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.

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.

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.
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.
CONCLUSIONS: 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.

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.

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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.
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov NCT05704205. Registered on December 8, 2022.

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.

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.

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).
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.
CONCLUSIONS: 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.

OBJECTIVE: 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.
OBJECTIVE: 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.
CONCLUSIONS: This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.