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.

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.

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.

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.

The constellation of dietary factors in adolescent acne: a semantic connectivity map approach.

BACKGROUND: Different lifestyle and dietetic factors have been linked with the onset and severity of acne. OBJECTIVE: To assess the complex interconnection between dietetic variables and acne. METHODS: This was a reanalysis of data from a case-control study by using a semantic connectivity map approach. 563 subjects, aged 10-24 years, involved in a case-control study of acne between March 2009 and February 2010, were considered in this study. The analysis evaluated the link between a moderate to severe acne and anthropometric variables, family history and dietetic factors. Analyses were conducted by relying on an artificial adaptive system, the Auto Semantic Connectivity Map (AutoCM). RESULTS: The AutoCM map showed that moderate-severe acne was closely associated with family history of acne in first degree relatives, obesity (BMI ≥ 30), and high consumption of milk, in particular skim milk, cheese/yogurt, sweets/cakes, chocolate, and a low consumption of fish, and limited intake of fruits/vegetables. CONCLUSION: Our analyses confirm the link between several dietetic items and acne. When providing care, dermatologists should also be aware of the complex interconnection between dietetic factors and acne.

MANAGEMENT OF PSORIATIC ARTHRITIS: SHOULD THE INTERACTION BETWEEN DERMATOLOGISTS AND RHEUMATOLOGISTS IN CLINICAL PRACTICE BE INTENSIFIED?

Psoriatic arthritis is an inflammatory seronegative spondyloarthropathy that occurs in approximately 25% of patients with psoriasis and is a progressive and severely disabling disease. Most patients have had psoriasis for several years before the development of arthritis or develop the joint and skin condition simultaneously. Given the absence of specific diagnostic test for psoriatic arthritis, clinical findings remain the standard criteria for the diagnosis. Patients with psoriasis presenting to the dermatologist for management of their skin disease may have joint symptoms related or not to psoriatic arthritis and similarly arthritic patients presenting to a rheumatologist for the management of psoriatic arthritis may have skin lesions related or not to psoriasis. In this paper an expert panel of specialist belonging to the “Associazione Dermatologi Ospedalieri Italiani” (ADOI) and “Collegio dei Reumatologi Ospedalieri Italiani” (CROI) analysed the international literature and scientific recommendations and also investigated the Italian setting. It has been demonstrated in the literature that a multidisciplinary clinical setting may benefit patients with psoriatic arthritis from both diagnostic and therapeutic points of view. The comparative analysis of the Italian clinical records used by ADOI and CROI have highlighted some substantial differences. Collaboration between the dermatologist and rheumatologist allows for a more complete appreciation of the overall skin and musculoskeletal disease burden, and subsequently leads to a more comprehensive treatment approach.

Biosimilar infliximab: an expert view.

CT-P13, a biosimilar of infliximab, was the first biosimilar monoclonal antibody to be approved in both the European Union and Korea. As a monoclonal antibody, CT-P13 is a large molecule with a high molecular weight, and as such it differs from other biosimilars currently in the market. The comparability exercise for CT-P13, therefore, requires special consideration, as it was the first demonstration of biosimilarity between a biosimilar monoclonal antibody and its originator. This paper summarizes current regulations on the approval of biosimilars, describes the evidence leading to the approval of CT-P13, and discusses the potential role of this molecule in the Italian scenario on the basis of the view of a group of experts.

Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline.

BACKGROUND: Dexamethasone is the corticosteroid most commonly used for the management of vasogenic edema and increased intracranial pressure in patients with brain tumours. It is also used after surgery (before embarking on radiotherapy), particularly in patients whose tumours exert significant mass effect. Few prospective clinical trials have set out to determine the optimal dose and schedule for dexamethasone in patients with primary brain tumours, and subsequently, fewer clinical practice guideline recommendations have been formulated. METHODS: A review of the scientific literature published to November 2012 considered all publications that addressed dexamethasone use in adult patients with brain tumours. Evidence was selected and reviewed by a working group comprising 3 clinicians and 1 methodologist. The resulting draft guideline underwent internal review by members of the Alberta Provincial cns Tumour Team, and feedback was incorporated into the final version of the guideline. RECOMMENDATIONS: Based on the evidence available to date, the Alberta Provincial cns Tumour Team makes these recommendations: Treatment with dexamethasone is recommended for symptom relief in adult patients with primary high-grade glioma and cerebral edema.After surgery, a maximum dose of 16 mg daily, administered in 4 equal doses, is recommended for symptomatic patients. This protocol should ideally be started by the neurosurgeon.A rapid dexamethasone tapering schedule should be considered where appropriate.Patients who have high-grade tumours, are symptomatic, or have poor life expectancy, can be maintained on a 0.5-1.0 mg dose of dexamethasone daily.Side effects with dexamethasone are common, and they increase in frequency and severity with increased dose and duration of therapy. Patients should be carefully monitored for endocrine, muscular, skeletal, gastrointestinal, psychiatric, and hematologic complications, and for infections and other general side effects.

A specific DNA methylation profile correlates with a high risk of disease progression in stage I classical (Alibert-Bazin type) mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma; in its classical presentation it evolves slowly, but it can have an aggressive course in a subset of patients. OBJECTIVES: To investigate the impact of epigenetic mechanisms on the progression of early stage MF. METHODS: We analysed DNA methylation at 12 different loci and long interspersed nucleotide elements-1 (LINE-1), as a surrogate marker of global methylation, on tissue samples from 41 patients with stage I MF followed up for at least 12 years or until disease progression. The methylation profiles were also analysed in two T-cell lymphoma cell lines and correlated with gene expression. RESULTS: The selected loci were methylated in a tumour-specific manner; concomitant hypermethylation of at least four loci was more frequent in cases progressing within 1-3 and 3-6 years than in late-progressive or non-progressive cases. LINE-1 methylation was significantly lower in rapidly progressive MF at 3 years (61%, P < 0·001) than in those at 12 years (67%). PPARG, SOCS1 and NEUROG1 methylation showed remarkable differences among the prognostic groups, but only PPARG was a significant predictor of disease progression within 6 years, after adjustment for patients' age or gender. Strikingly, a methylation profile similar to progressive cases was found in highly proliferative Sézary-derived HUT78 cells but not in MF-derived HUT102 cells. Exposure to a DNA demethylating agent restored sensitivity to apoptosis and cell cycle arrest. CONCLUSIONS: Epigenetic silencing of specific biomarkers can predict the risk of disease progression in early-stage MF, providing insights into its pathogenesis, prognosis and therapy.

Dermatology Life Quality Index score in vitiligo patients: a pilot study among young Italian males.

AIM: A negative impact on vitiligo patients in terms of quality of life (QoL) has been suggested. The aim of this report was to study the QoL in a sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. METHODS: A sample of forty seven vitiligo subjects, identified among 34,740 potential conscripts resident in southern Italy underwent the Italian version of the DLQI questionnaire. RESULTS: The median total DLQI score was 1 (IQR: 2; mean: 1.82). In univariate analysis, DLQI total score was significantly influenced by the clinical course of vitiligo, disease extension over the body, and location on face and/or hands. Multivariate analysis using logistic stepwise regression showed that only the localization on the hands and on the face influenced significantly the mean DLQI. CONCLUSION: Our study conducted on a random sample of individuals affected by vitiligo selected from the general young male population in Italy, does not document a large impact of vitiligo on QoL. However, variations exist and the location of lesions on the face and/or hands may impact on QoL. Population-based studies are not affected by selection biases connected with seeking medical care and should be more widely performed.

Vitiligo and autoimmunity: an epidemiological study in a representative sample of young Italian males.

BACKGROUND: It is stated that patients with vitiligo have an increased risk of developing autoimmune diseases. OBJECTIVE: The aim of this study was to estimate the prevalence of autoantibodies or overt autoimmune diseases in a group of vitiligo patients examined among a sample deemed to be representative of the general population of young men living in southern Italy. METHODS: A total of 60 vitiligo patients were identified among 34,740 potential conscripts visited to evaluate their fitness to compulsory service in Italian Navy, obtaining a prevalence of 0.17% (95% CI: 0.13-0.22), which was deemed the prevalence of vitiligo in the Italian general population of the same age and sex. Forty of these vitiligo patients underwent blood test including also the search of the main autoantibodies. RESULTS: Circulating autoantibodies were detected in 42.5% of subjects. Anti-thyroglobulin antibodies were documented in 27.5%, anti-thyroperoxidase in 22.5%, anti-smooth muscle in 17.3%, anti-nuclear, anti-mitochondrial and anti-gastric parietal cells in 2.5% respectively. Only in two cases (5%) an overt thyroid disease was diagnosed. No significant association between the extension of the skin involved / clinical course of the disease and circulating autoantibodies was detected. Circulating autoantibodies (particularly anti-thyroid antibodies) were statistically associated with a lower duration of the disease. CONCLUSIONS: In agreement with other studies, autoantibodies in the lack of clinical manifestations have been frequently observed in our vitiligo patients, especially during the early phase of the disease. The clinical significance of this finding seems to be limited, with the possible exception of thyroid disease, and it needs further exploration, through large cohort studies.

Erlotinib-induced pustular eruption.

The epidermal growth factor receptor (EGFR) inhibitor erlotinib was found to significantly improve overall survival, time to progression, and cancer-related symptoms in locally advanced or metastatic non small cell lung carcinoma (NSCLC). Unfortunately, cutaneous side effects are not rare, the most common one being a follicular acneiform eruption. As it has been observed a positive correlation between rash severity and objective tumor response, it is critical for dermatologists early distinguish it from rashes carrying a different prognosis and needing a different management.

The 'EpiEnlist' project: a dermo-epidemiologic study on a representative sample of young Italian males. Prevalence of selected pigmentary lesions.

BACKGROUND: Few studies on the prevalence and incidence of many skin conditions in the general population are available because it is difficult to submit to dermatologic examination large samples of seemingly healthy population. OBJECTIVE: The aim of this study was to estimate the prevalence of several skin conditions among a sample that is deemed to be representative of the general population of young men living in southern Italy. PATIENTS/METHODS: Potential conscripts resident in the coastal regions of southern Italy and called at the age of 18 to the Draft's Council Medical Unit in Taranto underwent a clinical and instrumental examination to evaluate their psycho-physical fitness to compulsory service in Italian Navy. From January 1998 to April 2004 a dermo-epidemiologic project named EpiEnlist (EPIdemiology in ENLISTed Men) project was carried out by the Department of Dermatology of the Italian Navy Hospital in Taranto under the auspices of the Italian Group for Epidemiological Research in Dermatology. All the subjects showing skin lesions evocative of neurofibromatosis (NF), congenital melanocytic nevus (CMN), Becker nevus (BN), and vitiligo were referred to the Department of Dermatology of the Italian Navy Hospital for confirming the diagnosis. The confirmed cases were recorded in a predefined patient's card, containing the main anamnestic, clinical, instrumental, and laboratory data. RESULTS: Because the recording of the various conditions started and ended in different times, the total number of examined subjects varied. NF type 1 was diagnosed in 6 of 34 740 subjects [prevalence 1:5735 or 0.017%; 95% confidence interval (95% CI), 0.0008-0.0037], CMN in 157 of 23 354 (prevalence 1:148 or 0.67%; 95% CI, 0.57-0.79). BN was observed in 70 of 27 954 young men (prevalence 1:399 or 0.25%; 95% CI, 0.15-0.35), and its mean age of appearance was 11.9 years (minimum 5-maximum 17). In 41 subjects (58.6%), the age of appearance was over 10 years. Vitiligo was recorded in 60 of 34 740 persons (prevalence 1:579 or 0.17%; 95% CI, 0.13-0.22). In 40 subjects with vitiligo, the blood test was done: in 40% of these circulating autoantibodies, mainly anti-thyroid (25.6%) and anti-smooth muscle (17.3%) autoantibodies were detected, but only in 5% of cases, a thyroid disease was diagnosed, and no other sign of autoimmune diseases was observed. CONCLUSIONS: The epidemiological data of the skin conditions considered in the present study can be considered roughly in agreement with those reported in the available surveys. Because they were obtained in a large sample of Italian young males from the general population, they can be useful for therapeutic and preventive interventions by the public health organizations.