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

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

Dupilumab-Associated Blepharoconjunctivitis: Clinical and Morphological Aspects.

PURPOSE: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment. METHODS: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy. RESULTS: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands. CONCLUSIONS: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature.

Is Pediatric Melanoma Really That Different from Adult Melanoma? A Multicenter Epidemiological, Clinical and Dermoscopic Study.

PURPOSE: To improve the diagnostic accuracy and optimal management of pediatric melanomas. METHODS: We conducted a retrospective descriptive, multicenter study of the epidemiological, clinical, and dermoscopic characteristics of histopathologically proven melanomas diagnosed in patients less than 18 years old. Data on sociodemographic variables, clinical and dermoscopic characteristics, histopathology, local extension, therapy and follow-up, lymph node staging, and outcome were collected from the databases of three Italian dermatology units. We performed a clinical evaluation of the morphological characteristics of each assessed melanoma, using both classic ABCDE criteria and the modified ABCDE algorithm for pediatric melanoma to evaluate which of the two algorithms best suited our series. RESULTS: The study population consisted of 39 patients with a histologically confirmed diagnosis of pediatric melanoma. Comparing classic ABCDE criteria with the modified ABCDE algorithm for pediatric melanomas, the modified pediatric ABCDE algorithm was less sensitive than the conventional criteria. Dermoscopically, the most frequent finding was the presence of irregular streaks/pseudopods (74.4%). When evaluating the total number of different suspicious dermoscopy criteria per lesion, 64.1% of the lesion assessments recognized two dermoscopic characteristics, 20.5% identified three, and 15.4% documented four or more assessments. CONCLUSIONS: Contrary to what has always been described in the literature, from a clinical point of view, about 95% of our cases presented in a pigmented and non-amelanotic form, and these data must be underlined in the various prevention campaigns where pediatric melanoma is currently associated with a more frequently amelanotic form. All the pediatric melanomas analyzed presented at least two dermoscopic criteria of melanoma, suggesting that this could be a key for the dermoscopic diagnosis of suspected pediatric melanoma, making it possible to reach an early diagnosis even in this age group.

Towards a better understanding of the use of additives in tattoos.

BACKGROUND: Tattooing is a popular practice worldwide, this practice is not free from complications and the last few decades have seen the raising occurrence of complications and adverse reactions. METHODS: The aim of this study is to evaluate which substances are commonly used as additives among a group of tattoo artists working in Florence, to understand if mixing of colors and dilution of inks can be considered a potential source of infection or hypersensitivity reaction. A questionnaire containing a list of substances suspected to be added during the process of tattooing, was administered in presence of an investigator. RESULTS: Forty-one licensed tattoo artists participated in the study. The cosmetic most frequently used as additive, resulted a rinse on cosmetic (36%) followed by distilled water (34%) and hamamelis lotion (17%). CONCLUSIONS: Our study provides new insights about the procedure of ink dilution and mixing of colors, shedding light on the possible risks related to the use of non-sterile products. The results of our study suggest that mixing of colors and ink dilution can be consider a potential source of infection and hypersensitivity reactions. Additional actions are necessary to strengthen and protect public health.

Effect of dupilumab on sleep disturbances in adult patients with severe atopic dermatitis.

BACKGROUND: Sleep disturbances are common in patients with atopic dermatitis (AD). Considering their relevant burden on health, routine screening of sleep disturbances seems to be very useful in AD adults' management. However, few studies have evaluated the association between sleep disturbances and AD in adults, and real-life data are lacking. The aim of this study was to assess the effect of treatment with dupilumab on sleep disturbances in adult patients with severe atopic dermatitis. METHODS: This is a retrospective, multicenter study including patients (age ≥18 y) with severe atopic dermatitis treated with dupilumab for at least 8 months from January 2019 to January 2020. Patients were evaluated three times: at treatment initiation (T0), at 4 (T4) and 8 months (T8) from the start of treatment. At each visit disease activity was assessed by severity score (Eczema Area and Severity Index [EASI]), patient-reported outcomes (Pruritus Numerical Rating Scale [NRS], Dermatology Life Quality Index [DLQI], and Pittsburgh Sleep Quality Index [PSQI]). Kolmogorov-Smirnov Test was performed to evaluate the normality distribution, Bartlett's Test for homoscedasticity. Since the assumptions were met, ANOVA for repeated measures was performed to evaluate the mean difference of PSQI, EASI, DLQI and pruritus NRS between baseline, the 4th month and the 8th month. In addition, χ2 for Trend Test was performed to evaluate the increasing/decreasing prevalence of poor sleepers. RESULTS: A total of 36 patients (15 females and 21 males) with a mean age of 42.5±14.3 (range 20-67) were included in the study. The mean score for PSQI at TO was 9.0±3.6. At week 16 (T4) the mean score for PSQI was 4.92±2.99 and at week 32 (T8), the mean score for PSQI was 4.3±3.0. EASI, NRS pruritus and DLQI significantly improved during follow-up (P<0.001) whereas PSQI improved significantly at 16 weeks (T4); however, no significant further improvement was observed at 32 weeks. Of the 31 patients (86%) with baseline PSQI≥5, 17 (54%) experienced sleep quality improvement during treatment. Overall, we observed a total of 22 patients (61.1%) having a PSQI<5 at 32 weeks. CONCLUSIONS: Our data show effectiveness of dupilumab in improving sleep disturbances in adult patients with severe AD. However, further studies are required to understand if PSQI could serve as useful evaluating tool.

DECISA Project (DErmatology Clinics in Italy: Survey on Alitretinoin): A real-life retrospective cohort multicenter study on 438 subjects with chronic hand eczema.

Alitretinoin is the only systemic agent approved to treat moderate-severe chronic hand eczema (CHE) unresponsive to potent topical corticosteroids. No nationwide Italian data regarding real-life efficacy, safety, and tolerability of treatment are available. The DECISA project (DErmatology Clinics in Italy: Survey on Alitretinoin) retrospectively examined data from a registry including 15 Dermatology Clinics authorized to prescription of alitretinoin for CHE patients. Disease severity was assessed at baseline, and after 3 and 6 months of treatment, using the 5-point Physician Global Assessment (PGA) and the modified Total Lesion-Symptoms-Severity (mTLSS) scores. Between November 2010 and July 2018, data of 248 male and 190 female patients (mean age 49.71 ± 13.20 years) treated with alitretinoin were collected. Of them, 43.2% had irritant contact dermatitis, 22.2% allergic contact dermatitis, 18.0% atopic dermatitis, 16.7% mixed (irritant/allergic) type of eczema. At 3 months, the 420 re-evaluated patients showed significantly reduced mTLSS and PGA (P < .0000001 vs baseline for both); PGA was clear/almost clear in 35.6% of cases. At 6 months, the 341 re-evaluated patients showed significant (P < .0000001) improvement of mTLSS and PGA vs baseline and 3 months (PGA clear/almost clear: 41.4%). Relapses occurred in 125 patients; 58 underwent an additional course of alitretinoin, with similarly good results. No relevant safety issues were reported; 86 patients experienced adverse effects, which forced 40 to prematurely stop treatment. The DECISA project results confirm the real-life efficacy, safety and tolerability of alitretinoin in the treatment of moderate to severe CHE refractory to standard topical therapies.

Dupilumab in Elderly Patients With Severe Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) in the elderly has been poorly investigated, although its incidence is gradually increasing mainly in industrialized countries. Age-specific factors in older patients must be considered when selecting treatment options. OBJECTIVES: To evaluate the efficacy and tolerability of dupilumab in treating elderly patients with severe AD. METHODS: This was a retrospective, multicenter study involving 26 elderly patients (age, ≥65 years) with severe AD who were treated with dupilumab for at least 16 weeks. Absolute and percentage frequencies were used to evaluate qualitative variables and mean and SD for quantitative ones. For Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), and Dermatology Life Quality Index (DLQI), the median was also calculated. Wilcoxon test was used to evaluate the variations in EASI, Pruritus NRS, and DLQI observed between the 2 examinations. RESULTS: After 4 months of therapy, the majority of patients showed a significant improvement in EASI (64.4%), Pruritus NRS (58.2%), and DLQI (44.9%). Only 11% of patients reported mild or moderate conjunctivitis. CONCLUSIONS: To the best of our knowledge, this is the first study concerning the use of dupilumab in the elderly with severe AD. Our data show the effectiveness of dupilumab in this particular population with a lower percentage of conjunctivitis than observed in studies on adults and also excellent control of itching. Only larger, controlled case studies will be able to clarify whether the dosage or frequency of administration of dupilumab in these patients should be different from the protocol used for adults.

Socio-economic burden and resource utilisation in Italian patients with chronic urticaria: 2-year data from the AWARE study.

INTRODUCTION: In Italy, the real-world evidence on the extent of adherence to guidelines and the benefits of recommended therapeutic medications and their impact on the quality of life (QoL) of H1-antihistamines (H1-AH) refractory chronic urticaria (CU) patients is limited. METHODS: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) was a global prospective, non-interventional study of CU in real-world setting which included patients aged ≥18 years with a medically confirmed diagnosed of CU present for more than 2 months. In this study, the disease characteristics, pharmacological treatments and patient-reported outcomes (PROs) are reported. RESULTS: In total, 159 patients from 24 study centres in Italy completed the study. At baseline, 221 (89.5%) and 8 (3.2%) patients had chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), respectively, while 18 (7.3%) patients had concomitant CSU and CIndU. For CSU patients, mean dermatology life quality index and CU quality of life questionnaire scores reduced to 3.0 ± 4.9 and 14.6 ± 18.6 at Month 24 from baseline scores of 7.5 ± 6.6 and 33.2 ± 19.5, respectively, indicating an improvement in QoL. This was reflected in their work-life as work productivity impairment reduced considerably after 2 years. Only 71.9% CSU patients had a prior treatment, while during the study, 96.8% of the patients were treated with a medication. At baseline, only 52.9% CSU patients reported nonsedating H1-antihistamines as first-line of treatment in prior medication, this increased to 89.6% during current medication. CONCLUSION: This study shows that CSU has a considerable socio-economic burden and an improvement in QoL can be achieved in CSU patients if an appropriate therapeutic path is followed.

Tuscan Consensus on the diagnosis, treatment and follow up of adult atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory disease with a chronic-relapsing course that is intensely itchy. A correct diagnosis of AD in adults and consequently appropriate clinical therapeutic management is a critical issue for extreme clinical expression heterogeneity and various grades of disease severity. In order to ensure high levels of care and standardization of clinical therapeutic management of Adult AD, the decision was taken to create an AD Tuscan Consensus Group (the Group), to work on and validate a consensus based regional clinical-therapeutic management model. The aims of the Group were to find agreement on the criteria for diagnosis, scoring of severity, multidisciplinary approach and treatment of adult atopic dermatitis and to create an easier way for patients to access specialized dermatology outpatient services and importantly to reduce waiting lists and costs related to the management of AD. The Tuscan Consensus Group adopted a simplified Delphi method, in three principal steps: 1) literature metanalysis and critical review of patient's clinical experience to identify the main areas considered questionable or uncertain; 2) discussion of those areas requiring consensus and statement definition through four different sub-committees (diagnosis, severity evaluation, scoring and comorbidities); 3) a consensus based simplified process with final approval of each statement by plenary vote with approval >80% of the participants. The Group here presents and discusses the consensus based recommendation statements on adult atopic dermatitis.

Management of chronic urticaria in children: a clinical guideline.

The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.

Efficacy and safety of S-acyl glutathione 2% cream vs. placebo against UVB-induced erythema: a randomized, double-blinded clinical trial.

BACKGROUND: Reactive oxygen species have a major role in the UV-induced short- and long-term damage, thus the exogenous supplementation of antioxidant molecules may allow better skin protection. Despite glutathione has pivotal properties in the complex cytoplasmic antioxidant system, its supplementation is hampered by limited transmembrane absorption. Modification of glutathione pharmacokinetic properties via acetylation with long-chain polyunsaturated fatty acid may improve its passage through phospholipidic membranes. METHODS: This was a single center randomized double-blinded clinical trial, versus placebo, cross-sectional pairwise at time 0. The participants were 10 healthy volunteers with skin phototypes II or III and age ≥18 years interested in performing minimal erythema dose (MED) evaluation performed by photoallergology unit of Division of Dermatology at P. Palagi Hospital, in Florence. Each volunteer underwent UVB phototesting, treating four different areas with increasing UVB doses in four different conditions. One arm was treated as standard procedure (naïve arm), one applying linolenic-glutathione conjugate (Lin-GSH) cream 2% before irradiation (pre-Lin-GSH arm), one with placebo (placebo arm) and one applying Lin-GSH cream 2% (SoloSale Srl, Florence, Italy) after irradiation (post-Lin-GSH arm). The main endpoint was to evaluate efficacy of Lin-GSH cream 2% before UVB irradiation compared with placebo. A secondary endpoint was the evaluation of the same cream applied after irradiation compared to no treatment. Another secondary objective is the evaluation of safety in both conditions. Mean MED was evaluated at distinct conditions. Safety was evaluated reporting all grade 3-4 adverse events up to 30 days after treatment. All volunteers were treated in all four experimental conditions. The pre-Lin-GSH and placebo arms were applied in a double-blind condition for each volunteer. Neither the volunteer nor the investigator executing MED evaluation knew which arm was given Lin-GSH and which one placebo. RESULTS: Ten volunteers among 12 recruited for the study were correctly randomized and completed all study evaluations. Recruitment went from April 1st, 2016 to May 1st, 2016, up to adequate population number. Mean MED in pre-Lin-GSH arm was superior to mean MED in placebo arm (135±5.53 mJ/cm2 vs. 105±7.64 mJ/cm2, P=0.0003). No difference was observed among mean MED in post-Lin-GSH and naïve arms. No grade 3-4 adverse events were reported. CONCLUSIONS: Lin-GSH 2% cream seems a safe and effective in producing a significant increase in MED compared with placebo thanks to its antioxidant properties.