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PubMed1994

Photochemotherapy beyond psoriasis.

Photochemotherapy involves the therapeutic use of nonionizing radiation in combination with a photosensitizing chemical to trigger a photochemical reaction that mediates a beneficial effect. The successful introduction and widespread use of psoralen photochemotherapy (PUVA) in the management of psoriasis was the chief stimulus for recent interest in the therapeutic use of nonionizing radiation in various other dermatoses. This article discusses the expanding spectrum of diseases responding to PUVA therapy. More than 30 conditions such as atopic dermatitis, mycosis fungoides, vitiligo, the photodermatoses, chronic graft-versus-host disease, and granuloma annulare have been successfully treated with oral psoralen photochemotherapy. Various mechanisms of response to treatment are discussed including photoimmunologic effects, selective cytotoxicity, alterations of cell function, and stimulation of melanocytes. Finally, the limitations to the use of PUVA therapy are identified and its future use in other cutaneous and systemic diseases are discussed.

Humans↗
PubMed1975

[Photochemotherapy of psoriasis: clinical experiences with 152 patients (author's transl)].

Photochemotherapy, a recently developed method of treatment, is based on the effect of light on a systemically administered photo-active substance. 152 patients with severe generalized psoriasis were exposed, after oral administration of 8-methoxy-psoralen, to a high-intensity UVA light source radiating at a continuous spectrum between 320 and 390 nm (maximum at 365 nm). Radiation doses ranged from 1.4 to 4.8 J/cm2 and were progressively increased. Complete remission occurred in 141 patients, satisfactory improvement in the remaining 11. It required 12+/-6 radiation sessions (-/x +/- s) to obtain remission, mean duration of treatment being 22 +/- 14 days. Apart from a neutral ointment no other local or systemic therapy was used. Photochemotherapy completely healed the psoriatic foci leaving evenly tanned, cosmetically appealing skin. All patients were treated at intervals as out-patients (average once a week or ev-ry other week), and remained without recurrence for up to 400 days. No local treatment is required with photochemotherapy, which is very effective, simple, harmless and does not stress patient or doctor. Interval treatment maintained the cure.

Adolescent↗
PubMed2000

PUVA-cream photochemotherapy for the treatment of localized scleroderma.

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.

Adult↗
PubMed1992

Onycholysis in a case of atopic eczema treated with PUVA photochemotherapy.

Onycholysis following the ingestion of psoralens and subsequent exposure to natural sunlight has been reported on several occasions and was first reported following photochemotherapy in 1978 by Ortonne and Baran from France and in 1979 by Mackie from Scotland. Mackie commented that she hoped to stimulate further reports of onycholysis induced by PUVA photochemotherapy in order to establish whether or not it was a definite complication of such treatment. Since then, there has been a dearth of similar reports. We describe a patient with severe atopic eczema and alopecia totalis who developed onycholysis of all finger nails and a toe nail during PUVA photochemotherapy.

Adult↗
PubMed1993

Extracorporeal photochemotherapy in progressive systemic sclerosis.

BACKGROUND: Extracorporeal photochemotherapy, an immune-modulating form of therapy, has been shown to be effective in the treatment of autoimmune diseases. We evaluated the effects of extracorporeal photochemotherapy in the treatment of patients with progressive systemic sclerosis (PSS). METHODS: Nine patients with active progressive systemic sclerosis were treated with extracorporeal photochemotherapy on 2 successive days monthly. The duration of therapy ranged from 6 to 21 months. RESULTS: A significant improvement was noted in the skin, musculoskeletal system, functional index, and symptoms including Raynaud's phenomenon, dyspnea, fatigue, dysphagia, and arthralgias, as well as improvement of cutaneous ulcers. Stabilization of the pulmonary function studies was also noted in the majority of patients over the course of therapy. No serious side effects were noted throughout the course of therapy in the 9 patients. CONCLUSIONS: The results suggest that photopheresis may be beneficial in selected early cases of progressive systemic sclerosis.

Activities of Daily Living↗
PubMed2002

Treatment of genito-anal lesions in inflammatory skin diseases with PUVA cream photochemotherapy: an open pilot study in 12 patients.

BACKGROUND: Localized skin lesions of the genito-anal region such as in lichen sclerosus et atrophicus or in lichen planus are a burden for many patients, and therapeutic efforts, including therapies with potentially hazardous side-effects, are often unsatisfactory. Recently, PUVA bath photochemotherapy has been proven highly effective in the treatment of various inflammatory skin diseases, including localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as PUVA bath therapy for palmoplantar dermatoses. OBJECTIVE: We evaluated the clinical effects of PUVA cream photochemotherapy in patients with genital lesions of inflammatory skin diseases. METHODS: Twelve patients with lichen sclerosus et atrophicus, lichen planus, vulvar eczema and pruritus vulvae were included in the study. PUVA cream therapy was performed up to 4 times a week. RESULTS: PUVA cream photochemotherapy induced a significant clinical improvement of genital lesions in most patients, as revealed by clinical examination. Clinical improvement (reduction in size of lesions of erythema, and/or of pruritus) was achieved in most patients after 10-20 treatments and was reduced in patients that had only received 5-15 treatments. Cumulative doses ranged between 4.5 and 180 J/cm(2); all patients tolerated PUVA cream phototherapy well without any side-effects. CONCLUSION: PUVA cream phototherapy represents a highly effective therapy that should be further investigated as an alternative treatment for patients with genital lesions of inflammatory skin diseases.

Adult↗
PubMed1990

[Comparison of the results obtained with ultraviolet radiation and photochemotherapy in the early stages of mycosis fungoides].

The Authors have performed a retrospective study, comparing the results obtained in two groups of patients affected by Mycosis Fungoides at early stages. Thirty-four patients were treated with ultraviolet rays, 32 with photochemotherapy. The patients, in the first stages of the disease, classified on the basis of TNM system, were treated with UVR or PUVA according to standard schedules. The results obtained in the two groups were the following: 1. UVR treated group: complete remission 32%, partial remission 65%, no results 3%; 2. PUVA treated group: complete remission 84%, partial remission 16%. These data show the evidence that photochemotherapy is undoubtedly more advantageous than simple phototherapy in inducing complete remission of early Mycosis Fungoides. UVR therapy still presents, however, as a worthwhile non-aggressive therapeutic choice when the disease has not a progressive character or when photochemotherapy has serious contraindications.

Follow-Up Studies↗
PubMedDate not supplied

[Results of photochemotherapy in a series of 47 patients with mycosis fungoides].

Oral photochemotherapy has been employed in the treatment of mycosis fungoides for more than 13 years. The Authors report their 9 year experience in a series of 47 patients affected by mycosis fungoides and treated by means of PUVA-therapy. All the patients were staged according to TNM system. 81.5% of 38 cases in the I stage of the disease obtained a complete remission, as did 50% of 6 cases in the II stage and one patient out of 3 in the III stage. Photochemotherapy seems to give satisfactory results mainly in the first stages of the disease. In fact, 45% of the patients who had obtained complete remission ot the end of the treatment were still free from disease after 5 years. Photochemotherapy, which in this series has not shown any important side effect, is a safe non-aggressive therapeutic choice in the management of the first stages of mycosis fungoides.

Adult↗
PubMedDate not supplied

Treatment of autoimmune disease with extracorporeal photochemotherapy: pemphigus vulgaris--preliminary report.

Extracorporeal photochemotherapy is a new form of immunotherapy which involves the extracorporeal photoinactivation of peripheral blood cells by 8-methoxypsoralen in the presence of ultraviolet A irradiation, followed by readministration of the cells. To explore the efficacy of this therapy in the treatment of autoimmune disease, four patients with a lengthy history of corticosteroid and immunosuppressive drug-resistant pemphigus vulgaris were initiated on extracorporeal photochemotherapy. Three patients experienced a complete remission in cutaneous disease expression, permitting discontinuation of medications in two and a substantial decrease in the third. Significant reductions in serum antiepidermal cell antibody titers occurred in all four patients. The treatments were well tolerated without the occurrence of adverse events. These results in a small number of patients suggest that extracorporeal photochemotherapy may prove to be a useful tool in the treatment of aggressive autoimmune disease.

Aged↗
PubMed1987

[Carcinogenic risks of phototherapy and photochemotherapy].

The data in the literature regarding the carcinogenic risks involved in both UVB phototherapy and 8-methoxypsoralen plus UVA photochemotherapy are discussed. Both modes of treatment can be mutagenic and can induce immunosuppression. Which of the two factors (the initiator or the promoter effect) is more responsible for the carcinogenic risks involved in phototherapy or photochemotherapy is a subject of much controversy. In addition to discussing the theoretical background, the present article also takes into consideration the long-term clinical studies that have been performed. Practical guidelines are given on how to apply phototherapy and photochemotherapy as safely as possible.

Humans↗
PubMed1976

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↗
PubMed1996

Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro.

We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5J/cm2 UVA), topical PUVA (0.3% 8MOP plus 200 mJ/cm2 UVA) or UVB (80 mJ/cm2) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean +/- SD) were 69.3 +/- 26.9%, 76.3 +/- 31.3% and 83.8 +/- 18.5%, respectively. Secondly, we investigated the effect of PUVA (0.001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm2 UVA) and UVB (10, 30, 50, or 100 mJ/cm2) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.

Adult↗
PubMed1979

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↗
PubMedDate not supplied

Laser photochemotherapy: a less invasive approach for treatment of cancer.

The effectiveness of combining surgery with chemo- and radiation therapy in treatment of human cancer provides a useful model for further development of new multimodality approaches including laser photochemotherapy. Laser endoscopy often is a useful treatment for obstructive tumors in airways, but interstitial laser fiberoptics is becoming a more precise, minimally invasive alternative for ablation of unresectable or recurrent neoplasms. Combining intratumor chemotherapy with laser energy delivery via interstitial fiberoptics should be most effective using drugs activated by photothermal energy. A number of investigators have shown that anthracyclines and cis-platinum are likely candidates for light or heat activation in cancer cells. An advantage of anthracyclines is their dual role as antitumor drugs and as photosensitizers. Because they are effective chemotherapy agents without photoactivation, two approaches are possible to increase tumor responses. Maximum tolerated dose followed by photoillumination via laser fiberoptics can be used to obtain better tumor palliation. Improved treatment response to lower intratumor drug levels after laser activation also should reduce systemic toxicity. Preclinical studies and recent case reports from several groups suggest photochemotherapy with currently approved drugs and lasers may soon become an attractive alternative for treatment of recurrent tumors in cancer patients.

Anthracyclines↗
PubMed2000

[The UV record. Document for quality control, therapy planning and risk assessment in dermatologic photo- and photochemotherapy].

Ultraviolet (UV-) radiation therapy as a mono- or combination therapy (UV-A, UV-A1, UV-B, SUP, UV-B311) or as photochemotherapy with photosensitization (systemic PUVA-, bath PUVA-, topical PUVA-therapy) are successfully used for the treatment of several dermatological disorders. Long-term side effects of natural UV (sun light) include photoaging and induction of skin tumors. At present, the relevance of in-vitro findings of potential tumor induction in animals through therapeutic levels of UV radiation is a matter of debate. To assess these risks, information on treated location, kind of UV radiation and cumulative UV doses are required. Practically this information is barely accessible. This makes decisions on possible therapies difficult. To solve this problem we propose to use an "UV pass". At the end of each UV radiation cycle, the body location, the type of radiation and the cumulative dose are documented and this pass is given to the patient. This will improve the information transfer if the doctor is changed, as well as facilitating decisions about certain therapies and calculation of long-term risks of UV radiation. Finally it will improve the quality of UV photo- and photochemotherapy.

Dose-Response Relationship, Radiation↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1992

The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD.

The therapeutic uses of naturally occurring psoralens in modern-day medicine (8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 4,5',8-trimethylpsoralen, and a few other synthetic psoralens) have evolved through five stages of development. (1) In the historical period (2000 BC to 1930 AD), the pigment-stimulating properties of naturally occurring plants containing psoralens were described anecdotally. (2) The second period (1930-1960) dealing with the chemistry of psoralens involved extraction, identification of their structure, synthesis, and the relationship between chemical structure and their photoreactivity and pigment-stimulating properties. The treatment of vitiligo with oral and topical 8-MOP became popular. (3) In the third period (1960-1974), we witnessed a new beginning and the growth of basic science studies and clinical investigations into various biological properties of psoralens including action spectrum studies, mutagenesis and carcinogenesis studies, in vitro and in vivo photoreactivity studies of various psoralens with DNA, RNA, proteins, and pharmacological and toxicological studies in vitiligo patients undergoing long-term therapy for repigmentation. (4) The fourth period (1974-1988) is recognized as the period of photochemotherapy and the development of the science of photomedicine which established the therapeutic effectiveness of psoralens in combination with newly developed UV irradiation systems that emitted high-intensity UVA radiation in the treatment of severe psoriasis, mycosis fungoides, and over 16 other skin diseases. The effectiveness of PUVA (psoralen + UVA) was confirmed by well controlled clinical trials in thousands of patients, both in the USA and in European countries. Combination therapy with oral retinoids and PUVA contributed to greater effectiveness and long-term safety of psoralen photochemotherapy. (5) In the fifth period (1989 and beyond), psoralens are now emerging as photochemoprotective agents against non-melanoma skin cancers and as immunologic modifiers in the management of certain patients with disorders of circulating T-cells using new techniques of photopheresis. In the final analysis, perhaps the application of pharmacological and therapeutic concepts and principles of using psoralens in combination with UVA has contributed to the development of a new science of photomedicine in which the interaction between basic scientists, photobiologists, and physicians has produced both basic and new clinical knowledge for the care and control of human suffering.

Furocoumarins↗