A Comprehensive Review of Phototherapy in Atopic Dermatitis: Mechanisms, Modalities, and Clinical Efficacy.

This literature review explores atopic dermatitis and its management, with a focus on phototherapy as a treatment modality. The primary objectives are to elucidate the pathophysiological mechanisms, clinical manifestations, diagnostic criteria, and epidemiology of atopic dermatitis. Additionally, it seeks to explain phototherapy mechanisms, different modalities, and other therapeutic approaches. In this review, we comprehensively examine atopic dermatitis by synthesizing findings from diverse sources over the past 20 years. We investigate the epidemiology, pathophysiology, clinical manifestations, diagnostic criteria, and role of phototherapy in treatment. We conduct thematic analysis, compare phototherapy modalities, consider contextual factors, and integrate patient perspectives while upholding ethical considerations. Limitations include potential publication bias, language barriers, temporal constraints, subjectivity, and limited generalizability. Atopic dermatitis has a complex pathogenesis and can be managed with diverse modalities. Phototherapy emerges as an effective and safe treatment, particularly when other therapies prove ineffective.

Phototherapy and DNA Damage: A Systematic Review.

Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.

Efficacy and Safety Comparison of Basic Fibroblast Growth Factor-Related Decapeptide 0.1% Solution (bFGFrP) Plus Oral PUVA Combination Therapy with Oral PUVA Monotherapy in the Treatment of Vitiligo.

Background: Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Materials and Methods: Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. Results: End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Conclusions: Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.

Risk of skin cancers in mycosis fungoides patients receiving PUVA therapy: A real-life experience from a single tertiary center.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Skin-directed therapies, including phototherapy, are the first-line treatment modalities. Psoralen plus ultraviolet A light photochemotherapy (PUVA) is quite effective in controlling the disease; however, long-term adverse effects, particularly carcinogenesis, are the cons of this treatment. OBJECTIVE: There are various studies on the negative impact of PUVA on skin cancer in patients with autoimmune skin diseases. The data on the long-term effects of phototherapy on MF patients are scarce. METHODS: All MF cases that received PUVA alone or combined with other treatments at a single tertiary center were analyzed. This study compared the development of non-melanoma skin cancers, melanoma, and solid organ tumors in MF patients with at least 5-year follow-up data with age- and sex-matched controls. RESULTS: A total of 104 patients were included in the study. Ninety-two malignancies were detected in 16 (15.4%) patients, and six developed multiple malignancies. Skin cancers consisted of 56 basal cell carcinomas, 16 Bowen's disease, four squamous cell carcinomas, three melanomas, two basosquamous cell carcinomas, one Kaposi sarcoma, and one keratoacanthoma were found in nine (8.7%) patients. Eight patients developed three solid cancers and six lymphomas. The risk of developing skin cancer was associated with the total number of PUVA sessions (<250 vs ≥250 sessions; hazard ratio (HR) 4.44, 95% confidence interval (CI) 1.033-19.068; p = .045). 9 (13.2%) of 68 patients who had follow-ups for at least 5 years developed skin cancer. Compared to an age- and sex-matched cohort, the prevalence of new skin cancer was considerably greater (p = .009). CONCLUSIONS: Patients with MF are predisposed to develop secondary malignancies, and continual exposure to PUVA may potentiate this risk. Annual digital dermoscopic follow-up in MF patients treated with UVA is advised for early diagnosis and treatment of secondary cutaneous malignancies.

Nb-UVB and PUVA therapy in treating early stages of Mycosis Fungoides: A single-center cross-sectional study.

INTRODUCTION: Mycosis fungoides (MF) and Sezary Syndrome are the most common forms of cutaneous T-cell lymphoma. Early-stage MF is known to have an indolent behavior, and the EORTC guidelines recommend treating patients with skin-directed therapies, such as phototherapy, instead of systemic therapies. Phototherapy is a popular therapeutic option, with two commonly used light sources-PUVA and narrow band-nb UVB. PUVA is less commonly used due to its potential carcinogenic role, but it has systemic effects, while nb-UVB has mostly skin-limited effects. There is ongoing debate regarding the role of UVB light, and in 2021, the Cutaneous Lymphoma Italian Study Group reached a consensus on technical schedules for NB-UVB and PUVA for MF. This study aims to analyze and compare the efficacy of the two phototherapy options in treating early-MF patients. MATERIALS AND METHODS: The study included patients diagnosed with stage IA/B MF in the last 10 years, who had at least 12 months of follow-up data and a minimum of 24 phototherapy sessions (PUVA or nb UVB) and treated with topical steroids apart from phototherapy. RESULTS: Results showed that the two phototherapy options were similarly effective in treating early MF, with no significant differences in clinical response, although PUVA was associated with more adverse effects. CONCLUSIONS: The study provides valuable insights into the use of phototherapy in early MF, and the results can be used to guide treatment decisions and improve patient outcomes.

Bath-PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB-UVB phototherapy.

BACKGROUND: Photochemotherapy with bathwater delivery of psoralens plus UVA exposures (bath-PUVA) is mainly used for those psoriatic patients who are not responsive to narrowband (NB)-UVB phototherapy and oral-PUVA therapy and belong to two categories (1) patients with psoriasis without systemic comorbidities who do not need long-term continuous treatment and (2) patients who have contraindications to immunosuppressive drugs and oral-PUVA or refuse systemic drugs, including oral ingestion of psoralens, for personal reasons. However, it is not known how many patients belong to the second group and how much bath-PUVA is effective and safe for them. METHODS: We have reviewed the treatment results of a cohort of 120 patients with clinical indication to bath-PUVA for the above-mentioned reasons between 2010 and 2019. These patients were selected among 2640 patients with moderate and severe psoriasis who were treated in our department in the same time interval. RESULTS: Ninety-six patients completed at least one treatment cycle with bath-PUVA. A per-protocol analysis showed that average number of treatment sessions was 21.3 ± 9.0 and the cumulative UVA dose was 80.4 ± 60.0 J/cm2 . The average PASI scores decreased from 20.8 ± 7.9 to 5.1 ± 5.4 (p < .01). Sixty-seven (69.7%) patients achieved at least a 75% improvement (PASI75 ) and, of them, 38 (39.6%) had an improvement greater than 90% (PASI90 ). Adverse effects were mild and transitory. CONCLUSION: These findings demonstrate that bath-PUVA is still a valuable treatment option for a high number of patients who reject systemic treatments or have contraindications to systemic immune-modifying drugs and have had a limited or no improvement with NB-UVB phototherapy.

PUVA therapy in persistent cutaneous histiocytosis: Case report and literature review.

BACKGROUND: Cutaneous and mucocutaneous histiocytosis (group C) comprise a wide variety of entities affecting skin and/or mucosae. Although they are considered as reactive proliferations, their exact pathophysiology remains unknown and, therefore, they lack a specific treatment. AIMS: The aim of this study is to review the evidence on cases of histiocytosis treated with UVB and/or UVA and to report a new case of relapsing group C histiocytosis that has been successfully treated with PUVA therapy. MATERIALS & METHODS: We have conducted a review of the literature published over the last 40 years on the treatment of histiocytosis with phototherapy in the online PubMed database. We also describe a new case of successful treatment of histiocytosis with PUVA therapy. RESULTS: Our patient was a 27-year-old man with persistent outbreaks of cutaneous histiocytosis over the previous 8 years. He responded successfully to PUVA therapy, and no relapse has been detected after one year of follow-up. DISCUSSION: Self-involution is usual in group C histiocytosis, so conservative management is usually the first approach. Relapsing cases pose a therapeutic challenge. Reported treatment options for these patients include isotretinoin, cryotherapy, immunosuppressants, low-dose chemotherapy, CO2 laser, radiotherapy, and surgery. Phototherapy and photochemotherapy have been used in a small number of patients with considerable success. The main limitation to provide firm recommendations on histiocytosis therapy is the absence of solid evidence, as the articles published are mainly case reports with a short follow-up. In our patient, despite the short follow-up we have considered photochemotherapy to be effective since no spontaneous remission had been achieved in the previous 8 years. CONCLUSION: PUVA therapy could be a safe and effective option to treat persistent cutaneous manifestations in patients with histiocytosis, although more evidence is required to support this statement.

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

Introduction: 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. Aim: 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. Material and methods: 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). Results: 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. Conclusions: 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.

Diet and Vitiligo: The Story So Far.

Vitiligo is an acquired skin pigmentation disease with a global burden of 0.5 to 2 percent of the population. Vitiligo therapy frequently poses a difficulty, which has sparked interest in alternative treatment modalities, including multivitamins and herbal supplementation. It has previously been established that nutrition plays a crucial role in developing, amplifying, or rehabilitating an array of human disorders. However, the correlation between diet diversity and immune-mediated skin diseases is still up to interpretation. Several supplements have been studied, including vitamins, minerals, and herbal supplements. Most studies agree that combining vitamin B12, folic acid, and sun exposure is good for inducing repigmentation. Supplementation of zinc and phenylalanine when used in conjunction with topical steroids or UV-B (ultraviolet B) treatment shows therapeutic effects on vitiligo due to their role in the melanin synthesis pathway. Investigations conducted on herbal supplements have revealed that most of them contain antioxidants, which aid in repigmentation. This narrative review's purpose is to discuss nutrition's function in immune-mediated inflammatory skin diseases from the perspective of the most recent and reliable information available.

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

Introduction: Morphea (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. Aim: To compare the clinical effect of PUVA photochemotherapy and UVA1 phototherapy and to evaluate the treatment response rates. Material and methods: It 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. Results: The 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. Conclusions: Our 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.

Risk of Skin Cancer with Phototherapy in Moderate-to-Severe Psoriasis: An Updated Systematic Review.

Phototherapy is a standard treatment for moderate-to-severe psoriasis. However, concern remains regarding the associated cutaneous carcinogenic risk. Our objective is to conduct a systematic review of skin cancer risk for psoriasis patients treated with phototherapy. To achieve our goal, we searched Cochrane, PubMed, and Embase databases. We aimed to evaluate existing literature (from July 1, 2010, to December 31, 2020) on phototherapy for all Fitzpatrick skin phototypes (FSP) which includes 71 articles, and eight articles being categorized in this review. Five studies did not report an increased skin cancer risk with narrowband-ultraviolet blue (UVB) and unspecified UVB for FSP II through VI, with one study not reporting FSP. Three studies did report an increased risk of skin cancer with narrowband-UVB and broadband-UVB for FSP I-VI, with one study also not specifying skin phototypes or UVB phototherapy type. Additionally, a study with psoralen and ultraviolet A with and without narrowband-UVB demonstrated an increased risk of skin cancer in phototypes III and IV. The most commonly reported secondary outcomes with phototherapy were actinic keratosis (123) and solar lentigines (10). Numerous patients were also on additional therapies including methotrexate, acitretin, and biologics. Study limitations include publication bias due to limited number of studies published on this topic in the last ten years along with heterogeneity in reporting. The relationship between phototherapy, psoriasis, and cutaneous oncogenic risk remains contradictory. While phototherapy for psoriasis is an efficacious therapy, further studies are needed to understand the cutaneous oncogenic risk based on FSP to help clinicals tailor treatment recommendations based on skin phototypes.

A novel mouse model of cutaneous T-cell lymphoma revealed the combined effect of mogamulizumab with psoralen and ultraviolet a therapy.

Mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8-methoxypsoralen (8-MOP), followed by ultraviolet A (UVA) irradiation (PUVA therapy) is an effective phototherapy for early-stage MF. However, the efficacy of PUVA therapy for advanced-stage MF is not satisfactory, and the ideal combination partner for PUVA therapy has not yet been found. In this study, we developed a new mouse model of CTCL in which efficacy of PUVA was detected and further evaluated the efficacy of combination treatment of PUVA and mogamulizumab, an anti-CCR4 monoclonal antibody. Cytotoxicity of PUVA therapy against HH cells, a CTCL cell line, was observed in vitro. The cytotoxicity was dependent on both 8-MOP and UVA. Using HH cells, we developed a mouse model in which HH cells were subcutaneously inoculated in the ear. In this model, PUVA therapy suppressed tumour growth with statistical significance, while 8-MOP or UVA alone did not. Combination therapy of PUVA and mogamulizumab showed greater antitumor activity than either monotherapy with statistical significance. In the histological analysis of the tumour tissue, PUVA accelerated tumour necrosis and then induced the infiltration inflammatory cells in the necrotic area, suggesting that these cells served as effector cells for mogamulizumab. This combination therapy is expected to be a beneficial option for CTCL therapy.

Risk of cutaneous carcinogenesis with phototherapy in Indian subpopulation: A 10-year analysis and a review of literature.

Phototherapy is an extremely effective and established therapeutic modality in a variety of dermatological disorders. However, there has been a constant concern with respect to its long-term usage as some of the studies have identified the risk of cutaneous malignancy associated with phototherapy. The carcinogenic potential of PUVA has been demonstrated in most US studies; however, the studies done on Asian and Arabian-African population have not corroborated similar findings, thus suggesting that the darker skin may confer protection against the development of cutaneous malignancy following phototherapy. The main aim of the present study was to assess the safety of phototherapy (bath PUVA and NBUVB) in Indian population (Fitzpatrick skin types IV and V) with respect to its carcinogenic potential and to determine the maximum cumulative dose that our patients could tolerate without developing any untoward complications such as cutaneous malignancy. All patients who received phototherapy between January 2006 and October 2016 were enrolled in the study. Details such as cumulative dose, number of phototherapy sessions received, indication for phototherapy, adverse effects such as pigmentary changes, new growths on the skin surface following the therapeutic sessions were entered in a predesigned proforma. This ambispective study had 1300 patients who had received phototherapy over a period of 10 years. A total of 929 patients had received PUVA, and the remaining 371 patients had received NBUVB for various dermatological indications. The average follow-up period for PUVA was 3 years and 6.5 years for NBUVB. The maximum cumulative dose of UVA and UVB that could be safely administered in our patients was 2085 J/cm2 and 1985 mJ/cm2, respectively. None of our patients developed any features of cutaneous malignancy during their follow-up. Both bath-PUVA and NBUVB are safe and efficacious in treating patients of darker skin types (IV and V). The risk of developing cutaneous malignancy is negligible in this subset of patients. However, more studies need to be done on the Asian population to substantiate the same.

Utility of phototherapy in patients with systemic sclerosis: Systematic review.

Phototherapy is a recommended treatment regimen for different scleroderma spectrum disorders, but so far it has been included neither by European nor by worldwide experts committee in recommendations for the treatment of systemic sclerosis (SSc). The aim of the study was to revisit the utility of dermatological phototherapy in patients with SSc. PubMed using medical subject headings was searched to identify studies evaluating response to dermatological phototherapy in SSc patients. Both UVA1 (340-400 nm) and PUVA (psoralen plus UVA) treatments were found to reduce skin thickening and increase skin elasticity, therefore allowing for the improvement of joint tension mobility, especially in hands. At least several papers showed efficacy of phototherapy in patients who remained non-responsive to previous immunosuppressive therapies. The most probable mechanisms of action of phototherapy in SSc include inhibition of T-cells and prevention from dermal fibrosis. Although most data on the efficacy of phototherapy come from small experimental studies and case reports, phototherapy based on UVA of wavelength manifests relatively mild spectrum of side effects and this should be considered as a treatment option for SSc with dominant cutaneous involvement.

In situ monitoring PUVA therapy by using a cell-array chip-based SERS platform.

Psoralen ultraviolet A (PUVA) therapy has thrived as a promising treatment for psoriasis. However, overdose of PUVA treatment will cause side-effects, such as melanoma formation. And these side-effects are often ignored during PUVA therapy. Hence, in situ monitoring therapeutic response of PUVA therapy is important to minimize side-effects. Aberrant expression of tyrosinase (TYR) has been proved to be associated with melanoma, indicating that TYR is a potential target for evaluation of PUVA therapy. Herein, we reported a strategy for in situ monitoring TYR activity during PUVA therapy by using a cell-array chip-based SERS platform. The cell-array chip was used to simulate cell survival environment for cell culture. Capture of single cells and living cell analysis were realized in the isolated microchambers. An enzyme-induced core-shell self-assembly substrate was used to evaluate TYR activity in living cells during PUVA therapy. The gold nanoparticle modified with a SERS reporter, 4-mercaptobenzonitrile (4-MBN), was used as the core. In the presence of oxygen and TYR, hydroxylation of l-tyrosine occurred, leading to the reduction of silver ion on the surface of gold cores. The growth of silver shells was accompanied by the increased SERS intensity of the reporter, which is related directly to TYR activity. The detection limit for TYR activity is 0.45 U/mL. Upregulation of TYR activity was successfully monitored after PUVA therapy. Notably, real-time and in situ information of therapeutic response can be obtained through monitoring PUVA therapy by using a cell-array chip-based SERS platform, which has great potential to guide the clinical application of PUVA therapy.

COVID-19 effect on phototherapy treatment utilization in dermatology.

BACKGROUND: At the end of 2019, an innovative coronavirus caused an outbreak of pneumonia cases in Wuhan, a city Hubei Province of China. Despite the direct effect on the routine of all life aspects, there are no clinical guidelines regarding phototherapy treatment during COVID-19 pandemic and as a result, phototherapies units continued to deliver this therapy for patients worldwide. OBJECTIVE: We wish to explore the phototherapy utilization among dermatologic patients. METHODS: We marked all patients that continue to arrive and being treated during COVID-19 pandemic. RESULTS: From March more than 50% of patients stopped arriving to treatments due to the fear of COVID-19 infection. CONCLUSIONS: COVID-19 has a major implication on chronic dermatology treatments such as phototherapy.

Light- and laser-based treatments for granuloma annulare: A systematic review.

BACKGROUND: Granuloma annulare (GA) is challenging to treat, especially when generalized. A systematic review to support the use of light- and laser-based treatments for GA is lacking. METHODS: We performed a systematic review by searching Cochrane, MEDLINE, and Embase. Title, abstract, full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Joanna Briggs Institute critical appraisal tool for case series. RESULTS: Thirty-one case series met the inclusion criteria, representing a total of 336 patients. Overall, psoralen ultraviolet light A (PUVA) showed the greatest frequency of cases with complete response (59%, n = 77/131), followed by photodynamic therapy (PDT) (52%, n = 13/25), ultraviolet light B (UVB)/narrowband UVB (nbUVB)/excimer laser (40%, n = 19/47), UVA1 (31%, n = 27/86), and lasers (29%, n = 8/28). Overall across treatment modalities, higher response rates were seen in localized GA compared to generalized GA. CONCLUSIONS: The body of evidence for light- and laser-based treatment of GA is sparse. Our results suggest that PUVA has a high clearance rate for GA but its use may be limited by concerns of carcinogenesis. Although PDT has the second highest clearance rate, adverse effects, small sample sizes, impractical treatment delivery (especially with generalized disease), and long-term concerns of carcinogenesis may limit its use. Although UVB/nbUVB/excimer laser appeared slightly less effective than other light therapies, we recommend UVB/nbUVB/excimer laser therapy as a first-line treatment for patients with generalized GA given wider availability and a favorable long-term safety profile.

Bath Psoralen Plus UVA Therapy Suppresses Keratinocyte-Derived Chemokines in Pathogenetically Relevant Cells.

Psoriasis is a chronic inflammatory proliferative skin disease involving various types of chemokines regulating immune cell migration, localization, and activation. Bath psoralen plus UVA (PUVA) treatment is an established phototherapy for psoriasis, but its effects on chemokine levels remain unknown. We investigated the levels of 22 serum chemokines in 20 patients with psoriasis first treated with bath PUVA therapy between 2007 and 2011 in a single center and analyzed the associations between the chemokines and disease severity (PASI) before and after therapy to investigate the mechanisms of action of bath PUVA therapy. Before bath PUVA therapy, the PASI scores correlated with the serum levels of CCL17 (r = 0.581), CCL18 (r = 0.462), CCL19 (r = 0.477), and CXCL16 (r = 0.524). After bath PUVA, the serum levels of CCL17, CCL22, CXCL1, and CXCL9 were significantly decreased. Heatmap clustering and network analysis based on statistically significant Spearman correlations among the chemokines showed distinctive changes in the chemokine signature. Our findings revealed that the levels of several chemokines correlated with the disease state of psoriasis. Furthermore, bath PUVA therapy reduced the secretion of keratinocyte-derived chemokines that induce the migration of immune cells important for psoriasis pathogenesis, partly revealing the mechanism of the therapeutic activity.