Search Results (5,110)

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Background/Objectives: Allopurinol, a first-line drug for gout and hyperuricemia, carries a risk of severe cutaneous adverse reactions (SCARs). Studies have established a strong association between HLA-B*58:01 and this adverse reaction. Although pre-treatment genotyping is recommended, the reliability of HLA-B*58:01 genetic testing varies across laboratories. This study aims to assess the performance of HLA-B*58:01 genetic testing of clinical laboratories in Shanghai through an External Quality Assessment (EQA) program, evaluating accuracy and standardization. Methods: The EQA program was carried out twice a year in 2023 and 2024. Each EQA sample panel consisted of five distinct samples, including HLA-B*58:01 allele-positive and -negative cell cultures. Sample panels were distributed to clinical laboratories through the cold chain system and results were analyzed and scored. Results: EQA samples used in this study were optimized for evaluating current HLA-B*58:01 genotyping assays, and the EQA samples were proved to be homogeneous and stable through each EQA period. In 2023, 17 and 16 clinical laboratories participated in the two EQA schemes; in 2024, 34 and 33 laboratories participated. A total of 14/17 (82.4%), 16/16 (100%), 33/34 (97.1%), and 33/33 (100%) laboratories achieved “optimal” scores. Conclusions: EQA results indicate that most of clinical laboratories in Shanghai exhibit constantly satisfactory performance for HLA-B*58:01 genotyping. However, a few laboratories still need further improvement. Additionally, EQA has demonstrated to be an important method for monitoring clinical laboratories’ performance. Full article

Cutaneous fibrosis is characterized by aberrant wound healing with excessive extracellular matrix deposition, sustained inflammation, and oxidative stress, while currently available therapies show limited efficacy and safety. A Dual Hyaluronic Acid Compound (DHC), consisting of high-molecular-weight, low-molecular-weight, and minimally cross-linked hyaluronic acid, has demonstrated regenerative and antioxidant properties, but its anti-fibrotic effects have not been fully explored. This study investigated the anti-fibrotic potential of DHC using a bleomycin-induced murine dermal fibrosis model and a UVB-irradiated ex vivo human skin model. In C57BL/6 mice, dermal fibrosis was induced by daily bleomycin injections for three weeks, followed by intradermal DHC administration. Histological and biomechanical analyses showed that DHC significantly reduced dermal thickness, collagen deposition, and skin hardness compared with untreated fibrotic controls. DHC decreased α-SMA expression and increased MMP1 levels, indicating attenuation of myofibroblast activation and enhanced matrix remodeling. It also reduced macrophage markers (CD68, CD163) and pro-inflammatory cytokines (IL-1β, TNF-α). Furthermore, DHC restored superoxide dismutase (SOD) and catalase (CAT) activity and upregulated NRF2, HO-1, and NQO1 expression in the in vivo model. Similarly, DHC upregulated SOD and CAT activity and reduced pro-inflammatory cytokines (IL-6, TNF-α) in the ex vivo human skin model. These findings suggest that DHC exerts multimodal anti-fibrotic effects through coordinated regulation of fibroblast activation, inflammation, and oxidative stress, supporting its potential as a therapeutic approach for cutaneous fibrosis. Full article

Background/Objectives: Accurate target delineation is critical in radiotherapy for head and neck non-melanoma skin cancer (NMSC), where tumor depth and subclinical extension are often underestimated by clinical and dermoscopic assessment alone. While high frequency ultrasound has shown value in surface-based radiotherapy techniques, the role of ultra-high frequency ultrasound (UHFUS) within external beam radiotherapy (EBRT) workflows remains poorly defined. Methods: We conducted a single-institution observational feasibility study including all consecutive patients with head and neck NMSC treated with definitive or adjuvant radiotherapy between July 2022 and July 2023 using a structured multidisciplinary workflow integrating pre-treatment UHFUS. UHFUS was systematically performed prior to CT simulation and incorporated into radiotherapy planning. The primary endpoint was the impact of UHFUS on radiotherapy decision-making, predefined as modification of target delineation, treatment intent, or beam modality selection. Secondary endpoints included feasibility, early local control, and late toxicity (descriptive). Results: Thirty patients were included (median age 85 years; range 66–99). UHFUS influenced at least one decision endpoint in 13 patients (43.3%). In the definitive radiotherapy cohort (n = 18), UHFUS modified gross tumor volume delineation in eight patients (44.4%), with an increase in median GTV from 17.5 cm³ to 24.3 cm³. Among patients initially referred for adjuvant radiotherapy (n = 12), UHFUS identified macroscopic residual disease in two cases, leading to a change in treatment intent from adjuvant to definitive radiotherapy. UHFUS supported beam modality selection in three patients by enabling safe use of electron therapy for superficial lesions. After a median follow-up of 24 months (range 12–24), no local recurrences were observed. Late toxicity was limited to grade 1 cutaneous events. Conclusions: Integration of UHFUS into EBRT planning for head and neck NMSC is feasible and clinically informative. UHFUS acts as a decision-shaping tool, influencing target delineation, treatment intent, and modality selection within a multidisciplinary workflow. These findings support further prospective evaluation of UHFUS-guided radiotherapy planning to standardize decision algorithms and assess long-term clinical impact. Full article

Chronic inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, are systemic immune-mediated disorders driven by dysregulated immune responses. The gut–skin axis is a bidirectional network linking intestinal microorganisms, their metabolites, and host immunity. It connects microbiome composition and function with systemic inflammation and cutaneous pathology, shaping disease-specific mechanisms such as Th2/IL-4/IL-13-mediated barrier dysfunction in AD and Th17/IL-23/IL-17-driven hyperproliferation in psoriasis. Microbiota-derived metabolites, including short-chain fatty acids, tryptophan-derived aryl hydrocarbon receptor ligands, and bile acid-dependent FXR/TGR5 signaling, modulate immune homeostasis and epithelial integrity. Gut dysbiosis, impaired metabolite production, and barrier dysfunction disrupt regulatory networks, amplifying inflammation. Microbiota-targeted interventions, including probiotics, synbiotics, postbiotics, and precision nutrition, may serve as adjunctive therapies, although further well-controlled clinical studies are needed. Integrating multi-omics, metabolomics, and functional microbial profiling, alongside investigations of the gut mycobiome and virome, will be critical to identify predictive biomarkers and optimize therapeutic strategies. These concepts remain mechanistically compelling but largely theoretical, requiring validation in longitudinal and interventional studies. Full article

Facial vascularized composite allotransplantation (fVCA) is one of the most complex forms of vascularized composite allotransplantation and requires lifelong immunosuppression to ensure graft survival. Despite significant advances in surgical techniques and postoperative care over the past two decades, the true incidence of cutaneous malignancies in fVCA recipients remains poorly characterized due to the limited number of procedures, heterogeneous immunosuppressive protocols, and relatively short follow-up. This narrative review summarizes current evidence on oncologic risk in facial VCA, focusing on the effects of different immunosuppressive regimens and the challenges posed by the high immunogenicity of skin and mucosa. Available data indicate that malignancies, including cutaneous and other neoplasms, occur in approximately 10% of recipients, based on heterogeneous case-series data with immunosuppressive therapies largely extrapolated from solid organ transplantation. Calcineurin inhibitors, corticosteroids, and azathioprine are associated with increased oncologic risk, whereas mycophenolate mofetil and mTOR inhibitors may confer a more favorable profile. Overall, fVCA, unlike solid organ transplantation, is a life-enhancing procedure, highlighting the need for tailored immunosuppressive strategies, rigorous dermatologic surveillance, and further research supported by dedicated registries to better define long-term malignancy risk. Full article

Background: High-frequency ultrasound (HFUS) represents a valuable non-invasive imaging modality for assessing cutaneous tumors. In basal cell carcinoma (BCC), preoperative estimation of tumor depth may support therapeutic decision-making and surgical planning. However, agreement between HFUS-derived and histopathologic depth measurements remains incompletely characterized, particularly with 20 MHz probes in routine clinical practice. Objectives: To evaluate agreement between 20 MHz HFUS and histopathology for BCC tumor depth using Bland–Altman analysis and to derive a preliminary correction equation to estimate histologic depth from HFUS measurements. Methods: This prospective observational pilot study included 15 patients with 16 histologically confirmed BCC lesions. All lesions underwent preoperative 20 MHz HFUS followed by surgical excision, with HFUS-derived tumor depth compared with histopathologic depth. Agreement was assessed using Bland–Altman analysis, and linear regression was performed to derive a preliminary correction equation. Results: Sixteen BCC lesions were analyzed. The mean difference between HFUS and histopathologic tumor depth was −0.07 mm, with 95% limits of agreement from −1.58 to +1.45 mm. HFUS and histopathologic depth measurements were highly correlated (R² = 0.99). A correction equation was derived: estimated histopathologic depth (mm) = −0.52 + 1.10 × HFUS depth (mm). Conclusions: Twenty MHz HFUS demonstrated good agreement with histopathology for tumor depth assessment in BCC, with clinically acceptable variability. The proposed correction equation may improve interpretation of HFUS measurements; however, further validation in larger cohorts is required. Full article

Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma (pCTCL) that generally has an indolent course with a favorable prognosis. However, numerous clinical variants have been described that differ substantially from classic Alibert–Bazin MF, resulting in altered prognosis, treatment response, and patient outcomes. This narrative review considers rare MF variants—bullous, ichthyosiform, hypopigmented, folliculotropic, poikilodermatous, granulomatous, granulomatous slack skin, pagetoid reticulosis and syringotropic MF—with emphasis on practical diagnostic approaches for clinicians. Given that MF can mimic more than 50 different dermatoses and is frequently associated with prolonged diagnostic delay, we provided detailed clinical and dermoscopic features that should raise diagnostic suspicion and guide biopsy decisions. We discussed extensive differential diagnoses for each variant and highlighted MF’s status as dermatology’s “great imitator.” Additionally, we addressed the risk of second primary malignancy in patients with MF, as well as the genetic and microenvironmental factors proposed to contribute to its clinical heterogeneity. Furthermore, we evaluated existing classification systems and suggested future directions that integrate molecular data and tumor biology to improve prognostic assessment and guide therapeutic decision-making. Full article

Background/Objectives: Wound healing is a complex biological process involving inflammatory, proliferative, and remodeling phases. Plant-derived essential oils are increasingly investigated as topical therapeutic agents, although their biological effects are strongly influenced by composition and formulation. The present study evaluated the effects of topical Mentha spicata essential oil on cutaneous wound healing in a rat excisional wound model and explored potential molecular mechanisms using a network-based bioinformatic approach. Methods: Twenty-one male Wistar rats were randomly assigned to three groups and treated twice daily for 14 days with a formulation containing 5% Mentha spicata essential oil diluted in olive oil, olive oil alone, or no treatment. Wound healing was assessed through macroscopic monitoring and histological scoring. The chemical composition of the essential oil was characterized using gas chromatography–mass spectrometry analysis. Predicted molecular targets of the major monoterpenes were analyzed through protein interaction networks and pathway enrichment analysis. Results: Macroscopic wound closure progressed in all groups by day 14. Histological analysis revealed that the olive oil group showed more advanced collagen deposition, re-epithelialization, and granulation tissue maturation, whereas the Mentha spicata group displayed a more pronounced inflammatory and proliferative histological pattern. Network-based analysis highlighted signaling pathways related to receptor-mediated cellular responses as potential molecular mechanisms associated with early inflammatory and proliferative processes. Conclusions: These findings suggest that the biological effects of Mentha spicata essential oil in wound repair may be phase-dependent and influenced by concentration and formulation. The results support further studies aimed at optimizing dose and delivery strategies for essential oil–based wound therapies. Full article

This case highlights the diagnostic value of high-resolution ultrasonography in identifying postoperative injury of the posterior branch of the medial antebrachial cutaneous nerve (MABCN) following cubital tunnel surgery. A 45-year-old man developed localized pain, warmth, and paresthesia extending from the medial epicondyle to the proximal anterior forearm one month after ulnar nerve decompression and anterior transposition. Physical examination revealed focal allodynia and a positive Tinel sign. Because previous surgery may substantially alter the anatomical location of the surrounding nerves, electrodiagnostic localization can be technically challenging and less reliable. Ultrasonography therefore played a key diagnostic role. The images demonstrated the normal sonoanatomy of the MABCN and its anatomical relationship with the basilic vein and ulnar nerve, followed by pathologic findings of focal enlargement of the posterior branch adjacent to postoperative scar tissue. These imaging features, together with a positive sonographic Tinel sign, supported the diagnosis of localized nerve irritation. Ultrasound-guided hydrodissection using 5% dextrose and methylcobalamin resulted in marked clinical improvement, with the Visual Analog Scale pain score decreasing from 9 to 2. This case is particularly illustrative because postoperative injury of the MABCN may mimic recurrent cubital tunnel syndrome yet typically produces purely sensory symptoms confined to the medial elbow region. Targeted ultrasonographic evaluation can reveal subtle postoperative nerve pathology and guide effective ultrasound-guided intervention. Full article

Pomegranate (Punica granatum L.) is a major fruit crop in tropical and subtropical regions, but changing climatic conditions—especially rising temperatures and intense solar radiation—are increasing physiological disorders. Sunburn, a key heat- and light-induced disorder, causes peel discoloration and tissue damage. This results in significant yield loss and reduced fruit quality. The objective of this study was to characterize sunburn-induced anatomical changes in the widely grown, highly sensitive Hicaznar cultivar in Türkiye, and to identify the optimal phenological stage for the application of sunburn-preventive practices. For this purpose, pomegranate fruit peels were fixed in FAA (Formalin–Acetic Acid–Alcohol) solution, embedded in paraffin blocks, and sectioned at a thickness of 5–7 µm. The sections were stained using the hematoxylin–eosin method and examined under a light microscope. The images captured with a digital camera wereanalyzed and revealed that sunburn damage in the pomegranate peel first appears in the cuticle layer, followed by disruption and fragmentation of the cutaneous and epidermal layers beneath it, and ultimately leads to damage of the parenchyma cells. Furthermore, Light microscopy showed that before visible discoloration, cells near the epidermis undergo phenolic accumulation, cell-wall thickening, and lignification, which are early indicators of sunburn. These microscopic changes provide early diagnostic features for detecting sunburn damage before external symptoms manifest. The study concluded that anatomical changes begin before the visible symptoms of sunburn appear on the fruit, and the most appropriate timing for applying preventive measures against sunburn has been identified. Light microscopy showed that before visible discoloration, cells near the epidermis undergo phenolic accumulation, cell-wall thickening, and lignification, which are early indicators of sunburn. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer diagnosed worldwide after basal cell carcinoma. CSCC represents a growing global public health challenge due to its higher potential of local invasion, recurrence, and metastasis. Incidence rates of cSCC are projected to increase due to rising exposures to risks factors. Ultraviolet light exposure is the primary cause, and lighter skin pigmentation, immunosuppressive conditions and skin phototype are the primary risk factors. CSCC typically presents as a red, scaly, flat lesion (in situ tumors) or a red, firm, raised lesion with scale or erosion (invasive tumors). Surgical excision remains the standard-of-care for localized cSCC and is often curative. Although, most patients achieve favorable outcomes, a subset of cSCC exhibits a highly aggressive and metastatic phenotype (postoperative recurrence rates are approximately 5%). Addressing the clinical challenge posed by these high-risk cases requires a more comprehensive understanding of the underlying molecular drivers. This review examines the interaction between transglutaminase 2 (TG2) and the G-protein-coupled receptor 56 (GPR56) as a pivotal driver of the aggressive cSCC phenotype. This molecular axis is particularly significant for its role in the maintenance of epidermal cancer stem (ECS) cells, which contribute to tumor progression and therapy resistance. While the definitive link between the TG2-GPR56 complex and systemic metastasis in cSCC is currently being elucidated, significant evidence from analogous malignancies and in vitro keratinocyte models provides a clear mechanistic roadmap for its involvement in tumor invasion. Full article

Multicentric reticulohistiocytosis (MRH) is a rare systemic histiocytic disorder of uncertain etiology characterized by papulonodular cutaneous lesions and potentially destructive polyarthritis, with variable multisystem involvement. Owing to its low prevalence, evidence for optimal management remains limited, and treatment responses are heterogeneous. Emerging reports suggest that Janus kinase (JAK) inhibition may provide benefit in refractory disease. We report a 60-year-old woman with MRH presenting with papulonodular skin lesions, symmetric polyarthritis, constitutional symptoms, and interstitial lung disease (nonspecific interstitial pneumonia pattern) in the context of co-existing primary biliary cholangitis and no evidence of malignancy. Prior therapies (glucocorticoids, methotrexate, leflunomide) achieved suboptimal control. Upadacitinib, a selective JAK1 inhibitor, induced rapid and complete remission of cutaneous and articular disease with improvement of pulmonary involvement. Secondary weight gain and incident diabetes were managed with tirzepatide. This case adds to the limited literature supporting JAK inhibition as a targeted option for refractory MRH, including multisystem disease with pulmonary involvement. Systematic evaluation of efficacy, durability, and safety is warranted. Full article

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. Although EGFR-TKIs can cause various adverse events (AEs), their profiles have not been fully elucidated in Thai patients. This study aimed to determine the incidence, characteristics, severity, and duration of the first AEs and to evaluate their association with tumor response in patients with NSCLC receiving EGFR-TKIs. Method: This retrospective cohort study was conducted at a super-tertiary care hospital in Thailand. Patients with NSCLC who received EGFR-TKIs between August 2021 and July 2024 were included. Descriptive statistics were used to summarize safety profiles and tumor response. The association between AEs and objective response was assessed using logistic regression. Results: A total of 187 patients were included in this study. Overall, 177 AEs were observed in patients receiving erlotinib, osimertinib, or gefitinib. The most common cutaneous AEs were rash (30.7%), xerosis (24.1%), and acneiform rash (19.3%), while diarrhea (20.3%) was the most frequent gastrointestinal toxicity. Most AEs were grade 1–2 and occurred within 1 month after treatment initiation. In multivariable logistic regression analysis, pruritus (OR 8.26, 95% CI: 1.00–67.75, p = 0.049) and treatment line (OR 0.27, 95% CI: 0.10–0.68, p = 0.006) were independently associated with objective response. Conclusion: Most of the AEs occurred early during EGFR-TKI therapy, with cutaneous reactions being the most common and generally mild to moderate. Pruritus and treatment line were independently associated with objective response, suggesting that pruritus may serve as a potential clinical indicator of treatment response and highlighting the importance of monitoring of the EGFR-TKI-related AEs during therapy. Full article

Background/Objectives: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, accounting for less than 1% of all breast tumors and approximately 2–3% of breast fibroepithelial tumors. They can be benign, borderline, or malignant, depending on cellular atypia and stromal invasion. Although most display local behavior, malignant forms can metastasize hematogenously, most frequently to the lungs, bones, and liver, with lymph node metastases being exceptional. Case Presentation: We analyzed the case of a 47-year-old woman with a phyllodes breast tumor weighing approximately 5 kg. The tumor evolved slowly over five years, followed by accelerated growth, cutaneous necrosis, superinfection, and severe anemia. Total mastectomy was performed, and histopathological examination confirmed the diagnosis of a malignant phyllodes tumor. Five months after surgery and adjuvant radiotherapy, the patient developed laterocervical metastases with thyroid invasion and life-threatening tracheal compression, an extremely rare presentation for this type of tumor in adults. Discussion/Conclusions: This case illustrates the aggressive and unpredictable behavior of malignant phyllodes tumors and underscores the necessity of careful oncological monitoring and a multidisciplinary approach, given their potential for dissemination to unusual locations. Full article