Dermamelan ® treatment for melasma and hyperpigmentation Jean Luc Levy Expert Laser, Dermatologist Lausanne, Switzerland [email protected] Incidence of Melasma Caucasian Melasma is estimated to occur in 50%-70% of pregnancies among US women, usually during the 2nd or 3rd trimester of pregnancy. Asian In Asian countries, the estimated prevalence of melasma within skin type III-V is estimated to be as high as 40% in females and 20% in males. Hispanic Among Mexican women, the incidence is estimated to be about 80%, with more than one-third of these patients having the disease for life. Retrospective Study on the Clinical Presentation and Treatment Outcome of Melasma in a Tertiary Dermatolofical Referral Centre in Singapore C L Goh, C N Dlova, Singapore Med J 1999; Vol 40(07): Melasma in Orientals. Sivayathorn A. Clin Drug Invest 1995; 10 (Suppl 2):24-40. ‘Utilizing combination therapy to optimize melasma outcomes’, M, I, Rendon(2004), Journal of Drugs in Dermatology, Sept-Oct. Facial melasma : Sun history Majority of melasma are very sensitive to sun exposure and tanned during summer - Sunblock regurlaly applied are poorly effective - During winter quality of life is better Some of them are poorly sensitive to sun exposure and colour acquired is near from the surrounding skin - During winter color differences between melasma and surrounding skin is high and covermark required Upper forehead without due to the tissue Sun exposed and non sun exposed areas Facial melasma : locations Forehead : with commonly a lighten aspect if hair is used as a sunblock Malar with possibly extension to lateral cheeks / unfrequently mandibular Upper lip sometimes as the first time or the alone locations Facial melasma : factors Current factors are : - sun exposure is common ( car, street walking ) - over sun exposure ( sun , sun bed ) and sometimes familiar suceptibility ² - infrared factors : kitchen ,IR through window , etc The goal is to find a chronology between the onset of first facial spots and a possible cause Our approach was to define WITH OR WITHOUT HORMONAL INFLUENCE ? Role of UV and hormonal influences JEADV 2009 1254-1262 Facial melasma : hormonal influences Pregnancy : pre , pregnancy , post pregnancy (even without sunexposure ) Oral contraceptives beginning treatment ( and uncommon treatment stopped) In vitro fertilization at the beginning of the treatment, therapy for endometriosis, oral corticosteroids, therapy for hypophysal adenoma Mirena® : intra uterine contraceptive device In our experience : we never observed the beginning of facial hormons melasma at or after menopause So called : hormonal melasma Hypothesis: Pathogenesis of melasma 17b-ESTRADIOL VOIE GENOMIQUE VOIE NON GENOMIQUE (E2) AC PLC GM-CSF ERK ER : Estrogen receptor ER a OCb ERE: Estrogen responsive element AC: Adenylate cyclase ERE PLC: Phospholipase C ERK: Extracellular signal-regulated kinase KERATINOCYTE N. Kanda et al. J Invest Dermatol. 2004;123:319-29 Hypermelanosis post UVB + œstradiol patch • Stimulation of • Melanogenesis • by oestrogenes Claudy AL. & JL Perrot. Dermatologica 1990;181:154-155 Facial melasma: non hormonal influence Epilation / discoloration of the upper lip hair Peeling or microirritation with redness with : peeling , laser , microabrasion , loofa , perfume oil , unadapted chronic cosmetic cares In this case : inflammatory factors So called : inflammatory melasma = PIH like melasma Facial melasma :Combined , Miscellaneous or unknown factors First inflammatory then hormonal factors First hormonal factors then inflammatory treatment Less than 5 % without any unknow factors ( especially over a longer period of melasma) Others factors : Very frequent : Vit A complex , caroten , lycopen Drugs : isotretinoin , antidepressive ( stress) , antibiotics , Clinic and UV photography does not help to determine not epidermal or mixed melasma , neither influences PIH hormonshormons Skin biopsy very useful to differenciate the 2 types but too invasive The role of melanophages is unknown Epidermal mixed Refectance Confocal Microscopy RCM shows 3 types of informations : -level melanocyte activity - Charged keratinocytes in melanosomes - amount of melanophages RCM : diagnosis of few melanophages Melasma is a epidermal RCM : diagnosis of large number of melanophages Melasma is mixed : epidermal and dermal To differenciate the diagnosis of Melasma fron others pigmentary disorders • Solar lentigo • lentigo simplex • Seborrheic keratosis • Neck : poikiloderma of Civatte • Melasma due to hormons exists en forearm • Melasma due to PIH exists in men In summary 1 • There are 2 main clinical types of melasma – With hormonal influence – Without hormonal influence - inflammatory factors including UV agressive exposure - others with recognized factors or unknown . • RCM shows dynamic informations on melanogenesis and the % and level of pigmentation ( epidermal or mixed) • However , active or non active is determined by the clinical history ! FACIAL MELASMA Clinical studies with Mesoestetic treatments options Dermamelan treatment ® Mesoestetic group, Barcelona, spain Material and methods : • 22 women • Prospective study • mainly melasma withrecognized hormons factors ( 20/ 22) • During summer season • From may 2005-october 2005 in Marseille , France • With or without oral contraceptive Material and methods : • Randomized split face study • Evening : - one side : Dermamelan ® mesoestetic, Barcelona, Spain - one side : Mela D ® la roche Posay , France Morning : SPF 25 UVB Sunscreen Evaluation : • Standardized and UV photographs ( frame , lighting, exposure) • MASI determination at baseline , D30, D120 • Mexameter : objective measurement of melanin content • MASI and mexameter analyzed with Wilcoxon signed rank test Results :MASI MASI 1,20 1,00 0,80 Amelan M 0,60 Mela D 0,40 0,20 0,00 T0 T1 T2 Results :Mexameter Mexameter results 530,00 520,00 510,00 Amelan 500,00 Mela D peau saine 490,00 melaninindex 480,00 470,00 T0 T1 T2 T0 / T1 : Dermamelan ® side before summer ( may- june) one month follow up T0 / T1 : Dermamelan ® side before summer ( may- june) T0 / T1 : Mela D ® side before summer ( may- june) T0 / T1 : Mela D ® side before summer ( may- june) T0 / T2 : Dermamelan ® side before and after summer ( May – september 4 months follow up) T0 / T2 : Dermamelan ® side before and after summer ( May – september 4 months follow up) T0 / T2 : Mela D ® side before and after summer ( May – september 4 months follow up) T0 / T2 : Mela D ® side before and after summer ( May – september 4 months follow up) T0 / T1 : Dermamelan ® side T0 / T1 : Dermamelan ® side T0 / T1 : mela D ® side T0 / T1 : mela D ® side T0 / T2 : Dermamelan ® side T0 / T2 : Dermamelan ® side T0 / T2 : mela D ® side T0 / T2 : mela D ® side Discussion : on photos • We evaluate efficacy by MASI score on normal lighting photographs and observed that both cream have a statistical significance between T0 / T1 and T0 / T2 Discussion : Mexameter • Dermamelan ® treated side has a significant decrease T0 / T1 and T0 / T2.(p<0.0001) • Between the 2 treated sides , Dermamelan ® has a significant decrease on mela D at all time study ( p < 0.0001) Disussion : conditions • Summer season : we can treat during summer without any risks • We can treat all phototypes even dark skin • Only 25 UVB sunscreen twice daily Conclusion of the study : • Dermamelan cream ® is mostly effective than mela D ® and very effective • Dermamelan cream ® is highly effective on melasma with hormonal influence • No need to stop oral contraceptives • Normal lighting and MASI is not sufficient to determine efficacy. • Mexameter and self questionnaire are the ideal tools to evaluate melasma treatments. JAAD 2013 Our comments to design a study • Randomized controlled study during summer season • Inclusion of selected type of melasma ( hormons or PIH , not miscellaneous) • Inclusion with « RCM histometry »(epidermal melanocyte account and dermal melanophages account) Pilot study of Dermamelan ® treatment with RCM ( reflectance confocal microscopy) in different types of Melasma University of Nice Pr Bahadoran Ph Dr Levy JL Pr Ortonne JP MATERIAL and METHODS • 10 patients , open pilot study • Non selected melasma : due to hormons and PIH : 2 types • Skintypes II, III, IV • Dermamelan ® (salicylic acid, acide azelaique, acide kojique, arbutin, glycirrhiza glabra = extrait de liquorice), 1 daily with a sunblock IP 50 le matin • Three months (oct-dec) • Evaluation MASI, photos (lumiere+UV) • Reflectance confocal microscopy (RCM) average MASI 25 20 15 average MASI 10 5 0 0 1 2 3 4 5 10 patientes - MASI 45 40 35 30 pat. 1 pat. 2 25 pat. 3 pat.4 MASI pat. 5 20 pat. 6 pat. 7 pat. 8 15 pat . 9 pat. 10 10 5 0 0 1 2 3 4 5 6 VISITES Melasma with hormonal influence Melasma with hormonal influence Melasma without hormonal influence • We confirmed the very quick efficacy of Dermamelan ® Treatment ( 2-4 weeks). • Especially in melasma hormons type than PIH type but without any statistical significance • RCM could separate the 2 types suspected by the clinical examination and confirmed that melanophages in the dermis are more difficult to treat. Summary 3 Our experiences and studies • Melasma with hormonal influence must be treated by Dermamelan treatment ®= average 60-70 % improvement in our series. • Melasma wiithout hormonal influence gave less lightening results with Dermamelan treatment ® ( reference treatment) = average 30-40 % improvement Melasma : treatment options • Topical based Hydroquinone treatments • Topical based Non-Hydroquinone treatments • Peeling