Efficacy of JAK inhibitors in the treatment of psoriasiform atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexisting of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-IL-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed JAK inhibitors (JAKi) as a viable alternative, even in the first line, in patients with different clinical phenotypes of AD, including psoriasiform AD. A retrospective analysis of patients in our dermatology clinic with moderate-severe AD and treated with JAKi was performed. Among the 192 overall patients, 21 had psoriasiform AD. EASI, p-NRS and DLQI were the severity scores considered and their reduction was observed in all 21 patients at weeks 4, 16 and 24 of treatment. At week 16 the percentage of patients achieving EASI-75 and EASI-90 was 80.95% and 66.67%, respectively. While at week 24 95.23% of patients achieved EASI-75 and 85.71% obtained EASI-90. No adverse event lead to treatment interruption. This study confirmed the clinical effectiveness of JAKi treatment in adult patients with moderate-to-severe psoriasiform AD, with a good safety profile. These drugs are proposed as the first choice for the treatment of this form of AD, although further studies with larger cohorts are required.

The new Italian SIDAPA Baseline Series for patch testing (2023): an update according to the new regulatory pathway for contact allergens.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease caused by delayed hypersensitivity to chemical and biotic contact allergens. ACD significantly affects the patients' quality of life negatively impacting both occupational and non-occupational settings. Patch testing is the gold standard diagnostic in vivo test to precise the ACD etiology and to correctly perform prevention. According to the Italian Medicines Agency (AIFA) legislative decree no. 178 of 29th May 1991, allergens are defined as medicines and therefore they are subject to strict regulation. In 2017, AIFA (decree no. 2130/2017) started a procedure to regulate contact allergens on the Italian market and actually the contact allergens temporarily authorized are reported in AIFA decree no. 98/2022, valid until November 2023. The availability on the market of contact allergens to diagnose ACD and continuous updating on the basis of new epidemiological trends are mandatory, jointly with the continuous update of the baseline and integrative series for patch testing. For this reason, the scientific community represented in Italy by the Skin Allergies Study Group of SIDeMaST (Italian Society of Dermatology and Venereology) and SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) are constantly working, in close relationship with the European scientific communities with large expertise in this important sector of the modern Dermatology. Herein, we report the setting up of regulatory legislation by AIFA and the new Italian Adult Baseline Series for patch testing.

Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus.

INTRODUCTION: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. METHODS: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. RESULTS: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. CONCLUSION: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Contact allergy to SIDAPA baseline series allergens in patients with eyelid dermatitis: An Italian multicentre study.

BACKGROUND: Eyelid dermatitis is a frequent reason of dermatological consultation. Its aetiology is not univocal, being contact dermatitis, both allergic and irritant, the most frequent. The primary sources of allergen exposure include cosmetics, metals, and topical medications, from direct, indirect, or airborne contact. OBJECTIVES: To define the frequency of positive patch test reactions to SIDAPA baseline series allergens, to document positive allergens, and to precise the final diagnosis in patients with eyelid involvement. METHODS: A total of 8557 consecutive patients from 12 Italian Dermatology Clinics underwent patch testing with SIDAPA baseline series in 2018 and 2019. Patients were divided into two groups: (i) with eyelid involvement with or without other involved sites (E-Group) and (ii) without eyelid involvement (NE-Group). The final diagnosis and the frequency of positive relevant patch test reactions were evaluated. RESULTS: E-Group consisted of 688 patients (females 78.6%, mean age 45.3 years), 8.0% of 8557 consecutively patch-tested patients. The final diagnosis in E-Group was ADC in 42.4%, ICD in 34.2%, and AD in 30.5%. The highest reaction rates were elicited by nickel sulphate and methylchloroisothiazolinone/methylisothiazolinone in both E-Group and NE-Group, even if these allergens were significantly more frequently positive in NE-Group patients than in E-Group ones. Positive patch test reactions to fragrance Mix II, dimethylaminopropylamine, and sorbitan sesquiolate were significantly more frequent in E-Group patients than in NE-Group ones. CONCLUSIONS: Eyelid dermatitis is a frequent dermatological complaint. Allergic contact dermatitis is the most frequent diagnosis commonly caused by nickel sulphate, isothiazolinones, and fragrances. The surfactants dimethylaminopropylamine and sorbitan sesquioleate are emerging causes of eyelid allergic contact dermatitis.

Considerations for managing elderly patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) diagnosis in elderly is challenging, due to its clinical polymorphism and the lack of diagnostic biomarkers. Moreover, the chronicity of the disease and the complex pathogenetic mechanism, make elderly AD management challenging. AREAS COVERED: A narrative review of the current literature was performed using the PubMed, Medline, Embase, and Cochrane Skin databases, by researching the following terms: 'atopic dermatitis,' 'clinical phenotypes,' 'eczema,' 'elderly patients,' 'elderly type atopic dermatitis,' 'eczema clinical presentation.' The aim was to report the current knowledge on pathogenesis, clinical presentation, and treatment options of elderly AD. EXPERT OPINION: Elderly type AD has recently been identified as a separate entity, with an increasing prevalence. With aging, both immunosenescence and barrier alterations can cause or modify AD presentation. Moreover, a chronic proinflammatory state (so-called 'inflammaging') is often present in elderly subjects. Older patients with AD may present with peculiar immunophenotypic profile, making AD diagnosis challenging. Similarly, the chronicity of the disease and the complex pathogenetic mechanism, make AD management a challenge. Indeed, systemic therapies for AD are often contraindicated or not tolerated and the management of elderly type AD is often burdened with numerous difficulties, leading to undertreated disease. Even if dupilumab and tralokinumab represent a valuable therapeutic weapon, more data on safety of JAK inhibitors are required.

Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis.

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18-75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020-August 2023. Upadacitinib survival was investigated through Kaplan-Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.

Injection site reactions after dupilumab or tralokinumab for atopic dermatitis.

Background: Injection site reaction (ISR) is a local phenomenon defined as a constellation of symptoms, including swelling, erythema, pruritus, and pain around the site of injection.Objective: ISR is reported as a frequent adverse event after subcutaneous injection (SCI) of several biologics.Methods: We performed an observational real-life study to compare dupilumab and tralokinumab as regards ISR, analysing frequency, duration and intensity of symptoms related to SCI. From January 2023 to June 2023, we enrolled adult patients affected by moderate to severe AD and being on dupilumab or tralokinumab treatment. A 12 items questionnaire was administered to all enrolled patients.Results and conclusions: Three hundred and ninety-two patients were included. ISR was a frequent occurrence in both the treatment groups, with tralokinumab causing ISR more frequently than dupilumab. However, the reactions were generally mild and no patient stopped therapy.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

Efficacy and Safety of Tralokinumab in Real Life: Possible Predictive Rapid Response Factors.

Background: Tralokinumab has been recently approved for the management of moderate-to-severe atopic dermatitis (AD). Despite its effectiveness and safety have been widely reported, there are no studies investigating factors that may affect clinical outcomes. Objective: To evaluate the effectiveness and safety of tralokinumab, also to investigate possible predictive response factors that may affect the time of onset of treatment response. Methods: A monocentric retrospective real-life study was performed enrolling AD patients undergoing treatment with tralokinumab for at least 24 weeks. AD severity was assessed at baseline and at week (W)16, and W24. Similarly, treatment-related adverse events (AEs) were evaluated at each follow-up visit. Results: A total of 57 patients were enrolled. AD severity started to improve at W4, continued to improve at W16 and W24. In our cohort, we found out that gender, age, atopic comorbidities, and previous treatments did not affect treatment outcomes. However, we observed that patients with higher Pruritus-Numerical Rating Scale (≥8), relapsing form of AD, Eczema Area and Severity Index (EASI) ≤24, and Investigator Global Assessment (IGA) ≤3 achieved more frequently EASI75 response at W16. No significant AEs were collected. Conclusions: Our study confirmed the effectiveness and safety of tralokinumab. In particular, a higher pruritus, a relapsing course of the disease, a reduced EASI, a reduced IGA, and a brief duration of the disease seem to be associated with the fastest onset of treatment effectiveness.

Safety of omalizumab in chronic urticaria during pregnancy: a real-life study.

BACKGROUND: Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant. OBJECTIVES: To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy. METHODS: We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception. RESULTS: Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group. CONCLUSIONS: Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.

AtopyReg®, the Prospective Italian Patient Registry for Moderate-to-Severe Atopic Dermatitis in Adults: Baseline Demographics, Disease Characteristics, Comorbidities, and Treatment History.

BACKGROUND AND OBJECTIVE: AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. METHODS: Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. RESULTS: A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18-90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. CONCLUSIONS: This baseline data analysis deriving from AtopyReg® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life.

Dupilumab-associated inflammatory arthritis: a literature review.

Dupilumab is a fully human monoclonal antibody that acts by inhibiting the interleukin (IL)-4 receptor subunit α, and hence the IL-4 and IL-13 signalling pathway. Dupilumab treatment has been linked to the onset of T helper 17-driven inflammatory diseases, including cases of seronegative arthritis and enthesitis. To date, dupilumab-associated inflammatory arthritis (DAIA) represents a relatively unknown adverse event, initially reported in single cases or case series reports. Indeed, the onset of DAIA may not be promptly recognized, and is probably underestimated. Here we have reviewed the available English literature regarding arthritis and enthesitis onset during dupilumab treatment for atopic dermatitis, aiming to improve rapid recognition and thus prompt treatment of these diseases.

Comparison of Long-Term Effectiveness and Safety of Upadacitinib for Atopic Dermatitis Between Dupilumab-Exposed and Dupilumab-Naïve Patients.

BACKGROUND AND OBJECTIVES: Upadacitinib is an oral selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients [Formula: see text] 12 years of age. In real life, upadacitinib currently represents a valid therapeutic option for patients failing available systemic therapies, in particular patients who discontinued dupilumab because of lack of efficacy or occurrence of adverse events. The objectives of the present study were to compare the effectiveness and safety of upadacitinib in patients affected by AD who had previously failed dupilumab therapy versus biologic naïve patients. METHODS: A retrospective, multi-centre, observational, real-life study was conducted in four Italian dermatological referral centres (Milan, Perugia, Naples and Vicenza). Baseline characteristics included age, sex, AD history and severity, prior treatments, comorbidities and concomitant therapies. AD severity was assessed at baseline and at week 4 (W4), W16, W24 and W52, using Eczema Area Severity Index (EASI), Dermatology Life Quality Index (DLQI) and Pruritus Numerical Rating Scale (P-NRS) scores. Full blood count, hepatic and renal function, lipid panel, and muscle enzymes [lactate dehydrogenase (LDH) and creatine phosphokinase (CPK)] were assessed at baseline and at each follow-up visit. RESULTS: A total of 113 patients (72 males, 63.7%; mean age: 37.22 ± 16.8 years) were included in the analysis, all patients were in treatment and underwent follow-up period until W16, whilst 91 (80.5%) and 75 (66.4%) patients were in treatment and in follow-up period until W24 and W52, respectively. Mean EASI score significantly changed from 24.30 ± 10.27 to 1.28 ± 4.34, 0.74 ± 2.31 and 0.25 ± 1.34 at W16, W24 and W52, respectively (p < 0.0001). Specifically, at W16 the percentage of patients achieving EASI-75, EASI-90 and EASI-100 was 85.21, 76.35 and 66.11%, respectively. At W24, EASI-75, EASI-90 and EASI-100 were reached by 88.54, 85.42, and 78.37% of patients, respectively. Finally, 90.1% of patients achieved EASI-75, 88.3% achieved EASI-90 and 83.0% achieved EASI-100 at W52. CONCLUSIONS: This study confirmed the clinical effectiveness of upadacitinib treatment in adult patients in a real-world setting with moderate-to-severe AD who had discontinued dupilumab due to poor effectiveness or adverse events and who were biologic naïve; therefore, previous treatments do not seem to affect the response to upadacitinib treatment.