Gianfranco Altomare

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.

Depression circumstantially related to the administration of finasteride for androgenetic alopecia

In this paper we report 19 patients (14 males, 5 females; mean age 28.16 years ± 7.68 SD) out of a series of 23 (17 males, 5 females) who developed a mood disturbance (moderate to severe depression) during treatment with finasteride, 1 mg/day orally, for androgenetic alopecia (Hamilton subtypes III–V; Ludwig subtypes I–II). Depression, which significatively impaired sociofamilial relations, sleep and eating behaviour, was associated to marked anxiety in some cases, developed after 9–19 weeks of treatment with finasteride, and promptly resolved after suspension of the drug. Two patients accepted reintroduction of the drug, and depression relapsed within 2 weeks. Depression as an adverse effect of finasteride has been reported only once. Further studies are needed to confirm our circumstantial observations, which are based on a retrospective series of patients.

Moderate and severe plaque psoriasis: cost-of-illness study in Italy

Psoriasis is a chronic inflammatory, immune-mediated skin disorder that affects 1.5–1.8 million people in Italy. The most common form of the disease is chronic plaque psoriasis, affecting about 90% of psoriasis patients, with about 20%–30% of them suffering from a moderate or severe condition. Little information is available about the economic impact of psoriasis in European countries. The primary objective of this study was to perform a cost-of-illness analysis of patients with moderate and severe plaque psoriasis in Italy. Therefore, direct, indirect costs, and intangible costs (quality of life – QoL) were assessed. In this national, multicenter, prospective, 3-month cost-of-illness study of moderate and severe plaque psoriasis, direct and indirect costs were assessed from the patient, third-party payer (National Health Service, NHS), and societal perspectives. From November 2003 to October 2004 consecutive patients were enrolled over a 1-year period, in order to minimize seasonal fluctuations in disease severity. 150 patients enrolled in 6 investigational sites in Italy, completed the study, and were eligible to be analyzed according to the study protocol. Intangible costs (QoL) were measured using SF36 and DLQI questionnaires. The mean total cost for psoriasis (average Psoriasis Area Severity Index [PASI] score 21.4), including direct and indirect items, was €8,371.61 per patient per year. The mean cost for patients with moderate disease (PASI ≤ 20) was €5,226.04, while the mean cost for patients with more severe disease (PASI > 20) was €11,434.40 per year. Disease heavily affected QoL measured using SF36, and the impairment was greater in patients affected by a more severe form of disease. Moderate and severe plaque psoriasis is associated with extremely high costs, which are related to disease severity. Data from this study show that the more severe plaque psoriasis, the higher the direct and indirect costs for its management. Direct costs are higher than indirect costs; hospitalization represents the most significant item, accounting for 30% of the total expenses. QoL in moderate and severe plaque psoriasis is low compared with the population at large, confirming the high impact of plaque psoriasis on QoL. The relatively high average annual costs per patient point to the need for a more efficient and long-term control of psoriasis.

T cell responses in psoriasis and psoriatic arthritis.

According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop. Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation. Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis. The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints.

Reduction of CD68+ macrophages and decreased IL-17 expression in intestinal mucosa of patients with inflammatory bowel disease strongly correlate with endoscopic response and mucosal healing following infliximab therapy.

Background:Antibodies against tumor necrosis factor represent an effective therapy for patients with inflammatory bowel disease. Despite their successful results, the exact mechanism by which infliximab suppresses intestinal inflammation is still a matter of debate. In this study, we used a translational approach to identify the key mechanisms associated with resolution of mucosal inflammation induced by infliximab. Methods:A total of 16 patients with active inflammatory bowel disease (9 with Crohns disease and 7 with ulcerative colitis) and 16 controls were enrolled in the study. Patients received infliximab infusions at 0, 2, and 6 weeks. At enrollment and at week 6, patients underwent flexible sigmoidoscopy, and biopsies were taken from the sigmoid colon. RNA was extracted, and mucosal expression of 96 immune-related genes was evaluated by qRT-PCR and confirmed by immunofluorescence microscopy on tissue. Correlation between infliximab-induced gene expression modulation and endoscopic response to therapy was calculated. Lamina propria mononuclear cell apoptosis induced by infliximab was evaluated on tissue sections by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results:We found that infliximab-induced downregulation of macrophage and Th17 pathway genes was significantly associated with both endoscopic response to the therapy and achievement of mucosal healing. Importantly, the observed reduction of lamina propria CD68+ macrophages was associated with an increased rate of macrophage apoptosis. Conclusions:The 2 mechanisms associated with infliximab-induced resolution of intestinal inflammation are the reduction of lamina propria infiltrating CD68+ macrophages and the downregulation of interleukin 17A. Moreover, the data suggest that infliximab-induced macrophage apoptosis may represent a key mechanism for the therapeutic success of anti–tumor necrosis factor antibodies.

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.

Pityriasis rubra pilaris and retinol-binding protein

Serum levels of retinol‐binding protein (the specific carrier of vitamin A) were measured in eleven patients with pityriasis rubra pilaris and in some of their close relatives. The level of retinol‐binding protein was markedly reduced in every patient, and in some of the relatives. It is postulated that defective synthesis of retinol‐binding protein is a biochemical marker for pityriasis rubra pilaris, probably transmitted as a Mendelian dominant.

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 peoples lifestyles with respect to smoking, drinking and diet.

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.

Disodium cromoglycate versus diet in the treatment and prevention of nickel‐positive pompholyx

In some cases that have been diagnosed as contact allergy to nickel, there are repeated cutaneous eruptions of pompholyx, even in areas with no direct contact with the metal. The possible alimentary origin of dyshidrotic eczema should be considered when deciding on therapy. We have collected the clinical data for 24 patients with dyshidrotic eczema caused by nickel, to evaluate the benefit of a low‐nickel diet versus treatment with oral disodium cromoglycate, comparing both objective and subjective symptoms. A low‐nickel diet does not improve these patients but those treated with DSCG reacted better, from both objective and subjective point of view, than either the controls or the patients treated by diet. We next did intestinal permeability tests before therapy and after 15 days of treatment. We found that nickel uptake diminishes simultaneously with the reduction of absorption through the smaller aqueous “pores”. This phenomenon was greatest alter DSCG. We suggest that DSCG can help selected cases of pompholyx.