Efficacy of certolizumab pegol in naïve versus multi-treated patients affected by psoriatic arthritis.

BACKGROUND: The efficacy and safety of certolizumab pegol over 52 weeks was compared in two groups of patients: Group 1 comprised patients naïve to biologic treatments; Group 2 comprised patients previously treated with one or more antitumor necrosis factor (TNF)-α and/or anti-interleukin (IL) agents. METHODS: We reported results in 50 patients affected by both mild psoriasis (PsO) and psoriatic arthritis (PsA). Primary endpoint was a reduction from baseline at week 52 of Disease Activity Score (DAS44-ESR) in both groups of patients. Secondary endpoints were a reduction from baseline at week 52 of Psoriasis Area Severity Index (PASI), Visual Analog Scale for Pain (PAIN VAS), ESR, CRP, and Dermatology Life Quality Index (DLQI). RESULTS: We observed a statistically significant improvement of both cutaneous and rheumatic disease in all patients, with a consistent reduction of DAS44-ESR, PASI, and PAIN VAS from baseline to week 52. DAS44-ESR decreased from 3.9 at BL to 1.5 at W52 (Group 1), and from 3.8 to 1.7 at W52 (Group 2). Mean PASI Score decreased from 3.2 at baseline (BL) to 0.4 at W52 (Group 1), and from 5.4 to 0.7 at W52 (Group 2). Mean PAIN-VAS decreased from a value of 73.5 at BL to 2.5 at W52 (Group 1), and from a value of 62.4 at BL to 9.2 at W52 (Group 2). We also found a reduction in ESR, CRP and DLQI values for each time point. CONCLUSIONS: Our results confirm that CZP can be administered safely and effectively to treat both psoriasis and psoriatic arthritis irrespective of previous treatments with biologic agents.

Characterization of comorbid conditions burdening hidradenitis suppurativa: a multicentric observational study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, disabling, inflammatory skin disorder that primarily affects the hair follicle localized at the apocrine-gland-bearing areas of the body, including axillary, inguinal, buttocks, and anogenital areas, and it may be associated with a wide array of comorbid conditions. This study aimed to described comorbid conditions affecting HS patients and to detect any correlation with disease severity. METHODS: Analyzing clinic database, we included all charts of patients visited at the HS outpatient clinic of three University Dermatologic Departments in order to describe demographic data, anthropometric measures, disease features, personal habits, clinical history, and presence of comorbidities. RESULTS: Two hundred thirty-four patients, mostly females (62%), were enrolled in this study. Based on Hurley staging classification 41% of patients were classified as Hurley Stage I, 43.0% as Hurley II, and 16% Hurley III, with a mean mSartorius Score value of 24.7 (SD: ±19.39) and a mean AISI score value of 12.5 (SD: ±11.93). The most frequently observed comorbidities were: obesity (26.1%), polycystic ovary syndrome (PCOS) (13.8% of the overall study population and 22.3% of females), hypertension (11.9%), dyslipidemia (9.9%), type II diabetes (9.5%), thyroid disorders (9.1%), nervous system disorders (7.1%), acne (6.7%), metabolic syndrome (4.4%), and Crohn's disease (3.6%). Obesity represented a key-comorbid condition increasing the likelihood of having more severe HS and PCOS (odds ratio 3.35 and 3.74, respectively). CONCLUSIONS: HS is associated with a variety of comorbid conditions that should be considered to perform targeted routine screening and to improve HS management.

Inflammasome Signaling and Impaired Vascular Health in Psoriasis.

Objective- Psoriasis is an inflammatory skin disease which heightens the risk of cardiovascular disease. This study directly investigated vascular endothelial health and systemically altered pathways in psoriasis and matched controls. Approach and Results- Twenty patients (mean age, 40 years; 50% male) with active psoriasis and 10 age-, sex-matched controls were recruited. To investigate systemically alerted pathways, a deep sequencing omics approach was applied, including unbiased blood transcriptomic and targeted proteomic analysis. Vascular endothelial health was assessed by transcriptomic profiling of endothelial cells obtained from the brachial veins of recruited participants. Blood transcriptomic profiling identified inflammasome signaling as the highest differentially expressed canonical pathway ( Z score 1.6; P=1×10-7) including upregulation of CASP5 and interleukin ( IL) -1ß. Proteomic panels revealed IL-6 as a top differentially expressed cytokine in psoriasis with pathway analysis highlighting IL-1ß ( Z score 3.7; P=1.02×10-23) as an upstream activator of the observed upregulated proteins. Direct profiling of harvested brachial vein endothelial cells demonstrated inflammatory transcript (eg, IL-1ß, CXCL10, VCAM-1, IL-8, CXCL1, Lymphotoxin beta, ICAM-1, COX-2, and CCL3) upregulation between psoriasis versus controls. A linear relationship was seen between differentially expressed endothelial inflammatory transcripts and psoriasis disease severity. IL-6 levels correlated with inflammatory endothelial cell transcripts and whole blood inflammasome-associated transcripts, including CASP5 and IL-1ß. Conclusions- An unbiased sequencing approach demonstrated the inflammasome as the most differentially altered pathway in psoriasis versus controls. Inflammasome signaling correlated with psoriasis disease severity, circulating IL-6, and proinflammatory endothelial transcripts. These findings help better explain the heightened risk of cardiovascular disease in psoriasis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT03228017.

Reducing the oral isotretinoin skin side effects: efficacy of 8% omega-ceramides, hydrophilic sugars, 5% niacinamide cream compound in acne patients.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease that manifests as open and closed comedones as well as inflammatory papules, pustules, and nodules localized on face and trunk. Oral isotretinoin demonstrated to be effective in controlling seborrhea, inflammation, Propionibacterium Acnes hyperproliferation and reducing scarring, nevertheless muco-cutaneous side effects, particularly dryness, itching, bruising are commonly seen in patients under treatment with isotretinoin reducing the compliance to the treatment. We conducted a randomized controlled trial to evaluate the efficacy of a cream compound formulated in order to reduce the oral isotretinoin side effects (redness, dryness, itching) in patients affected by severe acne of the face. METHODS: Twenty-seven patients undergoing treatment with 0.5-1 mg/kg/day for papulo-pustular or nodulo-cystic acne were randomized to additionally receive a cream composed of 8% omega-ceramides, hydrophilic sugars, 5% niacinamide applied twice daily (group A) or placebo cream (group B) applied 2 times per day. RESULTS: During the whole treatment period and after 6 months of treatment, patients in the group A showed a greater reduction of dryness, itching and redness compared to the group receiving the placebo cream. CONCLUSIONS: The cream formulated with 8% omega-ceramides, hydrophilic sugars, 5% niacinamide was effective in reducing xerosis and skin irritation, and was also successful in improving the patients' adherence to the oral isotretinoin treatment.

New therapeutic approaches in the treatment of anogenital lichen sclerosus: does photodynamic therapy represent a novel option?

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is an inflammatory, mucocutaneous disorder that affects male and especially female with a debilitating impact on the quality of life. Common localization is the anogenital area. If not treated LSA can leave scars, functional impairment and can evolve in squamous cell carcinoma. The first line of treatment is represented by topical, ultra-potent corticosteroids, but often patients are unresponsive; moreover this therapy is frequently associated to relapses of the disease after discontinuation. METHODS: In this prospective observational study, the efficacy of three different treatments - topical calcineurin inhibitors, avocado and soya beans extracts, and methyl aminolevulinate photodynamic therapy (MAL-PDT) - was evaluated, and an effort has been made to define a therapeutic algorithm according to the severity of the disease. RESULTS: Of the 150 patients who were referred to the outpatient clinic for a dermatological and gynecological visit, 33 met the inclusion criteria. Sixteen (88%) patients showed an improvement of the lesion and a reduction of the itch; 3 (16.7%) patients with sever itch and fissurated lesions were evaluated for the MAL-PDT therapy. A total of 9 patients, after accurate examination of the lesions, were treated with MAL-PDT. The totality of the patients experienced a resolution of the lesions. CONCLUSIONS: In the early stages the use of ASE can represent a valid alternative that is well tolerated by the patients reducing the itching, dryness and improving the mucosal texture. The use of MAL-PDT represents a valid treatment in the moderate-severe stages of LSA.

Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7.

The precise mechanisms governing invasion at the leading edge of squamous cell carcinoma (SCC) and its subsequent metastasis are not fully understood. We aimed to define the cancer-related molecular changes that distinguish noninvasive tumor from invasive SCC. To this end, we combined laser capture microdissection with complementary DNA (cDNA) microarray analysis. We defined invasion-associated genes as those differentially regulated only in invasive SCC nests, but not in actinic keratosis or in situ SCC, compared with normal epidermis. There were 383 upregulated and 354 downregulated genes in the "invasion set." SCC invasion was characterized by aberrant expression of various proteolytic molecules. We noted increased expression of MMP7 and IL-24 in invasive SCC. IL-24 induced the expression of matrix metallopeptidase 7 (MMP7) in SCC cells in culture. In addition, blocking of MMP7 by a specific antibody significantly delayed the migration of SCC cells in culture. These results suggest a possible contribution of IL-24 to SCC invasion via enhancing focal expression of MMP7, although IL-24 has been suggested to have antitumor growth effects in other cancer types. Identification of regional molecular changes that regulate cancer invasion may facilitate the development of new targeted treatments for aggressive cancer.