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Drug Design, Development and Therapy 2023In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to... (Review)
Review
In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.
Topics: United States; Humans; Isotretinoin; Dermatology; Acne Vulgaris; Retinoids; Skin Neoplasms
PubMed: 37649956
DOI: 10.2147/DDDT.S427530 -
American Journal of Clinical Dermatology Sep 2020Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it... (Review)
Review
Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it is the loss of balance between the different C. acnes phylotypes, together with a dysbiosis of the skin microbiome, which results in acne development. The loss of diversity of C. acnes phylotypes acts as a trigger for innate immune system activation, leading to cutaneous inflammation. A predominance of C. acnes phylotype IA has been observed, with a more virulent profile in acne than in normal skin. Other bacteria, mainly Staphylococcus epidermis, are also implicated in acne. S. epidermidis and C. acnes interact and are critical for the regulation of skin homeostasis. Recent studies also showed that the gut microbiome is involved in acne, through interactions with the skin microbiome. As commonly used topical and systemic antibiotics induce cutaneous dysbiosis, our new understanding of acne pathophysiology has prompted a change in direction for acne treatment. In the future, the development of individualized acne therapies will allow targeting of the pathogenic strains, leaving the commensal strains intact. Such alternative treatments, involving modifications of the microbiome, will form the next generation of 'ecobiological' anti-inflammatory treatments.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Anti-Inflammatory Agents; Dysbiosis; Humans; Immunity, Innate; Microbiota; Propionibacterium acnes; Skin; Symbiosis
PubMed: 32910436
DOI: 10.1007/s40257-020-00531-1 -
Drug and Therapeutics Bulletin Dec 2023Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to... (Review)
Review
Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to permanent scars or pigment changes. Guidelines unanimously advise topical treatments as first-line, although differ in recommending either topical benzoyl peroxide or topical retinoid (mainly adapalene) alone or in combination. Guidance published by the National Institute for Health and Care Excellence advises counselling patients regarding avoidance of skin irritation when starting topical treatments and promoting adherence (treatments take 6-8 weeks to work). Oral antibiotics are currently overprescribed for acne but have a role when coprescribed with a non-antibiotic topical treatment. Hormonal treatments, such as the combined contraceptive pill, are also effective and there is growing evidence for the use of spironolactone for women with persistent acne. Recent guidance from the Medicines and Healthcare products Regulatory Agency regarding isotretinoin has implications for specialist prescribing and monitoring, and increasing public awareness of potential risks of mental health problems and sexual dysfunction. Although acne is associated with psychiatric disorder, the mental health effects of isotretinoin remain controversial.
Topics: Humans; Female; Isotretinoin; Acne Vulgaris; Benzoyl Peroxide; Anti-Bacterial Agents; Adapalene
PubMed: 38154809
DOI: 10.1136/dtb.2023.000051 -
Journal of Cutaneous Medicine and... 2023Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid... (Review)
Review
Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid approved for treatment of acne. RAR-γ is the most common isoform of RARs in skin, and the strong selectivity of trifarotene for RAR-γ translates to efficacy in low concentration. Trifarotene, like other topical retinoids, acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces hyperkeratinization. Retinoids have also been shown to inhibit inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1. Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne. However, unlike all other retinoids, trifarotene is the first topical retinoid with rigorous clinical data on safety and efficacy in truncal acne. Data supporting use of trifarotene to manage acne are reviewed in this publication.
Topics: Humans; Dermatologic Agents; Administration, Cutaneous; Retinoids; Acne Vulgaris
PubMed: 36927117
DOI: 10.1177/12034754231163542 -
Cells Nov 2023This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth... (Review)
Review
This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch which enhances the transactivation of lipogenic and proinflammatory transcription factors, including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ) and signal transducer and activator of transcription 3 (STAT3), but reduces the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin's desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.
Topics: Humans; Isotretinoin; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Transcriptome; Acne Vulgaris; Mechanistic Target of Rapamycin Complex 1; Transcription Factors
PubMed: 37998335
DOI: 10.3390/cells12222600 -
Cells Jun 2021The relationship between endocrine disrupting chemicals (EDCs) and the pathogenesis of acne vulgaris has yet to be explored in the literature. Acne vulgaris is a chronic... (Review)
Review
The relationship between endocrine disrupting chemicals (EDCs) and the pathogenesis of acne vulgaris has yet to be explored in the literature. Acne vulgaris is a chronic inflammatory skin disease of the pilosebaceous unit. The pathogenesis of acne involves several hormonal pathways, including androgens, insulin-like growth factor 1(IGF-1), estrogens, and corticosteroids. EDCs influence these pathways primarily through two mechanisms: altering endogenous hormone levels and interfering with hormone receptor function. This review article describes the mechanistic links between EDCs and the development of acne lesions. Highlighted is the contributory role of androgen receptor ligands, such as bisphenol A (BPA) and mono-2-ethylhexyl Phthalate (MEHP), via upregulation of lipogenic genes and resultant exacerbation of cholesterol synthesis. Additionally discussed is the protective role of phytoestrogen EDCs in counteracting androgen-induced sebocyte maturation through attenuation of PPARy transcriptional activity (i.e., resveratrol) and restoration of estrogen-regulated TGF-B expression in skin cells (i.e., genistein). Examination of the relationship between EDCs and acne vulgaris may inform adjunctive avenues of treatment such as limiting environmental exposures, and increasing low-glycemic, plant-rich foods in the diet. With a better understanding of the cumulative role that EDCs play in acne, clinicians can be better equipped to treat and ultimately improve the lives of their patients.
Topics: Acne Vulgaris; Adolescent; Adult; Animals; Endocrine Disruptors; Female; Humans; Phytoestrogens; Young Adult
PubMed: 34207527
DOI: 10.3390/cells10061439 -
Skin Therapy Letter Jan 2022The pathogenesis of acne is multifactorial and involves inflammation, bacterial dysbiosis, and androgen stimulation. Existing systemic therapies target hormonal pathways...
The pathogenesis of acne is multifactorial and involves inflammation, bacterial dysbiosis, and androgen stimulation. Existing systemic therapies target hormonal pathways to mitigate acne lesions; however, their use is limited to the female population and associated with systemic adverse effects. Clascoterone is the first topical therapy to target the hormonal pathogenesis of acne approved to treat acne vulgaris. In two identical phase 3 trials, clascoterone showed favorable efficacy over placebo in treating acne, with higher treatment success and a greater reduction in acne lesions. Large scale trials are required to assess the efficacy of clascoterone against its comparators and in combination with existing acne therapies; however, results from the current phase 3 trials support the therapeutic value of clascoterone, suggesting that this novel topical androgen inhibitor represents a valuable addition to the catalogue of acne therapy.
Topics: Acne Vulgaris; Administration, Topical; Cortodoxone; Female; Humans; Propionates; Treatment Outcome
PubMed: 35081302
DOI: No ID Found -
The Yale Journal of Biology and Medicine Dec 2022Antimicrobial resistance is an increasing public health problem worldwide. The interest of a focus on antimicrobial resistance in acne lies on the facts that acne... (Review)
Review
Antimicrobial resistance is an increasing public health problem worldwide. The interest of a focus on antimicrobial resistance in acne lies on the facts that acne vulgaris (acne) is the most common skin disease worldwide, that the bacterium (, formerly ) plays a key role in the pathogenesis of acne, while at the same time being part of the skin flora, and that antibiotics are commonly recommended for acne treatment. The overuse of topical and/or systemic antibiotics, the long treatment courses used for acne, and the availability of over-the-counter antibiotic preparations, have led to the worldwide emergence of resistant strains in acne patients. In this review, we discuss the epidemiological trends of antimicrobial resistance in acne, the need to avoid the perturbation of the skin microbiome caused by anti-acne antibiotics, and the clinical practice considerations related to the emergence of resistant strains in acne patients. In light of the increasing risk of antimicrobial resistance, raising concerns over the misuse of antibiotics, prescribing patterns can be a critical target for antibiotic stewardship efforts. Also, the selection of non-antibiotic therapies for acne, whenever possible, may offer significant advantages.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Acne Vulgaris; Skin; Propionibacterium acnes
PubMed: 36568833
DOI: No ID Found -
American Journal of Clinical Dermatology Sep 2023Acne is a common, chronic inflammatory condition affecting millions of people worldwide, with significant negative impact on quality of life and mental health. Acne is...
Acne is a common, chronic inflammatory condition affecting millions of people worldwide, with significant negative impact on quality of life and mental health. Acne is characterized by comedones, inflammatory papules, pustules, and nodulocystic lesions, with long-lasting sequelae including scarring and dyspigmentation, the latter of which is more common in skin of color. The four main pillars of acne pathophysiology include alteration of sebum production and concentration, hyperkeratinization of the follicular unit, Cutibacterium acnes strains, and an inflammatory immune response. Newer research has provided greater insight into these pathophysiologic categories. This greater understanding of acne pathogenesis has led to numerous new and emerging treatment modalities. These modalities include combinations of existing treatments, repurposing of existing agents historically used for other conditions, new topical treatments, novel antibiotics, topical and oral probiotics, and various procedural devices. This article will provide an overview of emerging treatments of acne and their link to our current and improved understanding of acne pathogenesis.
Topics: Humans; Quality of Life; Acne Vulgaris; Skin; Administration, Topical; Anti-Bacterial Agents; Inflammation
PubMed: 37328614
DOI: 10.1007/s40257-023-00789-1 -
Journal of the American Academy of... May 2021Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and... (Review)
Review
Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and flash lamps. Photons from visible light are absorbed by photoreceptive chromophores (e.g., melanin, heme, and opsins), altering skin function by activating and imparting energy to chromophores. Additionally, visible light can penetrate the full thickness of the skin and induce pigmentation and erythema. Clinically, lasers and light devices are used to treat skin conditions by utilizing specific wavelengths and treatment parameters. Red and blue light from light-emitting diodes and intense pulsed light have been studied as antimicrobial and anti-inflammatory treatments for acne. Pulsed dye lasers are used to treat vascular lesions in adults and infants. Further research is necessary to determine the functional significance of visible light on skin health without confounding the influence of ultraviolet and infrared wavelengths.
Topics: Acne Vulgaris; Humans; Light; Low-Level Light Therapy; Skin; Skin Pigmentation; Treatment Outcome
PubMed: 33640508
DOI: 10.1016/j.jaad.2021.02.048