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

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

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

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

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Contact allergy to hydroxyisohexyl 3-cyclohexene carboxaldehyde in Italy: Prevalence, trend, and concordance with fragrance mix II.

BACKGROUND: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), contained in fragrance mix II (FM II), has been recognized as a contact sensitizer since the mid-1990s. After several attempts to reduce its use during the last two decades, HICC was permanently banned from the European market in August 2021. OBJECTIVES: To assess the prevalence and the time trend of contact allergy to HICC and to investigate the concordance of HICC allergy compared to FM II allergy in an unselected Italian patch test population. METHODS/PATIENTS: Retrospective analysis on demographics and patch test results of HICC-sensitized and/or FM II-sensitized patients was performed over a 6-year period (2016-2021) at 6 patch test Clinics in Italy. RESULTS: Among 7266 patients (4942 females, 68.0%, mean age 45.4 ± 20.6 years), 1% (70) resulted positive to HICC and 2.1% (153) to FM II. Clinical relevance was documented in 72.9% (51/70) of HICC positive patients. Among the 169 HICC and/or FM II positive patients, 9.5% had a positive reaction to HICC only, 31.9% to both HICC and FM II, and 58.6% to FM II only. The prevalence trend line of HICC positive reactions showed a decrease from 1.15% (2016) to 0.96% (2021). CONCLUSIONS: We documented a decreasing trend of HICC allergy in Italy, in line with the data recently reported in literature. Nevertheless, HICC should be maintained in the baseline series to monitor the benefits of its ban from the European market.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Contact allergy in children with and without atopic dermatitis: An Italian multicentre study.

BACKGROUND: Contact allergy and atopic dermatitis (AD) are both common inflammatory T cell-mediated diseases and many factors may influence the prevalence of contact allergy in AD patients. In children, their possible correlation was debated with conflicting results. OBJECTIVES: The present study aimed to assess the prevalence of contact sensitivity in children and to investigate the association with AD. MATERIALS AND METHODS: A retrospective multicentre study on children aged from 0 to 14 years patch tested between January 2017 and December 2018 was performed. Children were consecutively patch tested with the SIDAPA (Società Italiana Dermatologia Allergologica Professionale Ambientale) baseline series. RESULTS: Among the 432 children investigated for contact allergy, 125 (28.9%) showed a positive reaction to at least one of the allergens tested, with a higher prevalence of positive patch test reactions in girls (32.3%) than in boys (25.0%). The most frequent contact allergens were nickel sulphate (10.2%), cobalt chloride (6.7%), methylisothiazolinone (3.7%), fragrance mix-2 (3.2%), potassium dichromate (2.8%), fragrance mix-1 (2.1%) and methylchloroisothiazolinone/methylisothiazolinone (2.1%). One-hundred-three children (23.8%) suffered from AD showing a higher prevalence of positive patch test (36.9%) compared to children without AD (26.4%). CONCLUSIONS: Despite the topic being still controversial, the present study suggests a consistent prevalence of contact allergy among children with higher sensitivity rate among children with AD than without AD.

Effectiveness and safety of lidocaine patch 5% to treat herpes zoster acute neuralgia and to prevent postherpetic neuralgia.

Herpes zoster is often associated to acute neuralgia and postherpetic neuralgia (PHN). Their therapeutic management is still challenging: among therapeutic options, lidocaine patch 5% was rarely used in acute neuralgia on lesional skin, and its efficacy to prevent PHN was never studied. The efficacy and tolerability of lidocaine patch 5% was evaluated in 38 patients with acute neuralgia (19) and PHN (19). Pain intensity was investigated using DN4 questionnaire and NRS-11 scale at baseline and at week 2, 4, and 8. The use of rescue therapy was also evaluated. A significant reduction of DN4 and NRS-11 was observed already at W2, with further improvement at W4 and W8. A complete response to treatment (DN4 and NRS-11 = 0) at week 8 was higher in patients with acute neuralgia (63.2%) than PHN (31.6%). Rescue therapy gradually decreased in acute neuralgia patients from week 2 (57.9%) to week 8 (10.5%), with only two patients needing neuroleptics. In PHN patients rescue therapy remained stable (68.4%). According to our results, lidocaine patch 5% applied on lesional skin was well tolerated and ensured a rapid pain relief in acute neuralgia; if early used, it prevented PHN in almost all patients.

Atopic dermatitis in adolescents: Effectiveness and safety of dupilumab in a 16-week real-life experience during the COVID-19 pandemic in Italy.

Dupilumab showed significant improvement of adolescent atopic dermatitis (AD) signs and symptoms in clinical trials, with a good safety profile. Herein we report the real-word effectiveness and safety of dupilumab in adolescents with moderate to severe AD from January to October 2020, during the COVID-19 pandemic in Italy. All patients had a diagnosis of AD for a mean [SD] 12.8 [3.1] years. Baseline demographics, AD characteristics (EASI, cDLQI, NRS itch score, NRS sleep loss score) at baseline and week 16, and safety data were collected. Nineteen patients (52.6% men; mean [SD] age, 15.6 [1.4] years [range, 13-17 years]) were included in the analysis. All patients reached EASI-50 and 78.9% EASI-75, especially in those with EASI≥30 and BMI < 25 at baseline, with marked reduction for cDLQI (77.4%), NRS itch score (5.9 point), and NRS sleep loss score (87.5%). One patient contracted asymptomatic SARS-CoV-2 infection and 1 developed mild conjuntivitis, without stopping dupilumab. In this real-word experience the effectiveness of dupilumab was excellent and resulted higher than that observed in clinical trials, with a good safety profile during COVID-19 pandemic.

Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder.

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.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Patch testing of budesonide in Italy: The SIDAPA baseline series experience, 2018-2019.

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.

Dupilumab and COVID-19: What should we expect?

Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. There are very limited data on the interference of immunomodulating drugs on the risk of infection and on the course of the disease. In particular, there are no current clinical data about the interference exerted by dupilumab, a biologic drugs blocking IL-4 and IL-13, used for adult atopic dermatitis. The pathogenesis of COVID-19 is complex, characterized by an immune response mainly Th1/Th17. The hyper-activation of these cells may cause the release of pro-inflammatory cytokines that may result in lung impairment. IL-4 and IL-13 are Th2 cytokines, thus being part of a pathway not considered implicated in host defense mechanism against viral infections. Indeed, viral infections, including respiratory infections, have not been reported as a significant adverse event in clinical trials. Furthermore, dupilumab has been proved to be efficacious also in exacerbations of asthma, and it is known that viral infections can worsen asthma. Therefore, the current data seem to suggest that treatment with dupilumab should not be stopped during COVID-19 pandemic. Obviously, a careful assessment is mandatory for each individual patient and further studies are necessary to characterize the immunologic responses in COVID-19.

Effectiveness of dupilumab for the treatment of nummular eczema phenotype of atopic dermatitis in adults.

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.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

BACKGROUND: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year. METHODS: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. CONCLUSIONS: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Italian guidelines for therapy of atopic dermatitis-Adapted from consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis).

Atopic dermatitis (AD) therapeutic approach calls for a long-term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical-legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1-4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year.

Adalimumab in severe plaque psoriasis of childhood: A multi-center, retrospective real-life study up to 52 weeks observation.

The objective of this study is to determine drug effectiveness and safety of the tumor necrosis factor-alpha blocker monoclonal antibody adalimumab in a real-life cohort of 54 children and/or adolescents with severe plaque psoriasis. Retrospective, multicenter analysis over a 52-week period is discussed in this study. Efficacy was determined by the percentage of patients achieving Psoriasis Area Severity Index (PASI 75) and PASI 90 at weeks 16, 24, and 52 and the response in biologic-naïve versus non-naïve patients. Safety was assessed by the number of patients experiencing at least one adverse event. At week 16, 29.6% of patients achieved a 90% PASI score reduction (PASI 90), while 55.5% of patients achieved a 75% PASI score reduction (PASI 75). Effectiveness was sustained through week 24, since PASI 90 response increased to 55.5% and PASI 75 response increased to 74.0% of patients. The PASI response rates did not differ between biologic-naïve and non-naïve patients. The drug was well tolerated and no serious infections were observed. Adalimumab was effective and safe in this cohort of children with severe plaque psoriasis in a 52-week observation. Effectiveness did not differ between biologic-naïve and non-naïve patients.