Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings.

BACKGROUND: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting. STUDY DESIGN: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure. RESULTS: Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (<100,000 vs. 100,000-500,000 vs. > 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P < 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count <200 cell/mm3 was associated with the lowest probability of VS (91.5 %, P < 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase. CONCLUSIONS: Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice.

Latent tuberculosis infection screening in persons newly-diagnosed with HIV infection in Italy: A multicentre study promoted by the Italian Society of Infectious and Tropical Diseases.

BACKGROUND: The Italian Society of Infectious and Tropical Diseases performed a survey on the application of guidelines for the management of persons living with HIV (PLWH), to evaluate current practice and the yield of screening for latent tuberculosis infection (LTBI) in newly-diagnosed PLWH; in addition, the offer of preventive therapy to LTBI individuals and the completion rate were analysed. MATERIALS AND METHODS: Newly-diagnosed PLWH in nine centres were evaluated retrospectively (2016/2017) using binary and multinomial logistic regression to identify factors associated with LTBI diagnostic screening and QuantiFERON (QFT) results. RESULTS: Of 801 patients evaluated, 774 were studied after excluding active TB. LTBI tests were performed in 65.5%. Prescription of an LTBI test was associated with being foreign-born (odds ratio (OR) 3.19, p < 0.001), older (for 10-year increments, OR 1.22, p = 0.034), and having a CD4 count <100 cells/mm3 vs ≥500 cells/mm3 (OR 2.30, p = 0.044). LTBI was diagnosed in 6.5% of 495 patients evaluated by QFT. Positive results were associated with being foreign-born (relative risk ratio (RRR) 30.82, p < 0.001), older (for 10-year increments, RRR 1.78, p = 0.003), and having a high CD4 count (for 100 cells/mm3 increments, RRR 1.26, p < 0.003). Sixteen LTBI individuals started TB preventive therapy and eight completed it. CONCLUSIONS: LTBI screening is inconsistently performed in newly-diagnosed PLWH. Furthermore, TB preventive therapy is not offered to all LTBI individuals and compliance is poor.

Resistance detected in PBMCs predicts virological rebound in HIV-1 suppressed patients switching treatment.

BACKGROUND: Genotypic resistance test (GRT) performed in peripheral blood mononuclear cells (PBMC) represents a chance to evaluate resistance in virologically suppressed HIV infected patients. OBJECTIVES: To evaluate the impact of baseline resistance detected through PBMC GRT on virological rebound after switching treatment. STUDY DESIGN: Baseline genotypic susceptibility scores (GSS) from PBMC GRT (DNA-GSS) and from previous cumulative plasma GRTs (when available, pRNA-GSS) were evaluated. Survival analysis was used to assess the probability and predictors of virological rebound (VR). RESULTS: 227 virologically suppressed patients were analysed. Twenty-four months after switching therapy, the probability of VR was 15.3%. Patients showing an intermediate or full resistant DNA-GSS had a higher probability of experiencing VR compared to those carrying a fully susceptible DNA-GSS (27.2% vs. 13.7%, p = 0.001). By multivariable Cox regression, patients with an intermediate/full resistant DNA-GSS, with a nadir CD4 count <100 cell/mm3 and with a shorter time of previous virological suppression showed a higher adjusted hazard of experiencing VR. In a sub-group of 114 patients with previous plasma GRTs available, patients with an intermediate or fully resistance showed by both GSSs (from plasma and PBMCs) had the highest probability of experiencing VR. CONCLUSIONS: Resistance detected in proviral DNA, together with a low nadir CD4 count and a short previous virological control, predicts VR after therapy switching in virologically suppressed patients. PBMC GRT can be a useful tool for tailoring treatment switch, especially if paired with information about previous cumulative resistance and previous viro-immunological history.

Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter observational study.

BACKGROUND: Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). METHODS: Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. RESULTS: Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. CONCLUSIONS: In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

Genotypic resistance test in proviral DNA can identify resistance mutations never detected in historical genotypic test in patients with low level or undetectable HIV-RNA.

BACKGROUND: Beyond the detection of resistant HIV strains found in plasma samples, archival HIV-DNA in peripheral blood mononuclear cells (PBMCs) might represent a reservoir of additional resistance. OBJECTIVE: To characterize the HIV-1 resistance in PBMCs from patients with suppressed or low-level viremia (50-1000 copies/mL) and evaluate its added value compared to the resistance detected in previous plasma genotypic resistance tests (GRTs). STUDY DESIGN: HIV-1 infected patients selected for treatment change despite low/undetectable viremia were tested. Number and type of primary resistance mutations (PRMs) detected in PBMCs were compared to those detected in previous plasma GRTs. Logistic regression assessed factors associated with presence of at least one PRM in PBMCs. RESULT: 468 patients with a PBMC GRT were analyzed; 149 of them had at least 2 plasma GRTs performed before PBMC genotyping. 42.3% of patients showed at least one PRM in PBMCs. The highest proportion of PRMs in PBMCs was observed for NRTI class (30.6%), followed by NNRTI (22.2%), PI (14.1%) and INI (4.9%). In 20.1% of patients, PRMs were detected only in PBMCs and not in any of the plasma GRT previously performed. By using multivariable analysis, a higher number of previous regimens, injecting drug-use route and a lower nadir CD4 were associated with significantly higher risk of detecting PRMs in PBMCs. CONCLUSION: Our findings support the usage of PBMC GRT in addition to the current recommended plasma RNA test, especially when therapeutic and/or resistance information is not available.

Relationship between body mass index and bone mineral density in HIV-infected patients referred for DXA.

INTRODUCTION: Reduced bone mass density (BMD) is a frequent observation in HIV-infected persons. Relationship between body mass index (BMI), weight, height and BMD was reported for many populations. In particular, BMI has been found to be inversely related to the risk of osteoporosis. METHODS: This is a cross-sectional, monocentric study where all HIV-infected patients referred to first DXA scan in clinical routine during 2010-2013 were included. Osteopenia and osteoporosis were defined by T- score <-1 and <-2.5, respectively. Patients were categorized according to WHO BMI classification: underweight <18.5 kg/m(2); normal weight 18.5-24.9 kg/m(2); over weight 25-29.9 kg/m(2); obese >30 kg/m(2). Statistical analysis was carried using logistic regression. RESULTS: A total of 918 patients were included: median age 49 years (IQR, 44-55); 59.4% male; 93% Caucasian. Median anthrometric characteristics were: 68 kg (IQR, 59-78); 1.7 m (IQR, 1.6-1.75); 23.5 kg/m(2) (IQR, 21.4-26.2). Underweight was found in 5%, normal weight in 61%, overweight in 26% and obesity in 8% of patients. According to T-scores, 110 (11.2%) patients were osteoporotic and 502 (54.7%) had osteopenia. In the femoral neck area, the prevalence of osteoporosis was slightly lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T-scores for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and normal BMD values, respectively. T-scores at femoral neck or lumbar spine positively correlated with BMI (p<0.001) (Figure 1). Among predictors of osteopenia/osteoporosis, univariable analysis showed: older age (p<0.0001); lower weight (p<0.0001); increasing height (p<0.002). Patients underweight had a higher risk of osteopenia (p=0.02) as well as of osteoporosis (p=0.003). Patients with BMI above normal had a reduced risk of low BMD (osteopenia p<0.0001; osteoporosis p<0.03). Controlling for calendar year, gender, ethnicity, and age, BMI was confirmed as risk factor if below normal (AdjOR of osteopenia 2.42 [95% CI 1.16-5.07] p=0.02; AdjOR of osteoporosis 3.22 [95% CI 1.60-6.49] p=0.001). CONCLUSIONS: Our findings indicate that almost 66% of HIV-infected patients have subnormal bone mass. Further, as in other patient populations, in the HIV infection also low BMI is an important risk factor for osteopenia/osteoporosis. This finding highlights the compelling need for standardized screening actions, particularly in patients weighting below normal.

APRI and FIB-4 scores are not associated with neurocognitive impairment in HIV-infected persons.

INTRODUCTION: Chronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV-infected population with high HCV prevalence. Aim of the analysis was to assess the association between NCI and aspartate aminotransferase-platelet ratio index (APRI) or Fibrosis-4, which are non-invasive scores used to assess liver fibrosis. MATERIALS AND METHODS: Single-centre, retrospective, cross-sectional analysis of cART-treated HIV-infected patients undergoing neuropsychological assessment (NPA) by a set of 14 standardized and comprehensive tests on five different domains: concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual-spatial and constructional abilities. NPA obtained from the same patient were included, if collected while receiving different cART. Patients were classified as having NCI, if they scored >1 SD below the normative mean in at least two tests, or below >2 SD in one test. HIV-associated neurocognitive disorders (HAND) were classified according to Frascati's criteria, controlling for confounding comorbidities. Univariable analysis and multivariable logistic regression models were carried out. RESULTS: A total of 556 HIV-infected cART-treated patients from 2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm(3); median current CD4 501/mm(3); undetectable HIV-RNA in 368 (67%); and HCV-positivity in 150 (29%). Frequency among score levels was for FIB-4: min-1.44=404 (73%), 1.45-3.25=118 (21%), 3.26-max=28 (5%); for APRI: min-0.5=414 (75%), 0.5-1.5=112 (20%), 1.5-max=24 (4%). Median FIB-4 and APRI were 0.98 and 0.27 in HIV+/HCV- and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are shown in Table 1. CONCLUSIONS: In this large population, HAND was not associated with commonly used non-invasive liver fibrosis scores. As aetiology of cognitive dysfunction in HIV mono- and HCV co-infected patients is multifactorial and partially unknown, our results support the hypothesis of a direct or indirect effect on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.

Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter analysis.

BACKGROUND: To assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure. MATERIALS AND METHODS: Patients starting DT regimen composed by a boosted protease inhibitor (PI/r): darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug: raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF), this one generally used in HBV co-infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis. RESULTS: Overall, 480 patients from six reference Italian centres were included: all switched to DT with HIV-RNA <500 cp/µL, 376 of them at <50 cp/µL. Patients who switched at <50 cp/µL showed a significant lower risk of treatment failure (13.3% versus 23.3% at 1 year and 28.0% versus 44.6% at 3 years, p=0.005), thus the analysis was focused on this subgroup. Among the patients who switched at <50 cp/µL, the proportion of drug used in DT was: DRV/r 63.0%, RAL 53.7%, ETR 19.4%, ATV/r 18.4%, MRV 17.3%, LPV/r 12.8%, TDF 6.4% and 3TC 5.9%; DRV/r-RAL was the most widely used combination: 32.5%. Treatment failure was observed in 78 patients, of whom 38 virological and 35 for toxicity/intolerance, one patient died during follow-up and four patients interrupted for personal decision with undetectable HIV-RNA. At Cox Model, adjusted by gender, age, non-Italian origin, AIDS diagnosis, time on cART, number of regimens, CD4 nadir, baseline CD4, all the drugs had a positive effect on probability of failure (Figure), however the effect was significant for DRV/r (HR:0.21, 95% CI 0.07-0.59, p=0.03), ATV/r (0.30, 0.09-0.97, p=0.044) and RAL (0.37, 0.15-0.93, p=0.034); higher CD4 count at baseline was also associated with lower risk of failure while number of previous regimens with a higher risk. Moreover, ATV/r was found significant associated with significant higher risk of failure by toxicity (as well as LPV/r) but lower risk of virological failure, while both 3TC and RAL with significant lower risk of toxicity. CONCLUSIONS: Our analysis suggest that using PI/r-based DL is highly effective if switching from HIV-RNA <50 cp/µL; DL should be used with caution in patients with low CD4 count and longer history of treatment; DRV/r is the best compromise among PI/r, ATV/r is effective but is associate with frequent interruption by toxicity; RAL showed high tolerability so that its use is related to the lowest risk of failure as second drug.

Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa.

We report a long-term follow-up (6.5 years) of a phase I/II clinical trial envisaging the use of autologous genetically modified cultured epidermal stem cells for gene therapy of junctional epidermolysis bullosa, a devastating genetic skin disease. The critical goals of the trial were to evaluate the safety and long-term persistence of genetically modified epidermis. A normal epidermal-dermal junction was restored and the regenerated transgenic epidermis was found to be fully functional and virtually indistinguishable from a normal control. The epidermis was sustained by a discrete number of long-lasting, self-renewing transgenic epidermal stem cells that maintained the memory of the donor site, whereas the vast majority of transduced transit-amplifying progenitors were lost within the first few months after grafting. These data pave the way for the safe use of epidermal stem cells in combined cell and gene therapy for genetic skin diseases.

Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids.

BACKGROUND: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. METHODS: A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. RESULTS: One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. CONCLUSIONS: Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the Italian Psocare registry.

BACKGROUND: Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. OBJECTIVE: We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. METHODS: Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. RESULTS: In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). LIMITATIONS: There was a small number of patients with complete follow-up data. CONCLUSION: PASI 75 response in patients who switched from one anti-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first anti-TNF-alfa.

18beta-glycyrrhetinic acid and glabridin prevent oxidative DNA fragmentation in UVB-irradiated human keratinocyte cultures.

BACKGROUND: UVB radiation is the major etiological factor in the pathogenesis of skin aging and cancer development. New approaches to prevent and reverse UVB damage are needed to reduce sunlight-induced skin cancer. This study aimed to investigate a possible protective activity of liquorice root extracts glycyrrhizin (GL), 18ß-glycyrrhetinic acid (18ß-GA) and glabridin (GLB) against UVB radiation damage in human keratinocyte cultures. MATERIALS AND METHODS: The MTT test was performed to assess cell viability. DNA damage was evaluated by comet assay, whereas generation of intracellular reactive oxygen species (ROS) was measured by fluorescent 2'7'-dichlorodihydrofluorescein diacetate assay. In addition, the activation of p53, regulation of BCL-2 and PARP cleavage were analyzed by Western blot analysis. RESULTS: The treatment of human keratinocytes with 18ß-GA and GLB prevented direct and indirect DNA damage avoiding apoptosis activation. CONCLUSION: 18ß-glycyrrhetinic acid and glabridin are potent antioxidants that prevent oxidative DNA fragmentation and the activation of apoptosis-associated proteins in human keratinocytes.

Juvenile psoriasis and its clinical management: a European expert group consensus.

BACKGROUND: Psoriasis, an inflammatory disorder of the skin, can significantly impact on a patient's quality of life, affecting their daily activities and families. The onset of psoriasis in childhood is quite common; however, the treatment of moderate-to-severe disease in this population is challenging, with a paucity of data reported and few licensed agents available. METHODS: A Delphi survey was conducted among a panel of European expert dermatologists and physicians with a particular interest in pediatric inflammatory disorders. The survey covered the aspects of psoriasis types, psoriatic arthritis, diagnosis and treatment options in childhood. RESULTS: A series of consensus opinions were reached, detailing the current practice in Europe for the diagnosis and treatment of psoriasis in childhood. These opinions are presented in the context of evidence from the literature and the current licensure status and indications of therapies for psoriasis in childhood. CONCLUSIONS: These data provide detailed information on the current practices in Europe for treating psoriasis in childhood.

Incidence of psoriasis and association with comorbidities in Italy: a 5-year observational study from a national primary care database.

An observational study was conducted to estimate the incidence of psoriasis in Italy, as well as the utilization of healthcare resources and the association with selected comorbidities in psoriasis patients. The data source was the Health Search/Thales Database, containing computer-based patient records from over 900 primary care physicians (PCPs) throughout Italy. The study cohort comprised all adults receiving a first-ever diagnosis of psoriasis during the years 2001-2005. From a total sample of 511,532 individuals, the incidence of psoriasis was 2.30-3.21 cases per 1,000 person-years. Psoriatic arthritis was present in 8% of psoriasis patients. The comparison with matched controls showed that psoriasis patients were more likely to have comorbidities (e.g., chronic bronchitis, chronic ischemic heart disease, obesity and diabetes mellitus) and to undergo PCP visits and hospitalizations, and to refer for specialist visits. The use of non-steroidal anti-inflammatory drugs appeared to be significantly more prevalent in patients as compared to controls. Topical therapy with corticosteroids and non-steroidal preparations accounted for 45.3% and 47.2% of all cases, respectively. Only a minority of cases used systemic immunosuppressive drugs or acitretin. The incidence rate of psoriasis in our study was particularly high and might reflect an overestimation by PCPs. Our results show the association between psoriasis and multiple comorbidities.

Leser-Trélat syndrome in patients affected by six multiple metachronous primitive cancers.

Leser-Trélat syndrome is characterized by the eruptive appearance of multiple seborrheic keratoses in association with underlying malignant disease. Usually, the sign of Leser-Trélat is associated with adenocarcinoma, most frequently of the colon, breast, or stomach, but also of the lung, kidney, liver, and pancreas. Herein, we present a case that we believe is the first report of the sign of Leser-Trélat in association with occult gastric adenocarcinoma and the anamnestic oncologic history of five other multiple primitive cancers. Epidermal growth factor receptor (EGFR) immunohistochemical expression analysis of multiple seborrheic keratoses revealed an intense membranous staining in the basal keratinocytes and in all the upper epidermal layers. Patients with the sign of Leser-Trélat should undergo a diagnostic screening programme for malignant disease along with patients with known Leser-Trélat syndrome who present with a recent acute and florid eruption of their seborrheic keratoses. We propose the importance of combining the molecular features of multiple seborrheic keratoses with EGFR immunohistochemistry analyses to determine the likelihood of Leser-Trélat syndrome and the consequent high risk of underlying multiple visceral malignancies.

Cutaneous lesions as initial signs of interferon alpha-induced sarcoidosis: report of three new cases and review of the literature.

Sarcoid reactions are well-recognized adverse events during interferon (IFN) therapy. They are frequently underdiagnosed because misinterpreted as IFN-induced side effects. Sarcoid cutaneous lesions may therefore represent useful hints to an early diagnosis, but their incidence is unknown. We report three new cases of mono-localized, purely cutaneous IFNalpha-induced sarcoidosis. In addition, an extensive review of the literature, with special attention to skin involvement, was performed through a PubMed search. The analysis of the retrieved articles showed that cutaneous lesions are frequent signs of IFN-induced sarcoidosis. Skin involvement is documented in 56% of the reports and it appears among the presenting and diagnostic signs of a sarcoid reaction in 51%. Special attention to dermatologic signs is imperative in the course of IFN therapy because even minimal skin involvement may offer a clue to an early diagnosis of IFN-induced sarcoidosis.

Perception of disease and doctor-patient relationship experienced by patients with psoriasis: a questionnaire-based study.

Many studies have addressed the impact of psoriasis on quality of life, but few studies have investigated patient perception of the disease or the patient-physician relationship. As with most chronic diseases, improvement in the patient-physician relationship may be important in the proper management of patients with psoriasis. To assess how psoriasis and its treatments are subjectively experienced by patients as well as patient expectations with regard to the patient-physician relationship. A discussion agenda for 'focus group meetings' was organized by a group of sociologists, psychologists, educators, researchers, and clinicians active in the field of psychodermatology. Four meetings were held in Northern and Central Italy and participants included one moderator and either eight dermatologists or eight patients. Discussions were based on a predefined agenda and included: (i) the psychological representation of psoriasis; (ii) the hetero- and self-perception of the patient; (iii) the patient-physician relationship; and (iv) the development of an educational intervention for dermatologists in order to improve the patient-physician relationship. A questionnaire, based on the information gathered at the focus groups, was administered to 323 patients with moderate to severe chronic plaque psoriasis from 17 dermatology clinics throughout Italy. Three hundred patients completed the questionnaire. Psoriasis elicited anger, annoyance at the inconvenience of the disease, and irritation in approximately 50% of the patients, whilst 38% of patients were unable to describe their emotional state. Aspects of life that were limited by psoriasis included clothing (57%), social interactions (43%), and personal hygiene (31%). The disease was often seen by patients as incomprehensible, incurable, and uncontrollable. More than half of the patients stressed their need to be listened to by the treating physician, and their wish that the physician should use simple language and should improve their psychological skills and interpersonal communication techniques. Dermatologists need to convey to patients with psoriasis the feeling of 'understanding the disease,' of hope about its curability, and the 'perception of control.' These elements should be taken into account when treating patients and whenever educational interventions are planned.

Risk factors of hypertension, diabetes and obesity in Italian psoriasis patients: a survey on socio-demographic characteristics, smoking habits and alcohol consumption.

We evaluated risk factors such as socio-demographic characteristics, smoking habits and alcohol consumption, associated with hypertension, diabetes and obesity in psoriasis patients, in order to plan health education programs that could prevent the onset or progression of co-morbidities. The study population consisted of 1376 patients with psoriasis who were consecutively recruited at 21 Italian Departments of Dermatology. Information concerning socio-demographic variables, smoking and alcohol consumption, and the presence of chronic disorders such as hypertension, type 2 diabetes and obesity was collected. The risk of co-morbidities according to the various exposure variables was calculated using logistic regression models. Psoriasis patients living in extremely urban areas showed the highest risk of diabetes (OR = 1.99, 95% CI 1.06-5.23) and obesity (OR = 2.60, 95% CI 1.10-16.12), as compared to patients living in rural areas. The OR for hypertension was higher for smokers (> 15 cigarettes per day, OR = 1.37, 95% CI 1.01-2.03) and drinkers (> 2 glasses/day of wine, OR = 2.11, 95% CI 1.31-3.40). The OR for diabetes or obesity was higher for drinkers: 1 drink/day (OR = 1.93, 95% CI 1.01-3.67) and > 1 drink/day of spirits (OR = 2.90, 95% CI 1.43-5.82), respectively. The results of our survey highlight the need to detect psoriasis patients with different susceptibilities to co-morbidities in order to plan specific health campaigns aimed at changing people's lifestyles with respect to smoking, drinking and diet.

Etanercept provides a more physiological approach in the treatment of psoriasis.

Psoriasis is a common chronic inflammatory disease affecting the skin and joints. Moderate to severe psoriasis is traditionally treated with systemic treatments, which can be effective but are often associated with relevant adverse effects, even when administered intermittently or rotationally. Biologic therapies may provide high and consistent efficacy over time, long-term safety, and simple administration schedules compared with nonbiologic therapies, and can be used in patients intolerant and/or resistant to these therapies. TNF-antagonists have a definite advantage over other biologic agents (e.g., T-cell targeting drugs) in the early and late manifestations of joint involvement. TNF-antagonists are a class of drugs with distinct pharmacokinetic and pharmacodynamic properties, and different safety profiles. Etanercept provides a more "physiological" mechanism of action compared to anti-TNF antibodies. Etanercept has less dramatic effects on TNF homeostasis although it has been proved to be highly effective in blocking psoriatic joint erosions. It maintains stable efficacy over time on skin psoriasis, also when used intermittently. Moreover, etanercept has been shown to be not immunogenic, and it only slightly increases the risk of granulomatous infections compared to anti-TNF antibodies. According to the "physiologic" paradigm of selection among TNF-antagonists linked to more or less physiologic mechanism of action, etanercept appears to be the anti-TNF of choice for treating most patients with moderate to severe plaque psoriasis and psoriatic arthritis, possibly even at an early stage.