There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. However, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than rheumatoid factor in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency always causing hyperuricemia presents various degrees of neurological manifestations, the most severe which is Lesch-Nyhan syndrome. The HPRT gene is situated in the region Xq26-q27.2 and consists of 9 exons. At least 300 different mutations at different sites in the HPRT coding region from exon 1 to exon 9 have been identified. A new mutation in the HPRT gene has been determined in one patient with complete deficiency of erythrocyte activity, with hyperuricemia and gout but without Lesch-Nyhan disease. Analysis of cultured fibroblasts revealed minimal residual HPRT activity mainly when guanine was the substrate. Genomic DNA sequencing demonstrated patient's mother heterozygosity for the mutation and no mutation in her brother. The mutation consists in a C-->T transversion at cDNA base 463 (C463T) in exon 6, resulting in proline to serine substitution at codon 155 (P155S). This mutation had not been reported previously and has been designated HPRT(Sardinia). The mutation identified in this patient allows some expression of functional enzyme in nucleated cells such as fibroblasts, indicating that such cell type may add further information to conventional blood analysis. A multicentre survey gathering patients with variant neurological forms could contribute to understand the pathophysiology of the neurobehavioral symptoms of HPRT deficiency.

OBJECTIVE To estimate the prevalence of rheumatoid arthritis in an Italian general population. METHODS The study was conducted in the years 2002-2003 in Tempio Pausania's health district located on the North Sardinia and involved 30264 subjects aged 18 years or more treated by 29 general practices (GP). The GP was contact first by phone and letter and secondly a Rheumatologist administered a structured interview that included a screening questionnaire for RA. Cases were defined by the 1987 American College of rheumatology criteria adapted to epidemiological surveys. Every cases were examined by Rheumatologist and General practices together. The age and sex distribution of the sample were similar to those of the Italian population from the 2001 census. RESULT Of the 141 subjects who fulfilled the inclusion criteria, there were 113 women and 28 men, with a mean age at diagnosis of 45 years. The prevalence of RA was 0,46% in the general population, 0,73% in women and 0,19% in men. CONCLUSION Our results suggest that the prevalence of RA is comparable to that reported in other Mediterranean countries. Women are more affected than men. Our prevalence is higher than that observed in Chiavari in 1992.

SUMMARY There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. Hower, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than FR in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).

Transforming growth factor-β1 (TGF-β1) is a potent multifunctional polypeptide that is involved in normal renal function and in the development of glomerular sclerosis. It is also an important mediator of the immune and anti-inflammatory responses.The purpose of this study was to examine whether the measurement of urinary TGF-β1 excretion in patients with different types of renal diseases and in newly diagnosed type 1 diabetes mellitus represents a non-invasive tool to evaluate disease activity and to monitor response to therapy.We studied the urinary excretion of TGF-β1 in 57 nephropathic patients divided in different groups according to the underlying disease: 15 had mesangial glomerulonephritis (IgAGN), 9 membranous glomerulonephritis (MGN), 7 rapidly progressive glomerulonephritis (RPGN), 8 systemic lupus erythematosus (SLE), 9 interstitial nephritis (IN), 9 chronic renal failure (CRF). TGF-β1 was also measured in 38 patients with type 1 (insulin-dependent) diabetes mellitus (12 with newly diagnosed diabetes, 26 long-standing diabetes) and 31 healthy controls. Total urinary TGF-β1 concentration was assayed by enzyme-linked immunoassay (ELISA), and expressed as a ratio to urinary creatinine concentration. The urinary TGF-β1 levels were compared with the findings of biopsy and clinical parameters.Urinary TGF-β1 excretion was significantly increased in all groups except MGN, IN and CRF. In non-diabetic patients, urinary TGF-β1 levels correlated with crescent formation, floccular adhesion and mesangial proliferation, but not with the degree of tubulo-interstitial fibrosis. Urinary TGF-β1 levels did not correlate with indices of renal function (serum creatinine, glomerular filtration rate (GFR), albumin excretion rate [AER]). Among diabetic patients, HbA1C significantly correlated with TGF-β1 urinary excretion.Urinary TGF-β1 levels may represent a valid indicator of acute glomerular flogosis associated with mesangial proliferation in glomerulonephrities. In newly diagnosed diabetic patients, hyperglycaemia seems to represent the principal factor leading to TGF-β1 overproduction. Follow-up studies of urinary TGF-β1 levels measured during optimal glycaemic control are necessary to clarify the relationship between hyperglycaemia and TGF-β1 excretion.

Different degrees of hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency are associated with hyperuricemia, uric acid nephrolithiasis and severe gout. Up to 25-30% of HPRT deficient patients, indicated as neurological variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may develop neurological manifestation, from mild to severe; the most serious ones manifesting in the devastating Lesch-Nyhan syndrome, characterized by choreoathetosis or self-mutilation. Here we present a 30 years old male patient suffering from gout and mild psycho-motor impairment without Lesch Nyhan disease despite severe HPRT deficiency residual activity 0.02% with hypoxanthine, no activity at all with guanine as a substrate. The Curto's theory that neurologic impairment is dependent on VGPRT/VHPRT ratio is not confirmed by our observations. The finding of such a severe HPRT deficiency in a non-Lesch-Nyhan patient needs further investigation. G6PD deficiency was also referred together with beta-thalassemic trait. We have studied purine and pyridine nucleotide metabolism in the erythrocytes and discussed the literature. The bone marrow sample shows a megaloblastyc aspect.

Sarcoidosis is a systemic granulomatous disease of unknown etiology that has a wide variety of clinical manifestation. Lung involvement may slowly undergo pulmonary fibrosis. Chronic sarcoid arthritis is a rare, usually non destructive arthropathy; may be a mono, oligo or polyarthritis. Knees, ankles, shoulders, wrists and small joint of the hands and feet may be involved. It can involve skin, eyes, exocrine glands such as salivary and lacrimal glands, and many other tissues. We describe the case of a 77 years old woman with a history of rhinopharyngitis with epistaxis and chronic laryngitis since youth; a dry mouth and throat, a erythematous, infiltrative skin lesion in the forehead and in the nape of the neck, a purple lesion of the left ear and nose, skin dystrophy of the hands from 30 years before. She underwent an operation for a left femoral fracture with hemotransfusion 14 years ago. Then she developed a polyarthritis of the small joints of the hands (II, III and IV right DIP, I, III, e V left DIP; III and V bilateral PIP), knees, tarsi, toes and left elbow. An HCV chronic hepatitis was discovered 6 years before. She is affected by productive cough, dysphonia, dyspnoea at rest, fever, headache and asthenia for over 5 years. Laboratory examination revealed leukopenia, HCV hepatitis with anti HCV, HCV-RNA, transaminases elevated and cryoglobulinemia. HCV may be involved in the etiopathogenesis of rheumatic diseases, lung fibrosis and may moreover contribute to the onset or progression of sarcoidosis; the possible pathogenesis is discussed.

Background Adult onset Still’s disease (AOSD) was first described by Bywaters in 1971. Subsequently more than 300 cases have been reported. AOSD is a systemic inflammatory disease with high spiking fever, a typical rash and arthritis or arthralgia as major clinical features. The disease is accompanied by a neutrophylic leukocytosis. Other common features are sore throat, intensive myalgias, lymphoadenopathy, hepatosplenomegaly, pericarditis and pleuritis. A 48 years old white woman recently presented to our observation. She had been in her usual state of good health until 7 years before, when she developed fever, arthralgias, sore throat and euthyroid non-toxic goitre. Thyroid antibodies (Thyreoglobulin, microsomal, peroxidase) were elevated. She was diagnosed to have autoimmune thyroiditis and was treated with l-thyroxine and prednisone 25 mg daily. She has done well until eight months ago when she developed fever, arthralgias, sore throat and myalgias. One month later she was admitted to her local hospital with spyking fever of 39,0°C, pleuritic chest pain, dyspnea, hepatomegaly, palpitations, fatigue and weight loss. Chest radiograph revealed bilateral pleural effusion and echocardiogram demonstrated pericardial effusion. A thoracentesis removed 30 ml of pleuric fluid, wich had the characteristic of an exudate. Ultrasound abdominal investigation revealed mild hepstomegaly. Once with the fever spike (40°C) a mildly pruritic maculopapular evanescent rash located on the extremities was observed and interpreted as drug induced. Laboratory examination revealed haemoglobin 10,2 g/dl, Erythrocyte mean corpuscolar volume 71,2 fl, platelet count 628’000/mmc, White blood cell count 30’640/mmc with 96% neutrophils, ESR 76 mm/h, CRP 32,7 mg/dl, Rheumatoid Factor 121,0 UI/ml. ANA, ENA, ANCA, ACA and anti-DNA were normal. There was no serological evidence for active o recent infection and blood coltures were negative. Malignancies were excluded. There was no response to empiric antibiotics. Therapy with NSAIDs failed. Treatment with 3,5‑4,0 mg/Kg daily Cyclosporine for three months was ineffective. Prednisone 50 mg daily resulted in resolution of fever, systemic manifestations, sore throat and normalisation of her laboratory tests, including Rheumatoid Factor. Rheumatic diseases are, more frequently than suspected, associated with autoimmune thyroiditis. To our knowledge this is the second reported case of association between AOSD and autoimmune thyroiditis. Test for Rheumatoid Factor, ANA and other autoantibodies are generally negative in AOSD. Some criteria for the diagnosis of AOSD consider a positive Rheumatoid Factor as an exclusion criteria. But it may be positive in a transient manner in up to 4 to 6% of those patients. Objectives Methods Results Conclusion

OBJECTIVE:Several investigations indicate that glycosaminoglycans (GAG) are important components of the glomerular basement membrane (GBM) and that they play a remarkable role in the control of charge-selectivity in the glomerular capillary wall. In order to evaluate the possible use of GAG as a marker of glomerular disease, we evaluated urinary GAG excretion in 37 patients with systemic lupus erythematosus (SLE) grouped by disease activity and kidney involvement and in 17 healthy controls.METHODS:GAG were isolated from urine by using ion-exchange chromatography on DEAE Sephacel. GAG composition was determined by cellulose acetate electrophoresis and expressed as relative percentages by densitometric scanning of Alcian Blue stained strips.RESULTS:Total GAG levels were significantly increased only in active extra-renal SLE patients. Qualitative analysis of urinary GAG revealed the presence of a low sulphated chondroitin sulphate-protein complex (LSC-PG), whose frequency was higher in patients compared to controls. Moreover, inactive SLE was characterized by an alteration of the chondroitin sulphate/heparan sulphate ratio.CONCLUSION:These variations suggest the presence of an abnormal permeability of the renal filter in patients without other appreciable signs of kidney alteration. Therefore, qualitative-quantitative urinary GAG analysis could represent an additional diagnostic approach.

Gastrointestinal symptoms and lesions are often associated with the clinical use of non-steroidal antiinflammatory drugs (NSAIDs). An open-label, single arm multicenter Italian study evaluated if misoprostol, a prostaglandin E1 analogue with gastroduodenal mucosal protective activity, was effective in the prevention and treatment of NSAID-induced gastroduodenal lesions. Patients affected by rheumatoid arthritis (RA) or osteoarthritis (OA), in treatment with NSAIDs and suffering from gastric symptoms or gastroduodenal lesions related to NSAID use, were admitted to the study. Gastrointestinal and arthritic symptoms were assessed before and after 4 weeks co-administration of an NSAID (the most frequent was diclofenac, used in 35% of the RA and in 22% of the OA patients, followed by piroxicam and tenoxicam respectively) + misoprostol (200 mcg two times daily in 58% of the cases, 200 mcg three times daily in 39%, 200 mcg four times daily in 3%). On admission and after 4 weeks of therapy a gastrointestinal endoscopy was performed to evaluate the condition of the gastroduodenal mucosa. Final results showed that: (i) NSAID-related gastric lesions were more frequent than duodenal lesions; (ii) when patients were given misoprostol and NSAIDs, 96% of them did not develop gastric lesions and 97% did not develop duodenal lesions; (iii) even when NSAID therapy was continued, gastric or duodenal lesions induced by NSAIDs healed or in any case did not worsen in 92% and 91% respectively of the cases; (iv) during the period of coadministration of NSAIDs+misoprostol, NSAID-related UGI symptoms disappeared or improved in 77% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic urate nephropathy in the past decades was a frequent cause of renal failure in gouty patients but this entity has become very rare in the recent years and in many centers of hemodialysis the registries of chronic renal failure populations do not list gouty nephropathy as a cause. Some authors even discuss the existence of gouty nephropathy (1). In our series of 140 patients with primary gout (128 M, 12 F) including 20 patinets with late onset (over 65 years) of the disease (15 M, 5 F) we never observed renal insufficiency with serum creatinine over 1.5 mg/dl; but the urate nephropathy exist also as a rare familial form, inherited in a autosomal dominant manner and, more rarely, as an idiopathic form, without clinical evidence of gouty arthritis. Recently we observed an idiopathic form of this disease in a male patient, 51 years old, who presented a middle renal insufficiency (serum creatinine over 2.0 mg/dl and albuminuria). Ultrasonic kidney study and C.A.T. have shown numerous microcysts in the cortical of the kidney, but only the needle biopsy has confirmed the urate nature of the interstitial chronic nephropathy. 1- L.H. Beck Kidney Int. 30 (1986) 280-286.

The behaviour of gamma-GT, an enzyme whose activity is related with alcohol intake, was studied in three groups of patients with primary gout, divided on the basis of alcohol intake. Poor drinkers (A) and good drinkers (B) do not show significant differences in the serum levels of gamma-GT, uric acid and triglycerides. The above parameters are highest in the group of strong drinkers (C), in which the increase in serum gamma-GT activity is statistically significant and reaches values above the normal range.

We observed late onset - over 65 years of age - of gout in 15 patients or in 14% out of 104 patients. Comparative studies of clinic and physiopatological manifestations of these 15 patients revealed the following: - prevalence of females was higher (26.5%), familial incidence of: the disease was present only in 6%, overweight was uncommon (13%). In most cases hyperuricemia was present (mean value 8.3 mg%), with significant reduction of uric acid clearance (mean value 6.7 ml/min) while uricosuria was normal (mean value 672 mg/24h.) The site of initial attack was the first metatarsal falangeal joint (podagra) in 60%. Tophi were never found. Renal calculi were observed only in 2 cases (13%). Cholesterol and tryglicerides mean levels were normal meanwhile significantly lower levels of HDL-Cholesterol and of Apo-A Lipoproteins were observed in patients with coronary heart disease (20%). Hypertension was present in 33% of the patients. In these patients levels of ionized calcium were significantly lower (mean value 2.04 mEq/1) than in patients with normal blood pressure (mean value 2.18 mEq/1).

Lipoprotein abnormalities are common in gout. The most frequent is hypertriglyceridemia, which has been reported in three-quarters of patients with primary gout (1, 2). This alteration may or may not be related to obesity, alcohol consumption, and glucose intolerance (3). Patients with gout secondary to lead nephropathy do not have hypertriglyceridemia (4).