LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa.

Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional post­transcriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNA­microRNA regulatory network was also defined via reverse transcription­quantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNA­TINCR, lncRNA­RBM5­ASI1 and lncRNA­MRPL23­AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.

Italian S3-Guideline on the treatment of atopic eczema - First Update, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

The evidence- and consensus-based guideline on atopic eczema, published in JEADV on 18 August 2022 (part 1) and 3 September 2022 (part 2) was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. To reflect the most recent evidence on novel systemic medications, an update was published in October 2022. According to the purpose of the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA) to adapt the EuroGuiDerm guideline on the treatment of atopic eczema into the Italian Healthcare setting, the original update has been supplemented by inserting notes, well highlighted by the original text, to emphasize the laws, rules, procedures and suggestions of the Italian Ministry of Health and regional Health authorities.

Italian S3-Guideline on the treatment of atopic eczema Part 2: non-systemic treatments and treatment recommendations for special AE patient populations, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Occupational Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for pediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

Italian S3-Guideline on the treatment of Atopic Eczema - Part 1: Systemic therapy, adapted from EuroGuiDerm by the Italian Society of Dermatology and STD (SIDEMAST), the Italian Association of Hospital Dermatologists (ADOI) and the Italian Society of Allergological and Environmental Dermatology (SIDAPA).

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by atopic dermatitis. The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for pediatric, adolescent, pregnant and breastfeeding patients.

All for one: Collaboration between dermatologist, radiation oncologist and radiologist in the clinical management of "difficult to treat" non melanoma skin cancer.

This series introduces the clinical management of difficult-to-treat non-melanoma skin cancers (NMSCs) through a multidisciplinary approach, emphasizing the integration of dermoscopy and Ultra high-frequency ultrasound (UHFUS) for accurate diagnosis and treatment planning, particularly in cases referred for radiotherapy (RT). Dermoscopy aids in diagnosing both pigmented and non-pigmented skin lesions, guiding treatment margins and reducing the benign-to-malignant biopsy ratio. UHFUS provides valuable insights into tumor size, depth, and vascularity, complementing clinical evaluations and assisting in RT planning. Three challenging cases are presented, highlighting the pivotal role of dermoscopy and UHFUS in decision-making and treatment optimization. Collaboration between dermatologists, radiation oncologists, and radiologists enhances diagnostic accuracy, tailoring treatment plans to individual patient needs and preferences, ultimately improving patient outcomes and experience. The integration of these imaging techniques holds promise for optimizing non-surgical treatments like RT and monitoring treatment progress, offering a personalized approach to NMSC management.

Proposal of a new dermoscopic criterion for pigmented basal cell carcinoma: a multicentre retrospective study.

Dermoscopy is widely used for the diagnosis of skin cancer and it increases the accuracy of basal cell carcinoma (BCC) detection. BCC dermoscopic criteria have been updated and divided into vascular, pigment-related, and non-vascular/non-pigment-related. Our multicenter retrospective study tested a new dermoscopic pigment-related characteristic to detect pigmented BCC (pBCC) [brown homogeneous blotches (BHB)]. Cases of pBCC were collected from the databases of IDI-IRCCS of Rome and from three Italian private dermatology centers. BHB are confined patches of brown uniform pigmentation without dermoscopic features (net, fat fingers, etc.) or other internal dermoscopic structures, except for occasional vascular ones like arborizing vessels or globules/dots. Melanocytic and non-melanocytic controls were used. We reviewed photos of 270 pigmented lesions (female 145; 51.8%), including 90 histopathologically verified pBCC and 180 control cases (90 melanocytic and 90 non-melanocytic). BHB were found in 61 cases of 90 pBCC patients. The results showed a 67.8 sensitivity, 93.3 specificity, 83.6 positive and 85.3 negative predictive values, posLR 10.2, negLR 0.3, odds ratio 29.4, p<0.001. Our multicentre retrospective analysis suggested the BHB may be a novel dermoscopic pBCC diagnosis criterion.

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.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

Low-FODMAP diet and hidradenitis suppurativa: the role of nutritionists in the management of dermato-endocrine disorders.

Hidradenitis suppurativa (HS) is a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.

PRAME Is an Effective Tool for the Diagnosis of Nevus-Associated Cutaneous Melanoma.

(1) Background: Nevus-associated cutaneous melanoma (CM) is relatively common in the clinical practice of dermatopathologists. The correct diagnosis and staging of nevus-associated cutaneous melanoma (CM) mainly relies on the correct discrimination between benign and malignant cells. Recently, PRAME has emerged as a promising immunohistochemical marker of malignant melanocytes. (2) Methods: PRAME immunohistochemistry (IHC) was performed in 69 cases of nevus-associated CMs. Its expression was evaluated using a score ranging from 0 to 4+ based on the percentage of melanocytic cells with a nuclear expression. PRAME IHC sensitivity, specificity, positive predictive values, and negative predictive values were assessed. Furthermore, the agreement between morphological data and PRAME expression was evaluated for the diagnosis of melanoma components and nevus components. (3) Results: PRAME IHC showed a sensitivity of 59%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 71%. The diagnostic agreement between morphology and PRAME IHC was fair (Cohen's Kappa: 0.3); the diagnostic agreement regarding the benign nevus components associated with CM was perfect (Cohen's Kappa: 1.0). PRAME was significantly more expressed in thick invasive CMs than in thin cases (p = 0.02). (4) Conclusions: PRAME IHC should be considered for the diagnostic evaluation of nevus-associated CM and is most useful in cases of thick melanomas. Pathologists should carefully consider that a PRAME-positive cellular population within the context of a nevus could indicate a CM associated with the nevus. A negative result does not rule out this possibility.

Effectiveness, Tolerability, and Drug Survival of Risankizumab in a Real-World Setting: A Three-Year Retrospective Multicenter Study-IL PSO (ITALIAN LANDSCAPE PSORIASIS).

BACKGROUND: Risankizumab is a humanized monoclonal antibody that selectively inhibits interleukin-23. It has been approved for moderate-to-severe plaque psoriasis and has shown efficacy and safety in clinical trials and real-world experiences. This study aimed to evaluate the long-term effectiveness, safety, and drug survival of risankizumab in a real-life setting. MATERIALS AND METHODS: We included patients treated with risankizumab from January 2019 to February 2023. A Psoriasis Area and Severity Index score (PASI) was collected at weeks 0, 16, 28, 52, 104, and 156, when available. The occurrence of any adverse events was recorded at each visit. RESULTS: We enrolled 1047 patients. At week 52, a ≥90% improvement in PASI was observed in 81.44% of patients, with a continuous improvement throughout the study (88.99% and 99.07% at weeks 104 and 156, respectively). After three years of treatment, all patients involving the scalp, palms/soles, and genitalia and 95% of patients with nail psoriasis achieved a complete or almost complete skin clearance. No significant safety findings were observed, and 90.73% of the patients were still on treatment after 36 months. CONCLUSIONS: This study supports the long-term effectiveness and safety of risankizumab in a real-world setting, even in patients involving difficult-to-treat areas.

Association between maternal dupilumab exposure and pregnancy outcomes in patients with moderate-to-severe atopic dermatitis: A nationwide retrospective cohort study.

BACKGROUND: There is limited epidemiological evidence on outcomes associated with dupilumab exposure during pregnancy; monitoring pregnancy outcomes in large populations is required. OBJECTIVE: To investigate the potential association between exposure to dupilumab in pregnant women with atopic dermatitis and any adverse pregnancy, neonatal, congenital and post-partum outcomes. METHODS: We performed a multicentre retrospective cohort study across 19 Italian tertiary referral hospital. Childbearing women were eligible if aged 18-49 years and carried out the pregnancy between 1 October 2018 and 1 September 2022. RESULTS: We retrospectively screened records of 5062 patients receiving dupilumab regardless of age and gender, identifying 951 female atopic dermatitis patients of childbearing age, 29 of whom had been exposed to the drug during pregnancy (3%). The median duration of dupilumab treatment prior to conception was 22.5 weeks (range: 3-118). The median time of exposure to the drug during pregnancy was 6 weeks (range: 2-24). All the documented pregnancies were unplanned, and the drug was discontinued in all cases once pregnancy status was reported. The comparison of the study cohort and the control group found no significant drug-associated risk for adverse pregnancy, congenital, neonatal or post-partum outcomes. The absence of a statistically significant effect of exposure on the event was confirmed by bivariate analysis and multivariate analysis adjusted for other confounding factors. CONCLUSIONS: This cohort of pregnant patients exposed to dupilumab adds to the existing evidence concerning the safety of biologic agents in pregnancy. No safety issues were identified regarding the primary outcome assessed. In clinical practice, these data provide reassurance in case of dupilumab exposure during the first trimester. However, the continuous use of dupilumab throughout pregnancy warrants further research.

The Role of Sentinel Node Biopsy in the Era of Adjuvant Therapy for Melanoma.

Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.