Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Prepubertal acne: A retrospective study.

BACKGROUND: Acne vulgaris is a common skin disorder, but studies on the epidemiologic features of prepubertal acne are limited. OBJECTIVES: The aim of this study was to determine the prevalence and severity of prepubertal acne and to identify factors influencing acne severity and poor response to treatment. METHODS: A retrospective study was conducted on 683 patients with acne from our database who visited the dermatology department of Nantes University hospital between October 2014 and May 2018. Patients of prepubertal acne (7-12 years) were included in this study. RESULTS: Of the 683 patients with acne, 24 (3.5%) had prepubertal acne. Prepubertal acne was more common in female patients (75%). Acne severity assessment showed that severe acne (Groupe Expert Acné global acne severity scale 4) was the most common form (33%), and mild and moderate forms (Global Evaluation Acne Group, global acne severity scales 2 and 3) accounted for 25% each. There was a high predominance of phylotype IA1 of Cutibacterium acnes (belonging to CC18 subgroup). The analysis of patients' lifestyle and acne features identified three factors associated with an increased risk of poor response or resistance to acne treatment. Initially severe acne grading (grade 4) was the most strongly associated parameter (p < .028), followed by regular milk consumption and taking other medications in addition to acne treatment (p < .049 for each). CONCLUSION: This study reported on prepubertal acne features and identified three factors associated with a high risk of treatment failure or relapse. Adequate and prompt treatment is needed in this subgroup of patients to minimize disease burden and prevent subsequent disease worsening.

FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial.

BACKGROUND: Acne vulgaris has increased in women over the past 10 years; it currently affects 20-30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone's efficacy in order to establish it as an alternative to cyclines. METHODS: Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months. DISCUSSION: The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.

Confocal microscopy in adult women with acne.

BACKGROUND: Acne is an inflammatory disease of the pilosebaceous follicle, affecting 41-54% of adult women, with a particular form that involves the mandible. METHODS: We characterized infundibulum morphology in two groups of adult women using reflectance confocal microscopy. First, we investigated acne visually "healthy zones" on the forehead in 15 adult women with diffuse acne and compared with acne-free controls. We then compared healthy forehead and affected mandibular zone in 15 acne patients with mandibular involvement. Exposed results had a P < 0.05. RESULTS: Seven hundred and ninety-one follicles were observed on apparently healthy skin of 15 adult women with acne, with a larger diameter, thicker (68%), and hyper keratinized (65%) follicle border, and more keratin plugs (44%) than in controls. In the second group of 15 adult women with mandibular acne, we compared 569 follicles in the mandibular zone and 475 on forehead. In the mandibular area, follicles were significantly larger, thicker (76%), more hyper keratinized (72%), with more keratin plugs (47%) and increased inflammation (23%) compared with the forehead area. In the mandibular area, 0.2% of follicles showed isolated inflammation without hyper keratinization, and 15.3% had both thickened borders with an onion-like appearance and keratin plugs associated with inflammation. CONCLUSIONS: Hyper keratinization was higher in healthy skin of adult women with acne compared with controls, confirming that microcomedo is crucial in the development of acne lesions. We also demonstrate that the repartition of comedones and microcomedones is inhomogeneous with a great number in the mandibular area where acne lesions are located.

Phototoxicity of B-RAF inhibitors: Exclusively due to UVA radiation and rapidly regressive.

BACKGROUND: New targeted melanoma therapies such as B-RAF inhibitors have shown high and promising clinical benefit but have cutaneous side-effects, including photosensitivity, which is triggered in the UVA radiation spectrum. However, visible spectrum implication has not yet been investigated. We conducted a study to determine whether visible light also contributes to the phototoxicity action spectrum of vemurafenib. The secondary end points were to determine the time to complete regression of the phototoxicity post-vemurafenib discontinuation and whether there was a significant difference between the UVA radiation immediate reactivity cut-offs, in patients treated with vemurafenib vs. those treated with dabrafenib. METHOD: This prospective, observational study included patients with B-RAF mutant metastatic melanoma: 34 patients treated with vemurafenib and 9 with dabrafenib. RESULTS: The visible-light phototest results in patients treated with vemurafenib were all negative before and after 2 months of treatment. The UVA radiation phototests conducted 1 or 2 weeks post-vemurafenib discontinuation in 4 patients showed a normalised UVA-radiation reactivity cut-off. UVA radiation phototests after 2 months of treatment were conducted for all patients. The UVA radiation reactivity cut-off had been lowered for 30 patients (88%) on vemurafenib and 3 patients (33%) on dabrafenib. The median UVA radiation reactivity cut-off was 12 J/cm(2) for the patients on vemurafenib and 20 J/cm(2) for the patients on dabrafenib. CONCLUSION: B-RAF inhibitor phototoxicity is exclusively triggered by UVA radiation and resolves rapidly post-treatment discontinuation. A significant difference between the UVA immediate reactivity cut-offs, vemurafenib vs. dabrafenib, explains the difference in the clinical photosensitivity rates reported in the clinical trials.

Vemurafenib: an unusual UVA-induced photosensitivity.

Vemurafenib is a new-targeted therapy approved for the treatment of patients with V600E BRAF-mutant metastatic melanoma. Among the cutaneous adverse events reported, the photosensitivity is frequently experienced. We aimed to characterize more deeply the mechanism leading to this photosensitivity as well as the corresponding UV spectrum. Phototests showed that the phototoxicity was UVA-dependent since from normal value prior to vemurafenib treatment, the UVA-minimal erythema dose decreased in 17 of 18 patients (94.4%) while the minimal erythema dose remained unchanged. Furthermore, a vemurafenib-induced erythema appeared quickly during the UVA exposure contrarily to what is observed with a conventional drug-induced phototoxicity showing an erythema 12-24 h after the phototesting. Vitamin PP concentration decreased, and porphyrin level significantly increased after 2 months of vemurafenib. Our study confirms the high risk of vemurafenib-induced photosensitivity and indicates that it is possibly vitamin PP- and porphyrin dependent.