The influence of phototherapy on circadian melatonin and sleep regulation and potential benefits of these pathways in the management of vitiligo: a narrative review : Vitiligo, phototherapy, sleep and melatonin.

Ultraviolet B narrow band (UVB-NB) phototherapy is the gold standard treatment for vitiligo, primarily due to its immunomodulatory effects. Additionally, it may influence circadian melatonin balance, that may indirectly induce sleep regulation, which in turn could potentially contribute to vitiligo improvement. The association between melatonin, vitiligo and phototherapy has been little investigated. The aim of this study was to evaluate the current evidence regarding the effects of circadian melatonin regulation and sleep, particularly during vitiligo treatment with phototherapy. We undertook a narrative review to synthetize the evidence on this association through the MEDLINE/PubMed database, using combined search terms: melatonin, vitiligo, phototherapy, and circadian rhythm (sleep). A total of 56 articles were included. There are few studies on this relationship, and conflicting findings. Some studies have suggested that UV exposure and phototherapy might benefit vitiligo by stimulating melanocytes, which have melatonin receptors, and this could potentially synchronize the circadian regulation of melatonin. This improved melatonin balance could result in better sleep quality further enhancing the antiinflammatory properties of melatonin and contributing to vitiligo improvement. Less is known about the possible effects of the use of topical melatonin, with or without phototherapy, to treat vitiligo lesions. In conclusion, there is some evidence that circadian melatonin regulation plays an important role in the course of vitiligo, both through sleep regulation and its anti-inflammatory properties. The evidence suggests that the systemic and physiological properties of melatonin, especially its circadian behavior regulated by phototherapy, may be more effective in respect of vitiligo improvement than the use of topical melatonin. However, the effects of the oral intake of melatonin are less clear. Phototherapy, as a potential modulator of circadian melatonin rhythm, that influences sleep and clinical improvement of vitiligo, needs further examination, as does the use of melatonin as an adjuvant treatment to UVB phototherapy in vitiligo.

Efficacy and Safety of Orally Administered East Asian Herbal Medicine Combined with Narrowband Ultraviolet B against Psoriasis: A Bayesian Network Meta-Analysis and Network Analysis.

Psoriasis is a chronic, immune-mediated inflammatory skin disease with many complications and a poor prognosis that imposes a significant burden on individuals and society. Narrowband ultraviolet B (NB-UVB) represents a cost-effective non-drug therapeutic intervention for psoriasis. East Asian herbal medicine (EAHM) is currently being investigated for its potential as a safe and effective psoriasis treatment. Consequently, it has the potential to be employed as a combination therapy with NB-UVB. The objective was to ascertain the efficacy and safety of the EAHM with NB-UVB combination therapy and to identify important drugs for further research. In this study, randomized controlled trials (RCTs) were retrieved from ten databases in Korea, China, and Japan. All statistical analyses were conducted using R software version 4.3.0. The primary outcomes were the Psoriasis Area and Severity Index (PASI) and the incidence rate of adverse events (AEs), while the secondary outcomes were hematologic markers and the Dermatology Life Quality Index (DLQI), which reflect the immune-mediated inflammatory pathology of psoriasis. The analysis of 40 RCTs, including 3521 participants, demonstrated that EAHM with NB-UVB combination therapy exhibited a statistically significant superiority over NB-UVB monotherapy with respect to primary and secondary outcomes. The Bayesian network meta-analysis revealed that Investigator Presciption 3 and Ziyin Liangxue Decoction exhibited a consistent relative advantage with respect to each PASI-based efficacy metric. The network analysis estimated the potential influence ranking for all individual herbs according to PageRank centrality. The findings of this study suggest that EAHMs co-administered with NB-UVB may provide additional efficacy and safety-related benefits for patients with psoriasis. However, the quality of evidence is still low, and further high-quality trials are needed to reach more definitive conclusions.

Adjunctive treatment of atopic dermatitis with novel at-home handheld narrow-band UVB phototherapy.

While conventional in-office phototherapy has long been utilized as a successful treatment for atopic dermatitis (AD), it is associated with potential barriers including inconvenience, poor adherence, time and financial expense. In this retrospective study, we examine the efficacy, adherence, and patient-satisfaction of using adjunctive at-home, self-administered phototherapy utilizing a novel handheld narrow-band ultraviolet B (NB-UVB) device for the treatment of refractory mild to severe AD. Included AD patients were initially trained on proper use of the device. These patients treated involved areas three times per week for a period of 12 weeks. Phototherapy dosing protocol was based on skin type. The cohort included 52 patients, who were aged 20-69 and represented all skin types. They were initially categorized by disease involvement as mild, moderate, and severe. Patients were also queried to self-score their disease severity and level of satisfaction. Compared to baseline, at 12 weeks, 48% percent of patients indicated that at least one site was Clear/Almost Clear, 38% stated that more than 50% of body locations were Clear/Almost Clear, and 28% reported that 100% (all) treated sites were Clear/Almost Clear. After using at-home hand-held NB-UVB for the study duration, 67% (35/52) of patients experienced disease improvement. Mean overall satisfaction was extremely high at 4.43 on a 5-point scale. Skin type, age, gender, and disease severity at inception did not significantly affect patient satisfaction scores. Overall adherence rate among participants across all groups was 73%. In this small retrospective study, at-home handheld NB-UVB phototherapy was found to be an effective, well-tolerated, adjunctive treatment method for patients with refractory AD, which was associated with a high level of patient satisfaction and adherence.

Ghrelin induced by ultraviolet B exposure promotes the restoration of diabetic cutaneous wound healing.

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. CONCLUSION: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

The Effect of Phototherapy on Systemic Inflammation Measured with Serum Vitamin D-Binding Protein and hsCRP in Patients with Inflammatory Skin Disease.

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy.

The UPDATE trial (UVB Phototherapy in Dermatology for ATopic Eczema): study protocol for a randomized controlled trial of narrowband UVB with optimal topical therapy versus optimal topical therapy in patients with atopic eczema.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is commonly prescribed for patients with moderate-to-severe atopic eczema (AE). The efficacy of NB-UVB, however, has not yet properly been established, as current evidence is of low certainty. Our aim is to assess the short-term and long-term (cost-)effectiveness and safety of NB-UVB in adult AE patients by performing a pragmatic, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. This protocol outlines its methodology. METHODS: A pragmatic, multicenter, PROBE trial will be performed with 1:1 randomization of 316 adult patients with moderate-to-severe AE who have inadequate disease control with topical therapy and who are eligible for optimal topical therapy (OTT) or NB-UVB in combination with OTT as a next step. Participants in the interventional arm will receive a minimum of 3 months of OTT combined with 8 to 16 weeks of NB-UVB. The control group receives 3 months of OTT. Following the interventional phase, follow-up will continue for 9 months. Physician-reported and patient-reported outcomes (according to the Harmonising Outcome Measures for Eczema (HOME) Core Outcome Set) and adverse events are assessed at 4 weeks, 3, 6, 9, and 12 months. DISCUSSION: The UPDATE trial aims to provide high-quality evidence regarding the (cost-)effectiveness and safety of NB-UVB phototherapy in moderate-to-severe AE patients. Challenges that are addressed in the protocol include the possible bias arising from applying open-label treatment and the necessity of introducing OTT into the study design to prevent a high dropout rate. TRIAL REGISTRATION: ClinicalTrials.gov NCT05704205. Registered on December 8, 2022.

A Case of Noonan Syndrome and Kyrle's Disease: Coincidence or Causality?

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus and no chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle's disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d) but with complete and long-lasting resolution of symptoms as well. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD being debated, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroid, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PDs (3). NS is a relatively common RASopathy, an heterogenous group of genetic disease characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes were identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it was hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of our patient's illness. Our patient suffered from diffuse keratosis pilaris, and one of the possible pathogenetic mechanisms of KD was theorized to be an abnormal epidermal keratinization with a secondary inflammatory dermic response (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, and is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Phototherapy for the treatment of atopic dermatitis in Singaporean children and adolescents.

BACKGROUND/PURPOSE: Phototherapy has emerged as a safe yet effective form of treatment of atopic dermatitis (AD). Few studies have been done to evaluate the efficacy of phototherapy in Asian children. The aim of this study was to review the phototherapy experience in a cohort of Asian pediatric patients with AD at a tertiary dermatologic center in Singapore. METHODS: A retrospective study of patients 18 years and below with AD who had undergone phototherapy at KK Women's and Children's Hospital, Singapore, over a 4-year period was performed. RESULTS: Sixty-two patients were identified, between ages 4 and 16 years (mean age 11 years) at the time of commencement of phototherapy. Thirty-five (60%) patients were males and 23 (40%) were females. Most patients had moderate to severe disease, with 60.3% of the patients with an initial body surface area (BSA) involvement of 31%-60% and 13.8% of the patients with an initial BSA involvement of 61%-90%. For patients who had undergone narrowband ultraviolet B (NBUVB) and combined ultraviolet A (UVA) and NBUVB phototherapy, the mean reduction of the Eczema Area and Severity Index (EASI) scores were 11.4 and 7.9, respectively. Common side effects experienced include xerosis, pruritus, erythema, and pain. Other reasons for cessation of therapy in the NBUVB group included time commitment difficulty (9.3%), hyperactivity (2.3%), and claustrophobia (2.3%). Two patients that had photochemotherapy (psoralen + UVA) [PUVA] suffered from post-UVA burns requiring cessation of treatment. More than half of the patients (56.9%) treated with phototherapy experienced treatment success with improvement in Investigator Global Assessment and EASI scores. 86.2% of the patients had good compliance to the treatment regime, 12% had poor-compliance, and 3.4% were lost to follow-up. CONCLUSION: Phototherapy is a useful treatment adjunct for moderate to severe AD in Asian children.

Treatment of oral graft-versus-host disease with intraoral nbUVB phototherapy.

PURPOSE: There are limited treatment options available for hematopoietic stem-cell transplant patients (HSCT) with oral graft-versus-host disease (GVHD). Intraoral phototherapy is a novel, yet promising therapeutic regimen. RESEARCH QUESTION: To assess the safety and effectiveness of intraoral narrowband UVB (nbUVB) phototherapy in the treatment of oral GVHD. METHODS: This case series evaluated 10 patients with refractory oral GVHD, who were treated at Northwestern Memorial Hospital with nbUVB between July 2019 and October 2023. Primary outcomes were to evaluate the safety and efficacy of phototherapy. Efficacy was measured by objective improvement in symptom scores and subjective improvement in patient reported symptoms. Safety was determined by the withdrawal due to adverse events. Total nbUVB exposure, number of treatments, and change in systemic immunosuppressive medications were also examined. RESULTS: The study cohort comprised 10 patients who developed oral GVHD at a median of 9.5 months after HSCT. The total median dose of nbUVB was 36 J/cm2, and the median number of sessions was 55. All 10 patients demonstrated some degree of improvement in symptoms. Notably, there was a reduction in the number of patients who reported symptoms of oral pain (83%), bleeding (67%), xerostomia (50%), and oral sensitivity (78%) after initiating phototherapy. There was also a statistically significant decrease in the levels of pain, erythema, and edema (p ≤ 0.001, < 0.001, 0.01, respectively). Most patients tolerated phototherapy well, but 1 patient withdrew from treatment due to adverse effects. Seventy-five percent of patients who were on immunosuppressive medications were able to decrease or stop these medications. CONCLUSION: This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.

Effectiveness of narrowband ultraviolet B monotherapy versus combination therapy with systemic agents in patients with early-stage mycosis fungoides and the association with plaque lesions.

OBJECTIVE: Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. METHODS: This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. RESULTS: In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. CONCLUSIONS: Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.

Combination of total glucosides of paeony, narrow-band ultraviolet B, and oral corticosteroid mini-pulse therapy for nonsegmental vitiligo: A retrospective study.

BACKGROUND: The total glucoside of paeony (TGP) is recognized for its immunomodulatory properties and anti-inflammatory effects. This study evaluates the efficacy of TGP combined with oral mini-pulse therapy (OMP) and narrow-band ultraviolet B (NB-UVB) in treating active nonsegmental vitiligo (NSV). MATERIALS AND METHODS: The combination therapy was contrasted against those from a group treated solely with OMP and NB-UVB. Data from 62 patients undergoing TGP combination treatment and 55 without were analyzed over a 3-month period. After 6 months, the differences in recurrence rate were investigated by follow-up. RESULTS: The findings indicate that integrating TGP may yield superior outcomes compared to OMP + NB-UVB alone. Moreover, the patient's oxidative stress makers were significantly reduced after the treatment. The majority of patients in the TGP cohort exhibited enhanced skin pigmentation over the duration. Notably, no increase in side effects or recurrence was observed in this group. Especially, patients with vitiligo on their head and neck experienced pronounced improvements. CONCLUSION: The efficacy of the combination treatment group was better than that of the control group at 2 and 3 months, and there was no difference in recurrence rate and side effects, suggesting that TGP may continue to show efficacy in NSV for a longer period of time by reducing the level of oxidative stress, and is especially suitable for patients with head and neck lesions.

Spatial targeted delivery of riboflavin with a controlled corneal iontophoresis delivery system in theranostic-guided UV-A light photo-therapy.

Seven human donor eye globes underwent corneal cross-linking using theranostic UV-A device with accessory corneal iontophoresis system for patterned delivery of a 0.22% riboflavin solution. Theranostic-guided UV-A light illumination assessed riboflavin distribution and treated corneas at 10 mW/cm2 for 9 min with a 5.0-mm beam size. Corneal topography maps were taken at baseline and 2-h post-treatment. Analysis utilized corneal topography elevation data, with results showing controlled riboflavin delivery led to a consistent gradient, with 40% higher levels centrally (248 ± 79 µg/cm3) than peripherally (180 ± 72 µg/cm3 at ±2.5 mm from the center). Theranostic-guided UV-A light irradiation resulted in significant changes in corneal topography, with a decrease in best-fit sphere value (-0.7 ± 0.2 D; p < 0.001) and consistent downward shift in corneal elevation map (-11.7 ± 3.7 µm). The coefficient of variation was 2.5%, indicating high procedure performance in achieving significant and reliable corneal flattening.

Ultraviolet Light-Emitting Diode Radiation Kills Leukemia Cells Without Affecting Hematopoiesis of Hematopoietic Stem Cells in Mice.

OBJECTIVES: The eradication of leukemia cells while sparing hematopoietic stem cells in the graft before autologous hematopoietic stem cell transplant is critical to prevention of leukemia relapse. Proliferating cells have been shown to be more prone to apoptosis than differentiated cells in response to ultraviolet radiation; however, whether leukemia cells are more sensitive to ultraviolet LED radiation than hematopoietic stem cells remains unclear. MATERIALS AND METHODS: We compared the in vitro responses between murine leukemia L1210 cells and murine hematopoietic stem cells to 280-nm ultraviolet LED radiation. We also investigated the effects of ultraviolet LED radiation on the tumorigenic and metastatic capacity of L1210 cells and hematopoietic stem cell hematopoiesis in a mouse model of hematopoietic stem cell transplant. RESULTS: L1210 cells were more sensitive to ultraviolet LED radiation than hematopoietic stem cells in vitro, as evidenced by significantly reduced colony formation rates and cell proliferation rates, along with remarkably increased apoptosis rates in L1210 cells. Compared with corresponding unirradiated cells, ultraviolet LED-irradiated L1210 cells failed to generate palpable tumors in mice, whereas ultraviolet LED-irradiated bone marrow cells restored hematopoiesis in vivo. Furthermore, transplant with an irradiated mixture of L1210 cells and bone marrow cells showed later onset of leukemia, milder leukemic infiltration, and prolonged survival in mice, compared with unirradiated cell transplant. CONCLUSIONS: Our results suggest that ultraviolet LED radiation can suppress the proliferative and tumorigenic abilities of leukemia cells without reducing the hematopoietic reconstitution capacity of hematopoietic stem cells, serving as a promising approach to kill leukemia cells in autograft before autologous hematopoietic stem cell transplant.

Phototherapy for Psoriasis in the Age of Biologics.

Phototherapy has utility as a psoriatic therapy, given its relatively high clinical efficacy, low side effect profile, and lower cost compared to newer effective treatments like biologics and small molecules. Phototherapy has shown Psoriasis Area and Severity Index (PASI)-75 and PASI-90 rates comparable to those of biologics and small molecules, with similarly rapid onsets of action, rates of remission, and quality of life scores. Certain patients may particularly benefit from phototherapy, such as those with localized disease or contraindications to systemic immunomodulatory medication. Phototherapy can be more cost-effective than biologics and conveniently administered at home, making it a valuable therapeutic option for the right patient.

Carcinogenic risk in patients treated with UVA-1 phototherapy: A 5-year retrospective study.

BACKGROUND: UVA-1 phototherapy was first used to treat atopic dermatitis and afterwards to several other skin diseases. The contribution of UVA-1 in human photocarcinogenesis, skin photoaging, immune suppression, and hyperpigmentation is now well established. The actual contribution of UVA-1 radiation to the development of malignant melanoma (MM) in humans cannot be excluded. PURPOSE: The aim of the study is to evaluate the risk of developing skin cancers (non-melanoma skin cancers (NMSCs) and MM) in patients treated with UVA-1 phototherapy with a 5-year dermatological follow-up. METHODS: We conducted a retrospective cohort study with 31 patients with morphea and atopic dermatitis treated with medium dose UVA-1 phototherapy (34 J/cm2). All enrolled patients underwent an oncologic prevention visit annually with a 5-year follow-up with clinical evaluation of the entire skin surface. RESULTS: During the 5-year follow-up, we recorded a case of basal cell carcinoma (BCC) in the cervical region and one case of MM on the back (pT1a). In both cases, the patients were female and affected by morphea. The Glogau 3 group is prevalent (42%), which is consistent with moderate to severe aging; the data appear to be compatible with the age. CONCLUSIONS: This study attests that medium-dose UVA-1 phototherapy does not increase the risk of developing skin tumors and that UVA-1 phototherapy is not a worsening factor of facial photoaging. The main limitation of the study is the small sample size, avoiding to obtain statistically significant values. It was not possible to analyze individually the actual daily sun exposure during the 5-year observation period and to correlate it in terms of time and tumor development. Further studies with large sample sizes will be needed to confirm our data. Our study reaffirms how the dermatological examination performed annually is essential in the follow-up of patients undergoing this type of therapy.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Plexin B2 tissue expression and related gene polymorphisms in psoriasis and their relation to NB-UVB and Acitretin therapy.

Psoriasis is a chronic, immune-mediated, hyperproliferative skin disease. Etiopathogenesis of psoriasis is not well understood. Plexin B2 was found to have effects on CD100-mediated T-cell morphology and expressed in the immune system. It may play a role in the pathogenesis of psoriasis. To assess the tissue level of plexin-B2 and plexin B2 related gene polymorphism which is signal regulatory protein gamma (SIRPγ-rs71212732) in psoriatic patients before and after NB-UVB, acitretin therapy alone or in combination and to detect correlation between level of tissue plexin B2 and disease severity and improvement. This single blinded randomized controlled trial was carried on 50 psoriatic patients and 50 healthy controls. Psoriasis Area and Severity Index score (PASI) was used to evaluate the disease severity. Tissue plexin-b2 level was measured using ELISA and SIRPγ-rs71212732 (T\C) was assessed using TaqMan™ assays and real-time PCR. A significant lower tissue plexin-B2 level was observed in control group (2.9 ± 0.6 pg/g) than cases (25.8 ± 2.8, pg/g) (p < 0.001). Also, a significantly higher tissue plexin-B2 level was observed in sever psoriasis (32.7 ± 3.8 pg/ml) in than moderate psoriasis (13.6 ± 2.1 pg/ml, p = 0.001). Tissue plexin B2 was positively correlated with diseases severity. Significantly higher (TC& TT) genotypes and mutant (C) allele among patients compared to the controls, p < 0.001 for all. Tissue plexin-b2 level was high in psoriasis vulgaris with positive correlation with disease severity and decreased after treatment. This may indicate a role of plexin-b2 in psoriasis vulgaris pathogenesis.