitis suppurativa during examinations.

Pregnancy and breastfeeding in hidradenitis suppurativa: A review of medication safety.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionately affects women of childbearing age. Pregnancy influences HS severity for many women, thus diligent continued management throughout pregnancy and postpartum may be required. Herein, we provide an updated review of pregnancy and lactation safety data for HS medications, including topical antiseptic washes, topical and systemic antibiotics, biologic and nonbiologic immunomodulators, immunosuppressants, adjunct medical therapies, and pain medications, to help guide risk-benefit discussions between providers and HS patients.

Physician perspectives on complementary and alternative medicine in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic and often debilitating inflammatory condition characterized by frequent nodules, abscesses, sinus tracts, and scars impacting the intertriginous areas. Many patients with HS often report limited treatment success and symptom coverage with conventional therapies. Recent studies have reported the widespread use of complementary and alternative medicine (CAM) among patients with HS. In this study, our aim was to examine current physician practice patterns, opinions, and comfort with recommending CAM. Our results indicate that provider comfort and opinions on CAM varied based on the provider's experiences, demographics, and the CAM modality itself. Overall, nearly two-thirds (n = 30, 61.2%) of respondents agreed that CAM and conventional medicine were more effective together than either alone. Meanwhile, 44.9% (n = 22) of respondents routinely recommend CAM while 64.6% (n = 31) of respondents reported that they are routinely asked about CAM. The majority (n = 41, 83.7%) of respondents indicated a lack of scientific evidence in the medical literature as a barrier to recommending CAM along with efficacy concerns (n = 34, 69.4%) and ability to recommend reputable CAM products (n = 32, 65.3%) and practitioners (n = 32, 65.3%). Future investigations are warranted to establish a better understanding of the efficacy and benefit of CAM methods in conjunction with conventional methods.