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.

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.

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.

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.

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: 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.

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.

Beard Alopecia: An Updated and Comprehensive Review of Etiologies, Presentation and Treatment.

Facial hair is an important social and psychologic aspect of clinical appearance for men. The purpose of this review is to provide a comprehensive overview of the causes of alopecia of the beard including the prevalence, pathophysiology, clinical presentation, and treatment. In this review, we highlight more common causes of beard alopecia including alopecia areata and pseudofolliculitis barbae, infectious causes such as tinea barbae and herpes simplex folliculitis, and rare causes including dermatopathia pigmentosa reticularis and frontal fibrosing alopecia. This review serves as an important resource for clinicians when faced with patients suffering from beard alopecia.

Treatment of Androgenetic Alopecia: Current Guidance and Unmet Needs.

Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Traditionally, topical minoxidil and oral finasteride have been the standard of care yielding mixed results. New treatments such as Low-Level Laser Therapy (LLLT), microneedling, platelet-rich plasma (PRP), and others have been extensively studied in the literature, and the purpose of this review is to provide a comprehensive discussion of the latest treatment methods and their efficacy in treating AGA. Novel therapies such as oral minoxidil, topical finasteride, topical spironolactone, botulinum toxin, and stem cell therapy offer interesting alternatives to standard of care therapies for patients. In this review, we present data from recent studies on the clinical efficacy of these treatments. Furthermore, as new treatments have emerged, clinicians have tested combination therapies to assess whether there may be a synergistic relationship between multiple modalities. While there has been a great increase in the treatments available for AGA, the quality of evidence varies greatly and there is still a great need for randomized double blinded clinical trials to adequately assess the clinical efficacy of some treatments. While PRP and LLLT have demonstrated encouraging results, standardized treatment protocols are needed to adequately inform clinicians on how to use such therapies. Given the abundance of new therapeutic options, clinicians and patients must weigh the benefits and risks of each treatment option for AGA.

Platelet Rich Plasma Combination Therapies for Treatment of Androgenetic Alopecia: A Systematic Review.

Androgenetic alopecia (AGA) is the most common cause of alopecia in males and females. Minoxidil and finasteride are the only FDA-approved treatments for AGA. New treatments including Platelet Rich Plasma (PRP) and microneedling have shown promising results. The purpose of this literature review was to highlight recent studies examining the effects of topical minoxidil combined with PRP to minoxidil or PRP monotherapy. The method used for this paper includes a systematic review of the literature from 2010 to 2022 using the PubMed, EMBASE, and MEDLINE databases examining studies evaluating combination therapies for AGA. Three randomized control trials compared combination PRP + topical 5% minoxidil to either no treatment, 5% minoxidil, or PRP only. Two studies found increased hair growth at five months and at six months following combined therapy. Another study found an increase in hair density and improved patient satisfaction with combination therapy compared to monotherapy. A prospective study revealed that patients treated with combined 5% minoxidil, PRP, and microneedling reported the highest patient and physician satisfaction compared to minoxidil monotherapy. An observational study evaluating topical 5% minoxidil with PRP reported an increase in hair diameter after one year of combination treatment compared to minoxidil monotherapy. PRP therapy combined with minoxidil and microneedling in a retrospective study was shown to increase hair growth compared to PRP with minoxidil as well as PRP or minoxidil monotherapy. In conclusion, a variety of studies demonstrated superior treatment response with a combination of PRP and minoxidil therapy in patients with AGA. Limitations to this study include different PRP preparation protocols, few randomized control studies, and small sample sizes.

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.

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.

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.

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.

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.