Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Clinical and histological features and treatment outcomes of patients with Morbihan disease: a systematic review.

Morbihan disease (MD) is considered a rare complication of rosacea, which is difficult to diagnose and challenging to treat. Here, we performed a systematic review of available case reports and case series to summarize key clinical and pathologic features of and successful treatment regimens for MD. We conducted a search of the PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to the date of search on March 6, 2023. We found that MD affects patients in the fifth decade of life on average, more commonly reported in male than female (69% vs 31%). Clinically, MD affects the eyelids, cheeks, and forehead most commonly, presenting as non-pitting, erythematous edema or an edematous plaque. On biopsy, the pathologic features, such as dermal edema, sebaceous hyperplasia, perivascular and periadnexal inflammatory infiltrate, and granulomatous reaction, are frequently reported. Out of 55 patients who were able to achieve complete response without recurrence, 35% of patients were treated with isotretinoin and 22% were treated with tetracycline antibiotics with a daily dosage range of 20-80 mg and 40-200 mg, respectively. Out of those 55 patients, 22% and 7% were treated successfully with surgical intervention and intralesional injection of steroids, respectively. Additionally, lymphatic drainage has been shown to be an effective adjunctive therapeutic tool. More studies are necessary to understand the disease mechanism to improve the diagnosis of and develop evidence-based therapies for MD.

Overview of use, efficacy, and safety of dupilumab in complex patients: a retrospective, case-series study from a large, urban academic center.

Dupilumab has emerged as an effective treatment option for those suffering from moderate-to-severe atopic dermatitis (AD). Since its approval in 2017 by the United States Food and Drug Administration, dupilumab demonstrated efficacy in a wide range of "off-label" dermatologic conditions. With its increasing use, dermatologists must navigate prescribing dupilumab in complex patient populations. To that end, we performed a single-institution, retrospective, case-series study to assess efficacy, tolerability, and safety of dupilumab in elderly, patients on concomitant immunosuppressive/immunomodulating therapies, and those with pre-existing co-morbidities (e.g., malignancies, chronic renal and/or liver diseases, organ transplantation, hematologic malignancies, and infection). We conducted chart reviews of 248 patients who were prescribed dupilumab between January 1, 2017 and August 31, 2021, and identified 64 patients who met the criteria of being in the complex patient group as described above. Our results showed that 87.5% (56/64) of complex patients demonstrated improvement and/or disease clearance on dupilumab. 20.3% (13/64) of them experienced one or more side effects reported as conjunctivitis, seborrheic dermatitis, psoriasiform eruption, xerosis, facial burning sensation, anaphylactic reaction/angioedema, and worsening of AD. 9.4% (6/64) of them discontinued dupilumab due to the side effects. These findings demonstrated that dupilumab can be safely considered in certain complex patient populations such as elderly and those with significant pre-existing co-morbidities and can be safely combined with immunosuppressive medications and/or other biologic therapies. In the future, more studies with long-term follow-up are needed to validate the efficacy and safety of dupilumab in these challenging patients with complex medical histories.

Systematic review of TNFα-induced paradoxical psoriasis: Treatment outcomes of switching to alternative biologic therapies in inflammatory bowel disease patients.

OBJECTIVES: The objective of this systematic review was to evaluate the efficacies of different biologic therapies in treating tumor necrosis factor-alpha (TNFα)-induced paradoxical psoriasis (PXP) and controlling inflammatory bowel disease (IBD) symptoms. METHODS: We conducted a literature search of the Ovid EMBASE, Ovid Medline, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials databases from their inception to October 3, 2021. We considered all peer-reviewed, randomized controlled trials, chart reviews, and observational studies that discussed the TNFα-induced PXP treatment outcomes in IBD patients of switching to different biologic therapies. RESULTS: Switching to ustekinumab (UST) resulted in complete or partial resolution of TNFα-induced PXP in 83.1% of patients (74 out of 89 patients), while switching to either vedolizumab (VDZ) or secukinumab led to complete resolution in 100% of patients (eight out of eight patients). Approximately 75.4% of patients who were switched to UST remained in IBD remission, 4.6% in partial remission, and 20.0% in the flare of IBD. CONCLUSIONS: UST has sufficient data to demonstrate the efficacy in treating TNFα-induced PXP and controlling IBD symptoms concurrently. More data is needed to validate the efficacies of VDZ and SEC in treating TNFα-induced PXP in IBD patients.

Urgent referrals from primary care to dermatology for lesions suspicious for skin cancer: patterns, outcomes, and need for systems improvement.

Ideally, urgent dermatology referrals for evaluation of a lesion concerning for skin cancer should be triaged and processed with appropriate urgency by primary care and dermatology, respectively. We performed a retrospective single-institution study by conducting chart reviews of all dermatology referrals designated by primary care as urgent for evaluation of a lesion concerning for skin cancer. We identified 320 referrals placed between January 1 and December 31, 2018. Dermatology encounters for these patients occurred on or before 30 days for 50.6% of referrals and on or after 31 days for 38.4% of referrals, with 10.9% never completed. The percentage of all races excluding whites, non-Hispanic in the delayed appointment group (≥ 31 days) was 15.1% higher (95% CI 5.3-24.9) than in the timely appointment group (≤ 30 days). Similarly, the percentage of non-English languages in the delayed group was 7.1% higher (95% CI 0.5-13.7) than in the timely group. Overall, 15.8% of these referrals yielded diagnoses of malignancy, while 76.8% and 7.4% resulted in benign and pre-malignant diagnoses, respectively. The primary care team documented referral status (i.e., completed, incomplete, or pending) during their subsequent visits with the patients in only 37.5% of these referrals. Our findings demonstrate the need to improve the reliability of urgent referrals to ensure they occur in a timely manner with confirmation of "referral loop" closure at the referring clinician's end.

Cutaneous Manifestations of Inflammatory Bowel Disease: A Basic Overview.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal (GI) tract that is subdivided into Crohn's disease (CD) and ulcerative colitis (UC). CD is characterized by involvement of the entire GI tract, while UC mainly affects the distal GI tract. Moreover, both CD and UC can present with extraintestinal manifestations (EIMs) of the disease affecting multiple organ systems including the hepatobiliary tract, kidney, bones, eyes, joints, and skin. These complications can cause significant morbidity and negatively impact the quality of life for IBD patients. Although the pathogenesis of EIMs is not clearly elucidated, it is postulated that the diseased GI mucosa similarly stimulates excess immune responses at the extraintestinal sites. Cutaneous EIMs occur in up to 15% of patients with IBD, often predating their IBD diagnosis. They are categorized into (1) specific, (2) reactive, (3) associated, and (4) treatment-induced. Here, we review the epidemiological, clinical, diagnostic, and histologic features of the most commonly described cutaneous EIMs of IBD along with their respective treatment options.

Systemic comorbidities of rosacea: practice gaps among dermatologists.

Rosacea is a chronic inflammatory skin condition that is associated with multiple systemic comorbidities, with the strongest evidence linking rosacea to hypertension, dyslipidemia, inflammatory bowel disease, and anxiety and depression. To assess dermatologists' awareness of and screening practices for rosacea comorbidities, we developed a survey that was distributed to attendings and residents across four academic dermatology departments in Massachusetts. A total of 73 dermatologists with varying experience participated in the study. Findings demonstrated significant knowledge and practice gaps among academic dermatologists in managing systemic comorbidities in rosacea. In addition, dermatologists' awareness of rosacea comorbidities was negatively correlated with number of years out of residency training, highlighting the need to address this knowledge gap through increased continuing medical education. Importantly, we observed a low screening frequency despite a high awareness of the association between rosacea and ocular comorbidities, suggesting that additional financial, institutional, or practice barriers likely contribute to the low screening rate.

Rosacea, not just skin deep: Understanding thesystemic disease burden.

Rosacea is a common inflammatory skin condition with four main clinical subtypes: erythematotelangiectatic, papulopustular, rhinophymatous, and ocular. Although several genetic and environmental factors have been linked with triggering rosacea, the pathogenesis still remains poorly understood. There is an increasing evidence in the literature to support that rosacea is a harbinger of several systemic comorbidities and may represent a chronic, systemic, inflammatory state. We have provided the most up-to-date evidence on the association between rosacea and several systemic diseases, discussing that rosacea is not just a skin disorder but a systemic disease process.

Epigenetic-modifying therapies: An emerging avenue for the treatment of inflammatory skin diseases.

Epigenetic modifications include DNA methylation, histone modification and the action of microRNAs. These mechanisms coordinate in complex networks to control gene expression, thereby regulating key physiological processes in the skin and immune system. Recently, researchers have turned to the epigenome to understand the pathogenesis of inflammatory skin diseases. In psoriasis and atopic dermatitis, epigenetic modifications contribute to key pathogenic events such as immune activation, T-cell polarization and keratinocyte dysfunction. These discoveries have introduced new possibilities for the treatment of skin diseases; unlike genetics, epigenetic alterations are readily modifiable and potentially reversible. In this viewpoint essay, we summarize the current state of epigenetic research in inflammatory skin diseases and propose that targeting the histone machinery is a promising avenue for the development of new therapies for psoriasis and atopic dermatitis. Expanding on the progress that has already been made in the field of cancer epigenetics, we discuss existing epigenetic-modifying tools that can be applied to the treatment of inflammatory skin diseases and consider future directions for investigation in order to allow for the widespread clinical application of such therapies.

DNA methylation and inflammatory skin diseases.

Epigenetics is the study of heritable changes in gene expression that do not originate from alternations in the DNA sequence. Epigenetic modifications include DNA methylation, histone modification, and gene silencing via the action of microRNAs. Epigenetic dysregulation has been implicated in many disease processes. In the field of dermatology, epigenetic regulation has been extensively explored as a pathologic mechanism in cutaneous T-cell lymphoma (CTCL), which has led to the successful development of epigenetic therapies for CTCL. In recent years, the potential role of epigenetic regulation in the pathogeneses of inflammatory skin diseases has gained greater appreciation. In particular, epigenetic changes in psoriasis and atopic dermatitis have been increasingly studied, with DNA methylation the most rigorously investigated to date. In this review, we provide an overview of DNA methylation in inflammatory skin diseases with an emphasis on psoriasis and atopic dermatitis.

Successful treatment of ephelides in Asian skin using the picosecond 785-nm laser.

BACKGROUND: For ethnic skin, laser surgery for pigmented lesions presents a special challenge due to the increased risk of postprocedural complications-erythema, blistering, and postinflammatory dyspigmentation. AIMS: To describe the treatment of ephelides in Asian skin treated with a picosecond 785-nm laser. PATIENTS/METHODS: The first patient with ephelides on the cheeks and nose was treated with a picosecond 785-nm laser with the treatment parameter of 1.2 J/cm2 and 3-mm spot size. The second patient with ephelides on the cheeks was treated with a picosecond 785-nm laser with the treatment parameter of 1.3 J/cm2 and 3-mm spot size. RESULTS: After a single laser session, both patients achieved appreciable improvement without any complications. CONCLUSION: This is the first case series demonstrating the efficacy and safety of the picosecond 785-nm laser for the treatment of ephelides in Asian skin.

MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma.

Histone modifications, largely regulated by histone acetyltransferases (HAT) and histone deacetylases, have been recognized as major regulatory mechanisms governing human diseases, including cancer. Despite significant effort and recent advances, the mechanism by which the HAT and transcriptional coactivator p300 mediates tumorigenesis remains unclear. Here, we use a genetic and chemical approach to identify the microphthalmia-associated transcription factor (MITF) as a critical downstream target of p300 driving human melanoma growth. Direct transcriptional control of MITF by p300-dependent histone acetylation within proximal gene regulatory regions was coupled to cellular proliferation, suggesting a significant growth regulatory axis. Further analysis revealed forkhead box M1 (FOXM1) as a key effector of the p300-MITF axis driving cell growth that is selectively activated in human melanomas. Targeted chemical inhibition of p300 acetyltransferase activity using a potent and selective catalytic p300/CBP inhibitor demonstrated significant growth inhibitory effects in melanoma cells expressing high levels of MITF. Collectively, these data confirm the critical role of the p300-MITF-FOXM1 axis in melanoma and support p300 as a promising novel epigenetic therapeutic target in human melanoma. SIGNIFICANCE: These results show that MITF is a major downstream target of p300 in human melanoma whose expression is predictive of melanoma response to small-molecule inhibition of p300 HAT activity.