Search Results (34)

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Vitiligo is a chronic autoimmune dermatosis defined by selective melanocyte depletion and patchy depigmentation. IFN–γ-driven recruitment of autoreactive CD8⁺ T cells and induction of melanocyte apoptosis are central to its pathogenesis. Current therapies—including UVB phototherapy, tacrolimus, vitamin D3 analogs, and surgical methods—show limited and inconsistent efficacy. Emerging treatments like JAK inhibitors and WNT activators offer potential but require further validation. Translational progress is hindered by a lack of scalable human models. Here, we describe a tunable in vitro vitiligo platform in which human iPSC-derived melanocytes (iMc) are co-cultured with keratinocytes on Matrigel and exposed to precise graded IFN-γ concentrations. Our data revealed dose-dependent decreases in iMc survival and dendritic structure, faithfully mirroring derived melanocyte pathology. Leveraging this platform, we first evaluated the short-term efficacy of the ROCK inhibitor Y27632 under early-stage patient IFN-γ concentrations representative of patient lesional thresholds. At three days, Y27632 significantly upregulated adhesion molecules E-cadherin and DDR1, and two central factors—ET1 and bFGF. Importantly, ROCK inhibition reversed dendritic retraction and improved overall viability of iMc-keratinocytes. These findings position ROCK blockade as a promising adjunctive strategy and establish a pre-clinical platform for evaluating combination therapies for durable pigment restoration. Full article

Objective: To conduct a systematic review of the literature evaluating the efficacy of the 308 nm excimer lamp in comparison to narrowband ultraviolet B (NB-UVB) and the 308 nm excimer laser for inducing repigmentation in vitiligo. Methods: A comprehensive search was performed in PubMed, Embase, Cochrane Library, Scopus, Web of Science, and LILACS databases, as well as in gray literature sources including Google Scholar, OpenGrey, Livivo, and ProQuest. Risk of bias was assessed independently by two blinded reviewers using the Cochrane RoB 2 tool, with disagreements resolved by a third reviewer. The primary outcome was the degree of repigmentation. Results: Of 3825 records identified, four randomized controlled trials met the inclusion criteria. The findings suggest that the 308 nm excimer lamp provides superior repigmentation outcomes compared to NB-UVB and demonstrates comparable efficacy to the 308 nm excimer laser. Conclusions: Phototherapy using the 308 nm excimer lamp appears effective in promoting repigmentation in vitiligo patients and is associated with minimal adverse effects. Nevertheless, variations in treatment protocols and potential bias across studies warrant cautious interpretation of the results. Full article

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing symptom that affects both dialysis and non-dialysis patients, significantly impairing their quality of life. Despite its multifactorial pathophysiology, no gold-standard treatment has been established. This review explores various therapeutic options and evaluates their effectiveness based on recent clinical studies and meta-analyses. Therapies targeting novel mechanisms have evolved in recent years. Difelikefalin, a κ-opioid receptor agonist, represents a breakthrough in systemic treatment, demonstrating efficacy with a favorable safety profile. Another opioid-based therapy, nalfurafine, has shown notable symptom relief in multiple clinical studies, with a low risk of abuse. Sertraline, an antidepressant, offers another alternative, although its delayed onset remains a limitation. Nonpharmacologic approaches are also evolving. Phototherapy, particularly UV-B therapy, modulates the immune response, reduces inflammation, and effectively alleviates itching in hemodialysis patients. Personalized treatment strategies are crucial, as responses vary among patients. Further research, including comparative and long-term studies, is essential to refine treatment algorithms and improve patient outcomes. By integrating new pharmacologic and nonpharmacologic options, CKD-aP management is shifting toward a more tailored and effective approach that addresses the individual needs of each patient. Full article

Background/Objectives: Vitiligo is an autoimmune condition causing melanocyte destruction and skin depigmentation. First-line treatments for vitiligo include topical medications and phototherapy; however, access and utilization of these treatments vary, particularly in pediatric patients. This study evaluates nbUVB use in pediatric versus adult vitiligo patients to better understand utilization in the pediatric population. Methods: A retrospective chart review study was conducted, collecting demographics and treatment characteristics for 102 adults and 19 children with vitiligo treated with nbUVB phototherapy at one institution. Statistical analysis included comparisons for categorical variables made using Chi-squared test or Fisher’s exact test, as appropriate, and using a non-parametric Mann–Whitney U test for continuous variables. Results: On average, adults underwent nbUVB for 23.8 months (range 0.5–418, median 9), while children had an average duration of 14.8 months (range 2–60, median 8). The average number of nbUVB sessions for adults was 83.8, whereas children had an average of 33.5 sessions. Overall, 59.6% of adults and 60.0% of children experienced repigmentation with nbUVB. Conclusions: Retrospective analysis indicated that the duration and frequency of nbUVB sessions varied widely among both adults and children. While the average duration of treatment was comparable between the groups, children underwent fewer sessions on average. This may reflect differences in physician recommendation, scheduling constraints, or treatment adherence. Despite this variability, most pediatric patients exhibited repigmentation, supporting nbUVB efficacy. Our results suggest nbUVB is underutilized in pediatric vitiligo. Addressing obstacles to access is crucial for improving treatment outcomes and quality of life. Full article

UVB phototherapy effectively treats psoriasis. Although it suppresses both innate and adaptive immunity, it remains unclear why UVB irradiation is primarily effective for T-cell-mediated but not inflammatory skin diseases of other etiologies. Using a Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8⁺ T-cell clone, we recently demonstrated that in psoriasis, the major psoriasis risk allele HLA-C*06:02 mediates an autoimmune response of CD8⁺ T-cells against melanocytes by presenting a melanocyte autoantigen. We now investigate the effect of UVB irradiation on melanocyte immunogenicity using the psoriatic Vα3S1/Vβ13S1 TCR in a reporter assay. The immunogenicity of melanocytes for the Vα3S1/Vβ13S1 TCR depended on the up-regulation of HLA-C expression by IFN-γ. UVB irradiation reduced the stimulatory capacity of IFN-γ-conditioned melanocytes for the Vα3S1/Vβ13S1 TCR by suppressing key IFN-γ-induced MHC-class I transcriptional regulators (STAT1, IRF1, NLRC5), the HLA-C-specific transcription factor Oct1, and by inducing miR-148a, which specifically inhibits HLA-C expression. This resulted in the suppression of the IFN-γ-induced expression of HLA-class I molecules and, in particular, an almost complete loss of HLA-C expression. We conclude that suppression of the inflammatory increase in HLA-class I expression and antigen-presentation may contribute to the efficacy of UVB phototherapy in T-cell-mediated skin diseases. The pronounced downregulation of HLA-C on melanocytes could render psoriasis, as HLA-C-associated disease, particularly susceptible to this effect. Full article

Background: Psoriasis is a chronic, multi-system inflammatory disease frequently associated with metabolic syndrome and lipid disturbances. Apolipoproteins, as essential regulators of lipid metabolism, may play a critical role in these metabolic abnormalities, potentially influencing disease severity and systemic inflammation. The aim of this study was to compare serum concentrations of chosen apolipoproteins in patients with psoriasis before and after treatment with acitretin or narrowband UVB (NB-UVB). Methods: This study was conducted on 39 patients with psoriasis. The concentration of nine apolipoproteins and C-reactive protein was quantified using the Bio-Plex Immunoassay Kit. Results: The serum concentrations of ApoA2, ApoC1, ApoD, ApoE, and ApoJ were higher in the acitretin group compared to the NB-UVB group before treatment, while the ApoA1/ApoA2 ratio was lower. We also observed a negative association between the Psoriasis Area and Severity Index (PASI) and ApoA1/ApoA2 ratio in the patients before the treatment. Conclusions: The results of this study confirm the presence of metabolic disturbances in psoriatic patients. The treatment with NB-UVB or acitretin did not cause any significant changes in the apolipoproteins profile. Thus, we found no detrimental impact of acitretin on the apolipoproteins profile, despite the observed rise in total cholesterol concentration after the treatment. Further research is needed to explore whether specific therapeutic approaches can modify these disturbances and potentially improve long-term cardiovascular outcomes in this population. Full article

Vascular cell adhesion molecule-1 (VCAM-1) and E-selectin are involved in different inflammatory diseases and may be potential cardiovascular risk biomarkers in psoriasis. They play an important role in regulating the recruitment and adhesion to endothelial cells during inflammation, affecting various conditions like vasculitis, atherosclerosis, and cardiovascular diseases. Positive outcomes have been observed when using Tumor Necrosis Factor Alpha (TNF-α) inhibitors and biological therapies that target selectins to control the functioning of endothelial cells and reduce inflammation in psoriasis and related conditions. Moreover, the effects of systemic treatments and ultraviolet B (UVB) phototherapy on VCAM-1 and E-selectin levels in psoriasis patients highlights the potential to impact the severity of psoriasis and activation of endothelial cells. In addition, various factors such as age, sex, metabolic syndrome, hyperglycemia, migraines, and tobacco smoking have been found to affect levels of VCAM-1 and E-selectin. This sheds light on understanding the complex relationship between endothelial activation and the development of diseases. Studies show the potential of using the levels of VCAM-1 and E-selectin as indicators of systemic treatment effectiveness and the progression of the disease. In summary, this review highlights the importance of VCAM-1 and E-selectin as potential biomarkers for assessing inflammation, disease severity and cardiovascular risk in individuals with psoriasis. The shared mechanisms of psoriasis and atherosclerosis, along with the effect of treatments on endothelial activation markers, provide significant insights for further research and approaches to manage inflammatory diseases in the future. Full article

Background: Narrowband ultraviolet B (nb-UVB) is one of the most popular and effective modalities to treat vitiligo. Given the importance of nb-UBV, as well as its associations, this research searched the literature for answers on how to best treat vitiligo. Objective: To conduct a systematic literature review assessing the efficacy of narrowband ultraviolet B (NB-UVB) therapy for the treatment of vitiligo, in comparison with psoralen plus ultraviolet A (PUVA) therapy and other topical or systemic treatment modalities. Methods: The databases included were PubMed, Embase, Cochrane, Scopus, Web of Science, and LILACS. Gray literature was also used: Google Scholar, Open Grey, and Library of Thesis and Dissertations-CAPES. The search used the keywords: “Vitiligo” AND “Ultraviolet Therapy OR Actinotherapy”. The risk of bias was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool by two independent, blinded reviewers, with disagreements resolved by a third reviewer. The outcome assessed was repigmentation. Results: Three randomized controlled trials were selected from 2973 records. In three studies, Nb-UVB had superior effects to the comparator. Conclusion: Nb-UVB phototherapy improves repigmentation in patients with vitiligo, with few side effects. However, the variability in the protocols and the risk of bias require caution when interpreting the results. Full article

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. Full article

Background: The risk of developing non-melanoma skin cancers (NMSCs) in patients with psoriasis is highly debated, and, to date, there is no unambiguous consensus opinion. Psoriasis is known to be related to an increased likelihood of other comorbidities such as psoriatic arthritis, obesity, metabolic syndrome, depression, and cardiovascular disease. Regarding cancer risk, previous studies have reported a greater tendency for the development of cutaneous T-lymphomas and colon, breast, kidney, and lung cancers. Furthermore, data from network meta-analyses have shown that patients with psoriasis have a higher risk of developing squamous cell carcinomas (SCCs) and/or basal cell carcinomas (BCCs). Multiple factors may contribute to the development of NMSCs in psoriatic patients, ranging from immunosuppression induced by biologic agents to previous phototherapy. However, the extent to which each factor may impact this risk has not been entirely assessed. The aim of this study was to evaluate the risk of developing NMSCs in patients with psoriasis observed for at least 5 years, by directly comparing patients only treated with phototherapy and patients treated with anti-tumor necrosis factor α (TNFα) agents, naive to other systemic treatments or phototherapy. Methods: We conducted a single-center retrospective study at Siena University Hospital, Italy, on 200 adult patients with psoriasis divided into two groups: (i) group 1, including 100 patients treated with narrow-band UVB phototherapy (nb-UVB), and (ii) group 2, including 100 patients treated with anti-TNFα. The patients included in group 2 had to be naive to cDMARDs and biologics and treated with anti-TNFα continuously for 5 years without loss of efficacy. All patients were observed for 5 years and underwent annual dermatologic examinations to assess for the occurrence of BCC or SCC. Results: A total of 34 out of 100 patients treated with phototherapy had one BCC or one SCC and 10 out of 34 developed two skin cancers. In particular, five had both types (one BCC and one SCC), and five had two BCCs. Conclusions: The results of our study highlight how the risk of developing NMSCs is greater in patients undergoing phototherapy compared to those treated with anti-TNFα. It also draws attention to the consideration that patients with scalp psoriasis might need closer follow-up as they could be more at risk of developing NMSCs. Full article

The treatment of allergic conditions presents a challenge for both seasonal allergic rhinitis and perennial rhinitis sufferers. The increasing prevalence of both of these types of allergic responses requires the use of a range of treatments which can provide relief. The treatment of allergic rhinitis has been considered under the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines. Current treatment options include medication and avoidance for those with reduced responses, but more expensive treatments include immunotherapy and the use of monoclonal antibodies (mAb). All treatments target specific parts of the inflammatory response which includes mast cells, eosinophils and basophils. Phototherapy can be a useful addition to these treatments, and combinations of UV-B (5%), UV-A (25%) and visible light (70%) in phototherapy treatments have been shown to reduce the severity of symptoms. Phototherapy consisting of visible wavelengths and infrared light (660 nm 940 nm) was shown to be particularly effective in treating perennial rhinitis. The use of a range of wavelengths in the control of allergic responses is described in this paper. Phototherapy can form part of an effective treatment regime for allergic rhinitis sufferers which can exploit synergies in the control of the condition elicited through several pathways. Full article

The most frequent primary cutaneous lymphomas observed in childhood and adolescence are mycosis fungoides (MF) and CD30-positive lymphoproliferative diseases. We report a 22-year-old female who presented with a 6-year history of multiple well-demarcated large roundish-oval scaly and reddish-brownish patches and plaques on the trunk and extremities. Histopathology revealed the focal parakeratosis and prominent epidermotropism of atypical lymphocytes, which were positive for CD8, CD56, and TIA-1 and showed a loss of CD7 and CD5 expression. T-cell receptor (TCR) gene rearrangement analysis (multiplex-PCR, BIOMED-2) of the lesional skin demonstrated the rearrangement of the gamma chain (tube A: 162 nt). Based on clinicopathological findings and a complete work-up, she was diagnosed with juvenile non-poikilodermatous C8+/CD56+ MF in stage IA. Resolution of the skin lesions was achieved by 16-week narrowband UVB phototherapy and clobetasol propionate 0.05% ointment. Juvenile-onset non-poikilodermatous CD8+CD56+ MF represents a very rare MF subtype and is associated with an indolent course. In order to avoid too aggressive diagnostics and treatments, clinicians should be aware of this rare and indolent MF variant in childhood and adolescence. Full article

Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the LINE-1 retrotransposons. The ectopic expression of LINE-1 has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that LINE-1 reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of LINE-1 and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind LINE-1 mRNA were measured using RT-qPCR, and the expression of miR-16 was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces LINE-1 reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in miR-16 expression. Full article

Vitamin D is one significant prohormone substance in human organ systems. It is a steroidal hormone produced in the skin upon exposure to UVB rays. This paper presents a systematic review of the utilization of topical vitamin D, specifically cholecalciferol, calcipotriol, and tacalcitol, in the treatment of vitiligo. It considers the role of vitamin D in stimulating the synthesis of melanin and melanogenesis, which can help with the process of repigmentation. The inclusion of calcipotriol or tacalcitol in Narrowband Ultraviolet Phototherapy (NB-UVB) has shown the potential to enhance therapeutic outcomes for vitiligo. However, their effectiveness in combination with Psoralens Long Wave Ultraviolet Radiation (PUVA) and Monochromatic Excimer Light (MEL) treatment for vitiligo is limited. In contrast, combining topical corticosteroids with vitamin D analogues has demonstrated superior efficacy in treating vitiligo compared to using vitamin D analogues alone, while also providing the added benefit of reducing corticosteroid-related adverse effects. In addition, treating stable vitiligo with topical cholecalciferol and microneedling has shown success. Future studies are needed to ascertain an efficient method of administering vitamin D topically as an anti-vitiligo agent. Full article