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.

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.

Effects of oral isotretinoin treatment for acne vulgaris patients on anger responses and the relationship with temperament.

OBJECTIVE: Isotretinoin is the only medication against all the factors involved in acne vulgaris pathogenesis. The aim of our study was to verify whether patients with acne vulgaris receiving isotretinoin therapy exhibit elevated anger levels and to observe the correlation between age, temperament traits, and anger. METHODS: The study group comprised a sum of 100 cases, involving 50 individuals with acne vulgaris-required high-dose retinol therapy and 50 controls who did not start any medication. RESULTS: Our study showed that anger levels increased with drug use. A positive correlation between cyclothymic temperament, the anxiety-related behavior subdimension, and the introvert and passive-aggressive subdimension of interpersonal anger reactions has been recognized. In addition, a positive one was observed between hyperthymic temperament and the introvert subdimension, which is one of the anger-related thoughts and interpersonal anger reactions. CONCLUSION: This study elucidates anger dimensions such as anger-related thoughts, behaviors, and reactions in individuals who received retinol treatment for acne vulgaris. In addition to anger and its dimensions, temperament was also investigated. Although several studies have investigated the relationship between acne vulgaris and psychiatric symptoms, to the best of our knowledge, no research has been reported in the English-language literature regarding the relationship between anger dimensions and temperament after retinol treatment that might make our study an original and valuable contribution to the literature.

Does isotretinoin affect spermatogenesis in the long term? A rat model.

OBJECTIVES: Spermatogenesis, in which cell regeneration continues, can be affected by environmental, chemical, psychological factors or various diseases. There is conflicting information in the literature about the effect of isotretinoin, which is widely used in acne treatment, on testes and spermatogenesis. Therefore, we planned a rat study to evaluate the long-term efficacy of oral isotretinoin on testicular tissues and spermatogenesis. MATERIALS AND METHODS: The Group 1 (n = 6) 7.5 mg/kg/day and the Group 2 (n = 6) received isotretinoin at a dose of 30 mg/kg/day dissolved in sunflower oil, the Sham Group (n = 6) received only sunflower oil by gavage, and the control group (n = 6) received standard feed and water for four weeks. After the 4th week, all animals were fed with standard feed and water and followed for the next four weeks. At the end of the 8th week, all animals were sacrificed under deep anesthesia. Seminiferous tubule diameters, epithelial thickness, apoptotic index, sperm number and motility recorded Results: Sperm count, motility, vitality, diameter of seminiferous tubule and germinal epithelium thickness were decreased and apoptotic index increased in the groups received isotretinoin. There was no significant difference between the groups in terms of testosterone levels. CONCLUSIONS: We consider that further comprehensive studies, including human clinical trials, should be conducted to examine the negative effects of isotretinoin on spermatogenesis in the long term especially when there is a need using isotretinoin in men for various reasons and to eliminate the contradictions in the literature in this regard.

Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review. / Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura.

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: Reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin.

Scrotal calcinosis in a patient treated with isotretinoin: a rare entity.

Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The pathogenesis of this disease is poorly understood. The condition presents as several brown to yellowish asymptomatic nodules on the scrotum. Excision followed by scrotal reconstruction is the treatment of choice. It leaves a good cosmetic result with low chances of recurrence. Newer treatments, such as ablative lasers, have been proposed with very good results. We describe the case of a 28-year-old patient with a history of severe acne treated with oral isotretinoin that presented for scrotal nodules. On laboratory examination, hypercalcemia was found with normal phosphorus, parathyroid hormone, and vitamin D hormone levels. Hypercalcemia was linked to his isotretinoin therapy. Serum calcium concentrations normalized after cessation of isotretinoin and hydration. Because the patient refused surgery, a biopsy of the lesion confirmed the diagnosis of scrotal calcinosis. Then the patient was referred to a cosmetic laser center to treat his condition.

Voriconazole is superior to combined itraconazole/isotretinoin therapy and itraconazole monotherapy in recalcitrant dermatophytosis.

BACKGROUND: There has been an emergence of recalcitrant, recurrent, and difficult-to-treat tinea. Monotherapy with oral antifungals leads to partial clearance or high recurrence of lesions. Isotretinoin is a good adjuvant to systemic antifungals in chronic dermatophytosis. Voriconazole could be a future alternative due to its efficacy against dermatophytes and little resistance. OBJECTIVE: To evaluate the efficacy and safety of oral itraconazole, combined itraconazole/isotretinoin therapy, and voriconazole for recalcitrant tinea. PATIENTS AND METHODS: This study included 90 patients with chronic, recurrent and/or recalcitrant tinea. They were equally divided into three groups: itraconazole monotherapy, combined itraconazole/isotretinoin therapy, and voriconazole monotherapy. All patients received treatments for 6 weeks. The clinical response was classified as either a complete or incomplete clinical cure. Potassium hydroxide microscopy and culture were performed to identify mycological cure. Patients with complete cure were followed up for another 6 months to detect any recurrence. RESULTS: Complete clinical cure was observed in 53.3% of the itraconazole group, 70% of the itraconazole/isotretinoin group, and 83.3% of the voriconazole group. Mycological cure was detected in 56.7% of the itraconazole group, 83.3% of the itraconazole/isotretinoin group, and 86.7% of the voriconazole group. There was a statistically significant difference between the three groups in favour of voriconazole, then the combined group. No significant adverse effects were observed. The recurrence rate was significantly lower in the voriconazole group compared with the other two groups. CONCLUSIONS: Voriconazole could be a future alternative for the treatment of recalcitrant dermatophytosis.

Oral isotretinoin for acne: a complete overview.

INTRODUCTION: Acne is one of the most common and widespread skin conditions, affecting the health as much as patients' quality of life. A wide variety of treatments for acne, topical and systemics, could be prescribed, depending on its degree of severity. Isotretinoin, a derivative of retinol, has been widely used for the treatment of severe forms of acne and those forms not responding to conventional treatments. In literature, there are several studies describing its efficacy, also reporting side-effects related to the drug; therefore, this has led the scientific community to request further studies qualifying its characteristics and comparing its efficacy and safety with other classic acne treatments, as well as with different treatment regimes, in order to find the dose with the best efficacy/safety ratio. AREAS COVERED: The aim of this article is to provide a complete overview on the use of oral isotretinoin for the treatment of acne describing the efficacy, safety, and tolerability of the drug. EXPERT OPINION: Oral isotretinoin represents a valid therapeutic alternative in treating severe and mild-to-moderate acne lesions, also reducing scarring damage. There are no standardized protocols regarding the use of oral isotretinoin and its association with other therapies; however, the correct patient selection and a tailored treatment protocol according to acne lesions severity and type should be considered in order to obtain optimal results.

Effect of Evening Primrose Oil Supplementation on Selected Parameters of Skin Condition in a Group of Patients Treated with Isotretinoin-A Randomized Double-Blind Trial.

Background: Retinoids, which include isotretinoin, reduce sebum levels, the degree of epidermal wetness (CORN) and cause an increase in transepidermal water loss (TEWL). Weight gain has also been observed in isotretinoin-treated patients. An agent that can reduce the severity of isotretinoin side effects is evening primrose oil (Oenothera paradoxa). The purpose of this study was to evaluate the effect of evening primrose oil supplementation in patients with acne vulgaris treated with isotretinoin on skin hydration status (CORN), transepidermal water loss (TEWL), skin oiliness (sebum) and changes in body weight and BMI. Methods: Patients diagnosed with acne were assigned to the isotretinoin-treated group (n = 25) or the isotretinoin and evening primrose oil-treated group (n = 25). The intervention lasted 9 months. CORN (with a corneometer), TEWL (with a tewameter) and sebum (with a sebumeter) were assessed twice, as well as body weight and BMI (Tanita MC-780). Results: The isotretinoin-treated group showed statistically significant reductions in CORN (p = 0.015), TEWL (p = 0.004) and sebum (p < 0.001) after the intervention. In the group treated with isotretinoin and evening primrose oil, TEWL and sebum levels also decreased significantly (p < 0.05), while CORN levels increased from 42.0 ± 9.70 to 50.9 ± 10.4 (p = 0.017). A significant decrease in body weight (p < 0.001) and BMI (p < 0.001) was observed in both groups after 9 months of intervention. Conclusions: During isotretinoin treatment, supplementation with evening primrose oil increased skin hydration. However, there were no differences between groups in transepidermal water loss, skin oiliness, weight loss and BMI.

Efficacy and safety of low-level light therapy by delicate pulsed light combined with low-dose oral isotretinoin for the treatment of acne vulgaris: a randomized split-face study.

Acne vulgaris (AV) is a common dermatosis that causes psychological problems. Isotretinoin is the first-line treatment for moderate-to-severe AV, but its onset of effect is delayed. Although light-based therapy is widely used in the treatment of AV, there is a lack of reports on delicate pulsed light (DPL) which has a narrow therapeutic spectrum (500-600 nm). Low-level light therapy (LLLT) has shown an emerging role in anti-inflammatory effects and skin repair. This study investigates the efficacy and safety of low-dose oral isotretinoin combined with LLLT using DPL in patients with moderate-to-severe AV. Thirty-six patients with moderate-to-severe AV were enrolled and received low-dose oral isotretinoin (10-20 mg/day). The two sides of the face were randomly assigned to receive DPL (6-9 J/cm2) or not at an interval of 2 weeks for 4 treatment sessions (weeks 0, 2, 4, 6). Photos, GAGS score, counts of papules, pustules, comedones, TEWL, melanin and erythema index, side effects, efficacy, and satisfactory score were recorded at each visit and at 4 weeks after the final treatment (week 10). Thirty-three patients completed the study. DPL and oral isotretinoin combined therapy exhibited significantly improved GAGS score as well as the number of the lesions from week 2 and maintained until week 10. At the end of the observation, the improvement of GAGS was 70.88% on the DPL and isotretinoin combined side versus 62.12% on the side with isotretinoin monotherapy (p = 0.0009). The improvement for papule number was 61.58% on the DPL combined side versus 43.33% on the control side (p < 0.0001), for comedone was 63.15% versus 43.30% (p = 0.0008). TEWL and indexes of melanin and erythema also had better outcomes with DPL combined therapy at week 10. All the side effects were temporary and tolerable; no adverse effects were observed. Oral low-dose isotretinoin combined with LLLT by DPL offers a combination with reduced side effects and better outcomes within a limited treatment duration, which advances the onset of effect of isotretinoin monotherapy and improves lesion clearance.

Development, optimization, and validation of Inflammatory Bowel Disease rat model using isotretinoin.

BACKGROUND: and Purpose: Inflammatory Bowel Disease (IBD) is a persistent bio-psychological disorder with the absence of actual pathological reason. Association between IBD and isotretinoin has been reported by many human and in vitro studies. However, in this study, our focus is on finding the causal relationship between IBD and isotretinoin for the development of a new animal model. METHODS: Twenty-eight Sprague Dawley rats were taken for this study and divided into five groups (i.e. Group 1: Normal control, Group 2: Standard IBD Model Group (Indomethacin treated), Group 3: Isotretinoin low dose (7 mg/kg), Group 4: Isotretinoin medium dose (35 mg/kg), Group 5: Isotretinoin high dose (70 mg/kg). The rats were treated according to assigned treatment and observed on different days to evaluate the severity of IBD with the help of symptomatical (nausea, diarrhea, stool consistency, etc.) activity, biochemical parameters, macroscopy, and histological analyses. KEY RESULTS: During the entire study period, body weight, stool consistency and frequency of the animals had been observed daily. No significant reduction in body weight was observed between the disease induced and normal control animals; however, it was observed that the stool consistency of the animals became less (mucus in stool) day by day and stool frequency increased (frequent defecation) in the different isotretinoin groups compared to the control group. There was statistically significant increase in TBARS levels of isotretinoin low (p < 0.05), medium (p < 0.001) and high dose (p < 0.01) treated group was observed, as compared to control group. Similarly, statistically significant effects of isotretinoin on GSH level (p < 0.01), CAT activity (p < 0.01), and SOD (p < 0.01) were also observed. Increase in TNF-α levels found significantly higher in isotretinoin medium dose (35 mg/kg) treated group (p < 0.001) as compared with control group as well as standard IBD model group. All the three-isotretinoin treated groups (Isotretinoin low dose: p < 0.001; Isotretinoin medium dose: p < 0.001; Isotretinoin high dose: p < 0.001) depicted significant difference in macroscopic scores as compared with control group; these results are comparable with standard IBD model group. Histological analyses revealed that, among three-dose groups of isotretinoin, there was excessive amount of crypt abscesses, infiltration of inflammatory cells, and formation of ulceration observed in isotretinoin medium dose treated group. CONCLUSION: As standard indomethacin treated group, isotretinoin also caused significant damage to intestinal mucosa, and form ulceration in gastrointestinal tract. Compared to control group, isotretinoin significantly worsens the disease condition, which were comparable to the indomethacin-treated group; however, isotretinoin at the dose of 35 mg/kg caused maximum severe damage to the intestinal mucosa.

Effect of Evening Primrose Oil Supplementation on Biochemical Parameters and Nutrition of Patients Treated with Isotretinoin for Acne Vulgaris: A Randomized Double-Blind Trial.

Background: Acne vulgaris is one of the most common skin diseases. One of the therapeutic options recommended for severe acne or acne that has not responded to previous therapies is isotretinoin. However, its use may lead to adverse changes in the serum lipid profile and increased levels of transaminases. In this study, we evaluated the effect of supplementation with evening primrose oil in acne vulgaris patients treated with isotretinoin on blood lipid parameters and transaminase activity. Methods: Study participants were randomly assigned to two treatments: conventional with isotretinoin (25 patients) and novel with isotretinoin combined with evening primrose oil (4 × 510 mg/day; 25 patients) for 9 months. Results: Compared to isotretinoin treatment, isotretinoin treatment combined with evening primrose oil had a positive effect on TCH concentrations (mean: 198 vs. 161, p < 0.001), LDL (95.9 vs. 60.2, p < 0.001), HDL (51.0 vs. 48.0, p < 0.001), TG (114 vs. 95.0, p < 0.001), ALT (24.0 vs. 22.0, p < 0.001), and AST (28.0 vs. 22.0, p < 0.001), but had no effect on the energy and ingredient content of the diets (p > 0.05) after treatment. Conclusion: Evening primrose oil was found to have beneficial effects on lipid profiles and transaminase activity during isotretinoin treatment. However, longer studies are needed to make more reliable decisions regarding the use of evening primrose oil and its safety in clinical practice. The evening primrose oil treatment group also showed a reduction in dietary energy due to a reduction in dietary protein and carbohydrates.

Lip mesotherapy with dexpanthenol in the treatment of isotretinoin-induced cheilitis.

INTRODUCTION: Cheilitis is the most common mucocutaneous side effect of isotretinoin (ISO). Dexpanthenol (DXP) increases fibroblast proliferation and re-epithelialization in wound healing. We aimed to investigate the effect of DXP-mesotherapy in ISO-induced cheilitis in this study. METHODS: This study was conducted on patients who had been using ISO (0.5-1 mg/kg/day) for at least 2 months. Twenty-five patients who administered DXP-mesotherapy (mesotherapy group) and 33 patients without the procedure (control group, only ointment) participated in this study. All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm. The efficacy of the treatment was interpreted by the change in lip balm use frequency, quality of life, and Isotretinoin Cheilitis Grading Scale (ICGS). RESULTS: There was a statistically significant decrease in all ICGS-subgroups scores in the mesotherapy group after 1 month compared with the baseline (p = <0.001), although in the controls, erythema, crust, and fissure scores significantly increased (p = 0.001, p = 0.002).While there was no difference between the groups in terms of ICGS total scores at baseline, there was a significant difference after 1 month in favor of the mesotherapy group (p < 0.001). In the mesotherapy group, lip balms were needed significantly less frequently and there was a significant improvement in quality of life compared with both the control group and at baseline after 1 month (both; p < 0.001). On the other hand, the control patients suffered more from cheilitis and dryness than at baseline (p < 0.001). CONCLUSION: Dexpanthenol-mesotherapy seems to be a safe, and so effective method in management of ISO-related cheilitis.

Analysis of the effects of isotretinoin on the premature epiphyseal closure in pediatric populations: a literature review.

CONTEXT: Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U.S. Food and Drug Administration (FDA) has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne. It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen. OBJECTIVES: This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure. METHODS: Two databases were utilized for the literature review and were conducted at different time periods. Our literature review was conducted between December 2020 and June 2021, utilizing PubMed with the following search terms: "isotretinoin" and "isotretinoin and premature epiphyseal closure." In April 2021, we searched the FDA's "Drug Data and Adverse Event Report System" utilizing the terms "isotretinoin" and "epiphysis premature fusion." We included in our query reports of patients worldwide under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Studies published in English between 1980 and 2020 were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded. RESULTS: A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin. The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18 years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5 mg/kg/day for a few months to 3.5 mg/kg/day for years. CONCLUSIONS: Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur. A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded.

Treatment of rosacea during pregnancy.

BACKGROUND: Exacerbation of rosacea may occur during pregnancy and there are multiple associated cases of rosacea fulminans (RF). Treatment during pregnancy poses a significant challenge as many rosacea treatments are contraindicated or have limited evidence regarding potential adverse fetal effects. OBJECTIVE: Review the pregnancy categories of various treatments and develop algorithms for treating pregnant patients with rosacea and RF. METHODS: Rosacea treatments showing efficacy in randomized controlled trials were searched through DailyMed to review pregnancy labelling. Searching the PubMed/MEDLINE database for English articles using keywords "rosacea fulminans AND pregnancy" without publishing-time restrictions yielded 8 articles. We summarized treatments used in cases of RF during pregnancy. RESULTS: Topical ivermectin was more effective than metronidazole, but has a more concerning pregnancy category. Three pregnant women with RF were treated successfully with topical metronidazole in combination with other therapies. Azithromycin is the only oral rosacea therapy that is considered safe for pregnant patients and it has been used to treat RF. CONCLUSIONS: This review highlights the challenging aspects of treating pregnant patients with rosacea, as there is limited pregnancy-related treatment efficacy and safety data. The pregnancy categories of therapeutic options are summarized. Further studies are needed to learn which therapies are effective and safe for use during pregnancy.

Physeal Abnormalities in Children With High-risk Neuroblastoma Intensively Treated With/Without 13-Cis-Retinoic Acid.

BACKGROUND: This study aimed to investigate the presence of physeal abnormality and its effect on growth in children with high-risk neuroblastoma treated by intensive multimodal treatment with/without 13-cis-retinoic acid (13-CRA). METHODS: Fifteen patients diagnosed with high-risk neuroblastomas at the age of 1 to 10 years, who received treatment such as high-dose chemotherapy and autologous stem cell transplantation with/without 13-CRA, and with complete data during their >2-year follow-up were retrospectively reviewed. The physeal abnormalities were investigated by whole-body magnetic resonance imaging, serially performed every 3 to 6 months. The patients' height growth was also investigated and compared with that of age-and-sex-matched patients with brain tumors who also underwent high-dose chemotherapy and autologous stem cell transplantation. RESULTS: Six of 15 patients presented multifocal physeal abnormalities during follow-up, and all lesions occurred in patients with 13-CRA use. The lesions in 3 patients completely resolved spontaneously without any adverse effect on growth, but some lesions in the other 3 patients progressed to disturb the bony growth. Height growth of matched patients with brain tumors were not significantly different, and none of the matched controls showed definite bony deformity during the follow-up. CONCLUSIONS: Some children who were treated for high-risk neuroblastomas experienced multifocal physeal insults, probably due to the use of 13-CRA. Most lesions resolved spontaneously, but some led to bony deformity. If the lesions are not followed by premature physeal closure, there seems to be no further adverse effect of 13-CRA on leg length growth. Routine periodic screening for physeal status is needed for the patients with high-risk neuroblastomas using 13-CRA. LEVEL OF EVIDENCE: Level IV-prognostic study.