Photochemotherapy for psoriasis remission times. Psoralens and UV-A and combined photochemotherapy with anthralin.
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Adolescent↗
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[Photochemotherapy of psoriasis: increasing its effectiveness with an oral aromatic retinoid (clinical results in 134 patients) (author's transl)].
The effectiveness of photochemotherapy can be substantially increased by the concomitant administration of an oral aromatic retinoid. 134 patients with severe plaque-type or palmoplantar psoriasis were given various combined treatment schedules. In the initial (clearing) phase a significant synergistic effect was achieved if retinoid administration was started before photochemotherapy, and if the dose was 1.0 mg/kg body-weight. This shortened by half the time required in a control group given photochemotherapy alone (7.7 +/- 4.5 irradiation sessions within 14.1 +/- 8.6 days), and reduction of the total UVA energy necessary for complete clearing to one third (32.4 +/- 40.0 J/cm2). After clearing the patients received standard photochemotherapy maintanance treatment. The incidence of relapses observed during a 10-month follow-up was the same as that in patients cleared and maintained with photochemotherapy alone. Short courses of retinoid treatment in addition to photochemotherapy were highly effective in clearing patients who had failed to do so or had not been maintained in a cleared state on standard photochemotherapy.
Administration, Oral↗
Psoriasis treated with clobetasol propionate and photochemotherapy.
Comparable lesions in 16 patients with chronic plaque psoriasis were treated with clobetasol propionate or placebo ointments for 1 week before beginning photochemotherapy. The greater improvement of the steroid treated lesions was maintained after the ointment was withdrawn and there was a mean period of 31 days before those treated with placebo showed a comparable response to photochemotherapy. By the end of the study 8 patients were completely free of psoriasis, healing being achieved after a mean of 7.2 photochemotherapy treatments on the steroid treated lesions compared with 13.5 where a placebo ointment was used. No patient had any adverse reaction to treatment.
Adult↗
Photochemotherapy for mycosis fungoides: a clinical and histological study.
Nine patients with stages 2 or 3 mycosis fungoides (MF) and one with Sézary's syndrome were treated with oral methoxsalen and long-wave ultraviolet light. Previous therapy had either failed or achieved only partial control. Satisfactory clinical control was achieved in all but one case. Histological improvement was seen in all cases, but complete clearance of lymphoid infiltrate was noted mainly in epidermal and papillary dermal infiltrates. Lower dermal infiltrate remained largely unchanged. The case of Sézary's syndrome was inadequately controlled with systemic prednisone and cyclophosphamide, but addition of photochemotherapy improved the erythema and pruritus. This shows that photochemotherapy may have a place in MF treatment both alone and perhaps in conjunction with other treatments. An early relapse occurred on stopping photochemotherapy in four cases, but one patient has had three months' full remission.
Adult↗
Photochemotherapy for psoriasis with orally administered methoxsalen.
Photochemotherapy denotes a therapeutic approach that is based on the interaction of light and a photoactive drug. This study describes the efficacy of photochemotherapy, using orally administered methoxsalen and long-wave ultraviolet light in 91 patients with severe, generalized psoriasis. Oral administration of methoxsalen was followed by exposure to a high-intensity long-wave ultraviolet light source, emitting a continuous spectrum between 320 and 390 nm (peak, 365 nm) and an energy of 5.6 to 7.5 mw/sq cm at 15 cm. There was complete clearing of 82 patients (90%), a 90% to 100% clearing in seven (8%), and a satisfactory improvement in two (2%). A paired comparison study in 54 patients showed photochemotherapy to be far more effective than ultraviolet light emitted by fluorescent bulbs or a xenon source. Eighty-five percent of the patients receiving outpatient maintenance treatment have remained in remission for periods up to 400 days.
Administration, Oral↗
Photochemotherapy for psoriasis. A clinical cooperative study of PUVA-48 and PUVA-64.
A clinical cooperative study involving 14 centers evaluated photochemotherapy (psoralen and high-intensity long-wave ultraviolet light [PUVA]) for psoriasis. Results from 465 patients treated with a PUVA-48 unit (equipped with 48 high-intensity UVA bulbs) and 110 patients treated with a PUVA-64 unit (equipped with 64 high-intensity UVA bulbs) confirmed the effectiveness of photochemotherapy for psoriasis. Clearing of psoriasis occurred in 85% of patients on PUVA-48 therapy. Mean number of treatments, joules per square centimeter, to clear, and total joules at clearing were similar to other reported trials. The plateau method of clearing resulted in lower joules per square centimeter at clearing, total joules per square centimeter, and number of treatments than the nonplateau method. Maintenance therapy groups were mainly M1 (once weekly) or M4 (no treatment for more than 60 days). No meaningful laboratory abnormalities were detected and ophthalmologic examinations showed a few abnormal results following PUVA. Short-term side effects were mainly erythema, nausea, and pruritus. The effectiveness and short-term safety of PUVA for psoriasis has now been confirmed by a second large cooperative study.
Adolescent↗
Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in V-79 Chinese hamster cells. A first approach to a risk estimate in photochemotherapy.
The effect of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet irradiation (UVA) on cell killing and mutation induction was studied in V-79 Chinese hamster cells. No effect was observed after treatment with 8-MOP alone (50 microgram/ml, 4 h), UVA alone (9000 J/m2), or 8-MOP metabolized by rat-liver microsomes. Combined treatment with 8-MOP and UVA induced both cell killing and mutation. This was also observed under conditions approaching patient treatment with PUVA photochemotherapy with respect to the concentration of 8-MOP in the skin and the amount of UVA received by the epidermal cells. A simple relation proved to apply for mutation induction under different treatment conditions: 5.5 X 10(-8) per J/m2 per microgram 8-MOP/ml. On this basis the mutation induction in dividing cells per session of PUVA-photochemotherapy amounts to 12.4 X 10(-5), which is probably an over-estimation.
Animals↗
Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in diploid human skin fibroblasts: an improved risk estimate in photochemotherapy.
Cell killing and the induction of mutation were studied in dividing and non-dividing human skin fibroblasts as a result of treatment by 8-methoxypsoralen (8-MOP) and long-wave UV irradiation (UVA). The cytotoxic effect was highly dependent upon the duration of the UVA exposure. The frequency of mutations increased linearly with the UVA dose at concentrations of 10 and 0.25 microliter 8-MOP/ml, the latter representing the concentration in the skin during PUVA treatment. The number of mutations induced per unit dose (= per microgram 8-MOP/ml per joule UVA/m2) was calculated: for dividing cells this value was 3.3 X 10(-8) per cell and for non-dividing cells 0.6 X 10.8(-8) per cell. On the basis of these values the expected number of induced mutants in the human skin per session of photochemotherapy is 1.2 X 10(-5), and per 30 years of maintenance therapy 1.3 X 10(-2) per cell. A comparison was made between this frequency and the frequency to be expected from spontaneous mutation. In addition the significance of absence in patients of SCE induction by photochemotherapy is discussed.
Cell Survival↗
Risk of cutaneous carcinoma in patients treated with oral methoxsalen photochemotherapy for psoriasis.
A 2.1-year prospective study of 1373 patients given oral 8-methoxypsoralen photochemotherapy for psoriasis revealed 30 patients with a total of 48 basal-cell and squamous-cell carcinomas. The observed incidence of cutaneous carcinoma was 2.63 (95 per cent confidence limits = 1.91 to 3.90) times that expected for an age, sex and geographically matched population. Relative risk to patients with history of ionizing radiation was 3.68 (99 per cent confidence limits, 2.42 to 8.69). Patients with a previous cutaneous carcinoma had a relative risk of 10.22 (99 per cent confidence limits, 4.78 to 37.08). A higher than expected proportion of squamous-cell carcinomas and an excess of squamous-cell carcinomas in areas not exposed to sun were seen. New patients with known histories of ionizing-radiation exposure or of skin tumors should be given 8-methyoxypsoralen photochemotherapy only if they understand the risks and have disabling psoriasis untreatable by other means.
Administration, Oral↗
Oral photochemotherapy in the treatment of lichen planus (LP). Clinical results, histological and ultrastructural observations.
Seven patients with diffuse lichen planus were treated with oral photochemotherapy. Remission was effected in 6 cases. The only failure may be attributable to a low UVA dose. Histological examination after treatment showed disappearance of the superficial dermal lymphocytic infiltrate. Ultrastructural study revealed nuclear alterations of keratinocytes and nuclear and cytoplasmic changes in superficial dermal cells. Various theories concerning the mode of action of photochemotherapy in lichen planus are discussed in the light of these observations.
Adult↗
Photochemotherapy in treatment of psoriatic variants.
Our procedure for treating psoriatic variants--psoriasis pustulosa generalisata (PPG) and psoriasis erythrodermica (PE)--was based on the following points: (a) to quickly obtain a good tolerance level to photochemotherapy (PUVA) by applying corticosteroids and/or methotrexate (MX); (b) to discontinue the application of systemic drugs with the help of photochemotherapy, and (c) to maintain the improved condition by applying radiation in gradually prolonged intervals, thus enabling the biologic forces of the organism to participate, undisturbed by drugs, in the healing process. In some PE cases, sole PUVA therapy was sufficient, while in others small doses of MX were added to maintain the improved condition. In PPG, skin manifestations completely disappeared and general symptoms were calmed in the first application of this combined therapeutic procedure. However, in the later relapses PUVA had little share in such a combined treatment.
Adrenal Cortex Hormones↗
Photochemotherapy and psoriatic arthritis. A prospective study.
We have studied the temporal relation between psoriasis and psoriatic arthritis in 27 patients receiving photochemotherapy for treatment of psoriasis. Patients were classified as either spondylitic or nonspondylitic. For spondylitic patients, psoriasis was difficult to control, arthritis did not improve, and skin and joint activity appeared to vary independently. In contrast, 67% of nonspondylitic patients receiving photochemotherapy treatment remained clear of psoriasis, with 49% mean improvement in articular index. There was an inverse relation between initial percentage of psoriasis and improvement in peripheral arthritis. These results suggest that aggressive management of psoriasis helps control synovitis in at least a subgroup of patients with psoriatic arthritis.
Arthritis↗
[Oral photochemotherapy (author's transl)].
Photochemotherapy (PUVA) with oral administration of the photosensitizer 8-methoxypsoralen and irradiation with UVA light has become a proved method for the therapy of psoriasis. The treatment is based upon repeated PUVA exposures, which are monitored by exact dosimetry within the desired therapeutic ranges. The present study, which covers an observation period of 3 years, is engaged with the practicability of the PUVA method for the treatment of the various forms of psoriasis, mycosis fungoides, atopic eccema and lichen planus, and, on the other hand, with its side effects and potential long term hazards. Photochemotherapy was shown in clinical routine as an highly effective treatment, which lead to complete clinical remission in all diseases investigated. By maintenance treatment patients with psoriasis could be kept in remission even for long periods of time. Following the dosage parameters toxic side effects were rare and reversible. Histological, histochemical and ultrastructural investigations showed no alteration of skin under photochemotherapeutic conditions. Experimentally induced massive PUVA overdosage, however, led to damage of epidermis and corium and to long lasting benign changes of the melanin pigment system. To study potential long term side effects (hepatotoxicity of 8-methoxypsoralen, cataract formation, development of degenerative or hyperplastic skin changes and disturbances of the immunologic reactivity) laboratory investigations, histologic, ophthalmologic and immunologic studies have been performed. During an observation period of up to 3 years no evidence of long term side effects was found.
Adult↗
Topical methoxsalen photochemotherapy in the treatment of palmoplantar pustulosis and psoriasis.
Topical methoxsalen photochemotherapy has been assessed in 22 patients suffering from recalcitrant palmoplantar pustulosis or psoriasis predominantly involving the hands and feet. Although 20 out of 22 patients improved and good results were obtained in exactly half of those treated, only 4 patients were classified as being "clear" or "minimally involved" at the end of 12 weeks. Two patients have shown no improvement at all. Minor local side effects were relatively common and included symptomatic erythema, blistering and local pigmentation. The histological findings in post PUVA treated skin are discussed and the pros and cons of topical photochemotherapy in this group of diseases is reviewed.
Administration, Topical↗
[Photochemotherapy and cataract formation].
According to the literature combined treatment with 8-MOP and UVA has induced ocular damage in animals. Similar changes in humans on photochemotherapy have not yet been reported and therapeutic doses are considerably lower than the doses that proved toxic for the animal eye. The present paper reviews pertinent literature on the subject and discusses the conditions under which photochemotherapy for psoriasis seems acceptable in view of present day knowledge.
Animals↗
An estimate of genetic risk from 8-methoxypsoralen photochemotherapy.
A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and possesses properties that make it particularly amenable to this approach. It is concluded that treatment of males for a mean period of 10 years before their spermatozoa were involved in conception would increase the gene mutation rate in the male germ line by a factor of 0.00125. The implications of this for the incidence of sex-linked and dominant disease in man are elaborated and the assumptions and limitations are set out. The fragility of the estimates is emphasized.
DNA↗
Quantification of HTLA-positive lymphocytes during oral photochemotherapy of psoriasis.
T-lymphocyte count in the peripheral blood, based on the identification of anti-human lymphocyte antigen (HTLA) by an immunocytochemical method, was determined in 25 PUVA-treated psoriatics and in 25 controls matched by sex and age. The results demonstrate that the HTLA-positive lymphocyte counts of these two groups do not differ significantly. It is concluded that oral photochemotherapy does not induce quantitative modifications in the population of T-lymphocytes of the blood.
Administration, Oral↗
[Semen analysis under photochemotherapy (PUVA-therapy) (author's transl)].
In 9 male patients with psoriasis vulgaris a semen analysis before and during photochemotherapy with 8-methoxypsoralen and UVA (PUVA) was performed to rule out drug-induced toxic damage of spermatogenesis or impairment of fertility due to scrotal hyperthermia. Two hours after oral application of 40--60 mg 8-methoxypsoralen the patients had been irradiated in UVA high intensity treatment units. PUVA-treatments were performed four times weekly until total body clearing was achieved. For complete remission 13--26 (mean 20.5) PUVA-treatments were necessary. Corresponding total UVA-doses were 35.3--191.0 (mean 83.2) Joule/cm2. The investigated parameters total motility, progressive motility, spermatozoa density, total spermatozoa count, spermatozoa morphology, and seminal plasma fructose remained unchanged. Only the volume of the ejaculate showed a small decrease during 3 months of therapy. From this pilot study there is no evidence that PUVA-therapy leads to an impairment of fertility in male patients within their reproductive age.
Humans↗