Tralokinumab for the Treatment of Adult Atopic Dermatitis in Special Populations.

Introduction: Even if mild forms of atopic dermatitis (AD) are usually well controlled with topical prescription drugs and emollients, the management of severe forms of the disease may be challenging, especially in special populations (SPs). These patients include groups of disadvantaged people (elderly, patients with disabilities and serious medical conditions) who are usually excluded from clinical trials. As a consequence, most of the data about the efficacy and safety of a drug in these patients derives from post-marketing experiences. In this context, the aim of our study was to retrospectively investigate the effectiveness and safety of tralokinumab in the management of AD in SPs. Methods: A 24-weeks retrospective, dual-center study was performed enrolling patients with a diagnosis of moderate-to-severe AD undergoing treatment with tralokinumab at labelled dosage. Disease severity was assessed using Eczema Area Severity Index (EASI), Pruritus-Numerical Rating Scale (P-NRS), and Dermatology Life Quality Index (DLQI) score at baseline and after 4 weeks (W4), W16, and W24. Adverse events (AEs) were monitored at the same timepoints. Statistical significance of clinical improvement (EASI, P-NRS, DLQI) at week 4, week 16, and week 24 as compared with baseline was evaluated by using Student's t-test, considering significant a p-value <0.05. Results: Our study enrolling 27 SPs patients showed a significant improvement in EASI and P-NRS since week 4, continuing to improve up to week 24. Similarly, DLQI significantly decreases at each timepoint as compared with baseline. Finally, no AEs were reported during the study period. Of interest, our cohort included oncologic patients, a patient with a history of severe infection, as well as subjects affected by severe neurological, psychiatric, pulmonary, and/or cardiovascular disease. Discussion: Our experience showed that tralokinumab is effective and safe in elderly patients and subjects affected by severe comorbidities.

Hand eczema in Italian patients referred for patch testing: A retrospective SIDAPA study (2016-2023).

BACKGROUND: Hand eczema (HE) is a common skin disease with a negative impact on patients' quality of life in occupational and non-occupational settings. Up-to-date, data on HE in Italian patients referred for patch testing are lacking. OBJECTIVES: To characterise the profile in terms of demographics, aetiology and patch test results of Italian patients affected by HE referred for patch testing. METHODS: A retrospective descriptive study on consecutive patients affected by HE who underwent patch testing from 2016 to 2023 in eight dermatology clinics was performed. HE patients were divided into two groups according to the exclusive (HE-only group) and not-exclusive (HE+ group) hand involvement, and compared to patients with eczema localised in body areas other than hands (NHE group). RESULTS: One thousand five hundred and ninety-seven patients were affected by HE (35.3% males; mean age 42.7 years), 60.2% belonging to the HE-only group and 39.8% to the HE+ group. Occupational dermatitis was diagnosed in 33.2% of HE-only patients, 25.0% of HE+ patients and 5.2% of NHE patients (p < 0.001). HE-only patients presented: Allergic Contact Dermatitis (ACD), Irritant Contact Dermatitis (ICD), atopic HE in 48.1%, 47.5% and 7.1%, respectively; hyperkeratotic palmar, acute recurrent vesicular and nummular clinical subtypes in 52.2%, 43.9% and 11.9%, respectively; relevant positive patch test reactions in 48.1% (nickel sulphate 18.9%, methylchloroisothiazolinone/methylisothiazolinone 10.6%, methylisothiazolinone 8.6%, p-phenylenediamine 6.0% and potassium dichromate 4.7%). CONCLUSIONS: HE patients, and particularly those with exclusive hand involvement, show a particular profile in terms of demographic and clinical characteristics, etiologies and relevant positive patch test reactions.

Lichen planus following Covid-19 vaccination: a narrative review.

Lichen planus (LP) is an inflammatory disease that afflicts skin, mucous membranes, cutaneous appendages. Moreover, LP represents a prototype of lichenoid dermatosis, being characterized by the presence of a dense dermal cell infiltrate. Although most cases of LP are idiopathic, infectious and drug-related factors must also be considered in the etiology. In this context, the occurrence of LP and lichenoid drug eruption following different types of vaccination is a possible event. Therefore, the aim of our review is to provide a broad perspective to clinicians by analyzing the current literature cases of LP and lichenoid eruptions following COVID-19 vaccination, also investigating the possible pathogenetic mechanisms underlying this phenomenon. A total of 61 cases of LP and lichenoid eruption following COVID-19 vaccination have been collected. However, the number of cases of LP and lichenoid drug eruption is extremely low if compared to the number of vaccines administered overall, suggesting that the risk of LP and lichenoid eruption following COVID-19 vaccination is extremely low. Certainly, further studies are desirable to identify the population most at risk and the possibility of taking preventive measures.

Effectiveness and Safety of Upadacitinib for Adolescents with Atopic Dermatitis in a Real-World Setting.

BACKGROUND AND OBJECTIVE: The estimated prevalence of atopic dermatitis (AD) among adolescents (12-17 years of age) is about 14.8%. AD compromises sleep quality and may be associated with poor scholastic performance, mood disruptions, low self-esteem, and difficulty in building social relationships. Upadacitinib was recently approved by the European Medicines Agency for the treatment of moderate-to-severe AD in patients aged ≥ 12 years who are candidates for systemic treatment. The aim of this real-world study was to determine the effectiveness in disease control and safety of upadacitinib in adolescents aged 12-17 years with moderate-to-severe AD. METHODS: This is a retrospective study in adolescents with moderate-to-severe AD treated with upadacitinib 15 mg between July 2022 and February 2024 at six Italian dermatological referral centres. The primary endpoint was to analyse the evolution of the response in terms of absolute Eczema Area and Severity Index (EASI) value, as well as the percentage of patients achieving 75% and 90% improvement in EASI (EASI75 and EASI90) from baseline to weeks (W) 4, 16, 24, and 52. Secondary endpoints included the assessment of treatment efficacy in terms of Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), Children's Dermatology Life Quality Index (c-DLQI), and safety. RESULTS: Thirty-six patients [males: 18 (50%)] were evaluated. A statistically significant improvement of EASI was observed at each timepoint, as stated by a mean percentage reduction from baseline of 72.2% at W4, 82.7% at W16, of 86.4% at W24 (n = 34) and of 92.7% at W52 (n = 18) (p < 0.0001). At W4, 21/36 (58.3%) achieved EASI75 and 12/36 (33.3%) EASI90. At W16, 29/36 (80.5%) achieved EASI75 and 19/36 (52.8%) EASI90. At W24, 32/34 (94.1%) reached EASI75 and 24/34 (70.6%) EASI90. Finally, at W52 all the assessed patients (n = 18) maintained EASI75 and 14/18 (77.7%) reached EASI90. Likewise, a statistically significant reduction of c-DLQI, P-NRS and S-NRS was observed at each timepoint. CONCLUSION: Our real-world experience seems to confirm the efficacy and safety of upadacitinib for the long-term treatment of moderate-to-severe AD in adolescents.

Technostress: The impact of technology on Italian dermatologists' burnout.

Dermatologists' burnout is a growing phenomenon. During the last years, an important role on medical stress is played by the ever-increasing use of common technological devices (smartphones, smartwatches, PCs and tablets). The aim of the study was to investigate whether digital technology use causes burnout among Italian dermatologists, using a survey conducted among a group of Italian dermatologists. The final sample contained 194 responses valid for analysis. A positive and significant relationship between technostress, assessed through Technostress Inventory and burnout, assessed through Maslach Burnout Inventory, among Italian dermatologists was found. Our data seems suggesting a close relationship between technostress and dermatologist burnout.

Short-, mid- and long-term efficacy of dupilumab in moderate to severe atopic dermatitis: a real life multicenter Italian study on 2576 patients.

BACKGROUND: The efficacy and safety of dupilumab in atopic dermatitis (AD) have been defined in clinical trials but limited real-world evidence on long term treatment outcomes are currently available to inform clinical decisions. OBJECTIVES: to describe long-term effectiveness and safety of dupilumab up to 48 months in patients with moderate-to-severe AD. METHODS: a multicenter, retrospective, dynamic cohort study was conducted to assess long term effectiveness and safety of dupilumab in patients with moderate to severe AD in a real-world setting. Predictors of minimal disease activity (MDA) optimal treatment target criteria (defined as the simultaneous achievement of EASI90, itch NRS score ≤1, sleep NRS score ≤1 and DLQI ≤1) were investigated. RESULTS: 2576 patients were enrolled from June 2018 to July 2022. MDA optimal treatment target criteria were achieved by 506 (21.91%), 769 (40.63%), 628 (50.36%), 330 (55.37%) and 58 (54.72%) of those that reached 4, 12, 24, 36 and 48 months of follow-up, respectively. Logistic regression revealed a negative effect on MDA achievement for conjunctivitis and food allergy at all timepoints. Adverse events (AE) were mild and were observed in 373 (15.78%), 166 (7.02%), 83 (6.43%), 27 (4.50%) and 5 (4.55%) of those that reached 4, 12, 24, 36 and 48 months of follow-up. Conjunctivitis was the most frequently reported AE during the available follow-up. AE led to treatment discontinuation in <1% of patients during the evaluated time periods. CONCLUSION: High long-term effectiveness and safety of dupilumab were confirmed in this dynamic cohort of patients with moderate to severe AD, regardless of clinical phenotype and course at baseline. Further research will be needed to investigate the effect of Th2 comorbidities and disease duration on the response to dupilumab and other newer therapeutics for AD.

Efficacy of Janus kinase 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 coexistence of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-interleukin (IL)-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed Janus kinase inhibitors (JAKi) as a viable alternative, even as a first-line treatment, in patients with different clinical phenotypes of AD, including psoriasiform AD. We performed a retrospective analysis of patients in our dermatology clinic with moderate-to-severe AD who were treated with JAKi. Among 192 patients overall, 21 had psoriasiform AD. We used the Eczema Area and Severity Index (EASI), Pruritus-Numerical Rating Scale and Dermatology Life Quality Index for considering severity scores, and reduction was observed in all 21 patients at week (W) 4, W16 and W24 of treatment. At W16, 81% and 67% achieved EASI-75 and EASI-90, respectively, while at W24 95% of patients achieved EASI-75 and 86% obtained EASI-90. No adverse event led 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 treating this form of AD, although further studies with larger cohorts are required.

A Multidisciplinary Approach Is Beneficial in Atopic Dermatitis.

Atopic dermatitis (AD) is a highly heterogeneous chronic inflammatory skin disorder that is frequently associated with a plethora of comorbidities. AD is, therefore, considered a systemic disease impacted by a considerable burden and leading to poor quality of life, especially in patients with moderate-to-severe disease. Since atopic and non-atopic comorbidities can further worsen the disease course, accurate establishment of the patient's individual intrinsic risk profile and needs is crucial and may help in guiding the selection of the best treatment option. Better quality of care for patients with AD can be delivered through a multidisciplinary team led by a dermatologist, for comprehensive patient management. The implementation of a multidisciplinary approach for AD could enhance the delivery of optimised and safe treatments, improve the standard of care and patient outcomes in the short and long term, and prevent or delay the lifelong impact of uncontrolled AD. Understanding the unmet needs, assessing correctly the patient risk profile and enhancing the shared patient-physician decision-making process can lead to disease control and quality-of-life improvement, especially in the context of the introduction of newer treatment for AD. This narrative review is a call for more data to establish standardised patient profiles and multidisciplinary strategies in AD management. In view on the fast-evolving treatments for AD, this review aims at highlighting the importance of a multidisciplinary approach to a comprehensive assessment and holistic care in patients with moderate-to-severe AD.

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.

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.

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.