MELASMA Photoprotection and light devices

Transcription

1 MELASMA Photoprotection and light devices Pr. Thierry Passeron, MD, PhD Department of Dermatology & INSERM 05 team University Hospital of Nice, France Conflicts of interest Research grants and/or honoraria: Bioderma Beiersdorf DELEO Galderma L OREAL ISIS Pharma SVR Symrise Syneron-Candela Melasma is a long-lasting disorder INDUCTION TREATMENT -4 months MAINTENANCE TREATMENT Sun protection Spontaneous improvement during winter High rate of recurrences (after summer+++) Impact of UVB and UVA well demonstrated (check for PPD index) Visible light induces significant and long lasting hyperpigmentation in dark skin types (skin types III and higher) Only the shorter wavelengths of the visible light are propigmenting Mechanisms involved appear to be different to those involved in UVBinduced pigmentation Role of the visible light J Invest Dermatol 00; 0:09-7 Pigment Cell Melanoma Res. 04;7:8- Role of the blue/violet light in pigmentary disorders? Melasma?? Impact of protection against shorter wavelengths of visible light in melasma relapses Development of a visible light protection index Monocentric randomized comparative study on 40 patients with melasma Begin of the study the two first weeks of April End of the study the two first weeks of September Evaluation on MASI performed on standardized pictures (VISIA, Canfield) by two independent physicians blinded to the sunscreen received *,4 UVB/UVA/visible UVB/UVA No lost to follow-up No significant differences in the quantity of sunscreen used 0,45 D in mean MASI score between last and first visit * p<0.05 Interest of combining protection against UVB, UVA and shorter wavelengths of visible light for optimal protection in melasma J Am Acad Dermatol. 05;7:89-90 Photodermatol Photoimmunol Photomed. 07;:0-

2 Visible light Laser and light-based treatments of melasma Membrane of skin type III to VI melanocyte USF p8 USF 400 nm CREB -M 45 nm OPSIN P CaMKII P P -M Ca + Ca + Tyrosinase DCT TYRP Prolonged melanogenesis Tyr/P complex J Invest Dermatol. 08;8:7-78 Q-switched ruby, alexandrite or Nd:YAG lasers: Mild to moderate efficacy Constant relapses and high rate of PIH Intense pulsed light Mild to marked improvement reported in several studies Combination with Trio > Trio alone Decrease in MASI score remains at 44.9% at months in combination group Vs none in Trio alone Risk of PIH mostly in skin type IV to VI Australas J Dermatol. 05;5:5- Dermatol. Ther. 0; 5: Low-fluence QS laser and melasma Results : Low-fluence QS 04nm laser showed promising results in pilot studies Prospective randomized split face study patients with melasma % HQ vs %HQ + low-fluence QS Nd:YAG 04nm HQ started weeks before the laser treatment 5 weekly sessions of laser in total (spot mm; fluence to.8 J/cm²) Evaluation : MASI + colorimeter Follow-up: weeks after the end of the treatment Dermatol Surg 00;:7-87 End of Tx : ++ At weeks: Relapse in all the patients + 4 PIH Randomized controlled studies are required with long term follow-up are mandatory to confirm pilot studies Dermatol Surg 00;:7-87 Low-fluence QS laser side effects 4 cases of hypochromia sequella following repetitive use of lowfluence QS laser (9 for photo ageing and 5 for melasma) No or weak interest of lowfluence QS laser for treating melasma Laser Surg Med. 00;4:7-9 Non ablative fractional laser for melasma 550nm fractional laser showed interesting results for treating melasma in preliminary studies Open study: 5 patients One session every month for 4 months Evaluation: MASI and spectrophotometry Follow-up: months Derm Surg 009;5:

3 Results: After Tx: Marked improvement in 4% of patients At months: Constant but slight relapses MASI : mean 7. (. 4.7) at M0 to. (.8 0.) (p=0.0) Worsening of the hyperpigmentation in % of cases Derm Surg 009;5: Non ablative fractional laser for melasma Prospective comparative randomized study 0 melasma patients, skin types II to V Non ablative 550nm fractional erbium laser 8 passages (MTZ 000 to 500/cm; 0mJ) session every weeks for 8 weeks Vs Kligman s trio /d for 8 weeks Evaluation blinded to the treatment received Main criterion: PGA Follow-up wks, and months after the end of the treatment J Am Acad Dermatol 0;4:5- Both treatment are effective at weeks No significant statistical difference between the groups In both groups half of the patients relapsed at months Only 8 weeks of treatment with Kligman s trio (instead of weeks) Kligman s trio remains the gold standard treatment for melasma! Laser thulium 97 nm for melasma Laser thulium 97nm for melasma Encouraging results in a pilot study in 0 Retrospective study in 0 women with long term follow-up Skin type II to IV Derm Surg. 0;8: mj/cm² with 0-70% coverage Evaluation on MASI score up to months 5 patients seen at months Recurrence in 7 out of 5 patients PIH Lasers Surg Med. 0;45:95 0 One retrospective study combining Thulium and PDL on patients / had more than 50% of improvement No rebound, no PIH Lasers Surg Med. 07;49:0- No prospective randomized study available J Am Acad Dermatol 0;4:5- Picosecond laser for melasma Prospective, randomized, split-face, controlled study 40 patients with melasma 7 week % HQ (daily) on one side of the face 7 week % HQ (daily) + 5 weeks 5/04nm picosecond laser (weekly) Follow-up 8 weeks Main criteria : mmasi on standardized pictures 8 patients in per protocol analysis and 9 in mitt Lasers Surg Med. 07;49: Revisiting melasma pathology Increased number of melanocytes, increased epidermal and dermal melanin 9% moderate/severe elastosis 84% increased melanocytes Increased melanin at all level of the epidermis Dermal melanin in % with increased dermal melanin and melanophages (%) Melasma lesional skin 70% mild/moderate elastosis No increase in melanocytes Melanin not increases in the epidermis Dermal melanin noted in % of perilesional cases in Korean skin Perilesional normal skin Br J Dermatol 00; 4: 8-7

4 Melasma, a vascular disorder? Perilesional normal skin lesional skin Factor VIIIa-related antigen Factor VIIIa-related antigen Vessel density (mm²) Vessel size (µm²) Vessel area (%) Melasma Transcriptomic study Affymetrix platform more than probesets Statistical analysis selection of differentially expressed genes Bioinformatic analysis Gene ontology analysis Ingenuity pathway analysis Hierarchical clustering of lesional and perilesional normal skin of 0 melasma patients. A hierarchical clustering based on the genes that were considered as differentially expressed, where red/green color is the higher expression/lower expression groups, respectively. Normal Lesion Normal Lesion Normal Lesion J Dermatol Sci. 007;4:- J Invest Dermatol. 0;:9-700 Melasma Transcriptomic study Identification of genes differentially expressed in melasma lesional skin patients (only 0 evaluated) 79 genes significantly up or down-regulated in melasma lesional skin Up-regulation of many melanin bio-synthesis-related genes as well as melanocytes markers Increased expression of a subset of Wnt pathway modulator genes Prostaglandin metabolic process up-regulated Genes that regulate fatty and metabolism differentially expressed => Many cells and biological functions are involved in the pathophysiology of melasma J Invest Dermatol. 0;:9-700 UV p8 USF Regulation of skin pigmentation: A complex process USF PGE PGF ACTH amsh ET- ET- ET- SCF Keratinocyte HGF bfgf GM-CSF Proliferation Differentiation Melanin synthesis Dendrite genesis (Adapted from Hirobe 005) DKK, NRG, SCF, sfrp Fibroblasts? Role of skin microvascularization in pigmentation Perilesional Lesional Perilesional Lesional 00 benign vascular lesions High magnification digital dermoscopy (x50 X00) Laser confocal microscopy and histology Significant increase of pigmentation above and around vascular lesions Crucial role of endothelin secreted by endothelial cells 4

5 Control EDNRb inhibitor Control EDNRb inhibitor Mechanism of action of tranexamic acid in melasma? Prospective study with biopsies after weeks of treatment with TA - + HMVEC - + HMVEC - + HMVEC Melanocyte 0 week weeks Endothelial cell ET EDNRb ERK p8 P DCT TYR Pigmentation TA might act on melasma through a decreased production of endothelin J Invest Dermatol. 05;5:09-04 Clin Exp Dermatol. 0;4:480-5 PDL treatment for melasma Prospective randomized controlled slip face study 8 patients with melasma (skin types II to IV) Intervention: Stabilized triple combination cream Applied once a day for 4 months on the entire face PDL Start after month of triple combination cream sessions (every weeks) on hemi face st passage with pressure hand piece 0mm,.5ms, 7J/cm² nd passage with hand piece 7mm, 0ms, 0J/cm², DCD 0/40 Blinded evaluation after summer Results Mean difference between the groups in hemimasi score at V4 was.9 points (p=0.09) NS 9 8 * MASI TRIO * MASI TRIO PDL 7 p=0.0 NS Non significant 5 * p< p<0.0 * p< V0 V V V V4 Analysis was performed with Wilcoxon signed-rank test To account for multiple analysis a was reduced to 0.05 Results PDL and melasma Phototypes II and III V0 V V V V MASI TRIO 5 MASI TRIO PDL 4 0 Phototypes IV NS NS V0 V V V V4 MASI TRIO MASI TRIO PDL Promising results Need confirmation in larger series Optimal parameters and schedule of treatment have to be determined Results confirmed in a recent Korean prospective trial (IPCC 04 Pr YH Kang) and in a recent case report with long term follow-up IPCC 04. Com Pr YH Kang Dermatol Surg. 0;4:55-9 Risk of PIH in skin types IV and higher that limits this approach NS Non significant * p<0.05 p<0.0 Analysis was performed with Wilcoxon signed-rank test To account for multiple analysis a was reduced to 0.05 Interested of targeting vessels for treating melasma 5

6 Altered basal membrane VL WIF, DKK, NRG, SCF, sfrp Melasma SUN Therapeutics Photoprotection +++ UVA Melanocyte ET UVB amsh ET PGE SCF HGF bhgf Keratinocyte IL, IL, Vit D, Mélasma = UVB + UVB + Blue light + pigmentation + vascularisation + elastosis and fibroblast secreted factors + altered basal membrane => Global therapeutic approach Peeling (risk of PIH) 550nm fr laser (risk of PIH) 94nm thulium fr laser (few data and risk of PIH) IPL Pulsed dye laser Tranexamic acid Failure Kligman Trio for -4 months (including against shorter wavelengths of visible light) Discuss discontinuation of hormonal treatment +/- Avoid friction HQ 5% Tretinoin 0.% Dexamethasone acetate 0.% Success Maintenance treatment: Photoprotection++ Cosmetic blanching cream Risk of PIH in skin types IV and higher Off label used Fibroblast Endodelial cells Sebocyte Passeron T, Picardo M. Melasma a photoaging disorder. Pigment Cell Melanoma Res. 07 Dec 9. doi: 0./pcmr.84. Topical EDNRB inhibitors DKK agonists Chemical approaches to prevent visible light-induced pigmentation To be determined