Medicine and Pharmacology

Abstract: Background: Picosecond laser-induced optical breakdown (LIOB), particularly when generated using a diffractive lens array, creates spatially confined photomechanical microinjury with limited nonspecific thermal damage. This review evaluates the role of LIOB in melasma and photoaging, with emphasis on the distinction between pigment fragmentation and regenerative tissue re-sponses. Preclinical and translational studies indicate that LIOB may promote extracellular matrix remodeling through TGF-β/Smad signaling while attenuating matrix-degrading and inflamma-tory pathways, including MMP-9 and NF-κB. Cellular-resolution full-field optical coherence to-mography (CRFF-OCT), coupled with computer-aided image analysis, offers a non-invasive ap-proach for longitudinal assessment of melanin morphology, the dermal–epidermal junction, col-lagen architecture, and treatment-related structural change. Hyperbranched polymer dots (HPDs) are additionally considered as experimental nanozyme-based adjuncts because of their antioxidant and regenerative properties; however, their relevance to melasma remains preclinical. Collec-tively, LIOB, quantitative optical biopsy, and bioactive nanomaterials provide a conceptual preci-sion-medicine framework for treating melasma as a chronic photoaging-associated disorder, alt-hough further prospective validation is required before these components can be integrated into routine care. Objectives: To critically synthesize the available clinical and preclinical evidence on LIOB for melasma and photoaging, evaluate CRFF-OCT as a potential tool for structural assess-ment and treatment monitoring, and describe the current translational evidence for HPDs as ex-perimental adjuncts. Methods: A structured literature search was conducted using PubMed, Sco-pus, ScienceDirect, and Google Scholar, supplemented by manual screening of reference lists. The principal search period covered January 2015 to May 2026, with earlier landmark publications considered when relevant. Eligible publications addressed the clinical applications, biological mechanisms, imaging assessment, or potential adjunctive approaches related to picosecond LIOB, melasma, photoaging, and skin remodeling. Clinical, translational, and experimental evidence was considered. Findings were synthesized qualitatively because of the heterogeneity of the in-cluded evidence, and no meta-analysis was performed. The last search date for this study was February 23, 2026. Results: A total of 37 studies are included in this review, and they emcompass experimental studies, cohorts, and literature reviews. Available data suggests that LIOB may promote extracellular matrix remodeling through transforming growth factor-β (TGF-β)/Smad signaling while modulating matrix-degrading and inflammatory pathways, including matrix metalloproteinase-9 (MMP-9) and nuclear factor kappa B (NF-κB), which are key pathways to treating melasma and photoaging. Computer aided optical confluence tomography, combined with computer-aided image analysis, offers a noninvasive approach for longitudinal assessment of melanin morphology, the dermal–epidermal junction, collagen architecture, and treatment-related structural changes. Hyperbranched polymer dots (HPDs) demonstrate experimental antioxidant and regenerative properties, although their application as adjuncts in melasma remains at the preclinical stage. Limitations: The studies included in this review may demonstrate heterogeneity, as a formal risk-of-bias assessment was not conducted. Further prospective clinical studies may be required to establish the efficacy and safety of nanozyme-based approaches to treatment. Con-clusion: LIOB is a promising approach for addressing melasma and photoaging in terms of uti-lizing pigment fragmentation and triggering regenerative tissue responses in melasma. To moni-tor treatment results non-invasively, CRFF-OCT may provide valuable structural biomarkers as a reference. HPDs are an emerging adjunct to treatment monitoring as well. Protocol registration: The review protocol was not prospectively registered in a publicly accessible systematic review registry. Funding: No specific funding was provided for this systemati review.

Abstract: Objective: To compare the patient-level dermoscopic feature of early facial seborrheic keratosis (SK) and verruca plana (VP) and to identify patterns that may assist their differentiation. Methods: This retrospective cross-sectional study included 118 patients with early facial SK (280 lesions) and 61 patients with facial VP (252 lesions) evaluated between December 2021 and May 2025.A patient was classified as positive for a dermoscopic feature if it was present in at least one evaluated lesion. Between-group comparisons were performed using two-sided Fisher’s exact tests, with Benjamini-Hochberg false discovery rate adjustment for 16 comparisons. Results: The most frequent dermoscopic features in the SK group were moth-eaten borders (66.9%), light brown pigmentation (58.5%), fingerprint-like structures (41.5%), and a homogeneous pseudo-network (39.8%). In the VP group, dotted vessels (95.1%), a pinkish background (91.8%) predominated, followed by a skin-colored to light brown background (49.2%), a dermatoglyphic pattern (44.3%), grayish-white structureless zones (42.6%), and pale yellow structureless areas (32.8%). After false discovery rate adjustment, all evaluated features differed significantly between groups except hairpin vessels (adjusted P=0.052; all other adjusted P< 0.01) Conclusion: Early facial SK and VP showed distinct patient-level dermoscopic profiles in this cohort. Combined assessment of border, pigment, vascular, and background features may aid differentiation when interpreted with clinical findings. Our research has demonstrated that dermoscopy is a valuable tool differentiating these two entities, which can be particularly challenging to distinguish by clinical manifestation alone in their initial stages.

Abstract: Deep learning systems have matched dermatologists on curated skin cancer image sets for almost a decade, but evidence from patient care has accumulated slowly and unevenly. This systematic review mapped where that evidence now sits along the translational continuum. A reproducible PubMed search run in August 2026 identified 656 records; after single-screener selection against pre-specified criteria and full-text assessment of 39 reports, 29 clinical-stage studies (prospective, controlled, or real-world evaluations of AI for cutaneous malignancy in patients) were included and staged as prospective standalone accuracy (n = 19), prospective clinician-with-AI use (n = 5), controlled evaluation (n = 1), or real-world deployment (n = 4). Risk of bias, appraised with QUADAS-2, ROBINS-I, or JBI tools, was high or serious in 24 studies, most often because of partial verification and preselected lesion spectra, and the certainty of every principal finding was low or very low (GRADE). No included study was a randomised trial with patient outcomes, and none reported stage at diagnosis, mortality, or overdiagnosis. Across modalities, sensitivity held up in prospective use, commonly above 90% at the pre-set operating point, while specificity fell to between 9% and 85% and was frequently lower than that of the clinicians it was compared against. Performance moved with acquisition hardware, lesion spectrum, and skin type, and one market-approved dermoscopic classifier reached areas under the curve of 0.54 to 0.62 in two Australian primary care studies. One product family progressed from prospective accuracy to national-pathway deployment under a conditional health technology recommendation, with human second reading overturning a large share of automated discharges. We argue that the reported specificity loss reflects safety-first operating points, spectrum preselection, and the choice of comparator rather than model failure alone, and propose readiness criteria linking each translational stage to the evidence needed before autonomous or primary-care use. The review followed PRISMA 2020, was not registered, and received no external funding.

Abstract: Background: Fractional lasers have emerging evidence for actinic keratosis (AK) treatment and keratinocyte carcinoma (KC) prevention. The practical guidance for their clinical use remains less clear. Existing studies vary in laser type, treatment settings, PDT protocol, patient population, and follow-up, making it difficult to translate the literature into a usable clinical approach. Objective: To develop a clinician-facing framework for selecting patients and sequencing fractional lasers with field-directed therapy for AKs and field cancerization. Methods: We reviewed 48 manuscripts on fractional laser monotherapy, ablative fractional laser-assisted photodynamic therapy (AFXL-PDT), laser-assisted drug delivery, mechanistic studies, and high-risk populations. Evidence was mapped into a stepwise clinical algorithm. Results: The proposed algorithm first excludes patients with isolated AKs, suspicious lesions requiring biopsy, active infection, poor wound healing risk, or inability to tolerate recovery. Patients with multiple or recurrent AKs, diffuse photodamage, prior KC, or high procedural burden may be considered for fractional laser-based field therapy. AFXL-PDT is favored for thicker lesions, extensive field disease, or immunosuppressed patients, while non-ablative fractional lasers may fit selected patients who prioritize tolerability, cosmetic improvement, and limited downtime. Illumination and incubation choices should reflect the tradeoff between clearance, pain, convenience, and durability. Follow-up at 6–9 months is suggested because field control is not indefinite. Conclusion: Fractional lasers are best viewed as field-directed or adjunctive tools, not replacements for biopsy or standard oncologic care.

Abstract: Composite cutaneous malformations may comprise histologically distinct components that occur in an organized association within the same anatomical region. Their coexistence raises the possibility of a shared developmental disturbance, although it does not, in itself, establish that their constituent cells share a common origin or genetic alteration. In this article, we propose the concept of an ectomesenchymal developmental field disorder to describe spatially organized anomalies involving two or more tissue components whose association may plausibly be related to neural crest-derived progenitors, ectomesenchymal derivatives, or established embryonic interactions between these cell populations and neighboring tissues. Three mechanisms are considered, which may operate independently or overlap: disruption of a common progenitor, early somatic mosaicism, and reciprocal signaling between genetically distinct cell populations. We review representative models associated with GNAQ/GNA11 and PIK3CA, neurovascular interactions observed in certain plexiform neurofibromas, and interactions between the neural crest and placodes. We also propose a hierarchy of evidence, ranging from mere anatomical coexistence to molecular and functional demonstration of the underlying mechanisms. This framework complements the concepts of malformation, hamartoma, mosaicism, and syndrome, while emphasizing that neither ectomesenchymal origin nor a causal relationship can be established solely on the basis of morphology or the detection of a genetic variant in non-microdissected tissue.

Abstract: Dysregulated sebum production is associated with epidermal barrier impairment, oxidative stress, and cutaneous inflammation. We investigated whether heat treatment enhances the physicochemical and biological activity of Haliotis discus hannai shell extract. Material heat-treated at 300°C (H300) showed calcite-associated structural reorganization and increased calcium release. In LPS/TNF-α-stressed HaCaT keratinocytes, H300 reduced caspase-3, reactive oxygen species, and monoamine oxidase B while increasing BCL-2, filaggrin, claudin-1, and heme oxygenase-1. EGTA partially attenuated these responses, supporting a calcium-associated mechanism. H300-derived keratinocyte-conditioned media reduced lipid accumulation and PPARγ/SREBP1-associated lipogenic responses in SZ95 sebocytes while enhancing PKA/HSL/AMPK-related signaling. In THP-1-derived macrophages, conditioned media reduced CD80-associated inflammatory activation and NO/iNOS while increasing CD206 and IL-10. In a 14-day blinded exploratory human skin application study (n = 23), topical H300 was associated with reduced redness and oiliness, increased hydration, and improved participant-reported skin condition compared with non-heated extract. These findings suggest that H300 modulates oxidative stress and cutaneous cellular crosstalk through a calcium-associated, keratinocyte-centered mechanism.

Abstract: Background: Inherited epidermolysis bullosa (EB) comprises monogenic disorders characterised by tissue fragility, recurrent blistering, chronic wounds and multisystem complications. Although multidisciplinary supportive care remains fundamental, it cannot correct the molecular defect or prevent cumulative tissue damage. This narrative review examines emerging disease-modifying therapies for inherited EB, emphasising their application in clinical practice. Methods: Pub-Med/MEDLINE was searched using terms relating to EB subtypes and pharmacological, gene-, RNA-, protein-, cell- and genome-editing therapies. Reference lists, clinical guidelines, consensus statements and regulatory documents were also examined. Clinical studies and preclinical investi-gations were synthesised qualitatively; no meta-analysis was performed. Results: Recent advances have expanded treatment beyond conventional wound care. Oleogel-S10 enhances endogenous wound healing independently of genotype, whereas beremagene geperpavec delivers functional COL7A1 copies directly to dystrophic EB wounds. Prademagene zamikeracel combines ex vivo correction of autologous keratinocytes with epidermal grafting, offering potentially sustained clo-sure of selected chronic wounds. Nevertheless, these treatments remain predominantly local and do not fully address generalised skin fragility or extracutaneous disease. Mesenchymal stromal cells, haematopoietic stem cell transplantation, recombinant type VII collagen, RNA-based treatments and genome editing may provide broader or more durable benefits, but evidence remains limited and concerns regarding delivery, safety, durability and accessibility persist. Conclusion: Precision and regenerative therapies are transforming EB management but remain complementary to multi-disciplinary supportive care. Clinical evaluation should extend beyond wound closure to include pain, function, growth, quality of life and caregiver burden. Long-term surveillance and personal-ised combination strategies are essential to determine whether early treatment can safely alter the natural history of EB.

Abstract: Acquired aquagenic syringeal acrokeratoderma (ASA) is a rare dermatological disorder characterised by transient oedematous papules and palmar wrinkling following water exposure. Multiple treatment modalities have been described, however evidence supporting effective therapies is limited. We report a case of a 21-year-old Indian male with a 2-year history of painful palmar wrinkling, tingling, and stinging occurring approximately 15 minutes after water exposure, with associated pruritus and peeling following prolonged immersion. Clinical findings were consistent with acquired ASA, and investigations excluded systemic disease. Initial treatment with topical 20% aluminium chloride was discontinued because of excessive dryness. Subsequent treatment with topical glycopyrronium bromide 2% spray produced a 50% reduction in symptom severity without adverse effects, with sustained improvement over 1.5 years. This favourable response supports current evidence for a pathogenic role for eccrine gland dysfunction and sweating in ASA and suggests that epithelial transmembrane channelopathy with sweat leakage may contribute to disease development. Treatments targeting these pathways may therefore be effective strategies and topical glycopyrronium bromide can be a therapeutic consideration in ASA. Further studies are needed to validate these mechanisms and establish optimal management strategies.

Abstract: Background/Objectives: Basosquamous carcinoma (BSC) is regarded as a high-risk keratinocyte carcinoma, yet reported recurrence and metastasis rates vary widely and may reflect tumor size, site and margin status rather than histotype itself. We describe the clinicopathological spectrum and course of BSC in an unselected single-institution cohort. Methods: Consecutive patients with a pathology-record diagnosis of BSC between January 2018 and December 2023 were identified. All cases were reviewed by a board-certified dermatopathologist, and clinical and histopathological variables were retrieved from pathology and clinical records. Results: Thirty-two patients (32 tumors, 33 specimens) were included. Mean age was 78.2 years, 25 tumors (78.1%) arose in the head and neck region, 23/29 (79.3%) measured <2 cm and mean depth of invasion was 2.5 mm. A micronodular component, pure or within a mixed pattern, was present in 21/32 tumors (65.6%), and the squamous component involved ≥50% of the tumor area in 21/32. Perineural invasion was documented in 3/32 tumors (9.4%) and margin involvement in 4/31 excisions (12.9%). Over a median follow-up of 3.7 years, no histologically confirmed local recurrence and no metastases were observed. Conclusions: in our series, BSC followed a favorable course despite adverse histological features, supporting a risk-adapted interpretation of prognosis based on established clinicopathological risk factors rather than on histotype alone.

Abstract: Background/Objectives: Acute urticaria (AU) is generally self-limiting, but prospective data on its natural course and progression to chronic urticaria (CU) remain limited. To characterize the natural course of AU, determine the proportion of patients progressing to CU, and explore baseline clinical characteristics associated with subsequent progression. Methods: We conducted a prospective ob-servational study of 247 consecutive patients with physician-diagnosed AU presenting to a tertiary university emergency department. Patients were assessed at the index visit and followed at Day 15 ±1 and Day 45 ±1. Total disease duration was calculated from original symptom onset, and CU was defined as recurrent wheals and/or angioedema persisting for ≥6 weeks. Baseline associations with CU progression were explored with correction for multiple comparisons. Results: Overall, 229/247 patients (92.7%) achieved remission before 6 weeks and 18/247 (7.3%) progressed to CU. Among patients achieving remission, median episode duration was 7 days (IQR, 2–13); 78.6% and 96.1% achieved complete resolution within 14 and 28 days, respectively. Patients progressing to CU had longer symptom duration before emergency department assessment than those achieving remission (median, 144 vs 8 hours; FDR-adjusted p=0.001), although this reflected prior disease persistence and was not considered an independent prognostic factor. No other baseline characteristic remained significantly associated with CU progression after multiple-comparison correction. Conclusions: AU was predominantly self-limiting, with most patients achieving remission within the first weeks after symptom onset and 7.3% progressing to CU. These findings provide prospective data on the natural course of AU and the transition from acute to chronic disease. Further identification and validation of clinical and biological markers associated with disease persistence may support per-sonalized risk assessment and individualized follow-up.

Abstract: Androgenetic alopecia (AGA) is mainly characterized by androgen-dependent follicular miniaturization. However, increasing evidence suggests that inflammation, fibrosis and vascular changes may also affect the follicular microenvironment. This review summarizes the normal vascular and cellular regulation of the hair follicle and discusses how these processes may be altered in AGA. Human studies have identified perifollicular inflammation, reduced perfusion and changes in angiogenesis-related genes, but their causal roles remain unclear. Experimental studies further show close communication among dermal papilla cells, endothelial cells, immune cells and hair follicle stem cells. Current treatments mainly reduce androgen signaling or stimulate hair growth and may not fully address these microenvironmental changes. Emerging approaches, including anti-inflammatory treatments, nitric oxide and VEGF-based systems, microneedles, hydrogels and nano-enabled delivery, may regulate several pathways at the same time. However, most of these strategies remain preclinical. Future studies should clarify whether inflammation and vascular dysfunction are causes or consequences of follicular miniaturization and determine whether targeting these pathways can improve clinical outcomes in AGA.

Abstract: Background: Over-the-counter dietary supplements are commonly used by patients undergoing surgical procedures, but their perioperative effects are often incompletely characterized. S-adenosylmethionine (SAMe) is a widely available supplement used for several conditions, yet its potential effects on hemostasis and perioperative bleeding remain poorly understood. Objective: To map the available clinical and mechanistic evidence regarding SAMe, its related metabolic pathways, and potential effects on hemostasis and perioperative bleeding. Methods: We conducted a PRISMA-guided scoping review of PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov. Studies evaluating SAMe or related components of one-carbon metabolism in relation to perioperative bleeding, coagulation, platelet function, endothelial function, or other physiologic pathways relevant to hemostasis were considered. Conclusions: No human clinical evidence directly linking SAMe supplementation to perioperative bleeding was identified. Existing literature provides limited mechanistic evidence that SAMe and related one-carbon metabolic pathways may influence physiologic processes relevant to hemostasis, but these findings do not establish an association with surgical bleeding. Further clinical and mechanistic studies are needed to characterize the perioperative safety of SAMe.

Abstract: Background: Atopic dermatitis (AD) is generally considered polygenic but may occur as a predominant manifestation of inborn errors of immunity (IEI). Although dupilumab is effective in pediatric AD, evidence in IEI-associated severe atopic skin disease remains limited, with no longitudinal comparative studies available. We aimed to characterize clinical phenotype and compare effectiveness, quality-of-life, and safety of dupilumab in pediatric patients with severe polygenic AD and IEI-associated severe atopic skin disease. Methods: This multicenter retrospective observational study within the Italian Society of Pediatric Research Network included children and adolescents who initiated dupilumab before 18 years of age. Given IEI rarity, we accepted a numerically unbalanced but clinically meaningful cohort. Clinical outcomes were assessed longitudinally using EASI, pruritus NRS, and CDLQI scores. Achievement and maintenance of EASI-50/75/90 re-sponses were evaluated, together with adverse events and treatment discontinuation. Results: Among 127 patients, 116 had polygenic AD and 11 had IEI-associated disease. IEI patients more frequently had disease onset within 6 months (64% vs. 29%; p=0.037), severe recurrent infections (100% vs. 0%; p< 0.001), very elevated sIgE (91% vs. 14%; p< 0.001), and higher baseline EASI (median 50 vs. 25; p< 0.001). EASI, pruritus, and CDLQI improved significantly over time. EASI-50/75/90 were achieved by 88.2%/81.9%/66.1% and maintained by 84.3%/69.3%/47.2%. IEI patients showed steeper EASI decline but achieved EASI-75/90 later. Dupilumab was well tolerated with no unexpected safety signals. Conclusions: Dupilumab provided rapid, sustained improvement across both groups. Despite greater baseline severity and slower deep clearance achievement, IEI patients demonstrated substantial durable benefit, supporting dupilumab use in selected IEI-associated atopic manifestations.

Abstract: (1) Background: Herpes zoster results from reactivation of latent varicella-zoster virus and may cause serious complications. Although traditionally considered nonseasonal, recent studies have reported summer peaks in herpes zoster occurrence. Given these inconsistencies, this study evaluated monthly and seasonal variations in herpes zoster case rates and their implications for prevention. (2) Methods: In this retrospective cross-sectional study, the medical records of patients diagnosed with herpes zoster at a dermatology outpatient clinic between January 2017 and December 2025 were reviewed. Data on age, sex, and the year, month, and season of diagnosis were collected and analyzed using IBM SPSS Statistics for Windows, version 30.0. (3) Results: The highest proportion of herpes zoster cases occurred in patients aged 60–69 years. Visit-adjusted case rates did not differ significantly across months or seasons. A significant increasing trend in herpes zoster case rates was observed from 2020 to 2025. (4) Conclusions: Herpes zoster is a vaccine-preventable disease that may cause serious complications and shows an increasing trend in occurrence. Our findings suggest that herpes zoster does not exhibit a distinct seasonal pattern and occurs throughout the year, supporting the importance of maintaining year-round preventive strategies, including vaccination.

Abstract: Hair-follicle function depends on coordinated interactions among endocrine signaling, hair-shaft synthesis, inflammatory and redox regulation, cellular metabolism, vascular support, and regenerative capacity. This narrative review synthesizes current biological and clinical evidence within four interconnected domains of follicular function: (I) hormonal regulation, (II) structural integrity, (III) inflammatory-redox homeostasis, and (IV) metabo-lic-regenerative competence. The proposed Four-Pillar Model of Hair Health integrates these domains into a biologically grounded and clinically oriented framework for interpre-ting hair-loss phenotypes, patient-specific vulnerabilities, and therapeutic interventions. Each pillar represents a distinct but functionally interconnected requirement of follicular biology: regulation of growth and miniaturization, formation and maintenance of a struc-turally competent hair shaft, adaptation to inflammatory and oxidative stress, and preser-vation of the energetic, vascular, and regenerative processes required for repeated hair cycling. Their integration reflects the systems-level nature of follicular function, in which disturbances within one physiological domain may influence the functional state and adap-tive capacity of others. Nutraceutical interventions provide a clinically relevant example of this systems-oriented perspective. For selected compounds and formulations, mechanistic evidence and human clinical observations converge to support therapeutic potential within defined physiological domains, with reported effects on outcomes including hair shedding, density, count, growth, shaft characteristics, and perceived hair quality. Evidence strength nevertheless differs among compounds, formulations, doses, routes of administration, and patient popu-lations. Multi-domain activity should therefore not be equated with clinical efficacy, and therapeutic interpretation requires compound-specific evidence, consideration of baseline nutritional and biological status, safety, and demonstration of meaningful human hair out-comes. Within this framework, follicular resilience is conceptualized as an emergent systems pro-perty reflecting the capacity of the hair follicle to maintain or restore growth, structural and functional integrity, adaptive responses, and regenerative competence under biological stress. The Four-Pillar Model consequently provides a practical structure for connecting pa-tient-specific biology, diagnosis, evidence-based intervention, and longitudinal clinical outcomes. The available evidence supports the biological relevance of all four domains and demonstrates clinically relevant therapeutic signals for selected interventions. Prospective studies should now determine the additional value of their systematic integration for biolo-gical phenotyping, individualized treatment selection, and sustained hair-related outco-mes. The Four-Pillar Model therefore provides a testable foundation for a more biologically informed, individualized, and systems-oriented approach to hair health.

Abstract: Background/Objectives: Pruritus and depression are established contributors to sleep impairment in psoriasis, yet most studies assess pruritus using unidimensional intensity scales such as the Visual Analogue Scale (VAS). Whether a multidimensional pruritus instrument explains sleep impairment beyond conventional intensity measures has not been directly tested. This study compared the explanatory value of the multidimensional 5-D Itch Scale and unidimensional VAS for sleep impairment in psoriasis, identified independent predictors of sleep quality, and compared sleep, depression, and quality of life between patients with psoriasis and matched controls. Methods: This cross-sectional case-control study enrolled 63 patients with psoriasis and 63 matched controls at a tertiary center in Turkey (2023–2024). Assessments included the PSQI, BDI, DLQI, PASI, VAS, and 5-D Itch Scale. Multivariable and hierarchical re-gression identified independent predictors of PSQI and compared the 5-D Itch Scale against VAS, adjusting for BDI, PASI, BMI, and smoking status. Results: Patients had higher PSQI (median 6.0 vs 4.0; p=0.001), BDI (8.0 vs 6.0; p=0.015), and DLQI scores (15.0 vs 2.0; p< 0.001). Poor sleep quality (PSQI ≥5) occurred in 58.7% of patients versus 36.5% of controls. BDI (standardized β=0.643, p< 0.001) and the 5-D Itch Scale (β=0.315, p=0.002) were independently associated with PSQI after adjustment (ad-justed R²=0.599). Substituting VAS reduced model fit (adjusted R²=0.533); VAS was not significant (p=0.391). The 5-D Itch Scale explained significant additional PSQI variance beyond VAS (ΔR²=0.064, p=0.003). Conclusions: Depression and pruritus assessed with a multidimensional instrument were independently associated with sleep impairment. The 5-D Itch Scale provided significant explanatory value beyond VAS, supporting multidimensional pruritus assessment in psoriasis.

Abstract: The rapid integration of artificial intelligence (AI) and machine learning into medicine has launched a transformative epoch in dermatology, a specialty traditionally anchored in visual pattern recognition. While early machine learning research focused primarily on binary diagnostic classification, contemporary advancements have given rise to the para-digm of Synthetic Dermatology. This paradigm uses deep generative models such as Gen-erative Adversarial Networks (GANs) and Latent Diffusion Models (LDMs) together with personalized digital avatars, clinical large language models (LLMs), and multimodal tensor decompositions to synthesize complex clinical and histopathological images, gen-erate structured patient vignettes, and model real-world clinical trajectories. Herein, we review the state-of-the-art applications of synthetic technologies across three fundamental domains: clinical practice, dermatological research, and medical education, with a focus on personalizing dermatological care. By bridging the current clinical realities of hu-man-AI collaboration with a visionary perspective of the next decades, we outline how synthetic methodologies can mitigate data scarcity, address ethnic disparities in algo-rithmic diagnostics, optimize therapeutic regimens via cutaneous digital twins, and rede-fine student curricula. Finally, we critically appraise the technical, ethical, and regulatory hurdles that must be resolved to ensure the safe, equitable, and responsible translation of synthetic dermatology to patients.

Abstract: Periorbital hyperpigmentation (POH), commonly known as dark circles, is a highly prevalent, benign cosmetic concern with a heterogeneous etiology spanning constitutional (pigmentary), vascular, post-inflammatory, and structural (shadow/volume-loss) subtypes, which frequently coexist in the same patient. This narrative review draws on a literature search (PubMed, Cochrane Central and Google Scholar, conducted in September 2026) identifying 102 relevant sources spanning 1995–2026, of which 66 are directly cited, summarizing the evidence for each major treatment category, topical/cosmeceutical agents, chemical peels, laser and light-based devices, micro-needling, platelet-rich plasma (PRP), platelet-rich fibrin, carboxytherapy, dermal fillers, and autologous fat/nanofat grafting, organized around the presumed etiological subtype being treated. This review is an etiology-based framework to critically synthesize the treatment literature and distinguish replicated comparative evidence from isolated comparisons. Although improvement has been reported with many modalities, certainty remains limited by small samples, heterogeneous outcomes, inconsistent etiological classification, and short follow-up. We highlight replication of comparative trials with standardized outcome measures as the field's most pressing need.

Abstract: Background and Clinical Significance: Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus and disproportionately affects older adults. Antiviral therapy and systemic analgesia are well established, but local wound care of the eroded skin remains largely empirical: no dressing has been validated in controlled trials for this indication, and denuded HZ lesions are frequently mismanaged with dry gauze that adheres to the wound bed and aggravates pain. Case Presentation: An 85-year-old man with no known chronic disease presented with a one-week history of thoracic HZ unresponsive to outpatient antiviral therapy, requiring admission for uncontrolled pain (9/10 on the Numeric Rating Scale, NRS), vomiting, asthenia, and hyporexia. Examination revealed confluent, superficial-partial-thickness erosions across the T6–T8 dermatomes (12.5 × 24 cm). After a negative wound culture, a single polylactic-acid-based membrane (Suprathel®250) was applied over the entire denuded area. Pain fell from 9/10 to 2/10 on the NRS within seven days, the membrane fully resorbed with complete re-epithelialization by day 12, and the patient resumed independent daily activities by the third week without scarring. Conclusions: A polylactic acid membrane produced rapid pain relief and complete wound closure after a single application in an extensive HZ lesion, comparing favorably with published outcomes for hydrocolloid dressings and standard gauze-based care. Synthetic skin substitutes deserve controlled evaluation as a dedicated wound-care option for HZ, particularly for patients with extensive dermatomal involvement or poor tolerance of conventional dressings.

Abstract: Topical vitamin D analogs are well-established therapies for psoriasis, but their broader dermatologic potential increasingly depends not only on their biological activity but also on the ability of topical formulations to achieve effective and localized cutaneous delivery. This narrative review critically examines the emerging use of calcipotriol, tacalcitol, and calcitriol beyond psoriasis, with particular emphasis on formulation strategies, cutaneous drug delivery, and their relationship with clinical performance. Conventional topical dosage forms, including ointments, creams, and solutions, remain the principal delivery systems used in clinical studies. Their therapeutic performance is influenced by vehicle composition, skin-barrier integrity, local retention, application conditions, and the physi-cochemical properties of the vitamin D compound, which collectively determine cutaneous penetration, tolerability, and systemic exposure. Across the reviewed indications, formula-tions and treatment protocols vary considerably, contributing to heterogeneity in clinical outcomes. Vitiligo currently presents the strongest clinical evidence, particularly when topical vitamin D analogs are combined with narrowband ultraviolet B phototherapy, whereas encouraging results have been reported for morphea, acne vulgaris, and inherited ichthyoses. Evidence for atopic dermatitis, alopecia areata, and basal cell carcinoma re-mains limited or inconsistent. Beyond conventional vehicles, emerging delivery technolo-gies including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, hydrogels, and microneedle-assisted systems offer op-portunities to enhance skin targeting, improve local drug retention and reduce systemic exposure. However, evidence specifically evaluating these advanced systems for vitamin D analogs remains predominantly preclinical. Future research should integrate clinical evaluation with formulation optimization, cutaneous pharmacokinetics, and comparative delivery studies, as accumulating evidence suggests that formulation-dependent skin de-livery may be a critical determinant of therapeutic success beyond psoriasis.