Short-term effectiveness and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis: results from a 16-week real-world multicenter retrospective study - il AD (Italian landscape atopic dermatitis).

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

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

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

Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Current frequency of contact allergy to isothiazolinones (methyl-, benz- and octylisothiazolinone) across Europe.

BACKGROUND: The use of methylisothiazolinone (MI) as a preservative in cosmetic products caused an alarming increase in MI contact allergy across Europe in the 2010s. This was followed by regulations of use with a total ban on leave-on (implemented in 2017) and reduced use concentrations in rinse-off cosmetics (2018). OBJECTIVE: To follow-up on the prevalence of contact allergy to MI and the related benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in consecutively patch-tested patients in Europe. METHODS: A cross-sectional audit following the design of two previous audits on MI contact allergy from 1 May 2022 to 31 October 2022 included all patients patch tested with the European baseline series, including or supplemented with MI, BIT and OIT across 10 departments in eight European countries. RESULTS: A total of 2554 patients were consecutively patch tested with the three isothiazolinones during the study period. The prevalence of MI and BIT contact allergy was 2.9% (95% confidence interval [CI]: 2.3%-3.7%; range 1.1%-5.8%) and 3.1% (95% CI: 2.4%-3.9%; range 0.0%-6.6%), respectively; that of OIT was 0.7% (95% CI: 0.4%-1.1%; range 0%-3.2%). Rinse-off cosmetic (73.3%) and leave-on cosmetic products (13.3%) were still associated with eliciting allergic contact dermatitis to MI. CONCLUSION: We confirmed a positive impact of regulatory measures on the prevalence of MI contact allergy in Europe, which halved compared to 2015. However, our data suggest that consumers may still be exposed to older cosmetic products containing MI. BIT has superseded MI in causing contact allergy, despite not being allowed for use in cosmetic products.

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.

Italian National Registry of Alopecia Areata: an epidemiological study of 699 Italian patients.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease that affects the hair follicles of the scalp and the rest of the body causing hair loss. Due to the unpredictable course of AA and the different degrees of severity of hair loss, only a few well-designed clinical studies with a low number of patients are available. Also, there is no specific cure, but topical and systemic anti-inflammatory and immune system suppressant drugs are used for treatment. The need to create a global registry of AA, comparable and reproducible in all countries, has recently emerged. An Italian multicentric electronic registry is proposed as a model to facilitate and guide the recording of epidemiological and clinical data and to monitor the introduction of new therapies in patients with AA. METHODS: The aim of this study was to evaluate the epidemiological data of patients with AA by collecting detailed information on the course of the disease, associated diseases, concomitant and previous events, and the clinical response to traditional treatments. Estimate the impact on the quality of life of patients. RESULTS: The creation of the National Register of AA has proven to be a valid tool for recording, with a standardized approach, epidemiological data, the trend of AA, response to therapies and quality of life. CONCLUSIONS: AA is confirmed as a difficult hair disease to manage due to its unpredictable course and, in most cases, its chronic-relapsing course, capable of having a significant impact on the quality of life of patients.

Lichen Amyloidosis in an Atopic Patient Treated with Dupilumab: A New Therapeutic Option.

Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application.

Pembrolizumab-Induced Rupioid Psoriasis Treated by Apremilast Without Interrupting the Ongoing Antineoplastic Treatment.

We report the case of a 77-year-old man affected by a poorly differentiated metastatic pulmonary adenocarcinoma who, after the first course of therapy with cisplatin-pemetrexed-pembrolizumab treatment, developed rupioid psoriasis. We decided to discontinue pembrolizumab for four weeks until lesions improved and to start therapy with apremilast (an oral small molecule phosphodiesterase (PDE)4 inhibitor) in combination with systemic methylprednisolone 16 mg/day with consequent tapering until discontinuation in a few weeks. After accomplishing three months of treatment with apremilast, the patient gained complete remission of the rupioid lesions. Pembrolizumab therapy was reintroduced, and cycles were carried out without exacerbating the clinical picture. During the fourth month of therapy with apremilast, it was attempted to stop the treatment despite continuing the therapy with pembrolizumab. As a result, there was a relapse of the erythematous scaling plaques. After the subsequent reintroduction of apremilast, a new remission of the clinical picture occurred despite the absence of interruption of pembrolizumab. As far as we know, this is the second case of rupioid psoriasis induced by immunotherapy with pembrolizumab. Still, while the previous case was undergoing therapy with acitretin and methylprednisone, our patient is the first case treated with apremilast with excellent and rapid remission even after discontinuation and re-administration of pembrolizumab without exacerbation of dermatitis. In addition, the appearance of psoriasis during immunotherapy can be properly treated, which does not contraindicate the continuation of the antineoplastic treatment.

Tumid Lupus Erythematosus (TLE): A Review of a Rare Variant of Chronic Cutaneous Lupus Erythematosus (cCLE) with Emphasis on Differential Diagnosis.

Tumid lupus erythematosus (TLE) has been the subject of heated debate regarding its correct nosographic classification. The definition of TLE has changed over time, varying according to the different studies performed. In this review, we address the initial definition of TLE, the changes that have taken place in the understanding of TLE, and its placement within the classification of cutaneous lupus erythematosus (CLE), with a focus on clinical, histopathological, immunophenotypical, and differential diagnosis aspects.

The new Italian SIDAPA Baseline Series for patch testing (2023): an update according to the new regulatory pathway for contact allergens.

Allergic contact dermatitis (ACD) is a common inflammatory skin disease caused by delayed hypersensitivity to chemical and biotic contact allergens. ACD significantly affects the patients' quality of life negatively impacting both occupational and non-occupational settings. Patch testing is the gold standard diagnostic in vivo test to precise the ACD etiology and to correctly perform prevention. According to the Italian Medicines Agency (AIFA) legislative decree no. 178 of 29th May 1991, allergens are defined as medicines and therefore they are subject to strict regulation. In 2017, AIFA (decree no. 2130/2017) started a procedure to regulate contact allergens on the Italian market and actually the contact allergens temporarily authorized are reported in AIFA decree no. 98/2022, valid until November 2023. The availability on the market of contact allergens to diagnose ACD and continuous updating on the basis of new epidemiological trends are mandatory, jointly with the continuous update of the baseline and integrative series for patch testing. For this reason, the scientific community represented in Italy by the Skin Allergies Study Group of SIDeMaST (Italian Society of Dermatology and Venereology) and SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) are constantly working, in close relationship with the European scientific communities with large expertise in this important sector of the modern Dermatology. Herein, we report the setting up of regulatory legislation by AIFA and the new Italian Adult Baseline Series for patch testing.

Tattoo-Associated Skin Reaction in a Melanoma Patient Receiving B-RAF and MEK Inhibitors: A Case Report with an Emphasis on Etiopathogenic and Histological Features.

Tattoo-associated cutaneous reactions have become quite frequent given the increasing percentage of tattooed subjects globally and also in Italy. On the other hand, the increasing use of target therapy is showing the ability of these drugs to affect the immune system and also cause adverse tattoo-related reactions. In this paper, we report a case of a 42-year-old patient with stage-IIID melanoma undergoing treatment with Dabrafenib and Trametinib. The patient reported erythema, oedema and scaling in areas of the body containing a black tattoo, and, conversely, no signs and/or symptoms in areas with tattoos of a different color. Histopathological and immunohistochemical features indicated a lympho-histiocytic reaction with a granulomatous morphology, mainly distributed around the vessels and hair adnexa. By discussing the cases reported in the literature prior to ours, we concluded and provided the possible indications of the pathogenesis.

Drug Survival of Upadacitinib and Predicting Factors of Discontinuation in Adult Patients Affected by Moderate-to-Severe Atopic Dermatitis: An Italian Multicenter Analysis.

Background: Limited real-world data are available on upadacitinib drug survival in patients with atopic dermatitis (AD). Objectives: To investigate upadacitinib drug survival, and the reasons and predictors of drug discontinuation in AD patients. Methods: All consecutive patients aged 18-75 years, affected by moderate-to-severe AD, and treated with upadacitinib for more than 1 month at dermatological clinics were included during November 2020-August 2023. Upadacitinib survival was investigated through Kaplan-Meier survival analysis and the predictors through multivariable logistic regression analysis. Results: Overall, 325 adult AD patients (mean (SD) age, 38.6(15.6) years) had a 1-year and 1.5-year upadacitinib drug survival of 91.5% and 80.2%, respectively. The main reasons for drug discontinuation (25/325, 7.7%) were adverse events (4.9%), including cutaneous or infectious diseases (1.5%), such as acne and herpes zoster; blood test changes (1.2%), including hypercholesterolemia, creatine phosphokinase or liver enzyme elevation, and lymphopenia; urinary or respiratory infections (0.9%); deep venous thrombosis (0.3%); malignancies (0.3%); loss of consciousness (0.3%); and arthralgias (0.3%); followed by ineffectiveness (0.6%). No specific characteristic was significantly associated with an increased risk of upadacitinib discontinuation. Conclusions: Our findings show that upadacitinib was effective in moderate-to-severe AD after more than 1 year of continuous treatment but point to the need for clinical and laboratory monitoring of patients.

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.