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.

Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study.

BACKGROUND: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. RESULTS: A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). CONCLUSION: Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA.

Comorbidities and treatment patterns in adult patients with atopic dermatitis: results from a nationwide multicenter study.

Adult atopic dermatitis (adult AD) is a systemic inflammatory disorder, whose relationship with immune-allergic and metabolic comorbidities is not well established yet. Moreover, treatment of mild-to-moderate and severe atopic dermatitis needs standardization among clinicians. The aim of this study was to evaluate the distribution of comorbidities, including metabolic abnormalities, rhinitis, conjunctivitis, asthma, alopecia and sleep disturbance, according to severity of adult AD, and describe treatments most commonly used by Italian dermatologists. Retrospective, observational, nationwide study of adult patients over a 2-year period was performed. Clinical and laboratory data were obtained through review of medical records of patients aged ≥ 18 years, followed in 23 Italian National reference centres for atopic dermatitis between September 2016 and September 2018. The main measurements evaluated were disease severity, atopic and metabolic comorbidities, treatment type and duration. Six-hundred and eighty-four adult patients with AD were included into the study. Atopic, but not metabolic conditions, except for hypertension, were significantly associated with having moderate-to-severe AD in young adult patients. Disease duration was significantly associated with disease severity. Oral corticosteroids and cyclosporine were the most widely used immunosuppressant. Our study seems confirm the close relationship between adult AD and other atopic conditions, further long-term cohort studies on patients affected by adult AD need to be performed to evaluate the complex relationship between adult AD disease severity and metabolic comorbidities.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

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.

Sun-safe behaviours, personal risk, level of concern, and knowledge about cutaneous melanoma in italy: time for social marketing?

INTRODUCTION: The incidence of cutaneous melanoma is increasing, although 80-95% of all deaths caused by melanoma can be avoided through protective behaviours. There is evidence that social marketing as an approach in public health can improve health-related behaviours and encourage sun-safe behaviours. METHODS: A multicentre survey was conducted to collect and compare data about cutaneous melanoma risk, knowledge, concern, and protective behaviours across Northern, Central, and Southern Italy, and explore how these data could potentially inform a social marketing intervention to improve sun-safe behaviours. Data were analysed using descriptive and inferential statistics. RESULTS: A total of 1,028 questionnaires were collected. Apart from 'Personal Risk' no statistically significant differences were found between the three regions. About 30% (n = 344) of the total sample had high levels of personal risk, and low levels of concern and protective behaviour, and over 70% (n = 711) gave priority to sun tanning. The worst scores were related to knowledge about melanoma (30% wrong answers, and over 40% 'don't know'). Protective behaviour was moderately correlated with age (p = 0.03). Personal risk was significantly higher in women (10.84 vs 10.05), and lower in individuals with a degree (9.46 vs 11.38; p < 0.001). CONCLUSIONS: Over 70% of our sample gave priority to sun tanning, which combined with low levels of concern and knowledge about melanoma, and high levels of personal risk, confirm that much still needs to be done in terms of melanoma prevention, but all these are aspects that could be effectively addressed through social marketing interventions.

Association between genetic polymorphisms of glutathione S-transferase M1/T1 and psoriasis in a population from the area of the strict of messina (Southern Italy).

Glutathione S-transferases (GST) are antioxidant enzymes with frequent genetic polymorphisms. Homozygosis for gene deletion ("null" genotype) of GSTM1 and GSTT1, causing decrease of the antioxidant potential of the organism, is frequent, with variable frequency in different ethnic contexts. Although oxidative stress notoriously plays a role in the pathogenesis of psoriasis, few studies exist on the association between GSTM1/GSTT1 genotype and psoriasis, with different results. We aimed to assess the frequency of GSTM1/GSTT1 polymorphisms in Southern Italian psoriatic patients and controls and investigate the association of the GSTM1/GSTT1 genotype with individual and disease parameters. To this aim, the GSTM1/GSTT1 genotype of 148 psoriatic patients and 148 age- and sex-matched controls was defined by PCR on oral mucosa cells. GSTT1 null was associated with psoriasis (55.4% of patients vs. 25% of controls, p = 9.58 × 10-8, odds ratio 3.73), while GSTM1 null was not. The GSTM1/GSTT1 "double null" genotype conferred an even higher odds ratio for psoriasis (5.94). The association between psoriasis and GSTT1 null was stronger in women (54.1% of patients vs. 19.7% of controls, p = 8.13 × 10-5) than in men (56.3% of patients vs. 28.7% of controls, p = 0.0002). No association was found between GSTM1/GSTT1 genotype and psoriasis severity, age of onset or comorbidities (psoriatic arthritis, metabolic syndrome). The remarkable differences among the few available data on the association between GSTM1/GSTT1 polymorphisms and psoriasis suggest the need for further studies, on different and larger populations, to improve knowledge on the pathogenesis of psoriasis and possibly provide more precise and personalised prevention and treatment in the future.

Evaluation of cutaneous surface parameters in psoriatic patients.

PURPOSE: The purpose of this study was to compare cutaneous surface parameters in lesional and non-lesional skin of psoriatic patients and in corresponding areas of control subjects. METHODS: Sixty-six psoriatic patients (of any grade of severity, with or without arthritis, without any therapy other than systemic biologic drugs) and 28 healthy controls were enrolled in this observational, case-control study. Exclusion criteria were current or past sebo-psoriasis and seborrheic dermatitis, pustular or erithrodermic psoriasis; treatment with immune-suppressive agents, retinoids, or ultraviolet phototherapy in the last 6 months; topical treatment in the last 2 weeks. Corneometry, sebumetry, and pHmetry were evaluated on non-lesional skin of forehead, cheek, chin and volar region of forearm, and on a psoriatic plaque (on elbow or neighboring areas); in controls, the same areas were considered. RESULTS: Corneometry values were significantly lower in psoriatic plaques vs. elbows of controls. Sebumetry showed significantly higher values in non-lesional forearm skin and plaques of psoriatic patients vs. corresponding areas of controls. pH was significantly lower in all areas in psoriasis. No differences were found between patients treated or not with biologics and with or without arthritis. CONCLUSION: Evaluating surface skin parameters in psoriasis is useful to better understand the etiopathogenic mechanism and could suggest new therapeutic approaches.

IL-31 and IL-33 circulating levels in allergic contact dermatitis.

Enhanced IL-31 expression in skin biopsies is present in allergic contact dermatitis (ACD). IL-33 expression is induced in keratinocytes and in skin of ACD patients. This overexpression is present in both allergic and irritant conditions. The aim of this work was to test the systemic involvement of IL-31 and IL-33 in ACD. IL-31 levels were significantly higher in patients than in controls. IL-33 serum levels, on the contrary, were similar in patients and controls. This work shows a possible systemic involvement of IL-31 and the absence of a systemic involvement of IL-33 in ACD. IL-31 levels do not seem related to the allergen involved, and did not change on the strength of the allergen involved. More likely, IL-31 levels are related to the itch. IL-33, instead, is secreted from damaged or inflamed tissue and might function as an early warning system at the site of skin damage. In the future, IL-31 could be a possible therapeutic target of all pruritic skin diseases resistant to conventional therapies.