Efficacy and Safety of Micronized Isotretinoin Administered Once Daily Without Food in Patients With Recalcitrant Nodular Acne.

INTRODUCTION: Micronized isotretinoin 0.4 to 0.8 mg/kg/day administered in 2 divided doses with or without meals is approved for the treatment of severe nodular acne in patients aged 12 years or older. Although practitioners may suggest once-daily dosing to increase patient compliance, supporting data are limited. METHODS: In this pilot study, patients aged 12 years or older with severe nodular acne (Investigator's Global Assessment [IGA] =>4 and >5 facial nodules) received once-daily micronized isotretinoin 0.4 to 0.8 mg/kg/day without food for 20 weeks. The coprimary efficacy endpoints were changes from baseline in nodular lesion count (NLC) and percentage of patients with a =>90% reduction in NLC at week 24. Secondary endpoints included percentage of patients achieving IGA 0/1; reductions in inflammatory lesion count (ILC) and noninflammatory lesion count (NILC); adverse events (AEs); and severity of erythema, dryness, peeling, oiliness, burning, and pruritus. Analyses included all enrolled patients with the last observation carried forward. RESULTS: Twenty-two of 24 patients completed the study. From baseline to week 24, NLC decreased by a median (quartile [Q]1, Q3) of 6 (5, 7), all patients experienced complete clearance of nodules, 23/24 (96%) patients achieved IGA 0/1, and ILC and NILC decreased by a mean +/- standard deviation of 97.8% +/- 5.7% and 98.4% +/- 6.2%, respectively (all P<0.0001). There were small, significant, early increases in the severity of erythema, dryness, and peeling; 2 patients experienced 3 AEs considered unrelated to treatment. CONCLUSIONS: Once-daily micronized isotretinoin administered without food was efficacious and well tolerated in patients with severe nodular acne.  J Drugs Dermatol. 2024;23(6):423-428.     doi:10.36849/JDD.7863.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Isotretinoin's Effect on Fasting Lipid Profile in Acne Patients.

OBJECTIVE: To determine the isotretinoin's effect on fasting lipid profile in patients with acne. STUDY DESIGN: Observational study. Place and Duration of the Study: Outpatient Department of Dermatology, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan, from 22nd June to 21st December 2022. METHODOLOGY: Patients of clinically moderate and severe acne were selected and prescribed a dose of 0.5mg /kg cap isotretinoin for 6 months. They were advised to get a fasting lipid profile at the baseline and then after two months of isotretinoin therapy. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 grading system and Adult Treatment Panel III were used for the grading of abnormalities. McNemar Bowker test was used to assess the difference in variables [serum triglycerides (TGs), cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL)] at the baseline and after 2 months follow-up. RESULTS: A total of 214 patients were evaluated. After 2 months of isotretinoin therapy, TGs and cholesterol levels were elevated to higher grade in 2% of the patients. Likewise in 1% of patients, LDL levels rised to higher grade. Moreover, HDL levels declined to lower grade in 2% of the patients taking isotretinoin. CONCLUSION: Insignificant alterations in the various serum lipid parameters were observed in acne patients during isotretinoin therapy. It is advisable to obtain a baseline fasting lipid profile in all acne patients on isotretinoin and repeated in those with baseline abnormal levels and in patients with a clinical sign of metabolic syndrome and a family history of dyslipidemias. KEY WORDS: Acne, Hyperlipidemias, Isotretinoin, Laboratory monitoring.

Contraceptive counseling for iPLEDGE and its burden on dermatologists.

Since 2006, iPLEDGE, a risk evaluation and mitigation strategy (REMS), has attempted to prevent fetal exposures in people taking isotretinoin through contraceptive requirements and regular pregnancy testing. There has been criticism of iPLEDGE's requirements, results, and accessibility. iPLEDGE has placed significant burdens on physicians, patients, and administrative staff. Some level of burden is acceptable to prevent fetal exposures, but iPLEDGE burdens are so strenuous that physicians may choose not to prescribe isotretinoin because of them. There are several evidence-based adaptations that iPLEDGE and physicians can enact to improve the isotretinoin experience. First, physicians can practice shared-decision making in contraceptive counseling and educate patients on long-acting reversible contraceptives (LARCs) to improve the counseling process and outcomes. Second, physicians can take advantage of the reimbursed iPLEDGE contraceptive counseling sessions and refer patients accordingly. Finally, iPLEDGE should recognize the variation in efficacy among contraceptives. Specifically, LARCs and permanent surgical sterilization should be exempt from certain iPLEDGE requirements such as monthly pregnancy testing and attestations. iPLEDGE should work with dermatologists for the continual improvement of iPLEDGE. Communication, repetitive reassessment, and subsequent adaptations will result in better care for patients requiring isotretinoin.

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.

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.

Emergency Contraception for Patients Taking Isotretinoin.

This Viewpoint explains the need for emergency contraception as the last chance to avoid pregnancy for patients taking isotretinoin.

Editor's Highlights - April 2024.

In the April issue of the Journal, we highlight the topical application of honey and garlic, detailing their active ingredients and elucidating the mechanisms by which these natural agents work. Additionally, this issue will spotlight the disparities in laboratory monitoring among patients undergoing isotretinoin treatment and provide significant data regarding the nonassociation between isotretinoin use and impulsivity in individuals with acne.

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl – case report and literature review

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient’s features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent. (AU)

A review of isotretinoin in the treatment of frontal fibrosing alopecia.

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

Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review.

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

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.

A novel predictive method for risk stratification in acne patients receiving isotretinoin: an analysis of laboratory abnormalities and changes in inflammatory parameters.

INTRODUCTION: Isotretinoin is a widely used, effective medication for moderate to severe acne. It is typically used for several months, which necessitates regular laboratory monitoring. However, consensus on the optimal assessment frequency is lacking. METHOD: This is a single-center retrospective study on 1182 patients who received isotretinoin for acne at the Dermatology Clinic in Jordan University Hospital over 5 years. RESULTS: Of the 1182 patients, 892 (76.57% females) met the inclusion criteria. An increase in the proportion of patients with abnormal triglycerides and total cholesterol levels from baseline to the sixth month was observed (p < 0.05). Conversely, differences in the number of patients with abnormal AST, ALT, and CBC were not found throughout treatment (p > 0.05). Moreover, there was a decrease in the neutrophil-to-lymphocyte ratio (NLR) ratio and systemic inflammatory index (SII) after the sixth month of isotretinoin treatment compared to the baseline (p = 0.012 and p = 0.021, respectively). CONCLUSIONS: We found that a baseline cholesterol level of 163.9 mg/dl and a baseline triglycerides level of 85.5 mg/dL are highly specific and sensitive in detecting grade 1 abnormalities at the one-month follow-up. This novel prediction approach serves as an effective risk stratification method for isotretinoin acne patients.