Ultraviolet A1 Research Articles

Evaluating hyperpigmentation: is invasion of the skin necessary?

BackgroundThe combination of long wavelength ultraviolet A1 radiation (LWUVA1) and visible light (VL) has been shown to produce photodamage and the majority of organic sunscreens lack protection against this spectrum. Currently, established testing protocols for VL photoprotection are lacking.ObjectiveTo compare pigmentation assessment methods, including Investigator’s Global Assessment (IGA) scoring, Diffuse Reflectance Spectroscopy (DRS), and immunohistochemistry, to assess the utility of each in evaluating VL + LWUVA1 induced pigmentation.MethodsAnonymized IGA, DRS, and immunohistochemistry data for 37 subjects (Fitzpatrick skin phototypes IV-VI) was retrospectively analyzed for pigment evaluation. Pigmentation was induced on the subjects’ backs with VL + LWUVA1 (0%–0.5% UVA1) irradiation at a dose of 480 J/cm2. Comparisons were made for all three assessment techniques between non-irradiated skin and VL + LWUVA1 irradiated skin, as well as between pure VL (0% UVA1) and VL + LWUVA1 (0.5% UVA1) irradiated sites. All comparisons were made for data collected approximately 24 h after irradiation to evaluate persistent pigment darkening (PPD).ResultsAmong all 37 subjects, both IGA scores and DRS detected a statistically significant difference in PPD between irradiated and non-irradiated sites, as well as between VL + LWUVA1 and pure VL irradiated sites. However, MART-1/Melan-A did not indicate a statistically significant difference in PPD between irradiated and non-irradiated sites or between VL + LWUVA1 and pure VL irradiated sites.ConclusionSubjective and objective noninvasive assessments were more sensitive in detecting VL + LWUVA1 induced pigmentation and should be preferred over invasive methods. Researchers are advised to initiate assessments with IGA and subsequently incorporate DRS for more objective and comprehensive insights in pigment evaluation.

Influence of ultraviolet A1 exposures on mood states: a randomized controlled study

We investigated the effects of daily ultraviolet A1 (UV-A1, 340–400 nm) exposures on mood states (#R19055, approval on 21 October 2020). Based on our earlier findings of the influence of diurnal preference on mood, we investigated further whether diurnal preference plays a role in the influence of UV-A1 on mood states. Forty-one healthy participants aged 19–55 years were randomized to receive either UV-A1 (n = 21) or control (n = 20) exposures (violet light, 390–440 nm). The irradiations were administered on three consecutive mornings on the skin of the buttocks and middle back. Diurnal preference was assessed with the modified 6-item Morningness-Eveningness Questionnaire (mMEQ). Changes in mood were assessed with Total Mood Disturbance (TMD) score of the 40-item Profile of Mood States (POMS) before the first irradiation, immediately after each irradiation and one week after the last irradiation. Mood improved among those subjected to UV-A1 exposures compared with the controls (p = 0.031). Individuals with more pronounced morningness had mood improvement (p = 0.011), whereas those with more pronounced eveningness did not (p = 0.41). At follow-up of one week after the last irradiation the mood improvement had disappeared.

Clinical, histopathological and immunohistochemical evaluation of ultraviolet A1 treatment in early-stage mycosis fungoides.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas primarily involving the skin. Early-stage MF is characterised by non-specific skin lesions and non-diagnostic biopsies. While skin-focused treatments, such as PUVA and narrowband UVB (nbUVB), are the most frequently recommended treatments, the UVA1 efficacy has been researched in recent years. The purpose of this study was to evaluate the clinical, histopathological and immunohistochemical aspects of UVA1 treatment in patients with early-stage MF. The modified severity weighted assessment scale (mSWAT) was used for total skin body scoring before and after treatment. Skin punch biopsies were taken from the patients before and after treatment. UVA1 therapy was performed five times each week. This study included 26 patients with early-stage MF. The total number of UVA1 sessions varied between 15 and 34. Complete response was observed in 8 (30.8%) of 26 patients (30.8%). The median mSWAT score decreased statistically significantly from 7.1 to 2.0 after treatment (p < .001). Histopathological complete response was observed in 2 (9.5%) of 21 patients. A statistically significant decrease in dermal interstitial infiltrate was observed on histopathological examination after treatment (p = .039). Epidermal CD4/CD8 levels decreased statistically significantly higher from a median of 2.5-1.2 in the complete clinical response group after treatment (p = .043). According to our results, UVA1 treatment has an effect on early-stage MF in terms of clinical, histopathological and immunohistochemistry.

Evaluation of the protection of sunscreen products against long wavelength ultraviolet A1 and visible light-induced biological effects.

Long wavelength ultraviolet-A1 in combination with visible light induces hyperpigmentation, particularly in dark-skin phototypes. This study evaluated the efficacy of four sunscreen formulations in protecting against VL + UVA1 (370-700 nm). The test products (A-D) were applied to the back of 12 volunteers, then irradiated with 320 J/cm2 VL + UVA1 (3.5% UVA1 [370-400 nm]). Immediately after irradiation, and at Days 1, 7, and 14, erythema and pigmentation were assessed by investigator global assessment (IGA), colorimetry (Δa* and ΔITA) and diffuse reflectance spectroscopy (DRS)-measured relative dyschromia (area under the curve AUC). Control areas were irradiated without sunscreen. Product D, containing titanium dioxide 11%, iron oxides 1%, and antioxidants, provided the highest and most consistent protection. Compared with unprotected irradiated control, it had statistically significantly less erythema on IGA, DRS (Δoxyhemoglobin), and colorimetry (Δa*) at Day 0; less pigmentation on IGA at all time points, on DRS (relative dyschromia) at Days 7 and 14, and on colorimetry (ΔITA) at Day 0. Product B, containing zinc oxide 12% plus organic UV filters, iron oxides 4%, and antioxidants, also showed some efficacy. Of the sunscreens tested, the tinted products provided better protection against VL + UVA1 than the non-tinted products. Since the product with 1% iron oxides was superior to the product with 4% iron oxides, further studies are needed to evaluate whether iron oxide content correlates with better protection.

The realistic positioning of UVA1 phototherapy after 25 years of clinical experience and the availability of new biologics and small molecules: a retrospective clinical study

BackgroundSince the early 1990s, Ultraviolet (UV) A1 phototherapy has been described as an effective and safe treatment of a multitude of skin disorders. However, after 30 years, its use has remained limited to few dermatological centers.ObjectiveTo analyze the changes over the years and the current position of UVA1 phototherapy through a Real-World Evidence (RWE) study at a single tertiary referral center.MethodsWe reviewed the medical files of 740 patients treated between 1998 and 2022. Treatment results were collected, efficacy was assessed by a grading scale and acute adverse effects were registered.ResultsWe treated patients with 26 different diseases. We registered marked improvement (MI) or complete remission (CR) in 42.8% of patients with morphea, 50% with Urticaria Pigmentosa, 40.7% with Granuloma annulare and 85.7% with skin sarcoidosis. Good results were obtained also in the treatment of chronic Graft Versus Host Disease (GVHD), Eosinophilic Fasciitis, Sclero-atrophic Lichen, skin manifestations of systemic lupus erythematosus and psoriasis of HIV+ patients. Systemic Sclerosis, Romberg’s Syndrome, Bushke’s Scleredema, Nephrogenic Fibrosing Dermopathy, REM Syndrome, Follicular Mucinosis, Pretibial Myxedema, Scleromyxedema, pemphigus foliaceus, chronic cutaneous lupus erythematosus, erythroderma of Netherton Syndrome and Necrobiosis Lipoidica were no or poorly responsive. In clinical indications where UVA1 was used as a second line phototherapy after narrow-band (NB)-UVB, we saw good MI or CR rates in Mycosis Fungoides (57% of patients), Atopic Dermatitis (33.9%), Pitiryasis Lichenoides chronica (50%), Pityriasis Lichenoides et varioliformis acute (75%) and Lymphomatod Papulosis (62.5%). Short-term adverse events were uncommon and mild.ConclusionOver the past decade, the annual number of treated patients has progressively declined for several reasons. Firstly, UVA1 phototherapy has taken a backseat to the cheaper and more practical NB-UVB phototherapy, which has proven effective for common indications. Secondly, the emergence of new, safe, and effective drugs for conditions such as atopic dermatitis, GVHD, and connective tissue disorders. Finally, our research has shown that UVA1 therapy is often ineffective or minimally effective for some rare diseases, contrary to previous case reports and small case series. Nonetheless, UVA1 continues to be a valuable treatment option for patients with specific skin disorders.

UVA1 irradiation attenuates collagen production via Ficz/AhR/MAPK signaling activation in scleroderma

Scleroderma is an autoimmune disease mainly characterized by progressive fibrosis of the skin. There are two types of scleroderma, namely localized scleroderma (LS) and systemic sclerosis (SSc); skin lesions in both types of scleroderma are histologically identical. Progressive skin sclerosis induces psychological and ecological burden for scleroderma patients. However, there is no effective treatment for scleroderma due to its unclear etiology. Aryl hydrocarbon receptor (AhR) is recognized as an environmental chemical effector that can respond to ultraviolet radiation, which has been demonstrated to participate in the pathogenesis of SSc in our previous study. In this study, we verify whether the anti-fibrosis effect of ultraviolet A1 (UVA1) phototherapy could be partially induced through Ficz/AhR/MAPK signaling activation for fibrotic lesions in both SSc and LS patients. This is the first study to show the association between the AhR pathway and the anti-fibrotic mechanism of UVA1 phototherapy, which provides additional evidence of the role of AhR in the fibrotic mechanism of systemic scleroderma from different perspectives. Ficz and other AhR agonists may replace UVA1 phototherapy as anti-fibrotic agents in scleroderma.

Scleredema of Buschke in a little child and its successful treatment with ultraviolet A1 phototherapy

Scleredema of Buschke in a little child and its successful treatment with ultraviolet A1 phototherapy

Efficacy of ultraviolet A1 phototherapy for inflammatory, sclerotic and neoplastic dermatological diseases: A 10-year tertiary referral center experience.

Ultraviolet (UV) A1 phototherapy is considered a beneficial treatment for various inflammatory, sclerotic, malignant, and other skin conditions. However, the available data regarding its efficacy for different indications, the potential side effects, and the recommended treatment protocols are sparse. To assess the efficacy of UVA1 phototherapy and identify correlation between different indications and treatment protocols to response rates. We performed a retrospective study of a cohort of 335 patients treated with UVA1 phototherapy at the Department of Dermatology at Hadassah Medical Center, Jerusalem, Israel, between 2008 and 2018. The study population included 163 patients with inflammatory diseases (mainly atopic dermatitis and other types of eczema), 67 patients with sclerotic diseases (morphea and graft versus host disease), nine patients with neoplastic diseases (cutaneous T cell lymphoma), and 188 patients with other cutaneous disorders. Response rates ranged between 85% and 89% across indications, without differences in response rates among the indication groups (p=.941). In a multivariant logistic regression model, increased number of treatments and higher maximal dosages were associated with response to treatment (p < .001). Using ROC analysis, a cut-off of 8 UVA1 phototherapy treatments was chosen as predictive for beneficial response (86.4% sensitivity, 78% specificity). A cut-off of 40 J/cm2 was chosen as an optimal maximal dosage for differentiating between responders and non-responders (51.1% sensitivity, 83.1% specificity). UVA1 phototherapy is an effective treatment for a variety of skin conditions. In most patients, at least eight treatments of a medium-high dosage are required for clinical response.

617 The impact of the spectral composition of long-wavelength ultraviolet A1 and visible light on cutaneous biologic effects

Background & Aim: Recent studies have demonstrated visible light and long-wavelength UVA1 (VL+UVA1, 370-700 nm) to cause erythema in light skin and synergistically increased pigmentation in dark skin subjects.1, 2 Spectral compositions of VL+UVA1 may further impact these biologic effects. Yet, no phototesting guidelines exist, thus hindering the development of reliable sunscreens protective against this part of sunlight. The objective of this study was to optimize the spectral output of VL+UVA1 as a step to standardize the assessment of protection from VL+UVA1.

Evaluation of efficacy of antioxidant-enriched sunscreen prodcuts against long wavelength ultraviolet A1 and visible light.

The synergistic effects of VL and long wavelength UVA1 (VL + UVA1, 370-700 nm) on inducing pigmentation and erythema in skin have been demonstrated and linked to exacerbation of dermatologic conditions including melasma and post-inflammatory hyperpigmentation. This study aimed to compare the photoprotection of organic sunscreens enriched with antioxidant (AO) combinations against VL + UVA1 induced biologic effects. The efficacy was compared with that offered by a commercially available tinted sunscreen. Ten healthy adult subjects with Fitzpatrick skin phototypes IV-VI were enrolled (nine completed). VL + UVA1 dose of 380 J/cm2 was utilized. Assessment methods were polarized photography, investigator global scoring and diffuse reflectance spectroscopy (DRS). Measurements were obtained at baseline and immediately, 24h and 7 days after irradiation. Sites treated with tinted sunscreen product had significantly less pigmentation compared with untreated but irradiated skin at all time points. However, DRS results demonstrated that the 5-AO sunscreen performed comparably or better than all sunscreens tested with relatively lower dyschromia, delayed erythema and pigmentation. These results highlight the potential of AO-enriched sunscreens to be photoprotective against VL + UVA1. The combination of efficacy and the cosmetic appearance of this product may provide wider acceptability which is crucial considering the limited available means of protection against this waveband.

Visible Light and the Skin.

Visible light (VL, 400-700 nm) was previously regarded as nonsignificant with minimal to no photobiologic effects on the skin. Recent studies have demonstrated that in dark-skinned individuals (skin phototypes IV-VI), VL can induce more intense and longer lasting pigmentation compared to ultraviolet A1 (UVA1, 340-400 nm). Additionally, long wavelength UVA1 (370-400 nm) has been shown to potentiate these effects of VL. The combination of VL and UVA1 (VL + UVA1, 370-700 nm) was also able to induce erythema in light-skinned individuals (skin phototypes I-III), which is a novel finding since the erythemogenic spectrum of sunlight has primarily been attributed to ultraviolet B (UVB, 290-320 nm) and short wavelength UVA2 (320-340 nm) only. Although biologic effects of VL + UVA1 have been established, there are no guidelines in any country to test for photoprotection against this waveband. This invited perspective aims to present the evolution of knowledge of photobiologic effects of VL, associated phototesting methodologies, and current position on VL photoprotection.

Efficacy of a 365 nm Ultraviolet A1 light Emitting Diode (UVA1-LED) in invitro Extracorporeal Photopheresis.

Extracorporeal photochemotherapy (ECP) is one of the more effective cell therapies for graft-versus-host disease (GvHD). ECP is a widely recommended therapeutic approach for the treatment of chronic GvHD, particularly steroid-refractory GVHD. In recent years, the use of a light emitting diode (LED) in the clinic has attracted considerable interest. In this study, we examined the issue of whether an ultraviolet A1-light emitting diode (UVA1-LED) can be used as a light source in ECP. To compare the efficacy of ECP with conventional UVA lamp and a UVA1-LED, we established an invitro ECP model. Treatment efficacy was evaluated by measuring the % apoptosis and the inhibition of T-cell proliferation. To investigate the effect of ECP on the innate immune reaction, THP-1 cells with a luciferase reporter gene driven by a NF-kB response element (THP-1 luc NF-kB) were treated with ECP. The LED-ECP induced apoptosis and inhibition of T-cell proliferation as efficiently as a conventional ECP. However, LED-ECP induced less innate immunity in THP-1. Since LED devices are more compact compared with conventional UVA irradiation devices, the use of a UVA1-LED in the treatment of ECP may be a better alternative to conventional ECP therapy.

Phototherapy in Pediatric Dermatology

Background: Phototherapy is a safe and effective treatment modality for skin diseases in children such as psoriasis, atopic dermatitis, pityriasis lichenoides, vitiligo, cutaneous cell lymphoma, pityriasis rubra pilaris, and other skin disorders. It is reported to be effective with less side effects compare to the administration of systemic medicine. Short and long term side effects should be taken into account when applying this model of therapy, especially in children. Purpose: To identify special considerations regarding the use of phototherapy modalities in the field of dermatology in children. Review: Phototherapy is the use of ultraviolet (UV) radiation for therapeutic purposes. The various wavelengths of UV radiation used for phototherapy have their own respective photochemical and photobiological properties. There are modality choices that have been proven to provide benefits in treating various skin diseases, including broadband UVB and narrowband UVB, psoralen UVA photochemotherapy (PUVA), ultraviolet A 1 (UVA1), and targeting phototherapy. Special considerations regarding the use of this treatment modality in the pediatric population increase with safety and treatment tolerance. Conclusion: Special considerations should be taken when providing phototherapy treatment options to children with skin disorders requiring phototherapy. The therapies are generally well tolerated and mostly have minor adverse side effects, such as sunburn.

Phototherapy for atopic eczema.

Phototherapy for atopic eczema.

Phototherapy for atopic dermatitis: Systematic review and network meta-analysis of randomized controlled trials.

Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory. This study aimed to evaluate the efficacy of different phototherapies on AD. This systematic review and network meta-analysis included randomized controlled trials (RCTs) through searching keywords from PubMed, EMBASE, and the Cochrane library. We summarized different phototherapy types and scoring systems. Scoring Atopic Dermatitis (SCORAD) absolute score changes were estimated by mean differences (MDs) and standard deviations (SDs) and then included in the network meta-analysis. The effect sizes of comparison of different phototherapies were presented as MDs and 95% confidence intervals (CIs). Egger's test was used to evaluate publication bias. Eleven RCTs were included in the systematic review and 4 studies in the network meta-analysis. Based on the pooled estimates, medium-dose ultraviolet A1 (UVA1) cold light was superior to medium-dose UVA1 (MD 8.92; 95% CI: 5.60-12.24) but no significant difference between high-dose (UVA1) and medium-dose UVA1 cold light (MD 0.66; 95% CI: -5.57to6.90). Publication bias was not supported by Egger's test (P=.168). Due to possible long-term adverse effects of high-dose UVA1, medium-dose UVA1 cold light appears to be the superior form for AD.

Mitigating Visible Light and Long Wavelength UVA1-induced Effects with Topical Antioxidants.

The role of topical antioxidants (AOs) on visible light plus ultraviolet A1 (VL+UVA1)-induced skin changes were evaluated. Twenty subjects with skin phototypes (SPTs) I-VI had placebo and concentrations of an AO blend applied to their back (AO 0.5%, 1.0% and 2.0%). Treated and control sites were irradiated with VL+UVA1. Colorimetric and diffuse reflectance spectroscopy (DRS) assessments were performed immediately, 24 h and 7 days after irradiation. Subjects with SPT I-III had erythema that faded within 24 h, while SPT IV-VI had persistent pigmentation. SPT I-III demonstrated significantly less erythema at the 2% AO site while SPT IV-VI demonstrated significantly less immediate pigmentation at 2% AO site and less pigmentation (approaching significance, P = 0.07) on day 7 compared with control. Immunohistochemistry from biopsies of 2% AO and placebo at 24 h did not demonstrate a significant change in COX-2 or MART-1 for any SPT. There was a decrease in cyclin D1 for SPT IV-VI which was approaching significance (P = 0.06) but not for SPT I-III. The results indicate that topical AO inhibits erythema in SPT I-III and reduces pigmentation in SPT IV-VI caused by VL+UVA1. AO may help prevent worsening of pigmentary disorders and should be incorporated into photoprotection.

Review of the Current Medical and Surgical Treatment Options for Microstomia in Patients With Scleroderma.

Most patients with scleroderma suffer from microstomia, which can have debilitating consequences on their quality of life. Unfortunately, treatment options remain limited. No specific guidelines exist; hence, microstomia remains a challenge to treat in this patient population. This review aims to evaluate the different medical and surgical treatment modalities currently available for microstomia in patients with scleroderma and make recommendations for future research. A search of PubMed, Ovid MEDLINE, and Ovid Embase was conducted to identify articles discussing the treatment of microstomia in scleroderma. Twenty articles discussing surgical therapy and one article discussing medical therapy were reviewed. Mostly because of a scarcity of high-level evidence, no individual therapy has documented long-term efficacy. Some treatments demonstrate positive results and warrant further research. Given the variability of results, specific recommendations for the treatment of microstomia in patients with scleroderma are difficult to establish. A multifaceted approach that includes surgical and medical therapy is likely the best option to improve oral aperture in this patient population. Surgical treatments such as neurotoxins, autologous fat grafting, and ultraviolet A1 phototherapy may hold the most potential for improvement.

Effectiveness of PUVA vs. UVA1 phototherapy in the treatment of morphea patients.

IntroductionMorphea (localized scleroderma) is an inflammatory connective tissue disease, characterized by immune system dysfunction, vasculopathy and skin fibrosing. Phototherapy has been found to be effective in treating localized scleroderma. Psoralen + ultraviolet A (PUVA) and ultraviolet A1 (UVA1) phototherapy significantly enriched therapeutic possibilities.AimTo compare the clinical effect of PUVA photochemotherapy and UVA1 phototherapy and to evaluate the treatment response rates.Material and methodsIt was a retrospective one-centre research and observational study of all morphea patients treated with PUVA and UVA phototherapy. We reviewed phototherapy notes along with electronic and paper case records for all patients with morphea treated with PUVA and UVA1 phototherapy from January 2010 to December 2019.ResultsThe study shows that patients in both groups experienced improvement based on clinical measures, resulting in a reduction in the clinical score in all groups. There is positive short- and long-term efficacy of UVA1 and PUVA phototherapy in patients with morphea. There were no statistical differences between the treatment response rates. Limitations: We had a relatively small study sample and it was a retrospective, observational study.ConclusionsOur data suggest that ultraviolet PUVA and UVA1 should be considered for the treatment of morphea with disseminated lesions or not responding to topical treatment. UVA1 is free of side effects linked to oral psoralens such as nausea, vomiting, photokeratosis, but we showed that there was no statistical advantage in the effectiveness of both. UVA1 phototherapy is, however, a less accessible form of treatment, available in the centres of higher quality.

Concentrations of metalloproteinase-1 in patients with morphea treated with phototherapy: a preliminary study.

Morphea (localized scleroderma) is a rare, chronic, inflammatory connective tissue disease, characterized by immune system dysfunction, vasculopathy and skin fibrosis. One of the most effective treatments is phototherapy. Phototherapy has been found to be effective in treating localized scleroderma by inducing the expression of metalloproteinase-1. To compare the concentrations of metalloproteinase (MMP-1) before psoralen and ultraviolet A (PUVA) and ultraviolet A1 (UVA1) treatments in the serum of patients with morphea. The observational study was conducted in one research centre and included patients with generalised morphea who were treated with PUVA and UVA1 phototherapies. The mean age of all morphea patients included in the study was 55.7 years. The levels of MMP-1 were examined by ELISA (The Biorbyt Human MMP-1 ELISA - Enzyme-Linked Immunosorbent Assay). The study showed that patients treated with PUVA and UVA1 had an improvement based on clinical measures, resulting in a reduction of clinical score. However, we did not observe statistically significant differences in MMP-1 concentrations before and after treatment. Limitations: The study sample was relatively small. Further studies on a larger group of patients would be beneficial. Our data suggest that there is a possible correlation between MMP-1 concentrations and phototherapy. MMP-1 levels were found to be increased following phototherapy treatment, which may suggest a correlation with better response to treatment in patients with morphea. However, further research is needed.

12983 The effectiveness of high-dose ultraviolet A-1 phototherapy on acute exacerbated atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus, a chronic course of exacerbations and remissions. High-dose ultraviolet A-1 (UVA-1) phototherapy has been shown to be effective in the treatment of acute exacerbated AD, however, there was no previous case study in Asia. We present a retrospective review of our experiences with high-dose UVA-1 phototherapy. This study was conducted on 16 patients with acute exacerbation of AD. High-dose (100 J/cm2) regimens of UVA-1 therapy were employed. The therapeutic effectiveness was assessed according to the clinical examination and SCORAD index before and after the 5th and 10th sessions of treatment. In addition, side effects and recurrence during follow-up were retrospectively evaluated. The patients were between 7 and 50 years of age with average age of 25.8 years. The SCORAD index of 16 patients were between 41 and 89.5 with average score of 64.9. Among the 16 patients, two patients discontinued the treatement because of side effects such as erythema and pruritus. Of 14 patients who completed the 10 sessions of high-dose UVA-1 phototherapy, nine patients (64.3%) showed complete remission and five patients (35.7%) showed partial remission. The average SCORAD index was reduced from 64.2 (before treatment) to 23.3 (after 10th session of treatment). This is the first case study of high-dose UVA-1 phototherapy on Asian acute exacerbated AD patients, suggesting that high dose UVA-1 phototherapy can be a well tolerated and effective treatment for acute exacerbated AD. Afterwards, large-scale prospective studies are needed.