P .U .V .A .-PHOTOCHEMOTHERAPY OF PSORIASIS WITH ORAL 8-METHOXYPSORALEN AND LONG WAVE ULTRA VIOLET RADIATION

Approximately 15% of the patients seen at Derma­ tology clinics are psoriatics; hence it is a relatively common chronic skin disease. Its incidence in different countries is variable: Northern Ireland ................... 2 3% population United Kingdom ................... 1-2% population D en m ark ................................... 0,2-2% population South Africa ..........................., 0 , 2 1 % population (all social groups) There is particularly low incidence in the Japanese and Negro races (Rook et al., 1968). Although the aetiology is unknown, heredity may play some part. In some patients the onset is precipitated, by stress such as pregnancy, emotional strain, trauma, or infection e.g. streptococcal throat infection in children.

(all social groups) There is particularly low incidence in the Japanese and Negro races (Rook et al., 1968).
Although the aetiology is unknown, heredity may play some part. In some patients the onset is precipitated, by stress such as pregnancy, emotional strain, trauma, or infection e.g. streptococcal throat infection in children.

CLINICAL FEATURES
The typical lesion is a red patch of varying size covered with a thick layer of scales. These can be scraped off and have a characteristic silvery sheen.
Further scraping causes bleeding, but there is no serum exudate. The lesions are most often .present on the extensor surfaces but almost the whole body can be covered. The scalp is a common site and thisrej p a y fee hyperkeratotic areas on the palms and soles. .If-the nails become affected, they become thickened, pitted and striated. The condition usually persists for life with remissions and acute exacerbations.
Psoriatic arthropathy is seen in all age groups but particularly the middle aged and elderly. In .association with skin lesions there is a destructive polyarthritis, usually involving the hands and feet, and characteristi cally affecting the distal interphalangeal joints. Sacroiliitis may also be a feature and although the joint involvement may resemble rheumatoid arthritis, the rheumatoid factor is not present in the blood.
The term P.U.V.A. has been coined to define a form of treatment which combines the use of psoralen as a photo-sensitizing agent and irradiation of the skin with ultra violet light. The ultra violet radiation used in this treatment differs from that used in conventional physio therapy in that the middle and short waves are omitted: Exposure dose This is measured in Joules per square centimetre, (im !) and is the product of the radiation of the machinf) and the time the patient is exposed for.
: ? Radiation x exposure time = exposure dose. W /cm 2 x seconds = Joules/cm2 M W /cm2 mins x 60 Joules/cm2 For ready reference a slide rule made by Waldermann has been designed which cuts down much cal culation time.

Apparatus
The apparatus used in this study was the German manufactured Waldermann P.U.V.A. 6000, for total body irradiation, and a smaller version, the P.U.V.A. 200 for individual areas. These machines can be used either separately or in conjunction with each other depending on the area of the body to be treated. Waldermann has introduced other models which are constantly being modified.

8-METHOXYPSORALEN (8-MOP)
8-MOP is one member of a group of structurally related, heterocyclic, photoactive compounds called psoralens which are derived from furocoumarins. The# are naturally occurring compounds which can b l extracted from the Ami Majus (a weed which grows in the Nile Valley), parsley, parsnip, celery, lime, cloves and figs. It may be applied topically or administered orally.
Over ninety per cent of orally administered 8-MOP is absorbed from the gastrointestinal tract and is dis tributed to the various organs including the skin. The maximum concentration is found in the blood two to three hours after ingestion and this corresponds with the time of maximum photosensitivity of the skin. Over ninety per cent of the drug dose is excreted in the urine within twelve hours and the remainder within the next twelve hours. There is no accumulation of psoralen in the body with repeated daily consumption providing the patient has normal renal function.
8-MOP is dispensed in 10 mg tablets. The oral dose is given exactly two hours before treatment with a light snack and is based on body weight as follows: less than 50 kg -20 mg 50 -60 kg -30 mg 65 -80 kg -40 mg 80+ kg -50 mg In this study the 50 mg dose was not exceeded. The Royal Victoria Hospital Unit was opened in August 1977 in the Department of Physical Medicine, which is in close proximity to the Department of Dermatology. Close co-ordination has always been main tained with the staff in the Department of Dermatology. The Unit runs on a 9 a.m. -5 p.m. basis with one Senior Physiotherapist on duty in the morning when the Dermatology Clinics are running. New patients and those presenting problems can be seen at this time. The afternoon clinic for maintenance patients is run by a Basic Grade Physiotherapist who rotates on a six monthly rota. This system appears to work satisfactorily and permits training of physiotherapy staff. Patients are assessed initially for P.U.V.A. suitability by a Derma-R logist. This includes photographs of the skin lesions, a II optical examination, X-rays of joints if psoriatic arthropathy is clinically present, ECG and full blood analysis. (This is particularly important in those patients currently on a course of cytotoxic drugs, e.g. metho trexate).
Patients are then asked to discontinue all forms of treatment for psoriasis and to apply only bland aqueous cream or emulsifying ointment provided by the D epart ment. Only those patients on methotrexate therapy are allowed to continue their medication, the dose being gradually reduced as P.U.V.A. is increased.
In the Physiotherapy Department the assessment includes the patient's family history, occupation, skin type, joint involvement, present drug regime along with a stenciled diagram of the lesions at the time of starting treatment. Suitable patients are asked to purchase a pair of dark sunglasses which are tested by a spectrophoto meter (made possible by the Department of Biochemistry and Haematology) to ensure that they absorb a mini mum of 370 nm. (3 700A°).
FIRST ATTENDANCE This consists of Test Dosing the patient in the normal way using the anterior aspect of the forearm. Exposures of 0,5, 1, 2, 3 and 4 Joules/cm2 are used.
The onset of erythema is from ten to thirty hours after exposure, peaking between forty-eight and seventyfcvo hours. If the 8-MOP is not taken, there will be no Wythema. The U.V.A. dose producing a minimal ery thema is selected at 72 hours and used as a starting dose. Doses are kept to an absolute minimum, main tained for two consecutive treatments and then in creased by 0,5 J / cm2, providing the skin does not show an obvious erythema. A set of rules is handed to each patient (Appendix I).

ATTENDANCE
Patients attend for treatment three times weekly until tney are clear. They are then seen by a Dermatologist and put onto maintenance therapy, initially attending twice weekly with gradual reduction in attendance, pro vided they remain clear. The majority can be maintained on one or two treatments per month. Accurate record is kept of each patient's attendance including the dose given, machine intensity, 8-MOP ingestion time, treat ment time, skin condition and side effects. (Appendix . SIDE-EFFECTS In the trial patients complained of pruritus in the early stages of treatment, but this gradually diminished as treatment continued, and symptomatic relief was obtained with antihistamines. A number of patients complained of temporary nausea, headaches and sweating following 8-MOP ingestion. Two patients initially developed herpes simplex, but this was further prevented by screening the lips before radiation.

REPORT OF A TRIAL OVER ONE YEAR AT THE ROYAL VICTORIA HOSPITAL
Forty five patients with severe and resistant psoriasis were treated with P.U.V.A. therapy at the Royal Vic toria Hospital for a period of one year. They were selected for the trial under four groups: Group A Patients unresponsive to conventional tar and dithranol therapy. Group B Patients who had previously received large amounts of topically applied steroids. Group C Patients receiving methotrexate. It was hoped to be able to reduce and finally stop the methotrexate as the P.U.V.A. took over. Group D Psoriasis confined to the palms of the hands and soles of the feet.

Results
One hundred per cent clearing of plaques was achieved in 43 of the 45 patients treated (95,5%) and the other two were materially improved. What was significant here was the low exposure dose which was necessary to achieve these results. Previously recorded results by Melski et al. (1977) showed the average to be 14,3 J /crrr. This study showed a total average of 3,5 J /cm2.

Group C
The results of this group are recorded separately. These 5 patients had previously been treated with methotrexate.

Patient
No.