a full context abt PUVA

2. •Photochemotherapy with psoralens combines the
use of oral or topical Psoralens (P) and Ultraviolet-
A radiation (UVA) = PUVA

3. •Phototoxic compounds  enter cells  absorb
photons  produce photochemical reactions that
alters the function of cellular components
•Results in beneficial therapeutic effect after
repeated controlled phototoxic reactions

4. •Route of administration – oral
-- topical
(solutions,creams,baths)
•Types
1) Methoxalen or 8-methoxypsoralen(8-MOP)
2) Bergapten or 5-methoxypsoralen(5-MOP)
3) Trioxsalen or 4,5,8-trimethylpsoralen(TMP)

6. •PHOTOCHEMISTRY

7. •Pharmacokinetics
•Important steps between ingestion of a psoralen
and its arrival at the site of action include:
Absorption First-pass effect Blood
transportation Tissue distribution

8. •Oral psoralens
•Metabolised in the liver within 24hrs and excreted
via kidney
•Peak levels of psoralens in blood is 1-8hrs with a
mean of 2 hrs
•Photosensitivity is maximal upto 1- 2hrs after
ingestion of psoralen
•This forms the basic for giving UV radiation after 2
hrs of intake of psoralens

9. •Liquid preparations of 8-MOP & 5-MOP
•Give higher and earlier peak serum levels than
crystalline forms
•Before reaching skin  circulation,they are
metabolised during passage through the liver
•MOP have serum half life approx. 1hr but the skin
remains sensitive to light for 8-12hrs
•Despite widespread distribution of the drug
throughout the body, it is activated on the skin,
where UVA enters

10. •Topical psoralens when applied to skin they
rapidly penetrate and are detected in the urine
after 4hrs

12. •The action spectrum is reported to be between
320 and 400 nm.
•Common UVA sources are fluorescent lamps or
high pressure metalhalide lamps
•Typical fluorescent PUVA lamp has emission peak
at 325nm
•UVA doses are given in J/cm2, usually measured
with a max. Sensitivity at 350-360nm
•Although the action spectrum of antipsoriatic
activity & phototoxic erythema peaks at 335nm,
longer wavelengths have proved equally effective
in clearing psoriatic lesions

13. •PSORALENS- Photoconjugation of psoralens to DNA with
subsequent suppression of mitosis, DNA synthesis, and cell
proliferation  revert cell proliferation rates to Normal in
Psoriasis . They also stimulate melanogenesis
•PUVA - Revert pathologically altered patterns of keratinocyte
differentiation & the no. of proliferating epidermal
cells.
- Diminishes langerhans cell no’s within epidermis.
- Downregulates certain lymphocytes & APC functions
- Alters expression of cytokines and cytokine receptors

14. •Inflammatory response that manifests as delayed
phototoxic erythema, proportional to the dose of both
drug and UVA as well as to the individual’s sensitivity
to phototoxic reactions.
• PUVA erythema appears after 24–36 hours and
peaks at 72–96 hours, or even later
• Daily PUVA treatments can result in unexpected
severe delayed cumulative phototoxicity

15. •Severe PUVA reactions may lead to blistering
and to superficial skin necrosis, Pigmentation
•Overdoses of UVA  swelling, intense pruritus,
sometimes stinging sensation in the affected skin
area, possibly as a consequence of damage of
superficial nerve endings

17. •Application of 8-MOP as 0.15% in creams, ointments, or
lotions followed by UVA irradiation is effective in clearing
psoriatic lesions
•Disadvantages
Nonuniform distribution on skin surface phototoxic
erythema reactions and hyperpigmentation
Laborious and time consuming
Does not prevent apprearence of new active lesions in
previously untreated & unaffected areas
•Treatment of choice for limited plaque psoriasis and
palmoplantar disease

18. • DOSAGE
•8-MOP -- 0.6–0.8 mg/kg body weight OR
•5-MOP -- 1.2- to 1.8-mg/ kg body weight
Should be administered within 1-3 hrs before
exposure depending on absorption characteristics
of the particular drug.
Liquid drug preparations are absorbed faster and
yield higher and more reproducible serum levels
than microcrystalline forms

19. •The initial UVA doses are determined by either the
patient’s skin type or by MPD testing
•The MPD test should be performed on previously
nonexposed skin (e.g. buttocks).
•Time-consuming than phototyping, it allows for
more accurate and higher UVA doses during initial
treatment.

21. • MATERIALS REQUIRED:
• 3.75mg/L 8-MOP Or 0.33mg/L TMP in 100 ltrs of
water in a bath tub
• Whole body immersion- 15-20mins
• Immediate irradiation after bathing.
• Perform 2-4 irradiation /Week
• Trimethylpsoralen is preferred over 8-MOP as the
agent to add to the bathwater because of its
much higher photosensitizing capacity

23. INDICATIONS FOR BATH WATER
PUVA
Psoriasis
Scleroderma
Mycosis fungoides
Urticaria pigmentosa
Lichen planus
Prurigo nodularis
Subacute prurigo

24. • Several studies rated bath PUVA equally or even
better than systemic PUVA
• Advantages :
 No GI and hepatic side effects
 No need for eye protection.
 The total ultraviolet A dose required for bath PUVA is
3–6 times lower than oral PUVA.
• Disadvantages :
 Higher running costs due to greater complexity of
the procedure
 Low patient adherance

25. MATERIALS REQUIRED
plastic bucket
bathing suit made up of water absorbing material (flannel)
rain coat
2 LITRES of water
1 ml of 1% 8-MOP (3.75mg/l)
PROCEDURE
2LITRES of water + 3.75mg/l 8-MOP in a bucket and soaking
of bathsuit in this solution for 5mins pt wears bathsuit with
raincoat on top for 15 mins UVA radiation with starting dose
1-2J/cm2
Total of 15-20 treatments required for clearing psoriasis

26. Advantages
This method requires only 2 litres of water and 1 ml of
psoralen solution per treatment
•Therapy can be carried out at home with sunlight as the
UVA source.
Disadvantages
The entire body surface may not come in contact with the
bathing suit
•The concentration of psoralen may not be uniform in the
bathing suit.

27. MATERIALS REQUIRED
Plastic tub
3.75mg/l 8-MOP
2 litres of water
PROCEDURE
•Hands and/or Feet are soaked in a 3.75 mg/L solution of 8-MOP in
a small plastic tub or a basin for 20 minutes and then patted dry
•After another 30 minutes, the part is exposed to UVA in a hand
and foot unit
• Treatments are repeated 3–4 times/week
•If sunlight is used as the UVA source, the exposure time is 4–5
minutes initially with 1-minute increments every week up to a
maximum of 30 minutes.

29. INDICATIONS FOR SOAK
PUVA
Palmoplantar psoriasis
Chronic palmoplantar eczema
Palmoplantar pustulosis
Lymphomatoid papulosis
Twenty- Nail dystrophy
Congenital palmoplantar keratoderma

30. MATERIALS REQUIRED
Cotton cloth
3.75mg/l 8-MOP
2 litres of water
Small Plastic tub
PROCEDURE
•An absorbent cotton cloth is soaked for 30 seconds in a 3.75
mg/L solution of 8-MOP & gently squeezed to remove excess
water and wrapped around the head for 5 minutes.
•Repeated 4 times (a total of 20 minutes) and the area is then
exposed to UVA or sunlight.
If sunlight is used as the source of UVA, exposure starts with 5
minutes, increased by 1 minute with each exposure up to a
maximum of 15 minutes.
•treatment is given 3–4 times/week for 10–12 weeks

32. INDICATIONS FOR TURBAN PUVA
Alopecia areata
Chronic GVHD
Alopecia

33. Phototherapy-Responsive Diseases
Therapy of Disease
• Psoriasis
• Palmoplantar pustulosis
• Mycosis fungoides (stages IA, IB)
• Vitiligo
• Atopic dermatitis
• Generalized lichen planus
• Urticaria pigmentosa
• Cutaneous graft-versus-host
disease
• Generalized granuloma annulare
• Pityriasis lichenoides
• lymphomatoid papulosis
• Pityriasis rubra pilaris
• localized scleroderma
• Morphea
Prevention of disease
symptoms
• Polymorphous light eruption
• Hydroa vacciniformea
• Solar urticaria
• Erythropoietic protoporphyria
• Chronic actinic dermatitis

35. •SYSTEMIC PUVA
•Psoriasis involving >20% BSA
•Unresponsiveness to topical therapy
•LOCALIZED PUVA
•Localized psoriasis of hands and feet
•Localized disease not responding to other modalities of
therapy.

36. •Children aged less than 10 years. (Although in exceptional
circumstances, younger age groups may be considered for
treatment provided regular ophthalmologic evaluation is done
to rule out ocular toxicity)
•Pregnancy and lactation
•People suffering from photosensitivity disorders.

37. Differences btw the US and EUROPEAN protocols for PUVA therapy
US EUROPE
UVA dosimetry Predetermined dose
according to skin
phototype
Individualized dose
according to MPD
determination
Frequency of
treatment
2-3 times/week 4times/week
Dose
increments
0.5-1.5 j/cm2 0.5j/cm2 each
week

38. INITIAL TREATMENT (clearence phase)
0.6-0.8mg/kg body weight of oral 8-MOP
2-3 times per week
mild erythema moderate- severe erythema
dose reduced/constant treatment deferred
 15-25 sittings required for clearence phase
Final clearence dose of UVA 5-20 J/cm2
After 1-3hrs
Initially 2-3 J/cm2 UVA  0.5 j/cm2 UVA later on

39. MAINTANENCE TREATMENT
•The last dose of clearance phase is kept constant and the
frequency of treatment is slowly reduced to as low as once a
month.
TREATMENT OF RELAPSES
• If significant relapse of the disease occurs after treatment
discontinuation or during the maintenance phase, it is appropriate
to resume a clearance schedule.
• For minor recurrences occurring during the maintenance phase,
the frequency of treatments may be increased until disease control
is achieved.

40. 0.6mg/kg body wt of oral 8-MOP
1.5-2hrs
sunexposure for 10mins
2-3times/week
sunexposure 5mins/every week max of 30-45mins
 Use of eye protective glasses
avoidance of further sun exposure for the next 8h is to be followed to
prevent eye toxicity and darkening of the normal skin.

41. Topical Combinations: Topical adjuvant therapies with
•Glucocorticoids
•Anthralin
•Tar preparations
•Calcipotriol
•Tazarotene
Methotrexate:
•PUVA + methotrexate can the duration of treatment,
number of exposures, and total UVA dose and is also
effective in clearing patients unresponsive to PUVA
•safe if used during the clearing phase only
•Long term therapy skin cancers

42. Cyclosporine:
PUVA+ cyclosporine skin carcinogenesis
So, the combination is discouraged
Retinoids :
•The therapeutic efficacy of PUVA therapy is dramatically
increased by daily oral retinoid (etretinate, acitretin,
isotretinoin; 1 mg/kg) administration beginning 5–10 days
before the initiation of PUVA, and continued throughout the
clearing phase
•called RePUVA characteristically reduces the number of
exposures by one-third and the total cumulative UVA dose >
one-half
•MOA- accelerated desquamation that optimizes the optical
properties of the skin and reduction of the inflammatory
infiltrate

44. •Dark skinned people
•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.
•Patients with vitiligo affecting more than 30-40% body
surface area (BSA) do not respond well to medical
therapy like PUVA/PUVASOL

45. 8-MOP(0.6–0.8 mg/kg body weight) or TMP(3.6mg/kg bw)taken orally
UVA radiation
150-200 sessions in 2 yrs, every alternate day
complete or near-to-complete response
1-3hrs

46. Oral TMP( 3.6mg/kg body weight)
sunexposure(0.5-1min)
2-3 times/week
Within 1-3hrs
every week sunexposure 0.5-1min till erythema
appears
30-40 sittings no improvement Discontinued

47. 0.01-0.1% 8MOP in a cream or lotion base
UVA radiation
2-3 times/week
radiation 0.25 J/cm 2 every wk
After 30 mins

48. 0.1% 8MOP CREAM or LOTION
Sunexposure (0.5-1min)
2-3times/week
every week sunexposure 0.5-1min till erythema
appears
After 30 mins

51. •Calcipotriol and PUVA: Many studies show quicker
response to treatment with more intense repigmentation,
though acral vitiligo does not respond well.
-Concurrent topical calcipotriol may shorten the duration of
UVA exposure thus leading to reduction of PUVA-induced
side effects
•Low dose azathioprine also has been used to improve the
efficacy of PUVA in vitiligo.

53. •Treatment guidelines are same as psoriasis
•Moderate , severe, erythrodermic forms of atopic eczema
can benefit
•More difficult to treat, higher number of treatments required
•Even if cleared by PUVA, recurrence rates are higher
•Combination of PUVA+ corticosteroids better than PUVA
alone
•MOA- alteration of lymphocytic function in the dermal
infiltrate

55. •Alternative to systemic corticosteroids in generalised
lichen planus
•More treatment sessions and higher cumulative UVA
doses
•Side effect- Marked Post inflammatory
hyperpigmentation
•Combined RePUVA- disseminated and keratotic forms of
LP

57. •Temporary resolution of skin lesions probably due to
chronic degranulation of the mast cells.
•Treatment results in loss of Darier sign, relief of itching,
and flattening and even complete disappearance of
cutaneous papules and macules.
•Histamine-induced migraine and flushing improve
gradually as treatment is continued

59. •Acute and chronic cutaneous graft-versus-host disease
•Well circumscribed, localized forms respond with
softening of the fibrotic, sclerotic connective tissue
•But, widespread & disseminated lesions hardly
respond.
•Increase of the UVA dosage by 0.5 J/cm2 at maximum
after every 2nd to 4th exposure
•UVA radiation 3-4 times weekly

61. •Tolerance to sunlight can be induced in several
photodermatoses by PUVA therapy
•PMLE- PUVA an effective treatment
•3-4 week PUVA course of 2-3 treatments/wk suppress
the disease
•Only temporary, sunlight required for maintenance phase
•MOA- Hyperpigmentation and thickening of the stratum
corneum
•Solar urticaria- PUVA an effective preventive treatment
•Tolerance to sunlight can be increased 10-fold or more
after a single treatment course

63. •UV radiation and psoralens Worsen HIV disease
•Both UV radiation and psoralen photosensitization
activate the HIV promoter boost viral gene transcription
 virus production

65. •Treatment regimen is same as psoriasis
Clearing phase
Maintenance phase- two exposures per week for 1
month and one exposure per week for another month
Follow-up phase- monthly monitoring and later bimonthly
•Remission confirmed by histological examination
• Clinical remissions - phototoxic destruction of the
malignant lymphocytes that infiltrate the skin.
•Complete clearing may be induced when the cells are
confined to the epidermis and superficial dermis, the depth
of effective UVA penetration into the skin

66. CONTRAINDICATIONS FOR PUVA

67. SIDE EFFECTS OF PUVA

69.  FITZPATRICKS DERMATOLOGY IN
GENERAL MEDICINE
BOLOGNIA TEXTBOOK OF
DERMATOLOGY
IJDVL ARTICLES