Effect of isotretinoin on CYP2D6 and CYP3A activity in patients with severe acne.

AIMS: Previously, retinoids have decreased CYP2D6 mRNA expression in vitro and induced CYP3A4 in vitro and in vivo. This study aimed to determine whether isotretinoin administration changes CYP2D6 and CYP3A activities in patients with severe acne. METHODS: Thirty-three patients (22 females and 11 males, 23.5 ± 6.0 years old) expected to receive isotretinoin treatment completed the study. All participants were genotyped for CYP2D6 and CYP3A5. Participants received dextromethorphan (DM) 30 mg orally as a dual-probe substrate of CYP2D6 and CYP3A activity at two study timepoints: pre-isotretinoin treatment and with isotretinoin for at least 1 week. The concentrations of isotretinoin, DM and their metabolites were measured in 2-h postdose plasma samples and in cumulative 0-4-h urine collections using liquid chromatography-mass spectrometry. RESULTS: In CYP2D6 extensive metabolizers, the urinary dextrorphan (DX)/DM metabolic ratio (MR) (CYP2D6 activity marker) was numerically, but not significantly, lower with isotretinoin administration compared to pre-isotretinoin (geometric mean ratio [GMR] [90% confidence interval (CI)] 0.78 [0.55, 1.11]). The urinary 3-hydroxymorphinan (3HM)/DX MR (CYP3A activity marker) was increased (GMR 1.18 [1.03, 1.35]) and the urinary DX-O-glucuronide/DX MR (proposed UGT2B marker) was increased (GMR 1.22 [1.06, 1.39]) with isotretinoin administration compared to pre-isotretinoin. CONCLUSIONS: Administration of isotretinoin did not significantly reduce CYP2D6 activity in extensive metabolizers, suggesting that the predicted downregulation of CYP2D6 based on in vitro data does not translate into humans. We observed a modest increase in CYP3A activity (predominantly CYP3A4) with isotretinoin treatment. The data also suggest that DX glucuronidation is increased following isotretinoin administration.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Fractional Radiofrequency and Oral Isotretinoin-A Prospective Randomized Controlled Split-Face Trial Comparing Concurrent Versus Delayed Fractional Radiofrequency Treatment for Acne Scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional radiofrequency (FRF) in patients treated concurrently with ITN. METHODS: We conducted a prospective randomized control 3-arm comparative trial to evaluate the treatment of acne scars. Patients received one of three treatment options: (A) ITN and FRF concurrent treatment, (B) ITN monotherapy, and (C) FRF 6 months post-ITN treatment. Patients in the FRF cohorts received three monthly sessions. Patients were followed for adverse effects up to 6-9 months post-FRF treatment. Final cosmesis was scored by three independent dermatologists using two scales: the Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA) and an internal 5-point investigator's scale, indicating the percentage of improvement. Subjective analyses by patients were also assessed. RESULTS: Objective and subjective analyses revealed improvement in the ITN-FRF cohort, which was superior to the delayed FRF cohort and the ITN monotherapy cohort. Specifically, the concurrently treated cohort (ITN-FRF) had a significant reduction in acne scar volume from baseline mean (151.1 ± 44.7 to 97.0 ± 31.2, p < 0.005), outperforming both the delayed FRF and monotherapy ITN treatment cohorts, respectively (155.4 ± 37.8 to 122.0 ± 46.2, 144.6 ± 82.8 to 132.4 ± 62.7). Additionally, the concurrently treated cohort demonstrated improved ECCA scores (36.8 ± 15.5), significantly better than the ITN monotherapy cohort (101.5 ± 20.1, p < 0.01). LIMITATIONS: Limited patient sample size: 38 patients completed the study; mostly Fitzpatrick Type II-III skin; photographic assessments utilized. CONCLUSION: Per our prospective trial, concurrent treatment of ITN-FRF is superior to delayed FRF treatment 6 months post-ITN cessation.

Fractional ablative CO2 laser and oral isotretinoin-A prospective randomized controlled split-face trial comparing concurrent versus delayed laser treatment for acne scars.

BACKGROUND: Therapeutic dogma has been to treat acne scars with ablative fractional laser no less than 6 months after isotretinoin (ITN) cessation. OBJECTIVE: To evaluate the safety and efficacy of fractional ablative CO2 laser (FACL) in patients treated concurrently with ITN. METHODS: We conducted a prospective split-face randomized control trial in patients treated with FACL concurrently with ITN versus patients treated with FACL 6 months post-ITN treatment. Patients received 3 monthly sessions of FACL with concurrent ITN treatment on half of the face; the other side of the face received the same FACL treatment regimen 6 months post-ITN cessation. Patients were followed for adverse effects up to 6 months post-FACL treatment. Final cosmesis was scored using the Quantitative Global Acne Scarring Grading System (GASGS) by three independent dermatologists. RESULTS: The GASGS of the concurrent ITN-FACL treated side of the face was significantly lower than the side treated with delayed laser therapy (4.7 ± 2.5 vs. 7.7 ± 2.9, respectively, p < 0.001). LIMITATIONS: The laser's settings were standardized, and not adjusted per patient skin type. CONCLUSION: Per our prospective trial, concurrent treatment of FACL -ITN is superior to delayed FACL treatment 6 months post-ITN cessation. Fractional ablative laser treatment is effective in improving acne scars, which persist despite isotretinoin therapy.

Effects of isotretinoin on tooth movement, orthodontically induced and non-orthodontic root resorption: A micro-CT and study.

OBJECTIVES: This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. MATERIALS AND METHODS: Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. RESULTS: Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). CONCLUSIONS: Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

Linear eczema induced by oral isotretinoin.

Eczema can manifest in a linear arrangement, as can other inflammatory conditions. We report a case of a teenager who, during treatment with oral isotretinoin for acne, developed a generalized eczematous dermatitis together with a superimposed linear eczema on her posterior lower limb. We hypothesize that a postzygotic mutation caused an increased sensitivity to the impact of oral isotretinoin on the epidermal skin barrier structure and lipid composition within a specific skin segment.

The occurrence of mental health symptoms in isotretinoin-treated adolescents.

BACKGROUND: Isotretinoin treatment for acne can reduce adverse psychiatric outcomes in adults, but there has been little investigation of the incidence of psychiatric outcomes in treated adolescents. METHODS: This retrospective cohort study using the Rochester Epidemiology Project identified 606 patients aged 12-18 prescribed isotretinoin over a 10-year period between January 1, 2008 and December 31, 2017. Medical records were reviewed to identify psychiatric diagnoses before and during isotretinoin therapy, as well as psychiatric symptoms not captured by formal diagnoses and changes to isotretinoin dosing because of psychiatric diagnoses or symptoms. RESULTS: One hundred seventy-seven (29.2%) had a psychiatric diagnosis prior to isotretinoin initiation, but 98 (16.2%) had a new psychiatric diagnosis or psychiatric symptom while taking isotretinoin. Patients with a psychiatric history were no more likely than those without to receive a new psychiatric diagnosis during treatment (4.5% vs. 3.7%; p = .650), but did experience more psychiatric symptoms, primarily low mood and mood swings (23.7% vs. 7.7%; p < .001). Only 25.5% of the 98 with a new psychiatric diagnosis or psychiatric symptom had a subsequent dose change. A dose change was more likely if patients received a new psychiatric diagnosis (41.7% vs. 20.3%; p = .037) or patients did not have a psychosocial explanation for psychiatric symptoms (34.4% vs. 10.8%; p = .009). CONCLUSIONS: A substantial proportion of adolescent patients prescribed isotretinoin had a prior psychiatric diagnosis. This predicts more psychiatric symptoms during isotretinoin treatment. Adolescents with a psychiatric history who have worsening symptoms and those with new-onset psychiatric symptoms would benefit from close monitoring while taking isotretinoin.

Evaluating the Readability of the iPledge Comprehension Assessment and its Impact on Isotretinoin Accessibility.

Isotretinoin, the standard treatment for severe nodular acne, is subject to stringent iPLEDGE regulations due to its teratogenic risks, requiring monthly assessments for patients of childbearing potential. Analysis of the iPLEDGE Comprehension Assessment (iPCA) revealed an average readability score of grade 8.5, exceeding the recommended grade 6 level for optimal patient comprehension. The complex language of iPCA may hinder patients from accessing treatment, contributing to delays and potential discontinuation, especially among female patients. While the overall number of isotretinoin-exposed pregnancies has decreased since the inception of iPledge, several hundred pregnancies continue to be reported, and simplification of iPCA presents one avenue to improve patient comprehension, safety, and ensuring equitable access to isotretinoin.

Prescription retinoid and contraception use in women in Australia: A population-based study.

BACKGROUND/OBECTIVES: Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly. METHODS: This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level. RESULTS: There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021. CONCLUSIONS: Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Enhancing Bioavailability: Advances in Oral Isotretinoin Formulations.

Oral isotretinoin continues to be unsurpassed in efficacy for acne. However, it is associated with potential adverse events including risk of fetal defects, necessitating appropriate mitigation strategies. Furthermore, the variance in bioavailability of the original formulation when ingested in fed versus fasted conditions can lead to differences in daily dosing and duration of exposure. Advances in formulation, with lidose encapsulation and subsequently with micronization, have led to iterative improvements in reducing bioavailability variation between fed and fasted conditions. Differences in bioavailability during fasting were 60% less for originator oral isotretinoin, 33% less for lidose-encapsulated form, and 20% less for micronized-isotretinoin formulation. The latter also demonstrated overall greater bioavailability such that a 20% dose reduction was required compared to the originator and lidose-encapsulated formulations. By reducing the effect of high-fat/high calorie food co-ingestion, this micronized formulation may facilitate clarity in determining appropriate oral isotretinoin dose requirements in achieving optimal patient outcomes.

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.

Effect of isotretinoin treatment on inflammatory and hematological parameters in patients with acne vulgaris.

PURPOSE: Although the inflammatory and anti-inflammatory effects of isotretinoin (ISO) treatment in patients with acne vulgaris have been discussed in the literature in recent years, no sensitive and specific marker has been found in studies so far. Neutrophil/HDL (high-density lipoprotein) (NHR), lymphocyte/HD L(LHR), platelet/HDL (PHR), and lymphocyte/monocyte (LMR) are new biomarkers related to inflammation. Triglyceride/HDL (TG/HDL), LDL/HDL, and total cholesterol/HDL have been shown to be cardiometabolic risk factors predicting both cardiovascular disease risk and metabolic risk, rather than just a simple dyslipidemia scale. To our knowledge, the relationship between these parameters and ISO treatment has never been studied before. We aimed to evaluate the immuno-inflammatory response of ISO treatment in patients with acne vulgaris with NHR, LHR, PHR, LMR, TG/HDL, LDL/HDL, and total cholesterol/HDL parameters. MATERIALS AND METHODS: In this study, 153 patients who received oral ISO treatment for at least 3 months with a diagnosis of moderate-severe acne vulgaris were evaluated retrospectively. Patients were given oral isotretinoin at a dose of 0.5-1 mg/kg. Pre and post-treatment leukocyte (WBC), neutrophil (NE), lymphocyte (LY), platelet (PLT), red cell distribution width (RDW), plateletcrit (PCT), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), mean platelet volume (MPV), monocyte/lymphocyte (MLR), LMR, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, MHR, NHR, LHR, PHR, TG/HDL, total cholesterol/HDL, LDL/HDL parameters were evaluated. RESULTS: It was found that post-treatment WBC and MPV values increased statistically significantly; NLR, neutrophil, and PCT values, on the other hand, decreased significantly (p < 0.05). No statistically significant change was detected in PLR, MLR, LMR, MHR, NHR, LHR, PHR, lymphocyte, monocyte, platelet, and RDW parameters (p > 0.05). It was determined that post-treatment total cholesterol, triglyceride, VLDL, and LDL levels increased statistically significantly; however, the HDL level decreased significantly (p < 0.05). Levels of total cholesterol/HDL, TG/HDL, and LDL/HDL were also found to increase statistically significantly (p < 0.05). CONCLUSION: Our study suggests that the MPV and NLR ratio as biomarkers can be used as indicators of atherosclerosis-related inflammation due to ISO treatment, but the MHR, NHR, LHR, PHR, MLR, LMR ratios cannot be used. Moreover, we believe that the ratios of TG/HDL, LDL/HDL, and total cholesterol/HDL offer a new contribution as indicators of cardiovascular risk and systemic inflammation related to ISO treatment.

Evaluation of isotretinoin effects on depression, sleep apnea and sleep quality.

BACKGROUND: Isotretinoin is used to treat severe acne, treatment-resistant moderate acne, and acne that leads to scarring or psychological distress. It has many side effects and is also associated with depression, sleep apnea, and sleep disturbances. OBJECTIVES: In this study, we aimed to evaluate the effects of isotretinoin on depression, sleep apnea, and sleep quality. METHODS: A total of 42 patients diagnosed with acne and started isotretinoin treatment were included in the study. In order to compare the effects of isotretinoin, patients were asked to fill out a questionnaire containing the Beck Depression Inventory (BDI), the Berlin Questionnaire (BQ), and the Pittsburg Sleep Quality Index (PSQI) at baseline and third months of treatment. RESULTS: There was no statistically significant difference in BDI, BQ, and PSQI scores between the 1st and 3rd months of treatment (p = .53, p = .5, p = .35). CONCLUSION: This study showed that isotretinoin had no significant effects on depression and sleep quality.

Evaluation of the protective effects of curcumin-rich turmeric (Curcuma longa) extract against isotretinoin-induced liver damage in rats.

AIM: The aim of this study was to evaluate the protective effect of curcumin-rich turmeric (CRT) extract against isotretinoin (ISO)-induced liver damage through routine biochemical parameters and oxidative stress parameters that indicate liver damage. MATERIAL AND METHOD: 42 albino Wistar rats of 200 g were randomly grouped as Group I: Healthy control, Group II: Sunflower oil, Group III: Curcumin 200 mg/kg, Group IV: ISO control groups (7.5 mg/kg), Group V: Curcumin 50 mg/kg + ISO 7.5 mg/kg, Group VI: Curcumin 100 mg/kg + ISO 7.5 mg/kg, Group VII: Curcumin 200 mg/kg + ISO 7.5 mg/kg. At the end, after the rats were killed, their blood and liver tissues were collected. ALT and AST levels in serum; superoxide dismutase activity (SOD), GSH, and MDA levels in liver tissue were determined. RESULTS: Our results showed that ALT, AST, and MDA levels increased, and SOD and GSH levels decreased in the ISO-administered group compared to the healthy control group. CRT 50, 100, and 200 mg/kg groups were compared to ISO group. A dose-dependent increase in protective effect was observed. A decrease in ALT, AST, and MDA levels, and an increase in SOD and GSH levels were determined. A protective effect was found at all doses. The best protective effect was in the CRT 200 mg/kg group. CONCLUSION: CRT extract can be considered a candidate herbal medicine for the elimination of liver damage in individuals using ISO. However, further experimental and clinical validation should be studied.

Treatment of ocular rosacea: a systematic review.

Rosacea is a common chronic skin disease distributed primarily around the central face. Ocular manifestations of rosacea are poorly studied, and estimates of prevalence vary widely, ranging from 6% to 72% in the rosacea population. Treatment options for ocular rosacea include lid hygiene, topical and oral antibiotics, cyclosporine ophthalmic emulsion, oral vitamin A derivatives, and intense pulsed light; however, a direct comparison of treatment methods for ocular rosacea is lacking. This review aims to compare treatment efficacy and adverse events for different treatment modalities in ocular rosacea. We performed a systematic review by searching Cochrane, MEDLINE and Embase. Title, abstract, full text screening, and data extraction were done in duplicate. Sixty-six articles met the inclusion criteria, representing a total of 1,275 patients. The most effective treatment modalities were topical antimicrobials and oral antibiotics, which achieved complete or partial response in 91% (n = 82/90) and 89% (n = 525/580) of patients respectively, followed by intense pulsed light (89%, n = 97/109 partial response), cyclosporine ophthalmic emulsion (87% n = 40/46), and lid hygiene (65%, n = 67/105). Combination treatments achieved a complete or partial response in 90% (n = 69/77). Results suggest that topical antimicrobials, oral antibiotics, intense pulsed light. and cyclosporine were the most efficacious single modality treatments.

Assessing the Impact of Oral Isotretinoin on the Menstrual Cycle: A Prospective Study on Predictors of Menstrual Irregularities.

Background and Objectives: This study aims to evaluate the association between the use of oral isotretinoin and menstrual irregularities in acne patients with previously regular menstrual cycles. Materials and Methods: A prospective observational study was conducted on 58,599 female patients aged 14 to 36 at King Abdullah University Hospital in Irbid, Jordan. The patients were followed for a period of 4.5 to 8 months during treatment and for 2 months post-treatment. Menstrual cycle changes were documented, and statistical analysis was performed to identify any significant associations. Results: A total of 111 (37.1%) patients, who were previously known to have regular menstrual cycles, complained of menstrual changes while using oral isotretinoin. Ninety-nine of those patients who complained of menstrual changes had their cycles back to normal post-treatment. There is a significant difference in the total accumulative dose between those with changes in menses and those without; p-value [0.008]. The most common change that occurred was amenorrhea (p < 0.001), followed by oligomenorrhea and menorrhagia (p < 0.001 and p = 0.050, respectively). The duration of treatment was a significant predictor of menstrual irregularities, with an odds ratio (OR) of 5.106 (95% CI: 1.371-19.020, p = 0.015), indicating a higher likelihood of menstrual changes with increased treatment duration. The total accumulative dose was also significantly associated with menstrual irregularities (OR = 0.964; 95% CI: 0.939-0.990; p = 0.006). Additionally, a family history of PCOS significantly increased the odds of menstrual irregularities (OR = 3.783; 95% CI: 1.314-10.892; p = 0.014). Conclusions: The study identified that 37.1% of the participants experienced changes in their menstrual cycles while undergoing isotretinoin therapy, with the vast majority (89.2%) returning to normal within two months post-treatment. Our logistic regression analysis pinpointed the duration of isotretinoin treatment, the total accumulative dose, and a family history of PCOS as significant predictors of menstrual irregularities.

Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation.

Purpose: Isotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. Methods: According to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. Results: Characterization studies showed emulsion homogeneity and stability (%T 95.40-99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm-115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. Conclusion: These outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

Pityriasis Rubra Pilaris - a difficult path to optimal treatment. Case report.

Pityriasis Rubra Pilaris is a rare, chronic inflammatory dermatosis of unknown etiology, presenting with erythema and papular eruptions. Treatment is difficult due to the lack of causal therapy, guidelines and requires an individualized approach. The most common treatments are systemic retinoids, immunosuppressants, phototherapy and biological therapy. This article presents the case of a 73-year-old man suffering from type 1 pityriasis rubra pilaris. The patient was initially treated with acitretin, which was discontinued due to hypogammaglobulinemia. This rare side effect of acitretin has not been previously published. As a second-line treatment, the patient received methotrexate, but with no clinical improvement after 3 months and an increase in skin pruritus. Finally, the use of isotretinoin resulted in significant clinical improvement and was well tolerated.

Treatment response to isotretinoin correlates with specific shifts in Cutibacterium acnes strain composition within the follicular microbiome.

There are no drugs as effective as isotretinoin for acne. Deciphering the changes in the microbiome induced by isotretinoin in the pilosebaceous follicle of successfully treated patients can pave the way to identify novel therapeutic alternatives. We determined how the follicular microbiome changes with isotretinoin and identified which alterations correlate with a successful treatment response. Whole genome sequencing was done on casts from facial follicles of acne patients sampled before, during and after isotretinoin treatment. Alterations in the microbiome were assessed and correlated with treatment response at 20 weeks as defined as a 2-grade improvement in global assessment score. We investigated the α-diversity, ß-diversity, relative abundance of individual taxa, Cutibacterium acnes strain composition and bacterial metabolic profiles with a computational approach. We found that increased ß-diversity of the microbiome coincides with a successful treatment response to isotretinoin at 20 weeks. Isotretinoin selectively altered C. acnes strain diversity in SLST A and D clusters, with increased diversity in D1 strains correlating with a successful clinical response. Isotretinoin significantly decreased the prevalence of KEGG Ontology (KO) terms associated with four distinct metabolic pathways inferring that follicular microbes may have limited capacity for growth or survival following treatment. Importantly, these alterations in microbial composition or metabolic profiles were not observed in patients that failed to achieve a successful response at 20 weeks. Alternative approaches to recapitulate this shift in the balance of C. acnes strains and microbiome metabolic function within the follicle may be beneficial in the future treatment of acne.

Modified red light 5-aminolevulinic acid photodynamic therapy versus low-dose isotretinoin therapy for moderate to severe acne vulgaris: A prospective, randomized, multicenter study.

BACKGROUND: Modified 5-aminolevulinic acid photodynamic therapy (M-PDT) and isotretinoin (ISO) are effective treatments for moderate to severe acne vulgaris. OBJECTIVE: To evaluate the efficacy and adverse effects of M-PDT and ISO for moderate to severe acne vulgaris. METHODS: A multicenter, randomized clinical trial was conducted with participants randomly assigned to the M-PDT group (up to 5 weekly sessions following manual comedone extraction) or the ISO group (oral ISO, 0.5 mg/kg/d for 6 months) and followed up to 6-months after therapy. RESULTS: A total of 152 patients were allocated. The overall effective rates in the M-PDT group were significantly higher than the ISO group at 1 month (67.74% vs 10.26%), whereas the opposite was the case 1 month after treatment (75.81% vs 97.44%). Time to achieve 50% lesion improvement in the M-PDT group was significantly less than the ISO group (1 vs 8 weeks). Overall, 70.67% of the ISO group patients experienced systemic side effects such as hepatotoxicity, whereas side effects were skin-limited in the M-PDT group. LIMITATIONS: Limitations of this study included relatively low numbers of participants and high withdrawal rate. CONCLUSION: M-PDT offers a more rapid onset of improvement, comparable overall efficacy, good tolerability, and comparable durability of response compared with ISO.