MEDLINE Abstracts: UVA1 Phototherapy

April 29, 2002

MEDLINE Abstracts: UVA1 Phototherapy

Ultraviolet A1 (340-400 nm) Phototherapy for Scleroderma in Systemic Sclerosis

Morita A, Kobayashi K, Isomura I, Tsuji T, Krutmann J
J Am Acad Dermatol. 2000;43:670-674

Background: The presence of an inflammatory infiltrate consisting of helper T cells and a dysregulated matrix metabolism leading to excessive deposition of collagen are two pathogenetic factors responsible for the developments of fibrosis and sclerosis in patients with systemic sclerosis. In previous studies, ultraviolet A1 (UVA1) radiation phototherapy was shown to deplete skin-infiltrating T cells through the induction of T-cell apoptosis and to up-regulate the expression of matrix metalloproteinase1 (collagenase-1) in dermal fibroblasts.
Objective: Our purpose was to determine whether UVA1 phototherapy is effective for systemic sclerosis.
Methods: Lesional skin on the forearms of patients with systemic sclerosis (diffuse type, n =3; limited type, n =1) was exposed to medium-dose UVA1 radiation (60 J/cm(2)) daily.
Results: In all patients studied, UVA1 phototherapy-treated skin lesions were markedly softened after 9 to 29 exposures. Clinical improvement was associated with an increase in (1) joint passive range of motion values (P<.05), (2) skin temperature (thermography, P <.05), and (3) cutaneous elasticity (cutaneous elastometry, P <.05). Histologic evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers.
Conclusion: These studies indicate that UVA1 phototherapy is effective for patients with systemic sclerosis.

Changes in Collagen I and Collagen III Metabolism in Patients With Generalized Atopic Eczema Undergoing Medium-dose Ultraviolet A1 Phototherapy

Mempel M, Schmidt T, Boeck K, et al
Br J Dermatol. 2000;142:473-480

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.

Long-Term Efficacy of Medium-Dose UVA1 Phototherapy in Atopic Dermatitis

Abeck D, Schmidt T, Fesq H, et al
J Am Acad Dermatol. 2000;42:254-257

Background: UVA1 (340-400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore it seems appropriate to focus research activities on reducing the UVA1 dose applied during phototherapeutic regimens minimizing nonbeneficial side effects.
Objective: The present study was performed to evaluate the therapeutic effectiveness and long-term efficacy of medium-dose UVA1 irradiation in patients treated for acute exacerbated atopic dermatitis.
Methods: Thirty-two patients underwent a medium-dose UVA1 therapy consisting of 15 treatments applied from Monday to Friday for a period of 3 weeks. The applied dose per treatment was 50 J/cm(2) resulting in a cumulative dose of 750 J/cm(2). Clinical severity was assessed according to the SCORAD index before and after irradiation as well as in monthly intervals up to 3 months after cessation of phototherapy.
Results: Medium-dose UVA1 phototherapy is effective for alleviating acute exacerbated atopic dermatitis as shown by a significant reduction of SCORAD ratings (P <.001) at the end of the active UV treatment period. A significant skin improvement was still present 1 month later (P <.001). However, at the end of the 3-month posttreatment observation period the skin condition had reached the pretreatment level.
Conclusion: According to our data, medium-dose UVA1 phototherapy is a highly effective, nonsteroidal, therapeutic alternative for treatment of acute exacerbated atopic dermatitis. However, effectiveness is merely short term, limited, and is followed by recurrence of symptoms within a 3-month observation interval.

Medium-Dose UVA1 Cold-Light Phototherapy in the Treatment of Severe Atopic Dermatitis

von Kobyletzki G, Pieck C, Hoffmann K, Freitag M, Altmeyer P
J Am Acad Dermatol. 1999; 41:931-937

Background: Recently, conventional high-dose UVA1 phototherapy (340-400 nm) has been shown to be more effective than combined UVA-UVB therapy in the treatment of severe atopic dermatitis (AD). However, there are limitations of this treatment, such as intense sweating caused by the immense heat load during therapy and the high cumulative UVA1 doses that are required. For this reason, lavish UVA1 equipment was developed containing an advanced filtering and cooling system resulting in almost complete absence of heat load and sweating during therapy.
Objective: In this study we compared the monotherapeutic efficacy of conventional medium-dose UVA1, medium-dose UVA1 cold-light, and combined UVA-UVB phototherapy in the treatment of severe AD.
Method: The study involved 120 patients with severe AD. Fifty patients each received conventional UVA1 or UVA1 cold-light phototherapy (15 days, 50 J/cm(2)/day), and 20 patients were treated with combined UVA-UVB (15 days, minimal erythema dose dependent). Severity of AD was scored by means of the SCORAD score, and clinical improvement was additionally monitored by serologic cytokine markers.
Results: Six (12%) of 50 patients treated with UVA1, 2 (4%) of 50 patients treated with UVA1 cold-light therapy, and 4 (20%) of 20 patients treated with combined UVA-UVB therapy discontinued treatment prematurely because of an unsatisfactory clinical outcome or adverse reactions. Skin status improved or even cleared completely in 77.3% of the patients treated for 3 weeks with conventional UVA1 therapy and in 85.4% of the patients treated for 3 weeks with UVA1 cold-light therapy, resulting in a significant decrease in the SCORAD score in both UVA1 groups (P <.05 each). In the group treated with combined UVA-UVB, the SCORAD score also decreased but significantly less than in both groups treated with UVA1 photo-therapy (P <.05 each). At follow-up after 4 weeks, the patients treated with UVA1 displayed a more prolonged therapeutic benefit than the patients treated with UVA-UVB therapy. Plasma levels of soluble interleukin 2 receptors and soluble interleukin 4 receptors significantly decreased under both UVA1 and UVA1 cold-light phototherapy but not under combined UVA-UVB phototherapy.
Conclusion: Our study demonstrates that medium-dose UVA1 cold-light phototherapy displays advantages compared with conventional UVA1 phototherapy caused by the almost complete absence of heat load and intense sweating and is more effective than UVA-UVB phototherapy in the treatment of severe AD.

Mechanisms of Ultraviolet (UV) B and UVA Phototherapy

Krutmann J, Morita A
J Investig Dermatol Symp Proc. 1999;4:70-72

Ultraviolet (UV) radiation has been used for decades with great success and at a constantly increasing rate in the management of skin diseases, becoming an essential part of modern dermatologic therapy (Krutmann et al, 1999). For phototherapy, irradiation devices emitting either predominantly middlewave UV (UVB, 290-315 nm) or longwave UV (UVA, 315-400 nm) radiation are employed. In former years, patients were treated with broad-band UVB, broad-band UVA, or combination regimens. Broad-band UV phototherapy, however, is being replaced more frequently by the use of irradiation devices that allow treatment of patients' skin with selected emission spectra. Two such modalities which have their origin in European Photodermatology are 311 nm UVB phototherapy (which uses long-wave UVB radiation above 300 nm rather than broadband UVB) and high-dose UVA1 therapy (which selective employs long-wave UVA radiation above 340 nm). In Europe, 311 nm UVB phototherapy has almost replaced classical broad-band UVB phototherapy and has significantly improved therapeutic efficacy and safety of UVB phototherapy (van Welden et al, 1988; Krutmann et al, 1999). The constantly increasing use of UVA-1 phototherapy has not only improved UVA phototherapy for established indications such as atopic dermatitis (Krutmann et al, 1992, 1998; Krutmann, 1996), but has also provided dermatologists with the opportunity to successfully treat previously untractable skin diseases, e.g., connective tissue diseases (Stege et al, 1997; Krutmann, 1997). These clinical developments have stimulated studies about the mechanisms by which UVB and UVA phototherapy work. The knowledge obtained from this work is an indispensable prerequisite to make treatment decisions on a rationale rather than an empirical basis. Modern dermatologic phototherapy has started to profit from this knowledge, and it is very likely that this development will continue and provide dermatologists with improved phototherapeutic modalities and regimens for established and new indications. This review aims to provide an overview about current concepts of the mode of action of dermatologic phototherapy. Special emphasis will be given on studies that have identified previously unrecognized immunosuppressive/anti-inflammatory principles of UV phototherapy.

Ultraviolet A1 (340-400 nm) Phototherapy for Cutaneous T-cell Lymphoma

Plettenberg H, Stege H, Megahed M, et al
J Am Acad Dermatol. 1999;41:47-50

Background: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well.
Objective: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL).
Methods: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically.
Results: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed.
Conclusion: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Light and Death: Photons and Apoptosis

Godar DE
J Investig Dermatol Symp Proc. 1999;4:17-23

Phototherapies like photodynamic therapy (PDT), UVA1, UVB, and PUVA treat skin diseases. These phototherapies work because they alter cytokine profiles, change immune cytotoxicity in the skin, and directly kill diseased cells by apoptosis. Apoptosis is a term that only describes the morphologic changes a cell undergoes during this mode of cell death. The terms "immediate", "intermediate", and "delayed" apoptosis segregate the different apoptotic mechanisms into three kinetic categories, whereas the terms preprogrammed cell death (pre-PCD) and programmed cell death (PCD) describe the underlying mechanisms. Immediate apoptosis (T< or =0.5 h post-exposure) is triggered by singlet-oxygen damage that opens the mitochondrial megachannel, which can be mediated by PDT or UVA1 radiation. It is a pre-PCD mechanism of apoptosis, i.e., protein synthesis is not required post-insult, because all the necessary components are constitutively synthesized and only need to be activated. Intermediate apoptosis (T< or =4 h>0.5 h) is initiated by receptor cross-linking on the plasma membrane, which can be achieved using high doses of UVB or UVC radiation. It is also a pre-PCD mechanism. Delayed apoptosis (T>4 h) is induced by DNA damage that can be caused by X-rays, PUVA, UVC, UVB, UVA, and PDT. It is a PCD mechanism of apoptosis, i.e., protein synthesis is required post-insult. These three apoptotic mechanisms each access one of two "points-of-no-return" located on the mitochondrial membrane, which activate different, but not mutually exclusive, final pathways of apoptosis. This review discusses the latest findings on these apoptotic mechanisms and their implications in phototherapies.