Phototherapy of psoriasis Ljubomir B Novaković FRCP Consultant Dermatologist QEH and St. John’s Institute of Dermatology, London The Southeast of England Phototherapy Network 17th Update Meeting, St. Thomas’ Hospital, 19th June 2014

Phototherapy Traditionally means the use of artificial UVB irradiation delivered by fluorescent lamps without the addition of an exogenous photosensitizer Narrowband UVB (NB–UVB, TL–01) Broadband UVB (BB–UVB) 2

Photochemotherapy with psoralens Psoralens – naturally occurring phototoxic compounds; absorb photons and go on to interact with cell function via photochemical reactions PUVA = combined use of the furocoumarin drug psoralen (P) + ultraviolet A (UVA) Wholebody (oral, bath) Local (oral, paint, bath)

Phototherapy Mechanism of action UV radiation is absorbed by endogenous chromophores – nuclear DNA Alteration of the cytokine profile Promotion of immunosuppression Cell cycle arrest – induction of apoptosis

Phototherapy – safety Dosimetry and calibration Constancy of lamp output should be checked weekly using an independent hand–held dose meter Calibration of a UV dosimeter – on an annual basis BAD Working Party report on minimum standards for phototherapy services (www.bad.org.uk)

Minimal erythema dose (MED) and minimal phototoxic dose (MPD) The MED/MPD is the dose that provokes a just perceptible erythema Establishing MED/MPD – safe practice Skin type assessment – risk of burning

Phototherapy of psoriasis Moderate to severe psoriasis Psoriasis unresponsive to topical treatment “Thick” psoriasis – PUVA or combination therapy with UVB Children – UVB phototherapy Standard course – around 30 sessions

Phototherapy of psoriasis Protocol for oral PUVA With MPD testing (preferred) 8–methoxypsoralen (MOP) or 5–MOP Frequency of treatment: twice per week Initial dose: 70% MPD Increments: 20% Maximum single dose: 15 J/cm²

Bath PUVA Bath PUVA preferred to oral PUVA: in children significant hepatic dysfunction in patients with cataracts where psoralen–drug interaction anticipated i.e. warfarin No need for eye protection after therapy Lack of systemic side effects e.g. nausea

Phototherapy of psoriasis Protocol for bath PUVA With MPD testing (preferred) 8–MOP preferred to 5–MOP and TMP (increased risk of a blistering phototoxic reaction) Frequency of treatment: twice per week Initial dose: 50% MPD Increments: 20% Maximum single dose: 8 J/cm²

Hand and foot PUVA Frequency of treatment: twice per week Maximum single dose: 15 J/cm²

Phototherapy of psoriasis Protocol for NB–UVB With MED testing (preferred) Frequency of treatment: three times per week (preferred) Initial dose: 70% of MED Increments: 20% Maximum single dose: 5 J/cm²

Psoriasis NB–UVB is superior to BB-UVB Almost 30 years of clinical experience and data from several controlled studies have demonstrated that NB–UVB is more effective for psoriasis than NB–UVB

Randomized double–blind trial of the treatment of chronic plaque psoriasis: efficacy of PUVA vs NB–UVB therapy PUVA is significantly more effective than NB–UVB, requiring significantly fewer treatments for clearance, giving significantly longer remissions, and having a similar low incidence of short–term adverse effects However, because of better long–term safety of NB–UVB than PUVA, it should be preferred as a first choice, until disease response noted, PUVA being kept in reserve for NB–UVB failures Yones SS et al. Arch Dermatol 2006; 142(7): 836–42.

Median treatment numbers for clearance with PUVA and NB–UVB PUVA is significantly more effective than NB–UVB requiring significantly fewer treatments for clearance (PUVA median = 17, NB–UVB median = 28.5, p<0.001)

PUVA and NB–UVB are both effective Efficacy of PUVA therapy vs NB–UVB in chronic plaque psoriasis: a systematic literature review PUVA and NB–UVB are both effective PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance NB–UVB is preferred as first line phototherapy option because of long–term risks of PUVA Archier E et al.. J Eur Acad Dermatol Venereol 2012; 26 (Suppl 3): 11-21.

Phototherapy of psoriasis Minimising a risk Keep cumulative doses low Do not exceed a total number of sessions over 150 for PUVA and 200–300 for NB–UVB Combination therapy e.g. retinoids Regularly update and improve protocols; audit Life–long monitoring of patients who received excessive PUVA

Combination therapy Topicals: tar, dithranol, calcipotriol, tazarotene; corticosteroids Retinoids (Re–PUVA, Re–NB UVB) Methotrexate Biologics – main concern is potentially increased risk of skin cancer

Acute side effects of phototherapy Similar to sunburn Clinical features: erythema, edema, vesiculation and necrosis Peak before 24 hours – UVB Peak at about 72–96 hours – PUVA, related to psoralen phototoxicity More likely with topical PUVA Oral 8–MOP may cause nausea/vomiting Some patients may develop PLE

Long–term side effects of phototherapy UVB is known carcinogen No significant association between NB–UVB and BCC, SCC or melanoma in 3867 patients treated with NB–UVB in Tayside, Scotland However, cautious interpretation is required – relatively few patients who had a high treatment number and because the slow evolution of skin cancers may result in a delayed incidence peak Hearn RM et al. Br J Dermatol 2008; 159: 931–5 .

Long–term side effects of PUVA Premature photoageing Risk of cataracts PUVA lentigines Increased number of actinic keratoses SCC incidence in PUVA–treated psoriasis correlates with cumulative UVA dose Slightly increased risk of melanoma (Stern RS and the PUVA Follow-Up Study, 2001); cumulative dose or number of phototoxic episodes

Phototherapy of psoriasis Conclusion Phototherapy, in its different forms has proved itself to be well–established, safe, effective and reliable in the treatment of psoriasis NB–UVB should be preferred as a first choice because of better long–term safety PUVA is more effective than NB–UVB Combination with other treatment modalities should be considered in unresponsive patients Phototherapy will remain a cornerstone in the treatment of psoriasis