Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

BACKGROUND: The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. MATERIALS AND METHODS: The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. RESULTS: Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. CONCLUSION: HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

Ultra-High Frequency Ultrasound in Melanoma Management: A New Combined Ultrasonographic-Histopathological Approach.

OBJECTIVES: The main aim of this study is to evaluate the correspondence between the ultrasonographic thickness and the Breslow thickness in melanoma using ultra-high frequency ultrasound and the intra- and inter-operator repeatability in the ultrasonographic measurements of melanoma depth. Moreover, we propose a new protocol based on a combined ultrasonographic-histopathological approach. METHODS: We analyzed 27 melanomas in a population consisted of 27 patients (mean age 57.6 years, 51.8% males), who came at the Department of Dermatology (University of Pisa, Pisa, Italy) from April 2016 to March 2018 and had an ultrasonographic examination of a suspected lesion before the surgical removal using ultra-high frequency ultrasound (Vevo®MD, Fujifilm, Visualsonics, Toronto, Canada; 70 MHz probe). B-mode images were analyzed by two skilled and blinded operators, and the maximum depth of the lesions was measured using a dedicated graphical user interface developed in Matlab R2016b (MathWorks Inc., Natick, MA), to obtain repetitive measurements. RESULTS: All melanomas appeared as band-like or oval/fusiform shaped hypoechoic inhomogeneous lesions. We observed an excellent agreement between the Breslow thickness of melanomas and the ultrasonographic thickness, as well as a reduced intra- and inter-operator variability in the ultrasonographic measurements of melanoma depth. CONCLUSIONS: We propose a ultrasonographic-histopathological protocol which may help clinicians to reduce the diagnostic delay, improve prognosis and survival rates, perform a surgical excision with negative margins, and reduce the variability in the assessment of Breslow thickness.

The diagnosis, management and prevention of intertrigo in adults: a review.

Intertrigo is a common inflammatory skin disorder caused by skin-on-skin friction in skin folds, due to moisture becoming trapped because of poor air circulation. This can occur in any area of the body where two skin surfaces are in close contact with each other. The aim of this scoping review was to systematically map, review and synthesise evidence on intertrigo in adults. We identified a wide range of evidence and performed a narrative integration of this related to the diagnosis, management and prevention of intertrigo. A literature search was conducted within the following databases: Cochrane Library, MEDLINE, CINAHL, PubMed and EMBASE. After reviewing articles for duplicates and relevance, 55 articles were included. The incorporation of intertrigo in the ICD-11 provides a clear definition and should improve the accuracy of estimates. With regards to the diagnosis, prevention and management of intertrigo, the literature demonstrates consensus among health professionals in approach and this forms the basis for the recommendations of this review: identify predisposing factors and educate patient in reducing these; educate patients in skin fold management and adopt structured skin care routine; treat secondary infection with appropriate topical agent; consider using moisture-wicking textiles within skin folds to reduce skin-on-skin friction, wick away moisture and reduce secondary infection. Overall, the quality of evidence on which to determine the strength of any recommendations for practice remains low. There remains the need for well-designed studies to test proposed interventions and build a robust evidence base.

Impact of psychiatric comorbidities in psoriasis, hidradenitis suppurativa and atopic dermatitis: The importance of a psychodermatological approach.

BACKGROUND: There is a strong interaction between the immunological and nervous system in the skin. Lesions that are physically disfiguring and chronically relapsing have a high impact on quality of life (QoL) and can result in the emergence of psychiatric disorders. The literature data confirm a higher prevalence of psychiatric disorders in patients with psoriasis, hidradenitis suppurativa (HS) and atopic dermatitis (AD), but such data are compromised by low-quality evidence due to methodological heterogeneity. OBJECTIVES: The primary aim was to analyse the prevalence of psychiatric comorbidities in a group of psoriasis, AD and HS patients compared with a control group. The secondary aims were to evaluate the impact of psychiatric comorbidities on the disease development, severity, flare-ups and QoL. METHODS: A total of 59 cases and 64 controls were included. RESULTS: Generalized anxiety disorder and depressive disorder with anxious distress were found to be risk factors for AD. Age, smoking and substance-related disorder showed a specific association with HS. Major depressive disorder showed a specific association with dermatology life quality index (DLQI) and all the above disease flare-ups. CONCLUSIONS: Atopic dermatitis, psoriasis and HS are associated with psychiatric disorders. A psychodermatological approach improves outcomes in terms of QoL, disease flare-ups and long-term management.

Ultra-high frequency ultrasound detection of the dermo-epidermal junction: Its potential role in dermatology.

Traditional high-frequency ultrasound (HFUS; 20 MHz) is a non-invasive method used to study skin in vivo but is not able to measure skin thickness accurately and to identify the dermal-epidermal junction (DEJ). Ultra-high frequency ultrasound (UHFUS; 70-100 MHz) has sub-millimetre resolution comparable to histology. The aim of this study was to identify, by UHFUS, the DEJ and to describe skin differences in healthy individuals by providing a measure of skin thickness, based on age and gender. We also described the bullous pemphigoid lesion. We enrolled 42 patients divided into 2 groups: A and B. Group A included 32 healthy volunteers aged 22-74 years. Group B consisted of 10 patients with bullous pemphigoid. For each patient in group A, 8 ultrasound (US) clips by 70 MHz probe were performed at forehead, cheek, nose, forearm, abdomen, chest, back and leg. For each patient in group B, 5 US images were acquired at blisters roofs and edges. In each US image, we measured thickness of stratum corneum (α-ß), epidermis (α-γ) and epidermis plus dermis (α-δ). In both groups, we found the presence of 4 lines delimiting: the stratum corneum (the layer between α-line and ß-line), the epidermis (distance between α- and γ-line), and the boundary between dermis and subcutis (δ-line). The γ-line corresponds to the point of detachment of the bullae. The abdominal α-ß layer was thicker in males (p = 0.019) and α-δ thickness at cheeks (p < 0.001), chest (p = 0.007), back (p = 0.025) and forearm (p < 0.001). In females, α-γ thickness of the back was greater (p = 0.005). In old people compared to young, we noticed an increase of α-ß layer at forehead and chest (p = 0.014), an increase of α-γ layer at forearm (p = 0.001), back (p = 0.024) and leg (p = 0.010) and an increase of α-δ layer at forehead (p = 0.001) and nose (p = 0.049). UHFUS is an advanced imaging technique that can detect both the DEJ and the boundary between dermis and subcutaneous tissue so that epidermal and dermal thickness can be measured with good accuracy. Regarding gender and age, skin differences obtained with UHFUS were comparable to other non-invasive methods.

Ultra-high-frequency ultrasound and machine learning approaches for the differential diagnosis of melanocytic lesions.

Malignant melanoma (MM) is one of the most dangerous skin cancers. The aim of this study was to present a potential new method for the differential diagnosis of MM from melanocytic naevi (MN). We examined 20 MM and 19 MN with a new ultra-high-frequency ultrasound (UHFUS) equipped with a 70 MHz linear probe. Ultrasonographic images were processed for calculating 8 morphological parameters (area, perimeter, circularity, area ratio, standard deviation of normalized radial range, roughness index, overlap ratio and normalized residual mean square value) and 122 texture parameters. Colour Doppler images were used to evaluate the vascularization. Features reduction was implemented by means of principal component analysis (PCA), and 23 classification algorithms were tested on the reduced features using histological response as ground-truth. Best results were obtained using only the first component of the PCA and the weighted k-nearest neighbour classifier; this combination led to an accuracy of 76.9%, area under the ROC curve of 83%, sensitivity of 84% and specificity of 70%. The histological analysis still remains the gold-standard, but the UHFUS images processing using a machine learning approach could represent a new non-invasive approach.

A real-life experience as a proof of Guselkumab effectiveness and safety in patients with moderate to severe psoriasis.

Psoriasis is a skin disorder characterized by chronic inflammation driven by different immunologic pathways, among which the IL-23/Th17 axis plays a pivotal role. For this reason, the use of IL23p19 inhibitors in psoriasis treatment has been evaluated over the years. Guselkumab, a totally human IgG1 lambda monoclonal antibody, that selectively blocks the p 19 subunit of IL- 23 has demonstrated high efficacy and safety throughout several, randomized, double-blind phase III trials (VOYAGE 1 and 2, NAVIGATE and ECLIPSE). We designed a single-center retrospective cohort study in a population consisting of 46 patients followed from December 2018 to April 2021. After a diagnosis of moderate to severe psoriasis, all the patients were considered suitable to receive treatment with Guselkumab. In our population, among those who achieved clinical improvement in terms of Psoriasis Area Severity Index (PASI), PASI 75, 90, and 100 were achieved on average on weeks 14, 19, 21 respectively. We then analyzed a subgroup of our population, consisting of 35 patients, who had an identical follow-up time of 28 weeks, thus observing the trend in mean PASI at subsequent assessments and the number of patients who had reached PASI 75, PASI 90, and PASI 100 at week 4 (10; 3; 1), week 12 (12; 13; 11), week 20 (7; 6; 2), and week 28 (1; 4; 6), respectively. The results obtained are in line with those obtained from previous studies, thus confirming that Guselkumab is an excellent choice in terms of security, long-term efficacy, and overall tolerance.

Systemic antibiotics in hidradenitis suppurativa: efficacy and effects of body mass index and smoking pack-year on the response to therapy.

The combination of oral clindamycin with rifampicin is recommended by European guidelines as a first-line treatment in moderate-to-severe hidradenitis suppurativa (HS). Recent studies highlight that oral clindamycin in monotherapy (CM) may be a useful alternative treatment. We included 36 patients with a diagnosis of moderate-to-severe HS. A total of 19 patients were treated with combination oral clindamycin plus rifampicin (C + R) and 17 with oral CM for 12 weeks. The efficacy of CM vs C + R was analyzed by multilinear regression models which showed a higher reduction in mSartorius (Δ = -13.2, P = .058) and AISI (Δ = -4.91, P = .034) in the C + R group. In the C + R group, smoking pack-year was positively correlated with AISI (Spearman's rho = 0.51, P = .036) and with DLQI (0.47, P = .061). In the CM group, a positive correlation was found between BMI and AISI (0.47, P = .041). The data on the efficacy of C + R combination therapy are in line with guidelines, evidence-based approaches, and recommendations from the HS ALLIANCE working group. The rationale for combining these two drugs is to increase bactericidal action and to reduce rifampicin resistance, as rifampicin is highly mutagenic. Our results suggest that the antibiotic combination of C + R is still the treatment of choice in moderate-to-severe HS with abscesses, draining fistulae and ≥ 5 inflammatory nodules. High BMI and smoking habits seem to be predictive factors of a poor response to antibiotics. Further multicenter studies and prospective randomized controlled trials are needed to confirm these results. Potential alternative antibiotic therapies should also be investigated.

Ultrasound-guided injection of intralesional steroids in acute hidradenitis suppurativa lesions: A prospective study.

The management of hidradenitis suppurativa (HS) flares with intralesional steroids lacks strong scientific evidence but limited data suggest that it may be useful. The objective of this study is to assess the clinical and ultrasound responses of HS flares to ultrasound-guided injections of intralesional triamcinolone (40 mg/ml) with a dilution 1:4 versus 1:2 at 30-day (t1), 60-day (t2), and 90-day (t3) follow-up. We recruited patients with ≤3 acute lesions, unresponsive to topical therapy. At baseline we assessed lesions clinically and by ultra-high frequency ultrasound (48 or 70 MHz) and randomly performed an ultrasound-guided injection of triamcinolone. Assessments were repeated at t1, t2, and t3 follow-up, re-injecting the lesion in the case of no or partial response. We treated 49 lesions: 38.8% showed improvements at t1; 46.9% at t2; 6% at t3; and 8.3% showed no clinical and ultrasound improvements. Long-term follow-up data confirmed a statistically significant reduction in Visual Analogue Scale (VAS)-pain, Dermatology Life Quality Index (DLQI), and HS-Physician Global Assessment (HS-PGA), as well as edema and vascular signals. No adverse effects were reported. Our study suggests that ultrasound-injections with a 1:2 dilution are beneficial for HS flares that do not respond to topical treatment and should be included in the therapeutic algorithm.

Ultra-high-frequency ultrasound monitoring of plaque psoriasis during ixekizumab treatment.

BACKGROUND: High-frequency ultrasound (HFUS) is a non-invasive method that detects superficial skin features. Ultra-high frequencies (50-100 MHz) can reveal epidermis and dermis structures. OBJECTIVES: In this study, we describe the psoriatic plaque using a new device equipped with a 70 MHz probe (VEVO® MD, Fujifilm, VisualSonics) and we assess the lesion before and after ixekizumab. METHODS: We examined the superficial hyperechoic band, the subepidermal hypoechoic band (SLEB), and the vascularization of the plaque in ten patients affected by plaque psoriasis. RESULTS: The average superficial hyperechoic band thickness was 0.2157 mm before treatment, 0.1611 mm after 15 days, and 0.1354 mm (P < .05) after 30 days. The SLEB thickness was 0.7535 mm at baseline, 0.3300 mm after 15 days (P < .05), and 0.2007 mm (P < .05) after 30 days. The average percentage vascularization was 50.21% at baseline, 13.15% after 15 days (P < .05), and 5.97% after 30 days. UHFUS assessment highlighted the rapid action of the drug in terms of the decrease in vascularization after 15 days. It revealed a statistically significant reduction in SLEB thickness after 15 days and a significant reduction in the hyperechoic superficial band after 30 days. CONCLUSIONS: VEVO® MD provides physicians with high-resolution details of the psoriatic plaque, thus enabling tailored-made treatments.

PG-TIME: A practical approach to the clinical management of pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis which may be rapidly progressive. Standard guidelines for local treatment are lacking. Through our experience, we suggested a local treatment algorithm based on the tissue, infection, moisture balance, and epithelization (TIME) concept. The clinical and histopathological features of 52 patients with PG, the duration, and the evolution of the lesions were retrospectively evaluated. Systemic therapies, local treatments, and standard wound treatments were reported. We observed ulcerative PG in the majority of the patients (82.6%), followed by the pustular form (9.6%), the peristomal type (3.8%), the vegetative form (1.9%), and the bullous type (1.9%). The lower leg was the most commonly area affected (90.4% of cases). Pathergy was reported in 15.3% of cases. The first-line treatment was the use of oral glucocorticosteroids (GCSs). We observed healing after 3 weeks of GCS in 17.3% of cases. In 25% of all cases, we obtained complete healing with long-term low doses (<0.5 mg/kg) of GCS in the range of 2 to 6 months. We used second-line treatments in 57.6% of patients. Local, systemic treatment, and correct wound management can be associated with better clinical results. We suggest a new local therapeutic algorithm in both the inflammatory and noninflammatory healing phases.

Triticum vulgare Extract Modulates Protein-Kinase B and Matrix Metalloproteinases 9 Protein Expression in BV-2 Cells: Bioactivity on Inflammatory Pathway Associated with Molecular Mechanism Wound Healing.

Matrix metalloproteinases (MMPs) are a large family of ubiquitously expressed zinc-dependent enzymes with proteolitic activities. They are expressed in physiological situations and pathological conditions involving inflammatory processes including epithelial to mesenchymal transition (EMT), neuronal injury, and cancer. There is also evidence that MMPs regulate inflammation in tumor microenvironment, which plays an important role in healing tissue processes. Looking at both inflammatory and neuronal damages, MMP9 is involved in both processes and their modulation seems to be regulated by two proteins: tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). However other important genes are involved in molecular regulation of transcription factors, protein-kinase B (AKT), and p65. In addition, Triticum vulgare extract (TVE) modulated the biological markers associated with inflammatory processes, including p65 protein. While there are no evidence that TVE might be involved in the biological modulation of other inflammatory marker as AKT, we would like to assess whether TVE is able to (1) modulate phosphorylation of AKT (pAKT) as an early marker of inflammatory process in vitro and (2) affect MMP9 protein expression in an in vitro model. The BV-2 cells (microglial of mouse) have been used as an in vitro model to simulate both inflammatory and neuronal injury pathologies. Here, MMP9 seems to be involved in cellular migration through inflammatory marker activation. We simulate an inflammatory preclinical model treating BV-2 cells with lipopolysaccharide (LPS) to induce proinflammatory activation affecting pAKT and p65 proteins. TVE is revealed to restore the native expression of AKT and p65. Additionally, TVE extract modulates also the protein concentration of MMP9. Nevertheless, immunofluorescence confocal analyses revealed that both AKT and MMP9 are regulated together, synchronously. This work seems to demonstrate that two important genes can be used to monitor the beginning of an inflammatory process, AKT and MMP9, in which TVE seems able to modulate their expression of inflammation-associated molecules.

Surrounding skin management in venous leg ulcers: A systematic review.

OBJECTIVES: Chronic venous insufficiency may lead to the development of venous leg ulcers, the most common form of chronic wounds in the lower extremity. Key to venous leg ulcer care is the maintenance of healthy skin surrounding the ulcer, as failure to maintain skin integrity may influence the healing outcome. We thus reviewed the scientific literature looking for assessment and management instruments regarding this common but often neglected issue. METHOD: The search included all studies published between 2000 and May 2019. Keywords used were: "peri-wound skin care", "surrounding skin venous ulcers", "surrounding skin management leg ulcers", and "peri-lesional skin management". RESULTS: Management of moisture-balance with the selection of appropriate dressings is the most important target in surrounding-wound skin care. Moreover, contact dermatitis related to products and the dressings themselves is a neglected problem in patients with chronic leg ulcers which clinicians increasingly have to manage. The literature search revealed that there is an increasing interest in the use of noninvasive assessment tools in the field of wound care, and focusing on the surrounding-wound skin plays a role in assessing the potential of wound healing. Transepidermal water loss measurement (TEWL) and ultrasonography are two of the measurement techniques available. CONCLUSION: The integrity of the surrounding skin is necessary for wound healing, and appropriate management is needed to address this aspect which is part of an overall approach to treating wounds.

The impact of skin calcinosis on digital ulcers in patients with SSc: clinical and prognostic stratification using the "wound bed score".

Digital ulcers (DUs) represent one of the major burdens for patients with systemic sclerosis (SSc), especially when associated with skin calcinosis (SC). The aim of this work is to evaluate the impact of SC in DUs of patients with SSc for clinical characteristics and prognosis assessed by the wound bed score (WBS). We prospectively enrolled 55 patients with DUs and SSc followed in our dedicated wound care clinic. For all the patients we collected clinical and anthropometric data and characteristics of the DU, and we calculated the WBS for each DU. Ninety-nine DUs were evaluated (24 with SC). SC was prevalent in limited cutaneous SSc (75%) and in patients with longer disease duration (P = 0.02). SC-DUs were prevalent at the fingertip (P = 0.04). The healing time was significantly higher in patients with SC (10.4 ± 7.9 weeks) compared with non-SC (7.0 ± 5.7 weeks) P = 0.03. The WBS negatively correlated with the time to achieve complete healing (r = -0.237 P = 0.023) and the correlation was maintained in the non-SC (r = -0.46, P = 0.033). DUs in SSc patients with SC are common and difficult to heal. When DUs are treated in dedicated centres, the prognosis is good. The WBS is fast and easy and maybe commonly applied in clinical practice.

Biomodulation induced by fluorescent light energy versus standard of care in venous leg ulcers: a retrospective study.

OBJECTIVE: The recently completed EUREKA study confirmed the efficacy and safety profile of fluorescent light energy (FLE) in treating hard-to-heal wounds. To supplement the EUREKA prospective, observational, uncontrolled trial results, researchers selected one of the EUREKA clinical centres to conduct a retrospective analysis of matching wound care data for 46 venous leg ulcers (VLU) patients who had received standard wound care over a five-year period, compared with 10 EUREKA VLU subjects. METHOD: The study centre selected 46 patients with VLUs based on the matching criteria (wound age and size, patient's age and gender). They compared the healing rates of these matching VLUs with 10 VLU patients treated at the same centre during the EUREKA study. RESULTS: The EUREKA patients had larger and significantly older wounds (p<0.05) and significantly more risk factors (p<0.05) than the matching wounds. However, they had better outcomes (EUREKA: 40% versus matching group: 7% for full wound closure by 16 weeks). No wound breakdown was observed at 16 weeks in the EUREKA group, compared with 25% in the matching group. No EUREKA patient developed infections requiring antibiotics, compared with 37% in the matching group. EUREKA wounds had a mean relative wound area regression (RWAR) of 32% at week six and 50% at week 16, compared with -3% at week six and -6% at week 16 for the matching group. CONCLUSION: These findings show that the system based on FLE was well-tolerated and efficacious, with better clinical outcome results compared with the wounds analysed in this retrospective matching study and treated with standard of care alone.