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.

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.

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.

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

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

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

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.

Pityriasis Rubra Pilaris: An Updated Review of Clinical Presentation, Etiopathogenesis, and Treatment Options.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous reaction pattern with a significant impact on quality of life. Type I PRP is the most common PRP variant, presenting as erythematous papules emerging in a follicular distribution and later coalescing into plaques with characteristic islands of sparing; histologically, an alternating pattern of orthokeratosis and parakeratosis is considered the hallmark of PRP (checkerboard hyperkeratosis). Other PRP variants (types II-V) differ in their age of onset and clinical presentation. Type VI PRP is a rare PRP subtype associated with human immunodeficiency virus infection and is occasionally associated with diseases of the follicular occlusion tetrad. Caspase recruitment domain family, member 14 (CARD14)-associated papulosquamous eruption and facial discoid dermatitis are newly described disease states that have an important clinical overlap with PRP, creating shared conundrums with respect to diagnosis and treatment. The etiology inciting PRP often remains uncertain; PRP has been suggested to be associated with infection, malignancy, or drug/vaccine administration in some cases, although these are based on case reports and causality has not been established. Type V PRP is often due to inborn CARD14 mutations. Furthermore, recent literature has identified interleukin-23/T-helper-17 cell axis dysregulation to be a major mediator of PRP pathogenesis, paving the way for mechanism-directed therapy. At present, high-dose isotretinoin, ixekizumab, and secukinumab are systemic agents supported by single-arm prospective studies; numerous other agents have also been trialed for PRP, with variable success rates. Here, we discuss updates on clinical manifestations, present new insights into etiopathogenesis, and offer a survey of recently described therapeutic options.

Tumor necrosis factor-α inhibitor treatment of acne fulminans - a clinical and literature review.

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation.

Elastography findings in acne scar patients who were treated with microneedling.

BACKGROUND: Acne scar (AS) is a frequent sequela in patients with acne. In addition to advanced treatment methods, microneedling (MN) is still used as an effective option in the treatment of AS. However, similar to most diseases in dermatology, there is no objective tool to determine the severity of AS and to evaluate the treatment outcome. OBJECTIVES: In the current study, we aimed to evaluate skin elasticity in AS patients who have undergone MN therapy. Furthermore, other purposes were to determine the relationships between the history of isotretinoin use, demographic data, and changes in skin elasticity. METHODS: In order to evaluate the skin elasticity of 20 patients with AS, shear wave elastography (SWE) was performed before and after MN treatment. The physician's clinical assessment was evaluated with quantitative AS severity scale. In order to show that SWE is a consistent method, three repeated measurements were performed on 24 healthy participants. RESULTS: A significant increase was found between the shear-wave velocity (SWV) values that were measured baseline and after treatment in the patient group (P = 0.033). In the control group, there was no significant difference between the three repeated measurements (P > 0.05). A statistically significant decrease was also detected in the AS severity scores (P < 0.005). CONCLUSIONS: In AS patients who underwent MN treatment, a significant increase was found in skin elasticity compared to the baseline. We argued that SWE is a method that can be useful to evaluate skin elasticity before and after similar cosmetic procedures and dermatological diseases.

Efficacy of alitretinoin in the treatment of Darier disease: a case report.

Darier disease is a rare autosomal dominant genodermatosis that initially first presents in adolescence with scaly reddish brown keratotic papules and plaques with a seborrheic and intertriginous distribution. The absence of specific targeted medications complicates the treatment process, and managing resistant cases can prove challenging due to recurrent exacerbations that may result in serious complications such as secondary bacterial and viral infections. Treatments of choice include antiseptics, topical corticosteroids, and systemic retinoids, mainly acitretin and isotretinoin. We report the case of a female patient with Darier disease that was unsuccessfully treated with acitretin and isotretinoin but showed significant improvement with alitretinoin. Previous reports on the efficacy of alitretinoin in Darier disease are reviewed.

PAPA Syndrome: Challenges in Achieving Long-Term Remission.

For over two decades, the acronym PAPA syndrome has been used to describe an autoinflammatory condition caused by missense mutations in the PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1) gene and clinically characterized by the presence of pyogenic arthritis, pyoderma gangrenosum (PG), and acne (1,2). Due to the involvement of the PSTPIP1 gene in the regulation of innate immunity, mutations of this gene cause abnormal activation of inflammasomes, complexes of NLRP3/ASC/caspase-1 proteins. As a result, production of interleukin-1ß, a key molecule that triggers synthesis of cytokines necessary for the recruitment of neutrophils, is significantly increased (2,3). Additionally, the levels of other pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ) and interleukin 17 (IL-7) are also elevated, which further disrupts inflammatory mechanisms in the microenvironment (4). Since hyperproduction of IL-1 and other involved cytokines is the predominant event in the pathogenesis, these molecules are promising targets in the treatment of PAPA syndrome. Corticosteroids and biologics are currently the most commonly used agents for inducing and hastening remission of symptoms (5). A substantial step forward in the treatment of PAPA syndrome has been the introduction of medications blocking the cytokines crucial in the pathogenesis of this disorder, with TNF-α and IL-1 inhibitors being the most frequent choice of such biological therapy (6). We report the case of a 22-year-old male patient with PAPA syndrome who was referred to our department 18 months ago due to exacerbation of skin changes. Initial presentation and subsequent evolution of disease in this patient matched the typical clinical pattern of PAPA syndrome. The first symptoms occurred at the age of two in the form of unspecific joint disease that was diagnosed as juvenile idiopathic arthritis. Subsequently, in the early adolescence the patient presented with new skin changes manifesting as severe acne and persistent pyoderma gangrenosum-like ulcers. At the same time, severity of joint involvement gradually decreased. After the characteristic phenotype of the disease had fully developed, suspicion of possible syndromic origin of symptoms arose. For this reason, genetic analysis was performed as requested by attending pediatricians at the University Clinical Center in Sarajevo, and E250Q mutation of the PSTPIP1 gene was detected. Thus, the diagnosis of PAPA syndrome was confirmed. Throughout the duration of the disease, several types of medication had been introduced in the treatment with varying success. Earliest joint symptoms were alleviated with non-steroidal anti-inflammatory drugs, while repeated courses of corticosteroids were the mainstay of the therapy during a decade-long period. As a consequence of prolonged steroid therapy, growth disorder, among various other side-effects, had been especially pronounced. Acting as a classic steroid-sparing immunosuppressive agent, methotrexate had also been part of the patient's treatment regimen. Lastly, biologics, including both TNF-α and IL-a inhibitors, had been separately administered as the remaining treatment options. However, adalimumab expressed a predominant effect on joint symptoms, whereas re-activation of previously undetected Hepatitis-B infection occurred during the subsequent therapy with anakinra. Due to this adverse reaction, anakinra treatment was discontinued. At the initial examination, the patient presented with multiple erythematous, partially excoriated papules and nodules, along with residual post-inflammatory hyperpigmented patches and scars on the skin of the whole back, chest, shoulders, and upper arms (Figure 1, Figure 2). The presence of postoperative scars on the elbows, resulting from previously performed surgical procedures of persistently affected joints with the goal of achieving pain relief and functional improvement, was also observed. Several smaller ulcers with undermined edges (Figure 3), as well as residual hyperpigmentation and cicatrices (Figure 4) were visible on the lower extremities. Additionally, the patient reported appearance of pustules and non-healing ulcers after minor trauma, which corresponds to the pathergy phenomenon, a common feature of PAPA syndrome. In contrast to the severity of cutaneous changes, the joint symptoms were mild. After thorough assessment of the patient's medical history and current condition, a multi-agent regimen was initiated, consisting of adalimumab, isotretinoin, and prednisone. Regular check-ups during the 12 months of treatment showed that the applied agents stabilized the patient's condition, alleviated more severe and acute skin changes, and slowed down further exacerbation of symptoms. Due to the rarity of PAPA syndrome, data on its treatment is scarce. Official guidelines are non-existing, and available information is based on case reports, case series, and a few smaller retrospective studies (5,7). In general, response to therapy remains inconsistent between patients, despite introduction of novel drugs. Furthermore, single treatment regimens are often not equally effective for all manifestations of the disease, which in a number of cases results in the administration of multi-agent treatment (2). As described in our case report, we opted for a multi-agent regimen not only due to specific individual role of each drug in the treatment of PAPA syndrome but also because of the possible augmented effect of combined therapy. Initially, a short course of systemic corticosteroid (prednisone 30 mg/day for 3 weeks) was introduced in order to alleviate acute symptoms until other agents started showing their effects. The initial dose of administered corticosteroid was gradually tapered by 5 mg every week and soon discontinued. Adalimumab (40 mg every 2 weeks for 12 months) was chosen since its previous administration was without significant adverse effects and with more acceptable end results, unlike therapy with anakinra (8). In addition, TNF-α inhibitors, such as adalimumab, etanercept, and infliximab, have been generally regarded as a more effective treatment option for cutaneous changes, while anakinra, an anti-IL-1 agent, has been more beneficial in alleviating joint symptoms (9-11). Since the skin of our patient was significantly more affected than the joints, adalimumab was a preferred option for biological treatment. Finally, isotretinoin (0.5 mg/kg/day for 6 months) also found a place in our multi-agent therapy plan as a specific, supportive treatment agent for acne (12). Due to the fact that our national health insurance system covered the costs of treatment with TNF-α inhibitors for only 12 months, adalimumab had to be discontinued after the end of this period. Episodes of acute exacerbation that the patient experienced after the cessation of multi-agent regimen were addressed with systemic corticosteroids and symptomatic therapy. Based on case reports, corticosteroids are usually one of the first agents to be administered in patients diagnosed with PAPA syndrome. They are frequently effective in alleviating joint symptoms, but, on the other hand, high doses of corticosteroids can worsen acne lesions (6). Moreover, due to the multiple side-effects of corticosteroids, such as electrolyte abnormalities, hypertension, hyperglycemia, osteoporosis, growth suppression, and adrenal insufficiency (13), a steroid-sparing agent is typically introduced into treatment together with or after corticosteroid therapy. A substantial step forward in the treatment of PAPA syndrome has been achieved with the introduction of medications targeting cytokines crucial in the pathogenesis of this disorder. The two most commonly used groups of such biological drugs have been those that block TNF-α and IL-1. A longer lasting improvement of symptoms has been achieved in a number of cases with both types of agents. Since other medications have often failed to establish long-term control of PAPA syndrome, such effects can be seen as a valuable accomplishment (6,14). Regardless of this observation, the response to treatment still differs between patients. More variable effects have been documented for IL-1 inhibitors, such as anakinra, while TNF-α inhibitors, such as adalimumab, infliximab, and etanercept, have been associated with more steady responses (4,6,10). The inconsistent effect of biologic therapies could be explained by the fact that PSTPIP1 protein is involved in various biochemical processes in different cells of the immune system. Thuse, none of the medications has an adequate spectrum of activity to control all involved immunological pathways (5,15). Overall, due to scarcity of valid information and guidelines, there is an increasing need for multicentric randomized controlled trials that would provide evidence-based data on effective treatment options for PAPA syndrome. Despite the rarity of this disorder, extensive research should be performed in order to discover therapies that could successfully manage all different manifestations of PAPA syndrome. Consequently, such efforts and breakthroughs would lead to decreased mortality and improved quality of life for patients suffering from this debilitating disease. The case described herein shows that PAPA syndrome can remain undiagnosed for longer periods of time, resulting in delayed treatment. Furthermore, the available therapeutic options are not sufficient to achieve long-term remission in many patients. Thus, continuous and comprehensive research is vital for ensuring adequate care of patients with PAPA syndrome.

Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment.

This review on acne transcriptomics allows for deeper insights into the pathogenesis of acne and isotretinoin's mode of action. Puberty-induced insulin-like growth factor 1 (IGF-1), insulin and androgen signaling activate the kinase AKT and mechanistic target of rapamycin complex 1 (mTORC1). A Western diet (hyperglycemic carbohydrates and milk/dairy products) also co-stimulates AKT/mTORC1 signaling. The AKT-mediated phosphorylation of nuclear FoxO1 and FoxO3 results in their extrusion into the cytoplasm, a critical switch which enhances the transactivation of lipogenic and proinflammatory transcription factors, including androgen receptor (AR), sterol regulatory element-binding transcription factor 1 (SREBF1), peroxisome proliferator-activated receptor γ (PPARγ) and signal transducer and activator of transcription 3 (STAT3), but reduces the FoxO1-dependent expression of GATA binding protein 6 (GATA6), the key transcription factor for infundibular keratinocyte homeostasis. The AKT-mediated phosphorylation of the p53-binding protein MDM2 promotes the degradation of p53. In contrast, isotretinoin enhances the expression of p53, FoxO1 and FoxO3 in the sebaceous glands of acne patients. The overexpression of these proapoptotic transcription factors explains isotretinoin's desirable sebum-suppressive effect via the induction of sebocyte apoptosis and the depletion of BLIMP1(+) sebocyte progenitor cells; it also explains its adverse effects, including teratogenicity (neural crest cell apoptosis), a reduced ovarian reserve (granulosa cell apoptosis), the risk of depression (the apoptosis of hypothalamic neurons), VLDL hyperlipidemia, intracranial hypertension and dry skin.

The protective effects of hormonal suppression by a gonadotropin-releasing hormone agonist or an oral contraceptive on the decreased ovarian reserve in female rats exposed to isotretinoin.

OBJECTIVE: The objective of our study was to evaluate whether ovarian suppression by two different hormonal methods may spare the ovary the cytotoxic effects of isotretinoin in a rat model. MATERIALS AND METHODS: Four groups (n=8 Sprague-Dawley albino rats per group) were studied: control (Group I), 7.5 mg/kg/day isotretinoin (Group II), isotretinoin plus the combination of 0.030 mg ethinyl estradiol/0.15 mg levonorgestrel (combined oral contraceptive, COC), and isotretinoin plus 100 µg (microgram) leuprolide acetate (GnRHa) (Group III and IV, respectively). Four rats from each group were decapitated on the 30th day of treatment, and the remaining rats were decapitated on the 30th day of untreated follow-up. Serum anti-Mullerian hormone (AMH) concentrations, healthy and atretic follicle numbers, and apoptotic activity of follicles in oophorectomy specimens were compared between the groups. RESULTS: There were no significant differences in AMH levels among the study groups before, immediately after (first month), and one month after their last medication (second month) (p=0.08, 0.47, and 0.08, respectively). At the end of the first month, the control group had a higher median count of healthy primordial follicles compared to the study groups: 13.5 (8-22), 5.5 (3-11), 6 (2-13), and 1 (0-1) in control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). However, there was no statistically significant difference in the number of healthy primordial follicles between the groups one month after the last medication (p=0.33). The median atretic antral follicle counts in the first month were 2 (1-4), 3.5 (1-4), 0 (0-2), and 0 (0-0) in the control, isotretinoin, isotretinoin+COC, and isotretinoin+GnRHa groups, respectively (p=0.02). Otherwise, there were no significant differences in other types of follicles among the control and treated groups (p>0.05). There was also no statistical difference between the groups regarding immunostaining intensity for active caspase-3 evaluated in the first or second month of treatment (p=0.8 and 0.2, respectively). CONCLUSIONS: Our results show that GnRH agonists or COC have no protective effects on ovarian reserve when co-administered with isotretinoin in the rat model.

Evaluation of recovery time of tear film function and ocular surface after discontinuing oral isotretinoin treatment for acne vulgaris : Correlation between oral isotretinoin and tear film function.

PURPOSE: This study aimed to evaluate the recovery time of tear film function and ocular surface after discontinuing systemic isotretinoin treatment. METHODS: This was a prospective, cross-sectional study. 34 eyes of 17 patients treated with low- dose oral isotretinoin (< 0.5 mg/kg/day) were enrolled. The modified OSDI score, tear break-up time, Schirmer test, and corneal staining were performed in all patients at baseline, during the course of treatment and after withdrawing treatment every two weeks until the result returned to baseline. RESULTS: Tear breakup time appeared to be the most sensitive and changed significantly at 2 weeks after starting treatment (p < 0.001) and returned to baseline at 4 weeks after withdrawal from treatment (p < 0.001). The Schirmer test results significantly decreased at 6 weeks and returned to baseline at 4 weeks after withdrawal from treatment (p < 0.001). OSDI scores were significantly changed at 6 weeks after treatment (81.8%) and returned to baseline at 2 weeks (54.5%) after withdrawal from treatment. No significant change was found in the MGD. Corneal staining was significantly positive 90.9% 6 weeks after starting treatment and returned to baseline 6 weeks after withdrawal from treatment (p < 0.001). CONCLUSION: Dry eye disease can return to baseline levels after treatment withdrawal. At least 6 weeks later, they could wear contact lenses again, and it was useful to prepare all patients requiring further ocular surgery.

Oral Isotretinoin and Its Uses in Dermatology: A Review.

In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some "off-label" use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.

[A sick teenage boy with facial pustula and ulcerations]. / Een zieke tiener met pustels en ulcera in het gelaat.

A 15-year-old boy presented with acne and ulceration since 2 years. After treatment with antibiotics, excision and isotretinoïne, he developed progressive complaints of malaise and respiratory complaints including formation of nasal crusts. Diagnostic evaluation (CT-thorax, ANCA anti-PR3) revealed the diagnosis granulomatosis with polyangiitis (GPA).

Alpha-1 Adrenergic Antagonists Sensitize Neuroblastoma to Therapeutic Differentiation.

Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of approximately 50%. The multimodal therapeutic approach for NB includes treatment with the retinoid isotretinoin (13-cis retinoic acid; 13cRA), which is used in the post-consolidation phase as an antiproliferation and prodifferentiation agent to minimize residual disease and prevent relapse. Through small-molecule screening, we identified isorhamnetin (ISR) as a synergistic compound with 13cRA in inhibiting up to 80% of NB cell viability. The synergistic effect was accompanied by a marked increase in the expression of the adrenergic receptor α1B (ADRA1B) gene. Genetic knockout of ADRA1B or its specific blockade using α1/α1B adrenergic antagonists led to selective sensitization of MYCN-amplified NB cells to cell viability reduction and neural differentiation induced by 13cRA, thus mimicking ISR activity. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, in combination with 13cRA in NB xenografted mice exerted marked control of tumor growth, whereas each drug alone was ineffective. Overall, this study identified the α1B adrenergic receptor as a pharmacologic target in NB, supporting the evaluation of adding α1-antagonists to the post-consolidation therapy of NB to more efficiently control residual disease. SIGNIFICANCE: Targeting α-adrenergic receptors synergizes with isotretinoin to suppress growth and to promote differentiation of neuroblastoma, revealing a combinatorial approach for more effective management of the disease and prevention of relapse.