光疗及光化学疗法治疗儿童皮肤病

临床实践证实,光疗及光化学疗法可以治疗儿童银屑病、白癜风、特应性皮炎及副银屑病等疾病,并且疗效肯定。另外,在一些少见皮肤病中也有应用。但是出于对光疗和光化学疗法长期应用的潜在不确切的致癌性的考虑,以及用于儿童治疗时所采用方法的不统一,和儿童依从性差等问题,限制了其在儿童中的应用。为此,介绍光疗及光化学疗法在儿童皮肤病的应用情况及其安全性和治疗特点等。     

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.     

Phototherapy and photochemotherapy: an update

Three types of phototherapy and 2 forms of photochemotherapy are now available for treatment of more than 40 diseases of the skin. Broadband ultraviolet B (UVB) phototherapy and oral psoralen photochemotherapy (PUVA) therapy are most widely available while there has been increased interest in topical PUVA therapy. Narrow-band UVB phototherapy and UVA-1 phototherapy offer potential for the future.     

PUVA-cream photochemotherapy for the treatment of localized scleroderma

BACKGROUND: The efforts to treat localized scleroderma, including therapies with potentially hazardous side effects, are often unsatisfactory. Recently, PUVA-bath photochemotherapy has been proven highly effective in the treatment of localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen (8-MOP) containing cream or gel preparations, has been proven to be as effective as PUVA-bath therapy for palmoplantar dermatoses. OBJECTIVE: We sought to assess the efficacy of PUVA-cream photochemotherapy in patients with localized scleroderma. METHODS: Four patients with localized scleroderma were included in the study. Diagnosis was confirmed by 20 MHz ultrasound assessment as well as pretreatment skin biopsy specimens from lesional skin. PUVA-cream therapy was performed 4 times a week; all patients received 30 treatments. RESULTS: PUVA-cream photochemotherapy induced significant clinical improvement or clearance of localized scleroderma in all patients. Clearance was documented by clinical features as well as by 20 MHz ultrasound and histopathologic analysis. CONCLUSION: PUVA-cream phototherapy can be highly effective in patients with localized scleroderma even if previous therapy was unsuccessful.     

Differential expression of decorin in localized scleroderma following ultraviolet-A1 irradiation

Patients with localized scleroderma underwent an 8-week course of ultraviolet A1 phototherapy. At baseline, decorin levels of lesional skin were significantly lower than those of nonlesional skin and healthy control subjects. After ultraviolet A1 phototherapy, decorin levels of lesional skin were significantly higher than baseline. Decorin may be of significance in the pathogenesis of localized scleroderma.     

Treatment of genito-anal lesions in inflammatory skin diseases with PUVA cream photochemotherapy: an open pilot study in 12 patients

BACKGROUND: Localized skin lesions of the genito-anal region such as in lichen sclerosus et atrophicus or in lichen planus are a burden for many patients, and therapeutic efforts, including therapies with potentially hazardous side-effects, are often unsatisfactory. Recently, PUVA bath photochemotherapy has been proven highly effective in the treatment of various inflammatory skin diseases, including localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as PUVA bath therapy for palmoplantar dermatoses. OBJECTIVE: We evaluated the clinical effects of PUVA cream photochemotherapy in patients with genital lesions of inflammatory skin diseases. METHODS: Twelve patients with lichen sclerosus et atrophicus, lichen planus, vulvar eczema and pruritus vulvae were included in the study. PUVA cream therapy was performed up to 4 times a week. RESULTS: PUVA cream photochemotherapy induced a significant clinical improvement of genital lesions in most patients, as revealed by clinical examination. Clinical improvement (reduction in size of lesions of erythema, and/or of pruritus) was achieved in most patients after 10-20 treatments and was reduced in patients that had only received 5-15 treatments. Cumulative doses ranged between 4.5 and 180 J/cm(2); all patients tolerated PUVA cream phototherapy well without any side-effects. CONCLUSION: PUVA cream phototherapy represents a highly effective therapy that should be further investigated as an alternative treatment for patients with genital lesions of inflammatory skin diseases.     

Efficacy of UVA1 phototherapy in 230 patients with various skin diseases

OBJECTIVE: Investigation of the efficacy of ultraviolet (UV) A1 phototherapy on atopic eczema, scleroderma, granuloma annulare, urticaria pigmentosa, prurigo nodularis, lichen sclerosus et atrophicus, T-cell lymphoma, keratosis lichenoides chronica, chronic urticaria and some rare, sclerosing skin diseases. METHODS: The data of 230 patients treated with low-dose, medium-dose and high-dose UVA1 therapy during 6 years were retrospectively analysed. The mean single dose (J/cm(2)), the mean number of irradiations and the mean total dose (J/cm(2)) were evaluated. The efficacy of phototherapy was assessed by a grading scale and the number of patients was given in percentage for each group. RESULTS: Good therapeutic effects of UVA1 therapy were shown in patients with atopic eczema, scleroderma, lichen sclerosus et atrophicus, keratosis lichenoides chronica, prurigo nodularis and with cutaneous T-cell lymphoma. Positive effects in some patients were seen in the urticaria pigmentosa and granuloma annulare group, no change to slight improvement was seen in most of the patients with rare, sclerosing skin diseases and no effect was seen in the chronic urticaria group. CONCLUSION: Besides topical and systemic therapy, UVA1 radiation is a good option of treatment in various skin diseases. It is one of the first-line treatments for several sclerotic diseases and it often improves pruritus considerably.     

Eosinophilic fasciitis treated with psoralen-ultraviolet A bath photochemotherapy

Eosinophilic fasciitis is a rare disorder which can markedly affect the quality of life in individual patients. So far, no generally accepted and effective treatment modality has been available. Although the precise nature of eosinophilic fasciitis is still unknown, it is often regarded as a variant of localized scleroderma (morphoea). Phototherapy and photochemotherapy have been shown to be effective in the treatment of sclerodermatous skin lesions. We report a patient with eosinophilic fasciitis which was successfully treated with psoralen plus ultraviolet A bath photochemotherapy within 6 months.     

Localized scleroderma

Localized scleroderma (also called morphea) is a term encompassing a spectrum of sclerotic autoimmune diseases that primarily affect the skin, but also might involve underlying structures such as the fat, fascia, muscle, and bones. Its exact pathogenesis is still unknown, but several trigger factors in genetically predisposed individuals might initially lead to an immunologically triggered release of pro-inflammatory cytokines, resulting in a profound dysregulation of the connective tissue metabolism and ultimately to induction of fibrosis. To date, there are no specific serological markers available for localized scleroderma. Within the last years, several validated clinical scores have been introduced as potential outcome measures for the disease. Given the rarity of localized scleroderma, only few evidence-based therapeutical treatment options exist. So far, the most robust data is available for ultraviolet A1 phototherapy in disease that is restricted to the skin, and methotrexate alone or in combination with systemic corticosteroids in more severe disease that additionally affects extracutaneous structures. This practical review summarizes relevant information on the epidemiology, pathogenesis, clinical subtypes and classifications, differential diagnoses, clinical scores and outcome measures, and current treatment strategies of localized scleroderma.     

Phototherapy: Theory and practice

Despite the development of highly effective biologics for skin diseases such as psoriasis or atopic dermatitis, UVA and UVB therapy, alone or in combination, are still essential components of various guidelines. Phototherapy is not only a first-line treatment and highly effective for a number of skin diseases, but is also economical and has few side effects. The targeted use of UVA and UVB, if necessary, in combination with the photosensitizer psoralen in the context of PUVA therapy, enables the dermatologist to effectively treat a wide variety of skin diseases. Indications for phototherapy include epidermal diseases such as atopic dermatitis, psoriasis and vitiligo, as well as photodermatoses, mycosis fungoides, graft-versus-host disease and deep dermal diseases such as scleroderma. This article reviews the physical principles, molecular mechanisms, current treatment regimens, and individual indications for phototherapy and photochemotherapy.     

UVA1 phototherapy: a review of mechanism and therapeutic application

Ultraviolet radiation (UVR) phototherapy has been associated with both deleterious and beneficial effects to patients with both localized and systemic skin disorders. Phototherapy is advantageous in diseases of the epidermis and dermis, as it provides the most direct approach minimizing systemic side effects. Most recently, ultraviolet A1 (UVA1) phototherapy has emerged as a specific UVR phototherapeutic mechanism. It has shown to be therapeutic in a number of sclerosing skin conditions and other dermatitides, in many cases proving to be more effective than other phototherapy modalities. Treatment advantages of UVA1 phototherapy include the ability to penetrate into the deep layers of the skin to affect changes on disease‐causing T cells, as well as activation of endothelial cells to promote neovascularization. UVA1 therapy also has been shown to be relatively free of side effects associated with other phototherapy regimens, including erythema and cellular transformation. These properties make UVA1 phototherapy an important treatment option for many debilitating skin conditions.     

Low-dose broad-band UVA in morphea using a new method for evaluation

Until recently, various therapies for localized scleroderma have been used with limited success. Recently, phototherapy, with or without psoralen, was proposed as a successful treatment modality. The aim of this study was to evaluate the effect of broad-band low-dose ultraviolet A (UVA) phototherapy in patients with localized scleroderma, using a new method for evaluation. Twelve patients complaining of morphea were exposed to UVA irradiation at a dose of 20 J/cm2 3 times per week for 20 sessions. Selected covered plaques served as internal controls. The efficacy of therapy was judged clinically by sequential inspection and palpation. In biopsy specimens from exposed and covered plaques stained with hematoxylin and eosin (H & E) and Masson trichrome stains, the concentration of collagen per dermal surface area was measured with the use of a computerized image analyzer. All patients reported remarkable softening of skin lesions, confirmed by sequential palpatory assessment. A significant reduction in the mean concentration of collagen per surface area was detected in the plaques exposed to UVA (the P value being 0.007, P<0.01), whereas in the covered plaques the difference was not statistically significant (the P value being 0.10, P>0.05). The conclusion is that low-dose broad-band UVA phototherapy is a very effective and safe treatment modality for localized scleroderma.     

UVA1治疗皮肤病的现状

在过去的30年中,UVA1因能进入皮肤深层诱导T细胞凋亡,下调多种细胞因子,激活内皮细胞并促进血管新生,逐渐被用于治疗各种皮肤疾病.目前有随机对照队列研究证据的疾病包括特应性皮炎、局限性硬皮病、系统性红斑狼疮,其他的适应证还有皮肤T细胞淋巴瘤、系统性硬皮病、胫前黏液性水肿、结节性痒疹等.相比其他光疗法,UVA1的近期不良反应相对较少,远期副作用目前尚无报道,仍需跟踪随访.     

Mycosis fungoides with depigmentation secondary to treatment

A 51-year-old man presented with itchy, erythematous patches and plaques on his trunk, arms, and legs. A skin biopsy specimen showed mycosis fungoides. Initially the patient did not respond to PUVA photochemotherapy but later improved on NB-UVB phototherapy combined with bexarotene and interferon-alpha. The lesions progressed from erythematous patches and plaques to hyperpigmented patches with central depigmentation and localized areas of follicular repigmentation. The development of depigmentation after PUVA photochemotherapy for mycosis fungoides has been described in the literature and does not have associated prognostic implications. It is important to be cognizant of phototoxicity associated with PUVA photochemotherapy or NB-UVB phototherapy in patients with mycosis fungoides, who may be taking photosensitizing medications or have depigmented patches which renders them more sensitive to lower doses of ultraviolet light.     

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.     

Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.     

光疗在皮肤T细胞淋巴瘤中的应用进展

【摘要】 皮肤T细胞淋巴瘤（CTCL）是T细胞来源的恶性肿瘤，目前针对CTCL的治疗主要为了控制症状及长期缓解，光疗及其联合疗法是重要手段之一。应用于CTCL的光疗方法包括长波紫外线加补骨脂素、窄谱中波紫外线、宽谱中波紫外线、体外光化学疗法、光动力疗法、长波紫外线1、308 nm准分子激光等。光疗效果受多种因素影响，如疾病分期、皮损部位、皮肤光反应类型等。在临床应用中，光疗包括清除、巩固、维持阶段，但维持治疗能否控制复发仍存在争议。了解各种光疗的机制、适应证、临床疗效及不良反应有助于选择最佳治疗方案。     

Phototherapy

The efficacy of phototherapy is based on the interaction between ultraviolet (UV) radiation and the skin. The photobiological effects thus achieved depend on the wavelengths used. Targeted use of UVA and UVB, where indicated in combination with a photosensitizer such as psoralen, provides the dermatologist with a broad armamentarium for the treatment of a multitude of skin diseases. The spectrum of indications ranges from superficial dermatitis, psoriasis, and malignancies, such as cutaneous T‐cell lymphoma, to deep sclerosing conditions such as morphea. The objective of the present review is to highlight the photobiological effects of the various types of UV radiation as well as the resultant clinical indications for phototherapy.     

Mechanisms of phototherapy and photochemotherapy for photodermatoses

Most photodermatoses represent indications for preventive ultraviolet (UV) phototherapy and/or psoralen plus ultraviolet A (PUVA) photochemotherapy. The aim of treatment is to prevent the outbreak of disease by increasing the patient's tolerance to sunlight. The mechanisms by which ultraviolet B (UVB) and PUVA induce such tolerance are not completely understood. Pigmentation and skin thickening may be important factors in the protective effect, but they cannot sufficiently explain the degree of protection induced. Other mechanisms that may be of critical importance for the therapeutic efficacy encompass a variety of immunomodulatory effects on human skin known to be induced by UVA, UVB, and PUVA. Obviously the mechanisms of prophylactic phototherapy are strongly intertwined with the pathogenesis of the photodermatoses. The possible mechanisms of photoprevention are discussed for polymorphic light eruption (PMLE), actinic prurigo, chronic actinic dermatitis, and solar urticaria.     

Lokalisierte Sklerodermie (Morphea) im Kindesalter

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.