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Introduction: Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting., Methods: The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed., Results: Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure., Conclusion: Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments., Clinical Trial Registration: ClinicalTrials.gov identifier NCT03992417. Video Abstract., (© 2023. The Author(s).)

Competing Interests: Conflicts of interest the authors declare no conflicts of interest.

Background: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population., Methods: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated., Results: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts., Conclusion: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change., (© 2023. The Author(s).)

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_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_006846.4): c.957_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_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: Patients suffering from eczematous dermatitis always required moisturizing cream as a background therapy with the aim to reduce flares and minimize steroids use. The term emollients plus (EP) refers to a topical formulations with vehicle-type substances and additional active, non-medicated substances. We have conducted a study with a topical emollient containing urea 10% and amino-inositole on 20 patients affected from chronic eczematous dermatitis. Primary outcomes were to evaluate effectiveness, in term of Investigator Global Assessment (IGA), and tolerability of EP. Secondary aims included the comparison of NRS (numerical rating scale) itch and NRS-pain, DLQI (Dermatological Life Quality Index) between day one and day 28 and to evaluate the characteristics of EP., Methods: Subjects were instructed to apply the EP twice daily for 4 weeks on affected skin and use a soft soap while not to put any other topical or systemic product. Statistical analysis was conducted through the test t-Student by comparing IGA, itch-NRS, pain-NRS and DLQI at time 0 and day 28., Results: High statistically significant difference (P=0.0038) between IGA value at T0 and T4 has been demonstrated as for itch and pain (respectively P=0.0203 and P=0.0146). Almost all the patients (89.5%) have declared a good or better tolerability of EP. Two patients did not complete the study., Conclusions: Patients with chronic eczema could often resolve the dermatitis with the correct choice of emollient without steroids use, especially if it is an EP.

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.

Background: Moderate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD., Objectives: A multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined., Methods: Data of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes., Results: One hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event., Conclusions: Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting., Methods: Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months., Results: 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled., Conclusion: The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.

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., (© 2021. The Author(s).)

Competing Interests: A.C. served as advisory board member and consultant receiving fees and speaker's honoraria or has participated in clinical trials for AbbVie, Almirall, Biogen, Fresenius Kabi, Leo Pharma, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB Pharma. G.F. acted as speaker and consultant for AbbVie and Leo Pharma. G.G. has been principal investigator in clinical trials sponsored by and/or and has received personal fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Eli Lilly, Leo Pharma, Novartis, OM Pharma, Pfizer, Regeneron, Samsung, and Sandoz. A.O. has been a scientific consultant/speaker/clinical study investigator for AbbVie, Celgene, Janssen, Leo Pharma, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, Alfasigma, and Almirall. M.T.R. has received personal fee for advisory board meeting from Sanofi, AbbVie, Novartis, and Cantabria. L.B. reports personal fees from speaker and as consultant for AbbVie, Novartis, Janssen-Cilag, Pfizer, UCB, and Leo Pharma, outside the submitted work. L.S. has been principal investigator in clinical trials sponsored by and/or received personal fees from AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, and Sanofi-Genzyme. G.P. has been principal investigator in clinical trials sponsored by and/or received personal fees from AbbVie, Almirall, Eli Lilly, Leo Pharma, Novartis, and Sanofi. A.P. has served as a speaker and received honoraria from Sanofi-Genzyme for lectures, research grants, and as an advisory board member. C.F. has been speaker for Sanofi and AbbVie. M.C.F. has served on advisory boards, received honoraria for lectures, and research grants from Almirall, AbbVie, Galderma, Leo Pharma, Mylan, Medac Pharma, Celgene, Pierre Fabre, UCB, Eli Lilly, Pfizer, Janssen, Novartis, Sanofi Genzyme, Roche, Sun Pharma, and MSD. F.R. has served on advisory board, received honoraria for lectures and research grants from Novartis, AbbVie, Janssen-Cilag, Eli Lilly, Leo Pharma, and Sanofi-Genzyme. P.A. has received speaker honoraria from Sanofi, AbbVie, Janssen, Celgene, Novartis, and Sandoz. G.M. has been a scientific consultant/clinical study investigator for AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, and Novartis. C.P. has been a consultant and held sponsored conferences for AbbVie, Novartis, Pfizer, and Sanofi. I.Z. has been a consultant and/or speaker for Novartis, Celgene, and Amgen. K.P. reports grants and personal fees for advisory board meeting from Almirall, AbbVie, Biogen, Lilly, Celgene, Galderma, Leo Pharma, Novartis, Pierre Fabre, Sanofi, Sandoz, Sun Pharma, and Janssen. S.F. has been principal investigator in clinical trials by AbbVie and Sanofi-Genzyme, has served on advisory board, received honoraria for lectures and research grants from Novartis, Menarini, and Almirall. The remaining authors have no funding or conflicts of interest to declare.

Objective: To evaluate the role of tacrolimus ointment in the management of patients on dupilumab therapy for severe atopic dermatitis, in a real-life setting., Patients and Methods: Consecutive patients with severe AD treated with dupilumab were enrolled. Topical treatment was associated according to the clinical practice. Eczema Area and Severity Index (EASI), itching and sleep Numerical Rating Scale (NRS) and Dermatologic quality of Life (DLQI) were recorded at baseline and after 4, 16 and 52 weeks of treatment with dupilumab., Results: Overall, 342 patients were enrolled, and 307 were evaluable. Tacrolimus was used by 6.5% (n=20) of patients at baseline, 11%, 13.5%, and 11.3% after 1, 4 and 12 months, respectively; the mean time to introduce tacrolimus after initiation of dupilumab was 8.3 ± 0.3 months. Low EASI score (<7; mild disease) after 1 month of systemic therapy was more frequent in patients who applied tacrolimus at baseline than in patients who did not (72.2% vs. 55.8%, p=0.027). Female sex, low DLQI scores, low age at dupilumab initiation, and non-generalized AD were correlated with an increased probability to start tacrolimus at any time during the study., Conclusions: Data suggested that early treatment of localized areas with tacrolimus improves systemic treatment efficacy.

Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease, burdened by various comorbidities. AD most commonly occurs in children but may persist or present in adulthood becoming a lifelong condition. Therefore, AD requires an effective long-term treatment improving disease signs and symptoms but also of patients' quality of life (QoL). However continuous long-term use of most traditional AD immunosuppressive treatments is not recommended for safety reasons or insufficient efficacy data. Despite the available guidelines, there is still need for knowledge of AD long-term treatment, taking into account new disease measures and recent treatment options. Five Italian scientific societies implemented a joint consensus procedure to define the most appropriate clinical practice for the long-term management of adult moderate-severe AD. Through a modified Delphi procedure, consensus was reached by overall 51 Italian dermatologists and allergists (The Italian AD Study Group) experienced in the management of adult AD on 14 statements covering three AD areas of interest, namely diagnosis, definition of disease severity and clinimetrics, and a treat-to-target approach. This paper reports and discusses the agreed statements, which define disease and patient impact measures, therapeutic approach, and a treatment decision algorithm to support clinicians in the long-term management of adult patients with moderate-to-severe AD in their daily clinical practice.

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).)

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.)

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).)

Background: Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The aim of this study is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures., Methods: A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (group A; N.=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (group B; N.=25)., Results: The EAACI/GA 2 LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P<0.00001). When physicians were asked to indicate the type of laboratory examinations that were commonly performed in patients with longstanding and/or uncontrolled CSU, regardless of history, the investigations most frequently reported were full blood count and thyroid autoantibodies, followed by erythrocyte sedimentation rate and/or C-reactive protein and thyroid function tests., Conclusions: The results of the present pilot survey seem to suggest the heterogeneity of the approaches used for CSU management in clinical practice.

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.

Background: Budesonide was included in the European Baseline Series in 2000 as the most suitable marker forcorticosteroid hypersensitivity. In the last two decades, a decreasing trend of budesonide allergy has been observed., Objectives: To estimate the prevalence of positive patch test reactions to budesonide in a large, Italian patch test population, characterizing patients according to MOAHLFA index and evaluating the benefit with extended readings of budesonide patch test., Methods: Retrospective analysis of patient demographics and patch test results over a 2-year period (2018-2019) was performed at 14 patch test clinics in Italy., Results: Ninety out of 14 544 (0.6%) patients reacted to budesonide 0.01% pet.. Positive reactions were mild in 54.4% and late readings at day 7 showed new positive reactions in 37.8% of patients. The MOAHLFA index showed a significant positive association with male gender, atopic dermatitis, and age >40 years and a significant negative association with hand and face dermatitis., Conclusions: We documented a low prevalence of budesonide allergy in Italy, confirming its decreasing trend recently reported in the literature. Nevertheless, budesonide needs to be maintained in the baseline series for its good ability to detect corticosteroid sensitization., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks., Methods: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52., Results: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent., Conclusions: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Introduction : Omalizumab is used to treat severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU), and is approved for self-administration in prefilled syringes. It is thus important to understand the advantages, critical issues, and indications for home administration. Areas covered : The present review summarizes the available evidence on home administration of omalizumab in asthma and CSU to illustrate the advantages derived from self-administration of patients in this setting. Expert opinion : The available data suggest that patients can safely administer biologics at home with suitable training, and that home administration is time saving and cost-effective. The majority of patients with severe asthma or CSU treated with omalizumab are likely to be suitable candidates for self-administration, which can be proposed to anyone that the clinician deems suitable. In addition to clinicians, pharmacists can also play a key role in managing patients who are prescribed home administration. A practical flow chart is proposed on selection of patients and their management during home administration. Self-administration of biologics can be considered as a valid alternative to traditional injections in a clinical setting, and the evidence has shown that no major issues need to be overcome in terms of safety or efficacy.

Background: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known., Objectives: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined., Methods: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16 weeks of treatment., Results: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18-64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event., Conclusions: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly., (© 2020 European Academy of Dermatology and Venereology.)

Background: Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions., Methods: The prospective, observational EUROSTAD study enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics., Results: A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean [standard deviation] disease severity/burden measures were high: Investigator's Global Assessment (3.1 [0.8]), Eczema Area and Severity Index (16.2 [10.9]), Peak Pruritus Numerical Rating Scale (5.5 [2.5]), sleep impairment Visual Analog Scale (49.8 [31.6]) scores, and time lost from work (4.1 [13.7] days/year) or usual activities (16.8 [38.7] days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale., Conclusions: Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown., Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19., Materials and Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences., Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19., Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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.)

Nummular eczema (NE) is currently considered as one of the clinical phenotypes of atopic dermatitis (AD) of the adult. In this multicentre study, 30 adult patients (age ≥ 18 years) affected with nummular-like AD were treated with dupilumab, a monoclonal antibody against the receptor for interleukin(IL)-4 and IL-13. The evaluation of the results after 16 weeks of treatment showed a significant improvement of the disease, as demonstrated by reduction in Eczema Area Severity Score (EASI), visual analogue score (VAS) of pruritus, and Dermatology Life Quality Index (DLQI) scores. Conjunctivitis in one patient was the only side effect. In conclusion, dupilumab seems to be an effective and safe treatment in NE phenotype of AD of the adult., (© 2020 Wiley Periodicals LLC.)

Background: There is a need for validated tools to assess health-related quality of life (HRQoL) in routine clinical practice., Objective: The aim of this study was to validate the Chronic Urticaria Patient Perspective (CUPP) for assessment of patients with chronic urticaria (CU) in clinical practice., Methods: A provisional CUPP was developed from candidate items identified by following an iterative process in a retrospective analysis of 249 Chronic Urticaria Quality of Life Questionnaire questionnaires. The psychometric properties of the CUPP were then tested on a sample of patients enrolled in 13 Italian centers., Results: The study population in the validation phase comprised 152 patients. The 10-item version of the CUPP showed satisfactory internal consistency (Cronbach's alpha values of 0.76 at visit 1 and 0.90 at visit 2), good criteria, and discriminative and convergent validity. Reliability was assessed in 34 patients with no changes in health (Global Rating Scale = 0 at visit 2) and was satisfactory (CCC [concordance correlation coefficient] = 0.9). Changes in CUPP scores were significantly associated with changes in Urticaria Activity Score (UAS)-Hive count (r = 0.36, P < .001), UAS-Itch severity (r = 0.48, P < .001), and UAS-Total score (r = 0.342, P < .001), all of which indicated good responsiveness. The minimal important difference was 1.5., Conclusions: CUPP is a simple 10-question tool with good psychometric properties that provides a valid, reliable, and standardized measurement of HRQoL in patients with CU., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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.

Aim: Sclerodermus domesticus is an insect belonging to the order Hymenoptera. Female of S. domesticus feeds on larvae of xylophagous Coleoptera and Lepidoptera living in the galleries they dig in old wooden furniture. Human infestation is rare., Methods: In the last few months, we observed nine adult patients (7 males and 2 females) who were affected by S. domesticus infestation. Seven patients were antiquarians or restorers and two were housewives. The rash was characterized by erythematous-papular lesions, accompanied by pruritus and/or pain. In addition, 7 patients reported general malaise and fever. In all cases it was possible to find specimens of S. domesticus in furniture or house dust., Results: Complete remission was obtained with topical corticosteroids, oral anti-histamines and pest control of furniture., Conclusion: Antiquarians and restorers and, in general, the people in close contact with furniture infested by S. domesticus may be stung by these insects. S. domesticus infestation can therefore be considered as an occupational disease in these subjects.