Vitiligo Physical Treatments Torello Lotti University Unit of Dermatology University of Florence Florence, Italy
Vitiligo: a key concept <ul><li>Melanocytes are not completely absent in the depigmented epidermis  </li></ul><ul><li>Comm...
Should I treat vitiligo? <ul><li>16% of dermatologists in The Netherlands are in favour of active treatment of vitiligo </...
I have to treat vitiligo! <ul><li>Positive balance of active treatments of vitiligo patients* </li></ul><ul><li>Topical co...
So, how to treat vitiligo? <ul><li>Cosmetic camouflage (dihydroxyacetone) </li></ul><ul><li>Depigmentation ( Monobenzyl et...
Psoralen plus UV-A oral photochemotherapy (PUVA) …the classic <ul><li>Oral assumption of photosensitizers (Psoralenes) tak...
Psoralen plus UV-A oral photochemotherapy (PUVA) <ul><li>Possible side-effects: </li></ul><ul><ul><li>Nausea, vomiting, di...
Ideal treatment in vitiligo: phocused therapy  <ul><li>Efficacy </li></ul><ul><li>Rapid repigmentation </li></ul><ul><li>E...
Monochromatic treatment of vitiligo XTRAC  Xenon-Chloride Gas Excimer Laser (308 nm) EXCILITE  Xenon-Chloride Monochromati...
Laser treatment: Technical specifications <ul><li>XTRAC Excimer Laser </li></ul><ul><li>(Photomedex, USA) </li></ul><ul><l...
Monochromatic Excimer Light :  Technical specifications Int J Immunopathol Pharmacol 2002;13(1):11-13  <ul><li>Source  Exc...
Narrow Band UVB Excimer Laser (XeCl) and MEL <ul><li>UVB 308 nm </li></ul><ul><li>Only the hypopigmented areas are treated...
BEFORE AFTER 20 TREATMENTS J Korean Med Sci 2005; 20: 273-8
Narrow Band UVB and Microphototherapy - BIOSKIN <ul><li>UVB 311 nm </li></ul><ul><li>Only the hypopigmented areas are trea...
BIOSKIN ®  device simplified scheme 1) UVB generator 2) Visible and UV 4) Interference Filter 3) Time controlled Leaf Shut...
BIOSKIN ®  Microphototherapy
BIOSKIN ®  emission spectrum Intensity 10-100 mW/cm 2 DEM=40 mW  × 10 sec=400mJ/cm2
Microphototherapy <ul><li>This phototherapy permits a differentiated irradiation. </li></ul><ul><li>Thus is possible to ir...
BIOSKIN ®  and Microphototherapy <ul><li>UVB narrow band (311 nm) irradiated on vitiligo patches only </li></ul><ul><li>Lo...
Results of a study on 734 patients after 2 years of  BIOSKIN ®  treatment
 
Microphototherapy vs.  MEL and XTRAC <ul><li>MICROPHOTOTHERAPY </li></ul><ul><li>UVB 311 nm </li></ul><ul><li>Sessions: ev...
CONCLUSION? VITILIGO Both Narrow Band UVB Excimer Laser and Narrow Band UVB Light  show similar results in similar time of...
Vitiligo therapy & EBM: what is really effective? <ul><li>Several RCTs showed oral psoralen plus UVA (PUVA) and plus sunli...
Vitiligo therapy & EBM: what is really effective? <ul><li>Topical class 3 corticosteroids have been shown to be effective ...
Vitiligo therapy & EBM: what is really effective? <ul><li>One RCT showed that the combination of NB-UVB and tacrolimus is ...
Vitiligo combination therapy: our experience
Group 1 BIOSKIN ® alone Group 2 0.1%Tacrolimus+ BIOSKIN ®  Group 3 1% Pimecrolimus+BIOSKIN ® Group 4 Betamethasone dipropi...
Results <ul><li>13 subjects stopped the therapy for personal motivations before the end of the study </li></ul><ul><ul><li...
Percentage of repigmentation in patients treated with BIOSKIN ®  alone or in combination, or with active topicals alone. T...
Repigmentation rates: beginning of repigmentation (weeks) as assessed by clinical evaluation
Repigmentation rates and final repigmentation results: visual comparison of different treatment groups as assessed by clin...
Vitiligo and evidence based dermatology <ul><li>Dermatologists are prescribing less PUVA in favour of UVB </li></ul><ul><l...
Vitiligo and evidence based dermatology <ul><li>Both BIOSKIN ® and Potent topical corticosterod preparations alone are the...
How I treat vitiligo <ul><li>Correct diagnosis  </li></ul><ul><li>Comorbidities </li></ul><ul><li>Patient expectations </l...
Thank you for your attention professor @ torellolotti.it Future combination treatments are in the pipeline
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Phisical treatments in Vitiligo - Prof. Lotti Torello, MD

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Melanocytes are not completely absent in the depigmented epidermis
Comment:
A subpopulation of “resistant” epidermal melanocytes can persist independent of disease duration
Repigmentation can always occur independent of disease duration and with non-perifollicular pattern

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  • Still considered by many dermatologists as the first line treatment for vitiligo
  • Phisical treatments in Vitiligo - Prof. Lotti Torello, MD

    1. 1. Vitiligo Physical Treatments Torello Lotti University Unit of Dermatology University of Florence Florence, Italy
    2. 2. Vitiligo: a key concept <ul><li>Melanocytes are not completely absent in the depigmented epidermis </li></ul><ul><li>Comment: </li></ul><ul><ul><li>A subpopulation of “resistant” epidermal melanocytes can persist independent of disease duration </li></ul></ul><ul><ul><li>Repigmentation can always occur independent of disease duration and with non-perifollicular pattern </li></ul></ul>
    3. 3. Should I treat vitiligo? <ul><li>16% of dermatologists in The Netherlands are in favour of active treatment of vitiligo </li></ul><ul><ul><ul><ul><li>Njoo MD et Al, Int J Dermatol 1999;38:866-872 </li></ul></ul></ul></ul><ul><li>84% of dermatologists in The Netherlands are reluctant to start any active treatment in vitiligo; 82% in the Mediterranean area either prescribe placebos or treatments of cosmetic relevance only </li></ul><ul><ul><ul><ul><li>Lotti T. La vitiligine: nuovi concetti e nuove terapie. UTET – Torino, 2000 </li></ul></ul></ul></ul>
    4. 4. I have to treat vitiligo! <ul><li>Positive balance of active treatments of vitiligo patients* </li></ul><ul><li>Topical corticosteroids (max 6 months)  89% </li></ul><ul><li>PUVA treatment (max 12 months)  16% </li></ul><ul><li>PUVA treatment (max 9 months)  25% </li></ul><ul><li>UVB treatment (max 6 months)  87% (Broad + Narrow Band) </li></ul><ul><li>Surgical treatment (one shot + UVB)  68% </li></ul><ul><li>*evaluation made by Dermatologists </li></ul><ul><li>Int J Dermatol 1999;38:866-872 </li></ul><ul><li>Arch Dermatol 1999;135:1514-1521 </li></ul>
    5. 5. So, how to treat vitiligo? <ul><li>Cosmetic camouflage (dihydroxyacetone) </li></ul><ul><li>Depigmentation ( Monobenzyl ether of hydroquinone, Q-switched ruby laser) </li></ul><ul><li>Repigmentation (corticosteroids, psoralen photochemotherapy , UVB phototherapy ) </li></ul><ul><li>The efficacy of UVB in vitiligo therapy is probably due to: </li></ul><ul><ul><li>Its immunesuppressive effect </li></ul></ul><ul><ul><li>Stimulation of melanocytes </li></ul></ul>
    6. 6. Psoralen plus UV-A oral photochemotherapy (PUVA) …the classic <ul><li>Oral assumption of photosensitizers (Psoralenes) taken 2 hours before UVA (320-400 nm) exposure </li></ul><ul><li>8-Methoxypsoralen (8-MOP) 0.6-0.8 mg/kg, or 4,5,8-trimethylpsoralen 0.6 mg/kg </li></ul><ul><li>Treatments are given 3 times weekly but not on two consecutive days </li></ul><ul><li>Best results on the face and neck, worst on the extremities </li></ul><ul><li>Increased risk of skin cancer induction  photoprotection and maximum amount of treatments are to be considered </li></ul>
    7. 7. Psoralen plus UV-A oral photochemotherapy (PUVA) <ul><li>Possible side-effects: </li></ul><ul><ul><li>Nausea, vomiting, dizziness, sweating </li></ul></ul><ul><ul><li>Increased contrast between healthy and affected skin </li></ul></ul><ul><ul><li>Burns </li></ul></ul><ul><ul><li>Itch </li></ul></ul><ul><ul><li>Skin cancer induction </li></ul></ul><ul><ul><li>… </li></ul></ul>… The classic
    8. 8. Ideal treatment in vitiligo: phocused therapy <ul><li>Efficacy </li></ul><ul><li>Rapid repigmentation </li></ul><ul><li>Easy and quick esecution </li></ul><ul><li>Only the hypopigmented areas are treated </li></ul><ul><li>Safety </li></ul><ul><li>Pain free </li></ul>
    9. 9. Monochromatic treatment of vitiligo XTRAC Xenon-Chloride Gas Excimer Laser (308 nm) EXCILITE Xenon-Chloride Monochromatic Excimer Light (308 ± 1 nm) BIOSKIN Narrowband UVB (311nm)
    10. 10. Laser treatment: Technical specifications <ul><li>XTRAC Excimer Laser </li></ul><ul><li>(Photomedex, USA) </li></ul><ul><li>Source XeCl </li></ul><ul><li>Wavelength 308 nm </li></ul><ul><li>Treatment surface 3,2 cm 2 </li></ul><ul><li>Pulse duration 30 ns </li></ul><ul><li>Fluence 3 mJ/cm 2 </li></ul><ul><li>Pulse repetition 200 Hz </li></ul>J Am Acad Dermatol 2002 Jun;46(6):900-6
    11. 11. Monochromatic Excimer Light : Technical specifications Int J Immunopathol Pharmacol 2002;13(1):11-13 <ul><li>Source Excimer </li></ul><ul><li>Wavelength 308 nm  1 </li></ul><ul><li>Treat. Surface 36 x 14 cm </li></ul><ul><li>Irradiance 50 mW/cm 2 </li></ul><ul><li>Main supply 230 V ac -12A-50/60Hz </li></ul><ul><li>Dimensions 150cm(H)-50cm(W)- 105cm(D) </li></ul><ul><li>Weight 120 Kg </li></ul>
    12. 12. Narrow Band UVB Excimer Laser (XeCl) and MEL <ul><li>UVB 308 nm </li></ul><ul><li>Only the hypopigmented areas are treated </li></ul><ul><li>No contrast between normal and hypopigmented skin </li></ul><ul><li>Low dose of irradiation </li></ul><ul><li>Reduced short-term and long-term side effects </li></ul><ul><li>Treatment of limited body areas </li></ul>
    13. 13. BEFORE AFTER 20 TREATMENTS J Korean Med Sci 2005; 20: 273-8
    14. 14. Narrow Band UVB and Microphototherapy - BIOSKIN <ul><li>UVB 311 nm </li></ul><ul><li>Only the hypopigmented areas are treated </li></ul><ul><li>Particulary effective for the treatment of limited affected areas and segmental vitiligo. </li></ul><ul><li>Does not increase the colour contrast </li></ul><ul><li>Low dose of radiation </li></ul><ul><li>Low rates of short-term and long-term adverse events </li></ul>
    15. 15. BIOSKIN ® device simplified scheme 1) UVB generator 2) Visible and UV 4) Interference Filter 3) Time controlled Leaf Shutter 7) Specific Optical Fiber 5) N.B. UVB 8) Vitiligo patch 6) Iris Diaphragm
    16. 16. BIOSKIN ® Microphototherapy
    17. 17. BIOSKIN ® emission spectrum Intensity 10-100 mW/cm 2 DEM=40 mW × 10 sec=400mJ/cm2
    18. 18. Microphototherapy <ul><li>This phototherapy permits a differentiated irradiation. </li></ul><ul><li>Thus is possible to irradiate i.e. hands and feet with a dose 5 or 6 times higher than the dose used for eyelids. </li></ul>
    19. 19. BIOSKIN ® and Microphototherapy <ul><li>UVB narrow band (311 nm) irradiated on vitiligo patches only </li></ul><ul><li>Lotti T, Menchini G, Andreassi L. UV-B microphototherapy. An elective treatments for segmental vitiligo. J Eur Acad Dermatol Venereol. 1999;13:102-8 </li></ul><ul><li>Menchini G, Comacchi C, Tsoureli E, Lotti T. Microfototerapia BIOSKIN®. In: La vitiligine: nuovi concetti e nuove terapie. T. Lotti. 2000 Ed UTET periodici scientifici srl (MI). pp 108-114 </li></ul>
    20. 20. Results of a study on 734 patients after 2 years of BIOSKIN ® treatment
    21. 22. Microphototherapy vs. MEL and XTRAC <ul><li>MICROPHOTOTHERAPY </li></ul><ul><li>UVB 311 nm </li></ul><ul><li>Sessions: every 3 weeks </li></ul><ul><li>Repigmentation after 6 sessions </li></ul><ul><li>Permits a differentiated irradiation </li></ul><ul><li>MEL AND XTRAC </li></ul><ul><li>UVB 308 nm </li></ul><ul><li>Number of sessions: 1/week (MEL); 2-3/week (XTRAC) </li></ul><ul><li>Repigmentation after 10-20 sessions </li></ul>
    22. 23. CONCLUSION? VITILIGO Both Narrow Band UVB Excimer Laser and Narrow Band UVB Light show similar results in similar time of treatment even if they can be used only in limited skin surfaces.
    23. 24. Vitiligo therapy & EBM: what is really effective? <ul><li>Several RCTs showed oral psoralen plus UVA (PUVA) and plus sunlight (PUVAsol) efficacy vs. placebo in achieving >75% repigmentation, and one RCT* showed PUVA as more effective than placebo plus sunlight. </li></ul><ul><ul><li>*Pathak MA, Mosher DB, Fitzpatrick TB. Natl Cancer Inst Monogr 1984;66:165-73 </li></ul></ul><ul><li>Recent RCTs found that NB-UVB is more effective than PUVA in achieving repigmentation°. </li></ul><ul><ul><li>°Yones SS, Palmer RA, Garibaldinos TM, Hawk JL. Arch Dermatol 2007;143578-84 </li></ul></ul><ul><li>Some RCTs showed that combination of different phototherapies with both vitamin D analogues and topical corticosteroids may increase the response rates. </li></ul><ul><ul><li>Ermis O, Alpsoy E, Cetin L, Yilmaz E. Br J Dermatol 2001;145:472-5 (calcipotriol and PUVA) </li></ul></ul><ul><ul><li>Leone G, Pacifico A, Iacovelli P, Paro Vidolin A, Picardo M. Clin Exp Dermatol 2006;31:200-5 (tacalcitol and MEL-UVB) </li></ul></ul><ul><ul><li>Westerhof W, Nieuweboer-Krobotova L, Mulder P, Glazenburg EJ. Arch Dermatol 1999;135:1061-6 (fluticasone and UVA) </li></ul></ul>
    24. 25. Vitiligo therapy & EBM: what is really effective? <ul><li>Topical class 3 corticosteroids have been shown to be effective in localized vitiligo, while no significative difference was shown between class 4 corticosteroids or intralesional corticosteroids and their respective placebos. </li></ul><ul><ul><li>Njoo MD, Spuls PI, Bos JD, Westerhof W, Bossuyt PM. Arch Dermatol 1998;134:1532-40 </li></ul></ul><ul><li>Combination of topical calcipotriol and betamethasone dipropionate is more effective than each treatment given alone, reducing side effects. </li></ul><ul><ul><li>Kumaran MS, Kaur I, Kumar B. J Eur Acad Dermatol Venereol 2006;20:269-73 </li></ul></ul><ul><li>0.1% tacrolimus is as effective as 0.05% clobetasol propionate. </li></ul><ul><ul><li>Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB, Ortiz CA, Torres-Rubalcava AB. Arch Dermatol 2003;139:581-5 </li></ul></ul><ul><li>Tacrolimus plus excimer laser is more effective than excimer laser alone </li></ul><ul><ul><li>Kawalek AZ, Spences JM, Phelps RG. Dermatol Surg 2004;30(2 Pt 1):130-5 </li></ul></ul>
    25. 26. Vitiligo therapy & EBM: what is really effective? <ul><li>One RCT showed that the combination of NB-UVB and tacrolimus is no more effective than NB-UVB alone. </li></ul><ul><ul><li>Mehrabi D, Pandya AG. Arch Dermatol 2006;142:927-9 </li></ul></ul><ul><li>One RCT found pimecrolimus to be no more effective than placebo in achieving repigmentation. </li></ul><ul><ul><li>Dawid M, Veensalu M, Grassberger M, Wolff K. J Dtsch Dermatol Ges 2006;4:942-6 </li></ul></ul><ul><li>There are many reports about the efficacy of melagenine, pseudocatalase, levamisole, and systemic antioxidant therapy in vitiligo, but RCT evidence is really scarce. </li></ul><ul><ul><li>Souto MG, Manhaes AMH, Milhomens CH, Succi ICB. An Bras Dermatol 1997;72:237-9 </li></ul></ul><ul><ul><li>Agarwal S, Ramam M, Sharma VK, et al. Br J Dermatol 2005;153:163-6 </li></ul></ul><ul><ul><li>Rojas-Urdaneta JE, Poleo-Romero AG. Invest Clin 2007;48:21-31 </li></ul></ul><ul><li>Not enough RCT evidence is available nowadays about surgical treatments for vitiligo. </li></ul>
    26. 27. Vitiligo combination therapy: our experience
    27. 28. Group 1 BIOSKIN ® alone Group 2 0.1%Tacrolimus+ BIOSKIN ® Group 3 1% Pimecrolimus+BIOSKIN ® Group 4 Betamethasone dipropionate 0.05%+BIOSKIN ® Group 5 Calcipotriol ointment 50mcg/g+BIOSKIN ® Group 6 10% L-phenylalanine+BIOSKIN ® Group 7 0.1% Tacrolimus alone Group 8 Group 1 Group 9 Betamethasone dipropionate 0.05% Group 10 Calcipotriol ointment 50mcg/g alone Group 11 10% L-Phenylalanine alone
    28. 29. Results <ul><li>13 subjects stopped the therapy for personal motivations before the end of the study </li></ul><ul><ul><li>Of these 4 were on topical corticosteroid treatment alone </li></ul></ul><ul><ul><li>3 on Tacrolimus 0.1% ointment alone </li></ul></ul><ul><ul><li>1 on Calcipotriol ointment 50mcg/g alone </li></ul></ul><ul><ul><li>1 on 10% L-phenylalanine cream alone </li></ul></ul><ul><ul><li>1 with Pimecrolimus 1% cream alone </li></ul></ul><ul><ul><li>2 with BIOSKIN ®+0.05% Betamethasone dipropionate cream </li></ul></ul><ul><ul><li>1 with Tacrolimus 0.1% ointment + BIOSKIN ® </li></ul></ul>
    29. 30. Percentage of repigmentation in patients treated with BIOSKIN ® alone or in combination, or with active topicals alone. Treatment (n° of patients) Excellent (>75%) Marked (50-75%) Moderate (25-50%) Minimal (<25%) Group 1: BIOSKIN ® alone (100) 72% 19.8% 4.6% 3.6% Group 2: 0.1% Tacrolimus + BIOSKIN ® (59) 76.5% 18.2% 3.3% 2% Group 3: 1% Pimecrolimus + BIOSKIN ® (63) 76.1% 20.1% 2.7% 1.1% Group 4: Betamethasone dipropionate 0.05% + BIOSKIN ® (28) 90.2% 6.7% 2.2% 0.9% Group 5: Calcipotriol ointment 50 mcg/g + BIOSKIN ® (60) 75.6% 14.1% 7.4% 2.9% Group 6: 10% L-Phenylalanine + BIOSKIN ® (60) 74.8% 11.3% 10.1% 3.8% Group 7: 0.1% Tacrolimus alone (22) 61% 16.1% 18.4% 4.5% Group 8: 1% Pimecrolimus alone (19) 54.6% 18.4% 21.7% 5.3% Group 9: Betamethasone dipropionate 0.05% alone (23) 71.2% 25% 2.1% 1.7% Group 10: Calcipotriol ointment 50 mcg/g (18) 59.1% 10.6% 27.1% 3.2% Group 11: 10% L-Phenylalanine alone (18) 29.3% 8.1% 55% 7.6%
    30. 31. Repigmentation rates: beginning of repigmentation (weeks) as assessed by clinical evaluation
    31. 32. Repigmentation rates and final repigmentation results: visual comparison of different treatment groups as assessed by clinical evaluation
    32. 33. Vitiligo and evidence based dermatology <ul><li>Dermatologists are prescribing less PUVA in favour of UVB </li></ul><ul><li>Growing introduction of combined treatments targeted UVB + “active” topicals </li></ul><ul><li>Repigmentation rates show the therapeutic success of focused microphototherapy which is more remarkable when used in combination </li></ul>
    33. 34. Vitiligo and evidence based dermatology <ul><li>Both BIOSKIN ® and Potent topical corticosterod preparations alone are the first line treatment in vitiligo vulgaris affecting less than 10% of the skin surface </li></ul><ul><li>Association of these 2 treatments gives better results, with very high repigmentation rate in more than 90% of patients </li></ul><ul><li>High repigmentation rates are observed also for other combination treatments, while Tacrolimus and Pimecrolimus but not phenylalanine are relatively active when applied without UVB irradiation </li></ul>
    34. 35. How I treat vitiligo <ul><li>Correct diagnosis </li></ul><ul><li>Comorbidities </li></ul><ul><li>Patient expectations </li></ul><ul><li>Communication issue </li></ul>
    35. 36. Thank you for your attention professor @ torellolotti.it Future combination treatments are in the pipeline

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