Low-dose UVA Research Articles

The suppression of immunity by ultraviolet radiation: UVA, nitric oxide and DNA damage.

We have examined the mechanism by which solar-simulated ultraviolet radiation (ssUV) suppresses memory immunity to nickel in allergic humans. In initial studies, we used inbred mice to determine the contribution of different wavebands to sunlight-induced immunosuppression. We found that low dose UVA can enhance memory, medium dose UVA (half the amount in one minimum erythemal dose of ssUV) is immunosuppressive, but higher doses protect from UVB. This is genetically dependent, as it is not observed in all mouse strains. UVA caused a similar dose-related change in recall immunity in humans. ssUV dose responses determined the limits of protection provided by sunscreens from immunosuppression in humans. Immune protection factors calculated from these data correlated with UVA protection, but not with sun protection factor, showing that in commercial sunscreens that provide good UVB protection, UVA protection limits prevention of immunosuppression. N(G)-monomethyl-l-arginine acetate (l-NMMA) was used to inhibit nitric oxide (NO) production and T4N5 liposomes containing T4 endonuclease V to enhance DNA repair. Sub-erythemal ssUV caused a dose-related local suppression of recall immunity to nickel in humans. l-NMMA and the liposomes protected the nickel reaction, suggesting that NO and DNA damage are mediators of UV-induced immunosuppression in humans.

Effect of low doses of UV-A and UV-B radiation on photosynthetic activities inPhaseolus mungo L.

The effect of low doses of UV-A (320–400 nm) and UV-B (280–320 nm) radiation on photosynthetic activities inPhaseolus mungo L. was investigated under field condition. Supplementation of UV-A enhanced the synthesis of chlorophyll and carotenoids than the UV-B supplemented plants. Significant increase was seen in the concentration of UV-B absorbing compounds of UV-B treated plants. Increase of PS 2 activity in UV-A treated plants was seen. Changes in photosynthetic activity were measured in terms of PS 2 mediated O2 evolution and Chl a fluorescence.

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis

Background Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. Objective We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. Methods Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. Results UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. Conclusion Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Low-Dose UVA1 Reduces Dermal Collagen in Systemic Sclerosis

Progressive systemic sclerosis (PSS) is a multisystem disease characterized by the presence of specific autoantibodies, altered immune activation, and massive collagen deposition in skin and internal organs. Therapy, even potent immunosuppression, can be ineffective. Low-dose UVA1 has been reported to be successful in reducing the quantity of skin collagen in morphea and lichen sclerosus et atrophicus. …

Estudio morfométrico in vivo con microscopía confocal en tiempo real de las alteraciones epidérmicas de la piel tras dosis bajas y repetitivas de radiación ultravioleta A (UVA)

Introductionrepetitive exposure of skin to erythematogenic doses of UVA and UVB is known to produce epidermal changes in human skin. The aim of the present study is the use of high resolution in vivo confocal imaging to assess the effects of repetitive low-dose UVA irradiation on human epidermis. Methods and results1cm2 area on the inner aspect of the arm of 4 volunteers was exposed to a suberythemal dose (0.5 minimal erythema dose [MED]) of UVA once daily, 5 days a week, for 15 cummulative doses. In vivo epidermal changes were analyzed and quantified with a confocal microscope. In each imaging the thickness of the stratum corneum as well as the suprapapillary page (SPP) and rete page were evaluated. Both the stratum corneum and the suprapapillary epidermis showed a progressive increase in their thickness since the second (9 doses) and first (4 doses) evaluation, respectively. The increase was statistically significant since the third evaluation. On the other hand, the thickness of the rete page did not show significant changes. Conclusionreal-time reflectance confocal microscopy is a novel imaging tool that allows to assess in vivo optical sectioning of skin with high resolution and contrast. Hence, confocal microscopy can be very useful for the study of dynamic processes as photodamage.The results of this study demonstrate that low and repetitive doses of UVA include epidermal changes, mainly in the epidermal thickness, that probably represent a protective reaction of the skin against UVA radiation, and must be considered early changes of skin photodamage.

Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light

Long-wavelength UV light (UVA) is known to induce transcription of various genes in the cell and to cause a variety of pathological or protective responses in the skin. To find additional UVA-responsive genes, human skin-derived fibroblasts were exposed to UVA under non- or partially lethal conditions, and the effects of UVA on the transcriptional profile were examined by using DNA microarray and RT-PCR. Transcription of several genes including those already known to be UVA-responsive was induced to a significant extent under 50% lethal conditions of exposure. Among those, ATF3 was the most sensitive and its transcription was increased 10-fold within 1 h. Even at a non-lethal dose of UVA (8 J/cm 2), it was increased 8-fold, if cells were cultured for 3 h post-exposure. Typical immediate–early genes such as c- fos and c- jun were not affected at this dose. We thus suggest that ATF3 could be a key regulator for a variety of cellular responses in the skin, particularly to low doses of UVA.

Ultraviolet A1 phototherapy.

Long-wavelength ultraviolet A (340-400 nm; UVA1) therapy is currently available in only a few dermatology departments. Equipment capable of delivering this waveband has been available since 1981, but it is only over the past decade that increasing numbers of studies assessing the potential of this as a therapy have been published. High-dose UVA1, which requires expensive and space-occupying apparatus, is effective as a monotherapy for acute flares of atopic dermatitis, but it has not yet been formally assessed as an adjunct, rather than as an alternative to conventional therapies including potent and very potent topical corticosteroids. Low-dose (which can be administered using a standard phototherapy cubicle fitted with appropriate lamps) and medium-dose UVA1 may be less effective for this indication. Another condition for which UVA1 is effective, and is particularly promising because we have no reliably effective treatment already, is localized scleroderma. It also appears to be effective in systemic lupus erythematosus (although it is not yet clear when it is indicated, and its safety needs to be assessed in more patients) and in polymorphic light eruption (although there have been no studies suggesting that UVA1 will have any advantages over standard prophylactic phototherapies). Open studies and case series suggest that UVA1 may prove beneficial for various other diseases, including cutaneous T-cell lymphoma, lichen sclerosus, keloids, systemic sclerosis and hand dermatitis. In the centres where it is available, UVA1 has already proved a useful addition to the range of phototherapies previously available. However, much more research is needed to confirm its efficacy for many of its potential indications, and to determine when and how it should be used.

Tight control of matrix metalloproteinase-1 activity in human skin.

Chronic ultraviolet irradiation leads to photoaging in human skin, which is associated with degradation of connective tissue. This is partly due to the fibroblast collagenase (matrix metalloproteinase 1 [MMP-1]). Using complementary DNA array technique we demonstrate that after UV irradiation, MMP-1, MMP-3 and the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) are time-dependently induced on the messenger RNA level in dermal fibroblasts in vitro and in vivo in human buttock skin. This increase in gene expression is paralleled by an increase of latent and active MMP-1 protein after low-dose UV-A exposure in vitro. In vivo the concentration of latent MMP-1 in suction blister fluids peaks 24 h after irradiation with 2 minimal erythema doses of solar simulated radiation. However, only a small proportion of MMP-1 in vitro (5.5 +/- 1.5%) and in vivo is active, whereas the majority of MMP-1 remains in its inactive proform. Interestingly, in suction blister fluid the concentration and duration of TIMP-1 expression exceeds that of MMP-1. Taken together, these data indicate that MMP-1 activity is tightly regulated transcriptionally and posttranscriptionally. Furthermore, the pronounced individual differences in all targets investigated provide a possible explanation for the different susceptibility of individuals to UV exposure and, thus, to the clinical features of photodamage.

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: Results of a preliminary study

Background: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. Methods: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm2. Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm2. Results: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P < .05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P < .001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. Conclusion: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS. (J Am Acad Dermatol 2002;46:251-5.)

Pre-exposure with low-dose UVA suppresses lesion development and enhances Th1 response in BALB/c mice infected with Leishmania (Leishmania) amazonensis

This study was conducted to determine whether exposing mice to ultraviolet (UV) radiation would alter the pathogenesis of infection with Leishmania ( Leishmania) amazonensis ( L. amazonensis) which causes progressive cutaneous disease in susceptible mouse strains. BALB/c mice were irradiated with 10 and 30 J/cm 2 UVA on shaved skin of the back from Dermaray (M-DMR-100) for 4 consecutive days before infection with Leishmania promastigotes. The course of disease was recorded by measuring the size of lesions at various times after infection. Mice groups irradiated with UVA 10 and 30 J/cm 2 showed significantly suppressed lesion development compared with the non-irradiated mice. Light and electron microscopy revealed a few parasites at the site of inoculation in UVA-irradiated subjects. Sandwich enzyme-linked-immunosorbent-assay (ELISA) examination of sera showed dose dependently upregulated interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-12, and downregulated interleukin (IL)-4 and interleukin (IL)-10 levels in UVA-irradiated as compared with the non-irradiated mice. Positive signals for IFN-γ mRNA in irradiated mice were obtained by RT-PCR, while non-irradiated mice showed negative results. None of the examined samples showed signal for IL-4 mRNA. The present study disclosed that exposure of mice to different low-doses of UVA irradiation prior to infection may interfere with immunity to L. amazonensis in the murine model. This indicates that the cell-mediated response switch from Th2 to Th1 pattern suppressed the cutaneous lesions of L. amazonensis.

Adaptive antioxidant response protects dermal fibroblasts from UVA-induced phototoxicity

In response to the attack of reactive oxygen species (ROS) produced upon UV irradiation, the skin has developed a complex antioxidant defense system. Here we report that, in addition to the previously published induction of manganese superoxide dismutase (MnSOD) activity, single and, to a higher extent, repetitive low-dose UVA irradiation also leads to a substantial upregulation of glutathione peroxidase (GPx) activity. This concomitant adaptive response of two antioxidant enzymes acting in the same detoxification pathway coincided with the protection from high-UVA-dose-induced cytotoxicity conferred by low-dose UVA preirradiation. Whereas an interval of 24 h did not, an interval of 12 h did lead to the induction of MnSOD activity and, under selenium-supplemented conditions, of GPx activity as well, conferring definite cellular protection from UVA-induced phototoxicity. Moreover, under selenium-deficient conditions, which abrogate the UVA-mediated induction of GPx activity, adaptive protection against the cytotoxic effects of high UVA doses was significantly lower compared with selenium supplementation. Isolated 4.6-fold overexpression of MnSOD activity in stably transfected fibroblasts led to specific resistance from UVA-mediated phototoxicity under selenium-deficient conditions. Collectively, these data indicate that the concomitant induction of MnSOD and GPx activity is related to the optimal adaptive protection from photooxidative damage. This adaptive antioxidant protection clearly depends on the irradiation interval and a sufficient selenium concentration, findings that may have important implications for the improvement of photoprotective and phototherapeutic strategies in medicine.

Low Doses of UVB or UVA Induce Chromosomal Aberrations in Cultured Human Skin Cells

Chromosomal defects are frequently present in malignant and premalignant skin disorders; however, it is not known whether ultraviolet radiation from sunlight plays a role in their induction. To obtain information on the ability of ultraviolet A and ultraviolet B to induce chromosomal aberrations, cultured melanocytes and fibroblasts were exposed to physiologic doses of ultraviolet A or ultraviolet B and, for comparison, to gamma rays. As a measure of chromosomal aberrations, the formation of micronuclei was determined. To obtain sufficient statistical data on induced micronuclei and cell kinetics, a flow cytometry method has been modified and applied. The flow cytometry method analysis is based on staining the DNA with ethidium bromide and the cell membranes with 1,6-diphenyl-1,3,5,-hexatriene. We observed dose-dependent micronuclei formation after gamma or ultraviolet B irradiation in both cell types and also for ultraviolet A in fibroblasts. The yield of micronuclei induced in fibroblasts by ultraviolet A was only a factor 15 smaller than that induced by ultraviolet B (313 nm). The results indicate that 10 kJ per m2 (equivalent to 1 minimal erythema dose) of ultraviolet B and 150 kJ per m2 of ultraviolet A (0.2 minimal erythema dose) can induce 1% of micronuclei in fibroblasts, equivalent to the induction due to 0.6 Gy of gamma radiation. In conclusion, physiologic doses of sunlight can induce chromosomal aberrations at a level comparable with that observed after exposure to approximately 1 Gy of ionizing radiation. Therefore, sunlight can be considered a potential inducer of chromosomal aberrations in skin cells, which may contribute to skin carcinogenesis.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA1 therapy (single dose, 20 J/cm2, 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease. (J Am Acad Dermatol 2000;42:134-6.)

Relative roles of metal ions and singlet oxygen in UVA-induced liposomal lipid peroxidation

Unilamellar liposomes prepared from phosphatidylcholine were exposed to relatively low doses (36–72 kJ m −2) of UVA to study the relative role of metal ions and singlet oxygen. Electron spin resonance (ESR) spectroscopy showed that singlet oxygen was produced during UVA radiation of liposomes and that the signal was enhanced when liposomes and the buffer were prepared in D 2O. However, in liposomes and buffer prepared in deionized water (dH 2O), UVA-induced lipid peroxidation (measured as formation of thiobarbituric acid reactive substances, TBARS) was strongly dependent on adventitious metal ions because formation of TBARS was inhibited ∼80% by inclusion of 10 mM EDTA or desferrioxamine (desferal) during 1-h UVA radiation (72 kJ m −2). Dimethysulfoxide (DMSO) and mannitol had no effect and NaN 3 and histidine only slightly inhibited TBARS, suggesting that singlet oxygen is a minor factor in UVA-induced liposomal peroxidation. To further elucidate the relative roles of singlet oxygen and metal ions, Fe(III) was added to liposomes during UVA irradiation, which resulted in markedly enhanced formation of TBARS. Singlet oxygen was detected at UVA doses of 72 and 108 kJ m −2 by N,N-dimethyl- p-nitrosoaniline bleaching test carried out in D 2O but not in dH 2O. Formation of TBARS was completely inhibited by 10 mM EDTA and desferal but was unaffected by either 50 mM DMSO, 50 mM mannitol, 50 mM NaN 3, 4 mM tryptophan or 0.1 mM β-carotene. The present study demonstrates that, although singlet oxygen is produced by UVA radiation, its role in the formation of TBARS appears to be relatively minor compared with that of metal ions in unilamellar liposomes irradiated with physiological doses of UVA.

Half-side comparison of erythemogenic versus suberythemogenic UVA doses in oral photochemotherapy of psoriasis

Background: Early American and European multicenter trials on the efficacy of photochemotherapy (PUVA) for psoriasis have clearly shown that the treatment protocol has a crucial impact on the cumulative UVA dose required for clearing patients. Most, if not all, treatment protocols rely on the PUVA-induced erythema as a guideline for UVA dosimetry. Objective: Our aim was to investigate whether phototoxic erythema is integral to an optimized PUVA protocol or reflects an unnecessary overexposure of patients. Methods: A standard high-dose UVA regimen using minimal phototoxic doses (MPD) was compared against two different low-dose regimens. To this purpose a bilateral comparison study was performed on 31 patients and divided in two parts. In the first trial on 14 patients, half of each patient’s body was irradiated at each visit with 1 MPD, whereas the other half received only two thirds of the MPD. In the second trial on 17 patients treatment with 1 MPD was compared against treatment with one half of the MPD. Results: A total of 27 patients (12 patients in the first trial, 15 patients in the second trial) completed the study. In both trials the suberythemogenic doses were therapeutically as effective as the minimal phototoxic doses. Conclusion: We conclude that PUVA-induced erythema is not a prerequisite for effective psoriasis treatment and that a low-dose UVA regimen is a promising approach to increase the short- and long-term safety of photochemotherapy. (J Am Acad Dermatol 1999;41:408-13.)

Low-Dose UVA Illumination of Differentiating Stromal Cells Reveals Diverse Effects on Cell-Mediated Mineralisation in Culture

In the present study the effect of low dose UVA illumination on cell-mediated mineralisation was tested. Rat marrow stromal cells were stimulated with dexamethasone (DEX) to induce mineralisation in the cultures. Different cultures were illuminated with low UVA dose, 0.1 J/cm(2), using illumination protocols which differed either by day of exposure, for single-dose protocols, or by the number of exposure-days, for multiple-dose protocols. Different responses to UVA were induced by early (day 1) versus late (days 7-8) illumination. Single-dose illumination on days 1 or 8 decreased or increased day 21 mineralisation, respectively. The mineralisation differences were not equivalent to the differences in cell counts, and thus did not reflect selection of osteoprogenitor cells (OPC), in contrast to the effect of malonate found in previous studies. Late illumination, on day 7, resulted in a higher rhodamine 123 (Rho) retention on day 7 than the early (day 1) illumination effect on the day 7-Rho retention. The opposing effect of the early and late illumination protocols on mineralisation was also not accompanied by OPC selection. Thus, we have shown that low UVA dose modulates mineralisation together with modulation of mitochondrial Rho retention. These results suggest that low doses of UVA light may affect bone mineralisation.

Low-Dose UVA and UVB have Different Time Courses for Suppression of Contact Hypersensitivity to a Recall Antigen in Humans

This study investigates the relative effects of low-dose solar-simulated ultraviolet, ultraviolet A, and ultraviolet B radiation on the elicitation of contact hypersensitivity to nickel in nickel-allergic volunteers. A xenon arc lamp with changeable filters was used to irradiate groups of volunteers daily, on separate areas of their lower backs, with both solar-simulated ultraviolet (ultraviolet B, ultraviolet AII + ultraviolet AI) and ultraviolet A (same ultraviolet AII content but twice the ultraviolet AI as the solar-simulated ultraviolet spectrum) for 1 and 2 d; 3, 4, and 5 d; and from 1 to 4 wk. A fourth group was irradiated for 1-5 d with the ultraviolet B component of solar-simulated ultraviolet. Following the final irradiation in each group, nickel-containing patches were applied to both ultraviolet-treated sites and adjacent, unirradiated control sites. Erythema caused by nickel contact hypersensitivity at each site was quantitated 72 h later with a reflectance erythema meter. By comparing the nickel reactions of irradiated and unirradiated skin, ultraviolet immunosuppression was assessed with the different spectra and durations of ultraviolet exposure. We found significant immunosuppression with daily doses of ultraviolet B and ultraviolet A equivalent to approximately 6 min of summer sun exposure, and that ultraviolet A and ultraviolet B exerted their maximal immunosuppressive effects at different times. Solar-simulated ultraviolet-induced immunosuppression was significant after one exposure, near-maximal after two exposures and remained elevated thereafter. Ultraviolet B-induced immunosuppression was lower than that induced by solar-simulated ultraviolet, but followed a similar time-course. In contrast, ultraviolet A-induced immunosuppression was transient, peaking after three exposures. Immune responses returned towards normal with subsequent ultraviolet A exposure, suggesting that an adaptive mechanism may prevent immunosuppression by continued ultraviolet A irradiation.

UVA-induced oxidative damage to rat liver nuclei: reduction of iron ions and the relationship between lipid peroxidation and DNA damage

Lipid peroxidation and DNA damage and the relationship between the two events were studied in rat liver nuclei irradiated with low dose UVA. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) by spectrophotometric method and as malondialdehyde-TBA adduct by HPLC, and DNA damage was measured as 8-hydroxy-deoxyguanosine (8-OH-dGu) and strand breakage (or loss of double-stranded DNA) by a fluorometric analysis of alkaline DNA unwinding method. The results show that UVA irradiation by itself increased nuclear lipid peroxidation but caused little or no DNA strand breakage or 8-OH-dGu. When 0.5 mM ferric (Fe +3) or ferrous (Fe +2) ions were added to the nuclei during UVA irradiation, lipid peroxidation and DNA damage, measured both as 8-OH-dGu and loss of double-stranded DNA, were strongly enhanced. Lipid peroxidation occurred concurrently with the appearance of 8-OH-dGu. Fe 3+ ions were reduced to Fe 2+ in this UVA/Fe 2+/nuclei system. Lipid peroxidation and DNA damage were neither inhibited by scavengers of hydroxyl radical and singlet oxygen nor inhibited by superoxide dismutase and catalase. Inclusion of EDTA or chain-breaking antioxidants, butylated hydroxytoluene (BHT) and diphenylamine (an alkoxy radical scavenger), inhibited lipid peroxidation but not the level of 8-OH-dGu. BHT also did not inhibit the loss of double-stranded DNA in this system. This study demonstrates the reduction of exogenous Fe +3 by UVA when added to rat liver nuclei, and, as a result, oxidative damage is strongly enhanced. In addition, the results show that DNA damage is not a result of lipid peroxidation in this UVA/Fe 2+/nuclei system.

8-Methoxypsoralen potentiates the photocytotoxic effect of Photofrin II towards EMT-6 murine tumor cells

Pretreatment of EMT-6 murine tumor cells for 24 h with 10 −4 M 8-methoxypsoralen (8-MOP) increased the photocytotoxicity of Photofrin II (P2) after cell exposure to low doses (1–1.5 J/cm 2) of UVA by two- to three-fold. 8-MOP alone had no cytotoxic action under these experimental conditions and did not significantly change the amount of P2 recovered in cells. 8-MOP enhanced the lipid peroxidation end product formation measured as thiobarbituric acid reactive substances (TBARS) during cell photosensitization by P2. The psoralen alone also slightly increased the TBARS level after UVA exposure. These results suggest that 8-MOP, albeit non-photocytotoxic by itself under our experimental conditions, could enhance the efficiency of P2 by increasing cellular lipid peroxidation following light exposure.

Low-dose UVA 1 phototherapy for treatment of localized scleroderma

Background: For treatment of localized scleroderma numerous treatments, including ones with potentially hazardous side effects, are currently used with only limited success. Objective: We attempted to determine the efficacy of low-dose UVA 1 irradiation in patients with severe localized scleroderma. Methods: Patients were irradiated with 20 J/cm 2 UVA 1 for 12 weeks (total number of treatments: 30; cumulative UVA 1 dose: 600 J/cm 2). Results: Low-dose UVA 1 irradiation induced significant clinical improvement (clearance of>80% of lesions) in 18 of 20 patients. Clearance was documented by clinical score as well as by 20 MHz ultrasound and histopathologic analysis. Conclusion: Low-dose UVA 1phototherapy can be highly effective for sclerotic plaques, even in patients with advanced localized scleroderma and with lesions rapidly evolving despite conventional therapy. (J Am Acad Dermatol 1998;38:21-6.)