Differences in Osteoimmunological Biomarkers Predictive of Psoriatic Arthritis among a Large Italian Cohort of Psoriatic Patients.

(1) Background: In literature it is reported that 20-30% of psoriatic patients evolve to psoriatic arthritis over time. Currently, no specific biochemical markers can either predict progression to psoriatic arthritis or response to therapies. This study aimed to identify osteoimmunological markers applicable to clinical practice, giving a quantitative tool for evaluating pathological status and, eventually, to provide prognostic support in diagnosis. (2) Methods: Soluble (serum) bone and cartilage markers were quantified in 50 patients with only psoriasis, 50 psoriatic patients with psoriatic arthritis, and 20 healthy controls by means of multiplex and enzyme-linked immunoassays. (3) Results: Differences in the concentrations of matrix metalloproteases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), receptor activator of nuclear factor kappa-B- ligand (RANK-L), procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTx-I), dickkopf-related protein 1 (DKK1), and sclerostin (SOST) distinguished healthy controls from psoriasis and psoriatic arthritis patients. We found that MMP2, MMP12, MMP13, TIMP2, and TIMP4 distinguished psoriasis from psoriatic arthritis patients undergoing a systemic treatment, with a good diagnostic accuracy (Area under the ROC Curve (AUC) > 0.7). Then, chitinase-3-like protein 1 (CHI3L1) and MMP10 distinguished psoriasis from psoriatic arthritis not undergoing systemic therapy and, in the presence of onychopathy, MMP8 levels were higher in psoriasis than in psoriatic arthritis. However, in these latter cases, the diagnostic accuracy of the identified biomarkers was low (0.5 < AUC < 0.7). (4) Conclusions. By highlighting never exploited differences, the wide osteoimmunological biomarkers panel provides a novel clue to the development of diagnostic paths in psoriasis and psoriasis-associated arthropathic disease.

Blood to skin recirculation of CD4+ memory T cells associates with cutaneous and systemic manifestations of psoriatic disease.

Blood to skin recirculation could play a role in the pathogenesis of psoriasis. To investigate this possibility we dissected the phenotype of circulating T cells in psoriasis patients, calculated the correlation the clinical parameters of the disease and performed a parallel bioinformatics analysis of gene expression data in psoriatic skin. We found that circulating CCR6+ CD4+ TEM and TEFF cells significantly correlated with systemic inflammation. Conversely, the percentage of CXCR3+ CD4+ TEM cells negatively correlated with the severity of the cutaneous disease. Importantly CLA+ CD4+ TCM cells expressing CCR6+ or CCR4+CXCR3+ negatively correlated with psoriasis severity suggesting recruitment to the skin compartment. This assumption was reinforced by gene expression data showing marked increase of CCR7 and CLA-encoding gene SELPLG expression in psoriatic skin and strong association of their expression. The data enlightens a role for CD4+ T cells trafficking between blood and skin in cutaneous and systemic manifestations of psoriasis.

A role for CCR5(+)CD4 T cells in cutaneous psoriasis and for CD103(+) CCR4(+) CD8 Teff cells in the associated systemic inflammation.

Recent results have identified critical components of the T cell response involved in the initiation and amplification phases of psoriasis. However the link between T cell responses arising in the skin and the systemic inflammation associated with severe psoriasis is largely unknown. We hypothesized that specific subsets of memory T cells recirculating from the skin could play a role. We therefore dissected the circulating memory T cell compartment in patients by analyzing the TCM, TEM and Teff phenotype, the pattern of CCR4 and CCR5 chemokine receptor expression and the expression of the tissue homing molecule CD103. For each subset we calculated the correlation with the Psoriasis Area and Severity Index (PASI) and with the extent of systemic inflammation measured as serum level of the prototypic short pentraxin, C reactive protein (CRP). Validation was performed by comparison with gene expression data in psoriatic plaques. We found that circulating CD103(+)CCR4(+)CCR5(+) and CCR4(+)CCR6(-) CD8(+) Teff cells, were highly correlated with CRP levels as well as with the validated index PASI, reflecting a link between skin involvement and systemic inflammation in patients with severe psoriasis. In addition we observed a contraction of circulating CCR5(+) T cells in psoriasis patients, with a highly significant inverse correlation between CCR5(+)CD4 T cells and the PASI score. Increased expression of CCR5 and CCL5 genes in psoriatic skin lesions was consistent with an accumulation of CCR5(+) cells in psoriatic plaques indicating a role for CCR5/CCL5 axis in disease pathogenesis.

Skin microbiota of first cousins affected by psoriasis and atopic dermatitis.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin diseases, which negatively influence the quality of life. In the last years, several evidences highlighted the pivotal role of skin bacteria in worsening the symptomatology of AD and psoriasis. In the present study we evaluated the skin microbiota composition in accurately selected subjects affected by (AD) and psoriasis. METHODS: Three first cousins were chosen for the study according to strict selection of criteria. One subject was affected by moderate AD, one had psoriasis and the last one was included as healthy control. Two lesional skin samples and two non-lesional skin samples (for AD and psoriatic subjects) from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. For the healthy control, two skin samples from an area of 2 cm(2) behind the left ear were withdrawn by mean of a curette. DNA was extracted and sequencing was completed on the Ion Torrent PGM platform. Culturing of Staphylococcus aureus from skin samples was also performed. RESULTS: The psoriatic subject showed a decrease in Firmicutes abundance and an increase in Proteobacteria abundance. Moreover, an increase in Streptococcaceae, Rhodobacteraceae, Campylobacteraceae and Moraxellaceae has been observed in psoriatic subject, if compared with AD individual and control. Finally, AD individual showed a larger abundance of S. aureus than psoriatic and healthy subjects. Moreover, the microbiota composition of non-lesional skin samples belonging to AD and psoriatic individuals was very similar to the bacterial composition of skin sample belonging to the healthy control. CONCLUSION: Significant differences between the skin microbiota of psoriatic individual and healthy and AD subjects were observed.

Inhibition of CCR7/CCL19 axis in lesional skin is a critical event for clinical remission induced by TNF blockade in patients with psoriasis.

Despite the evidence that tumor necrosis factor (TNF) inhibitors block TNF and the downstream inflammatory cascade, their primary mechanism of action in inhibiting the self-sustaining pathogenic cycle in psoriasis is not completely understood. This study has the aim to identify early critical events for the resolution of inflammation in skin lesions using anti-TNF therapy. We used a translational approach that correlates gene expression fold change in lesional skin with the Psoriasis Area and Severity Index score decrease induced by TNF blockade after 4 weeks of treatment. Data were validated by immunofluorescence microscopy on skin biopsy specimens. We found that the anti-TNF-modulated genes that mostly associated with the clinical amelioration were Ccr7, its ligand, Ccl19, and dendritic cell maturation genes. Decreased expression of T-cell activation genes and Vegf also associated with the clinical response. More important, the down-regulation of Ccr7 observed at 4 weeks significantly correlated with the clinical remission occurring at later time points. Immunofluorescence microscopy on skin biopsy specimens showed that reduction of CCR7(+) cells and chemokine ligand (CCL) 19 was paralleled by disaggregation of the dermal lymphoid-like tissue. These data show that an early critical event for the clinical remission of psoriasis in response to TNF inhibitors is the inhibition of the CCR7/CCL19 axis and support its role in psoriasis pathogenesis.

Treatment of atopic dermatitis eczema with a high concentration of Lactobacillus salivarius LS01 associated with an innovative gelling complex: a pilot study on adults.

GOALS: To evaluate the efficacy of a highly concentrated Lactobacillus salivarius preparation containing a gelling complex formed by Streptococcus thermophilus ST10 and tara gum in the treatment of atopic dermatitis (AD). BACKGROUND: Previous studies have demonstrated an improvement in AD symptoms after administration of the probiotic strain L. salivarius LS01. S. thermophilus ST10 and tara gum create a gelling complex that adheres to intestinal mucus and improves barrier function. STUDY: A prospective, controlled pilot trial was carried out to evaluate how the association of S. thermophilus ST10 and tara gum could improve the activity of L. salivarius LS01 administered at high doses to adults with AD. Twenty-five patients were included into the study: 13 were treated for 1 month with the active formulation, whereas 12 represented the placebo group. Scoring Atopic Dermatitis index was determined before and at the end of probiotic administration. Fecal samples were also collected to evaluate changes in bacterial counts of Staphylococcus aureus and clostridia. RESULTS: A significant improvement in SCORAD index was observed in the probiotic group after 1 month of treatment, whereas no significant changes occurred in placebo patients. A slight decrease in fecal S. aureus count was observed in probiotic-treated patients. CONCLUSIONS: Data obtained in this study suggest a potential role for L. salivarius LS01 in the treatment of AD. The addition of tara gum and S. thermophilus ST10 seems to improve the overall efficacy of the probiotic strain, in particular shortening the time required for the onset of the positive effects. Further studies to investigate the activity of this preparation are advisable.

Quality of life assessment of patients with scalp dermatitis using the Italian version of the Scalpdex.

The aim of this study was to assess quality of life in patients with scalp dermatitis using the Italian version of the Scalpdex, and to validate the instrument in Italian. The survey was conducted in outpatients with psoriasis, seborrhoeic dermatitis, alopecia, or follicular lichen. Data were completed on 194 patients, 78% of whom had psoriasis. Scalpdex scores were always higher in women than in men, and in younger people compared to elderly people. The most frequent items were: being ashamed, embarrassed, bleeding scalp, feeling self-conscious, bothered that the condition is incurable, having the choice of colour of clothes affected, having a negative effect on daily life. The Italian Scalpdex showed good internal consistency, test-retest reliability, convergent validity, and responsiveness. In conclusion, the Italian version of the Scalpdex is a useful instrument to measure quality of life in patients with a scalp condition.

Safety of anti-TNFα agents in the treatment of psoriasis and psoriatic arthritis.

CONTEXT: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations. OBJECTIVE: This review presents and discusses current evidence on the safety of anti-TNFα agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance. METHODS: Key studies on the safety of anti-TNFα agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA), were included as appropriate when data in psoriatic disease were unavailable or insufficient. RESULTS: Available data on the safety of anti-TNFα agents such as etanercept in psoriasis and PsA appear reassuring, even if some concerns still exist. Most notably, data suggest a higher incidence of infection and lymphoma amongst patients treated with the anti-TNFα monoclonal antibodies infliximab and adalimumab compared with etanercept. CONCLUSION: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity.

Dual role of anti-TNF therapy: enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues.

The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with the clinical response and we monitored cytokine expression in biopsies from inflamed tissues. We evidenced a dual role of TNF-blockade. In peripheral blood, it increased the expression of cytokines such as IL-17, IL-10, and IFN-γ, and enhanced the expression of activation markers and the proliferative response of CD4 T cells to TCR stimulation. By contrast, in biopsies from target tissues, TNF-blockade diminished the expression of Th17/Th1 cytokine and early inflammatory genes. Importantly, the enhanced T cell responses to TCR-stimulation did not impair the clinical response to the therapy and, in responder patients, occurred with the concomitant down-regulation of inflammatory genes in the target tissues.

Metal sensitivity in patients with orthopaedic implants: a prospective study.

BACKGROUND: Sensitization to orthopaedic implant materials is an unpredictable event that might affect implant performance. OBJECTIVES: In candidates for hip or knee joint prosthesis implantation, to evaluate preoperative assessments for identifying patients with metal sensitivity, to determine the percentage of patients who developed metal sensitivity at 1 year after prosthesis implantation, and to examine the clinical relevance of patch tests and lymphocyte transformation tests (LTT-MELISA®) for the evaluation of metal sensitization. PATIENTS AND METHODS: A total of 100 patients referred for total hip or total knee arthroplasty were assessed preoperatively and then at 1 year post-implantation by means of patch tests with the metals present in the implant alloys. In a pilot study, 20 patients also underwent both patch testing and a lymphocyte transformation test (LTT-MELISA®) for the same metals. RESULTS: Only 72 of 100 patients were patch tested both before and after surgery, and 12 of 20 also underwent LTT-MELISA® before and after surgery. Of 31/100 patients with an apparent history of nickel sensitivity determined during preoperative assessment of subjects, 12 tested negative on both tests, and 4 with a negative history of nickel sensitivity tested positive. One year post-implantation (72 patients), 5 patients who had initially tested negative for a metal allergy became positive for at least one or more metal constituents of the prosthesis on at least one or the other test. CONCLUSIONS: Given the discrepancies between the information obtained while taking patient histories and test results, preoperative history-taking alone appears to be insufficient for identifying patients with metal sensitivity. Moreover, the increase in the percentage of patients who tested positive for metal sensitivity 1 year post-implantation suggests the possibility of prosthesis-induced sensitization. Therefore, objective determination of metal sensitivity at preoperative assessment should be considered in planning arthroplasty intervention, as it would help the surgeon in selecting the most appropriate prosthesis for the patient and could benefit implant performance.

Cost-effectiveness analysis of TNF-alpha blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system.

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-alpha agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48-50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48-50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.

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.

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.

Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis.

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis.

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.

Acquired lymphangiomas mimicking multiple hallux warts.

Lymphangioma is an uncommon benign vascular tumour that involves lymphatic vessels. It can be acquired or, most frequently, congenital. The acquired form presents with dilated lymphatic channels due to an obstruction. These lesions have no risk of malignant transformation, but they have a high rate of recurrence whether removed. We present a case of a 52-year-old woman with acquired lymphangiomas mimicking warts. She came to our observation for some keratotic lesions on her feet. Clinically, we found three warts on the sole of her left foot, but we also noticed the presence of swelling and papillomatous wart-like papules on both halluces. The hallux papules were studied by performing an excisional biopsy and were found to be lymphangiomas.

Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics.

Actinic keratosis (AK) is a common keratinocyte intra-epidermal neoplasia. To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

Methotrexate: practical use in dermatology.

Methotrexate (MTX) is an anti-inflammatory, anti-proliferative and immunosuppressant drug largely used worldwide with a well-known efficacy, and it is considered a safe and easy to use agent. MTX was first used in psoriasis, but it represents an effective and safe therapeutic option in a wide range of skin diseases. Despite its common employ, it is still the subject of numerous researches, with the purpose to develop new strategies to increase the manageability and evaluate the efficacy of the treatment, alone and in association with other therapies. Starting up from the official guidelines, we have reviewed the scientific literature, along with our clinical experience, in order to update the uses of MTX in dermatology.

T Helper Cell Subsets in Clinical Manifestations of Psoriasis.

Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis.

Cyclosporine in psoriasis: comparison of a 25-year real-world Italian experience to current European guidelines.

Cyclosporine (CsA) is an effective and safe therapeutic option in various dermatoses in both adults and children. Over the last 25 years, Italian dermatologists have gained relevant experience about the use of CsA in the treatment of psoriasis and atopic dermatitis, and an Italian Consensus Conference has recently provided recommendations in adult patients. A comparison between these real-world indications and current European guidelines is hereby provided.