Systemic Retinoids Research Articles

Use of retinoids in dermatology

Background: Retinoid, whose existence was first known in the 20th century, was initially referred to as a naturally occurring substance with vitamin A action. However, now it has become a generic term for all substances exhibiting an active action through the retinoid receptor located in the nucleus of the cells. Retinoids are biologically important substances involved in many functions, including reproduction, embryonic morphogenesis, regulation of epithelial proliferation and differentiation, reduction of sebaceous gland, immune and anti-inflammatory effects, tumor prevention, and effects on extracellular matrix components.Current Concepts: Topical retinoids are used to treat several conditions, including acne, photoaging, and psoriasis. Their side effects are dose-related skin irritations, while teratogenicity risk is rare to non-existent. Systemic retinoids are a treatment of choice for acne and keratinization disorders. They are also useful for the treatment of psoriasis, pityriasis rubra pilaris, cutaneous T-cell lymphoma, and chronic hand eczema. Systemic retinoid therapy requires the careful patient selection and monitoring due to associated teratogenicity. Other important side effects are hypertriglyceridemia, dryness of lips, blepharoconjunctivitis, bone pain, increased muscle tone, myopathy, hypothyroidism, and neutropenia.Discussion and Conclusion: Awareness of the side effects and proper use of retinoids are important for successful treatment outcomes of the above-mentioned dermatological conditions.

Efficacy of adding systemic glucocorticosteroids to standard therapy in adolescents with severe acne: a randomized controlled trial

Introduction. Isotretinoin is the first-choice drug in the treatment of severe forms of acne vulgaris. The combination of systemic retinoids with durant corticosteroids helps to reduce the likelihood of developing “retinoic” dermatitis and exacerbation of acne in the initial stages of isotretinoin therapy.Purpose of the study. Determination of the effectiveness of the combined use of isotretinoin and a durant corticosteroid in the treatment of severe forms of acne vulgaris.Materials and methods. Twenty six patients with “severe” or “very severe” grade on the IGA scale were included in this randomised, controlled comparative study. Thirteen patients (group A) were treated with isotretinoin 0.5 mg/kg/day (cumulative dose from 120 to 150 mg/kg) for 8 months and 2 injections of betamethasone dipropionate + betamethasone sodium phosphate at dose 1 ml (2 mg + 5 mg/1 ml) at first month (1 injection per two weeks) and thirteen patients (group B) were treated with combined therapy with isotretinoin at a dose of 0.5 mg/kg/day (cumulative dose from 120 to 150 mg/kg) for 8 months and assessment was based on the IGA scale, counting the number of inflammatory and non-inflammatory elements, indicators DIA (dermatological index of acne) and DLQI and was done at baseline, 1, 4 and 8 months of treatment.Results. At month 8, compared to group B, group A showed more significant decrease in IGA score and 76% patients achieved “clear” or “almost clear skin” degree (76% vs. 30%). The reduction in the number of inflammatory and non-inflammatory elements showed a marked clinical improvement in group A (89.2% vs 22.3 % for nodules). The decrease in DIA was 88.3% in group A and 71.3% in group B. Exacerbations of acne were recorded in 0% (group A) vs 38.0% (group B) of patients. We also found a relationship between the achievement of a 2-point reduction in the degree on the IGA scale after 8 months and the presence of exacerbations while taking isotretinoin (p = 0.012). Analyzing the DLQI between the two, we were unable to identify statistically significant differences.Conclusions. Combines use of long acting steroid with isotretinoin provides synergic effect while minimizing the side effect of isotretinoin (decreases the number of exacerbations), demonstrates a visible effect to patients within a month, thereby increasing compliance, improving the quality of life and reducing the risk of scarring.

Evaluation of serum hepcidin level in acne vulgaris patients

Background: Acne vulgaris is a pilosebaceous unit inflammatory condition. Although acne is not life-threatening, it can cause psychological issues such as low self-esteem and anxiety in people who suffer from it. Acne scarring is a common and unpleasant consequence of acne vulgaris. Predicting scarring liability can modify treatment protocol and aid in the prevention of such disfigurement. Methods: This study included 82 participants divided into 3 groups: 26 patients with acne vulgaris without scars, 36 patients with acne vulgaris with scars and 20 control. Serum hepcidin level was assessed by a commercially available double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: Serum hepcidin is significantly higher in patients suffering from acne without acne scars than patients suffering from acne with acne scars (p < 0.05). serum hepcidin is significantly higher in the control group than patients with active acne with scars (p < 0.05). There was a statistically significant difference between serum hepcidin level in control versus severe acne scars (p < 0.05). Serum hepcidin level acts as a predictor of occurrence of acne scars and occurrence of severe acne scars. Serum hepcidin level can be used as an indication for beginning aggressive and specific acne treatment as systemic retinoid.

A multidisciplinary approach in the management of patients with acne

The article summarizes the data of the scientific publications about the management of patients with androgen-dependent dermatopathies, namely acne, taking into account the current view on the pathogenesis, clinical manifestations and results of the examinations of this group of women. Androgen-dependent dermatopathies are not only a medical problem but also a socio-economic one, as they lead to impaired socialization and reduced quality of life. Acne is one of the most common dermatoses. Acne is a chronic multifactorial disease of the pilosebation complex, which is clinically manifested by polymorphic rash in the form of open and closed comedones, papules, pustules, nodules. The pathogenesis of the disease is based on four main links: changes in the quantitative and qualitative composition of sebum due to hypersecretion of androgens and/or increased sensitivity of receptors to their action, impaired follicular keratinization, inflammation and changes in skin microbiome. Besides the main pathogenetic aspects, trigger factors are taken into account, such as nutrition, stress, smoking, mechanical agents. The current treatment of acne according to dermatological protocols is presented in the article, which is based on a combination of topical therapy with local retinoids and antibiotics, benzoyl peroxide, azelaic acid, in case of severe or ineffective local therapy systemic antibiotics and systemic retinoids are used. However, despite the presence of many treatment regimens for dermatosis, it is often not possible to achieve a lasting effect of treatment, and the adherence of patients to follow the doctor’s recommendations decreases. Given that the leading role in the pathogenesis of acne is due to hyperandrogenic effects on the skin, as well as the fact that the disease reduces the quality of life and self-esteem in patients, it is necessary to involve a wider range of specialists, such as dermatologists, gynecologists, endocrinologists and psychotherapists for successful treatment and prevention of persistent aesthetic skin defects.

Safety, tolerability, and efficacy of a novel topical isotretinoin formulation for the treatment of X-linked or lamellar congenital ichthyosis: Results from a phase 2a proof-of-concept study

To the Editor: Clinical characteristics of congenital ichthyosis (CI) include hyperkeratosis, scaling, and erythroderma.1,2 The management of CI typically involves emollients and keratolytics.2,3 Patients with lamellar or X-linked recessive CI often have considerable hyperkeratosis and scaling, for which systemic retinoids are effective but may cause dose-limiting adverse events (AEs).2,4,5 PAT-001 is a patented, novel, topical isotretinoin ointment formulation to treat CI. We present the results from a phase 2a study evaluating PAT-001 in patients with lamellar or X-linked recessive CI.

A systematic review of oral retinoids for treatment of acneiform eruptions induced by epidermal growth factor receptor inhibitors.

Epidermal growth factor receptor inhibitors (EGFRi) are now standard of care in patients with EGFR mutations in non-small cell lung cancer (NSCLC) and are increasingly being used in other EGFR mutated cancers, including gastrointestinal, and head and neck. However, EGFRi are well known to cause acneiform eruptions, which are shown to positively correlate with tumor response to treatment, but may be severe enough to cause interruption of their treatment. Although most guidelines call for the use of tetracyclines to treat these acneiform eruptions, there is mounting evidence for the use of systemic retinoids instead. The objective of this review is to summarize available data on the use of systemic retinoids for management of acneiform eruptions on EGFRi. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE were searched from database inception until December 10th, 2021. All articles were screened and relevant data extracted independently in duplicate by two reviewers. In total, 16 case reports, case series and retrospective reviews were included. Forty-three patients were treated with retinoids for their acneiform eruption due to EGFRi. The majority (77%) noted moderate to significant improvement after treatment initiation with minimal adverse events (16%). The findings of this systematic review suggest that systemic retinoids are a safe and effective therapy for the management of acneiform eruptions induced by EGFRi.

Surgical View of Morphological and Pathogenetic Identity of Pilonidal Cysts and Acne Inversa.

<b>Introduction:</b> As a rule, the treatment of pilonidal cysts is based on a surgical approach. Surgical treatment depends on the form of the disease and surgeon's preferences regarding the method. The treatment process does not consider preoperative treatment that would affect the structural components of the skin involved in the pathological process. The results of surgical treatment remain unsatisfactory, leading to a significant number of recurrences and long-term healing of the postoperative wound. </br></br> <b> Materials and methods:</b> Morphological examination of the pieces of skin with altered sacrococcygeal tissues after radical surgical treatment of 46 patients with pilonidal cyst of the sacrococcygeal region was performed, and 46 patients with acne inversa of the intergluteal cleft, groin and scalp were selected. The sex distribution of patients with pilonidal cysts was as follows: 43 (91.3%) male patients, 3 (6.5%) female patients. Among 46 patients with acne inversa and dissecting cellulitis, the distribution was as follows: 32 (69.6%) male patients and 14 (30.4%) female patients. Patients with pilonidal cysts of the sacrococcygeal region underwent surgical treatment according to the developed method of economical median resection using sutures with internal fixation. </br> </br> <b> Results:</b> Considering and comparing the morphological picture observed in the pathomorphological examination of histological specimens in patients with pilonidal cysts, acne inversa, dissecting cellulitis, the similarity of changes in most patients is noteworthy. "Acne inversa" was first described in 1839 by Velpeau, who originally called the disease "hydradenitis suppurativa", believing that inflammatory changes occur in the sweat glands [1-3]. In 1854, surgeon Verneuil described this disease, and later it was named after him. We observed chronic proliferative inflammation in different layers of the dermis and subcutaneous tissue (the main focus is in the subcutaneous tissue, but closely related to the dermis and epidermis). </br></br> <b>Discussions:</b> Pilonidal cyst of the sacrococcygeal region, especially without hair in the cavity of the cyst, can be considered as a type of acne inversa with appropriate location. We believe that the use of local and systemic retinoids, namely isotretinoin, in the treatment of patients with this disease other than surgery, together with other groups of drugs traditionally used in the treatment of pilonidal cysts, may be promising in the treatment of pilonidal cysts.

Systemic nonbiologic treatments for hidradenitis suppurativa

AbstractHidradenitis suppurativa (HS) is a severe and painful chronic dermatologic condition affecting hair follicles with a significant negative impact on patient quality of life. Effective treatment of HS has proven challenging and often involves multiple modalities. These include topical treatments, systemic antibiotics, retinoids, hormonal therapies, biologic and nonbiologic immunosuppressants, small molecule inhibitors, surgery, and photodynamic/radiation therapy. This review outlines the nonbiologic systemic therapies for HS and describes the latest research on these therapies. Therapies covered in this review include systemic antibiotics, retinoids, hormonal therapies, nonbiologic immunosuppressants, and small molecule inhibitors.

Diffuse plate-like sheets of desquamation

Diffuse plate-like sheets of desquamation

Harlequin Ichthyosis: Folklore of Demon

Background: Harlequin ichthyosis (HI) is a severe and rare autosomal recessive congenital ichthyosis, characterized by severe hyperkeratosis, extensive fissuring and massive, diamond-shaped scales which limit the child’s movements. The term harlequin comes from the baby’s facial expression and diamond-shaped pattern of the scales like the 17th century entertainers, harlequins. The underlying genetic abnormality has been identified as a mutation in the lipid-transporter gene ABCA 12 on chromosome 2q35. Aim and objectives: To provide a comprehensive knowledge of severe forms of congenital ichthyosis, the harlequin ichthyosis and abolish the superstitious notion regarding the appearance of the neonate. Materials and Methods: The present report is case of premature girl baby delivered at MIMS, Mandya. The neonate presented plaques of rigid fixed skin, separated by deep red fissures, facial features were obliterated by thickened skin, undeveloped nose and pinna, severe ectropion and eclabium. Intensive care was given and survival was prolonged by systemic retinoids. The neonate succumbed to respiratory failure few days later. Results and conclusion: The present study gives a comprehensive knowledge of harlequin ichthyosis and provides emphasis on sensitization of the disease to prevent any misconception or superstition. Also lays emphasis on Genetic counseling of the couple to prevent further occurrences. KEY WORDS: Eclabium, Ectropion, Harlequin ichthyosis.

Verrucous Lichen Planus: A Peculiar Presentation with Excellent Response to Systemic Retinoids.

Verrucous Lichen Planus: A Peculiar Presentation with Excellent Response to Systemic Retinoids.

Efficacy and tolerability of system isotretinoin and effect of this therapy on the quality of life of patients with severe and moderate acne

Background. The relationship between acne and depression is being actively studied by the medical community. Question is depression a restriction in prescribing or a side effect when using systemic isotretinoin remains controversial. Noteworthy is the presence in the scientific literature of data on the possible positive effect of adequately and timely prescribed acne therapy on the psychoemotional state of patients with this ailment.
 Aims. The aim of our study was to evaluate the effectiveness of therapy with systemic isotretinoin in patients with moderate and severe acne, to assess the effect of the therapy on the quality of life of patients, as well as the persistence of remission after the end of the course of therapy with systemic retinoid.
 Methods. We observed 32 patients with moderate and severe acne, the average age of patients was 24 years, the duration of the disease was on average 8 years. All patients underwent therapy with systemic isotretinoin (Sotret) at an average daily dose of 0.51.0 mg/kg until a cumulative dose of 120150 mg/kg was reached. The effectiveness and tolerability of the therapy was assessed, as well as the quality of life of patients was assessed using the dermatological index of the quality of life (DQL), the dermatological akne index (DIA), the HADS scale (anxiety and depression scale). The indicators were assessed before the start of therapy, during therapy, at the end of the course of treatment with systemic isotretinoin, and also 12 months after the end of therapy.
 Results. 100% of patients achieved clinical remission as a result of treatment with systemic isotretinoin.
 Before starting therapy with systemic isotretinoin, the indices were as follows: DQL 18 (1520), HADS 10 (716) and DIA 13 (615) scores. By the end of the therapy, the indices decreased to 1 (01), 2 (04) and 1 (01) points, respectively (p 0.001).
 12 months (year) after the end of therapy with systemic isotretinoin, the indices remained at zero or one level in all patients: DQL 1 (01), HADS 0 (01) and CIA 1 (01) points (p 0.001).
 Conclusion. A causal relationship between the intake of systemic isotretinoin and the development of depression has not been established. Systemic isotretinoin therapy was effective in all patients (100%), was well tolerated and had a positive effect on the psychoemotional status of patients with acne. 12 months after the end of therapy with the drug Erase, stable remission of the disease was noted in all patients

Ultrasonic diagnostics of vascular complications after laser procedures

A clinical case of treatment of rosacea with a high-intensity laser at different stages, performed under control of high-resolution ultrasound (HRU), is presented. According to clinical guidelines, patients in the erythematous stage of rosacea (stage I) undergo selective coagulation of superficial vessels with a neodymium laser. Diagnosis and determination of the severity of the disease are carried out based on the presence of primary and secondary elements of the rash. There are no criteria for ultrasound assessment of the skin and its vascularization in patients with rosacea. During ultrasound examination after 4 laser procedures in B-mode, the dermis is heterogeneous due to hypoechoic papillary and hyperechoic reticular layers, without signs of infiltrative changes, in the color Doppler mapping mode there is a pronounced vascularization of the papillary dermis in the area of interest, represented by multiple vessels in contrast to single vascular structures seen on ultrasound after two laser treatments. According to the results of ultrasound examination, a more severe degree of the disease was diagnosed, which served as the basis for prescribing therapy with systemic retinoids. Clinical observation demonstrates the capabilities of ultrasound in planning laser procedures in order to reduce the risk of complications, their early diagnosis and monitoring of treatment if they occur.

Analysis of the effects of isotretinoin on the premature epiphyseal closure in pediatric populations: a literature review.

Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U.S. Food and Drug Administration (FDA) has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne. It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen. This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure. Two databases were utilized for the literature review and were conducted at different time periods. Our literature review was conducted between December 2020 and June 2021, utilizing PubMed with the following search terms: "isotretinoin" and "isotretinoin and premature epiphyseal closure." In April 2021, we searched the FDA's "Drug Data and Adverse Event Report System" utilizing the terms "isotretinoin" and "epiphysis premature fusion." We included in our query reports of patients worldwide under 18years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Studies published in English between 1980 and 2020 were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded. A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin. The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5mg/kg/day for a few months to 3.5mg/kg/day for years. Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur. A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded.

Retinoids are not linked to risk of multiple sclerosis: A Danish nationwide cohort study.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system with an undetermined etiology. Retinoids may have immunomodulatory effects that favorably influence MS progression. We aimed to explore the yet unknown relationship between exposure to retinoids and the risk of acquiring MS. We performed a nationwide cohort study in the Danish population in the period 1998-2016, comparing MS incidence in three groups: users of systemic retinoids; users of topical retinoids (negative control group); and users of non-retinoid acne drugs (control group). We used data from the Danish Multiple Sclerosis Registry (DMSR), the Danish National Prescription Registry and the Danish National Patient Registry. Linkage was obtained through the personal identification number (CPR number). We addressed confounding by three-way propensity score (PS)-matching weights. Additionally, to evaluate a cumulative dose-response effect for systemic retinoids on MS incidence, we conducted a case-control study, nested within the cohort. A total of 257,193 users of non-retinoid acne drugs, 130,560 users of topical retinoids, and 75,610 users of systemic retinoids were included. Systemic retinoid use was not associated with a reduced risk of MS compared to non-retinoid acne drug use in crude (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61 to 1.05]) and weighted analyses (HR 0.89, 95% CI 0.67 to 1.20). There was no evidence of a cumulative dose-response association between systemic retinoids and MS incidence. Use of systemic retinoids was not associated with a reduced incidence of MS compared to use of non-retinoid acne drugs in this study.

A саsе of effective treatment of acne in patient with secondary immune deficiency of the first degree

Acne is an urgent problem in modern dermatology. The management of this disease is a complex, lengthy and multi-step process that requires a combination of different treatment methods and an individualized approach.
 Objeсtive — to demonstrate a clinical case of effective treatment of acne in a patient with secondary immune deficiency of the first degree.
 Materials and methods. A clinical case is presented of treatment of a 23-­year­-old man suffering from papulopustular form of moderate acne developed on the background of secondary immune deficiency of the first degree. The disease had a chronic course and resistance to the therapy used. The retinoid drug isotretinoin was used for treatment with a gradual increase and then decrease in its daily dose; antibiotic therapy; the drug Propes as an immunomodulator; as well as a set of cosmetic measures — chemical peelings and laser skin resurfacing. After the onset of dryness of certain areas of the skin, as a side effect of isotretinoin, emollients were locally intended.
 Results and discussion. At the end of the seventh month of treatment, the inflammatory rash on the skin completely stopped. The phenomenon of postacne was eliminated. During the control immunogram 2 months after the start of complex therapy, there was complete normalization of its parameters. In addition, during the first month of taking the drug isotretinoin , the patient did not have the exacerbation of the inflammatory process on the skin which was usual for this stage of treatment.
 Conclusions. The success in the treatment of the patient with acne who had secondary immune deficiency of the first degree as concomitant pathology, in our opinion, is due to a well­chosen comprehensive treatment which included antibacterial therapy, systemic retinoid isotretinoin in an appropriate for this clinical stage dose, Propes medication of the defensins group as an immunomodulatory agent, as well as the use of a complex of cosmetic measures.

Keratosis pilaris atrophicans faciei: An observational, descriptive, retrospective clinical study.

Keratosis pilaris atrophicans faciei (KPAF) is a hereditary follicular disorder, an atrophicans subtype of keratosis pilaris (KP) with a highly elusive diagnosis. Clinically, it presents with follicular, horny papules surrounded by an erythematous halo of the cheeks, forehead, chin and eyebrows, and it is followed by a gradual hair loss on the lateral margins of the eyebrows. The onset is as early as a few months after birth, but it is mainly diagnosed in children and adolescents and it can persist through adulthood. At present, the natural progression of the disease is poorly understood, which makes a correct diagnosis highly unlikely. The aim of the present study was to describe the clinical characteristics of KPAF in patients encountered in daily practice, in order to find common characteristics that may aid in the earlier recognition of the disease. An observational, descriptive, retrospective study was performed on 14 patients diagnosed with KPAF between January 2000 and December 2020. The mean age at diagnosis was 17.04 years and the onset of clinical symptoms appeared at a mean age of 4.85 years. The first clinical symptom was KP involving either the upper or lower limbs, or both. Then, erythema of the face appeared at a mean age of 7.21 years, keratotic papules on the face at a mean age of 8.35 years and, finally, loss of hair on the lateral margins of the eyebrows at a mean age of 14 years. The patients also had concomitant xerosis cutis, multiple mole syndrome, acne, contact dermatitis and Laugier-Hunziker syndrome. Evidence of disease progression, associations, as well as efficacious treatment measures are lacking. An earlier diagnosis potentially allows for a more efficacious, targeted treatment option. Either topical emollients, systemic retinoids or laser therapy may prove effective for each patient individually.

Executive summary: Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents

Topical and systemic retinoids are often used long-term in the treatment of ichthyoses and other disorders of cornification. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address the numerous clinical concerns with use of these medications in children and adolescents and to establish best practices regarding the use of retinoids. Consensus was achieved using the Delphi process with recommendations based on the best available evidence and expert opinion. An executive summary of the results is presented herein.

Ichthyosiform Erythroderma, a Multifaceted Syndromic Entity.

Ichthyosiform Erythroderma, a Multifaceted Syndromic Entity.

Predictors of postdischarge follow-up attendance among hospitalized dermatology patients: Disparities and potential interventions

Predictors of postdischarge follow-up attendance among hospitalized dermatology patients: Disparities and potential interventions