Psoralen UVA Research Articles

Modulation of the skin microbiome in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model.

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.

Nonsurgical Treatment of Postburn Hypopigmentation: A Literature Review.

The treatment of postburn hypopigmentation was primarily surgical before the advent of new technologies. Medical devices and therapies are emerging to manage scar sequelae that can be disfiguring and associated with severe psychosocial impact. These innovations have been poorly investigated for hypopigmentation, but they represent a real hope. We reviewed all articles published on Pubmed up to June 2022. Included studies had to specifically focus on treating postburn hypopigmented scars. All articles evaluating transient solutions such as make-up, and articles describing inflammation-linked hypopigmentation with no etiological details or no burn injury history were excluded. Through this review, we have highlighted 6 different types of nonsurgical treatments reported in postburn leukoderma potentially allowing definitive results. Electrophoto-biomodulation or E light (combining intensive pulsed light, radiofrequency, and cooling), topical daylight psoralen UVA therapy, and lasers (fractional lasers using pulse energies or CO2FL devices, lasers-assisted drug delivery as local bimatoprost and tretinoin or pimecrolimus) have been explored with encouraging results in hypopigmented burns. Finally, other promising medical strategies include using FK506, a nonsteroidal anti-inflammatory drug, to induce melanogenesis or using melanocyte-stimulating hormones with fractional laser-assisted drug deliveries, which are expected to emerge soon.

Photochemical inactivation as an alternative method to produce a whole-cell vaccine for uropathogenic Escherichia coli (UPEC).

Lower urinary tract infection (UTI), caused primarily by uropathogenic Escherichia coli, represents a significant health burden, accounting for 7 million primary care and 1 million emergency room visits annually in the United States. Women and the elderly are especially susceptible and recurrent infection (rUTI) is common in those populations. Lower UTI can lead to life-threatening systemic infection. UTI burden is manifested by healthcare dollars spent (1.5 billion annually), quality of life impact, and resistant strains emerging from antibiotic overuse. A safe and effective vaccine to prevent rUTI would address a substantial healthcare issue. Vaccines comprised of inactivated uropathogenic bacteria have yielded encouraging results in clinical trials but improvements that enhance vaccine performance are needed. To that end, we focused on inactivation methodology and provided data to support photochemical inactivation, which targets nucleic acid, as a promising alternative to conventional protein-damaging inactivation methods to improve whole-cell UTI vaccines.

Phototherapy for atopic dermatitis: A survey of European practice.

Phototherapy is used to treat atopic dermatitis (AD). Evidence for its efficacy, impact on quality of life, cost-effectiveness and short- and long-term safety with real-life usage is weak. We established a taskforce to examine how phototherapy is currently being used as a treatment for AD across the United Kingdom and Europe to inform our understanding and guide future research into management of patients with AD using UV-based phototherapies. An anonymous electronic multiple-response survey exploring phototherapy prescribing practices and experience of phototherapy modalities was developed by the study authors and sent to members of phototherapy networks from the United Kingdom and Europe. Responses were received between February and July 2021. About 144 respondents from 27 European countries completed the survey. NBUVB was the most widely used [n = 138 (96%)]. Home-based NBUVB was available in 8/27 countries (25/144 respondents, 17%). Oral psoralen-UVA (PUVA) was more widely available than bath PUVA (n = 106, 74% vs. n = 60, 42%) and used mainly in adult patients. 49/144 (34%) of respondents had access to UVA1. Phototherapy would be considered instead of systemic treatment in 96% of adults and 82% of children for NBUVB, versus 40% of adults and 3% of children for PUVA. Starting doses, standard dosing increments, length of treatment courses, lifetime limits for treatments and thresholds for performing annual skin assessments varied between responders. NBUVB was the most widely used phototherapy for AD in adult and paediatric patients, while PUVA and UVA1 were less used. Prescribing practices varied considerably, highlighting the lack of consensus practice in many different aspects of phototherapy for the treatment of AD in children and adults. This indicates that further studies are required to determine optimal phototherapeutic regimens for AD and informs our understanding of parameters that should be included in future high-quality randomized controlled trials (RCT) of phototherapy.

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 in Dermatology

Phototherapy is a therapeutic procedure in dermatology. Phototherapy uses certain ultraviolet wavelengths classified into 3 types,broadband UVB (BBUVB), narrowband UVB (NBUVB), and psoralen UVA (PUVA). The most widely used is NBUVB for treating psoriasis, atopic dermatitis and vitiligo. The mechanism of action of phototherapy is to reduce epidermal proliferation, suppress the immune system, reduce the inflammatory process, and induce repigmentation. Before starting phototherapy, the dose adjustment depends on skin type and minimal erythema dose (MED). Frequency of use is recommended based on the severity of the disease, continuously administered needed. Besides of this therapeutic effect, some contraindications and side effects that need to be considered in the use of phototherapy such as drug interactions, photoallergic and risk of skin malignancy.

Synthesis and Photophysics of Water-Soluble Psoralens with Red-Shifted Absorption.

8-Methoxypsoralen (8-MOP) serves as a PUVA (psoralen + UV-A) agent in the treatment of certain skin diseases. Derivatives of 8-MOP with cationic aromatic substituents at the five positions were synthesized and characterized by steady-state, femtosecond and nanosecond spectroscopy as well as cyclic voltammetry. The aromatic substituents' positive charge increases the water solubility and the affinity toward intercalation into DNA. The aromatic substituents were supposed to lower the psoralen S1 energy and thereby suppress a photo-induced electron transfer (PET) with guanine-bearing DNA. Such a suppression of this PET is expected to increase the propensity of psoralens to photo-addition to DNA. For derivatives bearing methylpyridinium residues, femtosecond spectroscopy revealed an intramolecular PET occurring on the picosecond time scale. This PET precludes the population of the triplet state. As triplet states are the precursor state for the photo-addition to DNA, their intermolecular PET renders these derivatives ineffective in terms of PUVA. For two derivatives bearing trimethylphenylammonium moieties, such an intramolecular PET does not occur and the triplet state is populated. Surprisingly, these compounds also exhibit no PUVA activity. Based on these findings, implications for further optimization of PUVA agents are discussed.

Targeted and localized phototherapy for atopic dermatitis and psoriasis: An eight-year experience in a tertiary dermatological centre in Singapore.

Targeted phototherapy, including excimer light involves the localised delivery of ultraviolet (UV) light directly to lesional skin1,2 . Narrowband UVB as well as soak and topical psoralen-UVA (PUVA) can be used as localised phototherapy, whereby there is irradiation only to a localised area of the skin. Common indications include localised psoriasis, vitiligo, atopic dermatitis (AD)1 , and lymphoproliferative skin disorders involving a limited area of the body or difficult-to-treat anatomical areas3 . Phototherapy can be used as monotherapy, but is more often part of a multi-modal treatment regime involving topical and systemic agents1 .

Comparison of two modalities of phototherapy, narrowband UV-B and PUVA in the treatment of psoriasis: A study from Western Uttar Pradesh

Introduction: PUVA (psoralen + UV-A) has been used since long time ago in psoriatic patients, which has some adverse effects. Phototherapy in form of Narrowband UVB is advancement in the treatment of psoriasis and it has been found to be same efficacious and having lesser side effects than PUVA. Aim: The study was aimed to compare NBUVB and PUVA in chronic plaque psoriasis in terms of their efficacy and adverse effects. Methods: The study included 43 cases of chronic plaque psoriasis which were randomly divided into two groups. Patients were examined for body surface area involvement and PASI scoring. Narrow-band UV-B phototherapy was given to one group and the other group received PUVA therapy thrice-weekly for a duration of 3 months. Then they were compared for clearance of lesions and side effects. Results: Both groups showed decrease in the PASI scoring by at least 75%. It was observed that lesser number of treatment sessions and fewer days were required for clearance of the lesions in PUVA group than the group receiving NBUVB therapy. But in NBUVB group, mean cumulative clearance dose and adverse reactions were significantly lower. The percentage of patients maintaining remission at six months were more in PUVA group as compared to NBUVB group. Conclusion: Both modes of phototherapy are useful in psoriasis. Patients got clearance of the lesions faster in the PUVA group but the side effects were markedly less in the NBUVB group. Keywords: Narrow-band UV-B, Psoralen UVA, Plaque psoriasis.

Low-dose Psoralen–UV-A maintenance therapy prolongs disease-free remission rates in mycosis fungoides patients

A clinical decision report using Vieyra-Garcia P, Fink-Puches R, Porkert S, et al. Evaluation of Low-Dose, Low-Frequency Oral Psoralen–UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides. JAMA Dermatology. 2019;155(5):538. https://doi.org/10.1001/jamadermatol.2018.5905 for a patient weighing whether to continue treatment in light of socioeconomic circumstances.

Tracing the Photoaddition of Pharmaceutical Psoralens to DNA.

The psoralens 8-methoxypsoralen (8-MOP), 4,5′,8-trimethylpsoralen (TMP) and 5-methoxypsoralen (5-MOP) find clinical application in PUVA (psoralen + UVA) therapy. PUVA treats skin diseases like psoriasis and atopic eczema. Psoralens target the DNA of cells. Upon photo-excitation psoralens bind to the DNA base thymine. This photo-binding was studied using steady-state UV/Vis and IR spectroscopy as well as nanosecond transient UV/Vis absorption. The experiments show that the photo-addition of 8-MOP and TMP involve the psoralen triplet state and a biradical intermediate. 5-MOP forms a structurally different photo-product. Its formation could not be traced by the present spectroscopic technique.

Psoralens activate and photosensitize Transient Receptor Potential channels Ankyrin type 1 (TRPA1) and Vanilloid type 1 (TRPV1).

PUVA (psoralen UVA) therapy is used to treat a variety of skin conditions, such as vitiligo psoriasis, eczema and mycosis fungoides, but it is frequently accompanied by phototoxicity leading to burning pain, itch and erythema. We used a combination of calcium and reactive oxygen species (ROS) imaging, patch clamp and neuropeptide release measurement to investigate whether certain ion channels involved in pain and itch signalling could be responsible for these adverese effects of PUVA. Clinically used psoralen derivatives 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen at physiologically relevant concentrations were able to activate and photosensitize two recombinant thermoTRP (temperature-gated Transient Receptor Potential) ion channels, TRPA1 (Transient Receptor Potential Ankyrin type 1) and TRPV1 (Transient Receptor Potential Vanilloid type 1). 8-MOP enhanced ROS production by UVA light, and the effect of 8-MOP on TRPA1 could be abolished by the antioxidant N-acetyl cysteine and by removal of critical cysteine residues from the N-terminus domain of the channel. Natively expressed mouse TRPA1 and TRPV1 both contribute to photosensitization of cultured primary afferent neurons by 8-MOP, while direct neuronal activation by this psoralen-derivative is mainly dependent on TRPV1. Both TRPA1 and TRPV1 are to a large extent involved in controlling 8-MOP-induced neuropeptide release from mouse trachea. Taken together our results provide a better understanding of the phototoxicity reported by PUVA patients and indicate a possible therapeutic approach to alleviate the adverse effects associated with this therapy. Our work provides evidence for the involvement of thermoTRP channels TRPA1 and TRPV1 in the activation and photosensitization of peripheral nociceptors during PUVA (Psoralen UVA) therapy.

Fototerapi dalam Dermatologi

Phototherapy is a therapeutic procedure in dermatology. Phototherapy uses certain ultraviolet wavelengths classified into 3 types,broadband UVB (BBUVB), narrowband UVB (NBUVB), and psoralen UVA (PUVA). The most widely used is NBUVB for treating psoriasis, atopic dermatitis and vitiligo. The mechanism of action of phototherapy is to reduce epidermal proliferation, suppress the immune system, reduce the inflammatory process, and induce repigmentation. Before starting phototherapy, the dose adjustment depends on skin type and minimal erythema dose (MED). Frequency of use is recommended based on the severity of the disease, continuously administered needed. Besides of this therapeutic effect, some contraindications and side effects that need to be considered in the use of phototherapy such as drug interactions, photoallergic and risk of skin malignancy.

Evaluation of Low-Dose, Low-Frequency Oral Psoralen–UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides

Psoralen-UV-A (PUVA) photochemotherapy is standard first-line treatment for skin-limited, early-stage mycosis fungoides capable of producing high initial complete response (CR) rates. However, much remains unknown about PUVA's therapeutic mechanisms, optimal duration and frequency of treatment, dose escalation, or use as maintenance therapy. To evaluate low-dose, low-frequency PUVA, and whether maintenance treatment extends disease-free remission in patients with mycosis fungoides. This prospective randomized clinical trial with defined PUVA dosing regimen was carried out in 5 centers (Graz, Vienna, Hietzing, Innsbruck, and Salzburg) across Austria. Patients with stage IA to IIA mycosis fungoides (n = 27) were enrolled in the study beginning March 13, 2013, with the last patient enrolled March 21, 2016. These patients were treated with oral 8-methoxypsoralen followed by UV-A exposure 2 times per week for 12 to 24 weeks until CR. Patients with CR were randomized to PUVA maintenance for 9 months (14 total exposures) or no maintenance. The study was conducted from April 27, 2012, to July 27, 2018. Data analysis of the primary end point was of the intention-to-treat population, and the secondary end point analysis was of the evaluable population. Efficacy of the PUVA regimen was determined by the rate of CR as defined by a modified severity-weighted assessment tool (mSWAT) score reduction to 0. Levels of proinflammatory molecules in serum and histologic features and percentage of clonal T cells in skin were assessed to search for biomarkers of clinical response. In 27 patients with mycosis fungoides, 19 (70%) were male with mean (range) age 61 (30-80) years. At baseline, patients with CR had a mean (range) mSWAT score of 18.6 (1-66) compared with 16.8 (3-46) in patients with partial response. The 12- to 24-week PUVA induction regimen reduced the mSWAT score in all patients and led to CR in 19 (70%) of 27 patients and a low mean cumulative UV-A dose of 78.5 J/cm2. The subsequent standardized 9-month PUVA maintenance phase prolonged median (range) disease-free remission from 4 (1-20) months to 15 (1-54) months (P = .02). High density of histologic infiltrate and high percentage of clonal TCR sequences in skin biopsy specimens at baseline were inversely associated with therapeutic response. No severe adverse effects were seen during the PUVA induction or maintenance phase. This proof-of-concept study identifies potential biomarkers for therapeutic response to PUVA in mycosis fungoides; it also demonstrates that low-dose, low-frequency PUVA appears to be highly effective, and maintenance treatment may extend disease-free remission. ClinicalTrials.gov identifier: NCT01686594.

Penile cancer epidemiology and risk factors: a contemporary review.

Our objective is to present an overview of epidemiologic, clinical, and molecular risk factors with a focus on contemporary literature. Penile cancer is a rare and aggressive neoplasm that accounts for less than 1% of male malignancies in the United States. Geographical disparities in incidence of disease are evident with high rates concentrated in the developing world (2.8-6.8 per 100 000) where neonatal circumcision is low and socioeconomic conditions predispose patients to multiple risk factors. Western countries have a significantly lower incidence and can be as low as 0.3 per 100 000. Many risk factors have been identified including lack of circumcision, phimosis, balanitis, obesity, lichen sclerosus, smoking, and psoralen UV-A phototherapy. In addition, human papilloma virus (HPV) has been linked to nearly 40% of cases and molecular mediators continue to be investigated. Although Penile cancer can be a debilitating disease, several of the known risk factors are modifiable. Public health campaigns aimed to increase awareness, promote better hygiene, and deploy HPV vaccines have had varied success at decreasing disease burden. Focus should be placed on implementing such interventions in developing countries and at-risk populations.

Comparison of Narrowband UV-B With Psoralen–UV-A Phototherapy for Patients With Early-Stage Mycosis Fungoides

Phototherapy is one of the mainstays of treatment for early mycosis fungoides (MF). The most common modalities are psoralen-UV-A (PUVA) and narrowband UV-B (NBUVB). To compare the efficacy and adverse effects of PUVA vs NBUVB in early-stage MF. A systematic review was performed by searching Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid Medline, PubMed, Cochrane Library, American College of Physicians ACP Journal Club, and Database of Abstracts of Review of Effectiveness from inception to March 30, 2018. UV A, PUVA, mycosis fungoides, Sézary syndrome, cutaneous T-cell lymphoma, UV B, and UVB were used as either key words or MeSH terms. Studies of cohorts with histologically confirmed early-stage MF, defined as stages IA, IB, and IIA, that compared PUVA vs NBUVB, had at least 10 patients in each comparator group, and reported outcomes of response to therapy. Exclusion criteria were studies with patients with stage IIB or higher MF, pediatric patients, fewer than 10 in each comparator group, noncomparative studies, case reports, and abstract studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were pooled using a random-effects model with odds ratio (OR) as effect size. Main outcomes were complete response rate, partial response rate, disease recurrence, and adverse effects, including erythema, nausea, pruritus, phototoxic effects, dyspepsia, and pain. Seven studies were included with a total of 778 patients (405 of 724 [55.9%] men; mean age, 52 years); 527 were treated with PUVA and 251 with NBUVB. Most of the included studies were of poor to moderate quality. Any response was found in 479 of the 527 (90.9%) patients treated with PUVA vs 220 of 251 (87.6%) treated with NBUVB (OR, 1.40; 95% CI, 0.84-2.34; P = .20). Complete response was found in 389 of 527 (73.8%) patients who received PUVA vs 156 of 251 (62.2%) who received NBUVB, which was statistically significant (OR, 1.68; 95% CI, 1.02-2.76; P = .04). Partial response was similar (90 of 501 [18.0%] vs 64 of 233 [27.5%]; OR, 0.58; 95% CI, 0.33-1.04; P = .07). No significant difference was found between PUVA and NBUVB in terms of adverse effects of erythema (38 of 527 [7.2%] vs 17 of 251 [6.7%]; P = .54), nausea (10 of 527 [1.9%] vs 3 of 251 [1.2%]; P = .72), pruritus (2 of 527 [0.4%] vs 4 of 251 [1.7%]; P = .26), phototoxic effects (7 of 527 [1.4%] vs 2 of 251 [0.9%]; P = .72), dyspepsia (6 of 527 [1.2%] vs 0 of 251 [0%]; P = .59), or pain (0 of 527 [0%] vs 2 of 251 [0.9%]; P = .50). The findings suggest that PUVA is a potential alternative to NBUVB in the management of early-stage MF. These findings have implications for clinicians involved in the management of early-stage MF.

Efficacy of Narrow - Band UVB Phototherapy versus PUVA Chemophototherapy for Psoriasis in Vietnamese Patients.

BACKGROUND:Psoralen UVA (PUVA) and narrow-band UVB (NBUVB) chemophototherapy are treatment options for psoriasis.AIM:To compare the effectiveness of NBUVB with PUVA in Vietnamese psoriasis patients.METHODS:We conducted a non-randomized trial on 60 patients with plaque-type psoriasis (30 NBUVB, 30 PUVA). Both regimens were thrice-weekly. The extent of lesion was assessed by the Psoriasis Area Severity Index (PASI). Clearance was defined as a ≥ 75% reduction in a follow-up PASI score from baseline. Patients with clearance were followed-up until 6 months after stopping treatment. Relapse was defined as 50% or more of the original extent.RESULTS:The proportion of patients achieving PASI75 was comparable (76.7% in NBUVB versus 80% in PUVA; p > 0.05). Patients in both groups had a similar number of sessions to achieve clearance but patients in the PUVA group exposed to a significantly higher cumulative UV dose. After six months, the relapse rate was higher in the NBUVB group compared with in the PUVA group (p > 0.05).CONCLUSION:Thrice weekly NBUVB is as effective as thrice weekly PUVA in treating psoriasis for Vietnamese patients.

Drug and chemical induced photosensitivity from a clinical perspective.

Drug photosensitivity is a relatively common occurrence and a range of mechanisms may be involved. Some of these mechanisms will be discussed, including the most common, that of drug phototoxicity. Different types of photosensitivity are addressed with respect to clinical presentation, mechanisms and additionally the contribution to our understanding through clinically directed investigations and regulatory requirements. Repeated controlled therapeutic use of drug phototoxicity, with psoralen-UVA (PUVA) photochemotherapy and photodynamic therapy (PDT) will also be discussed. Finally, the potential for drug-induced photocarcinogenesis will also be covered.

A Perspective on the Use of NB-UVB Phototherapy vs. PUVA Photochemotherapy.

Narrowband UVB (NB-UVB) phototherapy and psoralen-UVA (PUVA) photochemotherapy are widely used phototherapeutic modalities for a range of skin diseases. The main indication for NB-UVB and PUVA therapies is psoriasis, and other key diagnoses include atopic eczema, vitiligo, cutaneous T-cell lymphoma (CTCL), and the photodermatoses. The decision on choice of phototherapy is important and NB-UVB is usually the primary choice. NB-UVB phototherapy is a safe and effective therapy which is usually considered when topical agents have failed. PUVA requires prior psoralen sensitization but remains a highly effective mainstay therapy, often used when NB-UVB fails, there is rapid relapse following NB-UVB or in specific indications, such as pustular or erythrodermic psoriasis. This review will provide a perspective on the main indications for use of NB-UVB and PUVA therapies and provide comparative information on these important dermatological treatments.

Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin.

Environmental exposure to solar ultraviolet (UV) radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of the cellular antioxidant response protecting skin against various environmental stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal keratinocytes can be activated using natural chemopreventive compounds such as the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient from the seeds of the achiote tree (Bixa orellana). Here, we tested the feasibility of topical use of bixin for NRF2-dependent skin photoprotection in two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2+/+ versus Nrf2-/-)]. First, we observed that a bixin formulation optimized for topical NRF2 activation suppresses acute UV-induced photodamage in Nrf2+/+ but not Nrf2-/- SKH1 mice, a photoprotective effect indicated by reduced epidermal hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that topical bixin suppresses PUVA (psoralen + UVA)-induced hair graying in Nrf2+/+ but not Nrf2-/- C57BL/6J mice. Collectively, this research provides the first in vivo evidence that topical application of bixin can protect against UV-induced photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation. Topical NRF2 activation using bixin may represent a novel strategy for human skin photoprotection, potentially complementing conventional sunscreen-based approaches.