Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Gender differences in adult atopic dermatitis and clinical implication: Results from a nationwide multicentre study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults. However, limited research has been conducted on gender differences in AD. OBJECTIVES: This study aimed to assess gender differences in adult AD patients, focusing on demographic and clinical features, comorbidities and treatment approaches. METHODS: In this multicentre, observational, cross-sectional study, we enrolled 686 adult patients with AD (357 males and 329 females). For each patient, we collected demographic data (age and sex), anthropometric measurements (weight, height, hip circumference, waist circumference and waist-to-hip ratio), clinical information (onset age, disease duration, severity, itching intensity, impact on quality of life) and noted comorbidities (metabolic, atopic and other). We recorded past and current topical and systemic treatments. We analysed all collected data using statistical techniques appropriate for both quantitative and qualitative variables. Multiple correspondence analysis (MCA) was employed to evaluate the relationships among all clinical characteristics of the patients. RESULTS: We found no differences in age at onset, disease duration, severity and quality of life impact between males and females. Males exhibited higher rates of hypertriglyceridaemia and hypertension. No significant gender differences were observed in atopic or other comorbidities. Treatment approaches were overlapping, except for greater methotrexate use in males. MCA revealed distinct patterns based on gender, disease severity, age of onset, treatment and quality of life. Adult males with AD had severe disease, extensive treatments and poorer quality of life, while adult females had milder disease, fewer treatments and moderate quality of life impact. CONCLUSIONS: Our study reveals that gender differences in adult AD patients are largely due to inherent population variations rather than disease-related disparities. However, it highlights potential undertreatment of females with moderate AD and quality of life impact, emphasizing the need for equitable AD treatment. JAK inhibitors may offer a solution for gender-based therapeutic parity.

New and emerging conditions of acquired cutaneous mucinoses in adults.

Cutaneous mucinoses are a heterogenous group of conditions, characterized by the deposition of glycosaminoglycans (mucin) in the dermis, follicles, or in the epidermis. Major cutaneous mucinoses include lichen myxedematosus, scleredema, mucinoses associated with thyroid disease, reticular erythematous mucinosis, papulonodular mucinosis associated with connective tissue diseases, and cutaneous focal mucinosis. The aim of this review is to provide an update of what has currently been reported in the last 30-year literature about several new or emerging conditions of acquired cutaneous mucinoses in adults. Two new clinico-pathologic entities have been described: (i) Obesity-associated lymphedematous mucinosis and pretibial stasis mucinosis; (OACM) (ii) Nodular mucinosis of the breast (NMB). Two relatively new disease categories encompassing cutaneous mucinoses with a common pathogenetic mechanism have been identified: (i) Cutaneous mucinoses associated with drug exposure including biologic therapy, anti-colony-stimulating factor 1 receptor (CSF1R) and subcutaneous intralesional interferons (toxic dermal mucinoses); (ii) Cutaneous mucinosis following physical agents including mechanical traumas and after knee replacement.

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study.

BACKGROUND: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited. METHODS: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks. RESULTS: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was -87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03). CONCLUSION: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials.

Comorbidities and treatment patterns in adult patients with atopic dermatitis: results from a nationwide multicenter study.

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.

Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European Consensus Project.

BACKGROUND: Histopathological classification of basal cell carcinoma (BCC) has important prognostic and therapeutic implications, but reproducibility of BCC subtyping among dermatopathologists is poor. OBJECTIVES: To obtain a consensus paper on BCC classification and subtype definitions. METHODS: A panel of 12 recognized dermatopathologists (G12) from nine European countries used a modified Delphi method and evaluated 100 BCC cases uploaded to a website. The strategy involved five steps: (I) agreement on definitions for WHO 2018 BCC subtypes; (II) classification of 100 BCCs using the agreed definitions; (III) discussion on the weak points of the WHO classification and proposal of a new classification with clinical insights; (IV) re-evaluation of the 100 BCCs using the new classification; and (V) external independent evaluation by 10 experienced dermatopathologists (G10). RESULTS: A simplified classification unifying infiltrating, sclerosing, and micronodular BCCs into a single "infiltrative BCC" subtype improved reproducibility and was practical from a clinical standpoint. Fleiss' κ values increased for all subtypes, and the level of agreement improved from fair to moderate for the nodular and the unified infiltrative BCC groups, respectively. The agreement for basosquamous cell carcinoma remained fair, but κ values increased from 0.276 to 0.342. The results were similar for the G10 group. Delphi consensus was not achieved for the concept of trichoblastic carcinoma. In histopathological reports of BCC displaying multiple subtypes, only the most aggressive subtype should be mentioned, except superficial BCC involving margins. CONCLUSIONS: The three BCC subtypes with infiltrative growth pattern, characteristically associated with higher risk of deep involvement (infiltrating, sclerosing, and micronodular), should be unified in a single group. The concise and encompassing term "infiltrative BCCs" can be used for these tumors. A binary classification of BCC into low-risk and high-risk subtypes on histopathological grounds alone is questionable; correlation with clinical factors is necessary to determine BCC risk and therapeutic approach.

Use of Dupilumab in 543 Adult Patients With Moderate-to-Severe Atopic Dermatitis: A Multicenter, Retrospective Study

Background: Dupilumab has proven to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, real-world experience with dupilumab in a broader population is limited.Methods: The study population comprised adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at 10 Italian teaching hospitals. We analyzed physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index [DLQI]), and serological markers (IgE and eosinophil count) after 16 weeks.Results: We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median (IQR) change from baseline to 16 weeks of treatment in the EASI score was –87.5 (22.0) (P<.001). The EASI-50, EASI-75, and EASI-90 response rates were 98.1%, 81.5%, and 50.8% after 16 weeks. At 16 weeks, 93.0% of the patients had achieved a 4-point or higher improvement in DLQI from baseline. During treatment with dupilumab, 12.2% of the patients developed conjunctivitis, and total IgE decreased significantly (P<.001). Interestingly, in the multivariate logistic regression model, the risk of developing dupilumab-related conjunctivitis was associated with early onset of AD (OR, 2.25; 95%CI, 1.07-4.70; P=.03) and presence of eosinophilia (OR, 1.91; 95%CI, 1.05-3.39; P=.03).Conclusion: This is the broadest real-life study in AD patients treated with dupilumab to date. We observed more significant improvements induced by dupilumab in adult patients with moderate-to-severe AD than those reported in clinical trials (AU)

Antecedentes: Se ha demostrado en ensayos clínicos que dupilumab es un tratamiento eficaz para pacientes con dermatitis atópica (DA)de moderada a grave. Sin embargo, la experiencia en vida real con dupilumab y con gran número de pacientes es más limitada.Métodos: Se incluyeron en el estudio pacientes adultos con DA de moderada a grave, definida como un índice de gravedad del área deeccema (EASI) de 24 o más, tratados con dupilumab en diez centros universitarios italianos. Se analizaron parámetros medidos por elmédico (EASI), por el paciente (puntuación de prurito y sueño, índice de calidad de vida dermatológica DLQI) y marcadores serológicos(inmunoglobulina IgE y recuento de eosinófilos en sangre) a las 16 semanas de tratamiento.Resultados: Se incluyeron 543 pacientes con DA de moderada a grave. Dos pacientes (0,4%) interrumpieron el tratamiento. La mediana± cambio porcentual intercuartílico desde el inicio hasta las 16 semanas de tratamiento en la puntuación EASI fue de -87,5 ± 22,0(p <0,001). Las tasas de respuesta de EASI-50, EASI-75 y EASI-90 fueron del 98,1%, 81,5% y 50,8% después de 16 semanas. En lasemana 16, el 93% de los pacientes habían logrado una mejora de 4 puntos o más en el DLQI desde el inicio. Durante el tratamiento condupilumab, el 12,2% de los pacientes desarrollaron conjuntivitis y la IgE total disminuyó significativamente (p <0,001). Curiosamente, enel modelo de regresión logística multivariante, el riesgo de desarrollar conjuntivitis relacionada con dupilumab se asoció con la aparicióntemprana de DA (OR, 2,25; IC del 95%, 1,07–4,70; p = 0,03) y presencia de eosinofilia (OR, 1,91; IC del 95%, 1,05–3,39; p = 0,03).Conclusión: Hasta la fecha, este es el estudio más amplio en vida real en pacientes con DA tratados con dupilumab. Se observaron mejorassignificativas y más importantes que las notificadas en los ensayos clínicos realizados con dupilumab (AU)

Real-life experience on effectiveness and safety of dupilumab in adult patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. OBJECTIVE: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. METHODS: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). RESULTS: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. CONCLUSIONS: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

2020 European guideline on the management of genital molluscum contagiosum.

Molluscum contagiosum is a benign viral epidermal infection associated with high risk of transmission. The guideline is focused on the sexually transmitted molluscum contagiosum. The diagnosis is clinical with characteristic individual lesions, termed 'mollusca', seen as dome-shaped, smooth-surfaced, pearly, firm, skin-coloured, pink, yellow or white papules, 2 - 5 mm in diameter with central umbilication. Dermoscopy may facilitate diagnosis. Therapeutic options are numerous, including physical treatments (cautery, curettage and cryotherapy), topical chemical treatments (e.g. podophyllotoxin and imiquimod) or waiting for spontaneous resolution in immunocompetent patients. In pregnancy, it is safe to use physical procedures (e.g. cryotherapy). Immunosuppressed patients develop severe and recalcitrant molluscum lesions that may require treatment with cidofovir, imiquimod or interferon. Patients with molluscum contagiosum infection should be offered to be screened for other sexually transmitted infections.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

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.