Italian evidence-based recommendations for the management of ankylosing spondylitis: the 3E Initiative in Rheumatology.

OBJECTIVE: The 3E (Evidence, Expertise, Exchange) Initiative is a multinational effort of rheumatologists aimed at developing evidence-based recommendations addressing specific questions relevant to clinical practice. The objective of the Italian part of the 3E Initiative was to develop new recommendations designed to help Italian rheumatologists in everyday clinical practice management of patients suffering from ankylosing spondylitis (AS). METHODS: An international scientific committee selected a set of questions concerning the diagnosis, monitoring, and treatment of AS using a Delphi procedure. Evidence-based answers to each question were sought by a systematic literature search in MedLine for papers published up to August 2006. A panel of 55 Italian rheumatologists with expertise in the field of AS used the evidence thus gathered to develop recommendations, filling gaps in evidence with their expert opinion. RESULTS: After discussion and votes, the panel developed 12 statements/recommendations: 3 concerning diagnosis (low back pain approach, early diagnosis, and GPs referral recommendations); 3 concerning monitoring (disease activity, severity, and prognosis), and 6 concerning treatment (bisphosphonates role; treatment of enthesitis; inter-agent safety/efficacy, long-term safety/efficacy, efficacy on different disease manifestations, and the role on inflammatory bowel disease flare precipitation of NSAIDs/COX-II inhibitors). CONCLUSION: Italian recommendations for the management of AS in everyday practice were developed. Their dissemination and implementation in daily clinical practice should help to improve practice uniformity and eventually optimize the management of AS patients.

Anti-GM1 and anti-sulfatide antibodies in patients with systemic lupus erythematosus, Sjögren's syndrome, mixed cryoglobulinemia and idiopathic systemic vasculitis.

OBJECTIVES: Over the last two decades, increasing interest has been focused on the association between autoimmune polyneuropathies and anti-neuronal autoantibodies in immune-mediated polyneuropathy. The possible appearance of these autoantibodies in systemic diseases that are not limited to the nervous system has not been fully addressed yet. METHODS: We evaluated 32 patients with systemic lupus erythematosus, 34 patients with hepatitis C virus-associated mixed IgM-k/IgG cryoglobulinemia, 19 with small vessel ANCA-associated vasculitis, and 20 patients with Sjögren's syndrome by means of an immunoenzyme method of anti-neuronal autoantibody detection. RESULTS: As compared to normals, a significant increase (p < 0.001) in plasma titers of both IgM and IgG anti-GM1 ganglioside and IgM and IgG anti-sulfatide was observed in patients with systemic lupus erythematosus, mixed cryoglobulinemia and Sjög-ren's syndrome. Idiopathic systemic vasculitis patients were found to have significantly increased levels of anti-sulfatide IgG autoantibodies (p < 0.001). Clinical and electrophysiologic studies revealed that abnormal titers of anti-neuronal antibodies were associated with evidence of neuropathy in patients with systemic lupus erythematosus and ANCA-related vasculitis (p < 0.05) as well as in patients with mixed cryoglobulinemia and Sjögren's syndrome (p < 0.001). CONCLUSION: Anti-GM1 and anti-sulfatide antibodies are frequently found in patients with small vessel ANCA-associated vasculitis and other multi-organ immune-mediated diseases. Upon detection of these antibodies, accurate neurologic examination should be carried out due to the significant association that can be found between these serologic abnormalities and the involvement of the peripheral nervous system as also detected by electrophysiologic studies. This study supports the unexpected possibility that anti-neuronal reactivity may be a direct trigger of neurologic injury in these systemic disorders.

[Italian Society of Rheumatology (SIR) recommendations for performing arthrocentesis]. / Raccomandazioni della Società Italiana di Reumatologia per l'esecuzione dell'artrocentesi.

Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR) produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a) arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b) the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c) ultrasonography should be used to facilitate arthrocentesis in difficult joints; d) fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e) careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f) contraindications are the presence of skin lesions or infections in the area of the puncture; g) the patient's anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h) joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts' opinion rather than on published evidence which is scanty.

[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.

Intravertebral vacuum cleft: notes on five cases.

Analysis of five personal cases of the intravertebral vacuum cleft phenomenon and a close examination of the literature, suggest that it is rather more frequent than it first appears. Intravertebral vacuum cleft tends to occur more readily in the vertebrae of the dorsolumbar hinge and mainly in the elderly, slightly more common in women than men. The main factors, from the pathogenetic point of view, are osteoporosis, a history of trauma and frequent occurrence of rheumatic problems which are often complicated by vasculitis. The comparison between excessive uptake of calcium-mimetic technetium and uptake deficit of technetium phytate by the vertebra with a vacuum cleft, leads us to consider it as an expression of osteo and bone marrow necrosis.

Primary biliary cirrhosis and rheumatic diseases: a clinical, immunological and immunogenetical study.

Clinical investigation of Primary Biliary Cirrhosis (PBC) patients showed an elevated frequency of rheumatic disorders, as well as their frequent appearance in asymptomatic PBC. Anticentromere region antibodies in PBC patients were pathognomonic for concomitant complete or incomplete CREST syndrome. These antibodies were only found on the HEp2 cell substrate. The constant finding of immune-complexes (IC) with IgM antibody component suggests that they play a role in the pathogenesis of PBC. No statistically significant correlation was found between the amount and classes of circulating IC, HLA class I antigens and rheumatic disorders during PBC.

HLA antigens and clinical manifestations in Crohn's disease.

A clinical, radiological and immunogenetical study was carried out on 51 Crohn's patients. Rheumatological disorders were found in 16 of them, with higher frequency in those with colon involvement only. A statistically significant increase in the frequencies of HLA-A9 and HLA-Cw3 was noted: Cw3 showed a particularly high frequency in males, and A9 in younger patients. The frequency of HLA-B27 was significantly increased in the patients with colon involvement. In the group of 16 patients with rheumatic diseases HLA antigen frequencies were not significantly different from the control population.

Lupus anticoagulant and thrombosis: role of von Willebrand factor multimeric forms.

OBJECTIVE: Patients with lupus anticoagulant (LA) have an increased incidence of venous and arterial thrombosis whose pathogenesis is still unclear. High molecular weight von Willebrand Factor (vWF) multimers seem to play a causal role in shear stress-induced platelet aggregation and thrombus formation. We studied whether in patients with LA, alterations in the vWF multimers might coexist. METHODS: The multimeric composition of plasma vWF was analysed by SDS-electrophoresis and immunoblotting in 43 subjects positive for LA. About 2/3 of the patients had had either ischemic stroke, recurrent abortions, deep vein thrombosis (DVT) or a combination of these; the remaining subjects had never had any thrombotic events. RESULTS: An abnormal vWf multimeric pattern was found in 16 patients (37.2%); no correlation was found with the diagnosis, but the presence of abnormal vWF significantly correlated with the site of the thrombosis: indeed, it was never detected in subjects with DVT, but was found in 71.4% of patients with multiple abortions, in 50% of those with stroke and even in 25% of non-thrombotic patients. CONCLUSION: The hypothesis is put forward that abnormal VWF may represent an additional risk factor to LA for arterial thrombosis.

[Chronic HCV hepatopathy and cryoglobulinemia. The associated clinical spectrum]. / Epatopatia cronica da HCV e crioglobulinemia. Lo spettro clinico associato.

BACKGROUND AND AIM: The hepatitis C infection (HCV) has numerous extrahepatic manifestations owing to the systemic nature of the infection itself. HCV infects the cells that carry a CD 81 receptor and show a marked tropism for hepatocytes, bone marrow staminal cells and circulating lymphomonocytes. One consequence of this tropism is the activation of B lymphocyte clones with the consequent production of autoantibodies and cryoglobulins. The secondary event is the formation of circulating immune complexes which, having precipitated at an intravascular level, may cause part of the extrahepatic manifestations associated with these infections. METHODS: This retrospective study evaluated the manifestations correlated and/or associated with HCV hepatitis and mixed cryoglobulinaemia. RESULTS: This analysis showed that 75% of consecutively studied patients reveal clinically important extrahepatic manifestations. CONCLUSIONS: This underlines the "broad spectrum" action played by the hepatitis C virus in the host organism.

[Pain patterns in Italian patients with osteoarthritis: preliminary results of the MI.D.A. Study (Misurazione del Dolore nell'Artrosi)]. / Caratteristiche del dolore in pazienti italiani con artrosi: risultati preliminari dello Studio MI.D.A. (Misurazione del Dolore nell'Artrosi).

OBJECTIVES: To evaluate the characteristics of pain in a cohort of Italian patients with osteoarthritis (OA) of the hip and knee. METHODS: The 657 general practitioners participating in the study were asked to enroll 10 consecutive patients with OA diagnosed according to the American College of Rheumatology (ACR) clinical criteria. A questionnaire evaluating demographic data, clinical characteristics of OA, including the "Questionario Semantico Reumatologico" (QSR) pain questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Lequesne indices, and information on previous diagnostic and therapeutic interventions was administered. RESULTS: A total of 4,109 patients were enrolled. Of them, 2356 were affected by knee OA and 1817 by hip OA. There were 2863 (69.7%) women and 1246 (30.3%) men. Median age was 68.2 years (range 50-103 years). Of the 4109 enrolled subjects, 3128 (76.1%) reported one or more medical comorbidities, mostly cardiovascular (52.7%), endocrinological (14.7%), gastrointestinal (13.4%), and respiratory (11.2%) disorders. The median pain visual analogue scale (VAS) score was 58.1+/-22.6 mm, higher in women (60.2+/-22.3 mm) than in men (53.3+/-22.6mm) (p<0.00001). OA pain was also higher in patients from Southern Italy (p<0.00001). NSAIDs were administered to nearly 70% of patients, COX-2 inhibitors to 55%, disease-modifying anti OA drugs to 19% and analgesics to 28.2%. Differences in drugs utilization were associated with OA localization and patient's geographical origin. Results of the WOMAC index were similar throughout groups. Responses to the QSR pain questionnaire showed differences, which are related to OA localization and geographical origin of the patients. CONCLUSIONS: The MI.D.A. study can help to better understand the patterns of pain in osteoarthritis and the associated treatment.

[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.

Family studies and HLA typing in ankylosing spondylitis and sacroiliitis.

The families of 21 ankylosing spondylitis (AS) and 16 sacroiliitis (SI) patients were investigated and typed for HLA markers. The association of HLA B27 with AS was confirmed, but no strong evidence for the same or other HLA markers being associated with SI was found. Inheritance patterns in families were analyzed according to the multifactorial and monofactorial models. It is proposed that a major gene associated or interacting with the B27 product controls the susceptibility to AS, and that this gene behaves as a dominant with incomplete penetrance. The problem as to whether linkage disequilibrium maintained by selective pressure, or functional epistasis between the "disease gene" and the B27 antigen may be the acting mechanism of association, remains to be elucidated.

Spondylodiscitis and ankylosing spondylitis: HLA typing and nosological implications.

Nine cases from among 64 patients with ankylosing spondylitis (AS) are described. In addition to bilateral sacroiliitis these cases had a peculiar type of spondylodiscitis characterised by quite diffuse and marked sclerosis of multiple vertebral bodies, with only minimal erosions of the adjacent vertebral plates while classical syndesmophytosis was absent. The antigen HLA-B27 was found only in 1 of these 9 cases. This type of spondylodiscitis could discriminate among all the patients with AS a subgroup with a peculiar clinical pattern and a probably distinctive pathological mechanism.

Sacroiliitis and HLA. A clinical and genetical study.

Among 39 patients (23 males, 16 females) with sacroiliitis (SI) 17 were HLA-B27 positive. The female/male ratio in the B27-positive group was 2/15. Seventy-four first-degree relatives of 26 probands were also investigated. A high occurrence of SI (20%) was observed in the families of B27-positive probands compared with only 3.7% in the families of B27-negative probands. In the former families SI occurred only in B27-positive subjects with an earlier onset of symptoms and a male prevalence. In the latter, the disease showed a later onset and a lack of male preponderance. The nosological and prognostic relevance of the B27 typing is stressed.