局限性硬皮病的UVA-1和PUVA治疗进展

局限性硬皮病是一种结缔组织病,以局限性或弥漫性皮肤硬化或伴有内脏器官纤维化为特征,治疗方法包括物理治疗、药物治疗、紫外线和光化学疗法.其中紫外线和光化学疗法由于效果明显且不良反应小而成为近期研究的热点.大量临床及基础试验证明,紫外线可阻止纤维化进程,使硬化的皮肤斑块变软,尤其是UVA-1(340～400 nm)和光化学治疗PUVA更是取得了很好的效果.但是,目前的大多数试验在实验设计和效果评价方面尚没有统一的标准.

Abstract：

Localized scleroderma (LS) is a connective tissue disease characterized by localized or diffused sclerosis of skin with or without the fibrosis of various internal organs.The management of LS includes physical treatment,drugs and phototherapy.Because of high efficiency and few side effects,phototherapy has become a hot spot of recent researches.Numerous clinical and basic researches have proved that phototherapy can block fibrosis progression,induce softening of already existing sclerotic lesions by suppressing inflammatory cell infiltration.In particular,long wave ultraviolet A1 (340-400 nm) and photochemotherapy (PUVA) have shown a satisfactory effect.However,no uniform standard is available for the design of trials and evaluation of efficacy.     

Evaluation of medium-dose UVA1 phototherapy in localized scleroderma with the cutometer and fast Fourier transform method

PURPOSE: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients with localized scleroderma. METHOD: A controlled pilot study with medium-dose UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin score and two objective methods for quantifying sclerosis (cutometer and fast Fourier transform method). Patients were treated 4 times a week for 5 weeks. The follow-up period was 12 weeks. RESULTS: All patients responded to therapy. Skin score and cutometer results showed improvement of skin elasticity of treated skin compared to control skin. Fast Fourier transform measurements showed no change in bundle orientation ratio and spacing. CONCLUSION: We concluded that treatment for 12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a well-tolerated treatment modality for localized scleroderma (morphea). After 12 weeks, improvement of skin sclerosis can be detected by skin score and cutometer measurements but not by the fast Fourier transform method.     

Successful ultraviolet A1 phototherapy in the treatment of localized scleroderma: a retrospective and prospective study

Background Ultraviolet (UV) A1 phototherapy is an effective anti‐inflammatory treatment modality that influences fibroblast functions. Objectives To document the effects of UVA1 treatment in patients with localized scleroderma (LS) in a retrospective study (at least 6 months after UVA1 treatment) and in a prospective study before and immediately after medium‐dose UVA1 irradiation. Methods In total, 30 patients (retrospective study n = 17, prospective study n = 13) with LS receiving UVA1 phototherapy five times weekly (for 3–6 weeks) were investigated. Improvement was documented using standardized questionnaires and clinical evaluation (using modified Rodnan skin score, Cutometer and 7·5‐MHz ultrasound measurements). Levels of collagen I and collagen III metabolites were measured in serum and urine. Results In the retrospective study, medium‐dose UVA1 phototherapy had been performed 6 months–3 years earlier (cumulative dose 750–1400 J cm^?2; mean ± SD number of irradiations 19·3 ± 3·8). Fourteen of 17 patients (82%) reported an improvement in symptoms following UVA1 therapy. In the prospective study, skin elasticity increased in 77% of the patients following medium‐dose UVA1 phototherapy (cumulative dose 750–1250 J cm^?2; mean ± SD number of irradiations 20·8 ± 4·0). 7·5‐MHz ultrasound measurements showed a mean reduction of lesional skin thickness of 13% compared with skin thickness before UVA1 phototherapy. The ratio of deoxypyridinoline to creatinine was significantly elevated in about two‐thirds of the patients. Conclusions This open study showed a positive short‐ and long‐term efficacy of UVA1 phototherapy in patients with LS, with a reduction in sclerotic plaques, an increase in skin elasticity and a reduction of lesional skin thickness. UVA1 phototherapy had a significant effect on collagen metabolism. UVA1 phototherapy can be regarded as a safe treatment modality for patients with LS.     

Ultraviolet A1 phototherapy for the treatment of localized scleroderma

Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1 phototherapy is also effective against the sclerotic lesions of systemic sclerosis and morphea. Currently, in Japan, access to UVA1 phototherapy is limited because the UVA1 phototherapy device has not yet been approved. On the basis of our experience, we report three patients with localized scleroderma who responded successfully to UVA1 phototherapy. Efficacy was assessed by histological analysis and elastography. UVA1 successfully ameliorated sclerotic lesions, including morphea, linear scleroderma and morphea lesions in a patient with limited cutaneous systemic sclerosis. No side-effects were observed during UVA1 phototherapy.     

Changes in collagen I and collagen III metabolism in patients with generalized atopic eczema undergoing medium-dose ultraviolet A1 phototherapy

Fourteen patients suffering from acute, exacerbated atopic eczema were screened for changes in collagen I and collagen III metabolism in serum (n = 11), urine (n = 11) and skin biopsies (n = 9) before and after medium-dose ultraviolet (UV) A1 phototherapy (15 exposures of 50 J/cm2 over a 3-week period, total dose 750 J/cm2). Mature collagen I and, to a lesser extent, mature collagen III were found to be decreased after the therapy in skin samples from the irradiated patients. As markers of collagen I degradation, the cross-links pyridoline and deoxypyridoline were analysed in urine using high-performance liquid chromatography. Both cross-links were found to be mildly increased after UVA1 phototherapy, without reaching statistical significance. As markers of de novo collagen synthesis we screened for the procollagen I-carboxyterminal peptide (PICP) and procollagen III-aminoterminal peptide (PIIINP) levels in serum and skin. The ratio of PICP to PIIINP in serum dropped significantly after the UVA1 phototherapy, suggesting a different impact of UVA1 on the two collagens. These findings were paralleled by a diminished ratio of PICP to PIIINP in tissue samples. Staining for matrix metalloproteinase 1 (MMP-1) and its specific counterpart, tissue inhibitor of MMP-1 (TIMP-1), showed slight increases for both proteins by therapeutic UVA1; this was also seen in serum for TIMP-1 but not MMP-1. In our study, high-energy UVA1 doses induced changes of the skin collagens in patients with atopic eczema which are measurable by their metabolites in serum and urine.     

Medium-dose UVA1 phototherapy in localized scleroderma and its effect in CD34-positive dendritic cells

BACKGROUND: UVA1 radiation seems to be effective in morphea. CD34+ dendritic cells are significantly decreased in lesional skin of morphea patients. OBJECTIVE: We evaluated the therapeutic effectiveness of medium-dose UVA1 phototherapy in localized scleroderma and its effect in the number of dermal CD34+ dendritic cells in skin biopsy specimens of these patients. METHOD: Patients were irradiated with UVA1 (30 J/cm(2)) 30 times. Dermal CD34+ dendritic cells were counted before and after therapy. RESULTS: There was clinical improvement after UVA1 irradiation. Dermal CD34+ dendritic cells significantly increased after UVA1 irradiation. CONCLUSION: Medium-dose UVA1 therapy is effective in the treatment of localized morphea. Effectiveness is associated with an increase in the number of CD34+ dendritic cells in the dermis.     

Case of localized scleroderma successfully treated with bath psoralen and ultraviolet A therapy

The patient was a 12-year-old girl with linear scleroderma distributed on the right abdomen, dorsal aspect of the right thigh, lower leg and foot. The initial regimen of oral prednisolone and methotrexate, or i.v. methylprednisolone failed in the treatment of the scleroderma. Then bath psoralen and ultraviolet A therapy (bath-PUVA) therapy of 0.2 J–4.0 J/cm² daily to total doses 62.8 J/cm² combined with oral prednisolone was started. After bath-PUVA therapy, regression of the skin sclerosis was observed, the possible mobile range of the right ankle was increased and histological examination confirmed improvement of the sclerosis. The successful results of bath-PUVA therapy in this case suggest its utility for localized scleroderma.     

Scleredema diabeticorum successfully treated with ultraviolet A1 phototherapy

Scleredema diabeticorum is an uncommon condition. It is one of the cutaneous manifestations in diabetes mellitus that mainly occurs in obese middle-aged men with insulin-resistant diabetes. This condition is generally recalcitrant to therapy. Various treatments have been tried with inconsistent results. Here, we describe two cases of scleredema diabeticorum with substantial clinical improvement from a course of medium dose (60 J/cm2) ultraviolet A1 radiation therapy.     

Persistent polymorphous light eruption after ultraviolet A1 phototherapy

Polymorphous light eruption (PMLE) is the most common photodermatosis and is characterized by the development of a pruritic skin eruption within a few hours to days after sun or artificial light exposure. The eruption usually takes up to two weeks to resolve in the absence of further ultraviolet radiation. PMLE has been reported as a side effect of ultraviolet A1 (UVA1) therapy but characteristics of the eruption, especially the duration until resolution after treatment, has not been described. A 37‐year‐old female developed an unusually persistent PMLE that lasted for 5 weeks after completion of UVA1 phototherapy.     

High-dose versus medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis

BACKGROUND: Several studies have demonstrated the efficacy of UVA1 (340-400 nm) phototherapy for patients with severe atopic dermatitis. However, the optimum treatment dose has yet to be determined. Although in seminal investigations high UVA1 doses were used, comparable results were reported in recent studies with a medium-dose regimen. OBJECTIVE: Our purpose was to compare the efficacy of high-dose with medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis. METHODS: Ten adult patients with a median baseline SCORAD score of 67 were enrolled in an investigator-blinded, bilateral comparison study. Treatment was given 5 times weekly over a period of 3 weeks on an outpatient basis. Irradiation was performed by exposing one half of the patient's body to high-dose UVA1 (< or =130 J/cm(2)), and the contralateral body side received only half that dose. The clinical response was assessed after 5, 10, and 15 treatments. After completion of the study, patients were followed up for 6 months to evaluate the duration of clinical improvement. RESULTS: All but one patient responded favorably to treatment. High-dose UVA1 led to a decrease of the median SCORAD score by 33.4% after 1 week, 38.4% after 2 weeks, and 34.7% after 3 weeks. The respective values for the medium-dose regimen were 29.7%, 36.4%, and 28.2%. The difference in efficacy between the two dosages remained below the level of significance at all time points. Relapses occurred after a median of 4 weeks. Time of onset and severity of relapse were the same for both doses. CONCLUSION: Our data support previous uncontrolled observations that medium-dose UVA1 is comparably as effective as high-dose treatment for patients with severe generalized atopic dermatitis. Irrespective of the dose regimen, follow-up examinations revealed early relapse in the majority of patients.     

Biological effects of a new ultraviolet A1 prototype based on light-emitting diodes on the treatment of localized scleroderma

Ultraviolet A₁ (UVA₁) phototherapy (spectral range 340-400 nm) is a well-established treatment option for various skin diseases such as localized scleroderma. Recent improvements of conventional UVA₁ light sources (metal-halide or fluorescent lamps) have brought attention to a new light-emitting diode (LED) technology with remarkable advantages in handling and clinical routine. This study provides a preclinical histological and molecular evaluation of an LED-based UVA₁ prototype with a narrower spectral range (360-400 nm) for treating localized scleroderma. Scleroderma mouse models and fibroblasts in vitro were exposed to LED-based UVA₁ phototherapy or to irradiation with a commercially available metal-halide lamp emitting low-dose (20, 40 J/cm²), medium-dose (60 J/cm²) and high-dose (80, 100 J/cm²) UVA₁ light. Both UVA₁ light sources affected inflammatory genes (IL-1α and IL-6) and growth factors (TGFß-1 and TGFß-2). Increased collagen type 1 was reduced after UVA₁ phototherapy. Matrix metalloproteinase-1 was more enhanced after a medium dose of LED-based UVA₁ phototherapy than after conventional treatment. In vivo, dermal thickness and the amount of collagen were reduced after both treatment methods. Remarkably, myofibroblasts were more effectively reduced by a medium dose of LED-based UVA₁ phototherapy. The study indicates that LED-based UVA₁ phototherapy yields similar or even better results than conventional treatment. In terms of biosafety and patient comfort, LED-based UVA₁ phototherapy offers clear advantages over conventional treatment because of the use of a narrower and less harmful UVA₁ spectrum, less heat generation and shorter treatment times at the same irradiation intensity. Clinical studies are required to confirm these results in patients with localized scleroderma.     

Role of ultraviolet A in phototherapy for psoriasis

Multiple studies have demonstrated that the doses of ultraviolet A (UVA) (320-400 nm) achieved with ultraviolet sources presently used for phototherapy for psoriasis are inadequate to induce coal tar phototoxicity (as manifested by delayed erythema). Some centers still use a phototherapy protocol that combines UVA, ultraviolet B (UVB), and tar for the treatment of generalized psoriasis. We designed a bilateral comparison study to determine whether the addition of UVA to one side, in doses sufficient to induce an immediate burning or smarting sensation in tar-treated skin, would add to the beneficial effects of UVB. The psoriasis of ten of thirteen ambulatory patients cleared in a mean of 26.1 treatments. Despite a mean cumulative UVA dose of 130.8 joules/cm2, none of the thirteen patients showed a better response on the side that received additional UVA. A "nonaggressive" inpatient protocol was designed to maximize the chances of demonstrating a beneficial effect of UVA. The psoriasis of eight of twelve patients cleared in a mean of 21.0 treatments. Despite a mean cumulative UVA dose of 40.3 joules/cm2, the twelve patients showed no difference in clearing between sides. The threshold for smarting increased throughout the treatment and provided a convenient guide to the delivery of increasing doses of UVA. In doses sufficient to induce coal tar phototoxicity manifested by the smarting reaction, UVA does not add to the known benefits of UVB phototherapy.