Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

Certolizumab pegol for the treatment of psoriasis.

INTRODUCTION: Psoriasis is a chronic immunomediated and inflammatory disease involving mainly skin and joints, often associated with several metabolic and non-metabolic comorbidities. TNF-alpha inhibitors have shown long-term efficacy and safety/tolerability in psoriasis, and preliminary data support the use of certolizumab pegol (CZP) as well. Areas covered: The authors review the pharmacological properties of CZP, as well as its safety data and efficacy profile. They also review the quality of life outcomes related to CZP in psoriasis. The authors also provide their expert opinion on the subject. Expert opinion: CZP is a promising treatment for psoriasis owing to its rapid reduction of disease activity, long-term therapeutic efficacy - both in bio-naive and non-bio-naive patients, long term safety and low rate of site injection reactions. CZP seems to be a promising therapeutic option for psoriasis patients, although further evidence supporting the continuing clinical program for development of CZP in psoriasis is needed.

T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: at the origin of the problem.

BACKGROUND: Atopic dermatitis (AD) is a chronic and inflammatory disease characterized by a marked imbalance of T helper (Th)2 vs. Th1/Th17 cells in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at the chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by AD. OBJECTIVES: To evaluate the relative expression of 22 genes encoding Th1, Th2 and Th17 cytokines and the secretion of the corresponding proteins in cutaneous mesenchymal stem cells (MSCs) isolated from skin of patients with AD (AD-MSCs) and their role in AD onset. METHODS: AD-MSCs were isolated, characterized and profiled by polymerase chain reaction array and enzyme-linked immunosorbent assay for the relative expression and secretion of cytokines involved in the Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy people were used as controls (C-MSCs). RESULTS: AD-MSCs showed an upregulation of many Th1/Th17 cytokines [interleukin (IL)-6, IL-8, IL-12, IL-13, IL-17A, IL-17F, transforming growth factor-ß, interferon-γ], while Th2 chemokines (IL-2, IL-4, IL-5, IL-23A) were downregulated in AD-MSCs. Finally, some genes/proteins (CCL1, IL-17C, tumour necrosis factor-α) did not show variations between C-MSCs and AD-MSCs. CONCLUSIONS: The profile of MSCs obtained from patients with chronic AD retraces the Th1/Th17 cell environment observed in differentiated cells of chronic AD. This evidence could open a new scenario in the pathogenesis of AD, according to which the inflammatory process may involve MSCs early on.

The effect of low-carbohydrates calorie-restricted diet on visceral adipose tissue and metabolic status in psoriasis patients receiving TNF-alpha inhibitors: results of an open label controlled, prospective, clinical study.

OBJECTIVE: TNF alpha inhibitors are usually associated with anthropometric changes over the time, however whether and how the visceral adipose tissue (VAT) is involved in this phenomenon, still remains unclear. Aim of the study is to evaluate if the increases in trunk fat percentage (TF%) and VAT are directly involved in anthropometric changes occurring during treatment, and whether and how a calorie restricted diet could prevent these changes. MATERIAL AND METHODS: Twenty patients receiving TNF-alpha inhibitors for psoriasis was evaluated at baseline (T0) and after 24 weeks of therapy (T24), and then compared with 25 patients receiving a combined treatment based on TNF alpha inhibitors and low-carbohydrates calorie-restricted diet. RESULTS: TNF-alpha inhibitors do not influence the VAT expression. The combined treatment is associated with a significant decrease in body weight (kg) (p < .0001), BMI (p = .0001), WC (cm) (p < .0001), TF% (p < .0001), VAT (p < .0001), serum levels of triglycerides (mg/dL) (p = .0018) and total cholesterol (mg/dL) (p = .0005). CONCLUSIONS: The administration of TNF-alpha inhibitors can induce anthropometric changes after 24 weeks, but it does not cause an increase in VAT. The association between low-carbohydrates calorie-restricted diet and anti-TNF-alpha therapy seems to be able to improve the anthropometric profile of psoriasis patients.

Ingenol mebutate in actinic keratosis: a clinical, videodermoscopic and immunohistochemical study.

BACKGROUND: Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm that typically develops on sun-damaged skin. The incidence of AK is increasing worldwide, and it is accepted as the most frequent pre-malignant lesion in humans. OBJECTIVES: To demonstrate that ingenol mebutate gel is effective in the treatment of actinic keratoses because of its clinical, dermoscopic, capillaroscopic, histopathological and immunohistochemical treatment outcomes. METHODS: Sixty individuals with multiple non-hypertrophic AKs were enrolled into this non-randomized, open-label, prospective, trial. Acquisition of clinical, dermoscopic and capillaroscopic images at baseline (T0), immediately after treatment on 3rd (trunk and/or extremities) or 4th (scalp and/or face) day (T1), 14 days after the end of the treatment (T2) and at 60 days (T3). A subgroup of 20 patients received a cutaneous biopsy both at baseline and at T3 for histological and immunohistochemical evaluation. RESULTS: Clinical improvement was observed in 100% of cases: total clearance in 41 patients (68.3%); partial clearance in 19 patients (32.7%). After treatment, dermoscopic improvement of all non-pigmented and pigmented AK lesions was observed. Most of the dermoscopic features disappeared with treatment. Total disappearance of specific vascular structures or significant reduction in the number and calibre of new blood vessels was capillaroscopically observed in all patients analysed (P ≤ 0.001). The immunohistochemical expression of p63 (P = 0.002), Ki-67 (P = 0.015) and VEGF (P = 0.016) significantly decreased. CONCLUSIONS: The clinical efficacy of ingenol mebutate on AKs is confirmed by its effect on angiogenesis, stem cell activity and cell proliferation in vivo.

Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts.

During the last decades, the advent of biological therapies has revolutionized the management of several immune-mediated inflammatory disorders, as inflammatory bowel diseases, autoimmune arthritis and psoriasis, which significantly impact both quality of life and health care economics. Biological therapies currently available can be divided into two main categories: the tumor necrosis factor-α antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol) and interleukin 12/23 monoclonal antibodies (ustekinumab). Biologics, reducing TNFα bioavailability or inhibiting proximal regulators of inflammatory cascade, represent an established therapeutic strategy of inflammatory autoimmune diseases, with remarkable efficacy and a safety profile that is extensively examined and monitored. The biology and the immunological effects of TNFα, IL-12, IL-23 and related signalling pathways are accurately summarized. The dosing regimens, methods of administration, pharmacodynamics profiles, and side effects of the currently licensed TNFα antagonists and IL12/IL23 inhibitor are discussed in detail.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of ß2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the ß-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased ß2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity.

Homocysteine plasma levels in psoriasis patients: our experience and review of the literature.

BACKGROUND: People with psoriasis are at higher cardiovascular risk. Plasma levels of homocysteine over the normal range have been recognized as marker of cardiovascular risk. Psoriasis patients express higher levels of plasma homocysteine than healthy people. OBJECTIVE: Our study aims to investigate the correlation between homocysteinaemia, severity and duration of psoriasis and psoriasis arthritis, and to evaluate the effect of a 12-week administration of a target therapy for psoriasis on homocysteinaemia. METHODS: Fifty-two psoriasis patients (study group) submitted to different kind of therapy for psoriasis (biological, systemic not biological and topical) and 24 healthy Italian subject (control group) were evaluated for their plasmatic homocysteine levels, both at baseline (T0) and 12 weeks after they a specific therapy for psoriasis. RESULTS: A significant difference between the homocysteinaemia of psoriasis patients (mean 19.71 ± 11.16) and control group (13.90 ± 11.18), P < 0.05 (Fig. 1), was found at baseline (T0). The mean plasma levels of homocysteine were directly correlated with disease severity (P = 0.0401), but not with disease duration (P = 0.6018) or presence of arthritis (P = 0.6221) at baseline. None among the treatments administered to psoriasis patients caused a significant reduction in homocysteinaemia after 12 weeks of treatment. CONCLUSION: Our results confirm that psoriasis patients with more severe disease, can have hyperhomocysteinaemia, without regard to disease duration or joint involvement. Hyperhomocysteinaemia is not influenced by a target therapy for psoriasis and it is as greater as psoriasis severity. However, limitation of our study is the relatively small number of cases. Homocysteine plasmatic levels should be advisable as a further independent risk factor for cardiovascular disease in psoriasis patients.

Skin features in myotonic dystrophy type 1: an observational study.

Poor data regarding skin involvement in Myotonic Dystrophy, also named Dystrophia Myotonica type 1, have been reported. This study aimed to investigate the prevalence and types of skin disorders in adult patients with Myotonic Dystrophy type 1. Fifty-five patients and one hundred age- and sex-matched healthy subjects were referred to a trained dermatologist for a complete skin examination to check for potential cutaneous hallmarks of disease. No difference in prevalence of preneoplastic, neoplastic, and cutaneous lesions was detected between the two groups. Among morphofunctional, proliferative and inflammatory lesions, focal hyperhidrosis (p < 0.0001), follicular hyperkeratosis (p = 0.0003), early androgenic alopecia (p = 0.01), nail pitting (p = 0.003), pedunculus fibromas (p = 0. 01), twisted hair (p = 0.01), seborrheic dermatitis (p = 0.02), macules of hyperpigmentation (p = 0.03) were significantly more frequent in patients compared with controls. In patients with Myotonic Dystrophy type 1 significant differences according to sex were found for: early androgenic alopecia, twisted hair and seborrheic dermatitis, whose prevalence was higher in males (p < 0.0001). Our preliminary results seem to rule out an increased prevalence of pre-neoplastic, and neoplastic skin lesions in Myotonic Dystrophy type 1. On the other hand, an increased prevalence of morphofunctional, inflammatory, and proliferative diseases involving adnexal structures seems to characterize adult patients with Myotonic Dystrophy type 1.

Use of infliximab in toxic epidermal necrolysis: a still opened challenge.

Toxic epidermal necrolysis (TEN), also known as Lyell syndrome, is a potential life-threatening muco-cutaneous disease with important systemic implications. It affects the skin and mucous membranes, with involvement of more than 30% of body surface and it is mostly caused by drugs. Although the pathogenesis is not fully elucidated, it is probably linked to the inability to detoxicate reactive metabolites of drugs, to genetic susceptibility and to immune factors leading to cellular apoptosis. Currently, there are no randomized control trials and stardardized therapeutical approaches for the management of Lyell syndrome; therefore controversial clinical responses to the most common used drug in TEN make it difficult for the clinical-therapeutic approach. The authors reported their experience on three patients affected by Lyell syndrome treated with infliximab.

Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis.

The expression of genes encoding for Th1, Th2 and Th17 cytokines has been extensively evaluated in differentiated skin cells of psoriatic patients. The microenvironment exerts a control on the phenotype of resident mesenchymal stem cells (MSCs) into the skin of psoriasis patients. Aim of the study was to extensively evaluate the relative expression of 43 genes encoding for Th1, Th2 and Th17 cytokines in MSCs isolated from skin of psoriasis patients. MSCs resident into psoriatic skin were isolated, characterized and profiled by PCR array for the relative expression of genes encoding for cytokines involved in Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy subjects were used as control. The MSCs isolated from skin of psoriasis patients showed a greater relative expression of the most part of the analyzed genes encoding for Th1 and Th17 cytokines: INF-γ, CCR5, CXCL9, CXCL10, IL6, IL8, TNF-α, IL23A, CCL2, CCL20, CXCL2, CXCL5, IL17C, IL17F, IL17RA, IL21, TLR2 than healthy subjects. On the contrary, the relative expression of genes encoding for Th2 cytokines: CCL1, CCL22, CXCL12, IL2, IL3, IL4, IL13B, IL 22, IL 27, TGF-ß1, was similar between the MSCs isolated from psoriasis and healthy subjects. In conclusion, the MSCs isolated from psoriasis show an imbalance between the Th1-Th17 and Th2 pathways, which reflects the well-known abnormal balance observed in differentiated skin cells. This evidence could strengthen the hypothesis of an early involvement of resident MSCs in the pathogenesis of psoriasis.

Electrochemotherapy: an effective local treatment of cutaneous and subcutaneous melanoma metastases.

Treatment of multiple cutaneous and subcutaneous melanoma metastases is still represents a therapeutic challenge for both dermatologists and oncologists. Electrochemotherapy (ECT) is a promising therapeutic procedure, owing to its ability to improve the penetration of cytotoxic drugs into cancer cells by application of current electric pulses. The aim of our study is to evaluate efficacy, tolerability and long-term efficacy of ECT in the treatment of advanced metastatic melanoma. Thirty patients affected by a total of 654 cutaneous and subcutaneous melanoma metastatic nodules were recruited. All patients were treated after they had undergone to a mild general anesthesia. Intravenous Bleomicina solution was administered 8 minutes before the application of electric pulses, generated by a Cliniporator (TM) (the device validated for ECT). The objective response rate of 100% (67.28% complete response and 32.72% partial response) was observed. A total of 214 metastatic lesions from 24 patients received a second ECT session, among them 141 showed a further complete response. Twenty-four months later, the local tumor control rate was 72%. The results of this study seem to demonstrate that ECT is an effective and valid therapeutic tool for the treatment of cutaneous metastases from melanoma. ECT can be considered a first-line palliative treatment since it is able to alleviate pain and reduce the tumor's spontaneous bleeding with a significant improve of patients' quality of life.

Onabotulinumtoxin type A (Botox(®)) versus Incobotulinumtoxin type A (Xeomin(®)) in the treatment of focal idiopathic palmar hyperhidrosis: results of a comparative double-blind clinical trial.

Focal hyperhidrosis often has a substantial psychological and social impact on quality of life, since it interferes with daily activities. To date, for the treatment of focal hyperhidrosis, the botulinum toxin type A is an effective second line tool. The purpose of this study was to compare Onabotulinumtoxin A (Botox(®)) and Incobotulinumtoxin A (Xeomin(®)) administration in the treatment of palmar hyperhidrosis. In a double-blind clinical trial, 25 patients with moderate or severe palmar hyperhidrosis received in the same session intradermal injections of Onabotulinumtoxin A on one hand and Incobotulinumtoxin A on the other. Several measures of efficacy and safety were evaluated: disease severity improvement, sweat reduction, hand-grip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were responsive to the treatments (HDSS at T4 vs HDDs at T0; p < 0.0001), and no significant difference between Onabotulinumtoxin A and Incobotulinumtoxin A in terms of anhidrotic effect (Minor's test at T4; p = 0.51), long-term efficacy (Minor's test at T12; p = 0.76), (Minor's test at T24; p = 0.58), subjective pain related to the injections (p = 0.88), muscle strength reduction after treatment (p = 0.56), and global satisfaction with the treatment (p = 0.26). Onabotulinum toxin A and Incobotulinumtoxin A seem to be comparable in terms of anhidrotic effect (short-term results), duration of benefits (long-term efficacy), muscle strength reduction (safety), pain related to injections (tolerability), and treatment satisfaction expressed by patients.

Treatment of palmar hyperhidrosis with botulinum toxin type A: results of a pilot study based on a novel injective approach.

Botulinum toxin type A (BoNT/A) improves symptoms of palmar hyperhidrosis, but some drawbacks related to its injection in the hands still persist (e.g., muscle weakness caused by drug diffusion, pain during injections, or delayed functional recovery of the hand when using wrist block). In this open, controlled, non-randomized, intra-individual clinical trial, 50 patients with severe palmar hyperhidrosis received in the same session intradermal injections of BoNT/A through a new injection technique (NA/BoNT/A) based on the use of a specific adapter for needles (PCT/IT2011/000299) in one hand, and BoNT/A injection following the anaesthetic block of the wrist (WB/BoNT/A) in the other. Several measures of efficacy and safety were evaluated both before (T0) and four weeks after the treatment (T4): disease severity improvement, sweat reduction, handgrip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were also re-evaluated through the gravimetric assessment of sweat production in both hands at T12 and T24 to compare the long-term efficacy of the two treatments. All patients were responsive to the treatments, and disease severity was significantly decreased at T4 compared to baseline (p < 0.0001). Both procedures were equally effective in reducing sweat production in the short term (p = 0.08 at T4), but WB/BoNT/A caused a higher decrease of handgrip strength compared with WB/BoNT/A at T4 (p < 0.0001). Finally, patients reported that NA/BoNT/A and WB/BoNT/A procedures were comparable for pain/discomfort (p = 0.204); however, they were globally more satisfied with the NA/BoNT/A rather than WB/BoNT/A method (p < 0.0001). No significant difference in percentage of clinical relapse at T12 and T24 was detected between hands treated via WB/BoNT/A or NA/BoNT/A (p = 0.70). The use of the described adapter to inject BoNT/A in the hands seems to lead the clinicians to obtain same therapeutic results of conventional method based on the use of anaesthetic block of the wrist. Moreover, this new injective approach seems to increase the safety of the treatment by reducing the extent of muscle weakness and is preferred by patients mostly because it makes the functional recovery of the hand faster.

Topical ozonated oil versus hyaluronic gel for the treatment of partial- to full-thickness second-degree burns: A prospective, comparative, single-blind, non-randomised, controlled clinical trial.

INTRODUCTION AND AIM: Several studies have demonstrated that ozonated oil is effective on cutaneous wound healing. This in vivo study has been conducted to evaluate the clinical effect of the topical application of ozonated oil for 12 weeks on second-degree skin burns. METHOD: A total of 30 patients suffering from second-degree skin burns in the phase of re-epithelisation were included in this study. Every skin burn was subdivided in two symmetrical parts. One part was treated with occlusive application of ozonated oil; the contralateral part of the lesion was treated with topical application of hyaluronic acid gel, once a day for 12 weeks. A clinical evaluation and an intra-vital video-capillaroscopy were performed on every patient at baseline, 6 and 12 weeks after. RESULTS: All treated lesions improved regardless of the treatment used. Ozonated oil was as effective as hyaluronic acid in improving erythema, tension, itching and burning sensation reported by patients, and it does not exert a specific anti-angiogenic effect compared to hyaluronic acid. However it seems more effective than hyaluronic acid in reducing post-lesional hyperpigmentation. CONCLUSION: Ozonated oil, topically applied for 12 weeks, seems to be as effective as hyaluronic acid in reducing symptoms related to skin burns, but it could be more effective in preventing the post-lesional hyperpigmentation.

Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis.

OBJECTIVE: To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM). MATERIALS AND METHODS: Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1α. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients. RESULTS: Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1α expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1α and VEGF and HIF-1α expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1α. CONCLUSIONS: Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1α expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.