Gender differences in adult atopic dermatitis and clinical implication: Results from a nationwide multicentre study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults. However, limited research has been conducted on gender differences in AD. OBJECTIVES: This study aimed to assess gender differences in adult AD patients, focusing on demographic and clinical features, comorbidities and treatment approaches. METHODS: In this multicentre, observational, cross-sectional study, we enrolled 686 adult patients with AD (357 males and 329 females). For each patient, we collected demographic data (age and sex), anthropometric measurements (weight, height, hip circumference, waist circumference and waist-to-hip ratio), clinical information (onset age, disease duration, severity, itching intensity, impact on quality of life) and noted comorbidities (metabolic, atopic and other). We recorded past and current topical and systemic treatments. We analysed all collected data using statistical techniques appropriate for both quantitative and qualitative variables. Multiple correspondence analysis (MCA) was employed to evaluate the relationships among all clinical characteristics of the patients. RESULTS: We found no differences in age at onset, disease duration, severity and quality of life impact between males and females. Males exhibited higher rates of hypertriglyceridaemia and hypertension. No significant gender differences were observed in atopic or other comorbidities. Treatment approaches were overlapping, except for greater methotrexate use in males. MCA revealed distinct patterns based on gender, disease severity, age of onset, treatment and quality of life. Adult males with AD had severe disease, extensive treatments and poorer quality of life, while adult females had milder disease, fewer treatments and moderate quality of life impact. CONCLUSIONS: Our study reveals that gender differences in adult AD patients are largely due to inherent population variations rather than disease-related disparities. However, it highlights potential undertreatment of females with moderate AD and quality of life impact, emphasizing the need for equitable AD treatment. JAK inhibitors may offer a solution for gender-based therapeutic parity.

Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

BACKGROUND: Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. OBJECTIVES: To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. METHODS: This observational, retrospective study enrolled adult patients (≥18 years) with moderate-to-severe plaque-type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. RESULTS: Seventy-eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow-up (n = 1) and surgical procedure (n = 1). CONCLUSIONS: Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.

Increased frequency of interleukin-4 and reduced frequency of interferon-γ and IL-17-producing CD4+ and CD8+ cells in scleromyxedema.

BACKGROUND: Little is known about the pathogenesis of scleromyxedema, a life-threatening fibromucinosis disease with immunological dysregulation. OBJECTIVES: To investigate on T-cell phenotype, function and cytokine biology in search of new insights supporting the immunopathogenesis of the disease. METHODS: We analysed the frequency of circulating lymphocyte subsets, the T-cell maturation stage, the generation of antigen-specific T-cell lines and T-cell cytokine secretion. RESULTS: The analysis of T-cell maturation stage and the TCR spectratyping findings revealed that scleromyxedema patients showed clear immunological signs of long-lasting immune system activation and stimulation leading to a skewed T-cell repertoire. Moreover, these analyses showed that both CD4+ and CD8+ T cells from scleromyxedema patients have a profound deficiency (even after stimulation) relatively to the production of IFN-γ and IL17 with respect to healthy donor control cells, while they are massively skewed towards IL4 secretion after stimulation. CONCLUSIONS: Our data indicate that a chronic Th2-skewed T-cell response against an unknown target antigen leading to abnormally high IL4 secretion, a pro-fibrotic cytokine, is a main immunological hallmark of scleromyxedema patients. These results, never reported before, may have a translational therapeutic value due to the availability of anti-IL4 agents such as dupilumab.

Certolizumab for the treatment of psoriasis and psoriatic arthritis: a real-world multicentre Italian study.

BACKGROUND: Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. OBJECTIVE: To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. METHODS: In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400 mg loading dose at 0, 2 and 4 weeks, followed by 200 mg every 2 weeks) for up to 52 weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). RESULTS: In the study were enrolled 153 patients (mean age: 55 years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P < 0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. CONCLUSION: Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.

The CHOPIn Study: a Multicenter Study on Cerebellar Hemorrhage and Outcome in Preterm Infants.

Cerebellar hemorrhage (CBH) is a frequent complication of preterm birth and may play an important and under-recognized role in neurodevelopment outcome. Association between CBH size, location, and neurodevelopment is still unknown. The main objective of this study was to investigate neurodevelopmental outcome at 2 years of age in a large number of infants with different patterns of CBH. Of preterm infants (≤ 34 weeks) with known CBH, perinatal factors, neuro-imaging findings, and follow-up at 2 years of age were retrospectively collected. MRI scans were reassessed to determine the exact size, number, and location of CBH. CBH was divided into three groups: punctate (≤ 4 mm), limited (> 4 mm but < 1/3 of the cerebellar hemisphere), or massive (≥ 1/3 of the cerebellar hemisphere). Associations between pattern of CBH, perinatal factors, and (composite) neurodevelopmental outcome were assessed. Data of 218 preterm infants with CBH were analyzed. Of 177 infants, the composite outcome score could be obtained. Forty-eight out of 119 infants (40%) with punctate CBH, 18 out of 35 infants (51%) with limited CBH, and 18 out of 23 infants (78%) with massive CBH had an abnormal composite outcome score. No significant differences were found for the composite outcome between punctate and limited CBH (P = 0.42). The risk of an abnormal outcome increased with increasing size of CBH. Infants with limited CBH have a more favorable outcome than infants with massive CBH. It is therefore important to distinguish between limited and massive CBH.

Physician-patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (AK-TRAIN): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in Italy.

BACKGROUND: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. OBJECTIVES: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. METHODS: In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm2 area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25-30 days) RESULTS: Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Δpre-post  = -4.00; other: Δpre-post  = -0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (ß = 0.4-0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). CONCLUSION: Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients' engagement and treatment alliance.

Autoantibody profile and clinical patterns in 619 Italian patients with cutaneous lupus erythematosus.

BACKGROUND: Anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case-series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. OBJECTIVE: To characterize the correlations between CLE subtypes as well as LE-non-specific skin lesions and their autoantibody pattern. METHODS: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE-non-specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. RESULTS: Anti-nuclear antibodies (P < 0.0001), anti-dsDNA (P < 0.0001), ENA (P = 0.001), anti-Sm (P = 0.001), anti-RNP (P = 0.004) and anti-histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti-dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti-dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti-Ro/SSA (OR = 0.49, P < 0.0001) and anti-dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti-Ro/SSA (OR = 3.83, P < 0.0001), anti-Smith (OR = 2.95, P = 0.004) and anti-RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti-dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE-non-specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti-Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. CONCLUSION: According to our findings, some well-known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE-non-specific skin lesions was highlighted. A strict association between anti-ENA and anti-Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Consensus on the management of patients with psoriatic arthritis in a dermatology setting.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable. OBJECTIVE: To provide practical recommendations for the management of patients with PsA in the dermatology setting including early diagnosis and treatment. METHODS: A consensus document was written by an expert panel composed by dermatologists (n = 12) and rheumatologists (n = 6). Eleven highly relevant questions were selected and elaborated with answers/statements based on a narrative literature review. The resulting document was discussed in a face-to-face meeting adopting a nominal group technique to reach consensus (i.e. 100% agreement) using the Delphi method. RESULTS: A consensus was achieved in defining the following: the clinical characteristics differentiating inflammatory and non-inflammatory signs and symptoms of joint disease; the most important differential diagnoses of PsA in clinical practice; the most useful screening questionnaires, serum laboratory tests and imaging techniques for the detection of early PsA; the criteria for dermatologist to refer patients with PsO to rheumatologist; the criteria for the diagnosis of PsA; the selection of the indices that the dermatologist could use for measuring the activity and severity of PsA in clinical practice; when systemic steroids and/or intra-articular steroid injections are indicated in the treatment of PsA. Finally, systemic treatments including synthetic and biologic disease-modifying antirheumatic drugs to be considered for the treatment of PsA have been reported. CONCLUSIONS: The implementations of these practical recommendations could be very helpful for the management of patients with PsA in the dermatology setting including early diagnosis and treatment.

Biomimetic proteolipid vesicles for targeting inflamed tissues.

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis.

Psoriasis is a common disease, which has a considerable impact on the healthcare system. Therefore, appropriate use of therapeutic resources is very important. Management of psoriasis in daily clinical practice is highly variable because many issues are still debated and not definitely addressed by the evidence-based medicine. Moreover, the different availability and reimbursability of drugs in each country justifies national guidelines. Expert consensus can provide helpful guidelines for optimizing patient care. A total of 20 dermatologists from different areas of Italy and with large experience in the treatment of psoriasis agreed to participate in the guidelines expert panel who aimed to reach consensus on the factors influencing psoriasis severity, the indications for systemic treatments, the parameters to be considered in the choice of treatment, and the factors to be considered in the choice of biological treatment. The recommendations for the use, screening and monitoring of systemic therapies were based on the 2015 S3 European Dermatology Forum/European Academy of Dermatology and Venereology psoriasis guidelines. Recommendations on the treatment of psoriasis in special patient populations were also agreed. The final document was discussed in a meeting moderated by a facilitator with participation of the entire group and adopting a nominal group technique to reach consensus. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts according to the Delphi procedure.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.