Transcript Phototherapy of Psoriasis

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)
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
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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:
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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
Skin type Palms and soles Dorsa of hands
I
1 J/cm²
0.5 J/cm²
II
1.5 J/cm²
1 J/cm²
III
2 J/cm²
1.5 J/cm²
IV
2.5 J/cm²
2 J/cm²
V, VI
3 J/cm²
2.5 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)
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
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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