Tuesday, October 13, 2009

Photochemotherapy

Photochemotherapy is the therapeutic use of ultra violet A (UVA) in the range of 320-400nm with photosensitizing agent psoralen. The action spectrum of psoralens is around 330nm. The first use of photochemotherapy dates back to over 2000 years ago, when Egyptians used Ammi majus plant seed extracts for treating skin condition. Subsequently many psoralens are used in treating the different kinds of skin conditions. The three most commonly used psoralens are 8-methoxypsoralen(8-MOP),5-methoxypsoralen (5-MOP) and 4,5,8-trimethylpsoralen(TMP). Among these most commonly used psoralen is 8- methoxypsoralen. After the oral intake of the crystalline form of the drug, the drug reaches the pick level in the skin in 2 hours, while intake of liquid form takes about 1 hour to reach the peak level in the skin. The absorption rate of 5-methoxypsoralen is only 25%,while the absorption of 8-methoypsoralen can be compensated by increasing dose by 1.2-1.5mg/kg. TMP is used as a topical or as PUVA bath as its poorly absorbed.
Psoralens act by the direct effect on the DNA. The two type of effects are well known; the first one is oxygen dependent DNA photo adduction associated with therapeutic effect. Second one is by oxygen dependent photodynamic reaction, which has some immunosuppressive action on the body

Indication
Psoralen is indicated in Psoriasis, Vitiligo, Hyper keratotic eczema, Morphea, Alopecia areata, Cutaneous T cell lymphoma, PLC, Prurigo nodularis etc.

Contraindication
The drug is contra indicated in pregnancy, lactating mother, children below 12 years, photosensitive diseases and collagen vascular diseases. However, when the drug is to be used for short duration it may be considered for use.
Minimal Phototoxic Dose(MPD)
Before starting PUVA therapy the patients Minimal phototoxic dose (MPD) or minimal erythema dose (MED) is determined to avoid phototoxic reaction. It is determined by irradiating UVA ray on the patients re-presented sites (about1cm) and such 6-8 sites are selected, either on the buttock or cover part of the body to be irradiated with UVA ray in a gradual increasing dose of UVA, after administering oral psoralen at the dose 0.4mg/kg. The UVA ray irradiation is carried out after 2 hour of psoralen intake. And these areas are read after 72 hour to look for the minimal erythema (pink erythema) induced by the lowest dose of UVA. The minimal dose of UVA required to induce erythema is regarded as the Minimal eythema dose for that particular individual.


Oral PUVA
Psoralen when used with UVA ray of artificial source is regarded as PUVA therapy; when the UVA ray of solar system is used it’s regarded as PUVA Sol.

Generally two protocol are followed while using PUVA/PUVA Sol as the mode for treatment for any photochemotherapy responsive condition.
In the American protocol the PUVA is given either twice a week or thrice a week. The UVA radiation is given 2 hours after the oral administration of psoralen, at the dose of 70-80% of the determined MPD to start with, then it’s dose is increased by 30% of the initial dose. In the European protocol the treatment is given 4days a week.

When UVA from solar source is used its called PUVA sol and the sun exposure is started by 5 minutes then it’s increased by 5 minutes every week until 30 minute is reached. The UVA ray reaches earth between 9am-3pm, and the best time for sun exposure to have maximum UVA is between 11.30-01.30 pm.

Patients eye and genitalia is protected during UVA exposure by using UVA blocking glasses and guards.


Topical PUVA
Here the psoralen is given in the form of bath(PUVA Bath) or bathing suit PUVA, psoralen soak and UVA exposure, direct psoralen application and PUVA, and PUVA comb are used to limit the side effect of psoralen.

Trioxalen bath solution is prepares by adding 100ml(0.05% solution) to 150L of water at room temperature. While, 8-Methoxlen bath is prepared by adding 50ml, 0.75% 8 MOP(commercially available at Indian market) to 100ml water, making the final solution 3.75mg/L.
The patient is soaked in the solution for about 15 minutes, dries off and irradiated with UVA in a conventional phototherapy unit.
For localized lesion we have been using topical psoralen in modified form (one drop of psoralen with 10-20 drops of water) applied on the lesion and after 20-30 minutes the area is exposed to sun for one minute and it’s washed off. In some centers in India instead of PUVA suit, Dermatologist are using trousers soaked in diluted solution of psoralen, worn for 15-20 minutes and then UVA ray is irradiated and soap bath is given to remove psoralen from the skin.

Side effects of oral psoralen are anorexia, nausea, vomiting, headache, dizziness, light headness, insomnia, depression, redness on skin, blister formation, dryness, pain on the skin, exacerbation of asthma, drug fever, maculopapular lesions on skin, urticaria, hypertrichosis, cataract, cutaneous aging, malignancy
Side effect of topical PUVA are redness, tenderness, blister formation, and hyperpigmentatio
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