[Recurrent acute idiopathic pericarditis: rheumatologic therapy, autoantibodies and long term outcome]. / Pericardite acuta idiopatica recidivante: terapia reumatologica, autoanticorpi e long term outcome.

OBJECTIVE: To evaluate therapy and rheumatologic aspects of recurrent acute idiopathic pericarditis (RAIP). METHODS: We studied 46 patients. We used non-steroidal anti-inflammatory drugs (NSAIDs) at high dosage. We did not start corticosteroid: if already started, we planned a very slow tapering; 37 patients (80.4%) were treated with colchicine. We also assessed the frequency of ANA, anti-SSA and Rheumatoid factor. RESULTS: With our protocol recurrences dropped from 0.46 to 0.03 attacks/patient/month (p<0.00001) within 12 months and remained at the same level (0.024) till the end of the follow-up (mean 8 years). In the 37 patients treated with colchicine recurrences dropped from 0.5 to 0.03 (p<0.0001) within 12 months, and in 9 patients not given colchicine from 0.27 to 0.045 (p<0.005). When colchicine was used the decrease was significantly higher (0.47 vs 0.23) (p<0.001). In 27 (58.7%) patients ANA were positive at a titre >1/80, in 7 (15.2%) >1/160. Rheumatoid factor was positive in 7 (15.2%) and anti-SSA in 4 (8.7%). During the follow-up 4 (8.7%) new diagnosis of Sjogren and 1 (2.2%) of Rheumatoid Arthritis were made. CONCLUSION: NSAIDs at high dosage, slow tapering of corticosteroid and colchicine are very effective in RAIP. The improvement is more dramatic in colchicine treated patients, but also other patients can achieve good control of the disease. The finding of ANA, anti-SSA and the new rheumatological diagnoses support the involvement of autoimmunity.

Early diagnosis of Alzheimer's disease using a grid implementation of statistical parametric mapping analysis.

A quantitative statistical analysis of perfusional medical images may provide powerful support to the early diagnosis for Alzheimer's Disease (AD). A Statistical Parametric Mapping algorithm (SPM), based on the comparison of the candidate with normal cases, has been validated by the neurological research community to quantify ipometabolic patterns in brain PET/SPECT studies. Since suitable "normal patient" PET/SPECT images are rare and usually sparse and scattered across hospitals and research institutions, the Data Grid distributed analysis paradigm ("move code rather than input data") is well suited for implementing a remote statistical analysis use case, described in the present paper. Different Grid environments (LCG, AliEn) and their services have been used to implement the above-described use case and tackle the challenging problems related to the SPM-based early AD diagnosis.

Therapy for recurrent acute pericarditis: a rheumatological solution?

OBJECTIVE: To assess the efficacy of a multidrug protocol in recurrent acute pericarditis. We tried also to assess the specific role of colchicine. METHODS: We studied 58 patients (34 males) in the largest monocentric observational study. All patients received prolonged courses of non-steroidal anti-inflammatory drugs; generally we do not start a corticosteroid in recurrent acute pericarditis, but if a steroid had already been started, we planned a very slow tapering; if necessary azathioprine, hydroxychloroquine, and other immunosuppressive drugs were used; 44 patients (27 males, 61.4%) were treated also with colchicine and 14 patients (7 males, 50%) were not given this drug. RESULTS: After starting our protocol recurrences dropped from 0.48 to 0.03 attacks/patient/month (p < 0.00001) within 12 months and remained at the same level till the end of the follow-up (mean 8.1 years) in the whole cohort. In the 44 patients treated with colchicine recurrences dropped from 0.54 to 0.03 attacks/patient/month (p < 0.00001) within 12 months, and in 14 patients not given colchicine recurrences decreased from 0.31 to 0.06 attacks/patient/month (p = 0.002). In patients treated with colchicine the decrease was significantly higher (0.51) than in patients not taking this drug (0.25) (p = 0.006). Colchicine was discontinued by 16.3% of patients because of side effects. CONCLUSION: A multidrug protocol including non-steroidal anti-inflammatory drugs at high dosage, slow tapering of corticosteroid, colchicine, reassurance and close clinical monitoring is very effective in recurrent pericarditis; this improvement is more dramatic in colchicine treated patients, but also patients who do not tolerate it can achieve good control of the disease.

[Italian consensus on EULAR recommendations 2005 for the management of hip osteoarthritis]. / Consensus italiana sulle raccomandazioni EULAR 2005 per il trattamento dell'artrosi dell'anca.

The recommendations for the management of osteoarthritis (OA) of the hip were proposed by EULAR in 2005. Among the most important objectives of the expert charged to provide these recommendations were their wide dissemination and implementation. Thus, the information generated can be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. According with that previously executed for the EU-LAR recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has organised a Consensus on the EULAR recommendations 2005 for the management of hip OA. To obtain an acceptability as large as possible, the group of experts was composed by many physicians interested in the management of hip OA, including Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim of the Consensus was to analyse the acceptability and applicability of the recommendations according to own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of hip OA strongly encourage the dissemination of the EULAR 2005 recommendations also in Italy.

[Italian consensus on Eular 2003 recommendations for the treatment of knee osteoarthritis]. / Consensus italiana sulle raccomandazioni dell'EULAR 2003 per il trattamento dell'artrosi del ginocchio.

The recommendations for the management of osteoarthritis (OA) of the knee firstly proposed by the EULAR in 2000, have been updated in 2003. One of the most important objectives of the expert charged to provide these recommendations was their dissemination. Thus, the information generated may be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. The Italian Society of Rheumatology (SIR) and the Italian League against Rheumatism (LIMAR) have organised a Consensus on the EULAR recommendations 2003 with the aim to analyse their acceptability and applicability according to our own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that specialists involved in the management of knee OA strongly encourage the dissemination of the EULAR 2003 recommendations also in Italy.

Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders.

We evaluated the prognostic features of 384 asymptomatic IgM-monoclonal gammopathies (aIgM-MGs) and 74 IgM-related disorders (IgM-RDs), two clinically distinct groups as proposed by the Second International Workshop on Waldenström's Macroglobulinemia (WM). The cumulative probability of evolution to lymphoid malignancy at 5 and 10 years was 8% (95% CI, 5-13%) and 29% (95% CI, 21-38%), respectively, in aIgM-MGs; it was 9% (95% CI, 4-20%) and 16% (95% CI, 7-31%), respectively, in IgM-RDs (P=0.26). At a median follow-up of 45 months (12-233), 45 aIgM-MGs (11.7%) evolved to symptomatic WM (n=41), non-Hodgkin's lymphoma (NHL) (n=2), IgM multiple myeloma (n=1), and primary amyloidosis (n=1). At a median follow-up of 60 months (13-195), seven IgM-RDs (9.5%) evolved to symptomatic WM (n=6), and B-chronic lymphocytic leukaemia (n=1). At univariate analysis, in aIgM-MGs bone marrow lymphoplasmacytic infiltration, high erythrocyte sedimentation rate (ESR), haemoglobin level, IgM size, and lymphocytosis significantly correlated with evolution probability. At multivariate analysis, the latter two parameters strongly correlated with prognosis, haemoglobin being associated with a trend for a higher progression risk. In IgM-RDs IgM size, neutropenia, lymphocytosis, detectable Bence Jones proteinuria, and high ESR were associated with evolution probability. In conclusion, asymptomatic IgM-MGs and IgM-RDs are distinct clinical entities with similar probability of transformation to lymphoid malignancy.

Direct and indirect costs of osteoarthritis of the knee.

BACKGROUND: Rheumatic diseases have an economic impact of 1-2.5% of GDP in industrialized countries and osteoarthritis is the most common joint disorder. Osteoarthritis of the knee is especially common and is a major cause of disability requiring extensive utilization of health care resources. OBJECTIVE: To estimate the burden of osteoarthritis of the knee in Italy, we studied retrospectively a cohort of 254 patients over a period of 12 months in 2000-2001. METHODS: Twenty-nine rheumatology institutes took part in the study. A bottom-up approach was used, analytically measuring pro capita consumption. We considered medical (hospitalization, diagnosis, and therapies) and non-medical costs (transport, temporary caregivers, and auxiliary devices) as direct costs. We calculated losses of productivity borne by patients and caregivers, and informal care provided by caregivers as indirect costs. RESULTS: Direct costs came to Euros 934 per patient per year: Euros 233 were spent on hospitalization, Euros 209 on diagnostic procedures (56% on visits and 44% on instrumental and laboratory tests), Euros 146 on therapy (58% on physiotherapy and 42% on drugs), and Euros 346 on non-medical costs (73% on salaries to temporary caregivers, 14% on transport, and 13% on auxiliary devices). It is interesting to point out that at least 37% of costs were charged directly to patients. Indirect costs were almost 30% higher and came to Euros 1236 per patient per year: 31% was due to loss of productivity of patients, 60% due to informal care provided by primary caregivers, and 9% by other caregivers. CONCLUSIONS: This study confirms that the direct and indirect costs attributable to osteoarthritis of the knee are substantial.

Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee.

OBJECTIVE: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index is a tested questionnaire to assess symptoms and physical functional disability in patients with OA of the knee and the hip. We adapted the WOMAC for the Italian language and tested its metric properties in 304 patients with symptomatic OA of the knee. METHODS: Three hundred and four consecutive patients, attending 29 rheumatologic outpatient clinic in northern, central, and southern Italy, were asked to answer two disease-specific questionnaires (WOMAC and Lequesne algofunctional index) and one generic instrument (Medical Outcomes Study SF-36 Health Survey-MOS SF-36). A sample of 258 patients was readministered the WOMAC 7-10 days after the first visit and the structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using intraclass correlation coefficients (ICCs), and construct and discriminant validity using Spearman's correlations, Wilcoxon rank sum test, and Kruskal-Wallis test. RESULTS: All WOMAC subscales (pain, stiffness, and physical function) were internally consistent with Cronbach's coefficient alpha of 0.91, 0.81, and 0.84, respectively. Test-retest reliability was satisfactory with ICCs of 0.86, 0.68, and 0.89, respectively. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, supporting the concepts of convergent construct validity. Very high correlations were also obtained between WOMAC scores and Lequesne OA algofunctional index. WOMAC physical function, but not WOMAC stiffness and pain subscales, was weakly associated with radiological OA severity (P=0.03). Also, WOMAC pain score was inversely correlated (P=0.01) with years of formal education. Examination of discriminant validity showed that the scores on the WOMAC and SF-36 followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. CONCLUSION: The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.

Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study.

Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplained pregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectively followed 100 anti-Ro/SSA positive women (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies). Anti-Ro/SSA antibodies were tested by immunoblot and counterimunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes (4.9 vs 8.1%), preeclampsia (6.6 vs 8%), intrauterine growth retardation (0 vs 2.3%)and newborns small for gestational age (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsible for congenital heart block but do not affect other pregnancy outcomes, both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, ifprospectively followed by multidisciplinary teams with ample experience in this field.

A multicenter cost-of-illness study on rheumatoid arthritis in Italy.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and disabling disease frequently leading to physical and psychological dependence, with considerable economic consequences. The aim of our study was to perform a cost-of-illness analysis for RA according to the four different levels of functional RA severity. METHODS: Direct costs (hospitalisations, treatments, diagnostics and the non-medical costs), indirect costs (productivity losses and informal care), and intangible costs (deterioration in the quality of life of patients, their families and friends assessed by the Medical Outcome Survey Short Form and the Stanford Health Assessment Questionnaire) were measured in 200 RA patients. RESULTS: The social costs--direct plus indirect costs--increased as RA worsened. The direct costs increase very significantly (p < 0.0005) among the four functional classes (respectively Euro 1643.4 - 2910.2 - 4236.5 - 5696.8), likewise the indirect costs (respectively Euro 2704.9 - 9566.4 - 12183.1 - 17249.2). Moreover social costs, analysed independently from the functional classes, are significantly higher in patients with other concomitant diseases. As far as the intangible costs are concerned, for all the areas explored by the scales used, the high impact of RA on the quality of life of RA patients was markedly evident. Female gender and co-morbidity are associated with higher costs. CONCLUSIONS: In Italy, the indirect costs account for the highest cost for management of RA patients. Considering that costs increase with RA progression, the patients who show a rapid evolution of the functional damages should be identified early based on risk indicators.

[Central nervous system involvement in patients with HCV-related cryoglobulinemia: literature review and a case report]. / Manifestazioni neurologiche centrali in corso di crioglobulinemia HCV correlata: revisione della letteratura e caso clinico.

INTRODUCTION: Few well-documented cases of central nervous system involvement in patients with mixed cryoglobulinemia and/or HCV infection have been reported. We can distinguish between acute or subacute diffuse and focal lesions (transient ischemic attack-like syndromes and cerebrovascular accidents). METHODS: A search of two electronic databases (Medline and EMBASE) was conducted from the year of their inception (1966 for Medline and 1988 for EMBASE) to September 2000. The search strategy employed entailed combining these terms: Cryoglobulinemia, Central Nervous System, Hepatitis C, Chronic Hepatitis. Cryoglobulinemia and Central Nervous System were also used as free test words. We analysed articles with case reports and the most frequent articles on the references list. PATHOGENESIS: The main pathophysiologic mechanism of cerebral involvement is ischemia (or rarely hemorrhage) due to diffuse or segmental vasculitis of the small cerebral vessels. In these cases a brain MRI usually shows single or multiple increased T2 signals. Furthermore an occasional occlusive vasculopathy without vasculitis was documented histologically. In these patients ischemia could be started or enhanced by the engorgement of the microvasculature by clumps of red cells and by aggregates of cryoglobulins. In the same patients vasculitis and hemorheological abnormalities can affect the clinical picture of the cerebral involvement in mixed cryoglobulinemia. Finally, the detection of HCV in the lesions induces a hypothesis that, in some cases, CNS involvement could be directly related to chronic HCV infection, even in the absence of cryoglobulin production. CASE REPORT: We describe a 63 year-old woman with acute severe encephalopathy. Laboratory evaluation revealed a high positive test result for rheumatoid factor (3390 U/ml) and hypocomplementemia (C4 less than 1.67 mg/dl). Protein immunofixation electrophoresis demonstrated 5% monoclonal proteins (IgM/k and IgG/k), 3% cryoglobulins were present, HCV antibody and HCV-RNA (type 2a-2c) were positive. Cryoglobulins were never typed, because they disappeared after plasma exchanges. Liver enzymes, renal function and findings on cerebrospinal fluid were normal. Cerebral CT and MRI were also normal. Antinuclear antibodies, anti nDNA antibodies, antiphospholipid antibodies, lupus anticoagulant, ANCA, Lyme disease serology, complete tests for thrombophilia were negative. Bone aspiration was normal. The patient, in coma, was treated with two plasma exchanges. During the first treatment she recovered consciousness. Prednisone (1 mg/Kg/day) and cyclophosphamide (400 mg iv for three days) were added. After a week two plasma exchanges were performed again. Liver enzymes and rheumatoid factor were analysed monthly for six months and than every two months for another six month period up to the present. Liver enzymes were always normal, rheumatoid factor was always at a lower level than the first evaluation (now it's 311 U/ml). At present she is taking Prednisone 5 mg once a day, neurologic symptoms are absent and neurologic examination is normal. DISCUSSION: We can conclude that: central neurologic involvement may be the clinical presentation of HCV infection and mixed cryoglobulinemia. HCV serologic tests and cryoglobulins should be considered in patient with encephalopathy of non-obvious cause; plasma exchange is the treatment of choice in acute severe forms; in some patients HCV could involve directly CNS, even in the absence of cryoglobulin production.

[Multiple Sclerosis and autoimmune diseases: clinical cases and review of the literature] / Sclerosi multipla e malattie autoimmuni: casi clinici e review della latteratura.

Multiple sclerosis (MS), the most frequent demyelinating disease in adults, is thought to be an autoimmune disease. Symptoms and signs observed in MS reflect lesions present mainly in the white matter of the central nervous system (CNS). The diagnosis remains difficult, at least concerning presenting symptoms, because of their low specificity. Diagnosis criteria are usually based on dissemination of signs in time and space, evoked potentials, findings of magnetic resonance imaging, results of cerebrospinal fluid examination, and the exclusion of other diagnosis possibly explaining the clinical signs. However, no clinical and paraclinical investigation can distinguish with certainty MS from other conditions such as autoimmune or inflammatory diseases predominantly affecting the central nervous system. These other disorders include systemic lupus erythematosus, antiphospholipid syndrome, Behçet disease, Sjögren syndrome, sarcoidosis and vasculitides. We present four clinical cases showing the difficulty in reaching a proper diagnosis.

Efficacy and tolerability of ketoprofen 200 mg controlled-release cps vs indomethacin 50 mg cps in patients with symptomatic hip osteoarthritis. A multicentre study.

BACKGROUND: An open-label, randomised, multicentre study was carried out to compare the efficacy and tolerability of indomethacin capsules and ketoprofen controlled-release capsules in the symptomatic treatment of coxarthrosis. MATERIALS AND METHODS: 113 out-patients were enrolled: 57 were assigned to receive indomethacin 50 mg twice daily and 56 ketoprofen 200 mg once daily for 4 weeks. RESULTS: Indomethacin and ketoprofen proved equally effective in relieving osteoarticular pain and stiffness and in improving the quality of life of patients. There was essentially no difference as to gastrointestinal adverse events which occurred in 25% of patients on indomethacin and in 27% of those on ketoprofen. Indomethacin caused more non-gastrointestinal untoward effects, especially CNS effects (headache and dizziness: 11%) which were not observed with ketoprofen. Indomethacin was discontinued because of adverse events in a larger proportion of patients (20%) than ketoprofen (11%).

Non-Hodgkin's lymphoma with rheumatism-like presentation and multiple cystic and nodular lesions in the liver.

We report the case of a non-Hodgkin's lymphoma in an isolated and not previously diagnosed "adult polycystic liver disease". In this case, a rheumatism-like presentation was associated with the discovery of multiple nodular and cystic lesions in the liver. Of these, the former were related to lymphoma involvement, the latter to pre-existent liver disease. The singularity of the case, not previously reported, and some difficulties met in diagnosing the two pathologies, justify the report.