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.

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.

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.

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.

Embryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report.

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.

How safe and effective is prescribing oral isotretinoin to treat acne in patients on renal dialysis? A systematic review.

BACKGROUND: Patients on renal dialysis often develop severe acne. In spite of this, the literature remains scarce about the use of isotretinoin for the treatment of acne in this group of patients, and many clinicians remain apprehensive and hesitant to use it. AIM: To systematically review the literature surrounding the safety and efficacy of isotretinoin for the treatment of acne in patients on renal dialysis. METHODS: Four electronic databases (MEDLINE, Embase, CINAHL, Emcare) were systematically searched in March 2021. The search strategy incorporated the terms 'isotretinoin', 'renal', 'kidney', 'dialysis' and 'acne', along with terms closely related to these. Studies were considered eligible if they reported the use of isotretinoin for treatment of acne in patients with renal impairment or on renal dialysis, and if they had relevant implications to this topic. RESULTS: The search resulted in a total of 63 results. Using the PRISMA approach, 11 articles were deemed relevant to this review: 1 randomized single-blinded placebo-controlled trial, 2 case series, 2 retrospective studies and 6 case reports. Hence the level of evidence was mostly low (Grading of Recommendations, Assessment, Development and Evaluations level 3). CONCLUSION: This review of the literature suggests that low-dose isotretinoin (10-20 mg) can safely and successfully be used to treat severe acne in patients on renal dialysis, leading to a significant improvement in their quality of life. As the current literature on this topic is scarce, more studies would be beneficial to further establish the safe use of isotretinoin in patients on renal dialysis.

A detailed regimen of isotretinoin for the successful treatment of severe keratosis pilaris.

Although a well-known recommended treatment option, there are currently no studies that describe the detailed regimen of isotretinoin for the treatment of primary keratosis pilaris. Based on previous studies involving other hyperkeratotic disorders, this report describes a safe and effective treatment course of isotretinoin for severe keratosis pilaris.

Oral isotretinoin: 29 years of medical malpractice cases in the United States.

BACKGROUND: Reviews of malpractice claims in the United States show trends of increasing payments with statistically higher payouts for more debilitating and permanent injuries. OBJECTIVES: To examine lawsuits involving notable associated adverse reactions of isotretinoin. METHODS: Court records of US legal trials from 1985 to 2014 were obtained from a major computerized database: LexisNexis. Data were compiled on the demographics of the defendant and plaintiff, litigation over adverse drug reaction, legal allegations, verdicts, and ruling decisions. RESULTS: Seventy unique cases met inclusion criteria and were selected for review. Forty-four cases cited physicians, and 26 cited a pharmaceutical company. When data from physician and pharmaceutical company litigations were combined, individuals 17 years or younger were more likely to be granted litigation outcomes in their favor compared with adults (P = .0016). Cases alleging failure to monitor were associated with an outcome in favor of the plaintiff (P = .0379). LIMITATIONS: Cases settled or terminated before going to court could not be reviewed. CONCLUSIONS: Familiarity with malpractice trends through precedent-setting cases will increase physician awareness of common pitfalls, potentially mitigating litigation risk and improving patient care.

ARTICLE: Advances in Oral Isotretinoin Therapy.

Since its approval in 1982, oral isotretinoin has revolutionized acne therapy. However, oral isotretinoin use has long been associated with challenges of variable bioavailability and food dependence. It is recommended to ingest oral isotretinoin with a high-fat meal in order to maximize absorption, but many patients fail to adhere to this recommendation. This may lead to inadequate isotretinoin absorption levels. Patients who fail to achieve isotretinoin target cumulative dose are more likely to experience symptom relapse. To address the challenge of traditional isotretinoin variable bioavailability, subsequent isotretinoin formulations have attempted to improve its absorption abilities. In 2014, an isotretinoin formulation utilizing Lidose technology, known as Absorica, showed significant improvements in absorption levels compared to traditional oral isotretinoin in the fasted state. In 2019, isotretinoin absorption levels were further advanced in a new formulation approved by the FDA known as Absorica LD. Utilizing advanced micronization technology that physically reduces the size of the drug molecule, Absorica LD exhibits twice the absorption levels of Absorica under fasting conditions. In the fed state, Absorica LD achieves similar plasma levels to Absorica with a 20 percent lower dose. Absorica LD also produces consistent serum isotretinoin levels irrespective of gastrointestinal contents. By eliminating the “food effect” seen in traditional oral isotretinoin, Absorica LD has the potential to improve patient adherence and long-term patient outcomes. J Drugs Dermatol. 20:5(Suppl):s5-11.

Prescribing Isotretinoin for Transgender Patients: A Call to Action and Recommendations.

Case Scenerio: A 26-year-old patient presents to the dermatology clinic with severe nodulocystic scarring acne. The patient identifies as a transgender male and notes that he has been receiving hormone replacement therapy for the past 4 years with weekly intramuscular testosterone injections.

Differences in Depression and Distress Between Acne Patients on Isotretinoin vs Oral Antibiotics.

BACKGROUND: Little is known regarding differential effects of systemic anti-acne treatments on mental health. OBJECTIVE: To determine whether differences exist in mental health outcomes between acne patients treated with isotretinoin versus oral antibiotics (doxycycline, minocycline, or tetracycline). METHODS: Population study utilizing the 2004-2017 Medical Expenditure Panel Survey. Depressive symptoms were assessed using Patient Health Questionnaire 2 (PHQ-2); psychological distress was measured by the Kessler 6-Item Psychological Distress Scale (K6). Acne patients completed both the PHQ-2 and K6 during treatment with isotretinoin or oral antibiotics. Lower scores on both measures indicate better mental health outcomes. RESULTS: After adjusting for socio-demographic characteristics, patients on isotretinoin had fewer depressive symptoms than patients on oral antibiotics, as measured by mean PHQ-2 scores (isotretinoin 0.280 vs oral antibiotics 0.656, difference=0.337, P<0.01). The adjusted comparison also showed patients on isotretinoin had less psychological distress than patients on oral antibiotics, as measured by K6 scores (isotretinoin 2.494 vs oral antibiotics 3.433, difference=0.759, P=0.043). LIMITATIONS: No direct assessment of acne severity. CONCLUSION: Acne patients on isotretinoin experienced less depressive symptoms and psychological distress as compared to oral antibiotics. J Drugs Dermatol. 2021;20(2):172-177. doi:10.36849/JDD.5559.

Isotretinoin plus 420 nm intense pulsed light versus isotretinoin alone for the treatment of acne vulgaris: a randomized, controlled study of efficacy, safety, and patient satisfaction in Chinese subjects.

Either isotretinoin or intense pulsed light (IPL) proved to be effective to alleviate acne lesions, but the combined treatment has rarely been reported. The study aimed to evaluate the efficacy, safety, and patient satisfaction of isotretinoin and 420 nm IPL combined treatment. Forty-seven patients with facial acne with Global Evaluation Acne (GEA) graded 2-4 were randomized into study group and control group. The patients in the control group received oral isotretinoin for 8 weeks. The patients in the study group were treated with oral isotretinoin for 8 weeks, together with a biweekly 420 nm IPL treatment for 4 weeks. Topical agents included adapalene and fusidic acid. Efficacy was evaluated using digital photographies taken at baseline and week 12 by an independent dermatologist, including GEA grade, lesion count, lesion reduction percentage, and effective rate. All patients completed a questionnaire about dermatology life quality index (DLQI) and satisfaction visual analog scale (VAS) on week 12, and were followed up for another 2 months. Adverse events were recorded. The patients in the study group experienced significant reduction in GEA grade, total lesions, and inflammatory lesions on week 12, compared with the control group (p < 0.05). The patients in the study group reported lower DLQI and higher VAS satisfaction (p < 0.05) and experienced lower incidence of relapse (p < 0.05). No severe adverse event was identified in both groups. Compared with isotretinoin alone, isotretinoin and 420 nm IPL combined treatment proved to be more effective within limited treatment duration. It was well-tolerated and the patients' satisfaction was high.

Lupus miliaris disseminatus faciei with complete response to isotretinoin.

Lupus miliaris disseminatus faciei is an uncommon type of granulomatous rosacea characterized by a papular eruption in the central regions of the face. A 43-year-old woman presented with an asymptomatic papular eruption on the face that had developed over a period of five months. Physical examination revealed multiple, small, reddish-brown papules, distributed symmetrically on the central area of the face. A biopsy was taken, showing dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. No foreign bodies were found in granulomas and no mycobacterial or fungal components were detected. On the basis of these findings, the diagnosis of lupus miliaris disseminatus faciei was made. The patient was given oral isotretinoin 20mg/day with initial slow response. After 6 months' treatment the lesions completely disappeared. Many authors consider this entity to be a variant of granulomatous rosacea. It is a chronic condition that primarily affects young adults. Treatment is usually unsatisfactory. Therapies with corticosterois, tetracyclines, retinoids, clofazimine or topical tacrolimus have been described but there is a lack of controlled studies and convincing results. Our success with a 6-month course of low dose isotretinoin suggests consideration of a longer trial prior to abandoning this as treatment.

Regorafenib is effective against neuroblastoma in vitro and in vivo and inhibits the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways.

BACKGROUND: Regorafenib is an inhibitor of multiple kinases with aberrant expression and activity in neuroblastoma tumours that have potential roles in neuroblastoma pathogenesis. METHODS: We evaluated neuroblastoma cells treated with regorafenib for cell viability and confluence, and analysed treated cells for apoptosis and cell cycle progression. We evaluated the efficacy of regorafenib in vivo using an orthotopic xenograft model. We evaluated regorafenib-mediated inhibition of kinase targets and performed reverse-phase protein array (RPPA) analysis of neuroblastoma cells treated with regorafenib. Lastly, we evaluated the efficacy and effects of the combination of regorafenib and 13-cis-retinoic acid on intracellular signalling. RESULTS: Regorafenib treatment resulted in reduced neuroblastoma cell viability and confluence, with both induction of apoptosis and of cell cycle arrest. Regorafenib treatment inhibits known receptor tyrosine kinase targets RET and PDGFRß and intracellular signalling through the RAS/MAPK, PI3K/Akt/mTOR and Fos/Jun pathways. Regorafenib is effective against neuroblastoma tumours in vivo, and the combination of regorafenib and 13-cis-retinoic acid demonstrates enhanced efficacy compared with regorafenib alone. CONCLUSIONS: The effects of regorafenib on multiple intracellular signalling pathways and the potential additional efficacy when combined with 13-cis-retinoic acid represent opportunities to develop treatment regimens incorporating regorafenib for children with neuroblastoma.

Premature epiphyseal growth plate arrest after isotretinoin therapy for high-risk neuroblastoma: A case series and review of the literature.

BACKGROUND: Vitamin A-derived retinoids have been reported to cause skeletal abnormalities ranging from hypercalcemia to premature epiphyseal closure. Isotretinoin is a retinoid used as standard therapy for high-risk neuroblastoma and has been reported to cause premature epiphyseal growth plate arrest. PROCEDURE: We identified patients from the Children's Hospital Los Angeles (CHLA) database with high-risk neuroblastoma diagnosed from 1991 to 2018 who experienced premature epiphyseal growth plate arrest and compared their characteristics to other patients with high-risk neuroblastoma. We then performed a literature review of this complication. Data collection included diagnosis age of neuroblastoma, presentation age, agent of exposure, dose, exposure range, and skeletal deformity. RESULTS: Among 216 patients, high-risk neuroblastoma was diagnosed before age of five years (n = 165), between ages of 5 and 10 years (n = 41), and after 10 years of age (n = 13). Three out of 216 patients developed premature epiphyseal growth arrest after isotretinoin exposure (overall incidence = 1.38%). The incidence of bony abnormalities was significantly higher in patients diagnosed in 5- to 10-year age group than in other two groups (P = 0.014). Literature review identified eight additional patients with neuroblastoma who presented with retinoid associated skeletal abnormalities. The median range of isotretinoin exposure for these 11 patients was between 6.5 and 7.625 years (range, 2-14) with no cases of isotretinoin therapy completion before age 5 years. CONCLUSION: Bone toxicity associated with isotretinoin exposure is a concern. Growth plate arrest is a serious adverse effect that is attributable to isotretinoin therapy. Our findings suggest the prepubescent growth plate may be most at risk, and we recommend special attention to this population.

The clinical utility of laboratory monitoring during isotretinoin therapy for acne and changes to monitoring practices over time.

BACKGROUND: As a result of concerns about hypertriglyceridemia, liver enzyme abnormalities, and leukopenia during isotretinoin therapy for acne, patients are often monitored closely with routine laboratory assessments, although the value of this practice has been questioned. METHODS: We conducted a cohort study of patients receiving isotretinoin for acne between January 1, 2008, and June 30, 2017, using the OptumInsights Electronic Health Record Database (Optum, Eden Prairie, MN) to evaluate the frequency of laboratory abnormalities. Poisson regression was used to evaluate for changes to the frequency of routine laboratory monitoring over time. RESULTS: Among 1863 patients treated with isotretinoin, grade 3 or greater triglyceride and liver function testing abnormalities were noted in fewer than 1% and 0.5% of patients screened, respectively. No grade 3 or greater cholesterol or complete blood count abnormalities were observed. There were no meaningful changes in the frequency of laboratory monitoring over time. LIMITATIONS: Limitations include that we are unable to evaluate the clinical notes to understand the exact clinical decision making when clinicians encountered abnormal laboratory values. CONCLUSION: Although laboratory abnormalities are rare and often do not influence management, frequent laboratory monitoring remains a common practice. There are opportunities to improve the quality of care among patients being treated with isotretinoin for acne by reducing the frequency of lipid and liver function monitoring and by eliminating complete blood count monitoring.

Isotretinoin: Still the cause of anxiety for teratogenicity.

Isotretinoin is known as a potent teratogenic agent. Pregnancy should be ruled out before isotretinoin is prescribed. In this study, we evaluated the fetal outcomes of pregnant women who had inadvertently been exposed to isotretinoin during or before pregnancy. We collected data of pregnant women who had admitted to the Teratology Information Service due to isotretinoin exposure. Data regarding medications and comorbidities were documented. Outcomes were grouped as: live births, stillbirths, live births with congenital malformations, induced abortions (due to fetal abnormalities), spontaneous abortions, and elective abortions. We found that three women had gone to elective abortions. Three babies were live born without birth defects, of which, maternal exposure periods were between 0 and 3 weeks, 9 and 10 weeks before last menstrual period. One woman, exposed to isotretinoin up to the fourth week of gestation, decided ongoing her pregnancy with no current drug-related complications. Although many risk management programs worldwide have been used to prevent isotretinoin-related teratogenicity, the results of the present study showed that women became pregnant during isotretinoin intake and opted for pregnancy termination. Attention should be paid to the risk management programs mandating effective contraceptions, in order to lessen the drug-related terminations.

The effects of isotretinoin therapy on the biliary system.

The aim of the present study was to investigate the potential effects of isotretinoin on the biliary system in patients with acne vulgaris receiving isotretinoin therapy. This was a preliminary retrospective study involving 40 patients with severe acne vulgaris who attended the dermatology clinic and were administered different doses (20 or 30 mg/day) of isotretinoin. Serum levels of AST, ALT, ALP, GGT, total bilirubin, direct bilirubin, and indirect bilirubin at the beginning and at the first month of therapy were scanned, recorded, and statistically analyzed. Total and indirect bilirubin levels at the first month of treatment in 30 patients, receiving isotretinoin at a dose of 20 mg/day, were significantly lower compared to the baseline values (p = .02 and p = .03, respectively), whereas AST and GGT serum levels were significantly higher (p = .003 and p = .006 respectively). No significant reduction in total and indirect bilirubin levels was detectable at the first month of treatment in 10 patients receiving isotretinoin at a dose of 30 mg/day; however, AST, ALP, and GGT levels were significantly elevated in these patients (p = .023; p = .004; and p = .001, respectively). To our knowledge, there is no previous study investigating the effects of isotretinoin on the biliary system, and, therefore, the present study is a preliminary one. Our findings implicate that low dose (20 mg/day) isotretinoin therapy can potentially reduce total and indirect bilirubin levels. Long-term, large-scale, prospective studies with patients receiving different doses of isotretinoin may provide more reliable information regarding the bilirubin lowering effects of isotretinoin and optimum dosing for achieving this clinical effect.