Search Results (605)

Background and Objectives: Janus kinase (JAK) inhibitors have expanded the therapeutic options for moderate-to-severe atopic dermatitis (AD). The possibility of dose modulation with abrocitinib (100 and 200 mg) and upadacitinib (15 and 30 mg), both selective JAK1 inhibitors, represents a potential clinical advantage, allowing dose escalation in cases of insufficient response and dose de-escalation in the setting of poor tolerability or during maintenance treatment. However, real-world data remain limited, and the rationale for dose adjustment is not always standardized. This study aimed to describe, using a real-world database, the frequency, timing, and reasons for dose modifications of these agents. Materials and Methods: We retrospectively analyzed the clinical data of 212 patients with moderate-to-severe AD treated with abrocitinib (n = 47) or upadacitinib (n = 165). Dose adjustments, including dose escalation and dose de-escalation, were recorded together with their timing and clinical reasons. Results: In the abrocitinib group, 34/47 patients (72.3%) initiated treatment at 100 mg, whereas 13/47 patients (27.7%) started at 200 mg. Six patients (12.8%) underwent a dose adjustment. One patient (2.1%) switched from 200 to 100 mg because of complete AD remission and concomitant menstrual cycle alterations, whereas five patients (10.6%) underwent dose escalation from 100 to 200 mg because of incomplete disease control. Among the six abrocitinib-treated patients who underwent dose adjustment, achievement of IGA 0/1 after dose modification was documented in all cases. In the upadacitinib group, 93/165 patients (56.4%) started at 15 mg, whereas 72/165 patients (43.6%) started at 30 mg. Overall, 44/165 patients (26.7%) underwent at least one dose adjustment, accounting for a total of 50 dose modifications: 27 escalations from 15 to 30 mg and 23 de-escalations from 30 to 15 mg. Among patients initiating treatment at 15 mg, 23/93 patients (24.7%) increased the dose to 30 mg after a median of 33.1 weeks because of suboptimal disease control. Among those starting at 30 mg, 21/72 patients (29.2%) reduced the dose to 15 mg after a median of 44.3 weeks. Of these, 12/21 patients (57.1%) reduced the dose because of adverse events, including herpetic infections and acne, whereas the remaining patients de-escalated because of optimal disease control. Some patients underwent multiple dose modifications: four followed a 30→15→30 mg sequence, with re-escalation after 13.2 weeks because of suboptimal disease control, and two followed a 15→30→15 mg sequence, with dose reduction after approximately 26.7 weeks because of herpes zoster. Overall, 29/44 patients achieved IGA 0/1 within 16 weeks and 38/44 within 32 weeks after dose modification. Conclusions: In this real-world cohort, dose adjustments of selective JAK1 inhibitors were frequently performed in patients with moderate-to-severe AD, particularly among those treated with upadacitinib. Dose escalation was mainly used to address suboptimal disease control, whereas dose de-escalation was performed in the setting of adverse events or optimal disease control. The availability of two dosing regimens may allow treatment intensity to be adapted to individual disease severity, response, and tolerability, supporting a personalized approach to AD management. Full article

The skin microbiome is essential for epidermal barrier integrity and immune homeostasis. This review explores the therapeutic shift in dermo-cosmetics toward probiotic, prebiotic, synbiotic, and postbiotic strategies for managing wound healing, “inflammaging”, and chronic dermatoses like acne, atopic dermatitis (AD), psoriasis, and rosacea. Mechanisms include gut–skin axis modulation, competitive pathogen exclusion, and the suppression of inflammatory pathways (e.g., NF-κB). While live probiotics demonstrate high clinical efficacy, their formulation is severely hindered by standard cosmetic preservatives and manufacturing thermal stress. Consequently, evidence suggests inanimate postbiotics have emerged as promising, stable alternatives, which may offer antimicrobial and tissue-repairing benefits without strict cold-chain requirements. However, the industry faces significant regulatory ambiguity and “probiotic-washing”, with most commercial products mislabeling postbiotic lysates as live cultures. Advancing this field requires standardized sampling protocols and transparent labeling. Ultimately, precision dermatology is likely to be driven by AI-assisted microbiome profiling, synthetic biology, and advanced delivery matrices (e.g., electrospun nanofibers, alginate microencapsulation), transforming skincare from reactive treatments into proactive, targeted ecological management. Full article

Skin health depends on the coordinated maintenance of barrier integrity, immune homeostasis, redox balance, microbial ecology, and systemic metabolic status. Among dietary constituents, polysaccharides have attracted increasing attention because they represent a structurally heterogeneous class of complex carbohydrates whose biological behavior is shaped by molecular weight, monosaccharide composition, glycosidic linkage patterns, branching, higher-order conformation, and physicochemical properties. However, many current skin-related studies remain primarily phenomenon-driven, with insufficient attention to how specific structural features influence biological function and dermatologic relevance. From a structure–function perspective, key structural features of dietary polysaccharides may influence several skin-relevant biological processes, including microbiota-associated signaling, immune regulation, barrier homeostasis, oxidative balance, and extracellular matrix protection. The relevance of these structure-linked functions differs across dermatologic contexts: it appears most direct in photoaging, more conditional in atopic dermatitis, and relatively indirect in psoriasis, whereas wound-repair-related settings are less closely aligned with strict dietary relevance. Current evidence therefore supports structure–function associations more strongly than direct associations between specific structural features and dermatologic outcomes. Dietary polysaccharides are not functionally interchangeable in skin-related contexts, and their skin-related effects depend on structural background, disease setting, and mode of application. Where non-dietary evidence is discussed, it serves primarily as mechanistic or translational contextualization rather than as a basis for nutritional recommendation. Clarifying these relationships may support future mechanistic research and facilitate more rational nutritional applications of dietary polysaccharides in skin health. Full article

Background: Janus kinase (JAK) inhibitors have expanded the therapeutic landscape for moderate-to-severe atopic dermatitis (AD), yet real-world comparative data on upadacitinib and abrocitinib remain limited. Objective: We aimed to compare the 24-week real-world effectiveness and safety of upadacitinib 30 mg and abrocitinib 200 mg in adult patients with moderate-to-severe AD, using EASI-75 as the primary efficacy endpoint, and to explore potential clinical factors associated with treatment response. Methods: This retrospective single-center study included adult patients with moderate-to-severe AD treated with upadacitinib 30 mg or abrocitinib 200 mg and followed for 24 weeks in routine clinical practice. A small pediatric subgroup (n = 3) receiving abrocitinib 100 mg was analyzed separately for descriptive purposes only. Clinical outcomes included Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50/75/90 response rates, and NRS-4 response. Safety was assessed using routinely documented adverse events. Exploratory analyses evaluated the possible influence of body mass index (BMI), baseline immunoglobulin E (IgE), and psychological stress on treatment response. Results: Both upadacitinib and abrocitinib were associated with rapid and sustained clinical improvement over 24 weeks. At month 6, EASI-75 response was 83.3% in the upadacitinib group versus 70.8% in the abrocitinib group (p = 0.27). EASI-50 response was significantly higher in the upadacitinib group (100% vs. 83.3%; p = 0.05). Exploratory findings suggested that higher BMI, elevated baseline IgE levels, and psychological stress may be associated with less favorable response trajectories. Both treatments demonstrated a generally favorable safety profile; however, one serious cerebrovascular thrombotic event occurred in a patient with pre-existing cardiovascular risk factors, highlighting the importance of individualized risk assessment when prescribing JAK inhibitors. Conclusions: In routine clinical practice, both upadacitinib and abrocitinib appeared effective for the management of moderate-to-severe AD over 24 weeks. Although upadacitinib 30 mg showed a numerically higher month-6 EASI-50 response, this finding should be interpreted cautiously given the modest sample size and the absence of broader between-group differences across other key efficacy outcomes. Larger prospective studies are needed to confirm comparative effectiveness and to clarify predictors of response and safety in real-world settings. Full article

The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host–microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii, Bifidobacterium, and Akkermansia muciniphila, has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments. Full article

Background and aims: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease among children. Our study aimed to evaluate the prevalence of hypogammaglobulinemia among pediatric patients with AD and to characterize the clinical and laboratory findings of patients diagnosed with AD and hypogammaglobulinemia. Method: The electronic files of 1850 patients aged 0–18 years diagnosed with AD between 2020 and 2022 in the Pediatric Immunology and Allergy Clinic of Bursa Medical Faculty City Hospital were retrospectively analyzed. During this period, all patients newly diagnosed with atopic dermatitis at our clinic were systematically screened for their serum immunoglobulin (Ig) levels (IgG, IgA, and IgM) at the time of initial presentation. We included 200 AD patients with hypogammaglobulinemia. Disease severity was classified using the Scoring Atopic Dermatitis (SCORAD) index. Multivariate logistic and linear regression analyses were performed to identify independent determinants of disease severity, considering age, sex, eosinophil counts, total IgE, food allergies, and baseline immunoglobulin levels. Results: The prevalence of hypogammaglobulinemia among the 1850 screened children with AD was 10.8% (200/1850). Of the 200 patients included in this study, 128 (64%) were male, and 72 (36%) were female. The median age at first clinic presentation was 8 months (interquartile range (IQR) 25–75%: 5–16). According to the Scoring Atopic Dermatitis (SCORAD) index, AD severity was mild in 150 (75%) patients and moderate-to-severe in 50 (25%). Food allergy sensitization was present in 72 (36%) patients. Patients with moderate-to-severe AD had significantly lower IgG (300 vs. 374 mg/dL; p < 0.001; r = −0.346), IgA (10 vs. 14 mg/dL; p = 0.004), and IgM (38 vs. 51 mg/dL; p = 0.001) levels when compared with those with mild disease. Multivariate logistic regression confirmed that lower IgG was the only immunoglobulin independently associated with moderate-to-severe AD (OR = 1.97 per 100 mg/dL decrease; 95% CI: 1.15–3.39; p = 0.013), while food allergy was the strongest independent predictor of the SCORAD index (β = +11.97; p < 0.001). None of the patients received intravenous immunoglobulin (IVIG) treatment. Of the 142 patients who underwent serial serum immunoglobulin measurements, 56 (39%) achieved age-appropriate normal IgG levels, while hypogammaglobulinemia persisted in 86 (61%). Conclusions: We found a higher frequency of hypogammaglobulinemia in patients with AD in our study, as compared with previously reported rates of THI in children from the general pediatric population. Although our study showed an increase in IgG levels during the follow-up period in many patients, it emphasizes the need for long-term immunological monitoring, especially in patients with moderate-to-severe AD. Full article

Background/Objectives: We conducted the first pharmacogenetic investigation of atopic dermatitis in a cohort of 43 Greek patients, focusing on key variants within the IL6/JAK/STAT signaling axis, a pathway central to inflammation and therapeutic targeting. Methods: Patients receiving dupilumab, JAK inhibitors, or topical corticosteroids were prospectively evaluated, with treatment response assessed by changes in the Eczema Area and Severity Index over four months. Targeted genotyping of IL6R rs2228145 A>C, JAK1 rs2780815 T>G, and TRAF3 rs12147254 G>A were performed using PCR-RFLP. Results: Across the full cohort, no robust pharmacogenetic effects were detected, while baseline disease severity was the strongest predictor of absolute clinical improvement. However, stratified analyses revealed a significant association between the IL6R rs2228145 minor allele and reduced upadacitinib response (p-value = 0.026). Consistently, the same variant demonstrated a nominal association with reduced likelihood of achieving ≥75% improvement (p = 0.065). Conclusions: Although limited by sample size, these findings suggest potential treatment-specific pharmacogenetic effects within the IL6 pathway, supporting further investigation in larger cohorts to inform personalized therapeutic strategies in eczema. Full article

Background/Objectives: This study aimed to determine the incidence of herpes zoster (HZ) and risk factors associated with its occurrence in patients receiving Janus kinase inhibitors (JAKis) for immune-mediated inflammatory diseases (IMIDs), while evaluating preventive strategies and zoster vaccine uptake. Methods: We conducted a retrospective single-center cohort study including patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, atopic dermatitis and alopecia areata treated with upadacitinib, baricitinib or tofacitinib. The primary outcome was incident HZ during JAKi exposure. Incidence rates (IRs) were calculated per 100 person-years (PY) and Cox regression identified factors associated with HZ. Results: A total of 292 patients contributed 565.5 PY of JAKi exposure. During follow-up, 23 patients (7.9%) developed HZ, corresponding to an overall IR of 4.07/100 PY (95% CI 2.40–5.73). Incidence rates were numerically lower with upadacitinib and varied across disease groups; differences were not statistically significant. Diabetes mellitus (HR 3.05, 95% CI 1.28–7.29) and chronic kidney disease (HR 3.24, 95% CI 1.17–8.95) were independently associated with HZ. Herpes simplex infection requiring systemic antiviral therapy was more frequent among patients who developed HZ. Recombinant zoster vaccine (RZV) uptake was low (9.9%), but higher among patients evaluated in a dedicated infectious risk consultation. No HZ events were observed among RZV-vaccinated patients. Although six HZ events (26.1%) were severe, all cases resolved completely. Conclusions: HZ remains a relevant complication of JAKi therapy across IMIDs. Diabetes mellitus and chronic kidney disease may help identify higher-risk patients, while structured infectious risk assessment could improve vaccine uptake. Full article

Background: Superficial fungal infections caused by dermatophyte and non-dermatophyte species are increasing globally. While several comorbid diseases and risk factors have been associated with fungal infections at the individual level, their epidemiological relationships at the population level remains poorly characterized. Objective: We aimed to examine population-level associations between the burden of superficial fungal infections and selected comorbid conditions and risk factors, stratified by age, sex and country. Methods: We obtained years lived with disability (YLDs) for superficial fungal infections, diabetes, psoriasis, and atopic dermatitis and summary exposure values (SEVs) for high body mass index (BMI) and high alcohol intake from Global Burden of Disease Study 2023. Data were obtained for Australia, Brazil, the United Kingdom and the United States for males and females younger than 20 years, 20 to 54 years and 55+ years old. Pearson correlation coefficients were calculated between fungal infection YLDs and each comorbid condition (YLDs) and risk factor (SEVs). Results: Significant positive correlations were observed between superficial fungal infection burden and diabetes (R = 0.6–0.98), high BMI (R = 0.75–0.95), psoriasis (R = 0.59–0.96), and atopic dermatitis (R = 0.51–0.93) in older adults (55 years+). Correlations with high alcohol consumption were more variable across regions and sex. In young–middle-aged adults (20–54 years), moderate-to-strong correlations (R ~ 0.8–0.9) were observed, although patterns were less consistent across countries. In individuals < 20 years, associations were generally weaker, with some positive correlations observed for atopic dermatitis (R = 0.4–0.7) in select countries. Conclusions: The findings demonstrate population-level associations between superficial fungal infections and metabolic, inflammatory, and behavioural risk factors, with stronger correlations observed in older age groups. These patterns may reflect shared demographic, epidemiologic, and clinical patterns across conditions. Full article

Chronic hand eczema (CHE) is a persistent and relapsing inflammatory dermatosis characterized by substantial functional impairment, psychosocial distress, and occupational disability. Although epidemiologically common and clinically burdensome, CHE has long suffered from nosological ambiguity, frequently interpreted as a localized manifestation of atopic dermatitis, psoriasis, allergic contact dermatitis, or cumulative irritant dermatitis. The recent regulatory approval of topical delgocitinib, a pan-Janus kinase (JAK) inhibitor specifically indicated for moderate-to-severe CHE inadequately controlled by topical corticosteroids, has reshaped both therapeutic strategy and conceptual framing of the disease. The introduction of a targeted therapy dedicated to CHE has reinforced its clinical identity while simultaneously highlighting its internal biological heterogeneity. Beneath the umbrella term “chronic hand eczema” lie distinct phenotypes characterized by variable barrier dysfunction, immune polarization, and environmental interaction. This review integrates current knowledge on epidemiology, pathophysiology, diagnostic stratification, therapeutic algorithms, phase III registrative evidence, emerging real-world data, and the central role of barrier restoration. Particular attention is devoted to the hand as a specialized barrier organ and to the interplay between inflammation and epidermal structural integrity. In the era of targeted therapy, precise diagnostic framing and barrier-oriented management are indispensable to optimize outcomes. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease increasingly prevalent in adults. Vitamin D plays an important role in regulating immune responses, cellular differentiation, and inflammation. Several single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been suggested as biomarkers of AD susceptibility and severity. The aim of this study was to investigate six SNPs in the VDR gene (rs3847987, rs731236, rs7975232, rs1544410, rs2228570, and rs11168293) and their association with AD and blood biomarkers. Genotyping was performed in 91 adult patients with AD and 102 controls using real-time polymerase chain reaction. The genotype and allele distributions did not differ significantly between AD patients and controls. However, the G and T alleles of VDR rs731236 and rs1544410 were more frequently detected in individuals with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/mL. In contrast, the VDR rs7975232 C allele appears to be associated with lower odds of having a serum 25(OH)D level above 30 ng/mL. In genotype-stratified analysis, the T allele of VDR rs11168293 was more prevalent among individuals with eosinophil counts of 300 cells/μL. These findings suggest that VDR polymorphisms may contribute to variability in vitamin D status and inflammatory responses in adults with AD. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory dermatosis characterized by pruritus, eczematous lesions, and a fluctuating course. It imposes substantial quality-of-life and economic burdens through sleep disturbance, pain, psychosocial distress, and frequent healthcare utilization. Recent global estimates suggest AD affects hundreds of millions worldwide, with meaningful prevalence in both children and adults. AD pathogenesis is multifactorial, reflecting the interaction of genetic predisposition, immune dysregulation dominated by type 2 inflammation, epidermal barrier impairment, neuroimmune itch pathways, and microbial dysbiosis. Clinical diagnosis remains primarily clinical, supported by classic criteria emphasizing pruritus, typical morphology, chronicity, and atopic history. Disease severity and treatment response are commonly quantified using validated measures such as EASI and SCORAD, enabling standardized monitoring and evidence-based escalation. Management has shifted from broad immunosuppression to a stepwise, endotype-aware approach integrating barrier repair, anti-inflammatory topical therapy, phototherapy, conventional systemic agents, and rapidly expanding targeted options. Recent guidelines and approvals highlight increasing roles for biologics and JAK pathway inhibition, alongside newer nonsteroidal topicals. This review summarizes current concepts and practical treatment integration, with emphasis on safety, monitoring, and future research directions. Full article

Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation. Full article

Background/Objectives: The itch–scratch cycle is a key driver of exacerbation in atopic dermatitis (AD) and requires objective monitoring, yet patient-reported itch scores are often unreliable in children. This study aimed to evaluate smartwatch-derived nocturnal scratching metrics as digital biomarkers of disease activity and treatment response in pediatric AD. Methods: In this prospective observational study, 50 children (median age 9 years) with physician-diagnosed AD wore an Apple Watch with the Itch Tracker application for 5–14 nights during initiation of topical therapy. Three scratch metrics—scratch count rate (SCR), scratch duration ratio (SDR), and scratch burden index (SBI, duration × intensity)—were analyzed. Associations with clinical outcomes [Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM)], serum thymus and activation-regulated chemokine (TARC), and itch numerical rating scale (NRS) were examined. Logistic regression models were evaluated to examine whether these metrics could identify children who achieved clinically meaningful improvement, defined as EASI-50 plus ≥ 4-point POEM reduction. Results: All scratch metrics correlated with baseline EASI (r = 0.60–0.64, p < 0.001) and serum TARC (r = 0.58–0.60, p < 0.001). Reductions in scratching paralleled clinical improvement (r = 0.67–0.71, p < 0.0001). Among models, the SBI-based logistic regression demonstrated the best discriminative performance (AUC = 0.78, 95% CI: 0.64–0.92). Conclusions: Wearable-derived nocturnal scratching metrics showed moderate but consistent associations with disease severity and short-term improvement. Although predictive capability remains to be established, these metrics may serve as treatment-responsive digital measures. Given the cross-sectional nature of biomarker analyses and other study limitations, further prospective validation is required before clinical application in real-world pediatric AD monitoring. Full article

Comano thermal water (CTW) is a hypotonic, bicarbonate–calcium–magnesium mineral water traditionally used to manage chronic inflammatory and relapsing skin diseases. This review summarises and discusses the available clinical, experimental, and translational evidence on CTW, with a particular focus on dermatological indications. The physicochemical properties of CTW, along with the presence of a stable, non-pathogenic microbial community, are examined in relation to their potential biological activity. Clinical studies indicate that CTW-based balneotherapy, alone or in combination with narrowband Ultraviolet B (UVB) phototherapy, is associated with improvements in disease severity, symptom burden, and quality of life in patients with psoriasis and atopic dermatitis, and has a favourable safety and tolerability profile. Experimental data further suggest that CTW may exert anti-inflammatory and immunomodulatory effects, modulate keratinocyte function, support skin barrier restoration, and influence the cutaneous microenvironment, including microbiome-related pathways. The review also outlines emerging evidence for CTW in skin regeneration and in upper airway inflammatory conditions treated via inhalation-based approaches. Overall, this review suggests that CTW may serve as a biologically active therapeutic resource, warranting further investigation as a complementary approach within integrative management strategies for inflammatory and barrier-related conditions. Full article