Treatment of Adult T Cell Leukaemia by Extracorporeal Photochemotherapy

Four patients with chronic or smouldering type adult T cell leukaemia (ATL) were treated by extracorporeal photochemotherapy (photopheresis). From 4 to 8 months after starting photo-pheresis, skin lesions with ATL cell infiltration began to disappear. Cell surface markers in three patients showed improvement. In one patient, a serial decrease of soluble interleukin-2 receptor levels (950 U/ml to 620) in the serum was observed after 4 months. This pilot study suggests that photopheresis may be successfully applied in ATL. It is still necessary to continue follow-up observations in these patients and to treat a larger number of cases, before definite conclusions can be drawn in the future     

Photochemotherapeutic Agent 8-Methoxypsoralen Induces Cytochrome P450 3A4 and Carboxylesterase HCE2: Evidence on an Involvement of the Pregnane X Receptor

8-Methoxypsoralen (8-MOP) is a prototype photochemotherapeuticagent and used to treat various skin disorders such as psoriasisand cutaneous T-cell lymphoma. Animal studies demonstrate thatrepeated treatment with 8-MOP markedly increases the capacityof drug metabolism. In this study, we report that 8-MOP is apotent inducer of cytochrome P450 3A4 (CYP3A4) and carboxylesterase2 (HCE2), two major human enzymes that catalyze oxidative andhydrolytic reactions, respectively. In human primary hepatocytes,8-MOP markedly induced the expression of CYP3A4 (approximatelysixfold) and HCE2 (approximately threefold) and the inductionoccurred in a concentration-dependent manner (0–50µM).RNA interference of the expression of the pregnane X receptor(PXR) proportionally decreased the induction. In a reporterassay, 8-MOP stimulated both CYP3A4 and HCE2 promoters, andthe stimulation was enhanced by cotransfection of PXR. Severalnatural variants of PXR differed markedly from the wild-typereceptor in responding to 8-MOP. In addition to human PXR (hPXR),8-MOP activated rat PXR, and the activation was comparable tothat of hPXR (EC₅₀ = 14µM). PXR is recognized as a masterregulator of the genes encoding drug-metabolizing enzymes andtransporters. The involvement of PXR in 8-MOP induction suggeststhat this chemotherapeutic agent causes a broader range of drug-druginteractions, and the differential activation of certain PXRvariants suggests that the magnitude of the interactions variesfrom person to person.     

UV-based therapy and vitamin D

The ultraviolet (UV) light spectrum has long been known to induce biologic effect on the skin. For a large number of cutaneous disorders, phototherapy and photochemotherapy are effective therapeutic options with excellent safety profiles and well-documented side effects. Despite their ease of administration and benefits, phototherapeutic treatment modalities require appropriate space for the equipment, trained staff, and patient education prior to initiating treatment. However, when the initial barriers to treatment can be overcome, UV therapy can offer patients significant relief from their cutaneous disease. Furthermore, UVB-based phototherapy can produce significant alteration to vitamin D levels. With the recent research implicating association of low vitamin D levels with a variety of health conditions, whether patients receiving phototherapy or, more specifically, those getting vitamin D supplement may be protected from these diseases remains to be established.     

Vitiligo: an update on current pharmacotherapy and future directions

Introduction: Vitiligo is a common pigmentary skin disorder, characterized by the appearance of white macules on the skin, mucosal or hair. Treatment is often a tough challenge and involves a wide range of therapies.

Areas covered: This review focuses on available first- and second-line pharmacological treatments for vitiligo. In particular, the mechanisms of action, the main indications, the efficacy and the most important side effects are reviewed. Moreover, a brief discussion is provided, regarding other nonpharmacological treatments, such as phototherapy and surgical options, due to their importance and successful outcomes in vitiligo treatment. Finally, a concise overview regarding the future directions in vitiligo therapy is presented.

Expert opinion: The promising outcomes reported here demonstrate that it is possible to achieve a satisfactory and often stable repigmentation of vitiligo lesions. Topical corticosteroids, calcineurin inhibitors, phototherapy and photochemotherapy represent the first-line therapeutic options, due to their safety and efficacy, whereas vitamin D analogues, targeted phototherapy, oral corticosteroids and surgery should be used as second-line therapies. Other therapies, such as antioxidants, can be used in association with other therapeutic options, whereas depigmenting agents should be used only in cases of extensive vitiligo, recalcitrant to other treatments.     

Improved photochemotherapy of malignant cells with daunomycin and the KTP laser

Laser photochemotherapy of malignancies may become an effective palliative treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fiberoptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhanced cytotoxicity after exposure to argon laser light at 514 nm. This short-term uptake leads to drug localization in cytoplasmic and membrane sites prior to nuclear accumulation and daunomycin topoisomerase inhibition. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochromatic green-wavelength light. Drug uptake and laser energy levels were optimized for maximum synergy. To test light-enhanced chemotherapy in vitro, the kinetics of cell uptake and toxicity of daunomycin was measured at 1, 2, and 5 μg/ml in three human tumor cell lines: P3 squamous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exposure to 300- to 900-nm visible light from a xenon lamp or monochromatic 532-nm green light from a KTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear phototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxicity is enhanced when exposed to 532-nm laser illumination in the three tumor types tested and confirm that the response is related to both energy level and drug dose. Lasers Surg. Med. 23:33–39, 1998. © 1998 Wiley-Liss, Inc.     

复方甘草酸苷联合光化学疗法治疗斑秃30例疗效观察

目的探讨复方甘草酸苷联合光化学疗法(PUVA)治疗斑秃的疗效和安全性。方法 90例斑秃患者随机分为3组,治疗组30例,外涂0.1%8-甲氧补骨脂溶液30min后,用UVA照射患处,2次/周,同时每天服用复方甘草酸苷75mg,3次/d;对照Ⅰ组30例,每天服用复方甘草酸苷;对照Ⅱ组30例,外涂0.1%8-甲氧补骨脂溶液30min后,用UVA照射患处,2次/周。3组疗程均为8周,观察疗效及不良反应。结果治疗组、对照Ⅰ组和对照Ⅱ组有效率分别为93.33%,70.00%和73.33%,治疗组与两对照组比较差异均有统计学意义(P均<0.05)。结论复方甘草酸苷联合光化学疗法治疗斑秃具有良好的疗效和较高的安全性。     

Half-side comparison study on the efficacy of 8-methoxypsoralen bath-PUVA versus narrow-band ultraviolet B phototherapy in patients with severe chronic atopic dermatitis

In patients with severe chronic atopic dermatitis (AD), both photochemotherapy [psoralen ultraviolet A (PUVA)] and narrow-band (TL-01) UV B phototherapy have been reported to be very effective. As no data exist on the relative therapeutic efficacy of these two regimens, we performed a randomized investigator-blinded half-side comparison study on 12 patients with severe chronic AD. Half-side irradiation with threshold erythemogenic doses of 8-methoxypsoralen bath-PUVA and narrow-band UVB was performed three times weekly over a period of 6 weeks. The severity of the disease was assessed separately for the paired halves of the patients' bodies by a modified SCORAD score at baseline and after 2, 4 and 6 weeks of treatment. Ten of the 12 patients completed the trial. All but one showed marked improvement or complete remission with both treatments. The mean baseline SCORAD score decreased by 65.7% by the bath-PUVA treatment and by 64.1% by the narrow-band UVB treatment (P = 0.48). No serious adverse reactions to either of the two regimens were observed. Our data confirm the high efficacy of bath-PUVA and narrow-band UVB phototherapy in the treatment of patients with chronic severe AD. Both regimens appear to be equally effective when administered in equi-erythemogenic doses.     

A review of ultraviolet treatment for psoriasis at Waikato Hospital

Details of 79 courses of UVB and 40 courses of PUVA for patients with chronic plaque psoriasis at Waikato Hospital were prospectively collected when a new Phototherapy Unit opened. Efficacy was assessed by clearance rates (73% for UVB, 87.5% for PUVA). There was significant improvement in Psoriasis Disability Index, which was derived from a questionnaire assessing functional disability and completed by the patients before and after treatment. It took a median number of 24 treatments for psoriasis in the patients receiving UVB to clear, and for the PUVA patients the median was 19 treatments. The efficacy could not be correlated with skin type. Fifty per cent of UVB patients and 25% of PUVA patients received symptomatic burns, all localized and minor in nature. Lifetime PUVA dose was calculated, 90% of patients having received less than 400 J/cm².     

Survey of phototherapy practice by dermatologists in Australia

A postal survey was sent to all dermatologists in Australia to determine current phototherapy practices. Questionnaires were returned by 158 (57%) of 277 dermatologists, of whom 112 (71%) provided phototherapy. Large variations existed in attitudes and practice, including indications, contraindications, dosage schedules, equipment maintenance, response to adverse events, and follow-up arrangements. Cumulative ultraviolet (UV) doses for psoralen and UVA (PUVA) were not calculated by 21%, while 30% did not calculate cumulative doses for UVB. Written informed consent was not obtained by 32%. Phototherapist dermatologists reported 25 patients developing melanoma following PUVA. Only 30% of Australian dermatologists organize regular follow up of patients after phototherapy. Australians have the highest rates of melanoma and non-melanoma skin cancers in the world, because of their ancestry and high solar exposure. This makes it inappropriate for Australian dermatologists to rely entirely on foreign safety data when assessing the risks and benefits of phototherapy in Australian patients. There is a need for standardized Australian guidelines that can be prospectively assessed to ensure phototherapy is used to maximize efficacy and minimize risks in Australian patients, given their unique ancestral mix and outdoor lifestyle.