Photochemotherapy for psoriasis remission times. Psoralens and UV-A and combined photochemotherapy with anthralin.
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Adolescent↗
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[Principles of photochemotherapy and of the determination of the initial dosage of long-wave ultraviolet rays in the photochemotherapy (PUVA) method of treatment].
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Dose-Response Relationship, Radiation↗
[Photochemotherapy and skin cancer. The occurrence of premalignant and malignant skin changes in patients with psoriasis treated with photochemotherapy (PUVA therapy)].
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Bowen's Disease↗
Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial.
BACKGROUND AND DESIGN: In a pilot study of extracorporeal photochemotherapy, two patients with systemic sclerosis who received this therapy experienced significant clinical improvement. These results prompted the development of a multicenter trial to examine the benefit of extracorporeal photochemotherapy in the treatment of systemic sclerosis. Seventy-nine patients with systemic sclerosis of recent onset (mean symptom duration, 1.83 years) and progressive skin involvement during the preceding 6 months entered a randomized, parallel-group, single-blinded clinical trial comparing extracorporeal photochemotherapy treatments given on 2 consecutive days monthly with treatment with D-penicillamine at a maximum dose of 750 mg/d. Blinded clinical examiners evaluated skin severity score (thickness), percent surface area involvement, oral aperture, and hand closure. Serial skin biopsies and pulmonary function studies were also performed. RESULTS: Following 6 months of treatment, significant improvement in skin severity score occurred in 21 (68%) of 31 patients receiving photochemotherapy and in eight (32%) of 25 receiving D-penicillamine treatment, while significant worsening occurred in three (10%) of 31 receiving photochemotherapy and in eight (32%) of 25 receiving penicillamine treatment, thus indicating a significantly higher response rate for individuals who received photochemotherapy (P = .02). At both the 6- and 10-month evaluation points, the mean skin severity score, mean percent skin involvement, and mean oral aperture measurements were significantly improved from baseline among those who received photochemotherapy. Mean right and left hand closure measurements had also improved significantly by 10 months of therapy. By comparison, among the patients treated with D-penicillamine, none of the parameters of cutaneous disease had improved significantly after 6 months of therapy, although for those individuals in whom treatment was continued, the mean skin severity score and mean percent skin involvement had improved by 10 months. Skin biopsy studies revealed a correlation between clinical improvement and decreased thickness of the dermal layer. Adverse effects of extracorporeal photochemotherapy were minimal and did not require discontinuation of treatment in any of the patients receiving this therapy; six patients permanently discontinued the use of D-penicillamine treatment due to adverse effects. CONCLUSIONS: For patients with systemic sclerosis of recent onset, extracorporeal photochemotherapy is a well-tolerated treatment that may partially reverse the process that results in cutaneous sclerosis.
Adult↗
Photochemotherapy inhibits angiogenesis and induces apoptosis of endothelial cells in vitro.
BACKGROUND: Photochemotherapy has long been used in the treatment of psoriasis; however, its mechanism has not been completely elucidated. Psoriasis is now regarded as an angiogenesis-related disease. Recent studies indicated that the inhibition of angiogenesis by photochemotherapy could be an underlying mechanism. It was found that photochemotherapy can downregulate the expression of angiogenic factors in keratinocytes. However, the direct effect of photochemotherapy on endothelial cells has not been studied. METHODS: In this study, we determined the effect of photochemotherapy on the proliferation of human microvascular endothelial cells through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and cell cycle analysis. The migration assay and in vitro tube formation assay were used to investigate the migration properties and tube formation ability of human microvascular endothelial cells after psoralen plus UVA (PUVA) treatment. The apoptosis of endothelial cells elicited by photochemotherapy was also analyzed with fluorescence-activated cell sorting analysis (FACS). RESULTS: UVA (0.8-5.0 J/cm(2)) irradiation with the presence of 8-methoxypsoralen (8-MOP) (300 ng/ml) resulted in a dose-dependent reduction in the cell viabilities of endothelial cells. FACS data showed an accumulation of cells in G0/G1 phase of cell cycle and apoptotic features of cell death after UVA irradiation with psoralen. The migration properties and tube formation ability of endothelial cells were dramatically inhibited by photochemotherapy. CONCLUSION: Our results showed that photochemotherapy inhibits angiogenesis and induces apoptosis of human microvascular endothelial cells in vitro, which may be a possible mechanism of photochemotherapy in the treatment of psoriasis.
Analysis of Variance↗
Extracorporeal photochemotherapy: a scientific overview.
Extracorporeal photochemotherapy was developed for treatment of cutaneous T-cell lymphoma (CTCL). Several independent and multicenter trials using lymphapheresis with 8-methoxypsoralen (8-MOP) activated by shortwave ultraviolet light have demonstrated the clinical benefit of this modality for treatment of advanced CTCL. Recently, trials using the combination of photochemotherapy and recombinant interferons or photochemotherapy and low doses of methotrexate have been initiated to enhance the response to photopheresis. Also, a multicenter study evaluating a new 8-MOP formulation that could be added into the leukocyte/plasma fractions prior to ultraviolet exposure is in progress in CTCL patients. The applications of photochemotherapy in the treatment of other disorders of T-cells are being examined in ongoing clinical trials. Pilot studies have been completed and controlled trials are under way in patients with autoimmune diseases. Important information has emerged regarding the potential use of photopheresis for prevention of solid organ allograft rejection. Several investigators have undertaken pilot studies comparing the efficacy of photochemotherapy with the conventional immunosuppressive therapy for treatment of cardiac transplant rejection. It is hoped that photochemotherapy can induce an immune tolerance in the allograft setting and therefore eliminate or reduce the use of cyclosporin. Other considerations have led to the use of photochemotherapy in the prevention and treatment of graft-versus-host disease after alloeneic and unrelated donor marrow transplantation. Randomized studies are required to evaluate the impact of photochemotherapy on the course of graft-versus-host disease and overall survival.
Humans↗
Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study.
BACKGROUND: Extracorporeal photochemotherapy has been proven effective in selected T-cell mediated diseases. AIM: To evaluate the safety and efficacy of extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease by an open, monocentric trial in three phases of 24 weeks each. METHODS: In phase 1 standardized steroid tapering was initiated in patients with a history of steroid-dependent Crohn's disease. Those with a prospectively evaluated maintenance dose of at least 10 mg/day prednisolone continued steroid-withdrawal under the application of extracorporeal photochemotherapy in phase 2. The duration of remission or response was followed during phase 3. Colonic tissue bioptically obtained before and after extracorporeal photochemotherapy was studied by immunofluorescence microscopy for the presence of photoadduct positive cells. RESULTS: Out of 24 patients included in phase 1, 10 entered phase 2 for extracorporeal photochemotherapy. Four subjects achieved remission and four others response. Significant reductions in serum C-reactive protein levels and intestinal permeability were measured, as well as increases in quality of life and plasma adrenocorticotropic hormone levels. No major side-effects were observed. Remission remained stable in three out of four patients during phase 3. In three patients, positive nuclear stainings of photoadducts were detected in colonic mononuclear cells after extracorporeal photochemotherapy. CONCLUSIONS: Extracorporeal photochemotherapy represents a safe steroid-sparing approach in patients with Crohn's disease and is associated with intestinal homing of photopheresed cells.
Adult↗
[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↗
Primate cardiac allo-and xenotransplantation: modulation of the immune response with photochemotherapy.
Survival of heterotopic allo- and xenografts was studied in a primate cardiac transplantation model. Initially, animals were presensitized to donor xenoantigens by blood transfusion and treated with strategies designed to elicit pretransplant immunosuppression. These animals underwent rapid rejection whether treated with ciclosporin and conventional immunosuppression, autologous sera, sensitized lymphocytes, or photochemotherapy. In a nonsensitized xenograft study, xenografts were maintained for prolonged periods with a combination of ciclosporin and photochemotherapy. All animals treated with photochemotherapy demonstrated periodic suppression of the mixed leukocyte culture response to their donor. Inhibition of lymphocytotoxic antibody was achieved only in animals treated with both ciclosporin and photochemotherapy. Xenosensitized animals were secondarily exposed to donor alloantigens. These animals were successfully allografted. Ciclosporin therapy was terminated and the animals maintained by photochemotherapy alone. This preliminary trial indicates that a combination of ciclosporin and photochemotherapy may be of value in maintaining concordant xenografts and preventing antibody mediated rejection.
Animals↗
Interstitial laser photochemotherapy of rhodamine-123-sensitized rat glioma.
The effect of interstitial laser photochemotherapy with the mitochondrial-specific intravital dye rhodamine-123 (Rh-123) was studied using a malignant rat glioma model system (RT2). Tumors were transplanted subcutaneously into the flank of athymic mice and into the cerebrum of adult rats. The Rh-123 photosensitization was produced by direct intratumoral injection of Rh-123 into the mouse RT2 flank tumors and by intravenous Rh-123 administration to adult rats with implanted RT2 intracerebral tumors. Intratumoral irradiation with 150 mW of argon laser light for an exposure time of 15 minutes was performed using a conical sapphire-tipped quartz optical fiber. Control groups of animals received either no treatment, Rh-123 injections, or administration of 150 mW of argon laser light for 15 minutes. Both flank and intracerebral tumors showed progressive diminution in size after treatment with Rh-123 photochemotherapy. There was no evidence of tumor recurrence in 60% of Rh-123 photochemotherapy-treated tumors. Recurrences in tumors treated with Rh-123 photochemotherapy usually appeared at the periphery of the original tumor at 10 days after treatment. Histologically, photochemotherapy-treated intracerebral tumors showed progressive shrinkage with increasing tumor necrosis over time. The finding of residual or recurrent tumor at the periphery of the original tumor mass suggests that the lack of penetration of the blue-green (argon) light was responsible for preventing complete tumor ablation. Our results suggest that Rh-123 photochemotherapy can destroy malignant gliomas in vivo; however, the poor penetrability of the photoactivating blue-green light may limit the effectiveness of this treatment for large or extensively invasive tumors.
Animals↗
[Photochemotherapy of cancer].
Photochemotherapy of cancer is a new modality of cancer treatment now being evaluated in clinical trials worldwide. It is based on injection of photosensitizing and tumour-localizing dyes followed by exposure of the tumour region to intense light, usually from a laser. A large number of different types of tumours respond to photochemotherapy. However, for photochemotherapy to be efficient, it is absolutely essential that the entire tumour can be reached by light. Thus photochemotherapy is rarely efficient for tumours thicker than 5-7 mm, unless the light is applied interstitially through fibres. Fibre optics can also be used for endoscopic applications. It has been reported that extracorporeal photochemotherapy of T-cells, using 8-methoxypsoralene as sensitizer, has given good clinical results in patients suffering from the erythrodermic form of cutaneous T-cell lymphoma. Extracorporeal photochemotherapy for elimination of residual tumour cells from autologous bone marrow grafts is also being evaluated.
Humans↗
Interaction of commonly used emollients with photochemotherapy.
BACKGROUND/AIM: Even though emollients are commonly used in combination with photochemotherapy, we still lack guidance for the selection of the appropriate emollient to be used in combination with photochemotherapy. The purpose of our study was to determine the interaction of commonly used emollients with photochemotherapy. METHODS: The study was carried on 75 healthy volunteers. In order to assess the effects of five different emollients--white petrolatum, 3% salicylic acid in white petrolatum, Balmandol, Decubal and Urederm hydro--the subjects were divided into five groups. Minimal phototoxic dose (MPD) was determined by irradiating two rows of six circular test fields on the back of the subjects with increasing doses of UVA. One of the emollients listed above was applied to the skin under the upper rows alternatively, whereas the lower rows served as control. RESULTS: Application of Urederm hydro and Decubal before exposure to UVA resulted in a statistically significant decrease in the MPD in all subjects. Even though application of white petrolatum and white petrolatum containing 3% salicylic acid decreased the MPD in most of the subjects and Balmandol application slightly increased the MPD, the results did not reach statistical significance. CONCLUSIONS: According to our findings, it is probable that the total dose of UVA needed to cause clearing of psoriasis would be decreased by application of Urederm hydro and Decubal prior to photochemotherapy. We noted a slight photoprotective effect of Balmandol in the UVA range, but this finding has to be further studied. Clinical studies are needed to clarify the effects of these emollients on the course and outcome of photochemotherapy.
Analysis of Variance↗
Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial.
BACKGROUND: Both interferon alpha and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). However, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better efficacy than for either interferon or extracorporeal photochemotherapy. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of combined interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. METHODS: A prospective controlled study was performed. Fourteen patients (all male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/IIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month for 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-2a subcutaneously 3 times a week in the maximal tolerable dosage (ie, up to 18 x 10(6) U). The effects were investigated by a skin score, staging, histologic score (density of the T-cell infiltrate; from 0 = absent to 3 = heavy), immunohistology, and laboratory investigations including total peripheral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2R). RESULTS: After 6 months, best response was a complete response (CR) in 4 patients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to best response was 4.3 +/- 1.4 months. The skin score decreased from 22.5 +/- 8.1 to 15.1 +/- 11.0 (P <.001), the histologic score decreased from 2.57 +/- 0.51 to 1.21 +/- 0.80 (P <.001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P =.038) and Ki-67-positive cells decreased from 6.7% to 2.4% (P =.001). The total T-cell count/microL decreased from 1018.9 +/- 557.1 to 667.9 +/- 417.9 (P =.012), and the CD4/CD8 ratio also decreased from 1.88 +/- 0.92 to 1.51 +/- 0.67 (P =.038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast to only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dose was decreased because of side effects. After 1 year of follow-up the total response rate was 46.2% (6 of 13 patients): 5 of 9 with stage IIa(55.6%) and 1 of 4 with stage IIb (25.0%). CONCLUSION: These results indicate that patients with CTCL stage IIa can achieve a total response rate of 56% with combined interferon alfa-2a and extracorporeal photochemotherapy. Responders seem to experience their best response within the first 6 months of treatment. The treatment is well tolerated and does not cause severe side effects.
Administration, Oral↗
Extracorporeal photochemotherapy induces a significant increase in CD36+ circulating monocytes in patients with mycosis fungoides.
BACKGROUND: In patients with Sezary syndrome undergoing extracorporeal photochemotherapy it is currently thought that photodamage of a congruent number of pathogenic circulating T cells is a necessary condition for a specific anticlonal response to be induced against these cells by the immune system. However other mechanisms of action, such as the induction of release by photoirradiated monocytes of some cytokines, are thought to cooperate in the induction of a therapeutic response. OBJECTIVE: We investigated the effects of extracorporeal photochemotherapy on peripheral blood mononuclear cells in seven stage Ib cutaneous T cell lymphoma patients. METHOD: Samples of peripheral blood were taken before starting extracorporeal photochemotherapy (baseline), and before the 3rd and 6th cycle of treatment, and then incubated with specific monoclonal antibodies. RESULTS: The results showed a significant increase of CD8+ and CD36+ and a significant decrease of CD25+ in all the treated patients. CONCLUSION: Our results show that extracorporeal photochemotherapy is able to induce an increase of CD36+ cell in peripheral blood of patients with mycosis fungoides in its early stages. This subset of monocytes could be involved in the complex mechanism of action of extracorporeal photochemotherapy.
Aged↗
Psoralen photobiology and photochemotherapy: 50 years of science and medicine.
In 1998 it is appropriate to commemorate the 50th anniversary of el Mofty's use of purified 8-methoxypsoralen (8-MOP) in the treatment of vitiligo (el Mofty AM. A preliminary clinical report on the treatment of leukoderma with Ammi majus linn. J R Egypt Med Assn 1948,31:651 65. el Mofty AM, el Sawalhy H, el Mofty M. Clinical study of a new preparation of 8-methoxypsoralen in photochemotherapy. Int J Dermatol 1994;8:588 92). Two young American dermatologists (Aaron Lerner and Thomas Fitzpatrick) were intrigued by the potency of this material. After Lerner determined that artificial long wavelength ultraviolet (320-400 nm, UVA) radiation was the most efficient for activating 8-MOP. the development of artificial sources enabled the efficient delivery of these photons to skin containing 8-MOP. Their initial studies for vitiligo led to further development of this therapy for the treatment of psoriasis (Parrish JA, Fitzpatrick TB, Tannenbaum L, et al. Photochemotherapy of psoriasis with oral methoxsalen and long-wave ultraviolet light. New Engl J Med 1974;291:1207-11. Honigsmann H, Fitzpatrick TB, Pathak MA, et al. Oral photochemotherapy with psoralen and UVA (PUVA): principles and practice. In: Fitzpatrick TB, Eisen AZ, Wolf K, editors. Dermatology in General Medicine. New York: McGraw-Hill, 1987:1728-54). This photochemotherapy came to be called 'PUVA' (psoralen + UVA). The position PUVA holds today as one of the most common procedures performed in dermatology can be traced to their initial curiosity and their subsequent ingenuity. Further developments in more recent years capitalized on their seminal work. The therapy met with unprecedented success from the outset, leaving little perceived need to understand underlying science. However, in recent years there has been a new found interest in the basic aspects of psoralen photobiology and molecular mechanistic events contributing to therapeutic responses as well as to the development of skin cancers in PUVA patients. These will be surveyed in this review commemorating the 50 years of modern psoralen photobiology and photomedicine.
Animals↗
Phototherapy and photochemotherapy of skin diseases.
One important aspect of photomedicine is the use of nonionizing electromagnetic radiation with and without exogenous photosensitizers to treat diseases. Phototoxicity (cell injury by photons) is a likely mechanism for phototherapy and photochemotherapy of several skin diseases. The mechanism of action for phototherapy of hyperbilirubinemia and of uremic pruritus appears to be photochemical alteration of extracellular metabolites. Psoriasis is an example of a disease benefitted by several forms of phototherapy and photochemotherapy with varying relative effectiveness and safety. Two successful forms of treatment are oral psoralen photochemotherapy and UVB plus topical adjunctive agents. New information about UVB therapy of psoriasis includes data about the therapeutic action spectrum and about the relative roles of various topical agents such as coal tar, mineral oil, "lubricants" and steroids. Although there are many surface similarities, phototherapy and psoralen photochemotherapy have fundamental differences which may alter longterm risks in quantitative and qualitative ways.
Heliotherapy↗
Treatment of capillary vascular malformation (port-wine stains) with photochemotherapy.
One-hundred and thirty patients (85 female, 45 male) with port-wine stains were treated with photodynamic therapy, also called photochemotherapy, which recently has become acknowledged as effective for a variety of malignant tumors. Probably based on the photochemical reaction with the generation of toxic species, photochemotherapy results in endothelial cell injury and death of abnormal capillaries under overlying epidermis. A retrospective review of 118 available patients with port-wine stains reveals that 98.3 percent responded to photochemotherapy with varying degrees of success after one-time treatment. Results were reported under a simple classification system ranging from ordinary to dilated to posttreatment type. In the ordinary group, the results evaluated as excellent, good, fair, and poor were 37.8, 53.7, 8.5, and 0 percent, respectively, before a second treatment; the treated area was an average of 9.8 (range 7 to 13) cm in diameter. In addition, hypertrophic scars, permanent hyperpigmentation, and hypopigmentation were not seen based on proper parameters. Photochemotherapy offers a potentially efficient and promising choice based on a completely different mechanism from that of selected photothermal therapy with the pulsed-dye laser.
Adolescent↗
[Cream PUVA photochemotherapy].
Bath-PUVA-photochemotherapy lacks systemic side effects and requires low cumulative UVA doses, but a major disadvantage is the logistical requirement for bath tubs in a practice. We have developed an alternative form of topical PUVA therapy using a lipophilic emulsion vehicle for the photosensitizer 8-MOP (cream-PUVA-photochemo-therapy). A 0.0006% 8-MOP containing water-in-oil emulsion (30% H2O) was optimal for inducing photosensitivity in treated skin areas without increasing 8-MOP plasma levels. Increased skin photosensitivity was maximal 1 hour after cream application and persisted for 3 hours. We next assessed the effectiveness of cream-PUVA-photochemotherapy in the treatment of patients with chronic recalcitrant palmoplantar eczema (n = 10). In seven patients complete, and in two patients partial, remissions were observed after 40 treatments. Thus, cream-PUVA-photochemotherapy, which is easier to perform than bath-PUVA-photochemotherapy, is an effective, safe and low-cost modality, which may prove to become the topical PUVA therapy of choice for dermatological practitioners.
Dose-Response Relationship, Drug↗