Transcript PUVA

PUVA THERAPY IN
D E R M AT O L O G Y
F.Fatemi,MD
Isfahan university of medical sciences
DEFINITION
PUVA is a kind of photo-chemotherapy using the sensitizing
effects of the drug psoralen :
is applied or taken orally to sensitize the skin,
then the skin is exposed to UVA.
Psoralens are photosensitizing agents found in plants.
SEVERAL CUMARINS ARE USED FOR PUVA
 8-MOP
 5-MOP
 4,5′,8- trimethoxypsoralen (as well as the traditional 8-MOP for
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bath PUVA )
Oral psoralens are metabolized in the liver within 24 hr.
The metabolites are excreted via the kidney.
The psoralens allow a relatively lower dose of UVA to be used.
When they are combined with exposure to UVA in PUVA, they are highly
effective
CHOOSING THE PROPER UV DOSE FOR PUVA
European clinics test the skin before the treatments, by exposing a small area
of the patient's skin to UVA, after ingestion of psoralen.
 The dose of UVA that produces uniform redness 72 hours later, called the
minimum phototoxic dose (MPD) becomes the starting dose for treatment.
 However others
(Americans) uses the skin-type–based PUVA protocol .
 choose a dose based on the patient's skin type.
 The dose will increase in every treatment until the skin starts to respond.
ORAL PUVA
THERAPY
 In the United States
and in Europe, 2
slightly differing
protocols of oral
PUVA were
Evaluated .
 in these trials
both proved
their efficacy.
C O M PA R I S O N O F E U RO P I A N & A M E R I C A N P ROTO C O L S
Although equally efficient in clearing psoriasis, the American scheme
needs 25% more UV exposures and almost 8 weeks more of
continuous therapy resulting in a 2.5-fold higher cumulative UV-A
dose until remission is achieved.
Therefore, newer guideline sencourage the use of the safer European
protocol instead of the American one, although precise determination
of MPD is a difficult in very dark-skinned individuals.
Despite such recommendations and because of the time saving aspect,
however, the skin-type–based PUVA protocol still has a lot of followers
Note :
Phototoxic reactions are delayed, with an erythema reaction peaking
48 to 72 hours after irradiation. Therefore, accurate UVA dosimetry
is distinctly required for PUVA therapy as overdosage can easily lead to
skin necrosis.
Sometimes, the patient's extremities (in particular the lower
extremities) arc exposed to higher doses than the trunk.
UV PHOTOTHERAPY & PUVA
RESPONSIVE DERMATOSIS
P U VA T H E R A P Y I N P S O R I A S IS
Localized PUVA
 Localized psoriasis of hands and feet (hand/foot unit)
 Localized disease not responding to other modalities of therapy
Systemic PUVA
 Psoriasis involving >20% body surface area
 Unresponsiveness to topical therapy
.
SYSTEMIC PUVA AS A EFFECTIVE MODALITY IN
THE TREATMENT OF PSORIASIS
 Guttate and seborrheic (minimally elevated) forms of psoriasis respond most
favorably and rapidly to broadband UVB, while chronic, plaque type is more
resistant.
 PUVA has proven its efficacy in virtually all subtypes of psoriasis
 Only generalized pustular psoriasis and erytherodermic psoriasis are difficult
to treat with PUVA alone and normally need a combination therapy with
retinoids (Re -PUVA)
Despite its proven efficacy, broadband UVB is certainly inferior to
PUVA, both in terms of clearing efficiency and duration of remission.
Oral PUVA therapy should be continued until the plaques are not
palpable anymore and scaling and intrinsic erythema are gone.
PIP is no indication for continuing treatment.
 In general no maintenance therapy should be done .
Some authors argue, however, that patients with more aggressive disease
should be subjected to a maintenance therapy once weekly for 2 months in
to assess the course of the response further.
SID E EF F ECTS OF ORAL PU VA
Early & Late effects
EARLY
EFFECTS
Oral PUVA is generally well tolerated; however, a number of
potentially serious side effects exists :
Phototoxic reactions : a prodromal state with general malaise and
itch precedes the rash.
GI symptoms (ie, nausea and vomitus) are not uncommon but can
often be improved by intake of 8-MOP with some food , especially
milk.
Rarely, increase in transaminase levels in the liver, and, thus liver
function tests should routinely be performed before starting oral
PUVA.
LATE
EFFECTS
 PUVA in the long term leads to a photoaged skin pattern with
elastosis, poikiloderma, and lentigines.
Of concern is the induction of NMSCs , which is proven and occurs
in more than 25% of PUVA-treated patients.
 Whether melanoma can be induced by PUVA has not been clarified.
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All patients who received several course of oral PUVA should
enter a long-term-follow up program for at least 25 years
THE RISK OF C ARCINOGENICITY , PUVA VS UVB
There is an increased risk of skin cancer following PUVA, shown by both US and
European studies.
The greater risk measured by the US studies may be at least partly explained by high
UVA dose exposure and the lighter phototypes of the patients.
The lack of prospective studies in psoriasis patients treated with NB-UVB
constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy
technique.
LATE EFFECTS CONT..
Eye problems :
Because psoralens bind to the proteins in the lens , there is further risk for cataract
evolution under PUVA therapy.
In addition , damage to the retina could also be possible due to the photooxidative reactivity of psoralens passing through the retinal vessels.
Therefore, eye protection has to be worn for at least 12 hours after PUVA
Studies have not shown an increased incidence of cataracts under eye
protection, so this preventive measure seems to achieve the desired effect.
ABSOLUTE
C O N T R A I N D I C AT I O N S :
Genetic dermatosis characterized by photosensitivity or high risk for skin
cancers(UVB,PUVA)
Treatment with cyclosporine (UVB,PUVA)
Previous history of skin cancer if current cancer ,especially SCC& MM (UVB,PUVA)
High cumulative number of PUVA treatment (>150-200 individual treatments) (PUVA)
Pregnancy or lactation (PUVA)
Child's age (young children) (PUVA)
R E L AT I V E
C O N T R A I N D I C AT I O N S
 Previous history of arsenic exposure, ionizing radiation (UVB,PUVA)
 Immunosupressive medication (UVB,PUVA)
 Atypical melanocytic nevi (UVB,PUVA)
 Seizure disorder,risk of fall/injury (UVB,PUVA)
 Poor compliance (UVB,PUVA)
 Men & women in reproductive age without contraception (PUVA)
 Impaired liver function or hepatotoxic medications(PUVA)
 Cataract(PUVA)
N E E D TO A D J U S T D O S E O R M O N I TO R C L O S E LY
Skin type 1 (UVB,PUVA)
Photosensitive dermatoses (UVB,PUVA)
Unavoidable systemic or topical phototoxic medications (UVB,PUVA)
Vitiligo (UVB,PUVA)
 possible interactions with medication : warfarin(PUVA)
PRE PROCEDURE RECOMENDATION
Advisable is to have :
eye examination
LFTs
RFTs
ANA ,anti-Ro antibody
PREC AUTIONS DURING PUVA THERAPY
 UV-blocking goggles are used to protect the eyes.
 If treatment is not required for facial involvement, the face is protected either by
use of a broad spectrum sunscreen with an SPF of 50+ or a cloth barrier.
Male genitalia are protected with the use of underwear or an athletic supporter
If PUVA is to be given to the genitalia, exposure at 25% of the ideal dose can be
safely undertaken
PREC AUTIONS AFTER PUVA THERAPY
 Patients must protect their eyes after ingesting psoralen. Wraparound UV-blocking glasses,
which give complete UVA photoprotection should be worn when the patient is exposed to
sunlight, from the time methoxsalen is ingested until sunset
 Sun avoidance is advised to minimize pigmentation from natural sunlight. Excessive pigmentation
may ultimately limit the effectiveness of PUVA therapy and require higher doses of UVA.
 The skin should be protected from natural sunlight through appropriate clothing and avoidance
 The amount of UVA emitted by common fluorescent lights is insufficient to activate psoralens. Thus,
photoprotection is not required in home or office settings.
BATH PUVA THERAPY
B AT H P U VA T H E R A P Y
Several studies rated bath PUVA equally or even better than systemic PUVA
Advantages :
 the lack of GI and hepatic side effects
 No need for eye protection.
Disadvantages :
 higher running costs due to greater complexity of the procedure
 Low patient adherance
Bathwater PUVA is not undertaken
during pregnancy or breast-feeding.
0.5-1 mg/L 8-MOP , 0.33 mg / L TMP
Start with 0.3 MPD
Perform 2-4 irradiation /Wk
Immediate irradiation after bathing ,constant 37°C temperature in the PUVA
bathwater.
In some publications, trimethylpsoralen is preferred over 8-MOP as the agent
to add to the bathwater because of its much higher photosensitizing capacity
Sheet bath PUVA
Bathing the patient on a foil in a
bath that is wetted with roughly 10 L
of 8-MOP containing warm water
medisun Balneo 2000 was developed specially for brine
and PUVA-foil baths with subsequent UV radiation..
How it works:
The patient lies in the bath solution separated from the
bath water by the foil (e.g. 5 liter brine or Meladinine
solution). The pressure of the bath water from all sides
ensures an even film of fluid on the patient
S I D E E F F E C T S O F B AT H
PUVA
Acute side effects such as phototoxic reactions, pruritus occur in the same
proportion as with oral PUVA.
A large study that found that bath PUVA carries a lower risk of skin cancer
development in the long term than oral PUVA.
The photo carcinogenic potential of PUVA is dose related & because bath
PUVA requires smaller cumulative UVA doses than systemic PUVA, the
cumulative risk must be lower for this treatment modality.
PUVA bath can be used to treat
local disease spots, particularly
palms and soles, without exposing
the rest of the body.
LOCAL BATH PUVA
 The skin is gently dried off. Some centres recommend a
waiting period of 15 to 30 minutes while the solution
penetrates into the skin, whereas others treat immediately.
 The affected skin is exposed to UVA emitted from special
fluorescent lamps.
 The treated skin should then be covered for the next 2-3 days,
especially when outdoors, to protect it from inadvertent
exposure to UVA.
PUVA TH ERAPY I N VI TI L I G O
Topical PUVA
Localized disease
Systemic PUVA
 Vitiligo involving more than 10% body surface area
 Patients with localized disease not responding to topical PUVA or
other modalities of treatment
TO P I C A L P U VA I N V I T I LI G O
Topical PUVA with 8MOP may be used in patients with smaller lesions
involving less than 5% of body surface area.
0.01-0.1% 8MOP in a cream or lotion base is applied to the affected area and
irradiation is done after 30 min.
A weekly increment of 0.25 J/cm 2 or by 20% of the previous dose is given till
onset of erythema.
Application of sunscreen to the surrounding uninvolved skin can prevent
undue tanning.
TMP and 5MOP are more phototoxic topically.
P AT I E N T S E L E C T I O N F O R S Y S T E M I C
PUVA IN VITILIGO
Darker skinned people respond better than those who are fair skinned.
 Head and neck lesions and lesions on hairy parts of the body respond best.
lips, dorsae of hands, acral parts, bony prominences, palms, soles, and
nipples are refractory to treatment.
Segmental vitiligo may or may not respond.
Duration of disease does not affect the response rate to PUVA.
P AT I E N T S E L E C T I O N F O R P U V A I N
VITILIGO
This treatment seldom achieves extensive repigmentation that is cosmetically
acceptable
Treatment response is often followed by relapse
 Response is denoted by the occurrence of perifollicular repigmentation and 70%
cases respond within 12-24 weeks. If there is no response even after approximately
50 sessions, PUVA should be discontinued
Patients with vitiligo affecting more than 30-40% body surface area (BSA) do not
respond well to medical therapy.
PATIENT SELECTION FOR PUVA IN VITILIGO
 For optimal and maximum pigment induction, prolonged therapy lasting for months
is required with as many as 100-200 exposures given 2-3 times a week
If response occurs and patient discontinues treatment, the newly acquired
repigmentation may be lost.
Completely repigmented areas may remain stable for more than 10 years.
P U VA V S U V B I N V I T I L I G O
NUVB phototherapy is now used more commonly than PUVA since it does not
require the use of the Psoralen.
 NBUVB does not cure the legs and hands, compared to the face and neck.
 To the hands and legs PUVA may be more effective.
The reason can be because UVA penetrates deeper in the skin, and the
melanocytes in the skin of the hands and legs is deeper in the skin. The Narrowband
UVB does not reach the melanocytes
In comparison studies of NUVB with PUVA, narrowband UVB was as effective as
PUVA also had:
 fewer side effects .
 In a recent randomized double-blind trial of non-segmental vitiligo, NUVB therapy was
superior to oral PUVA therapy and the color match of repigmented skin was
considered to be better in the patients treated with NBUVB.
PUVASOL
 PUVASOL stands for psoralen and UVA
obtained by solar light
 PUVASOL is advised for those patients
who cannot visit the hospital for
phototherapy.
Disadvantages:
 Difficulty in quantifying UV light.
 The total amount of UVA reaching the skin at any one time varies widely depending on the
season, time of the day, latitude, and conditions of the atmosphere.
 Difficulty in monitoring the dose of ultraviolet rays
 UVB ,IR and VL, which are not needed for PUVA therapy may lead to undesirable effects.
 UVB in sunlight can increase the thickness of epidermis and makes the sun-exposed skin
leathery and may interfere with the effectiveness of light therapy.
According to a study conducted by Balasara swathy et al., the best
time of the day for PUVASOL is between 9.15-11.15 a.m. and 2.303.30 p.m.
There is minimal unwanted exposure to UVB and infrared light at these
times.
SYSTEMIC PUVASOL IN PSORIASIS
 In two Indian studies, nearly 55% and 63% of patients have shown good to
excellent improvement with PUVASOL in psoriasis.
 8MOP in the dose of 0.6 mg/kg body weight is administered after breakfast. Nearly
1.5-2h later, sun exposure is advised for 10 min.
 Treatment is carried out 2-3 times/week and time of exposure is increased by 5
min every week till a maximum of 30-45 min.
 Use of eye protective glasses and avoidance of further sun exposure for the next 8h is
to be followed to prevent eye toxicity and darkening of the normal skin.
TOPIC AL PUVASOL IN PALMOPLANTAR PSORIASIS
Dilute 1 cc of 8-MOP 0.1 % in 1 lit tap water then soak hands and/or feet in
thissoltion for 15 min and then be expose immediately to sun light for 15 min.
3-4 s/w
Also indicated for palmoplantar LP or hyperkeratotic palmoplantar eczema
After puvasol wash the skin area and put zinc oxide or sunscreen for the
remaining of the day.
SYSTEMIC PUVASOL IN VITILIGO
In vitiligo, oral TMP is preferable to 8MOP due to its weaker phototoxic
effects.
Treatment should be given twice to thrice weekly, with a minimum gap of 1
day between treatments.
The duration of sun exposure is to be increased weekly until there is mild
erythema of the involved area after which, that time can be kept constant.
If there is no improvement even after
30-40 sittings, it should be discontinued.
TOPIC AL PUVASOL IN VITILIGO
Though topical PUVASOL is generally avoided due to the greater phototoxic
risk and frequent occurrence of painful blisters, it may be tried during rainy season
A total of 0.1% 8MOP is applied carefully over the vitiliginous patches (one part
of commercially available 8MOP lotion can be diluted with nine parts of eau-decologne and used). Propylene glycol can also be used as a diluent.
After 30 min, the patches are exposed to sunlight starting with 0.5-1 min.
Treatment is done 2-3 times/week and duration of sun exposure should be slowly
increased by 0.5-1 min every week till slight erythema appears after which the
time is kept constant.