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.     

Evaluation of subclinical atherosclerosis in Turkish patients with acne vulgaris receiving systemic isotretinoin

Studies conducted on isotretinoin have shown that it may indirectly lead to atherosclerosis. The objective of this study was to determine the effect of systemic isotretinoin on subclinical atherosclerosis. The present study included 63 patients with acne vulgaris who had used isotretinoin for 6 months. Glucose, insulin, and homeostatic model assessment of insulin resistance levels; body mass index; waist circumference; blood pressure; lipid profile; and lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), high‐sensitivity C‐reactive protein, and oxidized low‐density lipoprotein (Ox‐LDL) levels were compared in the patients at the initiation and discontinuation of the treatment. At the discontinuation of the treatment, LOX‐1 and Ox‐LDL levels showed a significant increase (P < .001 and P = .040, respectively). Differences in waist circumference were positively correlated with an increase in LOX‐1 levels (r = .274; P = .030). Isotretinoin causes an increase in the levels of subclinical atherosclerosis markers. Although the present study sample size was small, we believe that caution should be exercised considering the risk of atherosclerosis during isotretinoin use in men with high waist circumference and cardiovascular risk factors; further studies are warranted in this regard.     

Do acne treatments affect insulin‐like growth factor‐1 serum levels? A clinical and laboratory study on patients with acne vulgaris

Acne is a chronic inflammatory disease affecting sebaceous gland follicles. Lately, acne has considered an insulin‐like growth factor‐1 (IGF‐1) mediated disease. Recent research demonstrated that IGF‐1 levels decrease after 3 months of isotretinoin. The purpose of our study is evaluating the influence of acne treatments on IGF‐1 serum levels. Forty‐six subjects with acne vulgaris aged 14 to 30 years were subdivided into three groups according to their severity of acne and treated following the European Dermatology Forum guidelines. IGF‐1 was measured in patients before and after the treatment and then compared to the IGF‐1 of a healthy population of the same age. IGF‐1 resulted higher in patients than in controls but there was not a statistically significant variation after treatment. To the best of our knowledge, this is the first study evaluating the influence of topical and systemic acne treatment on IGF‐1 serum levels. In contrast with the literature, our results suggest that common therapies for acne are not able to significantly modify IGF‐1 serum levels.     

Evaluation of reliability and validity of the Patient Health Questionnaire‐9 in patients with acne

To evaluate the reliability and validity of the Patient Health Questionnaire‐9 (PHQ‐9) in patients with acne. Three hundred acne patients were enrolled from January 2019 to December 2019. PHQ‐9 and Hamilton Depression Scale(HAMD) survey was conducted to evaluate their depression status. Cronbach's α coefficient and test‐retest reliability after 1 week were used to analyze the reliability of PHQ‐9. Factor analysis, Spearman correlation analysis, receiver operating characteristic curve (ROC curve) were used for validity analysis of the PHQ‐9.The screening validity was analyzed in different subgroups. Two hundred fifty‐eight patients with acne completed the questionnaire. Forty‐seven were diagnosed with depressive disorder. The best cut‐off point for the PHQ‐9 score is 9 points, with a sensitivity of 95.7%,a specificity of 88.6% and the area under the ROC curve(AUC) of 0.973.In validity analysis, the correlation coefficient between the total score of PHQ‐9 and HAMD was 0.766,the kappa value was 0.530.Factor analysis revealed two common factors (cognitive‐affective factor and somatic symptom factor),which explained 65.52% of the total variances. In reliability analysis, the Cronbach's α coefficient of the PHQ‐9 was 0.851,the test‐retest reliability value was 0.824.The time to complete the PHQ‐9 was significantly less than the time to complete HAMD (P < .001).The PHQ‐9 shows good reliability and validity for the diagnosis of depression in patients with acne, and can be used for preliminary screening of depression.     

Efficacy of acne vulgaris treatment protocols according to its clinical forms

To compare results of different treatment regimens based on stratification of acne to prescribe the right treatment protocol according to clinical form and grade of acne. A transversal, cohort study conducted in 230 patients with acne vulgaris. Patients were divided into three groups according to acne severity and the results of each protocol determined in 0, 4, 6, 8, 12, 18 and 24 weeks. Statistical analysis was conducted using Wilcoxon and Mann‐Whitney tests 230 patients (99 females and 131 males) took part in the study. In first grade acne (70 patients), the most effective drug for papulo‐pustular lesions was azelaic acid, where the average value of the reduction was 1.03% per week. For comedone reduction, the most effective drug resulted retinol with 17.7% mean reduction per week. In second grade acne (66 patients), the most effective scheme was: doxycycline + topical retinoid + benzoyl peroxide. In the third grade (92 patients), the most effective drug was oral isotretinoin. Accurate stratification, based on clinical characteristics is required for better outcome. Treatment success is related to the respective individually tailored treatment schemes in patients with acne.     

Are therapeutic effects of antiacne agents mediated by activation of FoxO1 and inhibition of mTORC1?

Acne pathogenesis has recently been linked to decreased nuclear FoxO1 levels and increased mTORC1 activity. This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1. Benzoyl peroxide (BPO), by activation of oxidative stress‐inducible kinases, increases nuclear FoxO levels promoting Sestrin3‐mediated AMPK activation. Furthermore, BPO‐derived ROS may activate AMPK via ataxia–telangiectasia mutated. Isotretinoin and all‐trans retinoic acid may stimulate FoxO gene expression. Doxycycline may enhance FoxOs nuclear retention by inhibiting the expression of exportin 1. Suppression of TNFα signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKβ‐TSC1‐mediated mTORC1 activation. Erythromycin attenuates ERK1/2 activity and thereby increases TSC2. Azelaic acid may decrease mTORC1 by inhibiting mitochondrial respiration, increasing cellular ROS and nuclear FoxO levels. Antiandrogens may attenuate mTORC1 by suppressing mTORC2‐mediated Akt/TSC2 signalling. This hypothesis unmasks a common mode of action of antiacne agents as either FoxO enhancers or mTORC1 inhibitors and thus provides a rational approach for the development of new antiacne agents.