'High single-dose' European PUVA regimen also causes an excess of non-melanoma skin cancer.

We report the results of a long-term (12.8 years) follow-up study of the detection of malignant and benign skin tumours in patients with psoriasis, who were treated with PUVA according to the European, 'high single-dose' regimen. A total of 13 squamous cell carcinomas (SCC) and 24 basal cell carcinomas (BCC) were diagnosed in 11 of 260 patients. The incidence of both SCC and BCC was increased in comparison with the general Dutch population. The ratio of SCC to BCC in the general population was 1:8 but was 1:2.5 in our study group. A positive correlation was observed between the development of SCC and the total UVA dosage, the age of the patient at the start of the PUVA treatment and a history of arsenic use. This dose-related increase in the incidence of SCC, reported in studies from the U.S.A., has not been found in earlier European studies. The average time period between the start of PUVA therapy and the diagnosis of the first malignant skin tumour was 6.0 years for SCC and 4.7 years for BCC. Among the 49 benign skin tumours were actinic keratoses, a keratoacanthoma and 'PUVA keratoses', a newly described hyperkeratotic lesion, especially found in PUVA-treated patients.

[Fumaric acid therapy in psoriasis; a double-blind, placebo-controlled study]. / Fumaarzuurtherapie tegen psoriasis; een dubbelblind, placebo-gecontroleerd onderzoek.

Thirty-nine patients with psoriasis (12 females, 27 males) entered a randomised, double-blind, placebo-controlled study on the efficacy of fumaric acid therapy in an outpatient setting. During 16 weeks the patients were treated with tablets containing a combination of dimethylfumarate and different salts of monoethylfumarate, with octylhydrogen fumarate or with placebo tablets. All patients were treated with identical indifferent topical therapy and followed an elimination diet (avoidance of spices, wine and nuts). Thirty-four patients completed the study. Five patients dropped out because of side effects or aggravation of the skin lesions. The patients treated with the combination of monoethyl- and dimethylfumarate showed a significantly better therapeutic response compared with those who were treated with placebo or octylhydrogen fumarate. Side effects of the fumarate containing tablets were flushing, diarrhoea, a reversible elevation of transaminases, lymphocytopenia and eosinophilia. One patient developed a disturbance of the kidney function which normalised after discontinuation of the therapy.

[Canthaxanthin retinopathy]. / Canthaxanthin-Retinopathie.

The authors examined 32 patients with light-dermatosis or vitiligo who were being treated with orally administered Canthaxanthin and betacarotene. Eight had crystalline retinopathy with typical "gold dust" particles in the inner retinal layers, forming a band-shaped zone around the macula and, in more severe cases, also around the optic disk. No deterioration of visual function was found in any of these patients. Crystal deposition was correlated significantly to the total Canthaxanthin dosage but not to the duration of treatment.

UVB doses in maintenance psoriasis phototherapy versus solar UVB exposure.

A possible increase in the risk of skin cancer in psoriatic patients treated with long-term maintenance UVB phototherapy was assessed by comparing the cumulative doses of UVB with the amount of UVB received from sunlight by normal healthy people. The biologically-effective UVB dose (termed UVB(EE) ) was measured using polysulphone film and worn as a badge by individuals with either an indoor or an outdoor occupation during 4 summer months of 1983 in The Netherlands (52 degrees N). The calculated mean annual UV-B(EE) doses were 5.9 J/cm2 for persons with an indoor occupation and 134 J/cm2 for those with an outdoor occupation. The UVB(EE) doses received by psoriasis patients during an initial course of phototherapy, as well as during maintenance treatment, were also estimated and gave a mean value of 22 J/cm2. Mean annual amounts of solar UVB(EE) exposure were calculated and compared with the administered doses of UVB(EE) during maintenance phototherapy. A dose-response model is described in order to estimate the increased incidence of non-melanoma skin cancer associated with such therapy. The cumulative incidence among patients who received maintenance phototherapy for several decades was calculated to be a factor of 2.5 to 7.5 higher than the incidence among individuals with an outdoor occupation.

Comparison of phototherapy (UV-B) and photochemotherapy (PUVA) for clearing and maintenance therapy of psoriasis.

One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light (PUVA). Patients treated with PUVA, in the initial and maintenance period, achieved in general a higher therapeutic score (95% to 100% clearance) than those receiving UV-B therapy. However, taking 80% to 100% improvement as criterion, no difference was found between initial UV-B and PUVA therapy, if less than 50% of the skin surface was affected by psoriasis. If more than 50% of the skin was involved, PUVA was better than UV-B therapy. The maintenance treatment frequency for the UV-B-treated patients for more than a year seemed to be higher than for PUVA-treated patients. A positive correlation was found between response to sunbathing (questionnaire survey) and the response to UV-B phototherapy. An extra UV-B treatment to the leg lesions appeared useless.

Application of controlled high dose rates in UV-B phototherapy for psoriasis.

The use of a cabin fitted with Sylvania UV-21 tubes, which have a very high output of UV-B radiation, made it possible to treat psoriasis patients with a maximal exposure time of 5 minutes per session. An exposure-control unit was used to measure and regulate the applied dose to prevent overdosage. The clinical results obtained with two comparable groups of psoriasis patients treated with Sylvania UV-6 or UV-21 tubes were equal.

Influence of water and salt solutions on UVB irradiation of normal skin and psoriasis.

The influence of tap-water (TW) and salt solutions on the minimal erythema dose (MED) was investigated for normal human skin and uninvolved skin of psoriasis patients. MED (UVB) determinations on the forearm revealed that: (1) the MED definitely decreases whenever the arm is immersed in TW or NaCl solutions with a low concentration (4%) prior to UVB exposure, whereas almost saturated NaCl solution (26%), as well as locum Dead Sea water (LDSW), do not produce a change in the MED, and (2) the decrease in MED obtained by wetting the skin with TW was no longer present when the skin was allowed to dry for 20 min. A decrease in water uptake by skin (in vivo) and by callus (in vitro) was found as the salt concentration of the external solution increased. It is proposed that water taken up by the skin plays an important role in the sensitivity of the skin to UVB exposure. Bathing in TW or 4% NaCl prior to UVB exposure offered a slight to moderate improvement in psoriasis over UVB irradiation alone. Finally, it was shown that there is no obvious difference in clearance of the psoriatic skin between a bath in TW, 4% NaCl, or LDSW prior to UVB exposure.

Influence of UVA on the erythematogenic and therapeutic effects of UVB irradiation in psoriasis; photoaugmentation effects.

The effect of repeated exposure to an additive dose of long ultraviolet (UVA) radiation on the erythemogenic and therapeutic effects of middle ultraviolet (UVB) irradiation was investigated in 8 patients with psoriasis. The surface of the backs of these patients was divided into 2 parts, 1 of which received only UVB irradiation 4 times a week and the other UVA + UVB. UVB was provided by Philips TL-12 lamps and UVA by glass-filtered Philips TL-09 lamps. UVA was held constantly at 10 J/cm2, whereas UVB was increased. The erythemogenic effects of UVA + UVB and UVB alone were evaluated by 4 tests during the treatment to determine the minimal erythema dose (MED). Test I (at the start of the therapy) showed a photoaugmentative effect which was no longer apparent in test III (third week). Test III showed a reversal of the ratios of the MEDs of the sites irradiated with UVA + UVB and UVB (MED A + B/MED B). This is ascribed to the marked pigmentation which appeared after repeated irradiation with the UVA + UVB combination. Comparison showed for the improvement of the psoriasis no distinct differences between UVA + UVB irradiation and UVB alone, but the former had the cosmetic advantage of giving pleasing tan.

Photochemotherapy of psoriasis. Clinical study of clearing and long-term maintenance treatment.

PUVA therapy was administered to 140 patients with psoriasis. The results of clearing and long-term maintenance treatment are reported. Clearing requirements were in general similar to those reported by Melski and co-workers. The skin of a majority of the patients (79%) could be kept in a good condition by a maintenance-treatment schedule of once every 2 weeks or less. This result is better than the results reported by other authors. Extra topical treatment for residual lesions during maintenance consisted of small amounts of corticosteroids. The maximum length of the treatment intervals during maintenance showed definite individual variations. Patients who required one treatment a week or more to keep the skin cleared were dropped from the study.

Photochemical damage to skin fibroblasts caused by protoporphyrin and violet light.

Foreskin fibroblasts cultured in a medium containing protoporphyrin and exposed to violet light lose the capacity to proliferate. This phenomenon can be assessed on the basis of the ability of the irradiated cells to form colonies. Potentially lethal injuries can, however, be repaired during postirradiation incubation under optimal growth conditions. We investigated the photodynamically induced transformations of certain molecular targets in the irradiated cells. Biochemical analysis showed that only traces of unsaturated fatty acids were oxidized, but SH groups of both the membranes and the cytosol appeared to be very sensitive targets. Of the tryptophan content, 20% was damaged during irradiation. Recovery was observed during post-irradiation incubation. The tryptophan content and the SH groups recovered to some extent, and these results showed a good correlation with the regeneration of surviving cells.

UV-B phototherapy of psoriasis.

The effect of ultraviolet-B light provided by TL-12 fluorescent lamps was investigated in 45 patients with psoriasis vulgaris. 33 (73.3%) of the 45 patients showed considerable and rapid improvement during UV-B therapy. The initial (clearing) phase (4 irradiations a week) required an average of 23 irradiations (range: 9-33). During maintenance treatment, irradiation once every 1-5 weeks proved adequate in 64.4% of the patients.