Rheumatoid Arthritis: Punzi L

Zhang W, Doherty M, Leeb BF, Alekseeva L, Arden NK, Bijlsma JW, Dincer F, Dziedzic K, Hauselmann HJ, Kaklamanis P, Kloppenburg M, Lohmander LS, Maheu E, Martin-Mola E, Pavelka K, Punzi L, Reiter S, Smolen J, Verbruggen G, Watt I, Zimmermann-Gorska I, Anonymous00031. · Dr W Zhang, Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #18250111 No free full text.

Abstract: OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.

Fiocco U, Sfriso P, Oliviero F, Pagnin E, Scagliori E, Campana C, Dainese S, Cozzi L, Punzi L. · Rheumatology Unit, University of Padova, Via Giustiniani 2-35128 Padova, Italy. · Autoimmun Rev. · Pubmed #18718877 No free full text.

Abstract: Associations between rheumatoid arthritis (RA) susceptibility and polymorphism in multiple immunoregulatory genes suggest a role of altered T cell function in the disease. The growing relevance of the oxidative stress in RA synovitis, which results in a number of T cell signalling abnormalities, is reinforced by the demonstration of a direct NO inducing activity through the shared epitope of the HLA class II molecules HLA-DRbeta1, with secondary lymphocytes oxidative damage. Direct T cell/macrophage contact-dependent activation, one of the driving mechanisms of synovitis, is mediated by co-stimulatory molecules as well as cell membrane cytokines and may also result in an impaired suppressive function of T regulatory cells (Treg) in RA joints. The fusion of CTLA4 extracellular binding domain to the Fcgamma1 allows to obtain a soluble CTLA4 receptor, the dimeric recombinant human fusion protein abatacept (CTLA4-Ig). The improved knowledge of the CTLA4-B7 co-stimulation regulatory mechanisms by signals delivered into DCs and Tregs provides multiple potential targets for the abatacept treatment. CTLA4-Ig shows the capacity, either ex vivo or in vivo, to interrupt at multiple steps the ongoing inflammatory and destructive process, and to concur in restoring the immunoregulatory balance in RA.

Efthimiou P, Flavell RA, Furlan A, Gasbarrini G, Gava A, Koné-Paut I, Manna R, Punzi L, Sutterwala FS, Touitou I, Doria A. · Rheumatology Section, Lincoln Medical and Mental Health Center, New York, USA. · Clin Exp Rheumatol. · Pubmed #18570755 No free full text.

Abstract: The autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of seemingly unprovoked inflammation without significant levels of autoantobodies and antigen specific T cells. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been formally established, much ongoing research is aimed towards confirmation of that hypothesis. This article will review recent advances in the study of a subset of NOD-like receptors (NLRs), which control the activation of caspase-1 through the assembly of a large protein complex called inflammasome. Moreover, we will review recent progresses in understanding of a range of autoinflammatory conditions in humans.

Punzi L, Ramonda R, Sfriso P. · Division of Rheumatology, Department of Medical and Surgical Sciences, University of Padova-Policlinico Universitario, via Giustiniani 2, 35128 Padova, Italy. · Best Pract Res Clin Rheumatol. · Pubmed #15454130 No free full text.

Abstract: Erosive osteoarthritis (EOA) is believed to be a clinically uncommon subset of generalized osteoarthritis (OA) characterized by a clinical course, which is frequently aggressive. The diagnosis of EOA is accepted only for patients meeting American College of Rheumatology clinical criteria for OA of the hand and showing radiographic aspects of articular surface erosions. Conditions to be considered in the differential diagnosis include primarily nodal generalized OA, psoriatic arthritis and rheumatoid arthritis. It is possible to find erosive changes resembling EOA in endocrine diseases, microcrystal-induced diseases, chronic renal diseases, autoimmune diseases and others. Despite the absence of a clear etiology, immunogenetic studies are useful in identifying a possible predisposition to developing EOA in some subjects. No definitive therapeutic approach to EOA has been reported. It is reasonable to assume that in the presence of a symptomatic EOA our therapeutic approach should differ from that used for common, nodal, non-EOA.

Punzi L, Betterle C. · Division of Rheumatology, Department of Medical and Surgical Sciences, University of Padova, Via Giustiniani 2, Padova 35128, Italy. · Joint Bone Spine. · Pubmed #15288851 No free full text.

Abstract: A variety of rheumatic manifestations have been described in association with autoimmune thyroiditis. In the past, most of these manifestations were attributed to the underlying thyroid dysfunction, in particular hypothyroidism. However, a responsibility of the mechanisms involved in the autoimmunity rather than a direct action of thyroid hormones seems supported by the evidences that some rheumatic manifestations may occur even in euthyroid patients, or that they are more frequent in hypothyroid patient with autoimmune thyroiditis than in those without this disease. Rheumatic manifestations could be sometimes attributable to the autoimmune rheumatic diseases frequently associated with autoimmune thyroiditis, such as Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, or scleroderma. Among the most important or frequent rheumatic manifestations there are a mild non-erosive variety of arthritis, polyarthralgia, myalgia, and sicca syndrome without a true Sjögren's syndrome. Although the possible pathogenesis of these manifestations is not completely established, some hypotheses may be proposed, including a role of autoantibodies characteristics of autoimmune thyroiditis, a possible overlap between autoimmune thyroiditis and some autoimmune rheumatic diseases, and a systemic inflammatory reaction associated with thyroiditis.

Punzi L, Calò L, Plebani M. · Division of Rheumatology, Department of Medical and Surgical Sciences, University of Padova, Italy. · Crit Rev Clin Lab Sci. · Pubmed #11890208 No free full text.

Abstract: Cytokines are a complex family of small regulatory proteins able to mediate intercellular communication and play a crucial role in immunologic and inflammatory reactions. Many reports have demonstrated that some cytokines, in particular tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1beta, IL-6, and IL-8, so-called proinflammatory, may have a major role in the pathogenesis of joint diseases. Thus, high levels of these substances have been found in inflammatory arthropathies, in particular in those characterized by a more aggressive and destructive outcome, such as rheumatoid arthritis, gout, and infectious arthritis. In keeping with their role, the determination of cytokines in synovial fluid may be proposed for clinical purposes, including diagnostic and prognostic assessments. Furthermore, as some of these cytokines may reflect disease activity, their determination may also be useful in the evaluation of therapy.

Botsios C, Sfriso P, Furlan A, Ostuni P, Biscaro M, Fiocco U, Todesco S, Punzi L. · Cattedra e U.O.C. Reumatologia, Università-Azienda Ospedaliera di Padova, Italia. · Reumatismo. · Pubmed #17435840 links to  free full text

Abstract: OBJECTIVE: We evaluated both the efficacy and safety of anakinra in daily routine rheumatoid arthritis clinical practice. METHODS: We studied 60 cases, including patients with previous anti-TNFalpha exposure, treated with anakinra (100 mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or leflunomide (20 mg/die) in a two year observational study. Efficacy measures were assessed using the American College of Rheumatology (ACR) response criteria. Safety was evaluated according to a modified World Health Organization adverse reaction term dictionary. RESULTS: At week 14, ACR 20% response criteria have been fulfilled by 53 (91.3%) out of 58 patients, 51 (87.9%) of them achieving also an ACR 50%and 15 (25.8%) an ACR 70%response. Thirteen patients touched 102 weeks of treatment: ACR 20% response was achieved in 92.3%, while ACR 50% and ACR 70% were respectively found in 84.6% and 38.4% of the cases. The mean decrease in HAQ score was 0.38, p<0.001. Of the 16 patients who were previously treated with anti-TNFalpha blockers, 81.2% responded to anakinra. There was no significant difference in the ACR response between groups with and without previous anti-TNFalpha exposure. Seventeen patients (28.3%) stopped anakinra because of side-effects (5%) or failure to respond (23.3%). Only 4 cases of pulmonitis, of which 2 have been hospitalised, and 1 case with tuberculosis (previously treated with infliximab) were observed. CONCLUSIONS: Our clinical experience confirms that anakinra is effective and safe in the treatment of rheumatoid arthritis. Anakinra seems also useful in patients with previous anti-TNFalpha blockers failures. Even though major adverse events were rare, clinicians should be aware of such a possibility.

Oliviero F, Sfriso P, Baldo G, Dayer JM, Giunco S, Scanu A, Bernardi D, Ramonda R, Plebani M, Punzi L. · Department of Clinical and Experimental Medicine, University of Padova, Italy. · Clin Exp Rheumatol. · Pubmed #19327233 No free full text.

Abstract: OBJECTIVE: To investigate lipid and apolipoprotein (Apo) levels in synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). METHODS: SF of 44 patients (14 RA, 14 PsA, 16 OA) was tested for Apo A-I, HDL-C, total cholesterol (TC), IL-1Beta, TNF-alpha, white blood cell count (WBC) and polymorphonucleate (PMN) percentage. Blood samples, collected simultaneously to the SF, were examined for Apo A-I, HDL-C, TC, TNF-alpha, serum amyloid A (SAA) and C-reactive protein (CRP). Thirty-three healthy donors served as a control group. RESULTS: Serum levels of Apo A-I, HDL-C and TC were higher in OA as compared with RA, PsA and the control group. The patients with inflammatory arthritis had lower serum levels of Apo A-I and HDL-C than did the controls. Apo A-I concentrations were higher in SF of RA patients, while PsA showed the highest concentration of TC, though not reaching statistical significance. A negative correlation was found between serum Apo A-I and synovial WBC (r=-0.48 p=0.002) and IL-1Beta (r=-0.42 p=0.016). There was a strong positive correlation between the Apo A-I SF/serum ratio and synovial WBC (r=0.73 p<0.001), IL-1Beta (r=0.68 p<0.001) and a weak, yet significant, correlation with serum CRP (r=0.49 p=0.002) and SAA (r=0.41 p=0.008). CONCLUSION: Our study confirms that in RA Apo A-I and TC levels are decreased in plasma and increased in SF, thus suggesting infiltration of HDL particles in the inflamed joint with inhibition of the local production of proinflammatory cytokines. On the other hand, it can be hypothesized that the sequestration of Apo A-I in the inflamed tissue may, in part, account for the reduction of circulating HDL and the excess cardiovascular risk in RA and PsA patients.

Favero M, Schiavon F, Riato L, Carraro V, Punzi L. · Cattedra e UOC di Reumatologia, Università di Padova, 35128 Padova, Italia. · Reumatismo. · Pubmed #19132150 links to  free full text

Abstract: BACKGROUND: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. METHODS: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn't gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (< or =60, >60) and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. RESULTS: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients older than 60. Staphylococcus aureus caused septic arthritis in 70% of cases before 2001, and only in 35,8 % after 2001. Also, after 2001, some infections were caused by more unusual pathogens, prevalently in patients treated with TNFa inhibitors. Instead Streptococcus infections were found only in patients aged 70 and older. CONCLUSION: The incidence of bacterial arthritis has increased in the last six years and there was a modification of microorganisms involved, possibly related to a greater therapeutic aggressiveness. The increased frequency of joint disease and the use of immunosuppressive drugs in patients under the age of 60 could be responsible for a lower synovial white blood cell count in these patients.

Favero M, Schiavon F, Riato L, Carraro V, Punzi L. · Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Italy. · Autoimmun Rev. · Pubmed #18706527 No free full text.

Abstract: Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible functional loss. The reported incidence varies from 2-5 cases/100,000 person-years in the general population to 70 cases/100,000 person-years among patients with rheumatoid arthritis. In fact, individuals with rheumatoid arthritis are at particular risk for developing SA. This may be due to several reasons: joint disease predisposes to bacterial joint colonization and RA itself and its treatment with corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and biological therapies may decrease the immune function required for protection from pathogens. Steroids and DMARDs seem to affect the leukocyte synovial count; indeed, RA patients with SA have a leukocyte count in synovial fluid (SF) lower than patients with SA without underlying rheumatic diseases. The diagnosis of SA in RA patients can be difficult because the development of a hot painful joint is often confused with a relapse of the underlying joint disease leading to delay in diagnosis. For this reason the microscopic analysis and culture of synovial fluid are crucial to exclude septic arthritis.

Frallonardo P, Ramonda R, Salaffi F, Carotti M, Andretta M, Zucchetta P, Dorigo A, Campana C, Contessa C, Iagnocco A, Valesini G, Gerli R, Grassi W, Punzi L. · Cattedra e UOC di Reumatologia, Università di Padova, Via Giustiniani 2, Padua, Italy. · Reumatismo. · Pubmed #18651060 links to  free full text

Abstract: Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune etiology, that affects exocrine glands, in particular salivary and lacrimal glands. Among the diagnostic criteria of SS, imaging techniques play an important role. The aim of our study is to compare three imaging techniques, such as sonography, scintigraphy and sialography in the evaluation of major salivary glands. The use of the these techniques is of great importance for the diagnosis of SS. Sonography is the most frequently used for its prompt execution, non invasivity, great acceptance by the patient and low cost. In the diagnostic patient management of SS, sonography results are eventually confirmed by the other imaging techniques, sialography and scintigraphy.

Salaffi F, Carotti M, Iagnocco A, Luccioli F, Ramonda R, Sabatini E, De Nicola M, Maggi M, Priori R, Valesini G, Gerli R, Punzi L, Giuseppetti GM, Salvolini U, Grassi W. · Department of Rheumatology, Polytechnic University of the Marche Region, Ancona, Italy. · Rheumatology (Oxford). · Pubmed #18565986 No free full text.

Abstract: OBJECTIVE: To compare ultrasonography (US) of salivary glands with contrast sialography and scintigraphy, in order to evaluate the diagnostic value of this method in primary SS (pSS). METHODS: The diagnostic value of parotid gland US was studied in 77 patients with pSS (male/female ratio 3/74; mean age 54 yrs) and in 79 with sicca symptoms but without SS. The two groups were matched for sex and age. Imaging findings of US were graded using an ultrasonographic score ranging from 0 to 16, which was obtained by the sum of the scores for each parotid and submandibular gland. The sialographic and scintigraphic patterns were classified in four different stages. The area under receiver operating characteristic curve (AUC-ROC) was employed to evaluate the screening method's performance. RESULTS: Of the 77 patients with pSS, 66 had abnormal US findings. Mean US score in pSS patients was 9.0 (range from 3 to 16). Subjects without confirmed pSS had the mean US score 3.9 (range from 0 to 9) (P < 0.0001). Results of sialography showed that 59 pSS patients had abnormal findings at Stage 1 (n = 4), Stage 2 (n = 8), Stage 3 (n = 33) or Stage 4 (n = 14), and 58 patients had abnormal scintigraphic findings at Stage 1 (n = 11), Stage 2 (n = 18), Stage 3 (n = 25) or Stage 4 (n = 4). Through ROC curves US arose as the best performer (AUC = 0.863 +/- 0.030), followed by sialography (AUC = 0.804 +/- 0.035) and by salivary gland scintigraphy (AUC = 0.783 +/- 0.037). The difference between AUC-ROC curve of salivary gland US and scintigraphy was significant (P = 0.034). Setting the cut-off score >6 US resulted in the best ratio of sensitivity (75.3%) to specificity (83.5%), with a likelihood ratio of 4.58. If a threshold >8.0 was applied the test gained specificity, at the cost of a serious loss of sensitivity (sensitivity 54.5%, specificity 97.5%, likelihood ratio 21.5). CONCLUSIONS: Salivary gland US is a useful method in visualizing glandular structural changes in patients suspected of having pSS and it may represent a good option as a first-line imaging tool in the diagnostics of the disease.

Scanu A, Oliviero F, Braghetto L, Ramonda R, Luisetto R, Calabrese F, Pozzuoli A, Punzi L. · Cattedra e U.O.C. di Reumatologia, Università di Padova, Padova, Italia. · Reumatismo. · Pubmed #17435844 links to  free full text

Abstract: The study of the pathogenetic mechanisms of rheumatic diseases is in general carried out through "in vitro" systems based on cellular cultures models. The difficulties to achieve fresh human tissue prompted us to develop a simpler method to obtain fibroblast-like synovial cells from synovial fluid (SF). METHODS: SF was collected from the knees of 5 patients with rheumatoid arthritis (RA), 4 with osteoarthritis (OA) and 5 with psoriatic arthritis (PsA). The pellet obtained after centrifugation was resuspended in DMEM/HamF12 containing 10% foetal calf serum, 1% peni-streptomycin, 4 ng/ml of fibroblast grow factor and incubated at 37 degrees C in T25 culture flasks. Synoviocytes were also obtained from fresh synovial membranes (SM) by explants technique. Both types of cells were characterized by immunocytochemistry and their inflammatory response to synthetic monosodium urate crystals was studied through the measurement of nitric oxide (NO). RESULTS: Adherent synoviocytes were obtained from the culture of 2/5 SF from RA, 4/4 SF from OA and 5/5 SF from PsA. Synoviocytes isolated from both SF and SM expressed surface antigens CD90, CD55, and the intracellular prolyl-4-hydroxylase. Morphologically, the cells showed the typical spindle-shape fibroblast-like appearance. NO levels induced by UMS crystals in SF synoviocytes were similar to those obtained in SM synoviocytes. CONCLUSION: Adherent cells obtained from SF showed the phenotype and the reactivity of tissue synoviocytes. Due to the easy accessibility of SF, this method may represents an useful alternative when synovial tissues is not promptly available.

Masiero S, Boniolo A, Wassermann L, Machiedo H, Volante D, Punzi L. · Department of Rehabilitation Medicine, School of Medicine, University of Padova, Padova, Italy. · Clin Rheumatol. · Pubmed #17404783 No free full text.

Abstract: The aim of this study was to asses the effects on pain, disability, and health status of an educational-behavioral joint protection program in a group of moderate-severe rheumatoid arthritis (RA) patients. Eighty-five subjects with RA in treatment with anti-tumor necrosis factor alpha (TNFalpha) drugs (infliximab) were enrolled into the study and randomized into either an experimental group (46, EG) or a control group (39, CG). We organized four EG meetings, which included information on pathophysiology and evolution of RA, joint protection during normal activities of daily living, suggestions on how to adapt the surrounding environment, and self-learning exercises to perform at home. Sociodemographic characteristics and degree of knowledge of the disease, measured by the Health Service Interview (HSI), were recorded at baseline. The outcome measures included the Visual Analogue Scale (VAS), the Arthritis Impact Measurement Scale 2 (AIMS2), and the Health Assessment Questionnaire (HAQ), which were administered at the beginning and end of the trial. Thirty-six patients from the EG (7 men and 29 women; mean age 54.2 years) and 34 from the CG (6 men and 28 women; mean age 52.2 years) completed the trial. No statistical differences in baseline evaluations were found between the two groups. According to the answers given on the HSI, the majority of our patients had poor knowledge of RA and its consequences. After a mean time of 8 months, the patients receiving educational training displayed a significant decrease, compared to the CG, in the VAS (p = 0.001), HAQ (p = 0.000), and physical (p =0.000), symptoms (p = 0.049), and social interaction (p = 0.045) scores on the AIMS2, but not in other items. Our study showed that 8 months after attending an educational-behavioral joint protection program, subjects with moderate-severe RA presented less pain and disability and thus an enhanced health status. This approach may efficiently complement drug therapy in these patients.

Hoxha A, Ruffatti A, Grypiotis P, Podswiadek M, Botsios C, Fiocco U, Punzi L, Todesco S. · Cattedra e U.O.C. di Reumatologia, Università di Padova. · Reumatismo. · Pubmed #16829990 links to  free full text

Abstract: OBJECTIVE: We evaluated the induction and clinical significance of ANA, anti-dsDNA and anti-ENA during infliximab therapy in patients with Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS). METHODS: We tested sera from 30 RA and 30 AS patients before and during treatment with infliximab. ANA and antidsDNA were determined by indirect immunofluorescence and anti-ENA by an "in house" counterimmunoelectrophoresis. Statistical analysis was performed by X2 and McNemar's tests and U-test of Mann-Whitney. RESULTS: Eight of the 30 RA patients and 1 of the 30 AS patients were positive for ANA before treatment with infliximab. Eighteen of the 22 (81.8%) negative patients with RA and 11 of the 29 (37.9%) negative patients with AS became positive for ANA during infliximab treatment. No ANA positive patients became negative during the therapy. The difference between ANA before and after treatment resulted significant in both RA and AS patients (p=0.001). The frequency of anti-dsDNA and anti-ENA did not change significantly from baseline, in both RA and AS patients. Acquired ANA positivity was not associated with clinical signs of lupus syndrome and was not correlated with adverse events. The mean values of ESR and CRP in RA patients who became positive for ANA were significantly decreased (p=0.01 and p=0.02 respectively). CONCLUSIONS: Infliximab treatment induced a significant increase in the frequency of ANA in RA and AS patients. The significance of ANA development in these diseases is at present unknown. The significant decrease of ESR and CRP in RA patients who became positive for ANA after treatment should be investigated in a larger number of patients.

Sfriso P, Oliviero F, Calabrese F, Miorin M, Facco M, Contri A, Cabrelle A, Baesso I, Cozzi F, Andretta M, Cassatella MA, Fiocco U, Todesco S, Konttinen YT, Punzi L, Agostini C. · Department of Clinical and Experimental Medicine, Section of Rheumatology, Centro di Eccellenza per la Ricerca Biomedica, Padova, Italy. · J Immunol. · Pubmed #16456020 links to  free full text

Abstract: Expression of CXCR3-targeting chemokines have been demonstrated in several diseases, suggesting a critical role for CXCR3 in recruiting activated T cells to sites of immune-mediated inflammation. Sjögren's syndrome (SS) is an autoimmune disease characterized by a mononuclear cell infiltrate of activated T cells around the duct in the salivary gland. Analysis of minor salivary gland biopsy specimens from 20 healthy subjects and 18 patients with primary SS demonstrated that CXCR3, in particular, the B form of this receptor, is constitutively expressed by human salivary gland epithelial cells. Salivary gland epithelial cell cultures demonstrated that CXCR3 participate in removing relevant amount of agonists from the supernatant of exposed cells without mediating calcium flux or chemotaxis while retaining the ability to undergo internalization. Although in normal salivary gland epithelial cells, CXCR3 behaves as a chemokine-scavenging receptor, its role in SS cells is functionally impaired. The impairment of this scavenging function might favor chemotaxis, leading to heightened immigration of CXCR3-positive T lymphocytes. These findings suggest that epithelial CXCR3 may be involved in postsecretion regulation of chemokine bioavailability. They also support a critical role for CXCR3 in the pathogenesis of SS and identify its agonists as potential therapeutic targets.

Cervini C, Leardini G, Mathieu A, Punzi L, Scarpa R. · Clinica Reumatologica, Università di Ancona, Italia. · Reumatismo. · Pubmed #16380757 links to  free full text

Abstract: Because there is the impression that psoriatic arthritis is a composite disorder with mild forms close to more severe and aggressive ones, we conducted a multicenter study with the aim of characterizing disease expression in a large cohort of Italian patients. One-thousand-three-hundred-six patients fulfilled inclusion criteria and were analyzed in this study. Psoriasis antedated the onset of arthritis in the majority of the cases (67.7%). More rare was inverse or simultaneous onset which occurred in 17.3% and 15.0% of the cases, respectively. Peripheral articular involvement (mono-oligo or polyarthritis) was recorded in 88.7% of the cases while spondylitis occurred in 11.3%. Peripheral enthesopathies were found in 28.1% of the cases with a marked occurrence in patients with axial involvement (64.5% vs 35.5% in oligo or polyarthritis). Abnormal levels of ESR and CRP respectively occurred in 52.2% and in 52.6% of the cases, while rheumatoid factor was detected in 5.0% of the cases. On the basis of distribution of joint involvement, symmetry and presence of peripheral enthesopathies we recognized three clusters of arthritis. Patients included in Cluster 1 and Cluster 2 showed a severe form of polyarthritis in most of the cases (82.9%), with increased serum levels of inflammatory indices in more than 85% of the cases. Almost all the hospitalized patients (97.1%) were included in this two clusters. They markedly assumed steroids and methotrexate or another DMARD. About half of the patients (51.1%) included in Cluster 3 showed mono-oligo articular involvement. Serum inflammatory indices were increased in 20.8% of the cases while hospitalization occurred only in 2.9% of the cases and NSAIDs were the treatment of choice. The evidence in our country of a large prevalence of severe forms of arthritis needing specific and aggressive approach outlines the requirement of an intense educational action aimed at increasing the awareness of this condition.

Bernardi D, Podswiadek M, Zaninotto M, Punzi L, Plebani M. · Department of Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy. · Clin Chem. · Pubmed #14500601 links to  free full text

This publication has no abstract.

Sfriso P, Ostuni P, Botsios C, Andretta M, Oliviero F, Punzi L, Todesco S. · Department of Medical and Surgical Sciences, Section of Rheumatology, University of Padova, Italy. · Scand J Rheumatol. · Pubmed #12737324 No free full text.

Abstract: OBJECTIVE: To investigate serum and salivary neopterin and interferon-gamma as possible markers of immune system activation in primary Sjögren's Syndrome (pSS). METHODS: Serum and salivary neopterin and interferon-gamma concentrations were determined in 30 untreated patients with pSS and matched with several other clinical and laboratory parameters. RESULTS: The mean concentration of neopterin was significantly higher in pSS patients (8.12+/- 3.36 nmol/L in serum and 9.50 +/-7.61 nmol/L in saliva) than in normal controls (p<0.05). Significant correlations were found between serum neopterin and beta2-microglobulin, serum IgG as well as lip biopsy score. Salivary neopterin concentration was inversely related to Shirmer-I test, tear break-up time and stimulated salivary flow rate. Serum and salivary levels of interferon-gamma were normal and no correlation with the other parameters was found. CONCLUSION: In pSS patients serum neopterin may represent a useful marker of cell-mediated immunity. On the other hand, salivary neopterin seems to reflect theglandular damage.

Berthelot JM, Bernelot-Moens HJ, Klarlund M, McGonagle D, Calin A, Schumacher HR, Combe B, De Bandt M, Drosos AA, Flipo RM, Harris BJ, Kaarela K, Le Goff P, Meyer O, Punzi L, Zerbini CA, Saraux A, Anonymous00207. · Department of Rheumatology, Nantes University Medical School, CHU Nantes, France. · Clin Exp Rheumatol. · Pubmed #12051392 No free full text.

Abstract: OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.

Ostuni P, Botsios C, Sfriso P, Punzi L, Chieco-Bianchi F, Semerano L, Grava C, Todesco S. · Department of Medical and Surgical Sciences, University of Padova, Italy. · Joint Bone Spine. · Pubmed #11858357 No free full text.

Abstract: OBJECTIVE: To assess the prevalence of fibromyalgia in primary Sjögren's syndrome and to evaluate the clinical differences between patients affected with both primary fibromyalgia and primary Sjögren's syndrome and those affected only with primary fibromyalgia. METHODS: Clinical features of fibromyalgia were evaluated in 100 consecutive outpatients with primary Sjögren's syndrome and, as controls, in 90 patients with non-insulin-dependent diabetes mellitus, in 75 patients with primary fibromyalgia and in 30 healthy subjects. RESULTS: Fibromyalgia was recorded in 22% of patients with primary Sjögren's syndrome, in 12.2% with diabetes and in 3.3% of healthy controls. In the primary Sjögren's syndrome group the prevalence was significantly higher than in healthy controls (P < 0.01), but not significantly different than in diabetes. Moreover, primary Sjögren's syndrome with fibromyalgia and primary fibromyalgia patients did not differ with respect to the number of tender points, while the mean pain threshold was lower in the latter (P = 0.05). Purpura, hypergammaglobulinemia, rheumatoid factor, and a focus score > or = 1 on lip biopsy were significantly more frequent in primary Sjögren's syndrome patients without than with fibromyalgia. CONCLUSIONS: As recently reported by other authors, our study confirms the moderate increase of fibromyalgia prevalence in primary Sjögren's syndrome. Typical fibromyalgic findings are quite similar to those of primary fibromyalgia, but surprisingly, primary Sjögren's syndrome patients with fibromyalgia show a less severe global involvement than those with primary Sjögren's syndrome alone.

Berthelot JM, Klarlund M, McGonagle D, Bernelot-Moens HJ, Calin A, Harrison B, Schumacher HR, Kaarela K, Drosos AA, Hülsemann JL, Koh WH, Konttinen YT, Punzi L, Tanimoto K, Williams HJ, Wolfe F, Zerbini CA, Saraux A, Anonymous00239. · Department of Rheumatology, Nantes University Medical School, CHU Nantes, France. · J Rheumatol. · Pubmed #11361225 No free full text.

Abstract: OBJECTIVE: To determine how experts would classify 10 early-arthritis cases (7 atypical) and to study discrepancies in diagnoses relative to ACR criteria for rheumatoid arthritis (RA) or ESSG criteria for spondyloarthropathy (SpA). METHODS: Ten real cases (5 met ACR criteria for RA, 6 ESSG criteria for SpA, 3 both and 2 neither) followed for 28.5 +/- 4.8 months were sent as paper cases to 20 international and 12 French experts. Each expert selected a diagnosis among 8 possible choices and rated it on a 0-10 confidence scale. For each case, 3 analog scales (0-100 mm) were used to indicate the probability of RA, SpA or undifferentiated arthritis (UA). RESULTS: Experts often disagreed about diagnoses (up to 5 different diagnoses for a given case, with a mean of 3.9 per case). Similarly, expert opinions on probabilities for RA and SpA differed widely, with great overlap between confidence for RA, SpA and UA. Fulfilment of ACR or ESSG criteria was poorly related to the experts' diagnosis and evaluation of probabilities for RA and SpA. However, UA was a relatively infrequent choice (19%). CONCLUSIONS: There was no general consensus about the nosology of early RA and SpA. Classification of atypical early arthritis was not resolved by currently available criteria for RA and SpA. This may have implications for therapy in early disease.

Punzi L, Pozzuoli A, Pianon M, Bertazzolo N, Oliviero F, Scapinelli R. · Division of Rheumatology, University of Padova, Italy. · Rheumatology (Oxford). · Pubmed #11257158 links to  free full text

Abstract: BACKGROUND: Joint hypermobility (JH) is frequently seen in rheumatology; in some cases, such as rheumatoid arthritis (RA), it may represent a worsening of disease evolution. The aim of our study was to evaluate the influence of joint hypermobility on RA synovial fluid (SF) inflammation. Patients and methods. One hundred consecutive adult patients with RA and joint effusion of the knee were examined for the presence of JH. In the SF we evaluated volume, the number of white blood cells (WBC) and the levels of interleukin (IL)-1beta, IL-6 and IL-8 and prostaglandin E2 (PGE2). RESULTS: JH was associated with RA (JH-RA) in 18 patients, all of whom were female. Compared with non-JH RA, all the SF indices found in JH-RA were higher, although significant differences were observed only for volume, IL-8 and PGE2. CONCLUSION: In JH-RA, increased joint mobility seems to be associated with a more severe local inflammatory response, which may contribute to the more erosive evolution observed in our patients.

Punzi L, Peuravuori H, Jokilammi-Siltanen A, Bertazzolo N, Nevalainen TJ. · Division of Rheumatology, University of Padova, Italy. · Clin Exp Rheumatol. · Pubmed #11072604 No free full text.

Abstract: OBJECTIVE: Bactericidal/permeability increasing protein (BPI) is a leukocyte product exerting antibacterial activity. Its production may be stimulated by cytokines, mainly Tumor Necrosis Factor (TNF) alpha. We studied BPI in the synovial fluid (SF) of psoriatic arthritis (PsA), a disease suspected to be influenced by infectious agents. METHODS: The levels of BPI and various indices of SF inflammation, including cytokines and its receptors, were determined in the SF of 18 patients with PsA and compared with those of 12 patients with rheumatoid arthritis (RA) and 9 with osteoarthritis (OA). RESULTS: The lowest SF levels of BPI were found in PsA (145.3 +/- 97.3 ng/ml), significantly lower than in RA (307.7 +/- 42.8 ng/ml, p = 0.0001) and similar to those in OA (151.1 +/- 52.4 ng/ml). Furthermore, only in PsA, and not in the RA and OA subgroups, correlations were observed between BPI and the indices considered, including TNF alpha (r = 0.746, p = 0.0004). CONCLUSION: Due to its relationship with local inflammation, SF BPI may play a role in the pathogenesis of arthropathies, in particular PsA.

Cimmino MA, Salvarani C, Macchioni P, Montecucco C, Fossaluzza V, Mascia MT, Punzi L, Davoli C, Filippini D, Numo R. · Clinica Reumatologica, Dipartimento di Medicina Interna e Specialità Mediche, Università degli Studi di Genova, Italy. · Rheumatol Int. · Pubmed #11063290 No free full text.

Abstract: The aim of the study was to evaluate the frequency of extra-articular manifestations (EAMs) of rheumatoid arthritis (RA) in a series of patients from nine Italian rheumatology clinics. A total of 587 patients underwent direct questioning, complete physical evaluation, and review of medical records and laboratory data. The relationships between EAMs and the eosinophilic count, IgM rheumatoid factor (RF), and antinuclear antibodies (ANA) were studied. EAMs were present in 240/587 (40.9%) patients. The most common features were sicca syndrome (17.5%) and rheumatoid nodules (16.7%). EAMs were significantly more frequent in male patients (OR = 1.68), patients with ANA positivity (OR = 2.82), high anatomical class (OR = 2.3), and rheumatoid factor seropositivity (OR = 2.22). EAMs were more common in patients from southern Italy than in those from northern Italy (P < 0.001). EAMs seem to be rarer in Italy than in the Anglo-Saxon populations of northern Europe and the USA. Differences in prevalence of EAMs can exist even within the same country.