1. 1 PHOTOTHERAPY FOR PSORIASIS Marie-Claude Marguery, Dermatology Service Purpan Hospital, Toulouse

2. 2  Various phototherapies used  Therapies combined with phototherapies  Indication and choice of phototherapy  Sunbeds and psoriasis: what should we think? PHOTOTHERAPY FOR PSORIASIS

3. 3 Various phototherapies: systemic PUVA therapy topical PUVA therapy local or full body bath PUVA therapy narrow band UVB therapy (TL01-311 nm)

4. 4 Systemic PUVA therapy  Method comprising broad band UVA radiation after oral administration of psoralen, used for about 30 years, highly effective  Reference psoralen: 8-methoxypsoralen: 8-MOP Meladinine ® 10 mg tablets administered orally, 2 hours before UVA radiation 0.6 mg/kg 25 mg/m 2 SC in under-weight or obese patients  to avoid under- or overdose

5. 5  If digestive intolerance (nausea) caused by 8-MOP  Use 5-methoxypsoralen: 5-MOP Psoradem-5 ® : 20 mg tablets administered orally, 3 hours before UVA radiation 1.2 mg/kg Same number of tablets / Meladinine ® tablets

6. 6  Radiation equipment: low pressure mercury vapour fluorescent tubes  Type: Philips TL09, CLEO-UVA, or F85 Sylvania  Band: 320 to 450 nm, peak at 352 nm Systemic PUVA therapy

7. 7 Systemic PUVA therapy: contraindications  ABSOLUTE: basal cell naevus syndrome, hereditary dysplastic naevi syndrome, personal history of MM, SLE, DM, DNA repair disorders and diseases  RELATIVE MAJOR: age < 10, pregnancy and breastfeeding, history of cutaneous carcinoma, previous exposure to IR, actinic keratosis, concomitant immunosuppressant therapy, porphyria  RELATIVE MINOR: age < 16 years, cataracts, bullous autoimmune disorders, biological hepatic dysfunction, renal failure, long term course of phototoxic drugs, skin phototype 1 (red)

8. 8 Systemic PUVA therapy: pre-therapy assessment  Patient history: long term therapies + medical history  Dermatological clinical examination  Patient history + clinical examination  phototype ++++  Biology:* creatinine * transaminases * ± antinuclear antibodies  Ophthalmologic consultation desirable

9. 9 Systemic PUVA therapy: doses of UVA  3 protocols  Doses depending on phototype  Protocols: "gentle", "classical" and "aggressive", where doses are close to causing erythema  "Gentle" protocol with 8-MOP (0.6 mg/kg) Phototype Initial dose J/cm 2 Increment at each session J/cm 2 Maximum dose J/cm 2 II10.255 III1.50.257 IV20.509 V2.50.5011 VI3112

10. 10 Systemic PUVA therapy: UVA doses  "Classical" protocol with 8-MOP (0.6 mg/kg) Phototype Initial dose J/cm 2 Increment at each session J/cm 2 Maximum dose J/cm 2 II1.50.256 III20.258 IV30.5010 V4112 VI5115  "Aggressive" protocol: initial dose = phototype value!

11. 11 Systemic PUVA therapy: frequency of sessions  Aggressive therapy: 3 sessions/week for 4 to 5 weeks 2 sessions/week: as effective in comparative studies, but no reduction in total dose, of benefit if patient lives far away  Maintenance therapy: brief! 2 sessions/week for a fortnight 1 session/week for a fortnight

12. 12 Systemic PUVA therapy: Results  Efficacy +++  Lesions totally or almost totally cleared in 80 to 95% of cases  In 15 to 30 sessions  Average total dose of UVA: 100 J/cm 2 (60 to 150 J/cm 2 )  Remission after 1 year estimated to be approx 30 to 50%

13. 13 Systemic PUVA therapy: Precautions and Monitoring  Phototoxic erythema  adjustment of doses * delayed PUVA-induced erythema, 24 to 36 hours after radiation, maximum between 48th and 72nd hour  Eye protection during the session and for 12 hours following ingestion of psoralen  Carcinogenic risk of PUVA, dose-dependent, well-known

14. 14  Compliance with maximum cumulative doses: Over a course: 100 to 150 J/cm 2 Over a year: 30 sessions Over a lifetime:  150 to 200 sessions  1200 J/cm 2 : fair prototype  1500 J/cm 2 : dark prototype Systemic PUVA therapy: Precautions and Monitoring

15. 15 Other PUVA therapies 1)Topical PUVA therapy:  Application of psoralen in the form of a cream or lotion to lesions only, followed by UVA radiation  In France: weak meladinine ® solution, little used technique because of frequent phototoxicity and long- lasting and unattractive subsequent hyperpigmentation

16. 16 2)Bath PUVA therapy  Immersion of the whole or part of the body in water containing 8-MOP at 2.4 mg/l  Local BP: palmoplantar, meladinine ® weak solution, 1/2 vial in 5 litres of water  Whole body BP: meladinine ® strong solution, 2 vials in 150 litres of water  Duration of bath: 15 minutes  Water temperature: 37°  Skin to be patted dry, without rubbing  UVA radiation: immediately after the bath for whole body BP and 30 min after the bath for local BP

17. 17 Benefits of whole body bath PUVA therapy  In case of psoralen contraindications: hepatic failure, renal failure, cataracts.  In case of phototype VI as doses of UVA used are approximately 4 times lower  Lower carcinogenic risk? Negative response [8-MOP] which is involved in PUVA carcinogenesis, higher in BP. Carcinogenic risk identical for oral PUVA and bath PUVA therapy

18. 18 Narrow band UVB therapy  Used successfully since 1990-1995  Performed with Philips TL01 tubes  Phosphate fluorescent lamp  narrow band centred on 313 nm  Directly active radiation, reproducing sunshine on the Dead Sea coast  Contraindications similar to PUVA apart from pregnancy, liver dysfunction, renal failure and cataracts  May be performed on children but not highly recommended before the age of 10 years

19. 19

20. 20 Phototype II J/cm 2 Phototype III J/cm 2 Phototype IV J/cm 2 0.2000.2500.300 0.2400.3000.390 0.2900.3600.510 0.3500.4300.660 0.5000.5200.860 0.6000.6200.990 0.6600.7501.090 0.7300.9001.2 0.8001.0801.3 0.8801.5601.590 0.9701.61.750 1.0701.61.8 1.2901.61.8 1.41.61.8 UVB TL01

21. 21  Phototype II Dose 1: 0.200 J/cm 2  by 20% per session  0.600 J  by 10% per session  maximum dose of 1.4 J  Phototype III Dose 1: 0.250 J/cm 2  by 20% per session  maximum dose of 1.6 J  Phototype IV Dose 1: 0.300 J/cm 2  by 30% per session  0.900 J  by 10% per session  maximum dose of 1.8 J UVB TL01

22. 22 Narrow band UVB therapy  Aggressive therapy: 3 sessions/week obligatory 2 sessions/week, +++lower efficacy/3 sessions  Brief maintenance therapy, similar to PUVA therapy  Efficacy +++  Lesions cleared in 60 to 80% of cases  Cumulative dose: 15 to 30 J/cm 2, 20 to 30 sessions  Duration of remission after stopping: estimated at 5 months

23. 23 Phototherapy for Psoriasis: Combined therapies - Combination with oral retinoids (acitretin)  Re-PUVA or Re-TL01 Advantage of this combination demonstrated through open, controlled and comparative studies.  Quality of result.  Total dose of UVA or UVB approximately halved.

24. 24 Superior efficacy related to better UV penetration by  hyperkeratosis Soritane begun 15 days before phototherapy, continued during and after phototherapy  result maintained Re-PUVA or Re-TL01

25. 25 Phototherapy for Psoriasis: Combined therapies - Benefit of combination of calcipotriol (Daivonex ® ) - PUVA and calcipotriol - TL01 - Benefit of combination of tazarotene - phototherapy (PUVA or TL01)  Superior efficacy

26. 26 Indication and Choice of Phototherapy -Phototherapy: first line therapy for moderate to severe chronic plaque psoriasis (body surface > 10% and/or DLQI >10) -Pustular and erythrodermic psoriasis are not good indications (possible aggravation)

27. 27 Choice PUVA therapy /UVB-TL01 UVB TL01 to be used as a first line treatment because it is almost as effective as PUVA, easy to perform and carcinogenic risk presumed lower UVB TL01: preferable for psoriasis in children and pregnant women

28. 28 PUVA should be used as a first line treatment for severe and extensive psoriasis (very high PASI score) PUVA to be used as a second line therapy if resistance to TL01 (observed occasionally) or if relapse too soon after stopping TL01 Choice PUVA therapy /UVB-TL01

29. 29 Indication and Choice of Phototherapy - Full body bath PUVA therapy. Phototype VI. Psoralen contraindications -Local bath PUVA therapy. Palmoplantar psoriasis

30. 30 Sunbeds and psoriasis: what should we think? - Patients with psoriasis ask, or may ask, if using a sunbed could help control their psoriasis - Some patients  previous use of sunbeds to good effect - Dermatologist's response: sunbeds cannot be expected to be effective given the very low levels of UVB (0.7%) emitted

31. 31 Turner et al. Br J Dermatol 2000;143:957-963 - Randomised controlled study UVA from sunbeds/placebo (visible light) in 36 patients with slight to moderate stable psoriasis - UVA radiation of one lateral half of the body - Radiation by visible light of the other lateral half of the body by applying an opaque anti-UVA film on half the tubes - 3 sessions/week for 4 weeks, 12 sessions - Assessment: change in PASI score, target lesions severity score, patient questionnaire

32. 32 Turner et al. Br J Dermatol 2000;143:957-963 Results: -17 patients (47%) reduction of PASI was greater on the UVA side/placebo side -11 patients (31%): no difference -8 patients (22%): improvement more noticeable on the placebo side -Slight reduction in PASI: -4.4  3.9 UVA side -4.4  4.2 placebo side -P= 0.044

33. 33 Turner et al. Br J Dermatol 2000;143:957-963 -Target lesions severity score: significant  only regarding erythema -Patient questionnaire: 64% of patients thought the response was good enough to use sunbeds to treat their psoriasis

34. 34 -Low efficacy of sunbeds -Well-known risk of photoageing and malignant melanoma -Use of sunbeds not recommended for patients with psoriasis Sunbeds and psoriasis: what should we think?