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.

Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer.

Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.

Maculopapular sarcoidosis: the importance of skin signs.

Sarcoidosis is a multisystem disease that affects the skin in 20 to 30% of cases. Skin findings are often the initial presenting signs, and cutaneous sarcoidosis may appear with a wide variety of lesions; it is often considered an imitator of many other skin diseases. Clinical appearance and specific dermoscopic criteria, confirmed by a typical pathology, may guide to the correct diagnosis. We report the case of a man affected by maculo-papular sarcoidosis on the back, in which the detection of cutaneous lesions was the initial step to determine the systemic nature of the disease.

A consensus-based approach on the management of patients with both psoriasis and psoriatic arthritis in the dermatological and rheumatological settings in Italy: The ADOI PSO-Amore Project.

Psoriasis is a complex disease often needing a multidisciplinary approach. In particular, the collaboration between dermatologist and rheumatologist is crucial for the management of patients suffering from both psoriasis (PSO) and psoriatic arthritis (PsA). Here we report a series of recommendations from a group of experts, as a result of a Consensus Conference, defining the circumstances in which it is preferable or even mandatory, depending on the available settings, to rely on the opinion of the two specialists, jointly or in a deferred manner. Indications are given on how to organize a 3rd level joint Dermatology- Rheumatology care unit, in connection with 1st and 2nd level clinicians of both specialties, GPs, and other specialists involved in the management of psoriasis. A potential patient journey is suggested, that can be used as a basis for future design and validation of national and/or local diagnostic therapeutic and assistance pathways.

Therapeutic management of a symptomatic Kaposi's sarcoma patient with renal failure undergoing haemodialysis: A case report.

Kaposi's sarcoma (KS) is a rare inflammation- based vascular cancer involving the skin. The viral aetiology of KS is the Human Herpesvirus 8. KS may be frequently diagnosed in immunosuppressed kidneytransplanted patients, while is less common in patients with dialysis. It is known that various immunological abnormalities can lead to impaired immune status in uremic patients. It is noteworthy that despite the incidence of KS in patients with renal impairment, only few cases have reported efficacy and safety profile of KS targeting anti-cancer drugs in this kidney disease population. Herein, we report the first case of a symptomatic KS patient with renal disease in haemodialysis and focus on its therapeutic management. We also review the main data available from literature regarding the safety of KS therapy in dialysis patients.

A Vismodegib Experience in Elderly Patients with Basal Cell Carcinoma: Case Reports and Review of the Literature.

Cutaneous basal cell carcinoma (BCC) is the most common type of human tumor, and its incidence rate is increasing worldwide. Up until a few years ago, therapeutic options have been limited for patients with advanced BCC (including metastatic and locally-advanced BCC). Over the last few years, promising systemic therapies have been investigated for the treatment of advanced BCC. In particular, the Hedgehog signaling inhibition has shown remarkable results for this population. Hedgehog inhibitors, represented by vismodegib and sonidegib, have been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of both locally advanced and metastatic BCC, with, generally, a good safety profile. Notwithstanding the late onset of BCC in the global population, associated with life expectancy increase, only a few clinical trials have evaluated the efficacy and safety profile of Hedgehog inhibitors in this complex and neglected population. Herein, we review the major mechanisms implicated in the pathogenesis of BCC focusing on the Hedgehog signaling pathway and its therapeutic role in the elderly population. Finally, we report two case reports of BCC elderly patients in order to demonstrate both efficacy and safety of the Hedgehog inhibitors.

Aggressive weight-loss program with a ketogenic induction phase for the treatment of chronic plaque psoriasis: A proof-of-concept, single-arm, open-label clinical trial.

OBJECTIVES: A very low-calorie ketogenic diet (VLCKD) has been associated with a significant reduction in visceral adipose tissue and ketone bodies that likely possess antiinflammatory properties. We evaluated the efficacy of an aggressive weight-loss (WL) program with a ketogenic induction phase as first-line treatment for chronic plaque psoriasis. METHODS: Adult patients who were overweight or obese and drug-naïve (i.e., never treated, excluding the use of topical emollients; n = 37; 30% men; age: 43.1 ± 13.8 y) with stable chronic plaque psoriasis underwent a 10-wk, 2-phase WL program consisting of a 4-wk protein-sparing, VLCKD (<500 kcal/d; 1.2 g of protein/kg of ideal body weight/d) and 6-wk balanced, hypocaloric (25-30 kcal/kg of ideal body weight/d), Mediterranean-like diet. The primary endpoint was the reduction in Psoriasis Area and Severity Index (PASI) score at wk 10. Major secondary endpoints included PASI score responses of ≥50% and ≥75%, reduction in body surface area involved, improvement in itch severity (visual analogue scale), and Dermatology Life Quality Index score at wk 10. RESULTS: With a mean body weight reduction of 12.0% (-10.6 kg), the dietary intervention resulted in a significant reduction in PASI (baseline score: 13.8 ± 6.9; range, 7-32), with a mean change of -10.6 (95% confidence interval, -12.8 to -8.4; P < 0.001). PASI score responses of ≥50% and ≥75% were recorded in 36 patients (97.3%) and 24 patients (64.9%), respectively. Treatment also resulted in a significant reduction (P < 0.001) in the body surface area involved (-17.4%) and an improvement in itch severity (-33.2 points) and Dermatology Life Quality Index score (-13.4 points). CONCLUSIONS: In drug-naïve adult overweight patients with stable chronic plaque psoriasis, an aggressive dietary WL program consisting of a VLCKD, followed by a balanced, hypocaloric, Mediterranean-like diet, appeared to be an effective first-line strategy to reduce disease severity.

Anti-PD1 antibodies in patients aged ≥ 75 years with metastatic melanoma: A retrospective multicentre study.

BACKGROUND: Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients >65 years. However, data on patients >75 years are lacking as co-morbidities and logistics often exclude them from clinical trials. METHODS: We retrospectively reviewed the clinical records of older patients with advanced melanoma undergoing any-line treatment with an anti-PD1 (nivolumab/pembrolizumab) to investigate its clinical effectiveness and toxicity in a real-life setting. Clinical response was assessed using RECIST criteria and toxicity was evaluated according to CTCAE 4.0. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and the Cox model was used to assess potential prognostic factors. RESULTS: 174 patients were considered; 59.2% males, median age 79 years (range 75-93). The majority had a performance status of 0 and normal lactate dehydrogenase (LDH) levels (55.2% and 52.4%, respectively). 69.1% had multiple co-morbidities. 56.9% received nivolumab. 36.7% of cases showed an objective response and the disease control rate was 56.3%. Median OS was 17.2 months [95% CI: 8.87-not reached] and a better prognosis was observed for patients with normal LDH (p < .001) and lower performance status (p < .001). Treatment was well tolerated, only 11 patients experiencing severe (grade 3/4) toxicity. There were no treatment-related deaths. Adverse events were managed with corticosteroids and additional immunosuppressive agents were unnecessary. CONCLUSIONS: Anti-PD1 antibodies appear effective and well tolerated in older patients with advanced melanoma.

Management of long-term therapy with biological drugs in psoriatic patients with latent tuberculosis infection in real life setting.

Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long-term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate-to-severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti-TNF-α and/or anti IL 12, 23 and/or anti-CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X-ray suggestive, without clinical, or microbiological evidence of active disease. All patients received prophylactic therapy for 9 months with isoniazid (INH) 300 mg/day, starting 3 weeks before the beginning of biological treatment. Fifty-four patients completed prophylaxis with INH without any adverse events or intolerance; they continue the biological treatment without appearance of active tuberculosis. One patient developed tuberculosis pleurisy in course of treatment with etanercept. The infection has been treated and after a stable remission, treatment was restarted without tuberculosis reactivation. In this retrospective analysis, the prophylaxis of LTBI whit INH was effective and safe in longer follow-up period.

Electrochemotherapy induces apoptotic death in melanoma metastases: a histologic and immunohistochemical investigation.

BACKGROUND: Electrochemotherapy (ECT) is increasingly used in the treatment of primary and secondary skin tumors, but little is known about the pathologic mechanism responsible for tumor cell destruction in humans. Knowledge of detailed mechanism of host response after ECT may improve the treatment efficacy related to patient selection and technique refinements. AIM: The aim of the study was to investigate the histopathology and mechanism of cell death after ECT in cutaneous melanoma metastases. METHODS: Skin biopsy specimens were sequentially obtained after ECT of cutaneous melanoma metastases, during a follow-up period of 2 months. Results from histologic evaluation and immunohistochemical characterization of the inflammatory infiltrate (CD3, CD4, CD8, CD56, Granzyme-B) were compared with a panel of apoptosis-related markers. MAIN OUTCOME MEASURES: Evidence of the mechanism of tumor cell damage, identification of histological and immunohistochemical signs of apoptosis and/or necrosis underlining a possible time course of tumor destruction and inflammatory reaction after ECT. RESULTS: Early signs of epidermal degeneration, an increase of the inflammatory infiltrate, and initial tumor cell morphological changes were already detected 10 min after ECT. The cell damage progression, as demonstrated by histological and immunohistochemical evidence using apoptotic markers (TUNEL and caspase-3 staining), reached a climax 3 days after treatment, to continue until 10 days after. Scarring fibrosis and complete absence of tumor cells were observed in the late biopsy specimens. A rich inflammatory infiltrate with a prevalence of T-cytotoxic CD3/CD8-positive cells was detected 3 h after ECT and was still appreciable 3 months later. CONCLUSION: This study attempts to define the time course and characteristics of tumor response to ECT. The observations suggest both a direct necrotic cell damage and a rapid activation of apoptotic mechanisms that occur in the early phases of the cutaneous reaction to ECT. A persistent immune response of T-cytotoxic lymphocytes could possibly explain the long-term local tumor control.

An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity.

The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (<500 kcal/day; Oloproteic(®) Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome.

Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis.

Aggressive nutritional strategy in morbid obesity in clinical practice: Safety, feasibility, and effects on metabolic and haemodynamic risk factors.

BACKGROUND: In morbid obesity, optimisation of nutritional strategies impacting cardiovascular and metabolic risk profile is a desirable target in clinical practice. OBJECTIVE: To assess in morbid obesity the feasibility, safety and efficacy of a nutritional cycle comprising a short-term carbohydrates-free diet delivered by nasogastric tube followed by an almost equivalent oral diet. DESIGN: In our clinical practice, adults with body mass index (BMI)≥45kg/m(2), otherwise clinically healthy, signed informed consent for a 14-day stint of continuous and controlled carbohydrates-free nutritional regiment delivered via 8-Fr nasogastric tube (enteral nutrition, EN), followed by a 14-day stint of almost comparable oral nutrition (ON). Body metrics, insulin resistance, blood pressure (BP) and heart rate (HR), as well as parameters for safety were monitored. RESULTS: In 112 patients, EN significantly reduced BMI and waist circumference (WC), BP, insulin resistance while it increased urine ketones and uric acid increased (all p<0.01 independent to confounders), but had no clinically significant impact on kidney and renal function, and coagulation parameters as well. With ON, findings were consistent. No major safety concerns were recorded during the nutritional treatment. In a subset of patients sharing clinical characteristics with the whole sample, the nutritional strategy reduced the mesenteric fat assessed by ultrasound. CONCLUSIONS: In morbid obesity, an aggressive nutritional cycle comprising a short-term ketogenic EN followed by an almost carbohydrates-free ON may be feasible, safe, and highly effective in reducing body weight, WC, BP and insulin resistance.

Neonatal Norwegian scabies: three cooperating causes.

BACKGROUND: Norwegian or crusted scabies is seldom reported in infancy, usually in immune deficient patients. MAIN OBSERVATIONS: We report a case of an infant affected by atopic dermatitis since birth. The patient was ineffectively treated with topical and systemic steroids for several weeks for the insurgence of cutaneous xerosis and erithema. Clinical inspection and optical microscopic examination of skin scraped scales leaded to the diagnosis of crusted scabies. The physiological inability to scrapping reaction, the immunological profile deriving from atopy and finally iatrogenic immunodepression cooperating to conduce to crusted scabies. CONCLUSION: In our case iatrogenic immunosuppression, atopic dermatitis and the absence of skin scraping reaction because of the very young age might have contributed to the unusual presentation of scabies. This case suggests considering possible alternative diagnosis of scabies in the failure of the treatment for atopic eczema.