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Forty one patients whose psoriasis cleared with dithranol were given prophylatic photochemotherapy with psoralens and ultraviolet A once a week. With life table analysis the chance of remaining in remission for 16 months was shown to be 42% for these patients, compared with 13% for a group of patients who were not given prophylactic photochemotherapy.
We are reporting on a 22-year-old female patient with typical Netherton's syndrome who responded to photochemotherapy with the application of 8-MOP solution and irradiation with UVA. After two or three courses of PUVA therapy, each requiring 1 week, the skin condition improved. Maintenance photochemotherapy was necessary. Because there was a similarity between psoriasis and our case in the histological findings, this modality may be justified. No side effects were observed.
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.
The development of therapies which are selective for tumor tissues is one of the most important goals in anticancer research. Within this framework photochemotherapy can be considered a very promising approach. Its therapeutic effectiveness depends on two connected factors: drug and light. The drug (photosensitizer) is able to exert an antiproliferative effect only after interaction with suitable light. Both the photosensitizing drug and light alone are ineffective at doses used for these treatments. Nowadays, photochemotherapy is used in the treatment of cutaneous T-cell lymphoma and cavitary tumors. In the first case the photosensitizer is a psoralen derivative (P) and long-wavelength ultraviolet radiation (UVA) is used (PUVA therapy). In the second case, the treatment with porphyrins, porphyrin-based and non porphyrin-based photosensitizers is followed by irradiation with 600-1000 nm light (photodynamic therapy, PDT). This review is concerned with PUVA and PDT treatments of cancer. The molecular mechanisms considered accountable for the photochemotherapeutic effects are discussed, the development of new chemical structures aimed at improving the effectiveness and/or overcoming some undesired side effects will also be reported. Moreover, some clinical applications will be described.
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.
Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.
This is a review of present knowledge of the use of ultraviolet (UV) radiation in the treatment of skin diseases. Two methods are currently used: phototherapy with UVB, and photochemotherapy with UVA and psoralens as photosensitizers. Both forms have their place in dermatologic therapy. In particular, photochemotherapy has become a standard treatment for severe psoriasis, mycosis fungoides, vitiligo, and some other dermatoses; it is effective as prophylactic treatment in polymorphic light eruption and other photodermatoses. This report will focus on indications, possible mechanisms, and treatment results. In addition, the potential acute and chronic side effects of these therapies are reviewed with special emphasis on skin carcinogenesis.
The results of photochemotherapy of 5 patients with chronic benign familial pemphigus are described. Standard scheme with puvalen and PUVA-22A chamber (Finland) were employed. A course of inpatient treatment consisted of 10-25 irradiation sessions followed by outpatient maintenance photochemotherapy (once a week or two). Erosions and fissures started epithelializing after 8-12 irradiation sessions. A remission of up to 19 months was achieved in all the patients; it was more manifest and durable than after treatment with other schemes.
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.
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.
It was shown by in vitro studies that 8-methoxypsoralen (= 8 MOP) alone and UVA irradiation alone produces relatively little inhibition of the growth of Propionibacterium acnes and Propionibacterium granulosum, whereas a combination leads to an intense suppression of bacterial growth. It was further demonstrated by in vivo studies on 14 subjects that local treatment with 8 MOP and UVA significantly reduces the propionibacteria in the pilosebaceous duct. These results afford a possible explanation for the well known favorable effect of photochemotherapy on acne vulgaris. In addition, they contribute to explaining the drier appearance of the skin after photochemotherapy.
One patient with urticaria pigmentosa was treated with PUVA. This treatment resulted in generalized tanning, decrease of Darier's sign and improvement of pruritus. However, the hyperpigmented macules overlying the mast cell infiltrates showed some persistence. This patient was subjected to biopsy of lesional skin before, during and at the end of oral photochemotherapy. During and after PUVA-therapy, histological examination revealed an increased number of free granules and a progressive decrease in the number of dermal mastocytes. Ultrastructurally necrotic cellular changes in the dermal mastocytes were observed. This suggests that PUVA-therapy may exercise its beneficial effect in urticaria pigmentosa by direct destruction of these cells. In addition, PUVA stimulates mast cell degranulation. Histaminaemia was estimated in this patient, before and after several irradiations. No significant changes were observed. Furthermore, histaminaemia was assayed in 15 patients with various dermatoses undergoing PUVA-therapy. No significant changes were observed. It is concluded that histaminaemia assayed using the fluorometric method of Shore et al. remains unchanged during oral photochemotherapy.
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.
Psoralens (furocoumarins) are photosensitizers of plant origin. They are used in combination with near-ultraviolet (320-400 nm) light for the treatment of vitiligo, psoriasis, cutaneous T-cell lymphoma (CTCL), alopecia areata, eczema, and other skin diseases. Photobiological effects of psoralens in humans are numerous. They photosensitize erythema, hyperpigmentation, and skin aging, affect immune system, etc. Molecular mechanisms of photochemical reactions of psoralens with substrates are also numerous. The molecular basis and the relationships between different photobiological effects of psoralens remain the subject of discussion. The use of antioxidants is an essential instrument for clearing up these problems as well as for the progress of photochemotherapy. It was found that antioxidants (alpha-tocopherol, butylated hydroxytoluene, etc.) selectively inhibited the photochemical stage of erythema and hyperpigmentation but had no impact on the post-irradiation stages of these processes. Evidently, the basis of these processes is the reaction of psoralen-photosensitized oxidation of unsaturated lipids and the impairment of barrier functions of biomembranes, since the photochemical stage of these reactions is inhibited by the antioxidant. At the same time, antioxidants did not inhibit the therapeutic effect in the cases of psoriasis and CTCL. Thus, antioxidants can be used as a tool for improvement of psoralen photochemotherapy.
BACKGROUND: Localized scleroderma is known to be resistant to therapies. Recently, it has been reported that bath PUVA photochemotherapy is effective for treating this dermatosis. OBJECTIVES: Although according in earlier reports mainly white populations have been treated successfully with bath PUVA therapy, there is little knowledge of whether it is effective in treating colored populations. We treated a 64-year-old Japanese woman suffering from disseminated scleroderma with bath PUVA photochemotherapy to see its effects. CONCLUSION: Although rather high cumulative UVA doses were required for this patient compared with those needed in earlier reports, no adverse effects were observed. The lesions were markedly improved, suggesting that this therapeutic modality is well-tolerated and useful for colored patients such as the Japanese. Furthermore, it turns out that the thermographical assessment is useful to estimate clinical improvement of this sclerosing skin disorder.
Twelve patients with extensive lichen planus, resistant to different regimes of prior external and internal therapy, were treated with PUVA-bath photochemotherapy (psoralen bath followed by UVA irradiation) using bath water containing 0.5 mg/L of 8-methoxypsoralen (8-MOP). In 11 of the 12 patients, the skin lesions showed a significant improvement or even complete remission within six weeks of treatment. In one patient, only limited clinical improvement could be achieved. A mean of 19.1 (SD +/- 3.6) PUVA-bath treatments were carried out. The mean cumulative UVA-dose given until clearance of the lichen planus was 16.7 (SD +/- 4.8) J/cm2. No side effects were seen except an increased phototoxic reaction in two patients manifested as slight erythema. The results of this trial show, that PUVA-bath photochemotherapy with 8-MOP is an effective therapeutic alternative to all other known therapies in the treatment of extensive, exanthematic and also hypertrophic-hyperkeratotic lichen planus. In comparison to oral PUVA therapy and PUVA-bath therapy using 4,s',8-trimethoxypsoralen, balneophotochemotherapy with 8-MOP shows an excellent efficiency-side effect correlation. The clearance of the refractive skin lesions by balneophotochemotherapy with 8-MOP demonstrates the superiority of this therapy over all other common therapeutic modalities used for lichen planus.
A 70-year-old woman with long-standing hypereosinophilic dermatitis improved strikingly with PUVA-bath photochemotherapy. The single UVA doses ranged from 0.3 to 3.3 J/cm2. After 19 treatment sessions pruritus disappeared, and after 32 treatments the erythematous maculae completely cleared. Under continuous treatment three times a week, no relapse has occurred to date. PUVA-bath photochemotherapy seems to be a promising new treatment modality without systemic side effects for patients with hypereosinophilic dermatitis.
A 73-year-old man presented with severe, relapsing acrodermatitis continua of Hallopeau, which had been resistant to prior local and systemic therapy for eight years. The patient was treated with selective hand PUVA-bath photochemotherapy. The cumulative dose of UVA used over 10 weeks of treatment was 54.6 J/cm2 on the palms and 26.8 J/cm2 on the dorsum of the hands. The single UVA doses ranged from 0.5 to 2.5 J/cm2 on the palms and 0.2 to 1.4 J/cm2 on the dorsum of the hands. After 16 treatment sessions, the acrodermatitis continua started to improve, and after 24 treatments, had cleared completely. In the four months following the PUVA therapy, there was no relapse. PUVA-bath photochemotherapy is an efficient therapeutic alternative in the treatment of acrodermatitis continua due to its clinical effectiveness and lack of any systemic side effects. It also possesses the advantage of allowing selective photosensitization of certain areas of the skin such as the hands.