Systemic Retinoids Research Articles

Exploring Epidermodysplasia Verruciformis: A Case Report, Treatment Strategies, and Emerging Therapies

Abstract Introduction/Objective Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder with both inherited and acquired forms. Inherited cases involve mutations in genes such as ERV1 and ERV2, crucial for HPV immunity, while acquired cases affect immunocompromised individuals. EV is linked to cutaneous squamous cell carcinoma (SCC), highlighting the need for prompt diagnosis and treatment. Methods/Case Report A 54-year-old HIV-positive man was referred with a persistent, itchy eruption on his forearms despite given ARV regimen, oral retinoids and topical therapies. Physical examination revealed hypopigmentation and hyperkeratotic plaques on both forearms. Histologic examination revealed large cells with blue-gray cytoplasm and perinuclear halo in the upper epidermis, consistent with EV. Although advised for papilloma virus vaccination and planned for a trial of topical cidofovir, the patient was lost to follow-up. Treatment strategies for EV vary depending on lesion severity. Severe keratinized or precancerous lesions typically require surgical removal as the first-line approach. For early-stage EV with few small lesions, 5-FU, cidofovir, glycolic acid, and imiquimod is recommended. Tazarotene 0.5% cream used twice weekly has shown success in resolving lesions within 14 days. Topical imiquimod’s efficacy appears variable. In HIV-positive patients with EV, topical 1% cidofovir showed success in some cases. Systemic and topical retinoids are advised for diffuse lesions, with electrocautery or cryotherapy as options if initial treatments fail. HPV vaccination combined with oral acitretin, topical tretinoin and imiquimod led to lesion flattening. Continuous low-dose isotretinoin achieved prolonged remission of EV, but its efficacy in acquired EV remains unclear. Topical methyl aminolevulinate followed by photodynamic therapy has also shown promise. Results (if a Case Study enter NA) NA Conclusion Since its discovery in the 1970s, Acquired EV has been observed across diverse demographics, including HIV patients and organ transplant recipients. Advanced HPV typing and sequencing techniques aid in predicting SCC risk. Emerging treatments like topical cidofovir and combination therapies show promise, necessitating larger clinical trials for validation.

Methodology for Studying Interactions of Vitamin A Membrane Receptors and Opsin Protein with their Ligands in Generating the Retinylidene Protein.

Distribution of dietary vitamin A/all-trans retinol (ROL) throughout the body is critical for maintaining retinoid function in peripheral tissues and generating the retinylidene protein for visual function. RBP4-ROL is the complex of ROL with retinol-binding protein 4 (RBP4), which is present in the blood. Two membrane receptors, Retinol Binding Protein 4 Receptor 2 (RBPR2) in the liver and STimulated by Retinoic Acid 6 Retinol (STRA6) in the eye, bind circulatory RBP4 and this mechanism is critical for internalizing ROL into cells. Establishing methods to investigate receptor-ligand kinetics is essential in understanding the physiological function of vitamin A receptors for retinoid homeostasis. Using Surface Plasmon Resonance (SPR) assays, we can analyze the binding affinities and kinetic parameters of vitamin A membrane receptors with its physiological ligand RBP4. These methodologies can reveal new structural and biochemical information of RBP4-binding motifs in RBPR2 and STRA6, which are critical for understanding pathological states of vitamin A deficiency. In the eye, internalized ROL is metabolized to 11-cis retinal, the visual chromophore that binds to opsin in photoreceptors to form the retinylidene protein, rhodopsin. The absorbance of light causes the cis-to-trans isomerization of 11-cis retinal, inducing conformational changes in rhodopsin and the subsequent activation of the phototransduction cascade. Decreased concentrations of serum and ocular ROL can impact retinylidene protein formation, which in turn can cause rhodopsin mislocalization, apoprotein opsin accumulation, night blindness, and photoreceptor outer segment degeneration, leading to Retinitis Pigmentosa or Leber Congenital Amaurosis. Therefore, spectrophotometric methodologies to quantify the G protein-coupled receptor opsin-11-cis retinal complex in the retina are critical for understanding mechanisms of retinal cell degeneration in the above-mentioned pathological states. With these comprehensive methodologies, investigators will be able to better assess dietary vitamin A supply in maintaining systemic and ocular retinoid homeostasis, which is critical for generating and maintaining retinylidene protein concentrations in photoreceptors, which is critical for sustaining visual function in humans.

Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.

Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.

Challenges to Contraceptive Counseling With Isotretinoin Treatment and Future Directions for Dermatologists

Accutane, also known as isotretinoin, is an oral systemic retinoid utilized in the treatment of severe, treatment-resistant acne. Isotretinoin is a pregnancy category X drug, meaning that studies have documented congenital defects in pregnant patients on isotretinoin. Known abnormalities include ear abnormalities, facial dysmorphia, cleft palate, CNS abnormalities, thymus gland abnormalities, and parathyroid hormone deficiencies. With teratogenicity well-documented with isotretinoin use, the iPLEDGE system was created to educate prescribers, pharmacists, and patients about the risks of isotretinoin use. Utilizing iPLEDGE, individuals of child bearing potential (ICBP) are required to document two negative pregnancy tests before the initiation of isotretinoin therapy with two documented forms of birth control. We conducted a literature review utilizing the terms: accutane, isotretinoin, contraception, and birth control. We found that amongst multiple articles, the most popular primary contraceptive methods in iPLEDGE were abstinence (47% of users) and combined oral contraceptives (31% of users). Individuals have attributed their lack of contraceptive use to fear of birth control health impacts and belief in the equivalent effectiveness of non-accepted methods (e.g. withdrawal and natural family planning. Despite the establishment of iPLEDGE to systematically reinforce counseling requirements, the incidence of isotretinoin-exposed pregnancies continues to persist with approximately 100-200 pregnancies annually. Given these findings, it is clear that counseling is tantamount to dispelling misconceptions regarding contraception and optimizing rates of patient compliance. Despite this importance, counseling remains a large issue for dermatologists. Only half of board-certified dermatology residents surveyed in 2023 felt comfortable providing counseling on adverse effects of combined oral contraceptives (COCs), and only 38.8% felt comfortable providing counseling directions for COCs. Solutions for this include quickly accessing a referral to primary care or OB/GYN and potentially new avenues that are more easily accessible such as the progestin-only oral contraceptive pill that was recently approved for over the counter use by the United States Food and Drug Administration.

RETRACTED: Kosumi et al. Systemic Retinoids for Generalized Verrucosis Due to Congenital Immunodeficiency: Case Reports and Review of the Literature. Genes 2023, 14, 769.

The journal Genes retracts the article, "Systemic Retinoids for Generalized Verrucosis Due to Congenital Immunodeficiency: Case Reports and Review of the Literature" [...].

Loss of the systemic vitamin A transporter RBPR2 affects the quantitative balance between chromophore and opsins in visual pigment synthesis.

The distribution of dietary vitamin A/all-trans retinol (ROL) throughout the body is critical for maintaining retinoid function in peripheral tissues and for generating visual pigments for photoreceptor cell function. ROL circulates in the blood bound to the retinol binding protein 4 (RBP4) as RBP4-ROL. Two membrane receptors, RBPR2 in the liver and STRA6 in the eye are proposed to bind circulatory RBP4 and this mechanism is critical for internalizing ROL into cells. Here, we present a longitudinal investigation towards the importance of RBPR2 and influence of the diet on systemic retinoid homeostasis for visual function. Age matched Rbpr2-KO (Rbpr2 -/- ) and wild-type (WT) mice were fed either a vitamin A sufficient (VAS) or a vitamin A deficient (VAD) diet. At 3- and 6-months, we performed retinoid quantification of ocular and non-ocular tissues using HPLC analysis and complemented the data with visual physiology, rhodopsin quantification by spectrophotometry, and biochemical analysis. At 3-months and compared to WT mice, Rbpr2 -/- mice fed either vitamin A diets displayed lower scotopic and photopic electroretinogram (ERG) responses, which correlated with HPLC analysis that revealed Rbpr2 -/- mice had significantly lower hepatic and ocular retinoid content. Interestingly, with the exception of the liver, long-term feeding of Rbpr2 -/- mice with a VAS diet promoted all-trans retinol accumulation in most peripheral tissues. However, even under VAS dietary conditions significant amounts of unliganded opsins in rods, together with decreased visual responses were evident in aged mice lacking RBPR2, when compared to WT mice. Together, our analyses characterize the molecular events underlying nutritional blindness in a novel mouse model and indicate that loss of the liver specific RBP4-ROL receptor, RBPR2, influences systemic retinoid homeostasis and rhodopsin synthesis, which causes profound visual function defects under severe vitamin A deficiency conditions.

Systemic isotretinoin in modern clinical guidelines on acne management

Objective — to analyze the medical and technological documents developed on the basis of evidence­based medicine (guidelines, recommendations, consensuses) regarding the treatment of patients with acne of various degrees of severity with systemic retinoids (systemic isotretinoin preparations) dating from 2013 to 2023, as also to focus attention on the pharmacokinetic features of the original systemic isotretinoin according to innovative Lidose technology. Materials and methods. An analysis was conducted of clinical European guidelines (French guideline and those of the European Dermatology Forum), guidelines of the American Academy of Dermatology, the National Institute for Health Protection and Improvement of Medical Care (NICE) of Great Britain in conjunction with the British Dermatology Association and the Canadian Dermatology Association, recommendations of the American Academy of Pediatrics and the French Society of Dermatology, the International Consensus of the Global Alliance for the Improvement of Acne Treatment Outcomes, and consensus­based practical and daily guideline for the management of acne patients. The key words for the search were «acne», «clinical guideline», «consensus», «systemic treatment», «isotretinoin», «isotretinoin­ Lidose». Results and discussion. Clinical guidelines (2013, 2015, 2016) for the management of acne recommend isotretinoin at a dose of 0.5—1 mg/kg/day for 16—24 weeks to a total (cumulative) dose of 120—150 mg/kg for severe acne (nodular/conglobate acne). Low-­dose regimens of isotretinoin (< 0.5 mg/kg/day) have been used with varying degrees of success in the treatment of severe papulopustular/moderate nodular acnе. The International Consensus of the Global Alliance to Improve Acne Treatment Outcomes (2017) supports standard isotretinoin dosing for severe acne until the cumulative dose is reached. At the same time, for patients that have severe papulopustular acne, poor tolerance, risk of serious side effects, or rash regression before the cumulative dose is achieved it is recommended to continue taking the drug until the skin is completely cleansed of acne­elements and for additional 1—2 months. Such provisions are set out in the guidelines developed jointly with the British Association of Dermatologists (2021). According to the American Academy of Dermatology (2023) guidelines, standard isotretinoin or isotretinoin ­Lidose® is recommended for patients for whom isotretinoin is indicated, which is supported by high­quality evidence. Due to the Lidose technology, the soluble fraction of isotretinoin increases, while the insoluble fraction responsible for side effects, on the contrary, decreases. The bioavailability of the drug increases, which allows lowering the daily and course doses of the drug. Conclusions. Systemic isotretinoin has a convincing evidence base as highly effective treatment for severe and moderate forms of acne, providing a sustained therapeutic effect at standard or low doses. In current US guidelines, isotretinoin and isotretinoin­ Lidose® are recommended for the treatment of severe acne, as well as acne that causes psychosocial burden or scarring, or acne that does not respond to treatment with oral or topical therapy. The use of isotretinoin ­Lidose® due to extrabioavailability, high solubility, independence from food intake allows to obtain better clinical results, has a favorable safety profile, characterized by a minimal frequency of adverse reactions.

On the issue of the effectiveness and bioequivalence of isotretinoin Lidose

BACKGROUND: Acne is one of the most common dermatoses. The most effective drug for the treatment of severe forms of acne is systemic isotretinoin, which affects all links in the pathogenesis of acne. The article presents scientific data on the innovative drug Aknecutan, which uses the patented Lidose technology in its production. The use of isotretinoin in the composition of innovative product with Lidose technology makes it possible to reduce the amount of isotretinoin taken by the patient by 20% without compromising the therapeutic effectiveness of the drug. AIM: to analyze comparative studies of bioavailability and relevant pharmacokinetic parameters, which made it possible to prove that the initial dosages of 8 and 16 mg with Lidose technology are bioequivalent to dosages of 10 and 20 mg of the usual form of isotretinoin. MATERIALS AND METHODS: Over the past 7 years, 1044 patients have received acne treatment for moderate to severe acne (651; 62.4% women and 393; 37.6% men) in a daily dose of 0.4–0.8 mg per 1 kg of body weight with a total dose of the drug ― 100–120 mg/kg per course of therapy. RESULTS: After therapy, clinical remission was achieved in all patients, which required from 7 to 12 months of treatment, depending on the daily dose of the drug. Among the side effects in all patients, cheilitis and retinoic dermatitis of the face were noted, which were completely resolved when using moisturizers and sticks. An increase in liver enzymes, triglycerides and lipoproteins was noted in 5–10% and did not exceed 20–30% of the norm and did not require discontinuation of therapy. At the end of treatment, these indicators returned to normal. Other side effects were extremely rare. Relapses of the disease are most often caused by a low total dose of the drug or the presence of endocrinological and gynecological diseases. CONCLUSION: Thus, innovative product with Lidose technology is one of the most highly effective and safe systemic retinoids for the treatment of moderate to severe acne. Comparative studies of bioavailability and corresponding pharmacokinetic parameters have demonstrated the bioequivalence of isotretinoin in the composition of innovative product with Lidose technology, which fully corresponds to that in the original preparation.

Intralesional Kenalog Injections for Recurrent Cutaneous Rosai-Dorfman Disease (RDD) in the Lower Extremity

Rosai-Dorfman disease (RDD) is a rare disorder of histiocytic origin with nodal, extranodal, and cutaneous classifications often presenting as eruptive rashes, most commonly affecting the face, trunk, and thigh. Due to its rarity, no consensus exists regarding standard of care for these lesions, as most knowledge regarding treatment is provided by case reports. To our knowledge, we report the first case of a patient with a recurrent lower extremity mass consistent with cutaneous RDD, despite surgical excision and topical steroids treatment. A 51-year-old female presented with recurrent RDD after failed treatment with clobetasol ointment and surgical excision at an outside practice. Examination revealed violaceous plaques with overlying scale, without lymphadenopathy. With the failure of the previous excision, the patient was prescribed 5 mg/ml intralesional Kenalog (ILK) injections to suppress inflammation of the lesion. She experienced improved clinical response to treatment and remission of active disease with residual post-inflammatory hyperpigmentation at 10 months after two rounds of injections, although the patient reported vast improvement at 5 months as well. Treatment of RDD is difficult due to its rarity, hindering clinical trial development. Therapeutics reported to be efficacious include topical, intralesional, and systemic steroids, retinoids, methotrexate, chemotherapy, cryotherapy, phototherapy, and radiation. Clinical management is variable and often requires multiple forms of treatment on a case-to-case basis, highlighting the need for larger clinical studies to establish a standard of care. Our case poses interest in the use of ILK for RDD and should be considered in recurrent cases after prior surgical excision.

Topical and Systemic Retinoids in the Management of Hidradenitis Suppurativa: A Comprehensive Literature Review.

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.

A CASE OF TREATMENT OF CONGENITAL ICHTHYOSIS IN A NEWBORN CHILD

Congenital ichthyoses (CI) are a group of rare inherited disorders that cause keratinization defects. This group includes hereditary ichthyosis and hereditary syndromes with ichthyosiform lesions. Offi cial statistics are not yet available in Ukraine. The most common clinical manifestation is nonbullous hyperkeratosis characterized by thick hyperkeratotic scales, skin thickening, severe skin dryness and erythema. In more severe forms – ectropion, eclabion. Skin permeability is increased in CI patients, resulting in increased fl uid and calorie loss, diffi culty in thermoregulation, and reduced elasticity, which limits mobility. Symptoms can vary in severity, but severe manifestations at birth are not always indicative of a more severe course later in life. Challenges in defi nitive diagnosis are due to the need for karyotyping, which is quite expensive. Currently available treatment modalities include continuous moisturization, reduction of transepidermal water loss, control of hyperkeratotic layer thickness (reducing it to a minimum) with local keratolytics, emollients, and systemic retinoids in severe cases. The article presents a clinical case of successful local treatment of CI with a pronounced eff ect without the use of systemic retinoids. The publication of the materials has been approved by the Bioethics Commission of the CI «Regional Medical Center for Family Health» DRC». All anamnestic data, examination results and photographs are provided with prior written consent of the parents. Conclusion. Congenital ichthyoses require careful monitoring. The initial clinical manifestations can not be a marker for the severity of the disease course.

Side Effects of Treating Acne Vulgaris With Isotretinoin: A Systematic Review.

The treatment of acne vulgaris poses a significant challenge due to its chronic nature and potential influence on patients' quality of life. Isotretinoin, a systemic retinoid, has emerged as one of the most efficient treatment options for chronic, severe acne. However, the use of isotretinoin is associated with a range of side effects that require careful consideration. This review article provides a comprehensive overview of the side effects linked to isotretinoin treatment for acne vulgaris. Through an analysis of existing literature and clinical studies, we discuss the various adverse reactions, their incidence, management strategies, and the influence of these side effects on patients' quality of life.

Cheilitis: causes, therapy and prevention

Inflammation of the lip skin that can be characterized by peeling, erythema and swelling is known as cheilitis. This condition may be present in a number of skin and systemic diseases. The inflammation process is usually limited to the vermillion border of the lips, but in some cases, it may spread to the skin surrounding the lips and even to the oral mucosa. Cheilitis can be divided into several types due to its causes. Irritant contact cheilitis is the result of frequent hot or dry air exposure. Allergic cheilitis is a delayed reaction following contact with allergens. Atopic cheilitis occurs in individuals suffering from atopic dermatitis. Infection with Candida albicans or Staphylococcus aureus is a common cause of angular cheilitis, which also often occurs as a result of insufficient oral hygiene or improperly selected dentures. Drug-induced cheilitis occurs as a result of intake of certain medications, mainly systemic retinoids. Therapy for cheilitis depends on the factor that triggered the inflammation and is aimed at eliminating unpleasant symptoms. Due to variety of triggers for cheilitis, treatment of this disease may need to consider the involvement of different specialists: dermatologists, dentists, and in some cases, oncologists. Common elements of the treatment of cheilitis, regardless of its etiological factor, is the prescription of special-purpose care products that will have moisturizing and softening effects on the lip skin. This article describes several clinical cases demonstrating the effectiveness of lip care products, which composition provides anti-inflammatory, moisturizing and regenerating effects.

Differentiated approach to external acne therapy

Acne is a serious medical and social problem due to the widespread prevalence of the disease. Localized mainly on the face, acne leads to the development of disorders in the psycho-emotional sphere, significantly reducing the quality of life.
 The aim of the study was to study the effectiveness and safety of Epiduo/Effezel gel (adapalene 0.1% and benzoyl peroxide 2.5%) in patients with papulopustular acne.
 The Clinic of Skin and Sexually Transmitted Diseases of the Clinical Hospital No. 2 of Sechenov University has accumulated extensive experience in the treatment of acne. In the diagnostic and treatment department, patients with mild to moderate acne receive consultations and treatment almost every day. A dermatological examination is carried out visually with a simple count of eruptive elements: papules, pustules and nodes, on the basis of which the degree of severity is determined. Patients with severe forms of acne receive systemic retinoids with corrective therapy until a certain cumulative dose is reached, and then patients receive topical maintenance therapy intermittently for 12 months.
 Despite the development of effective methods for treating this dermatosis, patient adherence to treatment remains low. This is due, first of all, to the duration of therapy, not always the rapid achievement of the expected result, and to the development of psycho-emotional disorders in patients. In the latest edition of the Russian Society of Dermatovenerologists and Cosmetologists clinical guidelines for the treatment of mild to moderate acne with a high level of evidence A1, it is recommended to use benzoyl peroxide and a fixed combination of adapalene and benzene peroxide. When prescribing benzene peroxide (Baziron AS), we observed the best results in clearing the skin of rashes in the presence of a few papulopustular elements in the clinical picture due to the triple action of benzoyl peroxide ― antimicrobial, keratolytic and sebostatic. In our experience, it usually took 4 to 6 weeks to achieve clinical remission, and we did not note a single case of the development of bacterial resistance during treatment. For moderately widespread papulopustular acne rashes of moderate severity, as well as in cases of severe forms of the disease, when it is impossible to prescribe systemic isotretinoin or there is a tendency to scarring of the primary elements, we used a fixed combination of adapalene 0.1% and benzoyl peroxide 2.5% (Effezel) with anti-inflammatory, antimicrobial, keratolytic, sebostatic, comedolytic and anticomedogenic effects.
 In the arsenal of dermatologists and cosmetologists there are drugs for the external treatment of mild to moderate papulopustular acne with a high level of evidence. Thus, for papulopustular acne with a few inflammatory (papules and pustules) rashes, benzoyl peroxide gel may be recommended. For moderately widespread papulopustular acne with the presence of comedones (moderate severity), a fixed combination of adapalene and benzoyl peroxide can be recommended as the first line of therapy.

Comparative Study Between Tacrolimus 0.1% Ointment Versus Topical White Soft Petrolatum Jelly in the Treatment of Oral Retinoid-Induced Cheilitis.

Retinoids are used topically as well as orally, and the most commonly used oral retinoids are isotretinoin and acitretin. Mucocutaneous adverse effects are frequently seen with the use of systemic retinoids, the most common being cheilitis, which is dose-dependent and seen in almost all patients using it. To study the comparative effect of topical tacrolimus 0.1% ointment versus topical white soft petrolatum jelly in the treatment of cheilitis due to retinoids. A total of 26 patients with cheilitis post-treatment with isotretinoin were enrolled in this cross-sectional study conducted over a period of 6 months. They were randomized into two groups of 13 patients each to receive topical tacrolimus 0.1% ointment and soft petrolatum jelly twice daily, respectively. Patients were followed up weekly with clinical photographs. Resolution of cheilitis was assessed on the basis of photograph and ICGS score. About 84.6% of patients of group A and 53.8% of patients of group B showed resolution of symptoms within 1 week of treatment. A significant difference was seen in duration for complete cheilitis resolution and relapse rate in the two groups. Our study concludes that oral retinoid-induced cheilitis shows faster and more significant resolution with twice-daily topical tacrolimus 0.1% ointment application compared to twice-daily topical petrolatum jelly.

Senile Gluteal Dermatosis: Update on Etiopathogenesis, Diagnostic Criteria, and Management

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.

PHARMACEUTICAL CARE OF ACNE PATIENTS USING SYSTEMIC RETINOIDS

Aim. The research aims to study of the issue of pharmaceutical care of acne patients when using systemic retinoids.
 Materials and Methods. The following methods were used: systematic approach, bibliographic, questionnaire survey, statistical, pharmacoeconomic assessment. The objects of the study: relevant information sources; current standards of pharmacotherapy, instructions for medical use of isotretinoin of the State Register of Medicines of Ukraine (n=4), 14th edition of the State Drug Formulary; questionnaires of acne patients who use systemic retinoids (n=53); pharmacy quotes for isotretinoin drugs and laboratory quotes for liver biopsy and lipid testing. The subject of the study: appropriate pharmaceutical care of acne patients when using systemic retinoids.
 Results and Discussion. The results of the questionnaire showed that, despite high awareness, the practice of patients' compliance with the recommendations regarding the use of isotretinoin needs to be optimized, in particular by means of pharmaceutical care, which was provided in only 30.2% (95CI: 18.3-44.3%) cases according to the patients. As a result of the analysis of current regulatory-legal documents, 6 main guidelines were identified, including 10 key messages of pharmaceutical care. Considering the extremely low level of proper implementation of the Pregnancy Prevention Program when using systemic retinoids (3.7%; 95CI: 0.1-19.0%) and the severity of the consequences of neglecting the recommendations (teratogenic effect), pharmaceutical care should include the issue of effective contraception and pregnancy testing by not only informing but also finding and using other strategies to increase patient compliance with the recommendations, in our opinion. We consider that the discussion with the patient regarding the costs of pharmacotherapy with systemic retinoids (according to the results of our study - from ₴ 17919.20 to ₴ 25307.50), in addition to the cost of isotretinoin (from ₴ 15417.20 to ₴ 21550.00), should include the costs of conducting laboratory control of liver tests (from ₴ 1530.00 to ₴ 2340.00), lipidogram (from ₴ 972.00 to ₴ 1417.50) and meeting some other individual patient needs.
 Conclusions. Studying the issue of pharmaceutical care when using systemic retinoids allowed to determine the main guidelines (n=6) and key messages (n=10) that pharmacists can focus on during professional communication with acne patients, which makes it possible to increase the effectiveness and safety of pharmacotherapy.

Cutaneous squamous cell carcinoma with osteoclast-like giant cells in an 87-year-old male

Cutaneous Squamous Cell Carcinoma (SCC) with Osteoclast-Like Giant Cells (OLGCs) is a rare finding, with only 11 previous cases reported in the literature. The origin of the OLGC within carcinomas has been debated, and there are two prevailing theories regarding the cell origin. We report the 12th case of SCC with OLGCs, discuss the two theories, and analyze the common features among all twelve cases. Ultimately, there appears to be an association between OLGCs and poorly differentiated cutaneous squamous cell carcinomas. Consequently, OLGCs should lead to an increased index of suspicion, as they may be a predictor of poor outcomes. If OLGCs are identified on histology, the pathologist should consider the addition of Preferentially-expressed Antigen in Melanoma (PRAME) immunostaining as a means of more accurately determining the prognosis. In conjunction with clinical features, histology should guide clinical recommendations and may warrant chemoprevention with systemic retinoids in high-risk individuals.

Acitretin-loaded nanoethosomal gel for the treatment of psoriasis: Formulation, optimization, in vitro, and in vivo assessment

Acitretin (ACT) is a second-generation systemic retinoid used to treat severe psoriasis. However, its poor aqueous solubility and systemic adverse effects make it impractical for oral administration. The primary objective of this research is to prepare, optimize, and evaluate a nanogel consisting of acitretin-loaded ethosomes (ACT-ETH) for its anti-psoriatic potential. A 32 full factorial design was employed for optimization. Thin-film hydration was adopted to prepare ACT-ETH, and then their physicochemical characteristics were tested. The optimized ACT-ETH was converted into a carbopol gel and then evaluated for cytotoxicity, skin irritation, and anti-psoriatic properties. The vesicle size, zeta potential (ZP), and percent entrapment efficiency (% EE) of the optimal ACT-ETH are 147 ± 2.15 nm, −11.5 ± 0.25 mV, and 90.70 ± 0.89%, respectively. The fluorescence microscopy study has shown that ethosomes may go deeper into the skin layers. Compared to plain gel, ACT-ETH gel greatly increased skin permeability and deposition in the ex-vivo skin permeation and deposition tests. The in vitro cytotoxicity investigation revealed that the cytotoxicity of ACT against normal cells (L-929) was significantly reduced by ACT-ETH gel compared to plain ACT gel. The skin irritation study proved that ACT-ETH gel was well tolerated and safe for use on the skin. The in vivo anti-psoriatic study showed that using ACT-ETH gel to treat psoriasis on the skin led to a significant improvement in the therapeutic response. Based on these results, ACT-ETH gel has the potential to increase the topical anti-psoriatic action of ACT by mitigating its known drawbacks.

In vivo imaging of patients with chronic pruritus of unknown origin reveals partial sweat duct obstruction with partial itch resolution upon retinoid treatment.

Chronic pruritus of unknown origin (CPUO) is poorly understood and lacks effective treatment options. We aimed to elucidate abnormalities in the sweat apparatus of patients with CPUO, and to assess efficacy and safety of treatment with systemic retinoids. An initial case-control study included 20 affected patients and five healthy controls, for whom heat and sweating were induced, either through a standardized exercise protocol or ingestion of hot water. In vivo high-definition optical coherence tomography, whole-body starch-iodine testing, and skin biopsy for immunofluorescence staining were done to evaluate for sweat duct obstruction. A subsequent retrospective cohort analysis included 56 patients with CPUO, seen at an Itch subspecialty clinic of a single tertiary referral centre, who failed conventional treatments and were treated with isotretinoin and/or acitretin from May 2014 to November 2020. Treatment response to retinoids was defined as a sustained reduction in itch score of ≥2/10. Safety was assessed by proportion stopping treatment due to side effects. In vivo imaging in 19 (95%) patients revealed features of partial keratinaceous sweat duct obstruction with statistically significant luminal dilatation compared to controls. Immunofluorescence studies of three patients' paired lesional/non-lesional biopsies revealed dermcidin accumulation within sweat glands coupled with dermcidin leakage in itchy skin. Fifty-six patients (mean [SD] age 55.2 [17.5] years, 69.6% male) were treated with systemic retinoids. Mean (SD) duration of itch was 116.3 (140.4) months and mean (SD) itch score was 8.2 (1.8). Forty-one (73.2%) initially received isotretinoin, and 15 (26.8%) acitretin. At three months, mean itch score reduced by 2.38 (95% CI -3.2 to -1.6, p < 0.0001). Thirty-eight (67.9%) had a sustained response. Eight (14.81%) achieved an itch score of 0 or 1, with four stopping treatment for a mean (SD) of 318.5 (291.2) days without relapse. Eight (14.3%) stopped or switched retinoid due to adverse effects, with similar incidences between both retinoids, the commonest being dryness. Based on novel findings from physiological imaging studies identifying partial keratinaceous sweat duct obstruction in CPUO, we instituted systemic retinoid treatment to address the underlying pathology. In patients who failed conventional therapies, the treatment appears effective and safe.