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Introduction/Background Studies have shown that patients with vs without alopecia areata (AA) have a higher risk of developing atopic dermatitis (AD). However, the real-world prevalence and incidence of moderate-to-severe AD in patients with AA are not well characterized. Objectives To assess the real-world prevalence and incidence of comorbid AD among patients with AA using data from a US administrative claims database. Methods This retrospective analysis evaluated claims from the Merative Marketscan Commercial Claims and Encounters database. Eligible patients were aged ≥12 years at index date (first AA diagnosis), received an AA diagnosis (≥1 inpatient encounter or ≥2 outpatient encounters/claims based on International Classification of Diseases, Clinical Modification, 10th Revision [ICD-10-CM]: L63.x or 9th Revision [ICD-9-CM]: 704.01) between 01/01/2017–07/31/2023, and had continuous plan enrollment for 5 years prior to index. AA disease severity was evaluated during the 6-month follow-up period post-index date. Patients were considered to have moderate-to-severe AA if they were diagnosed with alopecia universalis (ICD-10-CM: L63.1) or alopecia totalis (ICD-10-CM: L63.0) or if they received prescriptions for any systemic immunomodulators, oral corticosteroids, nonsteroidal systemic agents, or phototherapy within 6 months post-index date. Very severe AA (subset of moderate-to-severe AA) was defined by a diagnosis of alopecia universalis (ICD-10-CM: L63.1) or alopecia totalis (ICD-10-CM: L63.0). AD was defined as ≥1 inpatient or ≥2 outpatient claims with diagnosis codes for AD (ICD-10-CM L20.x) or other AD-related conditions (ICD-9-CM 691.8). Moderate-to-severe AD was defined per the AD criteria plus claims indicating 1 of the following: ≥1 dispensing of dupilumab; ≥2 dispensing of high-potency topical corticosteroids or systemic immunosuppressants; or ≥3 dispensing of medium potency topical corticosteroids, topical tacrolimus, phototherapy, or oral/parenteral corticosteroids. AD prevalence was assessed during the 5 years pre-index period; prevalence was also assessed over a longer duration and included those with ≥1 AD diagnosis from 01/01/2007–index. AD incidence was assessed from the 7th month after the AA index date through the time of AD diagnosis or end of continuous enrollment. Relative risk for developing AD comorbidity among patients with AA was evaluated using Cox proportional hazards model, controlling for age, sex, obesity, Charlson Comorbidity Index (CCI), and geographic region. Results Of 429,903 patients identified with AA in the database, 10,863 met eligibility criteria and 9507 completed ≥6 months of follow-up post-index date (mild AA, n=7087; moderate-to-severe AA, n=2420; very severe AA, n=491). The 1-year period prevalence of AA in the US was 0.16% in 2022. Among the 10,863 eligible patients, 63.0% were female, the mean (SD) age was 40.4 (15.1) years, and the mean (SD) CCI was 0.7 (1.2). Among all eligible patients with AA (n=10,863), the prevalence (within 5 years pre-index date) was 3.1% for any AD and 2.3% for moderate-to-severe AD. Among patients with moderate-to-severe AA (n=2420), the prevalence was 4.8% for any AD and 4.2% for moderate-to-severe AD. The prevalence of any AD any time prior to index among all eligible patients with AA and moderate-to-severe AA was 11.9% and 14.6%, respectively. AD incidence at follow-up was 4 per 1000 person-years in patients with mild AA, 7 per 1000 person-years for moderate-to-severe AA, and 6 per 1000 person-years for very severe AA. Mean (SD) time to AD diagnosis after AA index date was 2.1 (1.7) years for patients with mild AA, 2.0 (1.7) years for moderate-to-severe AA, and 2.0 (1.7) years for very severe AA. Risk of developing AD was greater in patients with moderate-to-severe vs mild AA (adjusted hazard ratio 1.63 [95% CI 1.01, 2.64]). Conclusions Patients with moderate-to-severe vs mild AA had higher prevalence and incidence of AD comorbidity and higher prevalence of moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

The most effective way to move from target identificationto the clinic is to identify already approved drugs with the potentialfor activating or inhibiting unintended targets (repurposing or repositioning).This is usually achieved by high throughput chemical screening, transcriptomematching, or simple in silico ligand docking. We now describe a novelrapid computational proteochemometric method called “train,match, fit, streamline” (TMFS) to map new drug–targetinteraction space and predict new uses. The TMFS method combines shape,topology, and chemical signatures, including docking score and functionalcontact points of the ligand, to predict potential drug–targetinteractions with remarkable accuracy. Using the TMFS method, we performedextensive molecular fit computations on 3671 FDA approved drugs across2335 human protein crystal structures. The TMFS method predicts drug–targetassociations with 91% accuracy for the majority of drugs. Over 58%of the known best ligands for each target were correctly predictedas top ranked, followed by 66%, 76%, 84%, and 91% for agents rankedin the top 10, 20, 30, and 40, respectively, out of all 3671 drugs.Drugs ranked in the top 1–40 that have not been experimentallyvalidated for a particular target now become candidates for repositioning.Furthermore, we used the TMFS method to discover that mebendazole,an antiparasitic with recently discovered and unexpected anticancerproperties, has the structural potential to inhibit VEGFR2. We confirmedexperimentally that mebendazole inhibits VEGFR2 kinase activity andangiogenesis at doses comparable with its known effects on hookworm.TMFS also predicted, and was confirmed with surface plasmon resonance,that dimethyl celecoxib and the anti-inflammatory agent celecoxibcan bind cadherin-11, an adhesion molecule important in rheumatoidarthritis and poor prognosis malignancies for which no targeted therapiesexist. We anticipate that expanding our TMFS method to the >27 000clinically active agents available worldwide across all targets willbe most useful in the repositioning of existing drugs for new therapeutictargets. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to review published literature on antibiotic and antiseptic use and resistance, and explore the utility of benzoyl peroxide in this capacity for dermatologic surgery. METHODS: A literature review was performed to investigate the skin microbiome, guidelines on antibiotic and antiseptic use in dermatologic surgery, and the utility of benzoyl peroxide as an antiseptic. RESULTS: Antiseptics are commonly used in dermatologic surgery to prepare surgical sites, and antibiotics are also employed by some physicians to prevent post-operative infection despite the potential for antibiotic resistance. Benzoyl peroxide, known for its high threshold for antibiotic resistance, has been successfully used in orthopedic surgery to prevent surgical site infection, especially in sebaceous areas of the skin which house a distinct microbiota. LIMITATIONS: Limitations to this review include lack of high-quality, adequately powered research and studies which evaluate the clinical impact of anti-septic use, particularly benzoyl peroxide use, in dermatologic surgery. CONCLUSION: Benzoyl peroxide may be a used as an antiseptic in dermatologic surgery of sebaceous areas to prevent post-operative infections, with a low likelihood of causing microbial resistance. [ABSTRACT FROM AUTHOR]

The greatest risk factor for skin cancer is exposure to ultraviolet (UV) rays of the sun. Among the three types of solar radiation (UVA, UVB, UVC), UVB rays are most commonly associated with skin cancer. UVB exposure promotes the formation of cyclobutane pyrimidine dimers (CPDs) in the DNA of cells in the epidermal skin layers, which can lead to mutations as DNA repair machinery attempts to repair the damage. These mutations can lead directly to skin carcinogenesis. Previous studies in animal and in human ex vivo skin models have shown that topical application of acyclothymidine dinucleosides protects DNA from UV-induced damage by preventing the formation of CPDs and helps initiate repair through the activation of DNA repair enzymes. Here we review the biological evidence leading to the development and formulation of ProteXidineTM (Topix Pharmaceuticals, Inc., Amityville, NY), as a UV protective agent for topical human application. We also provide clinical data pertaining to four ProteXidineTM formulations (test materials 1-4) tested for their abilities to reduce CPDs in an ex vivo human skin tissue model. J Drugs Dermatol. 2024;23(11):953-956. doi:10.36849/JDD.8420.

What is the ideal topical acne therapeutic? Topical therapeutics for acne vulgaris have advanced considerably over the last decade. Novel vehicular technologies have increased transdermal penetration of active molecules, enhanced their distribution across the skin surface, improved tolerability, and allowed for the incorporation of previously incompatible active compounds. Thus, fixed-combination topical therapeutics were successfully developed and are able to target multiple aspects of acne pathogenesis leading to synergism and increased efficacy. These advancements have paved the way to optimizing acne treatment while incorporating antibiotic stewardship which has become an urgent necessity. J Drugs Dermatol. 2024;23:11(Suppl 1):s4-10.

Background: This paper examines alternative procedural interventions for Seborrheic Dermatitis (SD), aiming to offer clinicians more treatment options and encourage further research., Method: A search was conducted on PubMed using specific search terms related to SD and various dermatological procedures. Studies in English, focusing on SD in human patients, and in-office treatments were included. Data were analyzed for procedure type, effectiveness, and side effects., Results: Nine studies were reviewed, covering phototherapy, indole-3-acetic acid photodynamic therapy (IAA-PDT), Picosecond Nd:YAG laser, botulinum toxin (BoNT) injections, triamcinolone injections, hair growth factor therapy, and precision cryotherapy. Most showed significant efficacy in small cohorts with high patient satisfaction. Hair growth factor therapy had long-term benefits, while narrow-band ultraviolet B phototherapy showed relapse within one month. Intense pulsed light with supramolecular salicylic acid, IAA-PDT, and laser therapy reduced sebum output and Malassezia furfur. Triamcinolone injections were effective against SD's immunological aspects. Hair growth factor therapy and precision cryotherapy have been successfully used to treat scalp SD. The role of BoNT in SD is still being explored; however, current evidence does not support its use., Conclusion: Limited data reveal the need for further research on dermatological procedures for SD. These methods show promise for better patient compliance but face challenges such as cost, variable effectiveness, and unknown long-term safety. Future research should focus on protocol standardization and comprehensive evaluation of long-term outcomes. J Drugs Dermatol. 2024;23(10):819-824. doi:10.36849/JDD.8116.

Granuloma annulare is a benign, non-infectious cutaneous granulomatous disease. Its pathogenesis is not completely elucidated but has recently been thought to involve immunologic and cytokine receptor signaling dysregulation. This includes the involvement of both Th1 and Th2 pathways as well as Th17 and Th22 axes and the Janus kinase/signal transducers and activators of the transcription (JAK-STAT) pathway. First-line treatment is typically intralesional or topical corticosteroids, however, these therapies do not always provide consistent, long-term efficacy for all patients. The successful use of therapies that target the specific inflammatory and immunologic mechanisms that underlie the pathogenesis of GA has been described. Here we describe a case of long-standing GA treated with tapinarof cream 1% applied once daily for 30 days. To our knowledge, this treatment has not yet been adequately described in the literature. J Drugs Dermatol. 2024;23(10):889-893.  doi:10.36849/JDD.8321.

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.

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.

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.

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.

The ascent of polypharmacology in drug development has many implications for disease therapy, most notably in the efforts of drug discovery, drug repositioning, precision medicine and combination therapy. The single- target approach to drug development has encountered difficulties in predicting drugs that are both clinically efficacious and avoid toxicity. By contrast, polypharmacology offers the possibility of a controlled distribution of effects on a biological system. This review addresses possibilities and bottlenecks in the efficient computational application of polypharmacology. The two major areas we address are the discovery and prediction of multiple protein targets using the tools of computer-aided drug design, and the use of these protein targets in predicting therapeutic potential in the context of biological networks. The successful application of polypharmacology to systems biology and pharmacology has the potential to markedly accelerate the pace of development of novel therapies for multiple diseases, and has implications for the intellectual property landscape, likely requiring targeted changes in patent law.

We describe here RepurposeVS for the reliable prediction of drug-target signatures using X-ray protein crystal structures. RepurposeVS is a virtual screening method that incorporates docking, drug-centric and protein-centric 2D/3D fingerprints with a rigorous mathematical normalization procedure to account for the variability in units and provide high-resolution contextual information for drug-target binding. Validity was confirmed by the following: (1) providing the greatest enrichment of known drug binders for multiple protein targets in virtual screening experiments, (2) determining that similarly shaped protein target pockets are predicted to bind drugs of similar 3D shapes when RepurposeVS is applied to 2,335 human protein targets, and (3) determining true biological associations in vitro for mebendazole (MBZ) across many predicted kinase targets for potential cancer repurposing. Since RepurposeVS is a drug repurposing-focused method, benchmarking was conducted on a set of 3,671 FDA approved and experimental drugs rather than the Database of Useful Decoys (DUDE) so as to streamline downstream repurposing experiments. We further apply RepurposeVS to explore the overall potential drug repurposing space for currently approved drugs. RepurposeVS is not computationally intensive and increases performance accuracy, thus serving as an efficient and powerful in silico tool to predict drug-target associations in drug repurposing.

The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.