BACKGROUND:Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder, often associated with Down syndrome (DS), with a prevalence ranging from 2.1% to 3.02%. OBJECTIVES:Our aim was to describe the epidemiological and clinical features of patients with HS and concomitant DS in a relevant Italian cohort. METHODS:We conducted a real-life, multicentre, retrospective, and descriptive analysis of 70 HS-DS patients with 2-year follow-up. RESULTS:Seventy Caucasian adult patients (31 males and 39 females) affected by HS and DS were enrolled, with a mean age at baseline of 23.9 years. Mean body mass index (BMI) was 27.5 with obesity found in 20.9% of patients. Mean age at HS onset was 15.2, while at diagnosis was 18.6 with a diagnostic delay of 3.4 years. The groin was the most frequently involved site at HS onset and diagnosis, while the most common HS phenotype was the follicular one. At HS diagnosis, Hurley stage II was the most frequent with a median value of the International Hidradenitis Suppurativa Severity Score (IHS4) of 6 (moderate HS) while the most common therapy prescribed was systemic antibiotics, followed by topical treatments. Over follow-up, treatment patterns changed and IHS4, Dermatology Life Quality Index (DLQI) and pain numeric rating scale (NRS pain) scores decreased. CONCLUSIONS:Our patient cohort is characterized by female predominance, high BMI, early HS onset, predominance of follicular phenotype, and moderate disease severity. Given the recognized association between these two conditions, we recommend regular screening by pediatricians and dermatologists for early detection and management of HS in DS patients. Future comparative studies are needed to clarify which features may be specifically associated with HS and concomitant DS.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterised by an aberrant activation of innate immunity and increased production of pro-inflammatory mediators such as interleukin 17 (IL-17). IL-17 has been shown to play a key role in the pathogenesis of HS and evidence highlights the potential of IL-17-targeted therapies. The fully human IgG/κ monoclonal antibody secukinumab, which specifically targets IL-17A and inhibits interaction with its receptor, has recently been approved for the treatment of moderate-to-severe HS. Secukinumab offers patients an efficacious and well-tolerated treatment option in terms of sustained response by rapidly improving signs and symptoms, and preventing disease progression in the absence of loss of response. Being a challenging disease, HS is associated with a delay to diagnosis of 3–10 years and, consequently, late implementation of appropriate treatment, leading to disease progression. Misdiagnosis due to flawed understanding and lack of awareness among medical providers and patients is considered an important factor contributing to the delayed diagnosis. Thus, serious efforts must be made on a large scale to urgently reduce the delay in HS diagnosis and reduce the disease burden in patients, including raising awareness, implementation of education programmes at medical and specialisation schools, as well as continuous education of healthcare providers at different levels for the early detection of HS and initiation of appropriate treatment. Here, we present the main critical unmet needs in the diagnosis and treatment of patients affected by HS, address how disease awareness and comprehensive multidisciplinary management (offering both medical and surgical care) can benefit patients, and suggest therapeutic options, based on clinical characterisation and early identification and intervention (window of opportunity), to be adopted for a timely and better management of disease progression and to fill current gaps.

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for effective screening and early diagnosis procedures. We employed NMR-based salivary and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific alterations compared to healthy controls. These metabolic changes were more pronounced in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional, and healthy tissues. Our pilot study employing a metabolomics-based approach led to the development of salivary models that represent a complementary strategy for clinically detecting leukoplakia. However, larger-scale validation is required to fully evaluate their diagnostic potential and to effectively stratify leukoplakia patients according to dysplasia status.

Background Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe mucocutaneous fragility disorder due to mutations in the COL7A1 gene encoding collagen VII, the major constituent of anchoring fibrils essential for epithelial adhesion. RDEB is characterized by unremitting blistering, chronic painful wounds and fibrotic scarring that results in hand and foot pseudosyndactyly, microstomia, and esophageal strictures. RDEB complications include nutritional compromise, chronic anemia, failure to thrive, delayed puberty, osteoporosis, and renal involvement. In addition, early onset cutaneous squamous cell carcinomas (cSCC) represent the first cause of premature death. Despite recent progress in wound care, disease management still relies on symptomatic and preventive measures. No clinical practice guidelines specifically focused on the care of RDEB are currently available. The present multidisciplinary consensus recommendations were generated following a modified Delphi method with the aim to provide healthcare professionals with practical statements on RDEB management from birth to adulthood. Results Ten experts from six Italian EB reference centers developed 86 statements based on existing clinical practice guidelines and consensus recommendations for EB, literature data, and personal expertise. A multidisciplinary group of 30 members, representative of all major specialties relevant to RDEB management, participated to the anonymous online voting process. All statements reached consensus (> 75% agreement) at first voting round. Statements are divided into four major areas: (1) diagnosis, (2) neonatal age and infancy, (3) from childhood to adulthood, and (4) transversal age-independent issues, each of the last three comprising multiple domains of care. In particular, the section on patient care from childhood to adults deals with measures for management of wounds, gastrointestinal, eye and renal involvement, nutritional compromise, anemia, hand and foot deformities, cSCC, delayed puberty and osteoporosis, sexuality, pregnancy and delivery. Transversal issues comprise: pain and itch management, patient care in the operating theatre, physiotherapy and occupational therapy, therapeutic patient education and psychosocial support. Conclusions The proposed practical and synthetic recommendations cover all major issues in the management of patients with RDEB from birth to adulthood. They can represent a useful tool to support hospital healthcare personnel as well as primary care physicians in the complex multidisciplinary management of RDEB.

Oral lichen planus (OLP) is a chronic T-cell-mediated autoimmune disease, with low potential for malignant transformation. Its etiology remains unclear, necessitating immunohistochemical and molecular-level studies to enhance diagnosis and management. Thirteen patients diagnosed with OLP and 13 healthy controls (HCs) were enrolled from three centers. Mucosal tissue samples collected during diagnostic biopsies and unstimulated whole saliva samples were analysed. A comprehensive approach was taken, with high-resolution magic angle spinning (HR-MAS) 1H-NMR spectroscopy performed on biopsies and liquid 1H-NMR spectroscopy on saliva samples to identify potential biomarkers correlated with OLP. Multivariate analyses effectively distinguish OLP patients from HC based on metabolic profiles, with key metabolites contributing to the separation. In tissue, triglycerides were significantly elevated in OLP biopsies, whereas amino acids such as glutamate, glutamine, taurine, glycine and alanine were significantly decreased in OLP tissues compared with controls (p < 0.05). Salivary analysis revealed significant alterations in compounds of bacterial origin-such as isobutyrate, isocaproate, isovalerate and agmatine-suggesting dysbiosis in OLP patients. The metabolic alterations identified highlight the roles of oxidative stress and lipid metabolism in OLP pathogenesis and suggest potential biomarkers for OLP diagnosis. These findings provide new insights into the molecular mechanisms of OLP, which may have important clinical implications for future diagnostic and therapeutic strategies.

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease affecting various mucous membranes, with rare skin involvement. We present a case of a 40-year-old woman with recurring desquamative gingivitis, implicating etanercept, an anti-TNF-a a agent, in MMP-like lesions confined to the oral mucosa. Suspicion arose due to temporal correlation between drug administration and lesion onset, confirmed by recurrence upon resumption and resolution upon suspension. Laboratory findings supported MMP diagnosis. Notably, the patient had a history of autoimmune urticaria and axial spondylarthritis. A probable adverse drug reaction was established using the Naranjo scale. Possible mechanisms involve the role of TNF-a a in MMP pathophysiology and its interaction with viral triggers, exemplified by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. This case underscores the intricate relationship among autoimmune conditions, medications, and external factors in mucocutaneous disorders, advocating for comprehensive patient assessment and interdisciplinary collaboration for optimal management.

Background: The delayed diagnosis of skin tumors is associated with a worsened prognosis. The impact of the interruption of clinical and surgical health services during the COVID-19 pandemic lockdowns has been documented among many pathologies. The impact of delayed diagnoses on patients with cutaneous squamous cell carcinomas (cSCCs) is poorly defined. Objective: To compare patient and lesion characteristics and the surgical management of excised cSCCs prior to the pandemic shutdown of services (2018–2019) with the phase following the pandemic’s second wave (2021–2022). Methods: An observational, single-center, cross-sectional study of 416 surgically excised cSCCs over the course of two years was performed. Only patients with histologically confirmed cSCC were enrolled. Data collection included patient demographics and lesion characteristics, time to surgery, surgical approach, and histological data. Results: More cSCC lesions were excised prior to the interruption of services (n = 312 vs. n = 186). Lesions were significantly larger (1.7 ± 1.2 vs. 2.1 ± 1.5 cm; p = 0.006) and more invasive (52% vs. 89%; p < 0.001), in the period 2021–2022. Surgical reconstructive techniques were significantly different (p = 0.001). Metastatic involvement was confirmed in three subjects (one in 2018–2019 and two in 2021–2022). There were no significant differences in the time to surgery or patient characteristics. Multivariable regression analysis identified a 4.7-times higher risk of tumor invasion (OR 4.69, 95%CI 2.55–8.16, p < 0.001), a two-times higher chance of dermo-epidermal grafts (OR 2.06, 95%CI 1.09–3.88, p = 0.025), and a 3.2-times higher risk of positive surgical margins (OR 3.21, 95%CI 1.44–7.17, p = 0.004). Conclusions: Diagnostic delays of cutaneous SCCs associated with reduced patient access to clinical and diagnostic services are associated with a 4.7-times increased risk of more severe invasion, a three-times increased risk of positive surgical margins, and a significant impact on surgical management, compared to the pre-pandemic period. Comparable patient cohort characteristics and time to surgery remained unchanged.

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.

Acellular dermal matrices, currently represent a useful reconstructive method in onco-dermatologic surgery. Nevertheless, they have some limitations, especially in terms of costs and outpatient post-operative wound care. While some studies on their cost-to-benefit ratio in breast surgery have already been issued, evidence is currently lacking in onco-dermatological surgery. The aim of this study was to evaluate the clinical outcomes perceived by patients who had undergone onco-dermatologic surgery in which either acellular dermal matrices or skin grafts had been used as reconstructive methods. A study population of 150 patients was identified retrospectively and patients’ degree of satisfaction was assessed through the Global Aesthetic Improvement Scale and the Patient Scar Scale Questionnaire. Despite similar scores among the study groups, slightly better results were appreciable after single-stage grafting. However, to what extent these variations really represent a significant difference from a clinical point of view remains to be determined. Moreover, other potential bias in the interpretation of our results may reside in differences in terms of age, body location and baseline tumor size among the study groups. Therefore, further research is needed.

In patients with Epidermolysis Bullosa (EB), surgery may be required to remove Squamous Cell Carcinoma (SCC) of the hands or to correct pseudo-syndactyly. Dermal substitutes may represent a suitable tool to promote the healing of surgical wounds in EB. We review our experience with a collagen-elastin dermal matrix to promote surgical wound healing due to hand surgery to correct pseudo-syndactyly or SCC resection in patients affected by EB. Overall, 12 patients (mean age, 29±11 years, range 13-51; four females) with EB were considered, with a total of 25 different interventions (16 SCC removals; three amputations for recurrent infiltrating SCC; six pseudo-syndactyly corrections). All patients received a collagen-elastin dermal matrix sheet. Neodermis was achieved in all patients, and no adverse events potentially associated with the graft occurred. No SCC recurrence was reported at sites operated for either SCC resection or amputation. The opening of the first or second commissure appears to be maintained for over 1 year after the procedure, preserving digital function. We believe that the application of a dermal substitute, together with a close dressing protocol, may represent a suitable strategy for obtaining physiological tissue regeneration and maintaining proper hand function in patients with EB.

Background: Hidradenitis suppurativa (HS) is a relapsing–remitting inflammatory disease characterized by the progression of asymptomatic nodules to deep-seated lesions and fistula formation that leads to suppuration and scarring. Optical coherence tomography angiography (OCTA) is a new non-invasive imaging technique that carefully analyzes retinal microvasculature networks with high-resolution imaging. Recent studies have demonstrated that retinal vessel density and retinal perfusion reflect systemic inflammatory responses. This study’s aim was to analyze OCTA-derived retinal microvasculature parameters to understand if patients affected by HS and without any relevant ocular or systemic comorbidities showed impaired retinal vascular function and morphology. Method: We performed a case–control study of HS patients and age- and sex-matched control cohort. A total of 20 eyes from 10 HS patients and 30 eyes from 15 healthy controls were analyzed, and OCTA-derived microvasculature parameters were compared between groups. Results: OCTA images showed that HS patients, compared to healthy controls, were typically characterized by higher values of the foveal avascular zone (FAZ) both in the superficial capillary plexus (SCP) and in the deep capillary plexus (DCP), and by lower values of vessel density (VD)-SCP, VD-DCP, and vessel length density (VLD)-SCP in the foveal region. These findings partially reflect changes that have been demonstrated in diabetic patients that could be induced by a protracted metabolic or systemic inflammatory dysregulation. Conclusions: In conclusion, OCTA enables large-scale, non-invasive visual screening and follow-up of the retinal vasculature features, providing a new strategy for the prevention and monitoring of visual changes in HS patients.

Primary Sjögren's Syndrome (pSS) is a multi-system autoimmune disease that involves the exocrine glands. Lymphocytes infiltrate the gland tissue, leading to anatomical modification and hypofunction. Even if the prognosis of pSS is favorable, quality of life is typically reduced due to the diverse manifestations of the disease. The aim of this study is to compare the salivary metabolomes of pSS with healthy controls (HCs). Seven cases were selected from a cohort of pSS patients, and six age- and sex-matched HCs were recruited from a cohort of volunteers. Whole unstimulated saliva was collected for NMR analysis. Our metabolomic analysis focused on 360 ms total echo 1D 1H NMR CPMG spectra. Metabolites detected with CPMG NMR spectra were assigned through 2D NMR spectra (COSY, TOCSY, and HSQC). About 50 metabolites were detected and assigned. Unsupervised exploratory PCA returned partial clustering, and PLS-DA improved the separation between pSS and HCs, highlighting a pool of metabolites distinctly describing each group. Despite the limited number of samples, the presented preliminary data are promising. PLS-DA indicated well-defined group separation, suggesting that the application of 1H-NMR metabolomics is suitable for the study of pSS.

In this experimental study the autofluorescence of squamous carcinoma cells, stimulated by 6 different excitation wavelengths in the range 280-533 nm, has been compared with the autofluorescence of normal control keratinocytes. Skin cells were cultivated in vitro, to isolate their characteristic autofluorescence form the more complex one that would be originated by the complete skin tissue. Autofluorescence spectra in the visible range were complemented by absorption measurements. It was observed that the control cells showed characteristic emission (and absorption) structures due to typical endogenous chromophores [FAD and NAD(P)H, lipo-pigments, porphyrins], that were severely dumped in pathological cells. The autofluorescence spectra were then elaborated by multivariate analysis: after a first exploratory data analysis by means of Principal Component Analysis, the whole dataset was used to develop classification models using partial least squares-discriminant analysis, to differentiate between normal and pathological cells. This permitted us to identify the most suitable fluorescence spectral interval, in the 550-670 nm range, to discriminate between normal and pathological behavior, independently on the excitation wavelength.

Epidermolysis bullosa simplex (EBS) is a rare skin disease inherited mostly in an autosomal dominant manner. Patients display a skin fragility that leads to blisters and erosions caused by minor mechanical trauma. EBS phenotypic and genotypic variants are caused by genetic defects in intracellular proteins whose function is to provide the attachment of basal keratinocytes to the basement membrane zone and most EBS cases display mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes. Besides palliative treatments, there is still no long-lasting effective cure to correct the mutant gene and abolish the dominant negative effect of the pathogenic protein over its wild-type counterpart. Here, we propose a molecular strategy for EBS01 patient's keratinocytes carrying a monoallelic c.475/495del21 mutation in KRT14 exon 1. Through the CRISPR-Cas9 system, we perform a specific cleavage only on the mutant allele and restore a normal cellular phenotype and a correct intermediate filament network, without affecting the epidermal stem cell, referred to as holoclones, which play a crucial role in epidermal regeneration.

Background: MatriDerm and Integra are both widely used collagenic acellular dermal matrices (ADMs) in the surgical setting, with similar characteristics in terms of healing time and clinical indication. The aim of the present study is to compare the two ADMs in terms of clinical and histological results in the setting of dermato-oncological surgery. Methods: Ten consecutive patients with medical indications to undergo surgical excision of skin cancers were treated with a 2-step procedure at our Dermatologic Surgery Unit. Immediately after tumor removal, both ADMs were positioned on the wound bed, one adjacent to the other. Closure through split-thickness skin grafting was performed after approximately 3 weeks. Conventional histology, immunostaining and ELISA assay were performed on cutaneous samples at different timepoints. Results: No significant differences were detected in terms of either final clinical outcomes or in extracellular matrix content of the neoformed dermis. However, Matriderm was observed to induce scar retraction more frequently. In contrast, Integra was shown to carry higher infectious risk and to be more slowly reabsorbed into the wound bed. Sometimes foreign body-like granulomatous reactions were also observed, especially in Integra samples. Conclusions: Even in the presence of subtle differences between the ADMs, comparable global outcomes were demonstrated after dermato-oncological surgery.

Chronic wounds represent nowadays a major challenge for both clinicians and researchers in the regenerative setting. Obesity represents one of the major comorbidities in patients affected by chronic ulcers and therefore diverse studies aimed at assessing possible links between these two morbid conditions are currently ongoing. In particular, adipose tissue has recently been described as having metabolic and endocrine functions rather than serving as a mere fat storage deposit. In this setting, adipose-derived stem cells, a peculiar subset of mesenchymal stromal/stem cells (MSCs) located in adipose tissue, have been demonstrated to possess regenerative and immunological functions with a key role in regulating both adipocyte function and skin regeneration. The aim of the present review is to give an overview of the most recent findings on wound healing, with a special focus on adipose tissue biology and obesity.

Establishing a common language that allows univocal and objective communication in describing wounds and their healing is of utmost importance in defining the diagnostic hypothesis and proper wound management. To measure the level of agreement on the description of wounds, an international study was performed among experts of different professional backgrounds on several common terms used to describe ulcerative lesions. A panel of 27 wound care experts anonymously completed a multiple-choice questionnaire on 100 images of 50 ulcerative lesions. The participants were asked to describe each image using a set of pre-defined terms. An expert data analyst interpreted the questionnaires to map the level of agreement on the used terminology. Our findings show a very low level of agreement among experts in using the proposed terminology to describe the wound bed, the wound edge, and the surrounding skin conditions. Efforts should be planned to find a consensus on the correct use of terminology for wound description. To this aim, partnership, consensus, and agreement with educators in medicine and nursing are necessary.