[Treatment of mild to moderate acne].
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Biomedical subjects
Publications and source records attributed to M Chivot.
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Acne is a problem of the pilo-sebaceous follicle caused by the conjunction of three factors: seborrhea, follicle obstruction, and follicle inflammation. The key element, seborrhea, is under androgenic control. Acne in women is also influenced by developments and modifications in genital life, as well as by hormonal contraceptive and replacement therapies. Acne is rare prior to puberty, when it may indicate endocrine disease. At puberty, acne is quasi-physiological, because of the relative hyperandrogenism induced by the andrenarche preceding pubarche, as well as by the relative shortage of estrogens and progesterone during the first menstrual cycles. Other signs of hyperandrogenism, such as menstrual cycle difficulties and excess weight, which favor a hormonal origin, must be sought in cases of persistent or late-onset acne in adults. There is a mirror image of puberty during the peri-menopausal period, but with decreased seborrhea, so acne is rare. Finally, a tumoral origin must be sought in the rare cases of acne occurring after menopause. Hormonal investigation of acne should not be systematic, but is justified during prepuberty when other symptoms are associated with acne that resists well-conducted dermatological treatment. The therapeutic approach should be primarily dermatological, but hormone-oriented treatment should be considered when such therapy fails, or in the presence of other signs of hyperandrogenism. Sometimes the association of isotretinoin and an anti-androgen treatment are necessary to effectively treat such acne. Finally, particular attention must be paid to contraceptive therapies and hormone treatments, which can induce or aggravate acne, especially during the peri-menopausal period.
BACKGROUND: In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne. OBJECTIVE: To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris. METHODS: Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules). RESULTS: This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline). CONCLUSION: Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.
BACKGROUND: Isotretinoin treatment for acne can lead to inflammatory flare-ups or an aggravation, occasionally leading to acne fulminans. The purpose of this work was to examine our cases and to propose a classification system for management. PATIENTS AND METHODS: Over a 3-year period, we selected patients referred to our dermatology unit for paradoxical aggravation of acne under isotretinoin treatment. We recorded clinical data, drug prescriptions and the course of the flare-up. RESULTS: Over 3 years (1995-1998) we observed 32 cases of acne flare-up in patients taking isotretinoin, 6 women and 26 men. DISCUSSION: Four types of aggravation could be identified depending on their date of onset, the skin signs, and the presence or not of general signs. Systemic corticosteroids are generally required, together with a lower daily dose of isotretinoin and local care (excision of open and closed comedons). Factors predictive of aggravation are young age, male sex and sebaceous retention. CONCLUSION: Acne fuminans is exceptional in patients taking isotretinoin compared with the number of patients treated. Clinicians should nevertheless be aware of the risk in order to make the diagnosis and provide appropriate care.
BACKGROUND: Acne is the most common symptom prompting patients to consult a dermatologist. No previous study has been conducted in France to determine the prevalence of acne and describe the main epidemiological features. SUBJECTS AND METHODS: A cross sectional study was conducted in November 1996 and included 913 school children aged 11 to 18 years. This sample was statistically representative of the entire secondary school population in France during the 1996-1997 school year. The subjects were stratified by 5 criteria: age, sex, rural or urban residence, sun exposure, type of school. RESULTS: Taking the clinical diagnosis made by the dermatologist investigator as the main criteria, the overall prevalence of acne was 72 p. 100. It was 76.1 p. 100 using the new ECLA grading system previously described. The prevalence of acne was sex and age dependent: highest scores were found for girls aged 14-16 years and for boys aged 16-17 years. Genetic factors were very important for the outcome of acne. Finally, 41 p. 100 of the acneic subjects were following a treatment, prescribed by a dermatologist in two-third of the cases. DISCUSSION: These results are in agreement with those previously published in the literature although some differences were disclosed. It would appear important to distinguish between minimal acne with a few retentional pimples occuring during adolescence and severe acne (more than 20 pimples on the face) requiring early medical care to avoid scarring.
BACKGROUND: Different acne gradings have been proposed: global grading, semi-global grading, quantitative grading and photographic grading. They are mainly used in clinical studies for the evaluation of acne treatment. However, it would be important for physicians to have an acne grade which would be useful for assessing acne lesions prior to treatment and following treatment efficacy. METHODS: Six French dermatologists developed an acne grading scaled called "ECLA" which only takes 2 minutes to fill out and specifically designed for use by dermatologist practitioners. In addition, the intra- and inter-observer reliability of the grading scale was assessed. RESULTS: This analysis demonstrated the excellent reliability of the ECLA grading scale both in terms of intra- and inter-observer variability except for the retentional factor. The cross physician reliability decreased with time specificity for the retention factor, indicating that previous training prior to a multicentric clinical study would be necessary. CONCLUSION: ECLA grading appears to be an interesting and useful tool in dermatology for the follow-up of acne patients.
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An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.
To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.
Acne is easy to diagnose, but its physiopathology is complex and not yet fully elucidated. However, the three factors that are necessary to the genesis of acne are well defined, being seborrhoea, obstruction of the hair follicle and the sebaceous gland, and inflammation of the follicle. To this must be added a genetic predisposition. While the skin lesions leave little doubt about the diagnosis, a thorough examination is needed to evaluate the part due to sebum retention (comedos, microcysts) and that due to inflammatory elements (papules, pustules, nodules), for the lesions are so polymorphous that it would be better to speak of acnes rather than acne. A good knowledge of clinical and physiopathological data leads to the appropriate treatment, since almost all therapeutic failures result from a misappreciation of acne.
Acne is known to be one of the features of hyperandrogenism. The aim of the present work was to study women with persistent acne and without other evidence of hyperandrogenism, such as hirsutism, alopecia, or irregular menses. Among 87 female patients with acne and/or hirsutism, we defined three groups: group 1 (n = 29), patients having treatment-resistant acne without menstrual disturbance, alopecia, or hirsutism; group 2 (n = 27), patients with acne and hirsutism; and group 3 (n = 31), patients with hirsutism alone. Clinical chemistry criteria for hyperandrogenism were based on elevated values of one or more of the following parameters: plasma testosterone, delta-4-androstenedione, dehydroepiandrosterone, urinary 5 alpha-androstane 3 alpha-17 beta-diol, and 17-ketosteroids (with chromatography). Plasma and urine samples were drawn between the 18th and 25th days of the cycle. Among group 1 patients, we found 25 subjects (86%) with hyperandrogenism, according to these laboratory criteria. The etiologies were: polycystic ovary syndrome (36%), adrenal hypersecretion (40%, of which 12% showed secondary polycystic ovaries), isolated increase in 5 alpha-androstane 3 alpha-17 beta-diol (20%), and hyperandrogenism without diagnosis (4%). The parameters were found to be more elevated in these patients than in a control group of 30 normal volunteer women. In groups 2 and 3, the findings were essentially the same as in group 1, except for increased levels of testosterone and the testosterone/SHBG ratio. Furthermore, it was evident that persistent acne may be an isolated sign of hyperandrogenism.
A study was carried out involving 172 patients with acne which warranted treatment with isotretinoin. Patients were followed up for between 12 and 41 months after discontinuation of treatment and the number of relapses was assessed. 37 patients (21%) relapsed. These relapses were correlated with patients' age, length of disease progression prior to treatment, total dose received, daily dose, duration of treatment and severity of acne. It appeared that only young age and severity of acne influenced the percentage of relapse.
An in vitro study of the oxidation of squalene, and a description of factors acting on this transformation are presented. Thin layer chromatography was used to quantify the products generated by different oxidation processes. The results clearly show that squalene is a highly effective oxygen-scavenging agent. Its oxidation may first induce comedogenesis and, as a secondary event, cause a large reduction in oxygen tension in the human pilo-sebaceous duct. Porphyrins were confirmed to be highly efficient catalytic factors in the squalene oxidation process. The relationships between comedogenesis, bacterial colonization, and the role of sebum in the pathogenesis of acne are discussed in the light of these findings.
Skin surface lipids and lipids from open and closed comedones in acne patients were analysed by thin layer chromatography. The results showed that these lipids were enriched in polar lipids, as compared with the skin surface lipids obtained from controls without acne. In both open and closed comedones, these polar lipids appeared to be derived mainly from the oxidation of squalene, which is in agreement with our previous in vitro results. We suggest that squalene oxidation is the link between comedogenesis and bacterial colonization, and based on this, we propose a hypothesis of the pathogenesis of acne.
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Cytosol androgen receptor was assayed in 18 human skin biopsies by an exchange technique with a labelled potent synthetic androgen, methyltrienolone (R 1881), under conditions which measured total (i.e. both free and occupied) binding sites. Androgen binding sites were only present in skin biopsies from patients with marked seborrhoea often accompanied by acne (8 cases) and no sites were detected in normal skin biopsies (7 cases). Three biopsies from seborrhoeic patients, however, did not contain androgen receptor. Although no direct quantitative correlation could be drawn between binding site concentration and sebum excretion, it would seem that the androgen receptor content nevertheless constitutes an important parameter in the study of the hormonal control of seborrhoea.