Photo(chemo)therapy in private practice in Belgium, France and The Netherlands

Photo(chemo)therapy is used widely, and ultraviolet (UV) sources, protocols and indications are numerous. A survey was carried out to examine how photo(chemo)therapy is employed in private practice and to determine whether safety guidelines are respected. A questionnaire survey sent to Belgian, French and Dutch dermatologists generated 593 useful responses. UV sources, doses of UV and 8-methoxypsoralen (8-MOP), as well as the frequency of the treatment, were all different in the three countries. UV starting doses were rarely chosen according to the minimal phototoxic dose (MPD) or to the minimal erythema dose (MED). Total cumulative UV doses were not always determined. Maintenance PUVA therapy for psoriasis was still performed by 15 to 40% of dermatologists in the respective countries. Another striking fact was that genital protection is not universal. On the other hand, the irradiance of tubes is checked regularly, and contraindications are respected. Despite the availability of guidelines, clinicians seem to be inconstant in their assessment of the carcinogenic risk of UV radiation.     

Studies on the Chemistry of Photocarcinorin

Here presents a report on the preparation,chemical composition andphysico-chemical properties of photocarcinorin(PsD-007),a new drug ofphotolocalization and photochemotherapy for human malignancies.It was shownby the results of thin layer and high performance liquid chromatographic(TLC &HPLC)analyses that about 85% of its total weight are relatively hydrophorbicporphyrins of unknown structure,in which a fraction with the same retention timeas hematoporphyrin(Hp)monoacetate constitutes more over 60%.There are also4.2%,of Hp,8.6% of 3(8)-hydroxyethyl-8(3)-vinyl deuteroporphyrin(HVD)and0.6% of protoporphyrin(Pp)in this drug.The presence and amount of HVD inPsD 007 were determined by an authentic sample prepared by authors.Thechanges of the composition of PsD-007 on exposure to different doses of argonlaser(514.5+488nm)irradiation were detected by HPLC.The variations in Soretpeak of UV absorption spectra of PsD-007 protected from light at a constanttemperature were also determined.     

The North American Experience with Photopheresis

Photopheresis or extracorporeal photochemotherapy (ECP) is a novel immunomodulatory therapy based upon pheresis of light-sensitive cells. Whole blood is removed from patients who have previously ingested the photosensitizing agent 8-methoxypsoralen (8-MOP) followed by leukapheresis and exposure of the 8-MOP containing white blood cells (WBCs) extracorporeally to an ultraviolet A (UVA) light source prior to their return to the patient. In 1988, the Food and Drug Administration (FDA) approved photopheresis for the treatment of cutaneous T-cell lymphoma (CTCL). Treatment of CTCL with photopheresis has been reported in over 300 patients worldwide. Photopheresis has also demonstrated encouraging results in the treatment of solid organ transplant rejection, graft versus host disease, scleroderma, and other autoimmune diseases although fewer patients have been studied. This review will focus on the North American experience with photopheresis.     

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998

BACKGROUND: One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended. OBJECTIVES: To evaluate the relevance of this risk in routine clinical practice. METHODS: Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment. RESULTS: Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure. CONCLUSIONS: Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.     

Novel approaches to the treatment of chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) continues to be the major problem in long-term survivors of allogeneic haematopoietic stem cell transplants and is the principal cause of morbidity and non-relapse mortality. Over the past twenty years, diagnosis, prophylaxis and treatment of cGvHD have slowly evolved. An effective therapy for cGvHD is designed to prevent complications through targeting the disease mechanisms. None of the present therapies for cGvHD are successful in the majority of patients. Conventional drugs in different combinations can control the disease in approximately 50% of patients. Attempts to improve survival have led to evaluation of several alternative approaches in the treatment of refractory cGvHD with varying degrees of success. Clinical trials are needed to establish the role of these new approaches in the treatment of cGvHD as first line or salvage therapy without causing significant side effects. This review summarises the currently available knowledge on conventional and new treatment approaches for cGvHD.     

Extracorporeal photochemotherapy in the treatment of eosinophilic fasciitis

BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized clinically by symmetrical swelling, induration and thickening of the skin and histologically by thickening of the fascia with chronic inflammatory infiltrate containing eosinophils. The disease is classified in the spectrum morphea/systemic sclerosis and treated with systemic steroids and other immunosuppressant drugs. OBJECTIVE: The purpose of this study was to use extracorporeal photochemotherapy (ECP) in patients with EF to evaluate the effectiveness of this therapy. SUBJECTS AND METHODS: Three patients affected by EF were treated with ECP because they failed to respond or with contraindications to immunosuppressant treatment. The patients underwent ECP with a UVAR XTS apparatus. Subjects were treated on two consecutive days at 2-week intervals for the first 3 months and thereafter every 4 weeks on the basis of clinical response. The patients were assessed before therapy and then monthly by means of a clinical score. Changes in affected areas were evaluated at predetermined points by computerized skin elastometry (Cutometer SEM 474). RESULT: After 1 year of therapy we found considerable improvement of clinical parameters in two cases. There was less striking improvement in the other case. These clinical results were confirmed by the elastometry measurements. All patients reported improved quality of life, which enabled a reduction in the dose of immunosuppressants. CONCLUSION: ECP emerged as a safe and effective therapy in association with low doses of immunosuppressants in our three patients. A randomized comparative multicentre study between ECP as single therapy and ECP plus immunosuppressants and conventional therapies is required to firmly establish photopheresis as a possible basic treatment to combine with conventional therapies for EF.     

Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and γGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.     

Changes in the dermoscopic appearance of melanocytic naevi after photochemotherapy or narrow-band ultraviolet B phototherapy

BACKGROUND: Although phototherapeutic modalities are commonly used for the treatment of skin diseases, the effects of therapeutic ultraviolet (UV) irradiation on the dermoscopic appearance of melanocytic naevi are unknown. OBJECTIVES: We aimed to analyse the effects of photochemotherapy (psoralen plus ultraviolet A, PUVA) and narrow-band ultraviolet B phototherapy (NB-UVB) on the dermoscopic appearance of naevi. PATIENTS AND METHODS: We monitored 187 melanocytic naevi of 38 patients receiving NB-UVB or PUVA treatment for miscellaneous skin diseases. Dermoscopic images of naevi were taken before, shortly after, and after a median of 31 weeks after the UV therapy. A random selection of naevi was covered during UV treatment, the others remained uncovered. Baseline and follow-up images of naevi were viewed side by side on a computer screen to compare size, pigmentation, and dermoscopic structure of naevi. RESULTS: Twenty-one patients received NB-UVB treatment, and 17 patients received PUVA treatment. Of 187 naevi, 70 (37%) were covered and 117 (63%) were uncovered during UV treatment. When NB-UVB- and PUVA-treated patients were analysed together, an increase in size of uncovered lesions was seen in both treatment groups. Pigmentation appeared darker at the end of UV treatment in 67.5% (n=79) of uncovered naevi compared with 41.4% (n=29) of covered naevi (P<0.001). In patients receiving NB-UVB therapy, a significant increase in the number of dots or globules in 20.3% (n=14) of uncovered naevi compared with only 5.0% (n=2) of covered naevi (P=0.03) was found. This effect was not observed after PUVA therapy. With the exception of four naevi with continuous enlargement and seven naevi with a persisting increase in dots and globules, the observed changes were reversible. All naevi with persistent changes belonged to the NB-UVB group. CONCLUSION: In general, PUVA and NB-UVB therapy cause reversible dermoscopic changes in melanocytic naevi. Increase in dots and globules is more frequent with NB-UVB.     

The effects of long-term local PUVA treatment on collagen metabolism in human skin

Summary The effect of photochemotherapy on skin collagen metabolism was investigated in 57 patients with psoriasis. Twenty-eight patients were treated with trioxsalen baths and UVA irradiation, nine with ditranol and UVB irradiation, and 20 untreated psoriasis patients served as controls. No significant changes were found between the treated groups and the control group in urinary hydroxyproline excretion, skin hydroxyproline content, or in the activities of two enzymes catalyzing collagen biosynthesis, prolyl hydroxylase, and galactosylhydroxylysyl glucosyltransferase in the skin. When the same parameters were compared with the cumulative doses of UVA irradiation, skin prolyl hydroxylase activity slightly decreased with increasing UVA doses, whereas no changes were found in skin hydroxyproline content or galactosylhydroxylysyl glucosyltransferase activity. It was concluded that long-term local PUVA therapy does not significantly alter collagen metabolism in the skin.