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Introduction: Chronic hand eczema (CHE) is an inflammatory skin condition characterized by different pathomechanisms, clinical presentations, and prognoses. Treatment is often challenging because of limited approved drugs, and severe CHE is associated with reduced quality of life (QoL) and poor overall health measures in terms of psychological, functional, and occupational challenges. This study aims to describe the real-life management practices of Italian dermatologists who frequently treat patients with CHE, compare these practices with existing guidelines, and propose practical clinical recommendations for the management of these patients., Methods: An 11-question survey was administered to 14 participating dermatologists to gather their insights on the diagnosis, treatment, and management of CHE. Moreover, a comprehensive literature search was conducted over the previous 10 years as a starting point for discussion among experts., Results: CHE was the reason for 6.9% of dermatological consultations by the 14 experts. Median time to CHE diagnosis was 12 (range: 2-24) months. Fissuring and itching (85.7% for both) were the most frequently reported signs and symptoms of CHE. The survey highlighted the need for long-term treatment that is effective and well tolerated, with experts emphasizing the importance of improving disease awareness among physicians and patients. Practical clinical approaches were proposed, emphasizing the significance of a thorough medical history and identification of symptoms in the management of CHE. Experts advocated for specifically developed CHE treatment approaches, concentrating on alleviating symptoms and signs, minimizing adverse events/safety issues, enhancing the QoL of patients, and long-term disease control. Findings from this survey were further discussed and compared to recommendations of the available guidelines for the management of CHE., Conclusions: Managing CHE requires a comprehensive approach that considers both objective clinical factors and subjective patient expectations. Experts emphasized the need for effective and well-tolerated long-term therapies, improved disease awareness, and communication among physicians and patients., Competing Interests: Declarations. Conflict of Interest: The authors disclose the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Luca Stingeni has acted as Principal Investigator, speaker, and board member for AbbVie, Almirall, Amgen, Bristol Meyer Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis and Sanofi. Maria Concetta Fargnoli has served on advisory boards, received honoraria for lectures and/or research grants from Amgen, Almirall, AbbVie, Boehringer-Ingelheim, BMS, Galderma, Kyowa Kyrin, Incyte, Leo Pharma, Pierre Fabre, UCB, Lilly, Pfizer, Janssen, MSD, Novartis, Sanofi, Regeneron and Sun Pharma. Fabrizio Guarneri has served as advisory board member for Leo Pharma. Anna Balato has served as advisory board member, consultant and/or has received fees, speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Amgen, Boehringer-Ingelheim, BMS, LeoPharma, Eli Lilly, Incyte, Janssen, Novartis, Sanofi and UCB. Monica Corazza has acted as Principal Investigator, speaker, and board member for AbbVie, Almirall, Amgen, Janssen, Leo Pharma, Novartis and Sanofi. Anna Belloni Fortina has participated in advisory boards, acted as consultant and/or received fees from AbbVie, Amgen, Almirall, Sanofi Genzyme, Leo Pharma, Eli Lilly, Pfizer, Unifarco and Novartis. Piergiacomo Calzavara-Pinton served as advisory board member and consultant and has received fees and speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Cantabria, Galderma, Incyte, Janssen, Novartis, Biogen, Sanofi Genzyme, La Roche Posay, Naos, Boehringer-Ingelheim and Sun Pharma. Antonio Castanzo has served as advisory board member and consultant and has received fees and speakers’ honoraria or has participated in clinical trials for AbbVie, Almirall, Amgen Leo Pharma, Lilly, Galderma, Incyte, Janssen, Novartis, Sanofi Genzyme, Boehringer-Ingelheim and UCB. Silvia Mariel Ferrucci has acted as Principal Investigator in clinical trials, Speaker and Member of Advisory board for: AbbVie, Amgen, Almirall, Bayer, Sanofi Genzyme, Leo Pharma, Eli Lilly, Pfizer, Unifarco and Novartis. Luigi Naldi has been consultant and speaker for AbbVie, Almirall, Boheringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Novartis and Sanofi. Giovanni Pellacani has served as advisory board member, consultant and investigator for: AbbVie, Allergan, Almirall, Amgen, Beiersdorf, Boheringer, Canfield, Difa-Cooper Ifc, Eli Lilly, Galderma, Janssen-Cilag, Krymi, Kyowa-Kirin, Leo Pharma, L’oreal, Mavig, Menarini, Pfizer, Pierre-Fabre, Sanofi, UCB and Viatris. Ketty Peris received grants from: AbbVie, Almirall, Lilly, Novartis and Sanofi; Advisory Board or consulting fees from: AbbVie, Almirall, Biogen, Galderma, Leo Pharma, Lilly, MSD, Pierre Fabre, Sun Pharma, Janssen and Sanofi. Francesca Prignano has served as advisory board member and consultant and has received fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Leo Pharma, Lilly, Janssen, Novartis, Biogen, Sanofi Genzyme, UCB and Boehringer-Ingelheim. Giampiero Girolomoni has received personal fees from AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Leo Pharma, Merck Serono, Novartis, Pfizer, Pierre Fabre, Samsung Bioepis and Sanofi. Ethical Approval: This article is based on data derived from a survey conducted among dermatologists and previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Aim: Abrocitinib is a JAK-1 inhibitor approved for the treatment of moderate-to-severe atopic dermatitis (AD). We conducted a 16-week multicenter retrospective study to assess the short-term effectiveness and safety of abrocitinib in patients with moderate-to-severe AD., Our retrospective study included 85 adult patients from 14 Italian Dermatology Units affected by moderate-to-severe AD treated with abrocitinib 100/200 mg., Methods: Effectiveness of abrocitinib at weeks 4 and 16 was assessed by using the Eczema Area and Severity Index (EASI), the Investigator Global Assessment (IGA), the peak pruritus and sleep- Numerical Rating Scale (PP-NRS and S-NRS, respectively)., Results: At week 16, improvement of at least 90% in EASI (EASI90) and IGA 0/1 was observed in 49.4% and 61.2% of patients, respectively. A reduction of at least 4 points in PP-NRS and S-NRS compared with baseline was achieved by 70.6% of patients for both endpoints. No significant safety reports were observed during the study period. Naïve patients had better rates of EASI 90 compared to patients who previously failed dupilumab. Conclusion: Our data confirm the effectiveness of abrocitinib in a real-world setting with better clinical responses at weeks 4 and 16, compared with Phase-III clinical trials. Longer analyses are required to further establish the safety profile of abrocitinib.

Background : Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment for patients with chronic spontaneous urticaria (CSU) resistant to antihistamines, but about 10% are unresponsive. Our aim was to assess the effectiveness, safety, and drug survival (DS) of omalizumab by considering clinical and laboratory characteristics. Methods : We conducted a retrospective study on 296 patients with severe CSU treated with omalizumab. Disease activity, comorbidities, and serum levels of total IgE and anti-thyroid autoantibodies were evaluated over a period of up to 8 years. DS was analyzed using unadjusted Kaplan-Meier survival curves. When applicable, the risk of discontinuation was assessed using Cox regression analysis. Results : Out of 296 patients, 118 (40.4%) were early responders, 72 (25.0%) were late responders, 76 (26.0%) were partial responders, and 25 (8.6%) were non-responders. Early responders were more likely to be patients without associated inducible urticaria ( p = 0.021, χ 2 = 9.692), without autoimmune thyroiditis ( p = 0.007, χ 2 = 12.037), and those with higher IgE levels ( p = 0.039, χ 2 = 8.385). Overall, DS was 53.5% at 8 years, primarily due to clinical remission. DS due to inefficacy and clinical remission were 83.9% and 62.1%, respectively, at 8 years. No patients discontinued omalizumab due to adverse events. Patients with normal IgE levels ( p = 0.012, HR = 4.639, CI: 1.393-15.445) and those with autoimmune thyroiditis ( p = 0.028, HR = 3.316, CI: 1.128-8.718) had a higher risk of discontinuing omalizumab due to inefficacy. Conclusions : This study confirms the long-term effectiveness and safety of omalizumab in the treatment of CSU over a period of up to 8 years. Most patients discontinued omalizumab due to clinical remission, while only 5.1% discontinued it due to ineffectiveness.

Background : Dupilumab is a monoclonal antibody used for the treatment of moderate/severe atopic dermatitis (AD). In recent years, several studies have confirmed the positive association between AD and overweight/obesity, and a report demonstrated the effect of weight reduction on the improvement of AD symptoms. Methods : The weight of 170 patients under treatment with dupilumab was recorded at baseline and after 48 weeks (T48). Clinical monitoring was mainly conducted using the Eczema Area and Severity Index (EASI). The study aimed to assess a possible correlation between the clinical outcome of dupilumab therapy and BMI. Results : Although not statistically significant, patients with a BMI < 25 have a higher EASI percentage improvement than patients with a BMI ≥ 25 at any time point, and the percentage of overweight and obese patients that does not reach EASI-75 at T48 is higher compared to normal-weight patients (13.5% vs. 5.9%). Despite this, in the multivariate regression analysis, no baseline characteristic, including BMI, appears to increase the risk of not reaching EASI-75. In addition, the results show no differences in BMI between baseline and T48 in any age/sex group. Conclusions : The results suggest that overweight and obese patients have a lower response to dupilumab when considering the EASI score, but this difference does not appear to be clinically significant. Furthermore, dupilumab treatment does not seem to impact weight.

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background : Atopic Dermatitis (AD) is a prevalent inflammatory skin disease whose course is often complicated by the presence of concomitant anxiety and depressive disorders. Dupilumab has been demonstrated to be largely effective in AD. The aims of the present study were to (1) to verify the effectiveness of 2-year dupilumab treatment on the depressive and anxiety symptoms of patients affected by AD and (2) to identify predictors of the persistence of psychiatric symptoms despite maintenance treatment with dupilumab. Methods : A total of 331 patients with severe AD were assessed at baseline and at different times over 2 years by a large set of rating scales, including the Eczema Area and Severity Index (EASI), the Hospital Anxiety and Depression Scale (HADS), and the Dermatology Life Quality Index (DLQI). Paired sample t -tests were performed to verify the effectiveness of dupilumab on the severity of AD and mental health items. Two binary logistic regression models were then used to identify the predictors of the persistence of clinically significant depression and anxiety, defined by a score ≥ 8 on each sub-scale of the HADS. Results : After 2 years of treatment with dupilumab, the patients benefited, showing a significant improvement in both the dermatological disease and comorbid depression/anxiety ( p < 0.001 for all scales). Overall, 17.5% and 13% of patients, respectively, reported residual depressive and anxiety symptoms after the 2-year treatment with dupilumab. The baseline predictors of the persistence of clinically significant depressive symptoms after the 2-year treatment with dupilumab were found to be a higher body mass index (BMI) ( p = 0.012), a lower impact of dermatological disease on quality of life ( p = 0.015), and more severe depressive symptoms ( p < 0.01), while for anxiety, the only predictor was found to be female gender ( p = 0.03). Conclusions : Using a multidisciplinary approach, at baseline, dermatologists should more closely monitor patients who are at a greater risk of maintaining residual psychiatric symptoms despite therapy, such as those with more severe depressive symptoms and those who are overweight.

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.

Introduction: Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD)., Methods: We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year., Results: A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity., Conclusions: Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dubini, Benzecry, Rivolta, Sangalli, Marzano, Pravettoni, Tavecchio and Ferrucci.)

Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, resulting in a deficiency in its processed protein LEKTI. It is clinically characterized by the triad of congenital ichthyosis, atopic diathesis, and hair shaft abnormalities. The SPINK5 (NM&#95;006846.4): c.1258A>G polymorphism (rs2303067) shows a significant association with atopy and atopic dermatitis (AD), which share several clinical features with NS. We describe an NS patient, initially misdiagnosed with severe AD, who carried the heterozygous frameshift (null) mutation (NM&#95;006846.4): c.957&#95;960dup combined with homozygous rs2303067 in the SPINK5 gene. Histopathological examination confirmed the diagnosis, whereas an immunohistochemical study showed normal epidermal expression of LEKTI, despite the genetic findings. Our results corroborate the hypothesis that haploinsufficiency of SPINK5 , in the presence of a SPINK5 null heterozygous mutation in combination with homozygous SPINK5 rs2303067 polymorphism, can be causative of an NS phenotype, impairing the function of LEKTI despite its normal expression. Due to the clinical overlap between NS and AD, we suggest performing SPINK5 genetic testing to search for the SPINK5 (NM&#95;006846.4): c.1258A>G polymorphism (rs2303067) and ensure a correct diagnosis, mainly in doubtful cases.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type 2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of T helper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemic agents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability., (© 2023. The Author(s).)

The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity ( p = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response ( p < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.

Background: Chronic spontaneous urticaria (CSU) is defined as the recurrence of unprovoked transient wheals and itch for more than 6 weeks. Currently, there is an unmet need concerning response prediction in CSU. The present study investigated biomarkers of type I and type IIb autoimmunity as potential predictors of response to omalizumab in CSU. Materials and methods: Differences in levels of IgG and IgE autoantibodies targeting the high- and low-affinity IgE receptors (FcεRI and FcεRII, respectively), as well as spontaneous and specifically triggered leukotriene C (LTC)4 release by basophils from the investigated subjects, were evaluated in 18 consecutive, prospectively enrolled CSU patients and 18 age- and sex-matched, healthy non-atopic controls. Results: The patients with CSU had higher levels of anti-FcεRI IgE (542 (386.25-776.5) vs. 375 (355-418), optical density (OD), p = 0.008), and IgG (297 (214.5-431.25) vs. 193.5 (118-275) OD, p = 0.004) autoantibodies relative to the controls. Simultaneous anti-FcεRI IgG and IgE positivity (i.e., both autoantibody levels above the respective cut-offs) was recorded only in late- and non-responders (3/8 and 1/2, respectively). Discussion: Significantly higher anti-FcεRI IgE autoantibody levels were found in the CSU patients as compared to the controls, supporting FcεRI as an autoallergic target of IgE (autoallergen) in the complex pathophysiological scenario of CSU. The co-occurrence of anti-FcεRI IgG and IgE autoantibodies was documented only in late- and non-responders, but not in early ones, crediting the co-existence of autoimmune and autoallergic mechanisms as a driver of late/poor response to omalizumab.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease of the nose and paranasal sinuses with important economic and sanitary burdens, as well as having a great impact on patients' quality of life. In this field, a new therapeutic approach for those patients who have been described as affected by severe uncontrolled CRSwNP, resistant to medical and best surgical treatment, is represented by subcutaneous human monoclonal antibodies (including dupilumab) that block specific targets involved in the type 2 inflammatory pathway which most commonly drives CRSwNP pathophysiology. This paper aims to report our experience in the management of severe uncontrolled CRSwNP and, in particular, describe our diagnostic workup including baseline evaluation and follow-up visits in the first year of treatment. We also describe into detail our multidisciplinary approach to the disease. We finally report the outcomes of treatment in a real-life setting. In this outpatient real-life setting, our results confirmed the effectiveness of dupilumab in reducing the volume of nasal polyps and restoring nasal obstruction and sense of smell, as well as improving patients' quality of life. The adherence to the dupilumab treatment was very high. The dose of administration was never modified in patients in the first year of treatment. All the patients respected the plan of the visits at proposed time points. We believe that the structural organization of our outpatient clinic appears to be functional: it allows us to study patients thoroughly before starting treatment and to make a proper follow-up after it starts. We believe that sharing both our strict clinical flowchart and growing experience with dupilumab with the medical community can lead to more standardized and effective pathways of care for CRSwNP patients.

Atopic dermatitis (AD) is a common inflammatory skin disease often associated with a significant impairment in the quality of life of affected patients. The Italian Society of Dermatology and Venereology (SIDeMaST) planned a national information campaign, providing direct access to 27 dermatologic centers dedicated to the management of AD. The aim of this study aimed was to outline critical aspects related to AD in the general population. Overall, 643 adult subjects were included in this study, and in 44.2% (284/643) of cases, a diagnosis of AD was confirmed, whereas about 55% of subjects were affected by other pruritic cutaneous diseases. Higher intensity of pruritus and sleep disturbance, as well as an increased interference in sport, work, and social confidence was reported in the AD group compared to the non-AD group. In the AD subgroup, the mean duration of disease was of 15.3 years, with a mean eczema area and severity index (EASI) score of 11.2, and investigator global assessment (IGA) score of 1.9 and an itch numeric rating scale (NRS) of 6.9. Almost 32% of patients were untreated, either with topical or systemic agents, whereas 44.3% used routine topical compounds (topical corticosteroids and calcineurin inhibitors), and only 7.0% of patients were systemically treated. Only 2.8% of patients reported complete satisfaction with the treatment received for AD to date. This study reveals a profound unmet need in AD, showing a poorly managed and undertreated patient population despite a high reported burden of disease. This suggests the usefulness of information campaigns with the goal of improving patient awareness regarding AD and facilitating early diagnosis and access to dedicated healthcare institutions., Competing Interests: The authors declare no conflict of interest related to this study.

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non-scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522-8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726-32]. We report here a case to further support this hypothesis., Competing Interests: Silvia Mariel Ferrucci has been the principal investigator in clinical trials for AbbVie, Novartis, and Eli Lilly. The other authors declare no conflicts of interest., (Copyright © 2021 by S. Karger AG, Basel.)

Introduction: Previous drug survival studies of dupilumab in atopic dermatitis (AD) show that many patients continue treatment through 1 year, suggesting that patients experience clinically relevant benefits with long-term treatment., Methods: This post hoc analysis included data through week 100 from 391 adult patients from the dupilumab open-label extension (OLE) study who had not achieved the endpoints of at least 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) or an Investigator's Global Assessment (IGA) score of 0 or 1 with short-term (16 weeks, 300 mg qw or q2w) dupilumab treatment in the parent SOLO 1 or 2 studies. All patients received dupilumab 300 mg qw in the OLE study, irrespective of whether they received qw or 2qw dosing in the parent study., Results: Among those who had not achieved EASI-75 or IGA 0/1 during the 16-week parent study, the proportion of patients achieving EASI-75 by week 100 was 91%. The proportion achieving IGA 0 or 1 at week 100 was 45% for patients initially on q2w week dosing and 49% for those on initial qw dosing., Conclusion: Long-term dupilumab treatment may be associated with improvement in AD in patients with suboptimal responses during the initial 16 weeks of treatment., Clinical Trial Registration: LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743; EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769; EudraCT 2014-002619-40., Liberty Ad Ole: ClinicalTrials.gov Identifier NCT01949311; EudraCT 2013-001449-15., (© 2021. The Author(s).)

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases., (© 2021. The Author(s).)

The aim of this study was to detect demographic and clinical factors associated with affective symptoms and quality of life in patients with severe atopic dermatitis. First, one-way analyses of variance and correlations were performed to compare a large set of qualitative and quantitative clinical variables. Three final multivariable regression models were performed, with depression/anxiety subscales and Dermatology Life Quality Index scores as dependent variables, and the factors that were statistically significant on univariate analyses as independent ones. More severe anxiety symptoms and poorer quality of life (p < 0.01) were significantly associated with more severe depressive symptoms. Female sex and disturbed sleep (p = 0.03) were significantly associated with more severe anxiety. Finally, previous treatment with cyclosporine (p = 0.03) or methotrexate (p = 0.04), more severe depressive symptoms (p < 0.01), itch (p = 0.03), impaired sleep (p < 0.01) and perceived severity of dermatological illness (p < 0.01) were significant predictors of low quality of life. This study shows a complex interplay between the severity of atopic dermatitis, poor quality of life and presence of clinically relevant affective symptoms. These results will help dermatologists to identify patients who need psychiatric consultation within the framework of a multidisciplinary approach.

Toxic metals are not so rare but are often neglected causes of alopecia areata in men and women. Thallium, arsenic, selenium, and mercury are the most common cause of metals-related alopecia, which is what Vicky Yu and colleagues' found. Other than the presence of thallium, arsenic, mercury, and selenium, cadmium, bismuth, lithium, and copper should also be taken into account when dermatologists are considering toxic metals as a potential cause of alopecia areata in humans., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Purpose of the article: Baricitinib, a JAK 1/2 inhibitor, is approved for treating severe alopecia areata (AA). This study aimed to evaluate the long-term effectiveness and safety of baricitinib in a real-world setting over 52 weeks., Materials and methods: This multicenter retrospective study included 96 adult patients diagnosed with severe AA from 11 Italian Dermatology Units. All patients received 4 mg of baricitinib daily. Effectiveness was assessed using the Severity of Alopecia Tool (SALT) score, with the primary endpoint defined as achieving a SALT score ≤ 20 at week 52. Secondary endpoints included achieving a Clinician-Reported Outcome (ClinRO) score of 0 or 1 for eyebrow (ClinRO EB) and eyelash hair loss (ClinRO EL), with a ≥ 2-point improvement from baseline., Results: After 52 weeks, 61.5% of patients achieved a SALT score ≤ 20. Additionally, 67.6% and 69.7% of patients attained ClinRO EB and ClinRO EL scores of 0 or 1, respectively, with a ≥ 2-point improvement. No significant adverse safety events were reported during the study., Conclusions: The study confirms the long-term effectiveness and safety of baricitinib for severe AA in a real-world setting. These findings align with clinical trial results and reinforce baricitinib's role as a viable treatment option for severe AA.

Background: Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients., Methods: We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS., Results: The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 μg/L; mean in urine was 1.9 ± 2.5 μg/L; mean in scalp hair was 2.2 ± 2.5 μg/g; mean in saliva was 38.1 ± 52.1 μg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023)., Conclusions: Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.