Lifestyle and dietary habits of patients with gout followed in rheumatology settings.

Diet and lifestyles modification are core aspects of the non-pharmacological management of gout, but a poor consistency with suggested guidelines is reported. This study aimed to investigate dietary and lifestyle habits of patients with gout followed in rheumatology settings. Data were retrieved from the baseline dataset of the KING study, a multicentre cohort study of patients with gout followed in rheumatology settings. Dietary habits were assessed with the Italian National Institute of Statistics (ISTAT) food-frequency questionnaire and compared with reported data about general population. The relative increase of exposure was estimated by standardized prevalence ratios adjusted for gender, age and geographical distribution. The study population included 446 patients, with a mean age of 63.9 years and a M/F ratio of 9:1. Compared to the Italian population, gouty patients showed a higher prevalence of obesity [1.82 (1.52-2.18)] and a higher consumption of wine [1.85 (1.48-2.32)] and beer [2.21 (1.68-2.90)], but a lower prevalence of smoking and a lower intake of liquor. They showed a lower intake of red meat [0.80 (0.71-0.91)], but a similar intake of other tested dietary factors. Gouty patients' lifestyle is still partially different from the recommended.

The emerging problem of biological treatment in migrant and travelling populations: it is time to extend guidelines for the screening of infectious diseases.

The use of biological agents in the treatment of rheumatic diseases has been widely associated with an increased risk of reactivation of several latent infections. National and international guidelines recommend screening for infectious diseases before starting these drugs. In Western countries screening is limited to latent tuberculosis infection, HIV and viral hepatitis. However, the increasing globalisation and the remarkable number of migrating and travelling people worldwide make this approach no longer adequate. The Italian and Spanish Societies of Rheumatology and Tropical Medicine wish to issue a warning about the need to improve awareness of doctors about the risk of reactivation of infectious tropical diseases in migrant or travelling patients who undergo biological therapy. Thus, the Italian and Spanish Societies are now planning to issue specific recommendations, based on a multidisciplinary contribution and a systematic review of the literature, for screening and follow-up of active and latent chronic infections in candidate patients for biological agents, taking into account the patient's area of origin and risk of infectious diseases.

Emerging therapies for osteoporosis.

Currently available drugs for the treatment of osteoporosis can still be improved in terms of pharmacokinetics, pharmacodynamics and management. New approaches for the development of innovative drugs are possible thanks to our increasing understanding of the bone tissue biology and the cellular and molecular processes that regulate it. One of the new anti-bone resorption agents, odanacatib, a selective cathepsin-K inhibitor, is in late phase III clinical research. Among new bone anabolic drugs, those that have an action on the Wnt signaling pathway appear to be particularly promising. The development of new compounds for the treatment of osteoporosis represents an excellent example of translational medicine efforts aimed to extend the range of treatment options for osteoporosis, a very common disease with a high social and economic impact, particularly when causing fractures.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy.

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very frequent among RA patients; its prevalence was 60%, 52% and 38% in southern, central and northern Italy, respectively. Mean disease activity and disability scores were worse in southern regions of Italy. These scores were inversely related to 25OHD levels and this correlation remained statistically significant after adjusting for both body mass index (BMI) and sun exposure time. However, disease severity remained significantly higher in southern regions versus central-northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA Italian patients there are significant regional differences in the prevalence of vitamin D deficiency explained by different BMI, and sun exposure time, and inversely associated with disease activity and disability scores.

Italian Society of Rheumatology recommendations for the management of gout.

OBJECTIVE: Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. METHODS: The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. RESULTS: The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. CONCLUSIONS: The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.

Italian Society for Rheumatology recommendations for the management of hand osteoarthritis.

Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations' review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.

Validation and further development of the WHO 10-year fracture risk assessment tool in Italian postmenopausal women: project rationale and description.

The threshold for pharmacological intervention for osteoporosis remains controversial. Tools predicting the future risk of new fractures are increasingly used to establish a convenient individual risk/benefit ratio for a long term treatment. FRAX® is likely to become the most widely used tool for assessing fracture risk also for the WHO endorsement. The inevitable limitations will not hamper its value. As for any tool like this a continuous process of validation and further development is highly warranted. The predictive and clinical value of FRAX® has to be tested in individual countries by exploring also the inclusion of additional specific relatively uncommon risk factors. The DeFRA project is intended to validate in a large cohort of postmenopausal women a new algorithm derived from FRAX®. Both, the coefficients of continuous variable and the gradients for clinical risk factors should not be considered as conclusive for the routine clinical use. The new tool will be offered for the routine clinical use only at the completion of the DeFRA project, requiring the prospective collection of at least 60.000 patient-years. Here we report the rational and the design of the project.

Cerebellar tumour presenting with pathological laughter and gelastic syncope.

There is no report of patients in whom pathological laughter, a rare condition characterized by uncontrollable episodes of laughter usually triggered by unrelated stimuli, was ever closely associated with a loss of consciousness overtly linked with the onset of such uncontrollable laughter, also referred to as a gelastic syncope. A 53-year-old man presented with a 4-month history of syncope following intense and uncoordinated laughter. Physical and neurological examination was normal and the patient had no other typical cerebellar signs. We found a mass in the cerebellar vermis abutting the floor of the fourth ventricle, which upon histological examination after surgery proved to be an ependymoma. We emphasize that pathological laughter and gelastic syncope could represent unique and sole features of a cerebellar disorder.

Synovial fluid OX40T lymphocytes of patients with rheumatoid arthritis display a Th2/Th0 polarization.

Rheumatoid arthritis (RA) is an autoimmune disease in which T-cell activation plays a pivotal role in the induction of articular damage. CD4+/OX40+ T cells accumulate in the synovial fluid (SF) of RA patients, which suggests that they are involved in the pathogenesis of the disease. In this study, we assessed the intracellular cytokine production of peripheral blood and SF CD4+ and CD4+/OX40+ T cells from RA patients in order to evaluate their role in this disorder. Our results show that SF CD4+ cells are predominantly interferon gamma (IFN-gamma)-positive and express a Th1-like cytokine pattern. In SF, significantly more CD4+/OX40+ T cells expressed interleukin-4 (IL-4) and IL4/IFN-gamma than IFN-gamma alone. Our data demonstrate that SF CD4+/OX40+ T cells express a Th2/Th0 cytokine profile, which suggests that they are involved in inflammatory responses in RA joints.

[Study of vitamin D status of rheumatoid arthritis patients. Rationale and design of a cross-sectional study by the osteoporosis and metabolic bone diseases study group of the Italian Society of Rheumatology (SIR)]. / Studio dello stato vitaminico D in pazienti affetti da artrite reumatoide. Razionale e disegno della rilevazione cross-sectional programmata dal gruppo SIR per lo studio dell'osteoporosi e delle malattie metaboliche dello scheletro.

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.

Parathyroid storm: immediate recognition and pathophysiological considerations.

A 56-year-old white man was referred for evaluation of severe hypercalcemia following a three-week history of progressive weakness, nausea, and depression. Initial laboratory results showed serum total and ionized calcium (Ca++) values of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately performed and an extremely high value was obtained in just 30 min (1315 ng/l, normal values 6.4-70.4). The patient was therefore treated with saline solution and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and intact PTH during the first six days; then there was a trend to reach a steady-state until parathyroidectomy was performed. After withdrawal of calcitonin therapy it was possible to observe a positive uncoupling between bone formation (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate-resistant acid phosphatase) markers. On day 35 the patient underwent neck exploration, and an enlarged lower left parathyroid gland was removed that on macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic appearance was suggestive of a previous glandular infarction. This is the first time the daily clinical course of a parathyroid crisis has been documented. Furthermore, changes of biomarkers of bone turnover following calcitonin therapy show that high doses of the hormone may cause a prolonged positive uncoupling of the two processes of bone remodeling.

Severe thrombophilia with antiphospholipid syndrome and hyperhomocysteinemia in a patient with Schnitzler's syndrome.

Schnitzler's syndrome is a rare condition with chronic urticaria, intermittent fever, bone pain, and a monoclonal IgM gammopathy. Most patients have a chronic and indolent course, but a small number ultimately progress to a lymphoplasmacytic malignancy. We describe a patient with Schnitzler's syndrome who entered an accelerated phase of clinical deterioration with repeated thromboses of the cerebral and coronary arteries that ultimately led to a fatal outcome. We found that the he fulfilled the Sapporo criteria for definite antiphospholipid syndrome and had elevated blood levels of homocysteine during the active clotting phase of the disease. We suggest that the association with immune-mediated or metabolic disorders, such as the antiphospholipid syndrome and hyperhomocysteinemia, may unfavorably affect the otherwise chronic and stable course of patients with Schnitzler's syndrome. The systemic clotting disorder, the association with the antiphospholipid syndrome and hyperhomocysteinemia, and the biclonal rather than monoclonal IgM gammopathy were striking features of this atypical case of Schnitzler's syndrome.

Polyarticular pigmented villonodular synovitis associated with multiple congenital anomalies. A case of Noonan-like/multiple giant cell lesion syndrome.

A case of polyarticular pigmented villonodular synovitis associated with many congenital phenotypic peculiarities (such as shortness, blue sclerae, flattened nose, low-set ears, hypertelorism, curly hair and pulmonary stenosis) is described. The presence of many of the typical signs of the Noonan syndrome and the histological finding of giant cells on the synovial biopsy led to the diagnosis of Noonan-like/multiple giant cell lesion syndrome.

Atypical renal onset and involvement in primary antiphospholipid syndrome in a child.

A case of primary antiphospholipid syndrome (APS) with renal involvement in a 10-year-old child is reported. The peculiarity of the case resided not only in the apparent "primary" occurrence of APS in the pediatric age, but also in the involvement of the kidney. The renal picture in the case described consisted of a focal proliferative glomerulonephritis, without any sign of glomerular thrombosis. We conclude that this should lead to a consideration of primary APS in the differential diagnosis of nephropathies, also in childhood.

T lymphocytes in the synovial fluid of patients with active rheumatoid arthritis display CD134-OX40 surface antigen.

OBJECTIVE: To assess the percentage of T lymphocytes, bearing CD134, a member of the TNF receptor superfamily, primarily found on autoreactive CD4+ T cells in the peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: The surface expression of CD134 on SF and PB mononuclear cells was performed by flow cytometry in 25 RA patients and correlated to the disease activity. RESULTS: CD134 expression on CD3+, CD4+, CD8+ and CD25+ cells was higher in SF than in PB of RA patients (P < 0.001). No differences were observed in the percentage of CD134+/CD4+ T lymphocytes in the PB of RA patients and controls. Patients with active RA had significantly higher percentage of CD3+/CD134+, CD4+/CD 134+, CD8+/CD134+ and CD25+/CD 134+ than those with inactive disease. CONCLUSION: These findings suggest that CD134+ T cells are involved in the immunopathological process of RA synovitis, maybe mirroring some other autoimmune disease in which autoreactive T cell infiltrating the target tissues largely coexpress CD134.