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PHOTOTHERAPY FOR PSORIASIS

Marie-Claude Marguery,Dermatology Service

Purpan Hospital,Toulouse

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Various phototherapies used

Therapies combined with phototherapies

Indication and choice of phototherapy

Sunbeds and psoriasis: what should we think?

PHOTOTHERAPY FOR PSORIASIS

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Various phototherapies:

• systemic PUVA therapy

• topical PUVA therapy

• local or full body bath PUVA therapy

• narrow band UVB therapy (TL01-311 nm)

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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/m2 SC in under-weight or obese patients to avoid under- or overdose

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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

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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

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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)

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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

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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)

PhototypeInitial dose

J/cm2

Increment at each session J/cm2

Maximum dose J/cm2

II 1 0.25 5

III 1.5 0.25 7

IV 2 0.50 9

V 2.5 0.50 11

VI 3 1 12

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Systemic PUVA therapy: UVA doses

"Classical" protocol with 8-MOP (0.6 mg/kg)

PhototypeInitial dose

J/cm2

Increment at each session J/cm2

Maximum dose J/cm2

II 1.5 0.25 6

III 2 0.25 8

IV 3 0.50 10

V 4 1 12

VI 5 1 15

"Aggressive" protocol: initial dose = phototype value!

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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

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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/cm2 (60 to 150 J/cm2) Remission after 1 year estimated to be approx 30 to 50%

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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

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Compliance with maximum cumulative doses:

• Over a course: 100 to 150 J/cm2

• Over a year: 30 sessions

• Over a lifetime:

150 to 200 sessions

1200 J/cm2: fair prototype

1500 J/cm2: dark prototype

Systemic PUVA therapy: Precautions and Monitoring

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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

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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

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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

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Narrow band UVB therapy

Used successfully since 1990-1995Performed with Philips TL01 tubesPhosphate fluorescent lamp narrow band centred on 313 nmDirectly active radiation, reproducing sunshine on the Dead

Sea coastContraindications similar to PUVA apart from pregnancy,

liver dysfunction, renal failure and cataractsMay be performed on children but not highly recommended

before the age of 10 years

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Phototype II

J/cm2

Phototype III

J/cm2

Phototype IV

J/cm2

0.200 0.250 0.300

0.240 0.300 0.390

0.290 0.360 0.510

0.350 0.430 0.660

0.500 0.520 0.860

0.600 0.620 0.990

0.660 0.750 1.090

0.730 0.900 1.2

0.800 1.080 1.3

0.880 1.560 1.590

0.970 1.6 1.750

1.070 1.6 1.8

1.290 1.6 1.8

1.4 1.6 1.8

UVB TL01

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Phototype II

• Dose 1: 0.200 J/cm2

by 20% per session 0.600 Jby 10% per session maximum dose of 1.4 J

Phototype III

• Dose 1: 0.250 J/cm2

by 20% per session maximum dose of 1.6 J

Phototype IV

• Dose 1: 0.300 J/cm2

by 30% per session 0.900 Jby 10% per session maximum dose of 1.8 J

UVB TL01

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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/cm2, 20 to 30 sessions Duration of remission after stopping: estimated at 5 months

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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.

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• 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

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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

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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)

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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

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• 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

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Indication and Choice of Phototherapy

- Full body bath PUVA therapy

. Phototype VI

. Psoralen contraindications

- Local bath PUVA therapy

. Palmoplantar psoriasis

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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

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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

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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

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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

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- 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?