Systemic Isotretinoin Therapy Research Articles

Nail changes in patients receiving systemic isotretinoin therapy

In this study, it was aimed to describe isotretinoin-induced nail changes and increase patients’ treatment compliance. A total of 200 patients diagnosed with acne vulgaris were included in the study. 100 of the patients were started systemic isotretinoin treatment and 100 control patients were receiving topical acne treatment. Age and gender of all of the participants, duration of treatment, total doses per month, and type of nail changes were recorded. Patients with persistent nail changes were followed at the 3rd and 6th months after treatment. A total of 34 patients had nail changes in the isotretinoin group. These changes included onychoschizia (55.9%), leukonychia (11.8%), onychorexis (8.8%), median nail dystrophy (5.9%), pyogenic granulomas (5.9%), chronic paronychia and granulation tissue (5.9%), onycholysis (2.9%) and Beau’s line (2.9%). The rate of nail changes in the isotretinoin group was significantly higher than in the topical treatment group (34% vs. 11%, p:0.001). Isotretinoin increases the risk of nail changes, primarily onychoschizia. The risk of developing nail changes is not associated with treatment duration but is associated with the total cumulative dose. Nail findings induced by isotretinoin are completely reversible.

Increased femoral cartilage thickness in acne patients using isotretinoin: could it be a sign of early osteoarthritis?

Vitamin A derivatives have inhibitory effects on cartilage tissue, such as decreasing chondrocyte proliferation and collagen synthesis, and increasing the loss of glycosaminoglycans and proteoglycans. Therefore, isotretinoin (a vitamin A derivative) may play a role in the pathogenesis of cartilage-related diseases like osteoarthritis by affecting the balance of cartilage tissue. The aim of this study was to evaluate the distal femoral cartilage thickness in acne patients under the systemic isotretinoin therapy and to determine whether it constitutes a risk factor for the development of osteoarthritis. The study included 52 patients (42 female, 10 male, mean age 23.31 ± 3.89 years) who were prescribed systemic isotretinoin for acne and completed at least 3 months of treatment, along with 45 healthy controls ((35 female, 10 male, mean age 23.85 ± 4.77 years). Bilateral distal femoral cartilage thickness was measured by ultrasonography before isotretinoin treatment and after the completion of the third month of treatment. After treatment, a statistically significant increase was found in the thickness of the right medial, right lateral, left medial, left lateral, and left intercondylar cartilage (p = 0.014, 0.012, 0.019, 0.027, 0.002, respectively). There was also an increase in the right intercondylar cartilage thickness, but this was not statistically significant (p = 0.1). Systemic isotretinoin seems to make cartilage thicker. The increase in femoral cartilage thickness observed after short-term isotretinoin treatment might be an indicator of very early-stage osteoarthritis. Extended follow-up studies with larger participant pools are necessary to substantiate this result.

Modern approaches to acne therapy: review of clinical recommendations and analysis of clinical cases

This article provides an overview of modern guidelines for acne treatment. The issues of prescribing both topical and systemic acne therapy are discussed. Particular attention is paid to systemic isotretinoin therapy. Clinical examples of the use of the drug Erase for acne of moderate and severe severity are discussed.

The impact of systemic isotretinoin treatment on the tear film, meibomian glands, and corneal endothelium

Purpose The study aims to investigate changes in tear function, meibomian glands and corneal endothelium in patients receiving systemic isotretinoin therapy. Materials and methods This prospective study included 38 eyes from 38 patients (23 females and 15 males) treated with systemic isotretinoin (0.5–1 mg/kg/day) following the diagnosis of acne vulgaris. All patients underwent a comprehensive ophthalmologic examination at baseline, 1st month, and third month of treatment. Subjective complaints were assessed using the Ocular Surface Disease Index (OSDI). Tear functions were evaluated through non-invasive tear break up time (NIBUT) and Schirmer I test. Meibomian gland (MG) changes were examined using meibography. Corneal parameters, including endothelial cell density (ECD), coefficient of variation (CV), the number of cells with a hexagonal shape (6A), average cell area (AVG), and central corneal thickness (CCT) were assessed using non-contact specular microscopy. Results The mean age of the patients was 19.29 ± 2.83 years. Ocular surface-related discomfort, measured with OSDI scores, significantly worsened at the third month measurements compared to the pre-treatment values (p < 0.001). In the 1st month of treatment, there was a significant decrease in NIBUT (p < 0.05). No statistically significant difference was found in the Schirmer test results at each visit. According to the 1st and third-month analysis, there was a significant increase in MG loss compared to the pre-treatment period (p < 0.001). ECD, CV, 6 A, AVG measurements at the first and third months showed a significant change compared to the pre-treatment values (p < 0.001). No significant difference was observed in the CCT measurements during the treatment. Conclusion Systemic isotretinoin disrupted tear stability, caused MG loss, deterioration in corneal endothelium, and led to symptomatic complaints in patients.

Serum Catestatin Levels in Patients with Acne Vulgaris: Single-Center Prospective Study

Introduction: Recent studies showed that antimicrobial peptides have an essential role in the pathogenesis of acne vulgaris. This study aims to investigate serum catestatin levels in acne vulgaris patients and focuses on the change in serum levels after systemic isotretinoin therapy. Methods: This prospective study includes 101 acne vulgaris patients and 28 healthy controls. Serum catestatin levels were measured and compared between acne vulgaris and control group patients. Also, serum catestatin levels were measured again at the 24th week of isotretinoin therapy. Results: The serum catestatin levels in patients with acne vulgaris were statistically higher than in the control group (p < 0.001). In addition, serum catestatin levels were associated with the severity of acne vulgaris. A significant decrease in serum catestatin levels was detected after 24 weeks of systemic isotretinoin treatment. Conclusion: Catestatin was found to be significantly higher in the serum of patients with acne vulgaris compared to the control group. Although, the demonstration that catestatin levels decrease with isotretinoin treatment may indicate that it may have an important role in the pathogenesis of acne and could be used as a biomarker, future studies are needed to establish the role of catestatin in the pathogenesis of acne vulgaris.

Systemic isotretinoin therapy and central macular and choroidal thicknesses in acne vulgaris: is there any association?

Purpose To investigate the effect of oral isotretinoin therapy on central macular thickness (CMT) thickness and choroidal thickness (CT) using optical coherence tomography (OCT). Methods CT and CMT thickness of 43 eyes were evaluated at baseline, the third, and sixth month of isotretinoin therapy by spectral-domain OCT. For assessment of CT, OCT measurements were obtained at the fovea with six additional measurements at adjacent locations (at 500–1000 µm temporal to the fovea and 500–1000 µm nasal to the fovea). Results Forty-three eyes from 43 patients with acne vulgaris, including 33 females (76.7%), who had a mean age of 24.81 ± 6.60 years, completed the study. The mean CMT was 231.49 ± 19.52 at the baseline and significantly decreased to 229.0 ± 19.57 (p = 0.02) and 229.28 ± 18.83 after three and six months, respectively (p < 0.03). The change in the macular thicknesses measured at four quadrants and choroidal thicknesses were not statistically significant during the study (p > 0.05). Conclusion The result of our study demonstrated choroidal thickness change is not significant in patients with acne vulgaris after systemic isotretinoin therapy during six months of follow-up. The decreased CMT amount was 2.2 microns; even if statistically significant, this amount is clinically insignificant.

Effect of systemic isotretinoin therapy on semen parameters

Purpose Vitamin A has multiple functions in the human body, being involved in growth, epithelial differentiation, vision, immune function and reproduction. While normal spermatogenesis is influenced by several factors, it requires vitamin A. Systemic isotretinoin is a vitamin A derivative that is used in the treatment of many dermatological diseases, especially acne vulgaris (AV). There is limited research on the changes in semen parameters after systemic isotretinoin therapy in humans. Our study investigates the presence of varicoceles in patients undergoing systemic isotretinoin therapy for AV and examines whether there were any changes in the semen parameters before and after treatment. Methods Included in the study were 46 men patients who were scheduled for systemic isotretinoin therapy for AV. Before treatment, the patients underwent a physical examination and ultrasonography for varicoceles assessment. The patients underwent spermiogram before treatment and after 6 months of treatment. The spermiogram assessments included semen volume, sperm concentration, total sperm count, progressive motility, viability and sperm morphology. Results After treatment, there was an increase in semen volume, sperm concentration, total sperm count, progressive motility and vitality from the pre-treatment values, but a deterioration in the sperm morphology (p < .05). Comparing patients with and without varicoceles revealed more changes in semen parameters after treatment in those with varicoceles. There was a statistically significant difference in sperm concentration (p < .001). Conclusions Systemic isotretinoin therapy negatively affects sperm morphology, but has positive effect on other semen parameters, and these changes in semen parameters occur more frequently in patients with varicoceles. KEY MESSAGES Acne vulgaris is a very common disease and systemic isotretinoin is used as the most effective agent in its treatment. Systemic isotretinoin positively affects semen parameters except sperm morphology. Changes in semen parameters are more common in patients with varicocele.

Isotretinoin treatment upregulates the expression of p53 in the skin and sebaceous glands of patients with acne vulgaris

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.

Analysis of corneal topographic and densitometric properties in patients receiving systemic isotretinoin therapy

Purpose To evaluate dry eye parameters, corneal topographic features, corneal densitometric changes, and anterior segment parameters in patients receiving systemic isotretinoin treatment. Methods This prospective cross-sectional study included 66 eyes of 33 patients who were started on oral isotretinoin therapy for severe acne vulgaris. All patients were evaluated in terms of ocular surface tests such as tear break-up time (TBUT) and Schirmer-1 and were asked to fill in the ocular surface disease index (OSDI) questionnaire. Corneal densitometric and topographic measurements were obtained using the Scheimpflug imaging system. Results The mean age of the patients was 19.9 ± 1.6 years, and 21 (63.6%) of the participants were female. The mean OSDI score was significantly higher in the third month than before treatment (20.05 ± 19.38, vs. 26.96 ± 22.94, p = 0.00, respectively). The mean values of the TBUT test were significantly lower in the third month than before treatment (9.06 ± 4.40 sec, vs. 10.71 ± 4.61 sec, p = 0.02, respectively). Mean scores of the Schirmer 1 test showed no statistically significant difference between before treatment and the third month (16.08 ± 8.40 mm, vs. 16.08 ± 8.50 mm, p = 1, respectively). There was no statistically significant difference between before treatment and the third month in the majority of the densitometry measurements in concentric zones. However, the difference tended to be significant between the groups concerning posterior zone 0–2 mm (11.01 ± 0.85 GSU vs. 10.62 ± 0.89 GSU, p = 0.006). The RMS LOAs (front), RMS Total (Total), RMS LOAs Total (Total), RMS HOAs Total (Total), K max, CCT, and CoV values were significantly higher in the third month than before treatment (p < 0.05 for all). Conclusions The dermatology specialists should be aware of the ocular complications of systemic isotretinoin therapy. Therefore, a complete ophthalmologic examination for the prompt apprehension and management of ocular involvement is essential in patients under isotretinoin therapy to increase ocular comfort and adherence to the therapy.

Determination of key prognostic factors for the development of acne recurrence after systemic isotretinoin therapy

Since the 80s of the last century, the most effective drug for the treatment of acne is systemic isotretinoin (SI). The introduction of SI into practice makes it possible to achieve stable clinical remission or complete recovery in 80% of acne patients, regardless of the severity of the disease, however, 20% of patients may experience relapses in the next 1.52 years.&#x0D; Aim. To establish the factors determining the likelihood of acne recurrence after a course of therapy using the systemic isotrtinoin.&#x0D; Materials and methods. After examining 275 patients, 84 patients (50 women and 34 men) who had previously been treated with SI for acne took part in the study, 54 of them had relapses for at least 4 months and the comparison group consisted of 30 patients out of 221 surveyed who did not have relapses after treatment. As part of the study, a retrospective analysis of outpatient records was carried out, data on the history of life and illness, comorbid hormonal pathology in women, anthropometric characteristics were recorded, and the presence of heredity for acne was also taken into account, the severity of acne was assessed using the Investigator's Global Assessment scale; laboratory examination was performed to exclude insulin resistance.&#x0D; Results. The development of relapses after the first course of acne treatment using SI was registered in 19.63%, however, indications for a second course of treatment were stated in 12.00%. The analysis of the data obtained allowed us to determine the main factors that contributed to the development of relapses: severe acne severity, the presence of rashes on the trunk, body mass index more than 25, the presence of hormonal abnormalities in women, scarification, male sex, daily dose less than 0.5 mg/kg, the presence of heredity for acne in both parents, the course dose of SI120 mg/kg, insulin resistance.&#x0D; Conclusion. The issue of studying the factors that can cause the development of acne recurrence after the end of the course of therapy is an extremely urgent problem, due to the fact that taking them into account at the early stages of treatment of patients will increase the percentage of patients with complete clinical remission or recovery.

The effects of the systemic isotretinoin treatment on ocular surface and meibomian glands: a prospective longitudinal study

Purpose To assess the effects of systemic isotretinoin therapy (SIT) on the ocular surface, meibomian glands (MG) and cornea microstructure in acne vulgaris (AV) patients. Methods Patients with AV (n = 20) and healthy controls (n = 20) were enrolled in the study. All participants underwent ocular surface tests in the order of ocular surface disease index (OSDI) questionnaire, corneal sensitivity, tear break-up time (BUT), fluorescein and lissamine green (LG) staining and Schirmer II test with anaesthesia. MG alterations were evaluated with meibography for upper (UE) and lower eyelids (LE) separately. Corneal basal epithelium and subbasal nerve plexus (SNP) were evaluated using In Vivo Confocal Microscopy (IVCM). Results Schirmer II test with anaesthesia, BUT, corneal sensitivity, fluorescein and LG staining grades and OSDI score results showed no difference between the control group and the baseline of the patient group. Whereas the meibomian gland dysfunction (MGD) grades, UE and LE meiboscores were higher in the patient group at the baseline (p = 0.013, p = 0.004, p = 0.008 respectively). The Control group possessed higher numbers of total and long nerve fibres compared with patients at the baseline (p ≤ 0.001 for both two values). Compared to the baseline and the third month, BUT decreased and fluorescein staining grades increased (p = 0.017 and p = 0.043, respectively). MGD grades, UE and LE meiboscores increased in the third month compared to the baseline (p < 0.001, p < 0.001, p = 0.008 respectively). Basal epithelial cell density (BECD) decreased in the third month of SIT (p = 0.043). Conclusions This prospective study showed that systemic Isotretinoin treatment effects not only ocular surface parameters but also corneal and Meibomian glands structure. Considering early alterations in the course of treatment, ophthalmological assessment and follow-up during SIT are mandatory.

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.&#x0D; 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.&#x0D; 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.&#x0D; Results. 100% of patients achieved clinical remission as a result of treatment with systemic isotretinoin.&#x0D; 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).&#x0D; 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).&#x0D; 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

EVALUATION OF THYROID FUNCTION TESTS BEFORE AND AFTER SYSTEMIC ISOTRETINOIN TREATMENT OF ACNE VULGARIS PATIENTS

Background: Acne, also known as acne vulgaris, is a long-term skin disease that occurs when hair follicles are clogged with dead skin cells and oil from the skin. It is characterized by blackheads or whiteheads, pimples, oily skin, and possible scarring. Objective: To evaluate TSH, free T3 and free T4 in patients with acne treated with systemic isotretinoin at baseline and after three months of treatment to find any alteration in TFTs. Patients and methods: This study was conducted on thirty patients with treatment for acne vulgaris. The study was done in Al-Azhar university hospitals from June 2018-February 2019. Results: The mean and standard deviation of age was 30.62 ± (7.6) years. There was no statistical difference in age distribution, i.e. normally distributed. As regard sex, there was 38 (76%) females and 12 (24%) males. The ratio of female to male was 3:1.Serum levels of thyroid function tests were compared by using Wilcoxon comparison test for non-parametric tests. There was a statistically significant difference between both variables. TSH levels markedly elevated in comparison to before treatment. In contrast to TSH levels, T3 and T4 reduced significantly when compared to before treatment levels. Conclusion: Dermatologists need to be aware about possible TFTs abnormalities during systemic isotretinoin therapy. Clinical symptoms regarding thyroid disease for both hypothyroidism and hyperthyroidism should be evaluated regularly at visits, and patients with concomitant thyroid function disease should be monitored for TFTs.

What you need to know about treatment of acne?

In clinical practice, many drugs are used to treat acne, which can have both positive and negative effects. The frequency of adverse reactions can be reduced through the rational and controlled use of drugs, which is impossible without proper training of medical staff and provision of sufficient information to them. Today, the safety of medicines is given much attention in many countries around the world, where various methods of monitoring congenital anomalies and adverse reactions in fetuses and newborns are developed and successfully applied in practice. Systemic isotretinoin occupies one of the leading positions in prescriptions to patients with acne and recurrent acne. Drugs that have long been used in medical practice (Roaccutane) are well studied and their effects are predictable. There are many myths about retinoids. It is known that no drug is 100% safe, so it should be prescribed only when the expected benefits outweigh the risks of its use. It is necessary to prescribe the combined oral contraceptive Belara (in the absence of contraindications specified in the instructions) during treatment with Roaccutane. This is justified and mandatory in accordance with the current guidelines of the European Medicines Agency (EMA, 2018). The combined oral contraceptive must be prescribed 5 weeks before the start of systemic isotretinoin therapy and continued for 5 weeks after the end of retinoid therapy, if no maintenance treatment is required.

Adverse effects of systemic retinoids in treatment of acne: what are doctor and patient afraid of?

Since 1982, oral isotretinoin has been indicated for the treatment of severe nodular-cystic acne, but indications for its use have expanded significantly in recent decades. Dermatologists around the world have begun to actively use isotretinoin for moderate and even mild forms of acne, for acne that is resistant to standard treatment methods, as well as if the patient has a tendency to scar formation, which indirectly confirms that most often the benefits obtained from the use of the drug are significantly higher than the possible risk of side effects. Despite 38 years of experience with isotretinoin, currently some dermatologists unreasonably avoid prescribing the drug. Analysis of the literature and our own experience show that this attitude to acne therapy with systemic isotretinoin is usually associated with insufficient or inadequate awareness of doctors and patients. The most common reason why systemic isotretinoin therapy is not prescribed is fear of the risk of side effects during treatment.Therefore, the aim of the work was to determine the profile and frequency of side effects in acne treatment with systemic isotretinoin. For this purpose, we retrospectively analyzed 76 outpatient records of patients receiving systemic isotretinoin in the complex therapy of acne. Among the patients there were 51 women aged 13 to 42 years and 25 men aged 14 to 39 years. Roaccutane (F. Hoffmann-La Roche Ltd, Switzerland) was used as a systemic therapy for acne. The regimen of therapy with Roaccutane was as follows: for the first 2 months — 0.3—0.4 mg per 1 kg of body weight per day, then with normal biochemical parameters of liver, kidney function, lipid and carbohydrate metabolism, the daily dose increased to 0.5—0.7 mg per 1 kg of the patient’s body weight until a cumulative dose of 120 mg per kg of body weight is reached. In all patients who received Roaccutane for the treatment of acne, side effects were well tolerated, easily corrected and sometimes required only a temporary reduction in its daily dose. Changes in the biochemical blood test were transient: the indicators were restored to normal values after the end of the course of therapy.

Efficacy of omega-3 fatty acids and punctal plugs in the prevention of isotretinoin-associated ocular surface disease.

To investigate the effects of omega-3 fatty acids and punctal plugs on tear film and ocular surface parameters in patients receiving systemic isotretinoin therapy. This is a prospective randomized study that included 180 eyes of 90 patients who had systemic isotretinoin therapy (120-150 mg/kg for at least 4-6 months). Exclusion criteria: DED according to the diagnostic criteria of TFOS DEWS II. Patients were assigned into three groups; (1) O3FAs/PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral O3FAs two capsules twice daily total daily dose of 1040 mg/day for 6 months. (2) PPs group: A soft preloaded silicone plug was inserted in the inferior punctum of both eyes and received oral placebo. (3) Isotretinoin group: No intervention was done. At baseline, 1 week, 1, 3, and 6 months of study, Ocular surface evaluation tests were done in following order: OSDI, tear osmolarity, Schirmer's I test, TBUT, ocular surface staining score, and meibomian gland expression. The changes in measurement of ocular surface evaluation tests including ocular surface disease index (OSDI), tear film breakup time (TFBUT), corneal staining, tear osmolarity, and meibomian gland expression at 6 months. There are significant changes between all groups at 6 months follow-up. The ocular surface parameters were better for the PPs and O3FAs/PPs groups than the isotretinoin group. The isotretinoin group showed worsening of ocular surface parameters including a significant decrease of FTBUT and an increase of OSDI score, corneal staining score, tear osmolarity, and meibomian expression score. There was no significant difference in ST1 throughout the whole study in all groups. At 6 months follow-up, there were no statistically significant differences between PPs and O3FAs/PPs groups except meibomian expression score which showed a significant increase in PPs group. Our cohort highlights the beneficial effects of the combination of O3FAs supplementation with PPs in the prevention of isotretinoin-associated OSD in this sample study.

Treatment of Moderate to Severe Acne and Scars With a 650-Microsecond 1064-nm Laser and Isotretinoin

Background: Laser procedures for acne and acne scars have traditionally been postponed for at least 6 to 8 months after the end of systemic isotretinoin therapy. Lower dosages with more modern laser devices having unique energy parameters of high power in microsecond pulse durations have made it possible to administer laser therapy during or shortly after completion of isotretinoin therapy, thus reducing the risk of side effects of isotretinoin.Methods: Patients with moderate to severe facial acne (n=46) and atrophic scars enrolled in a 6-month study. Genetic analysis of patients revealed the presence of polymorphisms of genes Col1A2, MMP3, ESR1, MMP1, and MMP7, which can lead to scar formation. Patients underwent low-dosage isotretinoin therapy (0.2-0.3 mg/kg/day) in combination with facial laser treatment using a 650-microsecond, 1064-nm Nd: YAG laser. Acne severity was graded using the Investigators Global Assessment (IGA) scale and quality of life was evaluated by the Dermatology Life Quality Index (DLQI). Results: IGA parameters decreased from 1.8 ± 0.2 (mean ± SD) initially to 0.5 ± 0.4 at the end of the study, a 72.3% reduction which was significant (P<0.01). The DLQI index decreased from 10.1 ± 1.3 initially to 2.8 ± 1.2, a 72.3%, a significant reduction (P<0.01). Inflammatory elements resolved without scarring. Laser treatment was well tolerated and improvement in pre-existing scars was noticeable. Conclusions: The 650-microsecond, 1064-nm laser in combination with low-dose isotretinoin is safe and effective in patients with acne complicated by atrophic scars and genetically prone to post-acne scarring. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5108

Effects of oral ısotretinoin on normal and wounded nasal mucosa: an experimental study.

We aimed to investigate the effect of systemic isotretinoin therapy on normal and wounded nasal septal mucosa histopathologically in an experimental rabbit model. Circular mucosal defect with a 7mm diameter was made in the left septum of 12 New Zealand white rabbits. The rabbits were divided into two groups (six rabbits in each group) oral isotretinoin was given with olive oil at the operation day to the first group. The control group was only oil given group. The harvested septum mucosas were divided into four groups (1-wounded-drug given side, 2-unwounded and drug-given side, 3-wounded-control and 4-unwounded-control side). The diameter of the defect, mucosal thickness, epithelial thickness, ciliated cell level, goblet cell level and inflammation were evaluated every week for 4weeks. At both wounded and normal side, thinning of normal respiratory ciliated epithelium was observed in the postoperative period. In study group at the wounded side; mean mucosal thickness was measured 139.66µ (± 26.24), and in the control group, mean mucosal thickness was 238.33µ (± 39.7) at the wounded side. (p < 0.001). The difference between the groups in thickness of normal septal mucosa was also statistically significant (p = 0.016) [190µ (± 14.6) and 256.66µ (± 44.66)]. The average cilia level was observed 1.16 in the wounded study group, while the average level was 2.33 in the wounded control group (p = 0.012). Average score measurements of the regenerated mucosa suggested that isotretinoin-given wounded animals have reduced goblet cell recovery, compared to the control both on the regenerated and unwounded mucosas (p = 0.007, p = 0.002, respectively). Inflammation was significantly higher in the wounded isotretinoin group (p = 0.018). Oral isotretinoin has negative effects on epithelial and ciliary regeneration, significantly reduces mucosal thickness and goblet cell counts of the normal and regenerated mucosa, causes severe inflammation and significant reactive changes.

Re-evaluating the need for routine laboratory monitoring in patients taking isotretinoin: A retrospective analysis

Re-evaluating the need for routine laboratory monitoring in patients taking isotretinoin: A retrospective analysis

Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma

The discovery of new genetic determinants of inherited skin disorders has been instrumental to the understanding of epidermal function, differentiation, and renewal. Here, we show that mutations in KDSR (3-ketodihydrosphingosine reductase), encoding an enzyme in the ceramide synthesis pathway, lead to a previously undescribed recessive Mendelian disorder in the progressive symmetric erythrokeratoderma spectrum. This disorder is characterized by severe lesions of thick scaly skin on the face and genitals and thickened, red, and scaly skin on the hands and feet. Although exome sequencing revealed several of the KDSR mutations, we employed genome sequencing to discover a pathogenic 346 kb inversion in multiple probands, and cDNA sequencing and a splicing assay established that two mutations, including a recurrent silent third base change, cause exon skipping. Immunohistochemistry and yeast complementation studies demonstrated that the mutations cause defects in KDSR function. Systemic isotretinoin therapy has achieved nearly complete resolution in the two probands in whom it has been applied, consistent with the effects of retinoic acid on alternative pathways for ceramide generation.