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)

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.

Practice and attitude of general practitioners towards initiating isotretinoin for acne vulgaris in Fars province, Iran: cross-sectional study.

BACKGROUND: Since general practitioners manage acne-related referrals, there needs to be more information in Iran about how drugs such as Isotretinoin are prescribed and the treatment plan. Thus, this study aimed to evaluate general practitioners s' practices and attitudes in prescribing Isotretinoin for acne vulgaris in primary care. METHODS: This web-based cross-sectional descriptive study was conducted using two questionnaires designed with the target population of GPs working in Fars province in 2021 regarding the prescription of Isotretinoin. Moreover, demographic information, questions about interest in dermatology, and participation in dermatology workshops were gathered. RESULTS: A total of 308 complete questionnaires were obtained. According to our results, 85 (27.6%) GPs prescribed Isotretinoin in primary care. Based on our results, higher age (OR: 1.042; CI95%: 1.013-1.072; P-value:0.004) and attending dermatological courses (OR: 3.280; CI95%: 1.592-6.755; P-value:0.001) were significantly correlated with more frequent Isotretinoin administration. Among GPs who do not prescribe Isotretinoin, the most common causes are concerns about liver dysfunction (54.7%), teratogenic concerns (37.2%), and lack of familiarity with the drug (31.4%) respectively. CONCLUSION: The results of this study depicted the reluctance of most physicians to prescribe Isotretinoin and factors such as taking part in supplementary courses under the supervision of dermatologists and following national guidelines that could encourage them to prescribe Isotretinoin.

The impact of oral isotretinoin on ovarian functions of acne patients complaining of polycystic ovarian syndrome: a prospective study.

BACKGROUND: Women have polycystic ovarian syndrome (PCOS) at higher rates than any other endocrine condition with an average incidence rate of 6 to 8%. Acne is an immune mediate common condition frequently affecting adolescents and adults and is often associated with PCOS. The objective of the study was to assess the impact of oral isotretinoin on ovarian functions of acne patients suffering from PCOS. Forty women with a clinical diagnosis of acne as well as PCOS participated in this prospective clinical trial. Participants were given oral doses of isotretinoin ranging from 0.5 to 1 milligram per kilogram (mg/kg), for a total of 120 to 150 mg/kg. To establish baseline values of hormone levels, on days 2-5 of the menstrual cycle, venous blood samples were obtained. Moreover, global acne grading system (GAGS), follicle count, and bilateral ovarian volumes were evaluated both before and after isotretinoin treatment. RESULTS: A significant reduction in global acne score from pre-treatment levels to post-treatment levels was observed (11.58 ± 5.857 vs. 1.65 ± 1.369). Ovarian volume was significantly reduced from 10.26 ± 1.539 before treatment to 8.74 ± 1.436 after treatment on the right side (P < 0.001) and from 11.08 ± 1.564 before treatment to 9.36 ± 1.479 after treatment on the left side (P < 0.001). A significant reduction in free testosterone level and hirsutism scores were observed after treatment (P < 0.001; P < 0.01 respectively. CONCLUSION: Isotretinoin may exert beneficial effects in hyperandrogenic women with PCOS and needs to be further evaluated by large multicentre controlled trials.

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.

Use of isotretinoin among girls and women of childbearing age and occurrence of isotretinoin-exposed pregnancies in Germany: A population-based study.

BACKGROUND: Exposure to isotretinoin during pregnancy must be avoided due to its teratogenicity, but real-world data on its use are scarce. We aimed to describe (i) isotretinoin use in women of childbearing age in Germany; (ii) the occurrence of isotretinoin-exposed pregnancies; and (iii) malformations among children exposed in utero. METHODS AND FINDINGS: Using observational data from the German Pharmacoepidemiological Research Database (GePaRD, claims data from approximately 20% of the German population), we conducted annual cross-sectional analyses to determine age-standardized prevalence of isotretinoin use between 2004 and 2019 among girls and women aged 13 to 49 years. In cohort analyses, we estimated the number of exposed pregnancies by assessing whether there was prescription supply overlapping the beginning of pregnancy (estimated supply was varied in sensitivity analyses) or a dispensation within the first 8 weeks of pregnancy. Data of live-born children classified as exposed in a critical period according to these criteria were reviewed to assess the presence of congenital malformations. The age-standardized prevalence of isotretinoin use per 1,000 girls and women increased from 1.20 (95% confidence interval [CI]: 1.16, 1.24) in 2004 to 1.96 (95% CI: 1.92, 2.01) in 2019. In the base case analysis, we identified 178 pregnancies exposed to isotretinoin, with the number per year doubling during the study period, and at least 45% of exposed pregnancies ended in an induced abortion. In sensitivity analyses, the number of exposed pregnancies ranged between 172 and 375. Among live-born children, 6 had major congenital malformations. The main limitation of this study was the lack of information on the prescribed dose, i.e., the supply had to be estimated based on the dispensed amount of isotretinoin. CONCLUSIONS: Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there was a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany.

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.

Analysis of the use of isotretinoin as an adjuvant in rhinoplasty.

BACKGROUND: Isotretinoin has been used in the treatment of acne for decades through the reduction of sebaceous secretion. There are reports in the literature that isotretinoin may be associated with decreased skin thickness, especially in patients with thick nasal skin for whom rhinoplasty can be more challenging. The objective of this study was to quantify, through ultrasonography, the effect of the use of oral isotretinoin in patients undergoing rhinoplasty, pre- and postoperatively. METHODS: Twenty-four patients participated in this randomized, single-blind controlled pilot clinical trial. The intervention group used oral isotretinoin (20 mg/day) for 2 months before rhinoplasty and for 4 months after. Both groups underwent rhinoplasty in the same plastic surgery department and were submitted to high-frequency (22 MHz) ultrasound evaluation of the epidermis and dermis on the nasal dorsum, nasal tip, and left nose wing at the beginning of the study and 6 months after rhinoplasty, with the aim of assessing changes in skin thickness. RESULTS: Six months after rhinoplasty, a statistically significant reduction was observed in the thickness of the epidermis and dermis of the nasal dorsum and left nose wing, as well as of the epidermis of the nasal tip, but only in the intervention group. The results of the satisfaction questionnaire were better after rhinoplasty in both groups, with no statistical difference between them regarding the specific questions; however, the intervention group had significantly higher satisfaction scores than the control group. CONCLUSIONS: Isotretinoin was effective in reducing the thickness of the skin covering the nose of the evaluated sites.

Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis.

Importance: Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear. Objective: To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users. Data Sources: PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023. Study Selection: Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users. Data Extraction and Synthesis: Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed. Main Outcomes and Measures: Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users. Results: A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants' average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide. Conclusions and Relevance: The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.