Cord Blood Serum Levels of IL-31 and CCL17, Cutaneous Markers, and Development of Atopic Dermatitis.

Importance: Atopic dermatitis (AD) is the most prevalent chronic skin condition characterized by inflammation and itching. Currently, there is no reliable method for identifying which newborns might have an increased risk of developing AD. Objective: To evaluate the predictive value of serological biomarkers, such as CCL17/thymus- and activation-regulated chemokine, CCL18, CCL22, CCL27, IL-31, and thymus stromal lymphopoietin, with transepidermal water loss (TEWL) and hydration rate and the development of AD in infants. Design, Setting, and Participants: This observational prospective study included 40 consecutive full-term newborns from a single university hospital in Pisa, Italy. The cutaneous markers of infants were assessed at 1, 6, and 12 months of age, while the biomarkers from the 10-mL sample of cord blood taken at birth were measured after delivery. Data were collected from March to December 2018 and analyzed from January to April 2019. Main Outcomes and Measures: Level of serological biomarkers associated with TEWL and hydration rate, as well as the emergence of AD during the first 12 months of life. Results: All 40 included infants (27 male [68%]) completed the study. At 6 months, 16 infants presented symptoms and signs of AD (AD group) and 24 did not (non-AD group). Infants with AD signs had statistically significant anterior cubital fossa TEWL values at 1, 6, and 12 months of age compared to those without AD signs. No statistically significant correlations were observed between the TEWL measured at the anterior part of knee and hydration rate at the anterior cubital fossa at first month in the 2 groups. With regard to the blood biomarkers, at birth those in the AD group vs the non-AD group had statistically significant higher levels of CCL17/thymus- and activation-regulated chemokine (median [IQR], 716 [509-951] pg/mL vs 419 [24-566] pg/mL; P = .003) and IL-31 (median [IQR], 212 [114-409] pg/mL vs 97 [52-277] pg/mL; P = .04); in contrast, no statistically significant serum level differences were registered for thymus stromal lymphopoietin (median [IQR], 105 [66-295] pg/mL vs 88 [43-187] pg/mL), CCL18 (median [IQR], 1236 [1115-1605] pg/mL vs 1255 [1188-1677] pg/mL), CCL22 (median [IQR], 1032 [936-1454] pg/mL vs 1096 [932-1536] pg/mL), and CCL27 (median [IQR], 172 [122-251] pg/mL vs 120 [90-265] pg/mL). Conclusions and Relevance: In this observational study, the analysis of TEWL at the anterior cubital fossa area occurred prior to and correlated with the clinical signs of AD. Quantification of cytokines indicated that assessing cord blood serum levels of CCL17 and IL-31 could offer new perspectives in identifying newborns who might be susceptible to AD. Larger studies are needed to validate these findings.

Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Mitotic rate as a predictive factor for positive sentinel lymph nodes in pT1 and pT2 melanomas.

Sentinel lymph node biopsy is a crucial step in the management of patients affected by melanoma. The decision whether to perform it or not is based on different histological parameters, but the mitotic rate is no longer considered a prognostic variable after the release of the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines. Our objective was to investigate the risk factors that increase the chance for sentinel lymph node positivity in melanomas with a Breslow thickness of less than 2.00 mm, including the mitotic count. A retrospective single-center study was performed on a homogenous cohort of 408 patients treated for cutaneous melanoma. Histological and clinical features were gathered and correlated with the increased risk for sentinel lymph node positivity by means of univariate and multivariate analyses. A statistically significant correlation between a high mitotic index and a positive sentinel lymph node was found in pT1 and pT2 patients, suggesting that in the case of pT1a melanoma with a high number of mitoses, a discussion about whether a sentinel lymph node biopsy is required should be done.

Epidemiology of Merkel cell carcinoma in Tuscany (Italy), 2006-2021.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that still has a poor prognosis. MCC incidence has increased in recent years worldwide. The aim of our study was to perform an epidemiological retrospective study and to evaluate the impact of MCC clinical and pathological features on overall survival (OS) in a specific geographical area. We retrospectively collected 94 pathology reports from 2006 to 2021 that were present in the pathology archives of the University Hospital of Pisa and of the Hospital of Livorno. Laterality was different according to the site, and almost half of the lesions were T1 and nearly half of the patients had a clinical stage III. We reported a dramatic increase in MCC diagnoses in the last 5 years compared with the previous years, with a crude incidence rate of 1,15/100000 inhabitants, almost doubling the last reported data in Italy. Surgical margins status and ulceration were not related to OS. We have noticed some patients with a rapidly progressing disease and others showing a slow disease progression which should prompt the investigation of specific biomarkers or other features that could elucidate this striking difference in progression-free survival and could potentially identify different subtypes of MCC. Considering the generally low incidence of MCC worldwide, larger cohorts would be necessary to validate our data and to obtain a better prognostic stratification.

Attitudes among dermatologists regarding actinic keratosis treatment options.

Actinic keratosis (AK) is considered a precancerous lesion that can develop into invasive squamous cell carcinoma. Its prevalence is increasing, and it is estimated that it affects between 1% and 44% of the adult population worldwide. Advanced age, fair skin phototypes, and cumulative sun exposure are the main risk factors for AK. Therapies for AK consists of lesion-directed treatment (i.e., cryotherapy, curettage, electrocoagulation, and laser therapy) or field therapy [i.e., photodynamic therapy (PDT), 5-fluorouracil (5-FU), diclofenac sodium (DIC), imiquimod (IMQ), and ingenol mebutate (Ing Meb)]. The type of therapy chosen is determined by the number and location of AKs, the patient's condition, and the patient's tolerability and compliance. In this survey, we collected information from 110 Italian dermatologists about their knowledge and attitudes toward various AK therapeutic approaches. In our study, we discovered that cryotherapy and PDT are the most used treatments for AK, while surgery and laser therapy are the least commonly used. The most commonly used topical therapies are DIC and IMQ 3.75 percent cream, followed by IMQ 5 percent cream, Ing Meb, and 5-FU. The correct treatment for AK can be difficult to choose, but adherence to therapy is critical for good results. Given the high and continuing rise in the incidence of AK, dermatologists' knowledge of various therapeutic approaches is critical.

Pigmentary mammary Paget disease: Clinical, dermoscopical and histological challenge.

A very rare variant of mammary Paget disease (MPD) is the pigmented MPD, first described in 1956. It is very difficult to distinguish this variant from melanoma both clinically and dermoscopically. The diagnosis is confirmed by histopathology and immunohistochemistry. Correct diagnosis is crucial for surgical treatment, which is different for these two diseases. We report the case of a 92-year-old woman, who presented an asymptomatic pigmented lesion of the right nipple and areola. The lesion was arisen for about 6 months and was suspected for melanoma because of clinical and dersmoscopic characteristics. Incisional biopsy revealed tumor cells, that proliferate in the major mammary ducts, and tumor cells in the overlying epidermis of the nipple, thus diagnosing pigmented mammary Paget disease. The patient underwent radical mastectomy.

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.

Melanoma in children, adolescents and young adults: anatomo-clinical features and prognostic study on 426 cases.

PURPOSE: This study was conducted to determine the difference in anatomo-pathological and prognostic features of cutaneous melanoma in children, adolescents and young adults. METHODS: This is a retrospective review on 383 young patients ≤ 39 years of age with cutaneous melanoma, in a period from 2006 to 2016 in Area Vasta Nord Ovest, Tuscany, Italy. We subdivided patients in three groups (children ≤ 14 years, adolescents 15-21 years, young adults 22-39 years). We correlated all the anatomo-pathological parameters with age groups. RESULTS: We identified a total of 426 cases of cutaneous melanoma on an overall total of 383 patients. Mean age at diagnosis for all the patients ≤ 39 years of age was 31.2 years: in group A was 11.2 years, in group B 19.2 years and in group C 32.5 years. Incidence, in the subjects between 0 and 14 years, is 14 cases per million inhabitants, between 15 and 21 years of 145, and between 22 and 39 years of 394. Global incidence was 1.6 case per million for group A, 8.9 cases per million for group B, 105 cases per million for group C. No statistically significative correlation could be described for clinical parameters and age groups. CONCLUSIONS: Incidence of melanoma in our casuistry results as the highest in the world. These data open new study for this kind of cancer.