Stepwise approach of development of dermo-cosmetic products in healthy and atopic dermatitis paediatric population: safety evaluation, clinical development and postmarket surveillance.

BACKGROUND/OBJECTIVES: Paediatric skin, considered sensitive, and infant skin, more susceptible to percutaneous toxicity, require specially formulated cosmetic products. As recently shown, early use of emollients in infants "at risk" of developing atopic dermatitis has shown controversial results in reducing the incidence of atopic dermatitis. Development of dermo-cosmetic products for this specific population should especially ensure tolerance and safety. In absence of good clinical practice guideline, we propose here a stepwise approach for the development of paediatric cosmetic skincare products. METHODS: Our stepwise methodology for cosmetics aimed at paediatrics, starts with in vitro assessment of product's ingredients safety, followed by preclinical and clinical evaluations of the final product, including sequentially: (1) Repeated Open Application Test (ROAT), (2) Human Repeated Insult Patch Test (HRIPT), (3) In-use dermatological and ophthalmological tolerance studies (sequentially in 3a: healthy adults, 3b: healthy paediatric subjects and finally 3c: paediatric patients). We also describe the integrated cosmetovigilance-toxicological surveillance during the clinical development phase and postmarketing. RESULTS: As illustrated with one dermo-cosmetic product intended to be used as a preventative/maintenance treatment for atopic dermatitis in paediatric population, we show that using this stepwise methodology to test a product reduces potential risks of irritation and contact dermatitis in this sensitive population. CONCLUSION: Standardized ethical stepwise development approach is needed to ensure the commercialization of safe and well-tolerated dermo-cosmetics for paediatrics. The approach described here could potentially serve as guidance for evaluation of new paediatric cosmetic products.

Efficacy of a global supportive skin care programme with hydrotherapy after non-metastatic breast cancer treatment: A randomised, controlled study.

This study investigated the efficacy of post-treatment hydrotherapy as supportive care for management of persistent/long-lasting dermatologic adverse events (dAEs) induced in breast cancer survivors by adjuvant therapy, and its impact on quality of life (QoL). Patients in complete remission after standardised (neo)adjuvant chemotherapy, surgery and radiotherapy combination treatment for infiltrating HR+/HER2-breast carcinoma were enrolled in this randomised, multicentre controlled study 1-5 weeks after completing radiotherapy. The control group (CG, n = 33) received best supportive care and the treatment group (HG, n = 35) received 3-weeks of specific hydrotherapy. The primary criterion was change in QoL (QLQ-BR23) after hydrotherapy. Clinical grading of dAEs, cancer-related QoL (QLQ-C30), dermatologic QoL (DLQI) and general psychological well-being (PGWBI) were assessed. Significant dAEs were found at inclusion in both groups (n = 261). Most items showed significantly greater improvement in the HG versus CG group: QLQ-BR23 (breast [p = .0001] and arm symptoms [p = .0015], systemic therapy side effects [p = .0044], body image [p = .0139]), some dAE grading, DLQI (p = .0002) and PGWBI (p = .0028). Xerosis (88% of patients at inclusion) completely healed in all HG patients. Specific hydrotherapy is an effective supportive care for highly prevalent and long-lasting dAEs occurring after early breast cancer treatment, including chemotherapy, and leads to improved QoL and dermatologic toxicities.

Short- and medium-term efficacy of specific hydrotherapy in inherited ichthyosis.

BACKGROUND: Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients' quality of life (QoL). OBJECTIVES: To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. METHODS: In this 9-month prospective, open-label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3-week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self-assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. RESULTS: The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (-56% vs. baseline; mean ± SD 3·59 ± 4·30 at D18 vs. 8·35 ± 5·71 at D0; P < 0·0001), but also at 3 months (-28% vs. baseline; P = 0·01) and 6 months after hydrotherapy (-26% vs. baseline; mean ± SD 5·21 ± 5·11 vs. 6·89 ± 5·38; P = 0·03) (primary criterion). Clinical symptoms were also significantly improved at all post-treatment visits, with a decrease of the mean clinical ichthyosis score by -38% between D0 and D18, by -30% at 3 months and by -31% at 6 months vs. baseline. CONCLUSIONS: A 3-week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses.

Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

BACKGROUND: A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. OBJECTIVES: The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. METHODS: Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. RESULTS: At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. CONCLUSIONS: This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus.

[Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study]. / Intérêt d'un gel stérile anti-brûlure dans les radiodermites : résultats d'une étude comparative.

Trial objectives were to assess effectiveness and tolerance of sterilized Avène thermal spring water anti burning gel (ATSW gel) in prevention of radiation dermatitis in adults irradiated (6 weeks) for breast (n=61) or head and neck (n=8) cancer. Patients included in this open labelled, 2 parallel groups, multicentric study, were randomly assigned to apply five times daily for ten weeks either the Avène spring water gel (n=35) or trolamine cream (n=34). The median of emergence of the first objective radiation dermatitis signs was 31 days in the ATSW gel group and 29 days in the control group (p=0,924). The median incidence for pruritus in patients of the ETA gel group was 46 days versus 27 days (p=0,028) and 44 days versus 24 days for pain (p=0,426). Global efficacy was <> in 46,7 % of patients of the ETA gel group versus 17,2 % (p=0,029) and tolerance was <> in 65,5 % of the ETA gel group versus 40,7 % (p=0,107). No radionecrosis was observed. In conclusion, the efficacy of the Avène spring water gel was similar to the control product in prophylaxis of radiation dermatitis. Tolerance was better and the pruritus was significantly more delayed in patients who applied the Avène spring water gel than in controls.

Efficacy and safety of 0.1% retinaldehyde/ 6% glycolic acid (diacneal) for mild to moderate acne vulgaris. A multicentre, double-blind, randomized, vehicle-controlled trial.

BACKGROUND: Retinaldehyde and glycolic acid are both efficient in acne. OBJECTIVE: To evaluate the efficacy and tolerability of a 0.1% retinaldehyde/6% glycolic acid combination (Diacneal) for mild to moderate acne vulgaris. METHODS: Overall physician and patient ratings of acne symptom severity and tolerance were performed at baseline, months 1, 2 and 3. RESULTS: Mean numbers of papules, pustules and comedones were significantly reduced from month 1 onwards. A significant advantage of Diacneal over vehicle was demonstrated on the percentages of patients with ongoing healing lesions at month 2, healing ancient lesions from month 1 and patients with 'important/very important' global improvement from month 2 (50.0 vs. 26.3%) confirmed by patients at month 3 (86.1 vs. 58.8%). Products were well tolerated; only 1 patient had to stop the treatment. CONCLUSIONS: Diacneal, a combination of 0.1% retinaldehyde/6% glycolic acid, is effective and well tolerated in mild to moderate acne vulgaris.

[Influenza A infection in children. Clinical spectrum and comparison with respiratory syncytial virus infection during the winter 1989-1990]. / Infection à virus Influenza A chez l'enfant. Spectre clinique et comparaison avec l'atteinte par le virus respiratoire syncytial durant l'hiver 1989-1990.

BACKGROUND: Respiratory syncytial viral (RSV) infection can be rapidly differentiated from influenza viral infection by immunofluorescence techniques. These tests were used to identify some epidemiological and clinical characteristics of both infections. METHODS AND PATIENTS: 77 RSV and 22 influenza viral infections were detected during an outbreak (November 1989 to March 1990) in 210 children less than 6 years admitted for lower respiration tract infections. The fluorescent antibody assay was performed on nasal aspirates. RESULTS: The RSV outbreak ran from November to March, while the influenza outbreak was shorter, during December and January. The patients infected with RSV were younger (mean age: 6.7 months) than those infected with influenza virus (mean age: 20.9 months) (p < 0.001). Those with influenza virus infection presented with higher temperatures, more often had initial seizures (p < 0.05) and displayed fewer clinical or X-ray respiratory symptoms (p < 0.001). Mean durations of hospitalization were 9.9 days for RSV infection and 7.7 days for influenza virus infection. The therapeutic use of bronchial dilators, oxygen and steroids was correlated with the degree and duration of respiratory manifestations. A 3 month follow-up was insufficient to show any difference between recurrences or complications in the two groups. CONCLUSION: The clinical and radiological differences in these two groups of patients viral-infected are similar to those described in the literature. Variability from one outbreak to another precludes any extrapolation to other populations and justifies the systematic use of the fluorescent antibody assay, especially when a specific antiviral therapy is considered.