Dermato, Volume 6, Issue 2 (June 2026) – 11 articles

Background: Difficult-to-treat anatomical areas in atopic dermatitis (AD), including the head and neck, hands, genital and intertriginous regions, are frequently associated with therapeutic refractoriness, persistent pruritus, and substantial functional and psychosocial burden. Real-world evidence (RWE) regarding the effectiveness of Janus kinase (JAK) inhibitors in these site-dominant phenotypes remains fragmented. This structured narrative review aimed to synthesize available RWE on abrocitinib, baricitinib, and upadacitinib in AD involving difficult-to-treat areas. Methods: A comprehensive search of PubMed, Ovid MEDLINE, Scopus, Embase, and the Cochrane Library was conducted up to 31 December 2025. Real-world observational studies reporting site-specific outcomes in patients with AD treated with JAK inhibitors were included. Primary randomized controlled trial efficacy analyses were excluded, while relevant post hoc regional analyses were considered. A total of 22 studies met eligibility criteria for qualitative synthesis. Results: Across heterogeneous real-world cohorts, JAK inhibitors demonstrated clinically meaningful improvement in difficult anatomical regions, particularly the head and neck and hands. Rapid pruritus reduction was a consistent and clinically relevant finding. Safety profiles were broadly aligned with clinical trial data. Conclusions: Real-world data support JAK inhibitors as effective options for anatomically complex AD phenotypes, warranting further standardized regional assessment. Full article

Emerging research highlights the complex interplay between the gut microbiome, skin health, and environmental exposures, forming what is now recognized as the gut–skin–exposome axis. This narrative review explores the role of gut microbiome dysbiosis—a disruption in the balance of intestinal microorganisms—in the pathogenesis and progression of various non-communicable inflammatory skin diseases, including acne, atopic dermatitis, psoriasis, rosacea, systemic lupus erythematosus, chronic spontaneous urticaria, hidradenitis suppurativa, and alopecia areata. This review synthesizes mechanistic studies, clinical trials, and Mendelian randomization data to elucidate how altered gut microbial composition contributes to systemic and cutaneous inflammation. Key modifiable factors, such as diet, antibiotics, stress, and sleep, as well as interventions like probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, are discussed for their potential therapeutic value. By integrating clinical insights with microbiome science, this review underscores the importance of a holistic, systems-based approach in managing inflammatory skin diseases, offering clinicians evidence-based strategies to improve patient outcomes through gut microbiome modulation. Full article

Introduction: Alopecia areata (AA) is a chronic immune-mediated disorder characterized by non-scarring hair loss and a significant psychosocial burden. Ritlecitinib, a selective Janus kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, has recently emerged as a targeted systemic therapy for moderate-to-severe AA. While randomized clinical trials have demonstrated its efficacy, real-world evidence remains limited and heterogeneous. Methods: A structured narrative review was conducted to summarize current evidence on ritlecitinib in AA, with a focus on real-world outcomes. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to March 2026 using predefined keywords. Eligible studies included real-world observational studies, case series, and post hoc analyses of randomized controlled trials reporting clinical outcomes. Two independent reviewers performed study selection. Results: A total of 14 studies were included. Clinical trial analyses suggested sustained efficacy over time, with progressive improvement in Severity of Alopecia Tool (SALT) scores up to 24 months. Real-world studies reported clinically meaningful hair regrowth across diverse populations, including severe, pediatric, and treatment-experienced patients. Response rates increased over time, with a proportion of patients achieving SALT ≤ 20 or ≥80% improvement. Lower baseline severity and shorter disease duration were reported in several studies as potential factors associated with a better response. Safety profiles were favorable, with predominantly mild adverse events. Discussion: Ritlecitinib shows consistent effectiveness and acceptable safety in both clinical trials and real-world settings. Treatment response appears progressive and heterogeneous, supporting the importance of early intervention and adequate treatment duration. Further large-scale and long-term real-world studies are needed to better define predictors of response and optimize patient selection. Full article

Elderly psoriasis patients (≥65 years) demonstrate mainly preserved but substantially delayed therapeutic responses to IL-17 and IL-23 inhibitors, achieving lower PASI90 rates at early time-points with eventual “catch-up” by week 52, alongside increased adverse-event-driven discontinuation. This review synthesizes clinical efficacy data from real-world studies with emerging mechanistic evidence on immunosenescence and cellular senescence to propose the “Inflammatory Noise Floor” hypothesis. We postulate that senescent keratinocytes and fibroblasts constitutively secrete SASP cytokines (IL-6, IL-8, TNF-α) through pathways partially independent of IL-23/IL-17, potentially establishing a persistent baseline inflammation that IL-23/IL-17 blockade might not suppress. Concurrently, immunosenescence, characterized by CD8⁺CD28⁻ T-cell accumulation, exhaustion marker upregulation, and Treg dysfunction, is hypothesized to impair adaptive immune re-equilibration. This dual mechanism represents one plausible, albeit theoretical, explanatory framework for the temporal lag, PASI plateau effects, and infection risk observed in elderly patients. Optimizing outcomes in the elderly may require a pragmatic approach: accepting stable PASI 75-90 as a successful endpoint and prospectively validating extended assessment timelines. While a direct correlation remains to be proven, this framework identifies cellular and immunosenescence as potential targets for future senotherapeutic interventions. Full article

Background: Biotin (vitamin B7) is widely marketed and used as an over-the-counter supplement for hair, skin, and nails, despite uncertainty about its clinical benefit for alopecia and hair growth. While overt biotin deficiency can be associated with hair changes, clinically meaningful deficiency is uncommon in individuals consuming a balanced diet, and published findings on biotin status in hair loss populations are inconsistent. Methods: This is a systematic review following PRISMA. A search was conducted in PubMed/MEDLINE (PROSPERO: CRD420251274919) for human studies evaluating biotin (alone or in combination) and including hair outcomes. The synthesis was qualitative due to clinical and methodological heterogeneity. Results: Ten studies were included. Across controlled and quasi-experimental interventions, biotin monotherapy did not show consistent benefit on objective hair growth outcomes; when improvements were reported, they typically occurred in combined regimens and were difficult to attribute specifically to biotin. Studies showed mixed findings on “low” biotin levels in hair loss populations, whereas controlled studies in telogen effluvium found no significant differences in serum biotin versus controls. No serious adverse events attributable to biotin were identified; however, high-dose biotin may interfere with immunoassays, potentially leading to clinically relevant false laboratory results. Conclusions: Current evidence does not support routine biotin supplementation for alopecia in the absence of documented deficiency, although it may be considered in scenarios with risk or confirmation of deficiency/malabsorption. Full article

The skin serves as a primary defensive barrier to protect the body from environmental contaminants, infections and trauma. Unfortunately, skin barrier’s structural and functional integrity can be compromised, disrupted or impaired due to a combination of internal and external factors, making it vulnerable and often leading to a wide range of skin conditions characterized by dryness, heightened sensitivity, and increased susceptibility to damage and infections. In addition, the integrity of the skin barrier tends to deteriorate progressively with age. As people age, their skin naturally changes and can also be compromised by a plethora of factors that reduce its strength and resilience. The aging skin becomes thinner and more sensitive, coinciding with a variety of structural–functional alterations, decreased levels of natural moisturizing factor (NMF), lipid content and hydration, increased transepidermal water loss (TEWL), altered skin surface pH (pHss) and microbiome diversity. All these age-related skin integrity alterations make the skin drier, flakier, itchy, and fragile, and more susceptible to damage and breakdown, thus diminishing its ability to effectively protect, repair and heal efficiently. Identifying skin integrity issues before they progress will foster positive outcomes through effective preventive measures. Hence, it is important to understand the impact of skincare formulations on skin integrity in compromised aging skin. A well-considered, evidence-based approach to skincare can provide cleansing, moisturizing and protective benefits, while aiding the reduction in skin integrity issues like dry and itchy skin, sensitive skin, bruising, skin tears, pressure injuries (PIs), lower leg ulcers and moisture-associated skin damage (MASD). Managing skin integrity in compromised aging skin begins with gentle skin cleansing, adequate moisturization and protective barrier care to ensure the skin’s function is maximized. Full article

Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis characterized by recurrent nodules, abscesses, and sinus tract formation in intertriginous skin. Although HS is increasingly recognized as an autoinflammatory condition rather than a classical infection, antimicrobial therapies remain central to disease management, implicating a potential role for the cutaneous microbiome in disease activity. Recent advances in culture-independent sequencing techniques have enabled more detailed characterization of microbial communities in HS, revealing consistent alterations in microbial composition and diversity. Compared with healthy skin, HS lesions exhibit reduced microbial diversity, depletion of commensal organisms such as Cutibacterium acnes, and enrichment of anaerobic bacteria including Prevotella, Porphyromonas, and Finegoldia. These alterations are more pronounced in chronic, tunnel-forming disease and are frequently associated with biofilm formation, which may contribute to treatment resistance and persistent inflammation. Microbiome changes have also been observed beyond overtly lesional skin, suggesting a broader field effect. Evidence regarding extracutaneous microbial compartments, particularly the gut microbiome, remains limited and heterogeneous, while methodological variability in sampling, sequencing, and treatment exposure continues to complicate cross-study comparisons. Emerging data further suggest that immune-targeted therapies, including biologic and small-molecule agents, may indirectly influence microbial community structure through modulation of the inflammatory milieu. Collectively, the available evidence supports cutaneous dysbiosis as a characteristic feature of HS that may potentially interact bidirectionally with immune dysfunction. Future longitudinal, multi-omic studies integrated with clinical phenotyping will be critical to clarify causal relationships and to determine whether microbiome modulation can be leveraged to improve therapeutic outcomes in HS. Full article

Surgery continues to represent the central curative modality for melanoma despite major advances in systemic immunotherapy and targeted treatments. Contemporary surgical strategies aim to maintain oncologic safety while minimizing functional and aesthetic morbidity through optimized excision margins, highly selective use of sentinel lymph node biopsy (SLNB), and the omission of routine completion lymph node dissection (CLND). Rapid integration of neoadjuvant and adjuvant immunotherapies has begun to redefine surgical indications, timing, and extent—particularly for intermediate-stage and locoregionally advanced disease. Parallel innovations in Mohs micrographic surgery, reconstructive flap design, lymphatic reconstruction, and minimally invasive techniques further broaden the possibilities for individualized intervention. This expanded review synthesizes current evidence, ongoing controversies, and emerging trends that are shaping the future of melanoma surgery, highlighting how precision oncology, immunologic profiling, and technological advances are transforming the surgeon’s role and enabling more tailored, less invasive, and outcome-focused management. Full article

Background: Conventional therapies for moderate-to-severe inflammatory acne include topical agents, systemic antibiotics, hormonal treatments, and oral isotretinoin. However, increasing resistance of Cutibacterium acnes to antibiotics and the potential adverse effects of systemic agents have prompted growing interest in non-pharmacological alternatives such as fractional microneedling radiofrequency (RF-MN), recently introduced in the clinical practice. Objective: This report of five cases aims to document the clinical benefits and safety of RF-MN using the Focus Dual^® device in the treatment of moderate-to-severe inflammatory acne vulgaris. Methods: Five patients (2 male, 3 female; aged 19–28 years; Fitzpatrick skin types II–III) with moderate-to-severe acne were treated with two RF-MN sessions at 4-week intervals using the Focus Dual^® device (Med & Tech, Occhiobello (RO), Italy). Acne severity was assessed using the Face Global Acne Grading System (F-GAGS) and the 5-point Global Improvement Score (GIS), with evaluations performed by two independent blinded raters (G.P and O.R). Standardized photographic documentation and lesion counting were conducted at baseline (T0) and 4 weeks after the second session (T2). All individual F-GAGS scores for each of the five patients showed a reduction from baseline to T2, as consistently assessed by both evaluators. Two patients improved from moderate to mild acne, one improved from severe to moderate, and one remained mild. GISs indicated clinical improvement ranging from Grade 1 to Grade 2 in all cases, with individual improvements between 8.33% and 37.93%. No adverse events were reported during treatment or follow-up. Conclusions: RF-MN appears to be a promising therapeutic option for moderate-to-severe inflammatory acne, providing clinical improvement and reduction in acne severity without adverse effects. Prospective studies with a larger sample are needed to confirm these preliminary results and support the potential role of RF-MN as an adjunctive or standalone treatment in patients with limited tolerance or response to conventional therapies. Full article

Sensitive Skin Syndrome (SSS) is a worldwide condition characterized by sensory symptoms such as stinging, burning, and itching, often without visible signs. This pilot study investigated individuals with self-reported SSS, focusing on the specific skin conditions, motivations and barriers for seeking medical attention. SSS individuals were divided into two groups: those who consulted a doctor (n = 16) and those who did not (n = 10). While SSS symptom severity was similar in both groups, those with greater severity were five times more likely to seek medical help. Key symptoms prompting consultations included morphological symptoms (papules, macules), sensory symptoms (itch, discomfort), and inflammatory symptoms (redness, rash). Notably, altered sensation and macules/papules showed the strongest trends towards influencing care-seeking behavior. Differences in anatomical sites affected were significant, with the head and face having the highest odds of doctor visits. Barriers to care included high specialist costs, travel distances, and a lack of remote consultation options, particularly for rural residents. Although treatments recommended by healthcare providers often fell short of expectations, partially effective options were more acceptable when endorsed by doctors. Subjects reported improvements within weeks of starting new treatments, though many remained only partially satisfied. This study highlights important aspects of SSS and its entanglement with other skin conditions, as well as how individuals navigate their symptoms and make treatment decisions amidst their sufferings. Full article

Background: This study aimed to assess the prevalence of PD-L1 protein expression in dermatofibrosarcoma protuberans (DFSP) to provide insights into the potential use of immune checkpoint inhibitors. Methods: We retrospectively analyzed formalin-fixed, paraffin-embedded primary DFSP specimens (n = 17). Diagnoses were confirmed by two senior dermatopathologists according to guideline criteria, including diffuse CD34 positivity and storiform spindle cell morphology. All cases represented conventional DFSP without fibrosarcomatous transformation. PD-L1 immunohistochemistry was carried out using a rabbit monoclonal antibody (ab205921, clone 28-8; Abcam). Only membranous staining in viable tumor cells was scored as a tumor proportion score (TPS), where >1% was considered positive. Any cytoplasmic staining without convincing membranous accentuation was not scored. PD-L1 staining in tumor-infiltrating immune cells was recorded separately. Five pleomorphic dermal sarcomas served as positive controls. Results: The median age was 62 years (IQR 55–74); 12 patients were men and 5 were women. The primary sites were trunk (59%), upper extremity (35%), and lower extremity (6%); immunosuppression was present in 18%. By FNCLCC, 82% of tumors were G1 and 18% were G2; no G3 tumors were identified. All DFSPs were PD-L1-negative in DFSP cells (TPS ≤ 1%) and in tumor-infiltrating lymphocytess. Among controls, 3/5 pleomorphic dermal sarcomas were PD-L1-positive with the expected membranous pattern and variable intensity. Conclusions: PD-L1 expression was absent in this cohort of conventional, predominantly low-grade DFSP, suggesting that classic DFSP is generally not an ideal candidate for PD-1/PD-L1-directed checkpoint blockade. These conclusions should not be extrapolated to fibrosarcomatous DFSP or metastatic disease, where PD-L1 expression has been reported. Selective PD-L1 testing may still be warranted in clinically aggressive scenarios (e.g., fibrosarcomatous transformation, unresectable recurrence, or metastasis). Full article