PUVA therapy for photosensitive psoriasis

The purpose of this study was to assess the prophylactic effect of oral photochemotherapy with psoralens and UVA (PUVA) on patients with light-sensitive psoriasis. Of fifteen patients with photosensitive psoriasis, ten with a history of polymorphous light eruption (PMLE) slowly developing into psoriasis were treated with trimethylpsoralen (TMP) and UVA. Five patients with no preceding PMLE reaction were similarly treated; two with 8-methoxypsoralen (8-MOP), two with TMP and one in whom 8-MOP was later changed to TMP. Good to excellent results were obtained in 9/10 of the first category and in 3/5 of the second, giving an overall efficacy of 80%. Preexisting psoriatic lesions did not, however, heal during TMP therapy but did so when treated with 8-MOP. The results confirm, for light-sensitive psoriatics, the efficacy of PUVA in photosensitive disorders.     

Immunologic implications of PUVA therapy in psoriasis vulgaris

Summary During the combined effects of psoralen and UVA irradiation (PUVA therapy) a significant decrease (P<0.005 in T cells has been noted in 10 psoriasis patients and 10 healthy controls especially after four exposures. Based on the fact that the total number of circulating lymphocytes of the patients and the PUVA-treated healthy controls remained within the normal range, this decrease may be due to temporary physicochemical changes of the membranes of these cells but not to T cell lysis. After eight exposures these decreased T cell values returned to starting range. The starting T cell range in psoriasis patients is significantly lower (P<0.005) compared to that of healthy controls.It is of importance that before PUVA therapy in all the patients antibodies reactive with a basal cell nuclear antigen belonging to the four main Ig classes (IgM, IgD, IgE, and IgA) could be removed from the membrane of circulating lymphocytes by means of acid elution. In contrast, mainly the IgA antinuclear basal cell antibody could be eluted from circulating PMN leukocytes in the patients under investigation. After eight PUVA exposures, however, corresponding antibodies, belonging to the three main Ig classes (IgM, IgD and IgE) could also be eluted from the membranes of circulating PMN-leukocytes of the same patients. This implies an exchange of molecules during photochemotherapy. Finally, it could be shown that after effective PUVA therapy antinuclear basal cell antibodies of the psoriasis patients under study were reactive not only with the nuclei of the basal cell layer but also with almost all the nucleic of the epidermis of the uninvolved and lesional skin. The latter finding points to the fact that PUVA treatment causes at least antigenic changes of nuclear proteins in all the nuclei of the epidermis of the PUVA treated skin. Moreover, inflammatory cells with Fab fragments within the cells present in the lesional skin before PUVA disappear during this treatment.Based on a poster session presented at the occasion of the seventh joint meeting of the ESDR, Amsterdam, The Netherlands, May 1977     

PUVA treatment of psoriasis in the United Kingdom

Information concerning the operation of 134 PUVA units in 96 dermatology centres in the U.K. was collected by a postal questionnaire. The most common protocol was to give PUVA three times weekly in the treatment of psoriasis, and to choose the initial dose of UVA according to skin type. However, the initial UVA dose encompassed a range of five or more within each skin type.     

A comparison of psoralen plus ultraviolet A (PUVA) monotherapy,tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis

BACKGROUND: Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis. OBJECTIVES: To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments. METHODS: Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse. RESULTS: Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene. CONCLUSIONS: Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.     

Local PUVA therapy of patients with psoriasis

Various external photosensitizers have been compared in local PUVA therapy of 280 patients with psoriasis treated in Moscow at the Central Research Institute for Skin and Sexually Transmitted Diseases, the USSR Ministry of Health, and in Warsaw at the Dermatology Hospital. In Moscow 127 patients have been administered 0.3% ammifurin solution, 73 ones 0.1% psoralen solution; in Warsaw 50 patients have been administered 0.1% puvaderm ointment (Basan) made in Finland and 30 patients 0.1% oxoralen emulsion manufactured in Austria. A good clinical effect has been achieved in 252 patients (90%). Ammifurin 0.3% solution and puvaderm 0.1% ointment have proved to be the most effective. External photosensitizers are recommended for local or as a supplement to total PUVA therapy.     

Response of psoriasis to twice weekly PUVA

In the U.K., PUVA treatment for psoriasis is usually given three times weekly, with the starting dose of UVA chosen according to the skin type of the patient. Observations on the time-course and dose response characteristics of PUVA erythema suggest that larger doses of UVA could be used safely, provided that the frequency of PUVA treatment is reduced. We have examined this by treating 100 patients with chronic plaque-type psoriasis with a PUVA protocol in which treatment using oral 8-methoxypsoralen was given twice weekly, with the starting dose of UVA based on each patient's minimal phototoxic dose, and with weekly UVA dose increments calculated as a percentage of the dose used in the previous treatment.
Clearance of psoriasis was achieved in 92% of patients. The median number of treatments required for clearance was 12, and the median cumulative UVA dose for clearance was 52 J/cm² Although erythema occurred at some stage during the course of PUVA in 48% of patients, in only 16% of cases was the erythema of sufficient intensity to result in more than one treatment being missed.
These results compare favourably with previous studies in which treatment was given three or four times weekly. Thus, twice weekly PUVA treatment for psoriasis is at least as effective as treatment given more frequently, and may be safer, as lower cumulative UVA doses are required for clearance. It also allows for more efficient operation of a PUVA unit and is more convenient for patients.     

Low-dose PUVA maintenance in psoriasis following Ingram therapy

Following the initial treatment of severe psoriasis with conventional Ingram therapy, it is shown that PUVA maintenance at a mean dose-rate of 28·6 J/cm²/month increases the average period of remission from 7 weeks to more than a year. Surprisingly, the patients who withdrew from maintenance therapy whilst still in remission have so far continued (10 months) to show an extremely low relapse rate.     

A modified dosage schedule for increased efficiency in PUVA treatment of psoriasis

Ten patients with chronic widespread plaque psoriasis, all of whom had previously completely cleared and suffered a subsequent widespread relapse after conventional PUVA therapy, were treated with a modified UVA dosage schedule, with psoralen formulation and dosage unchanged. Initial and incremental UVA doses were maximized to near-erythemogenic levels as determined by weekly testing for minimal phototoxic dose (MPD), treatment being given three times a week. A comparison of complete psoriasis clearing between the modified treatment and the last PUVA course showed a geometric mean reduction in treatment duration of 55% (P less than 0.001) for a similar number of treatments each week, and a cumulative UVA dose of 31% (P less than 0.05), representing a reduction in treatment duration from 9.1 to 4.1 weeks and cumulative UVA dose reduction of 100.8 to 69.9 J/cm2. Such an improvement in efficiency permits a marked increase in treated patient numbers for the same cost, and is more convenient. The reduction in the total cumulative UVA dose given as larger individual doses also seems likely to lead to a lower incidence of cutaneous long-term, especially carcinogenic, adverse effects.     

Cutaneous neoplasia following PUVA therapy for psoriasis

Summary To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at our unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9·5 years. Fifty-nine per cent wore male, and 41% female. The median number of exposures was 59. and the median total dose was 133 J/cm² for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2·4%). Basal cell carcinoma occurred in fill six and one individual also developed four squamous cell carcinomas and Bowen's disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654J/cm². Compared with a control study population in West Glamorgan. Wales, there was a 1·4 (95% confidence limits (CL) 0·5 and 3·1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm². with risks of 3·7 (95% CL 1·0 and 9·5). and 4.0 (95% CL 1·1 and 10). respectively. A PUVA dose of < 250J/cm² or <100 exposures conferred a minimal increase in risk of NMSC in our study population.