Medicine and Pharmacology

Abstract: While anti-PD-1 immunotherapy has led to significant improvements in the outcome of advanced cutaneous squamous cell carcinoma (cSCC), over half of patients fail to respond, and there remains no established second line therapy. Here we present a systematic review of the literature and ongoing clinical trials to evaluate current evidence on treatment strategies in this setting. Following a comprehensive search, we identified 22 studies that were included in the final review. Data from the reported studies were compiled into the largest analysis on this topic to date, comprising 130 patients. Overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were compared using Fisher’s exact tests. Median progression free survival (PFS) and overall survival (OS) were pooled using a sample-size–weighted approach. Although the review is limited by small sample sizes and the frequent use of combination rather than monotherapy regimens, the evidence suggests that epidermal growth factor receptor (EGFR) inhibition represents the current best treatment strategy for advanced cSCC following anti-PD-1 failure, supported by favourable reported outcomes including ORR, PFS and OS. Other treatment strategies including ipilimumab and oncolytic therapy show clinical promise warranting further investigation.

Abstract: Background/Objectives: Systemic corticosteroids remain pivotal in the management of moderate-to-severe inflammatory and autoimmune dermatoses, yet contemporary Indian data linking prescribing behaviour with patient-reported outcomes, adverse drug reaction (ADR) profiling and guideline concordance are sparse. We evaluated prescription patterns, effectiveness, quality of life, ADRs, adherence and concordance with the Indian Council of Medical Research (ICMR) Standard Treatment Workflows (STW) 2022. Methods: In a six-month prospective observational study at a Western Indian tertiary-care teaching hospital, adult (≥18 years) dermatology outpatients started on any systemic corticosteroid were reviewed at baseline and day 30. Disease-specific severity indices (PDAI, BPDAI, CLASI, EASI, LPSI, SALT, SCORAD, VASI) and the Dermatology Life Quality Index (DLQI) captured effectiveness; ADRs were graded per episode using the WHO–UMC causality scale; adherence was measured with the 5-item Medication Adherence Report Scale (MARS-5). Results: Of 82 patients enrolled (mean age 42.4 ± 14.9 years; 58.54% female), 76 (92.68%) completed follow-up. Eczematous dermatitis (23.17%), immunobullous disorders (21.95%) and papulosquamous disorders (12.20%) predominated. Oral Prednisolone accounted for 63.41% of prescriptions, and 80.49% carried a documented taper. Improvement occurred in 56/76 (73.68%), and mean DLQI fell by 9.62 points (57.06%; p < 0.001), with disease-specific severity indices showing mean reductions ranging from 20.42% (VASI, vitiligo) to 59.08% (SCORAD, atopic dermatitis). ADRs affected 11/82 patients (13.41%) across 14 episodes, of which 71.43% were mild. High adherence (MARS-5 = 25) was reported by 76.32%. Overall ICMR STW 2022 concordance was 67.80% (40/59); recurring deviations were drug selection (8/59; discoid lupus erythematosus, moderate eczema, urticaria), missing baseline random blood glucose documentation (12/59, 20.34%), non-concordant tapering regimens (9/59, 15.25%) and dose non-concordance (8/59, 13.56%). Conclusions: Systemic corticosteroid prescribing was broadly consistent with ICMR STW 2022, with satisfactory tapering documentation, encouraging short-term efficacy, an acceptable ADR profile and high self-reported adherence. Deviations clustered in three actionable areas — drug selection in discoid lupus erythematosus, moderate eczema and urticaria; dose- and taper-regimen concordance; and pre-treatment metabolic screening (random blood glucose) — providing concrete targets for departmental educational intervention. Larger multicentre studies with longer follow-up are warranted.

Abstract: Skin biopsy is one of the most valuable diagnostic procedures in dermatology, particularly when clinical findings alone are insufficient to establish a diagnosis. However, obtaining an accurate histopathological diagnosis depends on multiple steps, and errors at any stage of the biopsy pathway may compromise the final result. This review synthesizes current evidence and available guidelines on best practices for skin biopsy, integrating the practical experience of four internationally recognized dermatopathologists to address areas where evidence is limited or poorly standardized. The review covers biopsy planning, selection of the optimal biopsy site and technique, specimen handling and fixation, grossing and laboratory processing, prevention of technical artifacts, the use of ancillary diagnostic techniques, and clinicopathological correlation, with particular attention to challenging anatomical sites and complex diseases. Diagnostic accuracy depends on obtaining a representative specimen, maintaining high technical standards throughout tissue processing, providing adequate clinical information, and ensuring close communication between the clinician and the dermatopathologist. In selected cases, multidisciplinary review is required to reach a definitive diagnosis. Adherence to these principles can optimize diagnostic yield, reduce avoidable errors, and ultimately improve patient care.

Abstract: Background: Hair loss is one of the most common reasons patients seek dermatologic evaluation. Although clinical examination and trichoscopy establish the diagnosis in most cases, scalp biopsy remains essential when findings are inconclusive, when cicatricial alopecia is suspected, or when histopathologic documentation is required before systemic therapy. Methods: This narrative review synthesizes evidence from PubMed/MEDLINE and Embase on the indications, biopsy site selection, sampling technique, specimen processing, and histopathologic interpretation of scalp biopsy in alopecia. Results: Diagnostic yield depends on appropriate patient selection, trichoscopy-guided site selection, meticulous sampling, and optimal processing. A 4-mm punch oriented parallel to the hair shafts and extending into the subcutaneous fat, combined with horizontal and vertical sectioning (HoVert or Tyler technique), allows the most comprehensive assessment of follicular architecture. Histopathology reliably separates scarring from nonscarring alopecia and, in cicatricial forms, classifies disease by the predominant inflammatory infiltrate following the NAHRS scheme. Ancillary studies, including direct immunofluorescence, periodic acid-Schiff staining, elastic fiber stains, and microbiologic cultures, are applied selectively when clinically indicated. Conclusions: Integrating clinical, trichoscopic, and histopathologic findings improves diagnostic accuracy and guides therapeutic decisions. Close collaboration between the dermatologist and dermatopathologist maximizes the diagnostic value of scalp biopsy.

Abstract: Background: With changes in lifestyle and increased psychological stress, the incidence of hair disorders has risen, creating an urgent clinical need for non-invasive and highly effective diagnostic and therapeutic methods. Ultrasound, with its advantages of being non-invasive, real-time, reproducible, and capable of deep imaging, has become a key technology for the auxiliary diagnosis and treatment of hair disorders. This article systematically reviews the basic principles of ultrasound diagnosis and treatment, summarizes the diagnostic value of high-frequency ultrasound in hair disorders, and elaborates on the principles underlying the application of focused ultrasound in the treatment of hair disorders. Methods: By searching databases such as PubMed, Web of Science, and OVID-MEDLINE, we included relevant original studies, reviews, and clinical guidelines on the application of ultrasound in hair disorders published over the past decade to conduct a narrative review. Results: High-frequency ultrasound can clearly display the structures of various scalp layers, hair follicle morphology, hair shaft echopatterning, and blood flow perfusion characteristics. It enables early assessment of hair follicle miniaturization, inflammatory infiltration, and lesion characteristics, thereby overcoming the limitations of dermatoscopy—which can only observe the surface—and invasive histopathology. Focused ultrasound not only precisely ablates pathological tissue but also synergizes with microbubble carriers to enhance the transdermal delivery efficiency of hair-growth agents such as minoxidil and gene therapies. Conclusion: Ultrasound shows significant potential in the non-invasive diagnosis, staging, efficacy monitoring, and targeted treatment of hair disorders; however, current challenges include high operator dependency, a lack of standardized parameters, and insufficient high-quality evidence-based research. Future large-sample, multicenter randomized controlled trials are needed to establish appropriate ultrasound frequencies, energy doses, and treatment protocols for different hair disorders, thereby promoting the standardized clinical translation and widespread application of ultrasound technology in hair medicine.

Abstract: Background/Objectives: Wound healing relies on oxygen availability and controlled reactive oxygen species (ROS) signaling. Excessive ROS hinder repair, whereas low, sustained levels promote angiogenesis, antimicrobial defense, and tissue regeneration. Oxygen-enriched oleic matrices (OEOMs), generated by ozonating vegetable oils, combine a moist lipidic environment with continuous ROS and pH modulation. This review summarizes their mechanisms and clinical applications. Methods: We analyzed preclinical and clinical studies addressing the chemistry, mode of action, and translational use of OEOMs. Evidence was appraised across burns, surgical wounds, oncologic settings, pediatrics, and chronic ulcers. Results: Ozonation stabilizes oleic acid into gel-like matrices that act as wound barriers while releasing hydrogen peroxide, oxygen, and fatty acids. These mechanisms reduce microbial growth, lower pH, and support keratinocyte and fibroblast activity. Clinically, OEOMs accelerate healing, reduce pain, and improve outcomes in burns, oral ulcers, and Stevens–Johnson syndrome. Postsurgical applications—including hidradenitis suppurativa and pilonidal sinus disease—show improved closure, scar quality, and lower recurrence. In oncologic and reconstructive surgery, OEOMs decrease pain, enhance satisfaction, and facilitate outpatient care. Chronic leg ulcers demonstrate granulation, re-epithelialization, pain reduction, and absence of infections. Most studies are case series or small cohorts, with consistent safety and tolerability. Conclusions: EOMs provide combined antimicrobial and pro-regenerative effects across diverse wound types. Current evidence supports their role as innovative wound dressings, though larger randomized trials are needed to validate efficacy and cost-effectiveness.

Abstract: Background/Objectives: Cutaneous T-cell lymphomas (CTCL), most commonly mycosis fungoides and Sézary syndrome, are rare non-Hodgkin lymphomas. Advanced disease responds poorly to current treatments, highlighting the need for new molecularly tar-geted therapies. WEE1 is a central regulator of the G2/M checkpoint and S-phase progression and has emerged as a therapeutic target in several malignancies, yet it has not been systematically explored in CTCL. Methods: We screened a library of more than 2,200 kinase inhibitors in CTCL cell lines and selected adavosertib for further study. Its effects were tested in four CTCL lines, in primary keratinocytes and fibroblasts, in patient-derived malignant CD4⁺ T cells and healthy donor CD4⁺ T cells, and in a MyLa xenograft model, using viability, apoptosis, cell-cycle, western blot, and phospho-protein array assays. Results: Adavosertib reduced viability at submicromolar IC₅₀ values (0.26–0.56 µM) across all four CTCL lines while largely sparing primary skin cells and was more active in malignant than in healthy donor CD4⁺ T cells. It induced apoptosis and cell-line-specific S-phase and/or G2/M accumulation, lowered WEE1 and phospho-CDK1 (Tyr15), and increased phospho-H2A.X. A phospho-protein array showed activation of checkpoint and stress signalling. In vivo, adavosertib slowed MyLa xenograft growth. Conclusions: These preclinical data identify WEE1 as a therapeutic target in CTCL and support further preclinical and early-phase clinical evaluation of adavosertib in this disease.

Abstract: Androgenetic alopecia is a progressive hair loss disorder characterized by reduced hair density and hair follicle miniaturization. Autologous blood concentrates, including platelet-rich plasma, platelet-rich fibrin, and concentrated growth factors, are increasingly utilized for wound healing and hair restoration. However, despite extensive clinical evidence, these therapies still lack a unified conceptual framework, and their underlying molecular mechanisms remain to be fully elucidated. This review summarizes the gradual optimization of platelet concentrates, while proposing extracellular vesicles as a potential key mediator in next-generation platelet concentrates. Moreover, we define the four core principles of “Instant Autologous Regenerative Medicine” and discuss the current limits and research priorities. This unifying framework will facilitate the development, standardization, and broader clinical application of point-of-care regenerative therapies.

Abstract: Background and Objectives: Rosacea is a chronic inflammatory facial dermatosis in which sensory symptoms can be as clinically important as visible erythema or inflam-matory lesions. In a subset of patients, facial dysesthesia, burning, stinging, warmth, pru-ritus, flushing, and marked trigger sensitivity dominate the disease burden and may im-pair quality of life. This narrative review aimed to reposition neurogenic rosacea as a sen-sory-predominant and translationally relevant presentation within the rosacea spectrum. Materials and Methods: A narrative literature review was conducted using Pub-Med/MEDLINE, Scopus, Web of Science, and Google Scholar through June 2026. Search terms combined rosacea, neurogenic rosacea, neuropathic rosacea, facial dysesthesia, sensory symptoms, neurogenic inflammation, mast cells, transient receptor potential channels, neuropeptides, and therapeutic approaches. Clinical, experimental, and trans-lational articles in English were selected according to relevance to the clinical phenotype, proposed mechanisms, and mechanism-based management. Results: Current clinical, experimental, and translational evidence supports a biologically plausible neurovascu-lar-immune framework linking sensory symptoms, trigger sensitivity, TRP-channel acti-vation, neuropeptide signaling, mast-cell activation, LL-37-MRGPRX2 signaling, and protease-dependent amplification in neurogenic rosacea. Conclusions: Neurogenic rosacea is best regarded as a clinically useful but incompletely validated senso-ry-predominant presentation. Its significance for clinicians and researchers lies in bridg-ing clinical symptoms such as patient-reported facial dysesthesia and quality-of-life im-pairment with plausible neurovascular-immune mechanisms and emerging therapeutic strategies. Standardized diagnostic criteria, validated symptom and quality-of-life measures, disease-relevant biomarkers, and phenotype-stratified trials are needed before neuromodulatory, mast-cell-directed, vascular-targeted, or combination approaches can be recommended as established phenotype-specific therapy.

Abstract: Cannabis sativa and Curcuma longa have traditionally been used for the management of skin disorders; however, scientific evidence supporting their combined topical use in eczema and psoriasis remains limited. To characterize the phytochemical composition, evaluate the biological activities, investigate potential molecular mechanisms, and assess the preliminary clinical performance of a topical herbal cream containing C. sativa and C. longa extracts. Ethanolic extracts were analyzed using UHPLC and GC-MS. Antioxidant, antibacterial, cytotoxicity, and nitric oxide inhibition assays were performed. Molecular docking studies were conducted against inflammation-related protein targets. A pilot clinical study evaluated the effects of the herbal cream in patients with eczema and psoriasis over four weeks using EASI, PASI, and DLQI scores. The herbal formulation contained cannabinoids, terpenoids, and curcuminoids with measurable antioxidant activity. The extract exhibited low cytotoxicity and moderate inhibition of nitric oxide production in LPS-stimulated macrophages. Docking analyses suggested favorable interactions between selected phytochemicals and inflammation-associated targets. Preliminary clinical observations indicated improvements in EASI, PASI, and DLQI scores among study completers. The herbal cream demonstrated antioxidant and anti-inflammatory properties and showed preliminary clinical potential in inflammatory skin disorders. Larger controlled clinical studies are required to confirm efficacy and establish therapeutic value.

Abstract: Subungual tumors are rare and often misdiagnosed, leading to unnecessary procedures or delayed treatment; thus, accurate identification of benign neoplasms such as fibrolipoma is essential to guide appropriate management. We report a 59-year-old man who presented with a several-year history of a painless subungual mass of the right great toe with progressive nail thinning and onychodystrophy. Imaging demonstrated soft-tissue swelling without bone involvement. Surgical exploration revealed two well-demarcated, lobulated subungual and periungual masses that were completely excised. Histopathology showed mature adipocytes with fibrous septa, and fluorescence in situ hybridization confirmed HMGA2 translocation without MDM2 or CDK4 amplification, establishing the diagnosis of fibrolipoma. Complete excision resulted in satisfactory nail regrowth at 1-year follow-up with no recurrence. This case highlights the importance of including fibrolipoma in the differential diagnosis of subungual masses and supports the value of histopathological and molecular analysis in achieving precise diagnosis and optimal surgical outcomes.

Abstract: Background: Hair shedding, reduced perceived hair density, brittle hair prone to falling, and scalp discomfort are common concerns in women. Objective instrumental methods such as digital phototrichogram can quantify hair density, anagen/telogen ratio, and hair shaft diameter, while scalp hydration, transepidermal water loss (TEWL), and sebum measurements can characterize scalp barrier status. Objective: To evaluate the efficacy of a 2% Oleosome-FGF-2 fusion extract scalp serum compared with placebo on hair density, anagen/telogen ratio, hair shaft thickness, and scalp biophysical parameters over 84 days. Methods: This randomized, single-blind, placebo-controlled pilot study enrolled 40 healthy female volunteers with telogen effluvium and/or brittle hair prone to falling out, ideally with dry or sensitive scalps. Participants received either 2% Oleosome-FGF-2 fusion extract Scalp Treatment (Serum A; n=20) or placebo scalp treatment (Serum B; n=20) and applied the product twice daily to the scalp for 84 days. Assessments were performed at baseline (T0), day 28 (T28), day 56 (T56), and day 84 (T84). Instrumental endpoints included anagen/telogen ratio, hair density, and shaft thickness using C-CUBE Pixience digital imaging, scalp hydration by Corneometer CM825, TEWL by Nano-Tewameter TM300, and sebum level by Sebometer SM815. Clinical hair-density scoring was performed at T0 and T84 using a 5-point Likert scale aligned with Ludwig-type clinical assessment. Results: At T84, Serum A increased anagen/telogen ratio by 17.0% versus -2.6% with placebo, hair density by 33.5% versus 7.2%, hair shaft thickness by 10.6% versus -1.6%, and scalp hydration by 22.2% versus -2.9%. Serum A reduced TEWL by 27.2% versus a 9.2% reduction with placebo and reduced sebum level by 30.2% versus a 2.7% increase with placebo. Between-group comparisons favored Serum A for anagen/telogen ratio at T56 and T84, hair density at T28, T56, and T84, hair shaft thickness at T84, TEWL at T56 and T84, sebum at T56 and T84, and clinical hair-density assessment at T84. Hydration differed significantly between groups at baseline and at all post-baseline time points. Clinical hair-density scores improved in 90% of Serum A participants and 35% of placebo participants at T84. Conclusion: In this exploratory randomized placebo-controlled pilot study, twice-daily use of a 2% Oleosome-FGF-2 fusion extract scalp serum for 84 days was associated with improved phototrichogram-derived hair density, anagen/telogen ratio, hair shaft thickness, and scalp barrier parameters compared with placebo. Larger double-blind studies with prespecified primary endpoints, individual-level datasets, and longer follow-up are warranted.

Abstract: Background and Clinical Significance: Iatrogenic atrophy following intralesional corticosteroid injections represents a rare but potentially disfiguring complication, particularly when administered in the facial region for the treatment of inflammatory acne. Unlike conventional post-acne atrophic scarring, corticosteroid-induced tissue loss involves both dermal and subcutaneous compartments, resulting in a clinically distinct presentation that poses significant therapeutic challenges, with no established consensus on optimal management. Case Presentation: We report the case of a 26-year-old Caucasian female (Fitzpatrick phototype III) presenting with severe iatrogenic facial atrophy of the left cheek, resulting from multiple intralesional corticosteroid injections performed by a previous physician for papulo-pustular acne. The condition had been clinically stable for approximately two years at first evaluation. The patient underwent a stepwise multimodal protocol over approximately 18 months, combining non-ablative fractional laser remodelling (LightScan – Eufoton), Autologous Regenerative Therapy (ART, Seffiller technique, Seffiline srl), hyperdiluted calcium hydroxylapatite (CaHA – Radiesse, Merz Aesthetics) biostimulation, and additional non-ablative fractional photothermolysis sessions, supported by a topical cosmeceutical protocol. Clinician-assessed scar severity improved from Goodman & Baron Grade 3 to Grade 2, and Vancouver Scar Scale score from 4–5/13 to 1–2/13. Global aesthetic improvement was rated as +2 ("Much improved") on the GAIS, with patient satisfaction of 5/5. Conclusions: This case demonstrates that a carefully sequenced multimodal approach combining energy-based devices, biological scaffolds, and biostimulatory agents can achieve substantial and durable correction of iatrogenic steroid-induced facial atrophy, providing a reproducible framework for managing this under-reported and therapeutically challenging condition.

Abstract: Background/Objectives: Alopecia areata (AA) is a widespread autoimmune condition causing non-scarring hair loss, significantly affecting the quality of life. Despite its prevalence, data on diagnostic and treatment efficacy and the quality of patients’ care in Poland remain unstudied. The aim of this study was to assess the current clinical approaches to the diagnosis and management of alopecia areata by dermatologists in Poland and to highlight the challenges encountered by Polish patients. Methods: A cross-sectional study was conducted regarding dermatologists and AA patients in Po-land. The data were gathered from distinct proprietary surveys: an original questionnaire for doctors, and DLQI, CDLQI, AAPPO, WPAI+CIQ:AS, and SF-36 questionnaires for patients. Results: The study included 100 dermatologists and 252 pa-tients from Poland. The study revealed that the care provided to patients with alopecia areata is inadequate and lacks a comprehensive approach, despite the negative disease impact on patients’ quality of life. A number of physicians do not follow the diagnostic and treatment guidelines. Despite the registration of next-generation treatments like Janus kinase inhibitors, access to these medications remained limited until recently. Conclusions: Alopecia areata in Poland poses significant diagnostic, therapeutic, and psychosocial challenges. While clinical practice largely aligns with international recommendations, notable gaps remain in the use of validated severity tools, psychosocial assessment, and access to advanced therapies. The recent reimbursement of ritlecitinib represents a breakthrough, bringing Polish care in line with global stand-ards. However, optimal management requires not only pharmacological advances but also interdisciplinary strategies integrating psychological support, patient advocacy, and public education to reduce stigma and improve overall quality of life for affected individuals.

Abstract: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease affecting more than 171 million individuals worldwide. Increasing evidence indicates that its pathogenesis extends beyond cutaneous immune dysregulation and involves systemic interactions mediated by the gut microbiome. This narrative review summarizes current knowledge regarding the gut–skin axis in AD and highlights three emerging areas of translational relevance: (i) the relationship between gut microbial dysbiosis, microbial metabolite alterations, and validated disease severity indices; (ii) the role of short-chain fatty acids (SCFAs), tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, and secondary bile acids as key mediators of gut–skin immune communication; and (iii) the integration of artificial intelligence (AI) and multi-omics technologies in precision microbiome medicine. Gut dysbiosis in AD is characterized by reduced abundance of beneficial taxa, including Bifidobacterium, Faecalibacterium prausnitzii, Blautia, and Akkermansia muciniphila, resulting in impaired regulatory T-cell function, enhanced Th2 polarization, increased IgE production, and disruption of epithelial barrier homeostasis. Altered concentrations of microbial metabolites, particularly SCFAs and tryptophan-derived compounds, are associated with disease activity and correlate with clinical severity scores, including the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD). Intestinal barrier dysfunction, reflected by elevated zonulin, lipopolysaccharide-binding protein, and Reg3A, further amplifies systemic inflammation and cutaneous sensitization. Microbiome-targeted interventions—including probiotics, synbiotics, dietary modulation, and fecal microbiota transplantation (FMT)—have demonstrated promising effects on disease severity, immune regulation, and the restoration of microbial diversity. Emerging AI-driven multi-omics approaches are enabling the identification of disease endotypes, microbial signatures, and metabolite profiles with potential diagnostic, prognostic, and therapeutic value. Additionally, evidence from critical illness research suggests that ICU-associated dysbiosis may represent an extreme model of gut–skin axis disruption, providing novel insights into microbiome-driven immune dysfunction. Collectively, current evidence supports the gut microbiome as a driver, biomarker, and therapeutic target in AD. Future research should prioritize standardized multi-omics studies, metabolite-based biomarkers, and precision microbiome interventions to facilitate the translation of discoveries from the gut–skin axis into clinical practice.

Abstract: Background/Objectives: Patients with severe psoriasis complicated by comorbidities such as cardiovascular disease, obesity, metabolic syndrome and/or with the involvement of high-impact areas constitute a clinical challenge. Tildrakizumab is a monoclonal antibody targeting the IL-23/Th17 axis with a proven record of efficacy and safety in these patients. Case presentation: Here we present four cases of patients with severe psoriasis and comorbidities including cardiovascular disease (Case 1), obesity (Case 2 and 3), metabolic syndrome (Case 3), and/or high-impact areas (Cases 2-4). Three patients (Cases 1-3) had previously received biologics but developed secondary failure or loss of efficacy; one patient was bio-naïve (Case 4). The treatment with tildrakizumab in all four patients led to a quick onset of complete and lasting remission with no adverse events reported. Conclusions: Tildrakizumab is a valuable therapeutic option for patients with psoriasis and complex clinical situations, and in particular, in cases with obesity and difficult-to-treat lesion location. Therapeutic success is often linked to an improvement in patient’s quality of life.

Abstract: A scar is the fibrous tissue that replaces normal skin after the proliferative and remodeling phases of wound healing. When healing is dysregulated, the result is a pathological scar: hypertrophic scars, which remain within the original wound margins, and keloids, which invade adjacent unwounded skin and behave as benign dermal tumors. Both arise when injury reaches the reticular dermis and provokes sustained inflammation and mechanical tension that drive the differentiation of fibroblasts into contractile myofibroblasts and the disorganized over-deposition of collagen and elastin. These lesions cause pain, pruritus, contracture, disfigurement, and considerable psychological distress, and they account for a multibillion-dollar global treatment burden. This review synthesizes the structural, cellular, and molecular basis of cutaneous scarring, distinguishes hypertrophic, keloid, atrophic, and fine-line scars by their clinical and histological features, and organizes the therapeutic landscape into conservative, topical, minimally invasive, surgical, and emerging modalities. We emphasize the convergent signaling axes, TGF-β/Smad, mechanotransduction through integrins and Rho/ROCK, and TNF-α/NF-κB inflammation, that represent rational therapeutic targets, and we highlight why combination and stepwise regimens outperform monotherapy while recurrence remains the central unmet challenge. Finally, we evaluate the feasibility of delivering the anti-fibrotic statin atorvastatin from a calcium-enhanced keratin hydrogel fabricated from residual human hair, an approach developed by our group that couples sustainable biomaterial sourcing with localized, sustained release. We argue that biomaterial-mediated, mechanism-targeted local delivery is a promising direction for converting the broad pleiotropic anti-fibrotic activity of statins into a practical scar therapy.

Abstract: Background: Onychomycosis is a common nail disorder caused by a wide range of pathogenic organisms and is often associated with underlying non-dermatological conditions and lifestyle-related factors. Emerging evidence suggests an increasing role of non-dermatophyte moulds (NDMs), previously regarded as contaminants. However, data describing the epidemiology and causative organisms of onychomycosis in South Africa remain limited. Methods: A retrospective cross-sectional study was conducted at the Dermatology Department of Livingstone Hospital, Gqeberha, from 01 January 2019 to 31 December 2023. Clinical and laboratory records of patients with suspected onychomycosis were reviewed, and only mycologically confirmed cases were included. Diagnosis was established using potassium hydroxide microscopy, fungal culture, and/or Periodic Acid–Schiff staining. Demographic, clinical, and mycological data were analyzed using descriptive and inferential statistical methods. Results: Of 112 clinically suspected cases, 103 were laboratory confirmed. The median age was 57 years, with a slight female predominance (54.4%). Toenail involvement (70.9%) was more frequent than fingernail involvement (43.7%). Nearly all patients (95.1%) had at least one clinical risk factor or comorbidity. Nail discoloration (98.1%), particularly hyperpigmentation, was the most consistent clinical feature, followed by subungual hyperkeratosis (77.7%), onycholysis (59.2%), and nail dystrophy (52.4%). NDMs were the predominant pathogens (57.3%), followed by yeasts (36.9%) and dermatophytes (8.7%). Alternaria, Penicillium, and Aspergillus were the most common NDMs, while Candida parapsilosis, Candida albicans, and Trichosporon species were the leading yeasts. Dermatophyte infections were significantly associated with younger age (p = 0.035) and the presence of tinea (p = 0.025). Non-dermatophyte infections were significantly associated with dermatitis (p = 0.035) and toenail involvement (p = 0.023). Yeast infections were strongly associated with paronychia (p < 0.001) and fingernail involvement (p = 0.026). No independent predictors were identified on multivariable analysis. Conclusions: Nail discoloration remains the most consistent clinical feature of onychomycosis. The high burden of comorbidities underscores the strong association between the condition and underlying conditions. Non-dermatophyte moulds predominate as causative organisms in this setting, highlighting the importance of accurate laboratory diagnosis to guide appropriate management.

Abstract: Rosacea and topical corticosteroid-induced rosacea-like dermatitis (TCIRD) are cutaneous conditions that manifest as erythema, telangiectasia, papules and pustules on the face, accompanied by impairment of the skin barrier. Platelet rich plasma (PRP) constitutes a therapeutic procedure that utilizes a centrifuge to separate a concentrated platelets fraction from a low-volume plasma specimen. Use of PRP has expanded beyond wound healing and skin rejuvenation to include the treatment of inflammatory dermatological conditions. This review explores the clinical ramifications of PRP in the treatment of rosacea and TCIRD, conditions marked by inflammation in the skin. The study places particular emphasis on the effect of PRP on the pathogenesis of rosacea. A comprehensive search of the literature was conducted in this review to identify the efficacy of PRP as a therapeutic modality for rosacea and TCIRD. The effectiveness of PRP in the patient's clinic and the pathogenesis of these skin conditions have been thoroughly documented. Treatment outcomes demonstrated efficacy in addressing symptoms related to rosacea and TCIRD, with improvements observed and symptoms alleviated in these cases following PRP intervention. PRP may represent a potential therapeutic option for rosacea and TCIRD; however, further well-designed studies are required to establish its efficacy and optimal treatment protocols.

Abstract: Plerixafor is a clinically approved CXCR4 antagonist that mobilizes hematopoietic stem cells by disrupting CXCL12/CXCR4 retention signaling. However, its biochemical effects on melanocytes and pigmentation remain unexplored. We investigated how plerixafor modulates CXCR4 sig-naling in melanocytes and evaluated its potential as a pro-melanogenic agent using in vitro and in vivo approaches. Human PIG1 melanocytes were treated with 10 nM plerixafor with or without hydro-quinone (HQ), followed by qPCR for MITF and tyrosinase expression, flow cytometry for CXCR4/CXCR7 and integrin profiling, transwell migration assays, β-arrestin siRNA knockdown, Western blotting, subcellular fractionation, and ChIP-qPCR for β-catenin binding to MITF regu-latory regions. A murine HQ-induced depigmentation model was used to test topical plerixafor on pigmentation, hair follicles, melanogenic gene expression, and systemic safety markers. Plerixafor significantly increased MITF and tyrosinase mRNA and enhanced melanocyte migration, while counteracting HQ-induced suppression of melanogenic genes. Plerixafor reduced cell-surface CXCR4 (consistent with β-arrestin–mediated receptor internalization) without altering CXCR7, c-KIT, or N-cadherin. β-arrestin knockdown abolished plerixafor-induced ERK phosphorylation and melanogenic responses, confirming β-arrestin dependence. Plerixafor promoted β-catenin nuclear translocation and direct β-catenin occupancy at MITF promoter/enhancer TCF/LEF motifs. In vivo, topical plerixafor restored HQ-induced depigmentation, increased hair follicle number and melanin content, and upregulated cutaneous MITF and tyrosinase without hepatic, renal, or inflammatory toxicity. Plerixafor functions as a biased CXCR4 ligand in melanocytes, engaging a β-arrestin–β-catenin–MITF signaling axis to drive melanogenesis and repigmentation. These findings identify β-arrestin–dependent CXCR4 signaling as a tractable pharmacologic mechanism for therapeutic repigmentation in pigmentary disorders.