Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses.

Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

A Practical Algorithm for Integrating Skincare to Improve Patient Outcomes and Satisfaction With Energy-Based Dermatologic Procedures.

BACKGROUND: Medical aesthetic procedures for facial antiaging with laser and energy-based devices (EBDs) are rapidly increasing, but standards integrating skincare before, during, and after these treatments are lacking. The algorithm for integrated skin care for facial antiaging treatment with EBDs aims to stimulate healing, reduce downtime, and improve comfort and treatment outcomes. METHODS: A panel of 8 global physicians employed a modified Delphi method and reached a consensus on the algorithm integrating skincare based on the best available evidence, the panel's clinical experience, and opinions. RESULTS: The algorithm has a pretreatment (starts 2 - 4 weeks before the procedure) and treatment (day of treatment) section, followed by care after the procedure (0 - 7 days) and follow-up care (1 - 4 weeks after the procedure or ongoing). Applying a broad-spectrum sunscreen with an SPF 50 or higher, combined with protective measures such as wearing a wide-brimmed hat and sunglasses, is recommended to protect the face from sun exposure. Dyschromia is a significant concern for those with skin of color (SOC). Clinicians may recommend skincare using a gentle cleanser and moisturizer containing vitamins C and E, retinoid, or other ingredients such as niacinamide, kojic acid, licorice root extract, azelaic acid, and tranexamic acid, depending on the patient's facial skin condition. CONCLUSION: Medical aesthetic procedures for facial antiaging with EBDs integrating skincare or topical treatments may improve outcomes and patient satisfaction. Topical antioxidants and free radical quenchers can combat photodamage and may offer a safe alternative to topical hydroquinone.  J Drugs Dermatol. 2024;23(5):353-359.     doi:10.36849/JDD.8092.

Deucravacitinib in moderate-to-severe plaque psoriasis: Pooled safety and tolerability over 52 weeks from two phase 3 trials (POETYK PSO-1 and PSO-2).

BACKGROUND: Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. OBJECTIVES: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. METHODS: Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. RESULTS: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib. CONCLUSIONS: Deucravacitinib was well-tolerated with acceptable safety over 52 weeks in patients with psoriasis.

Misconceptions of photoprotection in skin of color.

Terrestrial sunlight is the portion of electromagnetic radiation that is emitted by the sun and reaches Earth's surface. It encompasses 3 major components: UV radiation (290-400 nm), visible light (400-700 nm), and infrared radiation. The deleterious effects of UV radiation have been appreciated for decades, particularly among those with light skin tones (Fitzpatrick skin types I-II) who primarily manifest with burns of varying degrees of severity with sun exposure. In recent years, studies have increasingly shown the negative impact of visible light on skin health, particularly in individuals with skin of color (Fitzpatrick skin types IV-VI), including the exacerbation of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation, as well as induction of the former. Recommendations from medical societies and the US Food and Drug Administration for photoprotection have been evolving along with the knowledge base. Yet, misconceptions about skin damage related to sunlight and the benefits of photoprotection (particularly among those with Fitzpatrick skin types V-VI) are still prevalent among both clinicians and patients. Among patients with skin of color, disorders of hyperpigmentation and other consequences from sun exposure have been associated with impaired skin health and negative burden on quality of life. This review summarizes currently available evidence of the impact of both UV and visible wavelengths and the low utilization of photoprotection measures among people with skin of color, with the goal of providing recommendations to help educate patients.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products. METHODS: Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review. RESULTS: Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances. CONCLUSIONS: The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Pretibial Myxedema in a Euthyroid Patient.

Pretibial myxedema (PM) is a rare extrathyroid condition seen in about 0.5 to 4.3 percent of individuals with hyperthyroidism due to Graves' disease, often presenting with associated thyroid orbitopathy. In most cases, patients with PM have elevated levels of thyroid antibodies, such as thyroid peroxidase (TPO), thyroglobulin, and-most especially-thyroid-stimulating hormone receptor antibodies. We present a rare case of biopsy-proven PM in a euthyroid patient with no history of Graves' disease or Hashimoto's disease. TPO and thyroglobulin antibody counts were slightly elevated but less than what is typically seen in PM and thyroid-stimulating hormone receptor antibodies (thyrotrophin-binding inhibitor immunoglobulin) were negative.

Racial and Ethnic Differences in Self-Assessed Facial Aging in Women: Results From a Multinational Study.

BACKGROUND: Racial/ethnic variations in skin structure and function may contribute to differential manifestations of facial aging in various races/ethnicities. OBJECTIVE: To examine self-assessed differences in facial aging in women by race/ethnicity and Fitzpatrick skin phototypes. METHODS: Women aged 18 to 75 years in the United States, Canada, the United Kingdom, and Australia compared their features against photonumeric rating scales depicting degrees of severity for 10 facial aging characteristics. Impact of race/ethnicity (black, Hispanic, Asian, and Caucasian) and skin phototypes on severity was assessed. RESULTS: In total, 3,267 women completed the study. Black women reported the least severe facial aging; Caucasian women reported the most severe facial aging, with Asian and Hispanic women falling between these groups. Similarly, women with a skin phototype V/VI reported lesser aging severity than women with phototypes I through IV. More than 30% of black women did not report the presence of moderate/severe aging of facial areas until 60 to 79 years; most Hispanics and Asians did not report moderate/severe facial aging until 50 to 69 years and Caucasians, 40 to 59 years. CONCLUSION: In this diverse sample, black women reported less severe aging of facial features compared with Hispanic, Asian, and Caucasian women. These results were supported by Fitzpatrick skin phototype analyses.

Patient-focused Solutions in Rosacea Management: Treatment Challenges in Special Patient Groups

Rosacea is among the most common facial skin conditions diagnosed by dermatologists. Typical clinical features include erythema, flushing, telangiectasia, papules, and pustules distributed on the central face. While the prevalence of rosacea is highest among white populations of Northern European descent, recent reports have found that rosacea frequently occurs in people from a broad range of racial/ethnic backgrounds and skin types. When rosacea presents in darker skin types, the diagnosis is often more challenging due to masking of features by increased epidermal melanin. As such, under-diagnosis and underreporting may contribute to misconceptions about the prevalence of rosacea in populations with skin of color. Recognizing the unique presentations and complications associated with darker skin types is necessary to reduce the disparities in rosacea treatment, especially as the American population continues to become increasingly heterogeneous. Although rosacea is most common in middle-aged females, patients of other demographics may have more negative impacts on quality of life due to their disease. In this article, we review rosacea management with a focus on special patient groups: people with skin of color, and less common forms of rosacea, in order to diminish the physical and psychosocial burden of rosacea in all patient groups. Due to the variability inherent to rosacea, we advocate for an individualized, patient-centered approach to disease management.

Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation.

BACKGROUND: African Americans (AA) are disproportionately impacted by atopic dermatitis (AD), with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American (EA) patients. These studies are absent in AA, hindering development of effective treatments for this population. OBJECTIVE: We sought to characterize the global molecular profile of AD in the skin of AA patients as compared with that of EA AD and healthy controls. METHODS: We performed RNA-Seq with reverse transcription polymerase chain reaction validation and immunohistochemistry studies in lesional and nonlesional skin of AA and EA AD patients vs healthy controls. RESULTS: African American AD lesions were characterized by greater infiltration of dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor (FcεR1+) compared with EA AD (P < .05). Both AD cohorts showed similarly robust up-regulation of Th2-related (CCL17/18/26) and Th22-related markers (interleukin [IL]-22, S100A8/9/12), but AA AD featured decreased expression of innate immune (tumor necrosis factor [TNF], IL-1ß), Th1-related (interferon gamma [IFN-γ], MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G, CXCL1) vs EA AD (P < .05). The Th2 (IL-13) and Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity (Scoring of Atopic Dermatitis [SCORAD]) in AA. Fillagrin (FLG) was exclusively down-regulated in EA AD, whereas loricrin (LOR) was down-regulated in both AD cohorts and negatively correlated with SCORAD in AA. CONCLUSION: The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.

Global epidemiology and clinical spectrum of rosacea, highlighting skin of color: Review and clinical practice experience.

Rosacea has been reported less frequently among individuals with skin of color than in those with white skin, but rosacea is not a rare disease in this population. In fact, rosacea might be underreported and underdiagnosed in populations with skin of color because of the difficulty of discerning erythema and telangiectasia in dark skin. The susceptibility of persons with highly pigmented skin to dermatologic conditions like rosacea, whose triggers include sun exposure, is probably underestimated. Many people with skin of color who have rosacea might experience delayed diagnosis, leading to inappropriate or inadequate treatment; greater morbidity; and uncontrolled, progressive disease with disfiguring manifestations, including phymatous rosacea. In this article, we review the epidemiology of rosacea in skin of color and highlight variations in the clinical presentation of rosacea across the diverse spectrum of patient populations affected. We present strategies to aid in the timely diagnosis and effective treatment of rosacea in patients with skin of color, with an aim of promoting increased awareness of rosacea in these patients and reducing disparities in the management of their disease.

Current Concepts in Acne Pathogenesis: Pathways to Inflammation.

Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the roles of hormones (insulin, insulin-like growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate immune responses are induced through interaction with toll-like receptors and inflammasome activation initially and subsequently through adaptive immune activation. These insights into pathogenic inflammatory pathways can translate into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60-S62 ©2018 published by Frontline Medical Communication.

Advances in Acne and Rosacea Therapy.

New topical therapies have demonstrated efficacy in patients with moderate or severe acne who might otherwise have required therapy with systemic antibiotics or isotretinoin. Increasing knowledge about the pathogenesis of acne has facilitated the development of therapies with novel modes of action. New and investigational therapies also are available or in development for the treatment of both the papulopustular and erythematous manifestations of rosacea. Semin Cutan Med Surg 37(supp3):S63-S66 © 2018 published by Frontline Medical Communications.

Treating Acne in Adult Women.

Acne can persist into adulthood or erupt de novo at any point after adolescence. Adult acne is more common in women than in men. Considerations for treating acne in adult women include childbearing potential, pregnancy, lactation, and concomitant skin conditions. Semin Cutan Med Surg 37(supp3):S67-S70 © 2018 published by Frontline Medical Communications.

Treating Acne in Patients With Skin of Color.

Patients with skin of color are more likely to develop acne and postinflammatory hyperpigmentation (PIH). Many therapies for acne have demonstrated efficacy in darker skin types and in the treatment of PIH. Semin Cutan Med Surg 37(supp3):S71-S73 © 2018 published by Frontline Medical Communications.

Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation, Pathogenesis and Treatment.

Postinflammatory hyperpigmentation (PIH) is a reactive hypermelanosis that develops following cutaneous inflammation. Common causes of PIH include intrinsic skin conditions (e.g., acne and eczema) as well as external insults to the skin, such as burn injuries and dermatologic procedures. PIH more commonly occurs in individuals with darker skin, for whom it is often a source of significant psychological distress. Several therapeutic modalities are available for the treatment of PIH, including topical agents, chemical peels, and energy-based devices. We review the epidemiology, clinical presentation, pathogenesis, and treatment of PIH.

Nonablative Fractional Laser Resurfacing for Acne Scarring in Patients With Fitzpatrick Skin Phototypes IV-VI.

BACKGROUND: There is a paucity of studies investigating laser resurfacing in Fitzpatrick skin phototypes (SPT) IV to VI. OBJECTIVE: To assess the efficacy and safety of fractional nonablative laser resurfacing in the treatment of acne scarring in patients with SPT IV to VI. METHODS AND MATERIALS: The authors conducted a randomized, investigator-blinded and rater-blinded, split-face comparative study of adults with SPT IV to VI and facial acne scars treated with 2 different density settings and the same fluence. RESULTS: Quantitative global scarring grading system (QGSGS) scores were significantly improved from baseline at 16 and 24 weeks (p = .0277). Improvements in QGSGS scores after higher and lower density treatments were statistically similar (p = .96). The live-blinded dermatologist, the blinded dermatologist photoraters, and the patients rated scars as being significantly more improved by visual analog scale at weeks 16 and 24 compared with baseline (p < .001) for both treatment densities. Five of 7 and 3 of 7 patients in the higher and lower density group, respectively, experienced mild or moderate hyperpigmentation as an investigator observed site reaction. CONCLUSION: The nonablative 1550-nm fractional laser is safe and efficacious in treating acne scaring in Fitzpatrick skin types IV to VI. Self-limited postinflammatory hyperpigmentation was a common occurrence, especially with higher treatment densities.

A retrospective chart review to assess the safety of nonablative fractional laser resurfacing in Fitzpatrick skin types IV to VI.

BACKGROUND: Laser resurfacing in patients with Fitzpatrick skin phototypes (SPT) IV to VI is associated with a higher risk of pigmentary alteration. There is a paucity of studies evaluating optimum treatment parameters for fractional lasers in darkly pigmented skin types. METHODS: This is a retrospective review of medical records for patients with SPT IV to VI who were treated with a 1,550 nm erbium-doped fractional nonablative laser (Fraxel Re:Store SR 1550; Solta Medical, Hayword, CA). Data were collected from patient charts and the clinic laser logbook from January 2008 to January 2012. The frequency of treatment-associated postinflammatory hyperpigmentation (PIH) and treatment settings used were evaluated. RESULTS: A total of 115 total laser sessions (45 patients) were included in our analysis. Five of the sessions (4%) were accompanied by PIH, 2 of which occurred in a single patient. Only 1 episode of PIH lasted longer than 1 month (2 months). Two of the 5 cases had only transient PIH (≤7 days), one of which was reported by the patient and not clinically evident on examination. CONCLUSION: The 1,550 nm erbium-doped fractional laser is well tolerated in SPT IV to VI. Fractional laser resurfacing, with the settings used and pretreatment and posttreatment hydroquinone 4% cream, was associated with a low risk of PIH in darker skin types.

Effectiveness and safety of once-daily doxycycline capsules as monotherapy in patients with rosacea: an analysis by Fitzpatrick skin type.

Rosacea is often under-recognized or misdiagnosed in patients with skin of color (Fitzpatrick Skin Types [FST] IV-VI). Subtle clinical features and a low index of suspicion likely contribute to less frequent diagnosis in this population. Clinical trials of therapeutic agents for rosacea generally include few patients from nonwhite racial/ethnic groups and therefore, potential differences in treatment outcomes have not been previously studied. The objective of this prospective analysis was to fill the gap in knowledge of the effectiveness and safety of treatment for rosacea in patients with skin of color. We analyzed data from 826 adults aged ≥ 18 years with papulopustular (subtype 2) rosacea (663 FST I-III; 163 FST IV-VI). All patients received doxycycline 40 mg capsules (30 mg immediate release and 10 mg delayed release beads) once daily as monotherapy for 12 weeks in this open-label, multicenter, community-based study. Investigators assessed disease severity with the Investigator's Global Assessment (IGA) and erythema with the Clinician's Erythema Assessment (CEA). Significant improvement in disease severity and erythema was obtained in patients with FST I-III and IV-VI at week 12 (P<.001). Treatment success, defined as an IGA score of 0 or 1 was achieved in 74.6% and 74.3% of patients with FST I-III and IV-VI, respectively. Approximately 12% of patients experienced adverse events with no difference between the two skin type groups. The results of this prospective subgroup analysis of data from a large community-based trial suggest that doxycycline produced similar effectiveness and safety profiles in patients with FST I-III and IV-VI.