INDIVIDUAL ARTICLE: Update on Combined Topical Products for Treating Acne: Leaping From Dyads.

Antibiotic resistance and treatment adherence remain significant challenges for acne treatment. Advances in topical formulations have ushered in an era of fixed combination topical therapeutics that are well-tolerated and more efficacious. In addition, their once-daily application leads to increased treatment adherence. This article discusses formulation strategies that allow for the coadministration of active drugs and reviews all commercially available fixed-combination topical acne treatments.  J Drugs Dermatol. 2024;23:4(Suppl 2):s4-10.

INDIVIDUAL ARTICLE: Antibiotic Stewardship in Acne: 2023 Update.

Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of individuals have received antibiotics as part of their treatment resulting in a worldwide pandemic of antibiotic resistance not only for C. acnes but also many other pathogens. With the increasing prevalence of acne and exponentially increasing utilization of antibiotics, prescribers must urgently embrace the notion of antibiotic stewardship to maintain the efficacy of acne treatments while attenuating the rise of resistance. This paper serves as an update on C. acnes resistance to antibiotics commonly employed in the treatment of acne and the necessity of implementing benzoyl peroxide in the treatment regimen as monotherapy or combination antibiotic therapies for overcoming and preventing resistance. J Drugs Dermatol. 2024;23:1(Suppl 2):s4-10.

First Use of Combination Oral Deucravacitinib With Tapinarof Cream for Treatment of Severe Plaque Psoriasis.

Plaque psoriasis is a chronic, immune-mediated, cutaneous, and systemic inflammatory dermatosis. Its pathogenesis involves the dysregulation of the interleukin (IL)-23/IL-17 signaling pathway. There are a range of treatment options available, encompassing topical agents, biologics, oral systemic therapy, and phototherapy. The utility of combination treatment has also been described and is a budding field of research. Here we describe the first case of adult severe generalized plaque psoriasis treated with once-daily oral deucravacitinib 6 mg combined with tapinarof cream 1% applied once daily. To our knowledge, the combination of these agents has not yet been described in the literature. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8091.

Rapid Remission of Plaque Psoriasis With Bimekizumab Treatment.

Bimekizumab is a novel humanized bispecific monoclonal immunoglobulin G1 (IgG1) antibody that dually inhibits both IL-17A and IL-17F. Investigation of the pivotal role of IL-17A, and more recently, IL-17F, in the pathogenesis of psoriasis has underscored the utility of biologics targeting these cytokines in the treatment of the disease. Treatments include the anti-IL-17 biologics specifically targeted against IL-17A (secukinumab and ixekizumab) or its receptor (brodalumab). Recent clinical trials proved the efficacy and safety of bimekizumab in the treatment of moderate-to-severe plaque psoriasis and even showed it to be superior to other psoriasis biologic treatments in regards to efficacy and rapidity of response. These are important factors to consider when discussing treatment options with patients as psoriasis patients commonly desire fast-acting results. In this case, we describe clearance of moderate-to-severe plaque psoriasis within 72 hours of treatment with bimekizumab, one of the fastest reported clearance times in the medical literature. J Drugs Dermatol. 2024;23(8):694-696. doi:10.36849/JDD.8381.

The Use of Natural Therapies in Patients With Skin Cancer: A Scoping Review.

Complementary and alternative medicine (CAM) use has become a field of growing interest in dermatology. However, the prevalence of CAM use is difficult to quantify as it varies based on many factors. Given the exploratory nature of the topic, a scoping review was conducted to identify studies that quantify biologically based CAM use in skin cancer patients. A comprehensive search of Embase, PubMed, and Web of Science databases from inception to August 28th, 2023, was performed. A total of 3,150 articles were identified through the database search. After article screening, 6 studies were suitable for inclusion in this review. Articles included were all questionnaire, survey, or interview style. Biologically based CAM use is prevalent in skin cancer patients. It can be associated with many factors such as location, stage of cancer, and age. CAM use can interact with conventional therapy; therefore, physicians should employ a culturally competent approach to inquiring about CAM use in order to improve patient outcomes and identify patterns and predictors of use.J Drugs Dermatol. 2024;23(5):322-326. doi:10.36849/JDD.8077.

Supplement Individual Article: A Reappraisal of Fixed-Combination Halobetasol Propionate and Tazarotene for the Treatment of Psoriasis: Biological Underpinnings, Therapeutic Mechanisms, and Economic Considerations.

Psoriasis is a complex inflammatory disease, which can be triggered by the interplay among keratinocytes, various immune cells, and even dermal vascular endothelial cells. Understanding of the key players and cytokine/chemokine messengers involved in the initiation and maintenance of psoriasis has significantly evolved and led to numerous systemic biologic therapies targeting those specific components. These therapies, despite their successes, do not ubiquitously affect all pathogenic cellular pathways. They also carry their risks and may be contraindicated in certain patient populations. Therefore, other therapeutics are still necessary. Tazarotene, a decades-old topical retinoid, has been successfully used for treating cutaneous psoriasis. Its retinoid effect via binding to retinoic acid receptors (RAR)/retinoic X receptors (RXR) alters cellular gene expression of numerous pathogenic cells and leads to a long-standing maintenance effect despite discontinuation - a phenomenon known as remittance. Concurrent use of tazarotene with topical corticosteroids results in reduced incidence of treatment-related adverse events. A fixed-combination lotion containing halobetasol propionate (HP) and tazarotene (HP 0.01%/TAZ 0.045%, Duobrii, Ortho Dermatologics) was developed implementing polymeric emulsion technology that demonstrates efficacy in psoriasis while mitigating adverse events associated with each component alone as monotherapy. In this paper, we review the pathogenesis of psoriasis and illuminate the effect of tazarotene and HP on key cellular pathways. In addition, we review the clinical efficacy of fixed-combination HP 0.01%/TAZ 0.045% lotion in psoriasis as well as its long-term treatment maintenance, applicability in skin of color, and beneficial economic impact for patients and healthcare stakeholders. As HP 0.01%/TAZ 0.045% lotion is safe and exhibits excellent efficacy, it should be within the therapeutic toolbox for every psoriasis patient.J Drugs Dermatol. 2023;22:1(Suppl 1):s3-10.

Individual Article: Updated Review of Topical Pharmaceuticals and Complementary and Alternative Medications for the Treatment of Onychomycosis in Both General and Special Populations in the United States.

Onychomycosis is a prevalent condition affecting the United States and global population. Treatment options are limited, with only 3 topical anti-fungal medications garnering approval in the US within the last 25 years: ciclopirox, tavaborole, and efinaconazole. The economic impact and quality of life burden due to onychomycosis are high. Here we provide an up-to-date review of all approved topical anti-fungal therapies for toenail onychomycosis. We discuss treatment efficacies, pharmacology, and use in special populations, as well as current evidence for complementary and alternative medicine.  J Drugs Dermatol. 2023;22:9(Suppl 1):s5-10.

Individual Article: Brodalumab Is an Efficacious, Safe, and Cost-Effective IL-17 Receptor Blocker for the Treatment of Moderate-to-Severe Plaque Psoriasis: 2023 Update.

Psoriasis remains a highly prevalent condition in the United States and worldwide. Preclinical research has been triumphant in elucidating the critical immunological pathways involved in psoriasis. There has been an evolution in biologics that paralleled the understanding of these pathways beginning with anti-tumor necrosis factor (TNF) inhibitors and now most recently the interleukin (IL)-23 and IL-17 axes. Numerous evidence-based studies demonstrate the efficacy of these agents for skin clearance in moderate-to-severe plaque psoriasis. Brodalumab, a fully humanized IL-17 receptor A (IL-17RA) antagonist, is wholly unique in that it binds to a cytokine receptor and not a cytokine itself unlike the other biologics indicated for psoriasis. This unique mechanism has lent an advantage where not only is brodalumab effective in treating moderate-to-severe plaque psoriasis, but it is also successful in psoriasis patients whose disease did not respond to other biologics. This review provides a summary of the efficacy of brodalumab in plaque psoriasis and difficult-to-treat locations (ie, scalp, nail, palmoplantar), in patients with psoriasis who failed to achieve minimum clearance with other biologics, and it illuminates the most recent pharmacovigilance data obtained from the past 5 years. Furthermore, the cost effectiveness of brodalumab is also discussed. J Drugs Dermatol. 2023;22:10(Suppl 1):s5-14.

INDIVIDUAL ARTICLE: Prurigo Nodularis: Current Clinicopathologic Overview and Psychodermatological Perspectives.

Prurigo nodularis (PN) is a quintessential neurocutaneous condition characterized by neural sensitization and intractable itch leading to intense scratching. This causes the formation of nodules with epidermal thickening and further release of pro-inflammatory mediators that recruit immune cells and increase dermal nerve proliferation and hypertrophy perpetuating the itch-scratch cycle. Those with PN have a significant quality-of-life (QoL) burden due to itch, anxiety, and sleep disturbance. In addition, PN exhibits psychiatric comorbidities that affect mental wellbeing such as depression, mood disorders, and substance abuse. This paper serves as an overview of the clinicopathologic aspects of PN, the burden of PN on QoL, and the psychodermatological aspects of the disease state.  J Drugs Dermatol. 2023;22:12(Suppl 2):s6-11.

Review of Superficial Cryotherapy for the Treatment of Alopecia Areata.

Cryotherapy has recently been examined as a potential treatment for alopecia areata (AA). AA is classically managed with intralesional or systemic steroids but relapse rates among those with longstanding disease are high. This narrative review serves to describe the existing studies evaluating cryotherapy for the treatment of AA and examine studies comparing cryotherapy with intralesional steroid injection for the treatment of AA. A review of the literature from 1990 to 2022 was conducted looking for keywords such as “alopecia areata” and “cryotherapy". A total of 8 studies were identified. Three studies assessed the efficacy of liquid nitrogen cryotherapy for the treatment of AA and found approximately 60% of patients responded to treatment and achieved hair regrowth. Three studies compared cryotherapy with intralesional corticosteroid injection, and 2 studies compared cryotherapy with topical corticosteroid therapy. There was no statistically significant difference in efficacy, but there is some evidence to suggest that relapse rates were lower in the cryotherapy group. Treatment protocols differed between studies regarding the number of cycles used for cryotherapy, dosage of intralesional steroids, and patient populations used. Some studies examined cases of recalcitrant AA while other studies examined all cases of AA. More research with larger sample sizes and with similar experimental procedures is necessary to assess the clinical efficacy of cryotherapy.Kaiser M, Issa N, Yaghi M, et al. Review of superficial cryotherapy for the treatment of alopecia areata. J Drugs Dermatol. 2023;22(8):802-809. doi:10.36849/JDD.7431.

Machine and deep learning approaches for cancer drug repurposing.

Knowledge of the underpinnings of cancer initiation, progression and metastasis has increased exponentially in recent years. Advanced "omics" coupled with machine learning and artificial intelligence (deep learning) methods have helped elucidate targets and pathways critical to those processes that may be amenable to pharmacologic modulation. However, the current anti-cancer therapeutic armamentarium continues to lag behind. As the cost of developing a new drug remains prohibitively expensive, repurposing of existing approved and investigational drugs is sought after given known safety profiles and reduction in the cost barrier. Notably, successes in oncologic drug repurposing have been infrequent. Computational in-silico strategies have been developed to aid in modeling biological processes to find new disease-relevant targets and discovering novel drug-target and drug-phenotype associations. Machine and deep learning methods have especially enabled leaps in those successes. This review will discuss these methods as they pertain to cancer biology as well as immunomodulation for drug repurposing opportunities in oncologic diseases.

Alopecia After Cosmetic Injection Procedures: A Review.

BACKGROUND: Cosmetic procedures for antiaging carry inherent risks of adverse events. One that has not yet been well characterized is transitory or permanent alopecia. This is attributable to numerous mechanisms including pressure, ischemia, inflammation, and necrosis. Cases of postcosmetic procedure alopecia have been reported after mesotherapy as well as hyaluronic acid filler, deoxycholic acid, and botulinum toxin injections. OBJECTIVE: This review serves to describe the currently known causes of postcosmetic procedure alopecia and the mechanisms by which alopecia is attained. Furthermore, this review highlights the risk of unregulated mesotherapy injections for cosmetic enhancement and to bring attention to the increasing number reports of alopecia after these procedures. METHODS: A systematic review of the literature from 2000 to 2022 was conducted looking for keywords such as "alopecia," "cosmetic procedures," "mesotherapy," and "hyaluronic acid" in Google Scholar and PubMed. RESULTS: Ten articles met the criteria set forth in the authors' literature review. Many of the procedures resulted in partial or complete resolution of alopecia. CONCLUSION: Alopecia after cosmetic injection procedures is an underreported adverse effect. More research is needed to further characterize the risk of alopecia after mesotherapy and other injection procedures.

Novel Regimen of IL-17A Inhibitor Secukinumab for the Remission of Severe Hidradenitis Suppurativa: Case Report.

Hidradenitis suppurativa (HS) is a morbid, recurrent skin condition that presents a major challenge to clinical therapy. Investigation into the pathogenesis of HS has implicated local and systemic pro-inflammatory cytokines, particularly TNF-α and IL-17A, as major determinants of disease progression and severity. This has ushered in a revolution in HS therapy with biologics targeting these cytokines. We report a case of a 36-year-old man with extensive and treatment-resistant Hurley Stage 3 HS. After undergoing numerous unsuccessful trials of topical, systemic, and biologic therapies, secukinumab therapy with 150 mg weekly injections was initiated. HS clinical response was seen after 20 weeks and was maintained for almost two years. Secukinumab 150 mg or 300 mg once weekly may be an effective and safe therapeutic option for moderate-to-severe chronic HS. J Drugs Dermatol. 2022;21(12):1358-1360. doi:10.36849/JDD.6752.

SUPPLEMENT INDIVIDUAL ARTICLES: Update on Truncal Acne: A Review of Treatments for a Neglected Disease and the Re-Emergence of Tazarotene.

Acne vulgaris of the trunk carries with it a major psychosocial impact and an unmet need for adequate management. Approximately 50% of patients with facial acne also exhibit involvement of the back, chest, and/or upper arms. The trunk poses a therapeutic challenge given its occlusion by clothing, the tendency for mechanical rubbing, a sebum physiology that differs from the face, as well as the fact that there is a large surface area for topical therapies to cover. Furthermore, truncal acne is underreported for a variety of reasons such as cultural barriers, sentiments of embarrassment, and prioritization of facial acne. To date, few medications have been studied specifically for truncal acne. In this article, an updated review of truncal acne and available therapies is provided. The most recent evidence for tazarotene, a third-generation retinoid previously approved for psoriasis and facial acne vulgaris over two decades ago, is also reviewed and compared to trifarotene, a fourth-generation retinoid that is the only approved tropical retinoid for both facial and truncal acne. J Drugs Dermatol. 2022;21:12(Suppl):s5-14.

A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer.

Environmental chemical (EC) exposures and our interactions with them has significantly increased in the recent decades. Toxicity associated biological characterization of these chemicals is challenging and inefficient, even with available high-throughput technologies. In this report, we describe a novel computational method for characterizing toxicity, associated biological perturbations and disease outcome, called the Chemo-Phenotypic Based Toxicity Measurement (CPTM). CPTM is used to quantify the EC "toxicity score" (Zts), which serves as a holistic metric of potential toxicity and disease outcome. CPTM quantitative toxicity is the measure of chemical features, biological phenotypic effects, and toxicokinetic properties of the ECs. For proof-of-concept, we subject ECs obtained from the Environmental Protection Agency's (EPA) database to the CPTM. We validated the CPTM toxicity predictions by correlating 'Zts' scores with known toxicity effects. We also confirmed the CPTM predictions with in-vitro, and in-vivo experiments. In in-vitro and zebrafish models, we showed that, mixtures of the motor oil and food additive 'Salpn' with endogenous nuclear receptor ligands such as Vitamin D3, dysregulated the nuclear receptors and key transcription pathways involved in Colorectal Cancer. Further, in a human patient derived cell organoid model, we found that a mixture of the widely used pesticides 'Tetramethrin' and 'Fenpropathrin' significantly impacts the population of patient derived pancreatic cancer cells and 3D organoid models to support rapid PDAC disease progression. The CPTM method is, to our knowledge, the first comprehensive toxico-physicochemical, and phenotypic bionetwork-based platform for efficient high-throughput screening of environmental chemical toxicity, mechanisms of action, and connection to disease outcomes.

ES-Screen: A Novel Electrostatics-Driven Method for Drug Discovery Virtual Screening.

Electrostatic interactions drive biomolecular interactions and associations. Computational modeling of electrostatics in biomolecular systems, such as protein-ligand, protein-protein, and protein-DNA, has provided atomistic insights into the binding process. In drug discovery, finding biologically plausible ligand-protein target interactions is challenging as current virtual screening and adjuvant techniques such as docking methods do not provide optimal treatment of electrostatic interactions. This study describes a novel electrostatics-driven virtual screening method called 'ES-Screen' that performs well across diverse protein target systems. ES-Screen provides a unique treatment of electrostatic interaction energies independent of total electrostatic free energy, typically employed by current software. Importantly, ES-Screen uses initial ligand pose input obtained from a receptor-based pharmacophore, thus independent of molecular docking. ES-Screen integrates individual polar and nonpolar replacement energies, which are the energy costs of replacing the cognate ligand for a target with a query ligand from the screening. This uniquely optimizes thermodynamic stability in electrostatic and nonpolar interactions relative to an experimentally determined stable binding state. ES-Screen also integrates chemometrics through shape and other physicochemical properties to prioritize query ligands with the greatest physicochemical similarities to the cognate ligand. The applicability of ES-Screen is demonstrated with in vitro experiments by identifying novel targets for many drugs. The present version includes a combination of many other descriptor components that, in a future version, will be purely based on electrostatics. Therefore, ES-Screen is a first-in-class unique electrostatics-driven virtual screening method with a unique implementation of replacement electrostatic interaction energies with broad applicability in drug discovery.

Trichoscopy for the Hair Transplant Surgeon-Assessing for Mimickers of Androgenetic Alopecia and Preoperative Evaluation of Donor Site Area.

Preoperative diagnostic confidence and donor site assessment are important for all hair transplant surgery patients. While the majority of patients seek hair transplantation for male or female pattern hair loss (androgenetic alopecia [AGA]), there are mimickers that must be differentiated from patterned hair loss, as they alter the candidacy of the patient for transplantation. They are termed mimickers as they also can present with patterned hair loss. The use of trichoscopy has become increasingly popular for such use. Patterned hair loss mimickers, which include the underappreciated alopecia areata incognita (AAI) and fibrosing alopecia in patterned distribution (FAPD), can be identified clinically with key trichoscopic findings such as yellow dots and peripilar casts, respectively, that correlate with their histologic diagnosis. Donor hair density and putative hair pathology of the safe donor area can also by assessed via trichoscopy. This article discusses the use of trichoscopy, particularly for diagnosing mimickers of patterned hair loss as well as preoperative donor site assessment.