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Objective: Carotenoids are lipophilic plant molecules with antioxidant properties. Some carotenoids such as β-carotene also serve as vitamin A precursors, playing a key role in human health. Carotenoids are transported in lipoproteins with other lipids such as cholesterol, however, the mechanisms responsible for carotenoid storage in tissues and their non-enzymatic elimination remain relatively unexplored. The goal of this study was to examine the contribution of the low-density lipoprotein receptor (LDLR) in the bodily distribution and disposal of carotenoids. Methods: We employed mice lacking one or both carotenoid-cleaving enzymes as suitable models for carotenoid accumulation. We examined the contribution of LDLR in carotenoid distribution by crossbreeding these mice with Ldlr-/- mice or overexpressing LDLR in the liver. Results: Our results show that LDLR plays a dual role in carotenoid homeostasis by simultaneously favoring carotenoid storage in the liver and adipose tissue while facilitating their fecal elimination. Conclusions: Our results highlight a novel role of the LDLR in carotenoid homeostasis, and unveil a previously unrecognized disposal pathway for these important bioactive molecules.

The article discusses two cases of successful treatment of Disseminated Superficial Porokeratosis (DSP) using 2% crisaborole ointment. Patients with pruritic red papules on the skin were treated with the ointment, resulting in significant improvement and relief of symptoms. Crisaborole, a topical phosphodiesterase-4 (PDE-4) inhibitor, showed promise in treating DSP by reducing keratinocyte proliferation and relieving pruritus, with fewer side effects compared to other medications. The study suggests that crisaborole could be a beneficial therapeutic option for DSP, although further research is needed to determine its effectiveness for other forms of porokeratosis. [Extracted from the article]

Juvenile pityriasis rubra pilaris is a rare inflammatory skin disorder currently without any FDA‐approved treatments, and lesions can be refractory to conventional treatment with topical corticosteroids, methotrexate, and oral retinoids. We herein present a case of a 6‐year‐old boy who attained clearance of extensive juvenile pityriasis rubra pilaris within 2 weeks of starting ixekizumab therapy. Therapeutic effect has been durable at 6 months, and patient continues on therapy without adverse effects. Our case highlights a new, rapidly effective treatment option for pediatric patients with this rare condition. [ABSTRACT FROM AUTHOR]

In the eye, the isomerization of all-trans-retinal to 11-cis-retinal is accomplished by a metabolic pathway termed the visual cycle that is critical for vision. RPE65 is the essential trans-cis isomerase of this pathway. Emixustat, a retinoid-mimetic RPE65 inhibitor, was developed as a therapeutic visual cycle modulator and used for the treatment of retinopathies. However, pharmacokinetic liabilities limit its further development including: (1) metabolic deamination of the γ-amino-α-aryl alcohol, which mediates targeted RPE65 inhibition, and (2) unwanted long-lasting RPE65 inhibition. We sought to address these issues by more broadly defining the structure-activity relationships of the RPE65 recognition motif via the synthesis of a family of novel derivatives, which were tested in vitro and in vivo for RPE65 inhibition. We identified a potent secondary amine derivative with resistance to deamination and preserved RPE65 inhibitory activity. Our data provide insights into activity-preserving modifications of the emixustat molecule that can be employed to tune its pharmacological properties.

The vertebrate eye was described by Charles Darwin as one of the greatest potential challenges to a theory of natural selection by stepwise evolutionary processes. While numerous evolutionary transitions that led to the vertebrate eye have been explained, some aspects appear to be vertebrate specific with no obvious metazoan precursor. One critical difference between vertebrate and invertebrate vision hinges on interphotoreceptor retinoid-binding protein (IRBP, also known as retinol-binding protein, RBP3), which enables the physical separation and specialization of cells in the vertebrate visual cycle by promoting retinoid shuttling between cell types. While IRBP has been functionally described, its evolutionary origin has remained elusive. Here, we show that IRBP arose via acquisition of novel genetic material from bacteria by interdomain horizontal gene transfer (iHGT). We demonstrate that a gene encoding a bacterial peptidase was acquired prior to the radiation of extant vertebrates >500 Mya and underwent subsequent domain duplication and neofunctionalization to give rise to vertebrate IRBP. Our phylogenomic analyses on >900 high-quality genomes across the tree of life provided the resolution to distinguish contamination in genome assemblies from true instances of horizontal acquisition of IRBP and led us to discover additional independent transfers of the same bacterial peptidase gene family into distinct eukaryotic lineages. Importantly, this work illustrates the evolutionary basis of a key transition that led to the vertebrate visual cycle and highlights the striking impact that acquisition of bacterial genes has had on vertebrate evolution.

Abstract Introduction Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. Methods Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator’s Global Assessment or Evaluator’s Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. Results Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: − 11.5; 95% confidence interval [CI]: − 14.39, − 8.62), NILC (MD: − 12.25; 95% CI: − 15.21, − 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: − 12.8, − 11.2, and − 10.1, respectively), NILC (MD: − 11.6, − 13.9, and − 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). Conclusion No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12 weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions.

Abstract Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment.

Objectives: Burning mouth syndrome is an intraoral chronic pain condition characterized by a moderate to severe sensation of burning from the oral mucosa. No clinical signs are found and there is no efficient treatment. Method and materials: This pilot study included 10 women that were resistant to other previous treatments or noncompliant to systemic medications. Patients were asked to apply tretinoin gel 0.05% on their tongues twice daily for 14 days. Treatment effectiveness was assessed by completing a pre-study psychologic questionnaire and recording a daily wellbeing and pain log. Results: Significant pain-score decrease in 50% of the patients (delta numerical rating score -3.15 ± 3.02, P value = .005) was recorded. This finding was in concordance with the verbal statements including major quality-of-life improvement (P value = .05), without any treatment positive or negative predictive factors. Conclusions: Topical tretinoin exhibits potential efficacy in patients with treatment resistant burning mouth syndrome and may also be used as a primary treatment modality. [ABSTRACT FROM AUTHOR]

The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly transparent to infrared (IR) light. The interface between the retina and the retinal pigment epithelium (RPE) is especially informative, because it reflects the health of the visual (retinoid) cycle and its changes in response to external stress, genetic manipulations, and drug treatments. Vitamin A-derived retinoids, like retinyl esters, are natural fluorophores that respond to multi-photon excitation with near IR light, bypassing the filter-like properties of the cornea, lens, and macular pigments. Also, during natural aging some retinoids form bisretinoids, like diretinoid-pyridiniumethanolamine (A2E), that are highly fluorescent. These bisretinoids appear to be elevated concurrently with aging. Vitamin A-derived retinoids and bisretinoidss are detected by two-photon ophthalmoscopy (2PO), using a new class of light sources with adjustable spatial, temporal, and spectral properties. Furthermore, the two-photon (2P) absorption of IR light by the visual pigments in rod and cone photoreceptors can initiate visual transduction by cis-trans isomerization of retinal, enabling parallel functional studies. Recently we overcame concerns about safety, data interpretation and complexity of the 2P-based instrumentation, the major roadblocks toward advancing this modality to the clinic. These imaging and retina-function assessment advancements have enabled us to conduct the first 2P studies with humans.

Senile gluteal dermatosis (SGD) is an underdiagnosed skin condition that mostly affects the elderly. It appears as hyperkeratotic or lichenoid papules or plaques over the gluteal area, unilaterally or bilaterally. The etiopathogenesis of this condition is not yet known, but it is considered to be caused by prolonged mechanical stress on the affected area leading to neovascularization and epidermal hyperplasia. SGD poses unique problems in diagnosis and management due to its clinical characteristics and histological findings matching other common conditions. Due to its lesser‐known status, it is frequently misdiagnosed as lichen simplex chronicus, inverse psoriasis, or cutaneous amyloidosis, which results in a variable response to treatment. Lifestyle modifications aiming at reducing pressure at the affected site remain the mainstay of treatment, but some reports have shown better results with topical or systemic retinoids. SGD is underreported in the scientific literature and is still not mentioned significantly in textbooks. This review attempts to give a thorough overview of SGD regarding its clinical presentation, etiology, pathogenesis, dermoscopy, diagnostic standards, differential diagnoses, and accessible treatments. Healthcare practitioners can enhance early recognition and provide the right care for afflicted people by raising knowledge and understanding of this disorder. [ABSTRACT FROM AUTHOR]

All-trans retinoic acid (ATRA), the major active metabolite of all-trans retinol (vitamin A), is a key hormonal signaling molecule. In the adult organism, ATRA has a widespread influence on processes that are crucial to the growth and differentiation of cells and, in turn, the acquisition of mature cell functions. Therefore, there is considerable potential in the use of retinoids to treat diseases. ATRA binds to the retinoic acid receptors (RAR) which, as activated by ATRA, selectively regulate gene expression. There are three main RAR isoforms, RARα, RARβ, and RARγ. They each have a distinct role, for example, RARα and RARγ regulate myeloid progenitor cell differentiation and hematopoietic stem cell maintenance, respectively. Hence, targeting an isoform is crucial to developing retinoid-based therapeutics. In principle, this is exemplified when ATRA is used to treat acute promyelocytic leukemia (PML) and target RARα within PML-RARα oncogenic fusion protein. ATRA with arsenic trioxide has provided a cure for the once highly fatal leukemia. Recent in vitro and in vivo studies of RARγ have revealed the potential use of agonists and antagonists to treat diseases as diverse as cancer, heterotopic ossification, psoriasis, and acne. During the final drug development there may be a need to design newer compounds with added modifications to improve solubility, pharmacokinetics, or potency. At the same time, it is important to retain isotype specificity and activity. Examination of the molecular interactions between RARγ agonists and the ligand binding domain of RARγ has revealed aspects to ligand binding that are crucial to RARγ selectivity and compound activity and key to designing newer compounds. [ABSTRACT FROM AUTHOR]

Objectives To compare the risk of PsA in psoriasis (PsO) patients treated with acitretin vs DMARDs. Methods This retrospective study used Taiwan's National Health Insurance Research Database from 1997 to 2013. Adult PsO patients without PsA prescribed acitretin or DMARDs for ≥30 days within a year were assigned to the acitretin cohort or DMARDs cohort, respectively. Patients in the acitretin cohort prescribed DMARDs for >7 days, or in the DMARDs cohort prescribed acitretin for >7 days, were excluded. Cumulative incidence of PsA were determined within both cohorts using the Kaplan–Meier method. The hazard ratio (HR) comparing acitretin to DMARDs was calculated with Cox regression models, adjusting for demographic and clinical covariates including the use of NSAIDs and comorbidities. Results The study included 1948 patients in each cohort. The 5-year cumulative incidence of PsA in the acitretin cohort was lower than that in the reference cohort (7.52% vs 9.93%; P  = 0.005), with a more pronounced difference in the subpopulation receiving NSAIDs treatment. However, in subpopulations without NSAIDs treatment, the 5-year cumulative incidence of PsA in the acitretin cohort was comparable to the DMARDs cohort (5.26% vs 6.98%; P  = 0.106). Acitretin was not associated with PsA development in PsO (HR 0.83, 95% confidence interval 0.65–1.05). This risk remained consistent regardless of adjustments for NSAID treatment and comorbidities. Other independent risk factors for PsA included female and NSAIDs treatment. Conclusion Compared with DMARDs, acitretin was not associated with increased PsA risk in PsO patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a heterogeneous group of drugs may exacerbate or induce skin lesions. The aim of this study was to identify the pharmacological management and medications related to the exacerbation of skin lesions in patients diagnosed with acne. METHODS: This was a cross-sectional study that identified the outpatient medication prescription patterns of patients with acne from a dispensing database of 8.5 million members of the Colombian Health System. Sociodemographic and pharmacological variables and the identification of prescriptions that were potentially inappropriate due to the risk of worsening acne were considered. RESULTS: A total of 21,604 patients with acne were identified. Median age was 20.8 years (interquartile range: 17.3-27.3 years), and 60.7 percent were female. Treatment mainly involved antibiotics (79.9% of patients), especially doxycycline (66.0%), and retinoids (55.7%). A total of 17.2 percent of patients had potentially inappropriate prescriptions, predominantly progestogens with androgenic properties (8.9%). Female patients (odds ratio [OR]: 3.55; 95% confidence interval [CI]:3.24-3.90) and patients with pathologies such as systemic lupus erythematosus (OR: 18.61; 95% CI: 7.23-47.93) and rheumatoid arthritis (OR: 10.80; 95% CI: 5.02-23.23) were more likely to receive inappropriate prescriptions, and the risk increased with each year of life (OR: 1.02; 95% CI: 1.02-1.03). LIMITATIONS: Access to medical records was not obtained to verify clinical characteristics of acne. CONCLUSION: Patients with acne are excessively treated with systemic antibiotics, counter to clinical practice guidelines. Approximately one-fifth of these patients received some potentially inappropriate medication that could exacerbate their skin lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Sézary syndrome (SS) is a rare and aggressive form of cutaneous T-cell lymphoma. Despite various treatments, it remains incurable, with a median survival of only 2.1 years. This retrospective study of 17 SS patients in West Sweden from 2012 to 2024 aimed to understand demographic characteristics, treatment effectiveness, and disease progression. Only 35% of patients showed the classic symptoms at diagnosis, indicating the need for personalized diagnostic approaches. Different treatment modalities were used, but combination therapy showed advantages in median survival over monotherapies. Notably, triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP) exhibited the longest median time to the next treatment, at 14.1 months. However, early initiation of ECP did not improve outcomes. This study underscores the complexity of SS, emphasizes the urgent need for more effective treatments, and highlights the importance of future prospective research in optimizing treatment strategies. Sézary syndrome (SS) is a rare primary cutaneous T-cell lymphoma variant. Despite various treatment options, it remains incurable, with a poor prognosis. There is an urgent need for additional descriptive research to enhance our understanding and treatment of SS. The aim of this retrospective register-based study was to outline patients' demographic characteristics; investigate the clinical, histopathological, and molecular findings; and assess treatment effectiveness with a focus on time to next treatment (TTNT) and disease progression. Data on 17 patients with SS were obtained from the primary cutaneous lymphoma register in West Sweden between 2012 and 2024. The results revealed that not all patients exhibited the classical triad of symptoms at diagnosis, emphasizing the need for personalized diagnostic approaches. The median survival was only 2.1 years, which reflects the aggressive nature of SS. The longest median TTNT was observed in triple therapy involving retinoids, interferon alpha, and extracorporeal photopheresis (ECP). There was no significant difference in TTNT between various lines of treatment. Early initiation of ECP treatment did not result in improved outcomes. This study highlights the importance of combination therapy for improved outcomes and underscores the need for future studies to identify optimal treatment approaches. [ABSTRACT FROM AUTHOR]

Communication between cells in the nervous system is dependent on both chemical and electrical synapses. Factors that can affect chemical synapses have been well studied, but less is known about factors that influence electrical synapses. Retinoic acid, the vitamin A metabolite, is a known regulator of chemical synapses, but few studies have examined its capacity to regulate electrical synapses. In this study, we determine that retinoic acid is capable of rapidly altering the strength of electrical synapses in an isomer- and cell-dependent manner. Furthermore, we provide evidence that this acute effect might be independent of either the retinoid receptors or the activation of a protein kinase. In addition to the rapid modulatory effects of retinoic acid, we provide data to suggest that retinoic acid is also capable of regulating the formation of electrical synapses. Long-term exposure to both all-trans-retinoic acid or 9-cis-retinoic acid reduced the proportion of cell pairs forming electrical synapses, as well as reduced the strength of electrical synapses that did form. In summary, this study provides insights into the role that retinoids might play in both the formation and modulation of electrical synapses in the central nervous system. NEW & NOTEWORTHY: Retinoids are known modulators of chemical synapses and mediate synaptic plasticity in the nervous system, but little is known of their effects on electrical synapses. Here, we show that retinoids selectively reduce electrical synapses in a cell- and isomer-dependent manner. This modulatory action on existing electrical synapses was rapid and nongenomic in nature. We also showed for the first time that longer retinoid exposures inhibit the formation of electrical synapses. [ABSTRACT FROM AUTHOR]

Introduction: Frontal fibrosing alopecia (FFA) is characterized by scarring alopecia of the frontotemporal scalp and facial papules. Isotretinoin is a vitamin A‐derived retinoid discovered in 1955 and approved for treating nodulocystic acne. This drug can also affect facial papules and frontotemporal hair loss in patients with FFA. In this article, we conducted a review of the available studies investigating the use of oral isotretinoin for FFA treatment. Our study provides insights into the efficacy and safety of isotretinoin as a potential treatment option for FFA and highlights areas for future research. Method: In this study, we aimed to investigate the potential advantages and disadvantages of isotretinoin as a treatment for FFA. To identify all relevant articles, we developed a comprehensive search strategy and conducted a thorough search of three major databases: PubMed, Embase, and Science Direct. We retrieved a total of 82 articles from the search results. Two independent reviewers then screened each of the 82 articles based on our inclusion and exclusion criteria, resulting in the identification of 15 articles that were deemed relevant to our study. Results: Across the 15 articles, 232 patients who suffered from FFA were involved. Nearly 90% of patients experienced a significant reduction of symptoms after receiving oral isotretinoin at 10–40 mg daily. We conclude that isotretinoin can positively affect facial papules and help suppress hair loss. [ABSTRACT FROM AUTHOR]

Background: Historically regarded as a protective barrier organ, the skin is now recognized as an active endocrine organ capable of synthesizing, and secreting diverse hormones and signaling molecules. This review intends to investigate the endocrine function of the epidermis, focusing on its role in hormone synthesis, metabolism, and signaling pathways. Objective: This article aims to provide a comprehensive overview of the endocrine function of the skin, including the identification of key hormones generated in the skin, their regulation, and their physiological significance. In addition, it intends to investigate the relationship between the epidermis and the endocrine system to elucidate the mechanisms underlying hormonal communication within the body. Methodology: Using electronic databases, including PubMed, Scopus, and Web of Science, a comprehensive search of the literature was conducted. Included are relevant studies, evaluations, and articles published between 1990 and 2023. The search strategy centered on the epidermis, endocrine function, hormones, and signaling pathways-related keywords. The retrieved literature was evaluated, and significant findings were analyzed. Results: The epidermis produces and responds to numerous hormones, including corticosteroids, sex hormones, thyroid hormones, Vitamin D, and growth factors, according to the findings. These hormones influence processes, including hair growth, wound healing, immune response, inflammation, and cell proliferation. In addition, the epidermis functions as a target for circulating hormones, participating in feedback loops, and regulating endocrine homeostasis. Conclusion: The skin's endocrine function extends beyond its barrier function to play a significant role in hormonal regulation and communication. Enlightening the precise mechanisms and clinical implications of the endocrine function of the epidermis is necessary for the development of novel therapeutic approaches and interventions. [ABSTRACT FROM AUTHOR]

Background: Topical Vitamin A analogs (Retinoids) are approved treatments for acne vulgaris impacting the quality of life. Self-prescription of retinoids is often encountered by dermatologists, and it is driven by factors such as mild symptoms and cost-saving. This study aims to assess the prevalence of self-prescription of Vitamin-A analogs and awareness of their adverse effects among the general population. Methods: An online questionnaire was formulated by the research team through an extensive literature review and was validated by three experts in dermatology. It was distributed and collected from the five regions in Saudi Arabia. Results: The present study included 2150 participants, primarily female (76.3%), aged 18-24 (50.6%), and over 60% holding bachelor's degrees. Social media (29.5%) and physicians (26.2%) were common sources of information about Vitamin A analogs for acne treatment. Nearly half had been diagnosed with acne, and 42.5% were aware of adverse effects, with dryness being the most reported (59.7%). Acretin (28.1%) was the most used medication. Awareness of avoiding Vitamin A analogs during pregnancy was 47.0%. Sociodemographic factors such as age, region, and acne history were significantly associated with the awareness regarding Vitamin A use during pregnancy. Conclusion: The present study revealed a substantial prevalence of self-prescribed Vitamin A analogs for acne, particularly among young, educated individuals. The high awareness of potential adverse effects underscores the need for improved education. Sociodemographic associations highlight the importance of targeted interventions in promoting safe practices. [ABSTRACT FROM AUTHOR]

Introduction: While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options. Methods: We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing. We identified the top 10 most highly up- and down-regulated genes and cellular processes that these genes corresponded to. For the most highly dysregulated genes, we identified potential therapeutic options that favorably regulate their expression. Results: The dysregulations in gene expression corresponded to hyperkeratinization (upregulation of genes involved in keratin production and keratinocyte differentiation) and cellular proliferation (downregulation of cell cycle regulating and pro-apoptotic genes). Genes involved in retinoic acid (RA) metabolism and signaling were dysregulated in a pattern suggesting local cellular RA deficiency. Consequently, RA also emerged as the most promising potential therapeutic option for ITS, as it favorably regulated seven of the ten most highly dysregulated genes. Conclusion: This is the first study to characterize the role of hyperkeratinization and dysregulations in RA metabolism and signaling in the disease pathophysiology. Given the ability of RA to favorably regulate key genes involved in ITS, future studies must explore its efficacy as a potential therapeutic option for patients with recalcitrant ITS. [ABSTRACT FROM AUTHOR]

Vision starts in retinal photoreceptors when specialized proteins (opsins) sense photons via their covalently bonded vitamin A derivative 11cis retinaldehyde (11cis-RAL). The reaction of non-enzymatic aldehydes with amino groups lacks specificity, and the reaction products may trigger cell damage. However, the reduced synthesis of 11cis-RAL results in photoreceptor demise and suggests the need for careful control over 11cis-RAL handling by retinal cells. This perspective focuses on retinoid(s) synthesis, their control in the adult retina, and their role during retina development. It also explores the potential importance of 9cis vitamin A derivatives in regulating retinoid synthesis and their impact on photoreceptor development and survival. Additionally, recent advancements suggesting the pivotal nature of retinoid synthesis regulation for cone cell viability are discussed. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) can be a promising alternative for patients with acne vulgaris. Our study aimed to evaluate the efficacy and safety of red light photodynamic therapy with BF-200 ALA gel in the treatment of different types of acne vulgaris. Methods: We performed a retrospective, observational study of a series of 22 cases. All patients were treated according to a mild PDT protocol. After a careful wash of the affected skin areas, BF-200 ALA gel was applied to the skin in a thin layer and incubated for 30 min, followed by illumination using narrow-spectrum red light (635 nm) at a dose of 4 J/cm2. Most patients received one (36.4%), two (27.3%), or three (22.7%) PDT sessions. About a third of the patients received concomitant acne treatment with topical retinoids. Results: Patients of 25.1 ± 8.9 years suffering from papulopustular (45.5%), nodular (27.3%), and comedonal acne (27.3%) in the face were included. Irrespective of acne type or severity, 95.5% of patients had good or excellent responses to the treatment with PDT (≥60% lesion clearance). We found no association between concomitant acne medication and the favorable results achieved by PDT. Most patients reported no adverse events (72.7%), except for six patients who experienced erythema. The good efficacy results were maintained over a follow-up period of 12.5 ± 10.8 months. Conclusions: In this study, we show that PDT with BF-200 ALA gel and low light dose is an effective and long-lasting option for the treatment of different acne types. [ABSTRACT FROM AUTHOR]

Acne is one of the most common dermatological conditions to affect women of childbearing age, so it is important to consider the safety of long-term acne treatments on women who could become pregnant. In this review article, we clarify what management options are available to treat acne during pregnancy. Topical treatments, typically first-line for acne, such as azelaic acid, clindamycin, erythromycin, metronidazole, benzoyl peroxide, salicylic acid, dapsone, and retinoids, were reviewed. Systemic treatments, such as zinc supplements, cephalexin, cefadroxil, amoxicillin, azithromycin, erythromycin, and corticosteroids, typically second-line for acne, were also reviewed. Alternative treatments such as light therapy and cosmetic procedures were also evaluated. Due to recommendation of sunscreen utilization during acne treatments, sunscreen usage during pregnancy was also assessed. Management of acne during unplanned pregnancy was discussed in further detail regarding safety and adverse effects. Through summarized tables and examples of studies demonstrating safety and efficacy of treatments, the following is a resource for providers and patients to utilize for management of acne during pregnancy. [ABSTRACT FROM AUTHOR]

The development of numerous drugs is often arrested at clinical testing stages, due to their unfavorable biopharmaceutical characteristics. It is the case of fenretinide (4-HPR), a second-generation retinoid, that demonstrated promising in vitro cytotoxic activity against several cancer cell lines. Unfortunately, response rates in early clinical trials with 4-HPR did not confirm the in vitro findings, mainly due to the low bioavailability of the oral capsular formulation that was initially developed. Capsular 4-HPR provided variable and insufficient drug plasma levels attributable to the high hepatic first-pass effect and poor drug water solubility. To improve 4-HPR bioavailability, several approaches have been put forward and tested in preclinical and early-phase clinical trials, demonstrating generally improved plasma levels and minimal systemic toxicities, but also modest antitumor efficacy. The challenge is thus currently still far from being met. To redirect the diminished interest of pharmaceutical companies toward 4-HPR and promote its further clinical development, this manuscript reviewed the attempts made so far by researchers to enhance 4-HPR bioavailability. A comparison of the available data was performed, and future directions were proposed. [ABSTRACT FROM AUTHOR]

Over the past decades, increasing evidences have demonstrated that five retinoids, including retinol (ROL), retinol acetate (RAc), retinol propionate (RP), retinol palmitate (RPalm), and hydroxypinacolone retinoate (HPR), can be potential therapeutic agents for skin photoaging. However, therapeutic efficacies and biosafety have never been compared to these compounds. This study aimed to determine the optimal retinoid type(s) for anti‐photoaging therapy both in vitro and in vivo. Our data demonstrated that four retinoids (RPalm, RP, HPR and ROL) but not RAc were effective for anti‐photoaging treatment at 5 μg/mL in vitro, with action mechanisms associated with antioxidative, anti‐inflammatory and anti‐skin ECM degradation activities. Notably, both RPalm and RP appeared superior to HPR and ROL for those activities. Importantly, both RPalm and RP were shown to be optimal for anti‐photoaging therapy when topically applied at 5 mg/kg in a UVB‐induced mice model of photoaging, which is consistent with their high anti‐photoaging activities in vitro. Additionally, topical application of these five retinoids showed satisfactory biosafety without causing significant apoptosis in animal organs, although RP application led to a slight decline in animal body weights. Collectively, these data have laid a good foundation for the next development of the clinical application of these retinoids for skin healthcare. [ABSTRACT FROM AUTHOR]

Acne is a common skin condition that can have profound physical and psychological impacts. This article outlines its clinical presentation and recommended management in primary care and discusses when referral to secondary care is necessary. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Keratosis palmoplantaris striata type I (SPPK‐I) is a rare autosomal‐dominant type of hereditary epidermolytic palmoplantar keratoderma, which can be caused by mutations in desmoglein‐1 (DSG‐1). Patients suffer from hyperkeratotic plaques and painful palmoplantar fissures. Unfortunately, treatment options including salicylic vaseline, topical corticosteroids, phototherapy, and retinoids are inefficient. Hereditary palmoplantar keratodermas (PPKs) represent a heterogeneous group of rare skin disorders with epidermal palmoplantar hyperkeratosis. Mutations in the desmoglein 1 gene (DSG1), a transmembrane glycoprotein, have been reported primarily in striate PPKs. We report a patient with keratosis palmoplantaris striata type I (SPPK‐I) with a specific pathogenic variant [c.349C>T, p.(Arg117*)] in DSG1. Despite increased understanding, effective treatment options for PPK, including SPPK‐I, remain limited. [ABSTRACT FROM AUTHOR]

Introduction: Acne vulgaris, a chronic inflammatory condition, is associated with significant physical and psychosocial burden. Since 2019, three new topical agents for acne vulgaris have been approved in the USA and Canada. We performed a systematic review and meta-analysis to compare the efficacy between twice-daily clascoterone cream 1%, once-daily trifarotene 0.005% cream, and once-daily tazarotene 0.045% lotion for acne treatment. Methods: Randomized controlled trials (RCTs) comparing clascoterone, trifarotene, or tazarotene with vehicle in patients with moderate-to-severe acne were identified from a systematic literature review and included in a meta-analysis. Primary outcomes were percentage reduction in inflammatory and noninflammatory lesion count (ILC and NILC, respectively) and treatment success rate (≥ 2-grade improvement in Investigator's Global Assessment or Evaluator's Global Severity Score and a rating of clear or almost clear) at week 12. DerSimonian and Laird random-effects models with the inverse variance method were used to calculate the mean difference (MD) for percentage reduction in ILC and NILC, and odds ratios (ORs) for the rate of treatment success. Results: Six Phase 3 RCTs were included in the meta-analysis. The analyses showed robust differences favoring the interventions for ILC (MD: − 11.5; 95% confidence interval [CI]: − 14.39, − 8.62), NILC (MD: − 12.25; 95% CI: − 15.21, − 9.29), and treatment success rate (OR: 2.14; 95% CI: 1.81, 2.53). No differences were observed between clascoterone, trifarotene, and tazarotene for ILC (MD: − 12.8, − 11.2, and − 10.1, respectively), NILC (MD: − 11.6, − 13.9, and − 12.8, respectively), or treatment success rate (OR: 2.9, 1.9, and 2.1, respectively (all P > 0.05). Conclusion: No significant differences in efficacy were observed between clascoterone, trifarotene, and tazarotene after 12 weeks of treatment in patients with moderate-to-severe acne. Differences in application frequency and safety profile should also be taken into consideration when making treatment decisions. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a debilitating chronic skin disorder characterized by painful inflammatory nodules, abscesses and sinus tracts involving intertriginous areas and has an adverse impact on patient quality of life. Over the past decade, the therapeutic options of HS have increased significantly to comprise multiple modalities, including topical medication, systemic therapies (mainly antibiotics, retinoids, and biologics), surgical approaches, and lifestyle modifications. Biologics alone or in combination with surgery remain the treatment of choice for moderate to severe disease. However, non-biologic therapies (including retinoids) may be used as monotherapy for mild disease and in combination with biologics and surgical treatment in moderate to severe disease. Retinoids, specifically isotretinoin, acitretin, and alitretinoin, are historically used in the management of HS, supported by anecdotal evidence and with variable treatment response. Although the current American and European guidelines offer different recommendations on the use of retinoids in HS, retinoids remain a valuable ally in HS management. This review provides a comprehensive analysis of the current scientific literature on retinoid therapy (topical and systemic) in HS, highlighting disparities in mechanisms of action, efficacy, and safety to clarify their role in HS treatment. [ABSTRACT FROM AUTHOR]

Background: Plantar warts are benign epithelial tumors that are forced inward due to pressure on the toes or sole of the foot and may become very painful if not treated. Many treatment options are available including topical treatments, lasers, and immunotherapy. However, data about systemic therapies are lacking. Objective: To compare the efficacy and safety of acitretin versus oral isotretinoin in the treatment of multiple plantar warts. Patients and methods: This randomized comparative double-blinded study included 80 adult patients with multiple plantar warts. The cases were divided into two groups: acitretin group (40 cases with a dose of 0.5 mg/kg/day) and isotretinoin group (40 cases with a dose of 0.5 mg/kg/day). The reduction in wart size and photographic comparisons at the beginning and every 2 weeks for 3 months were used to assess the treatment efficacy in the two groups. After therapy ended, a follow-up was conducted every month for 6 months to observe any recurrence. Results: Complete response was observed in 30%, partial response in 55%, and no response in 15% of patients of acitretin group while complete response was achieved in 15%, partial response in 45%, and no response in 40% of patients of isotretinoin group with statistically significant difference in favor of acitretin (P=0.03). Compared with acitretin, oral isotretinoin was associated with a shorter duration to a complete response (83.3% of cases achieved complete response in <2 months compared with only 16.7% in acitretin group) (P=0.006). Conclusion: Acitretin is superior to oral isotretinoin as a therapeutic option for plantar warts, but both are effective and safe. Since they are resistant to other traditional therapy techniques, they can be seen as valuable therapeutic choices for multiple plantar warts. [ABSTRACT FROM AUTHOR]

Vitamin A, an essential micronutrient, is integral to various biological processes crucial for organismal development and maintenance. Dietary sources of vitamin A encompass preformed retinol, retinyl esters, and provitamin A carotenoids. Retinoic acid (RA), a key component, plays pivotal roles in vision, cell proliferation, apoptosis, immune function, and gene regulation. Drug repurposing, an effective strategy for identifying new therapeutic applications for existing drugs, has gained prominence in recent years. This review seeks to provide a comprehensive overview of the current research landscape surrounding retinoids and drug repurposing. The scope of this review encompasses a comprehensive examination of retinoids and their potential for repurposing in various therapeutic contexts. Despite their efficacy in treating dermatological conditions, concerns about toxicity persist, driving the search for safer and more potent retinoids. The molecular mechanisms underlying retinoid activity involve binding to retinoic acid receptors (RARs) and retinoid X receptors (RXRs), leading to transcriptional regulation of target genes. This review seeks to shed light on the possibilities for repurposing retinoids to cover a wider spectrum of therapeutic uses by exploring recent scientific progress. It also aims to offer a more comprehensive understanding of the therapeutic prospects of retinoids and the broader impact of drug repositioning in contemporary medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the most well-known molecular mechanism in essential thrombocythemia (ET) is the activation of JAK2/STAT, the study of mechanisms that are independent of JAK2/STAT activation related to the disease is on the rise. Previous studies in a C. elegans model revealed that the overexpression of nhr-2 counterparts could be a JAK2/STAT-independent mechanism, derived from CALR mutations in ET patients. In this work, we evaluated the expression of potential orthologs of nhr-2 in human cell lines and in mononuclear cells from ET patients with CALR or JAK2 mutations. The results show that mutant calreticulin is associated with an overexpression of RXRA in patients with ET, which could be relevant in the disease, pointing to the need for future research testing retinoids and other drugs targeting RXRα for the treatment of these patients. Essential thrombocythemia (ET) is a blood cancer caused by mutations in JAK2 and CALR. It is widely recognized that both mutations lead to the constitutive activation of JAK2/STAT signaling, although other JAK/STAT-independent pathogenic mechanisms triggered by these alterations have also been described in ET. In an attempt to study JAK2/STAT-independent mechanisms derived from CALR mutations, our research group created a C. elegans model with patient-like mutations in calreticulin that lacks JAK counterparts. The introduction of patient-like mutations in the calreticulin of C. elegans leads to an increase in the transcriptional expression of nhr-2, independently of JAK2/STAT activation. In the present study, we aim to verify if this mechanism is conserved in patients with ET harboring CALR mutations. To do so, we evaluated the expression of potential orthologs of nhr-2 in human cell lines of interest for the study, as well as in bone marrow (BM) or peripheral blood (PB) mononuclear cells from patients with CALR or JAK2 mutations. The results revealed that this mechanism is conserved in CALR-mutated ET patients, since CALR, but not JAK2 mutations, were associated with an overexpression of RXRA in patients with ET. The use of drugs targeting the activation or blockade of this target in the analyzed cell lines did not result in changes in cell viability. However, RXRA might be relevant in the disease, pointing to the need for future research testing retinoids and other drugs targeting RXRα for the treatment of ET patients. [ABSTRACT FROM AUTHOR]

Early developmental exposure to environmental toxicants may play a role in the risk for developing autism. A variety of pesticides have direct effects on retinoic acid (RA) signaling and as RA signaling has important roles in neurodevelopment, such compounds may cause developmental neurotoxicity through an overlapping adverse outcome pathway. It is hypothesized that a pesticide's embryonic effects on retinoid function may correspond with neurobehavioral disruption later in development. In the current studies, we determined the effects of RA-acting pesticides on neurobehavioral development in zebrafish. Buprofezin and imazalil caused generalized hypoactivity in the larval motility test, whereas chlorothalonil and endosulfan I led to selective hypoactivity and hyperactivity, respectively. With buprofezin, chlorothalonil, and imazalil, hypoactivity and/or novel anxiety-like behaviors persisted in adulthood and buprofezin additionally decreased social attraction responses in adulthood. Endosulfan I did not produce significant adult behavioral effects. Using qPCR analyses of adult brain tissue, we observed treatment-induced alterations in RA synthesis or catabolic genes, indicating persistent changes in RA homeostasis. These changes were compound-specific, with respect to expression directionality, and potential patterns of homeostatic disruption. Results suggest the likely persistence of disruptions in RA signaling well into adulthood and may represent compensatory mechanisms following early life stage exposures. This study demonstrates that early developmental exposure to environmental toxicants that interfere with RA signaling causes short as well as long-term behavioral disruption in a well-established zebrafish behavioral model and expand upon the meaning of the RA adverse outcome pathway, indicating that observed effects likely correspond with the nature of underlying homeostatic effects. [ABSTRACT FROM AUTHOR]

Bakuchiol (BAK) is a natural phenolic meroterpene isolated from the fruits of Psoralea corylifolia that exhibits a variety of pharmacological effects, including anti-aging, anti-microbial, hyperpigmentation, and anti-cancer activities. Furthermore, the usage of BAK is gaining popularity amongst researchers since it does not induce the same negative reactions as topical retinoids, such as blistering and scaling, allowing greater adoption for individuals with sensitive skin. The growing trend towards "clean" skin care products, as well as the hunt for retinoid substitutes, has elevated BAK to the status of a "must have" component in cosmetology and dermatology. Although, the pathogenesis of BAK is not completely understood yet it is known to play a pivotal role in acting as a scavenger of free radicals thus exerting an antioxidant effect which is helpful in the management of various skin disorders. It also regulates the expression of collagen and extracellular matrix synthesis enzymes which aids in reversing the signs of photo-aging. Moreover, natural sources of BAK are also being employed in traditional Chinese and Indian medicines due to their antitumor and anti-inflammatory properties. In this review we have provided the occurrence, extraction, isolation methods and structure-activity relationships of BAK. Moreover, this review discusses the pharmacological benefits of BAK, its novel and marketed formulations and a brief overview of its patents. [ABSTRACT FROM AUTHOR]

Background: Topical antioxidants and retinoids are foundational components of an effective skincare regimen. Pyrroloquinoline quinone (PQQ) is a potent free radical scavenger that supports efficient mitochondrial energy creation. An advanced antioxidant combines topical allyl PQQ with existing WEL antioxidant technology (TAP) to comprehensively address extrinsic and intrinsic skin aging. In conjunction with TAP, a double‐conjugated retinoid/alpha hydroxy acid (AHA‐Ret) designed to minimize irritation and optimize delivery was used over 12 weeks to improve the appearance of photodamaged skin. Patients/Methods: Twice‐daily application of TAP and nightly application of AHA‐Ret was evaluated in female participants aged 40–65 years with FST IV–V and mild (3) to moderate (6) facial photodamage using a 10‐point grading scale. Visible improvements from baseline in lines/wrinkles, skin texture, skin tone, skin dullness and erythema were assessed using a six‐point grading scale (0 = None to 5 = Severe). Adverse Events (AEs) were captured throughout the study period. Results: Participants (N = 21; mean age, 56 years) equally represented mild and moderate photodamage, and FST IV and V (41%, Hispanic; 36%, African American; and 32%, Caucasian). Significant mean improvements from baseline occurred in skin dullness, skin texture, and skin tone (all, p < 0.0001), and significant mean reductions from baseline were demonstrated in erythema and melanin at Week 12. Mild, transient AEs were reported. No participant discontinued study participation due to an AE. Conclusions: A skincare regimen comprised of an advanced antioxidant and AHA‐Ret cream, in conjunction with daily use of a broad‐spectrum sunscreen (SPF 56), led to significant improvements at 12 weeks in the appearance of photodamaged skin in females with FST IV and V. [ABSTRACT FROM AUTHOR]

Introduction and Aim. Premature skin aging results from both intrinsic and extrinsic factors, requiring a comprehensive management strategy. This review evaluates current and emerging approaches for preventing and treating premature skin aging, focusing on efficacy and safety. Materials and Methods. A review of recent scientific literature on topical, oral, and procedural interventions for managing premature skin aging was conducted. Analysis of Literature. Topical treatments, particularly retinoids and antioxidants, are key in skin regeneration and oxidative stress reduction. Oral interventions, including systemic retinoids and nutraceuticals, support overall skin health. Procedural methods like laser therapies, microneedling, and chemical peels are effective in skin rejuvenation. Preventive measures, such as photoprotection and lifestyle changes, are crucial. Emerging therapies, such as stem cell treatments, show promise in reversing age-related skin changes. Conclusion. Managing premature skin aging requires a combination of topical, oral, and procedural treatments with preventive strategies. Future research should focus on refining protocols, assessing novel therapies' long-term safety, and developing personalized approaches considering genetic, environmental, and lifestyle factors.

Introduction: Isotretinoin (13-cis-Retinoic Acid) is a part of the retinoid group, and is used in dermatology for the treatment of acne, due to its demonstrated inhibitory effect on sebaceous gland activity and proliferation. Isotretinoin is a highly lipophilic drug, for this reason taking it with food, doubles the bioavailability of the substance, during systemic treatment. Isotretinoin as a drug has been used effectively for more than 40 years in the treatment of acne, although its exact mechanism of action is not known. Objective: The objective of this study is to gather and analyze literature regarding the adverse effects of isotretinoin therapy on mental health and the digestive, cardiovascular, immune, urinary, and reproductive systems. Materials and Methods: A literature review was conducted using the PubMed database with the following search terms : retinoids, isotretinoin, acne, 13-cis-retinoic acid. Current Knowledge: Isotretinoin therapy has a vast spectrum of side effects affecting various systems of the human body. During the use of isotretinoin, special caution should be taken in patients with depression, lipid disorders, and abnormal liver function. In addition, in patients of childbearing age, make sure to use contraception one month before, during and one month after the end of isotretinoin therapy due to its teratogenicity. Conclusion: Isotretinoin is still the most effective drug in the systemic treatment of severe forms of acne, nevertheless its potential side effects should be kept in mind. Regular monitoring of patients should be a mainstay during isotretinoin therapy, especially with regard to lipid profile and liver parameters.

For sustained vision, photoactivated rhodopsin (Rho*) must undergo hydrolysis and release of all-trans-retinal, producing substrate for the visual cycle and apo-opsin available for regeneration with 11-cis-retinal. The kinetics of this hydrolysis has yet to be described for rhodopsin in its native membrane environment. We developed a method consisting of simultaneous denaturation and chromophore trapping by isopropanol/borohydride, followed by exhaustive protein digestion, complete extraction, and liquid chromatography-mass spectrometry. Using our method, we tracked Rho* hydrolysis, the subsequent formation of N-retinylidene-phosphatidylethanolamine (N-ret-PE) adducts with the released all-trans-retinal, and the reduction of all-trans-retinal to all-trans-retinol. We found that hydrolysis occurred faster in native membranes than in detergent micelles typically used to study membrane proteins. The activation energy of the hydrolysis in native membranes was determined to be 17.7 ± 2.4 kcal/mol. Our data support the interpretation that metarhodopsin II, the signaling state of rhodopsin, is the primary species undergoing hydrolysis and release of its all-trans-retinal. In the absence of NADPH, free all-trans-retinal reacts with phosphatidylethanolamine (PE), forming a substantial amount of N-ret-PE (∼40% of total all-trans-retinal at physiological pH), at a rate that is an order of magnitude faster than Rho* hydrolysis. However, N-ret-PE formation was highly attenuated by NADPH-dependent reduction of all-trans-retinal to all-trans-retinol. Neither N-ret-PE formation nor all-trans-retinal reduction affected the rate of hydrolysis of Rho*. Our study provides a comprehensive picture of the hydrolysis of Rho* and the release of all-trans-retinal and its reentry into the visual cycle, a process in which alteration can lead to severe retinopathies.

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat-/- mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). In particular, retinoid treatment enhanced responses from the ipsilateral eye, restoring the normal balance of eye-specific responses in V1. Additionally, the treatment rescued the modulation of cortical responses by arousal. These findings illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases.

Background. Acne is a common, complex and multifactorial inflammatory disease that results from a variety of causes. Acne therapy is an urgent problem of dermatocosmetology. The clinical manifestations of dermatosis can be alleviated, and its long-term consequences can be prevented by early diagnosis and timely initiation of treatment, affecting multifaceted all parts of the pathogenesis. Aims. To evaluate the clinical efficacy and safety of the use of monotherapy of 0.1% adapalene cream (Adaclean) with combined external therapy of 0.1% adapalene cream (Adaclean) with 20% azelaic acid cream (Azix-Derm) in the treatment of mild to moderate acne. Methods. Under our supervision at the Department of Plastic Reconstructive Surgery, Cosmetology and Regenerative Medicine of the State Budgetary Educational Institution of Higher Professional Education Rost of the State Medical University of the Ministry of Health of Russia, the clinics “Ekaterininskaya” and “MIR-O-MED” there were 50 patients aged 12 to 50 years (18 (36%) men and 32 (64%) women) with mild and moderate acne. Patients with comedonal acne, in the absence of multiple inflammatory elements, which made up group 1 of observation (n = 16), were prescribed Adaclean cream, 1 time per day (evening) against the background of skin care. In the group with mild to moderate papulo-pustular acne and post-inflammatory changes (group 2, n = 34), patients were prescribed a combination of 0.1% adapalene cream and 20% azelaic acid cream (Adaclean (evening) and Azix-Derm (morning)). The follow-up period was 6 months. Results. Total clinical remission after 6 months therapy was achieved in 70% of cases, a significant improvement — in 28%, improvement — in 2%. In patients with a comedonal form of acne against the background of monotherapy with Adaclean cream, clinical recovery was obtained in 44% of patients, a significant improvement — in 50%, and an improvement — in 6%. In patients from the group of papulo-pustular acne of mild to moderate severity, after 3 months the use of complex therapy Adaclean and Azix-Derm noted almost complete relief of the inflammatory process; after 6 months therapy clinical recovery was recorded in 58%, significant improvement — in 36%; 6% showed partial improvement, which is associated with irregular use of drugs and skin care products. After 6 months combined treatment was able to achieve regression of dyschromia in 18–46% of patients, atrophic scars — in 5–22%, which significantly improved the results of therapy and made it possible to achieve a good cosmetic effect. Conclusion. The combined use of drugs for external use of adapalene (Adaclean) and AK (Azix-Derm) in the treatment of papulo-pustular acne of mild and AK (Azix-Derm) in the treatment of papulo-pustular acne of mild and moderate severity can significantly increase the effectiveness of treatment, achieve a stable clinical effect and remission of the disease, as well as improve the quality of life of patients.

We retrospectively analyzed the clinical data of 1 case of disseminate and recurrent infundibular folliculitis (DRIF) in our hospital and 31 cases of DRIF reported in previous domestic and international studies. There were 32 cases, including 22 males and 10 females, with a mean age of onset of 24.72 ± 13.68 years. Skin lesions were more likely to occur on the trunk and proximal extremities and may involve the face, neck, and genitals. Typical histopathology revealed mild thickening and spongy edema of the spinous layer, different degrees of pigmentation increase in the basal layer, and mild to moderate spongy edema and inflammatory cell infiltration (predominantly lymphocytes and neutrophils) in the infundibulum and around the hair follicle. DRIF is a chronic disease more prevalent in young men of African descent and individuals with Fitzpatrick skin types 4-6. This disease is diagnosed based on clinical features and histopathology and is preferentially treated with retinoids. Keywords: Disseminate, infundibular folliculitis, isotretinoin, recurrent, Author(s): Qifeng Meng [1]; Qunyan Li [2]; Yingdong Wang [1]; Haoran Li [1]; Yu Zhang (corresponding author) [2] Introduction Disseminate and recurrent infundibular folliculitis (DRIF) is a rare skin disease [...]