Transcript Adverse Events in Phototherapy - Yorkshire Phototherapy Network

Adverse Events in Phototherapy
Kathryn Thomson
• Phototherapy involves exposure of the skin to
ultraviolet light with or without the use of a
phototoxic drug
• Ultraviolet light is known to cause DNA damage
and predispose to skin cancer
• Phototherapy also has a number of other
potential side-effects that need to be considered
before starting treatment
• It is essential to know about these in order to
advise patients appropriately, prevent where
possible and treat if not
Adverse Events
• Short Term/ Acute Events
• Long Term / Chronic risks
• Potential adverse events vary according to type of
phototherapy used, extent of treatment (local/
whole body),previous treatments, patient specific
factors
• Differences between PUVA and UVB
Adverse Effects of PUVA
Four main variables;
The Psoralen (drug choice and mode of
delivery)
The ultraviolet radiation
The patient (skin type/ photosensitivity/ patient
size)
The equipment
Adverse Events related to Psoralen
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Nausea: common with 8MOP, rarer with 5MOP
Headache, dizziness, sweating, general malaise
Itch- more common with 8MOP
Rarer side-effects include rashes, asthma,
deranged LFTs
Exacerbation of cold sores
Drug interactions
Exacerbation of photosensitivity eg PLE
PUVA blisters (lesional and perilesional)
Contraindications to oral PUVA
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Pregnancy
Severe Liver or renal disease
Immunosuppressant agents
Previous skin cancers
Previous severe adverse reaction to psoralen
Patients where compliance with eye
protection cannot be ensured
Drug History
Medications may interact with psoralen or cause
photosensitivity or phototoxicity
• Coumarin anticoagulants eg warfarin .
Manufacturers recommend that they are not
used together
• Tolbutamide causes increased photosensitivity
• Anticonvulsants can reduce psoralen levels
Psoralen Pharmacology
• A light meal increases bioavailability of 8MOP by up to
50%, heavy meals decrease peak concentration and
increase time taken to reach peak
• Psoralen binding in tissues is shortlived- 24 hours after
taking minimal psoralen detected in skin and organs
• psoralen is rapidly metabolised in liver, but once the
enzymes are saturated psoralen is allowed to
accumulate. Over the threshold small increases in dose
result in larger increases in plasma levels ie dose
increase of 10-40mg results in 25 x one hour plasma
level
How to Manage Psoralen Induced
Events
Nausea:
1) take psoralen with food (light low fat meal as
high fat diets reduce psoralen absorption) or
2) Prescription anti-emetics
3) switching to 5MOP which is absorbed more
slowly and has a lower peak plasma level
PUVA Itch
1)Emollients
2)Antihistamines
3) Switch to 5MOP
4)Switch to bath PUVA (can still occur but is less
common)
5) Consider TLO1 or other treatments if
persistent
Can be painful- PUVA pain
Ultraviolet triggered events
Cold sores
1) Ask about history before treatment
2) Consider visor / sunblock to protect the
affected site
PLE
Consider changing to TLO1 with lower dose
regime.
Acute Ultraviolet Reactions
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Sunburn like erythema
Redness, oedema and potential blistering
Oral PUVA peak: 2-3 days
Bath peak: 3-5 days
More common in normally covered
protuberant areas
• Can be graded on basis of severity (see later)
• Localised burning in bath PUVA
Chronic Adverse Effects of PUVA
• Skin aging- epidermal thinning, wrinkling, loss of
elasticity, leathery texture, elastotic
degeneration, uneven pigmentation (hyper and
hypo), PUVA keratoses
• Eyes- cataracts (eye protection for oral PUVA for
24 hours)
• Non-melanoma skin cancer: steep dose response
curve seen, highest risk at male genital skin: risk
increased if on immunosuppression, type I and II
skin, previous skin cancer, keratoses, previous
radiotherapy
Adverse Events in UVB
Acute
• Erythema and sunburn-like reaction (more common than
with PUVA). Reactions are maximal at 24-36 hours
• Transient erythema- starts a few minutes after UV exposure
and persists for up to 8 hours. Not visible by next
appointment
• Itch: less common than with PUVA
• Cold sores: as with PUVA
• Eyes: keratitis and conjunctivitis (eyes feel gritty)
• Facial pigmentation (particularly with pregnancy/
hormones)
• Facial dermatitis- mild seen in around 5% patients
Chronic Effects of UVB
• Premature ageing- less than with UVA
• Non melanoma skin cancer: risk is probably
lower than with PUVA, although not fully
established
Clinical Assessment of Erythema
(taken from Cardiff phototherapy manual 2010)
E0: no erythema
E0+: patient reported initial erythema but
settled by attendance
E1: barely perceptible asymptomatic erythema
E2: well defined erythema, with mild discomfort
E3: symptomatic painful well defined erythema
E4: painful erythema with blisters
Erythema Grading
E1
E2
E3/4
Erythema Protocols
ADVERSE EFFECTS
a)
Grade 1 erythema (mild) - barely perceptible erythema repeat previous dose consider reduction to 10% increments
b)
Grade 2 erythema (moderate) - well defined symptomatic
erythema postpone until settled then give penultimate
dose at next visit and thereafter reduce to 10% increments
c)
Grade 3/4 erythema (severe) - symptomatic erythema and/or
bullae. No treatment and reviewed by a doctor on call. When
settled treat at 50% of previous dose
Risks of Carcinogenesis
• Risks of skin cancer are hard to quantify
• Increased risk with immunosuppressants, fair
skins (red hair and freckling), high levels of sun
exposure
• Risk thought to be significantly higher after 200
exposures of PUVA and 500 exposures of TLO1
(some centres use 300)
• Annual skin surveys are recommended for
patients with high treatment levels and other risk
factors
Reducing Risk
• Optimum phototherapy regime achieves
complete clearance with minimum exposure
numbers, low cumulative dose and fewest
possible side effects
Reducing Acute Adverse Events
• Careful assessment of patients considering all absolute and
relative contraindications
• Written information sheets
• Clear information about good practice in the cabinet
• Advice about topical applications/ cosmetics/ deodorants
• Avoid hair cuts
• MED/ MPD pre treatment
• Accurate and careful record keeping to ensure correct
dosing
• Adverse incident recording
• Audit
Reducing Long Term Risks
• Cover areas not needing treatment (genital and
ocular protection, visors)
• Minimise use in patients with high treatment
numbers
• Use adjuvant therapies where possible to reduce
exposure numbers
• Ensure phototherapy used appropriately (ie not
just to avoid topical treatments)
• Annual screening for patients with high
cumulative treatment numbers
Reducing Risks (continued)
• Regular discussion about adverse events to
look for trends
• Audit