Rheumatoid Arthritis: Epis O

Meenagh G, Filippucci E, Delle Sedie A, Riente L, Iagnocco A, Epis O, Scirè CA, Montecucco C, Bombardieri S, Valesini G, Grassi W. · Antrim Hospital, Antrim, United Kingdom. · Clin Exp Rheumatol. · Pubmed #19210859 No free full text.

Abstract: One of the largest challenges to the field of musculoskeletal ultrasonography is attempting to accurately quantify the changes seen in chronic arthritis. With advances in ultrasound technology, researchers have been increasingly exploring ways of more accurately assessing these changes and attempting to reach consensus with agreed scoring systems. This review presents the main scoring systems developed for quantifying sonographic findings indicative of synovitis and joint damage in patients with rheumatoid arthritis. Further investigation is required to attain international consensus on such scoring systems and to evaluate their impact on therapeutic decision-making.

Filippucci E, Meenagh G, Epis O, Iagnocco A, Riente L, Delle Sedie A, Montecucco C, Valesini G, Bombardieri S, Grassi W. · Cattedra di Reumatologia, Università Politecnica delle Marche, Ancona, Italy. · Clin Exp Rheumatol. · Pubmed #18328139 No free full text.

Abstract: Despite its indubitable potential, ultrasonography still has limited diffusion in rheumatology related principally to the image acquisition process due to at least five main factors: the steep learning curve, lack of standardisation of the technique, intra- and inter-observer variability, time consumption and the high initial cost of top quality sonographic equipment. Of all these barriers, the first four are undoubtedly the most difficult to overcome. This review discusses the available evidence supporting the potential of three-dimensional ultrasound with high-frequency volumetric probe to overcome the first four barriers. The challenge to three-dimensional ultrasound is to prove itself to be a method that requires no particular skills that can be mastered in just a few minutes and is not operator-dependant [corrected]

Caporali R, Bonacci E, Epis O, Bobbio-Pallavicini F, Morbini P, Montecucco C. · Department of Rheumatology, University of Pavia, IRCCS San Matteo Foundation, Pavia, Italy. · Arthritis Rheum. · Pubmed #18438907 links to  free full text

Abstract: OBJECTIVE: To analyze the safety of our biopsy technique and the effectiveness of minor salivary gland biopsy (MSGB) for the diagnosis of Sjögren's syndrome (SS) and amyloidosis. METHODS: We conducted a retrospective analysis of 452 patients with suspected SS and 50 with suspected amyloidosis and negative periumbilical fat aspiration analysis who underwent MSGB at a single center. Diagnostic evaluation for SS included Schirmer's test, unstimulated whole salivary flow, detection of antinuclear antibodies and anti-SSA/SSB, erythrocyte sedimentation rate, C-reactive protein, IgM rheumatoid factor, and serology for hepatitis C virus. For all biopsy samples, a cumulative focus score on multilevel sections was calculated. SS was diagnosed according to American-European Consensus Group (AECG) criteria. Histologic evaluation for amyloidosis was performed using Congo red staining and polarized-light microscopy. Adverse events were recorded on a questionnaire immediately after the procedure and 7 days, 14 days, and 6 months thereafter. RESULTS: Sixty-four patients (12.7%) reported transient adverse events: 40 paresthesias lasting <7 days, 17 paresthesias lasting <14 days, 27 cases of local swelling, and 8 external hematoma. One patient has had local paresthesia for 2 years. A total of 498 (99.2%) samples provided adequate material for histologic analysis. Of 452 patients evaluated for SS, 378 were finally evaluated. Ninety-three patients (24.5%) had a cumulative focus score > or =1, and 87 (94.5%) of 93 satisfied the AECG criteria. Classification of SS was possible for 124 (32.8%) of 378 patients. In 51 (41%) of 124, MSGB was essential to reach the number of criteria needed for classification. Of 50 patients evaluated for amyloidosis, 10 (20%) had positive Congo red staining. CONCLUSION: MSGB is a simple, safe, and reliable tool for the diagnosis of SS and amyloidosis, and therefore is suitable for more extensive application.

Scirè CA, Epis O, Codullo V, Humby F, Morbini P, Manzo A, Caporali R, Pitzalis C, Montecucco C. · Chair and Division of Rheumatology, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi 12, I 27100 Pavia, Italy. · Arthritis Res Ther. · Pubmed #17903238 links to  free full text

Abstract: The aim of the present study was to perform an immunohistological assessment of the synovial tissue from involved small joints in rheumatoid arthritis (RA) and to explore the reliability of a mini-invasive ultrasound (US)-guided technique of small joint synovial biopsy for the histopathological assessment. Synovial tissue collected during arthrotomic surgery of small joints in nine patients served as the gold standard for the validation of the histological assessment. Small hand-joint synovial biopsies from an additional nine patients with erosive RA were obtained by a mini-invasive US-guided procedure, performed percutaneously by the portal and rigid forceps technique. Using digital image analysis, the area fractions of synovial macrophages (CD68 cells), T cells (CD3 cells) and B cells (CD20 cells) were measured in all high-power fields of every sample at different cutting levels. The representative sample was defined as the minimal number of high-power fields whose mean area fraction would reflect the overall mean area fraction within a percentage mean difference of 10%. For each patient, a range of three to five large samples for surgical biopsies and a range of 8-12 samples for US-guided biopsies were collected and analysed. In arthrotomic samples, the analysis of a randomly selected tissue area of 2.5 mm2 was representative of the overall value for CD68, CD3 and CD20 cells. US-guided samples allowed histological evaluation in 100% of cases, with a mean valid area of 18.56 mm2 (range 7.29-38.28 mm2). The analysis of a cumulative area of 2.5 mm2 from eight randomly selected sections (from different samples or from different cutting levels) allowed to reduce the percentage mean difference to less than 10% for CD68, CD3 and CD20 cells. In conclusion, US-guided synovial biopsy represents a reliable tool for the assessment of the histopathological features of RA patients with a mini-invasive approach.

Caporali R, Bonacci E, Epis O, Morbini P, Montecucco C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #17666442 No free full text.

This publication has no abstract.

Vitali C, Palombi G, Baldini C, Benucci M, Bombardieri S, Covelli M, Del Papa N, De Vita S, Epis O, Franceschini F, Gerli R, Govoni M, Bongi SM, Maglione W, Migliaresi S, Montecucco C, Orefice M, Priori R, Tavoni A, Valesini G. · Villamarina Hospital, Piombino, Italy. · Arthritis Rheum. · Pubmed #17599741 links to  free full text

Abstract: OBJECTIVE: To develop valid instruments for the assessment of disease-related damage and disease activity in Sjögren's syndrome (SS). METHODS: Data on 206 patients with primary SS were collected in 12 Italian centers. Each patient was scored by 1 investigator, on the basis of a global assessment of the degree of disease damage and disease activity. Patients judged to have active disease at the time of enrollment underwent a second evaluation after 3 months. Univariate and multivariate analyses were performed to select the clinical and serologic variables that were the best predictors of damage and of disease activity, and these variables were used to construct the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI). The weight of each variable in the index was determined by the beta coefficients in multivariate regression models. Scores obtained using the SSDDI and the SSDAI were compared with scores initially given by the investigators. Finally, a receiver operating characteristic (ROC) curve was used to determine the cutoff value in the SSDAI with the highest level of accuracy in identifying patients with a significant level of disease activity. RESULTS: A multivariate model with 9 variables was the best predictor of investigator scores of damage. The scores obtained using the SSDDI were closely correlated with investigator ratings (R = 0.760, P < 0.0001). A model composed of 11 variables was the best predictor of investigator scores of disease activity. The scores obtained using the SSDAI were strongly correlated with the investigator ratings both at the time of enrollment and 3 months after enrollment (R = 0.872, P < 0.0001, and R = 0.817, P < 0.0001, respectively). The differences between scores given by investigators at study enrollment and after 3 months, a measure of variation of disease activity over time, were also closely correlated with the differences calculated using the SSDAI (R = 0.683, P < 0.0001). The ROC curve analysis showed that patients with the highest level of disease activity could be identified on the basis of an SSDAI score of >or=5. CONCLUSION: Our findings indicate that the SSDDI is an adequate instrument to objectively measure damage in patients with SS, and that the SSDAI is a valid tool to measure disease activity when used either as a single-state index or as a transition index.

Morbini P, Manzo A, Caporali R, Epis O, Villa C, Tinelli C, Solcia E, Montecucco C. · Department of Pathology, IRCCS Policlinico S Matteo, Pavia, Italy. · Arthritis Res Ther. · Pubmed #15743482 links to  free full text

Abstract: The recently observed low reproducibility of focus score (FS) assessment at different section depths in a series of single minor salivary gland biopsies highlighted the need for a standardized protocol of extensive histopathological examination of such biopsies in Sjogren's syndrome. For this purpose, a cumulative focus score (cFS) was evaluated on three slides cut at 200-mum intervals from each of a series of 120 salivary biopsies. The cFS was substituted for the baseline FS in the American-European Consensus Group (AECG) criteria set for Sjogren's syndrome classification, and then test specificity and sensitivity were assessed against clinical patient re-evaluation. Test performances of the AECG classification with the original FS and the score obtained after multilevel examination were statistically compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance of AECG classification significantly improved when the cFS was entered in the AECG classification; the improvement was mostly due to increased specificity in biopsies with a baseline FS >or= 1 but <2. The assessment of a cFS obtained at three different section levels on minor salivary gland biopsies can be useful especially in biopsies with baseline FSs between 1 and 2.

Porta C, Caporali R, Epis O, Ramaioli I, Invernizzi R, Rovati B, Comolli G, Danova M, Montecucco C. · Istituto di Medicina Interna ed Oncologia Medica, Università degli Studi di Pavia e I.R.C.C.S. Policlinico San Matteo, Pavia, Italy. · Bone Marrow Transplant. · Pubmed #14743200 No free full text.

Abstract: We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.

Caporali R, Montecucco C, Epis O, Bobbio-Pallavicini F, Maio T, Cimmino MA. · Cattedra di Reumatologia, Università di Pavia, Pavia, Italy. · Ann Rheum Dis. · Pubmed #11602472 links to  free full text

Abstract: OBJECTIVE: To evaluate in a prospective study whether patients with polymyalgia rheumatica (PMR) and patients with rheumatoid arthritis (RA) with PMR-like onset show distinctive clinical and laboratory features. METHODS: A cohort of 116 consecutive patients with bilateral girdle pain for at least one month and raised erythrocyte sedimentation rate (ESR) was studied and followed up for 12 months. Laboratory tests included determination of ESR, IgM rheumatoid factor, haemoglobin, white blood cell count, platelet count, percentage of CD8 lymphocytes, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutamyltransferase concentrations. RESULTS: At first examination, RA was diagnosed in 22/116 (19%) patients and PMR in 94 (81%) patients. During the follow up period, 19 additional patients developed RA, and the diagnosis of PMR was confirmed in 65 (56%) patients at the end of the study. Of the clinical and laboratory features, only the presence of peripheral synovitis could differentiate patients who will develop RA from those with "true" PMR, but the positive predictive value of this feature was poor. CONCLUSION: At present, there are no clinical or routine laboratory features allowing early differentiation between PMR and RA with PMR-like onset.

Cavagna L, Caporali R, Epis O, Bobbio-Pallavicini F, Montecucco C. · Chair of Rheumatology, University of Pavia, Policlinico San Matteo, Piazzale Golgi no. 2, 27100 Pavia, Italy. · Clin Exp Rheumatol. · Pubmed #11407090 No free full text.

Abstract: In this study we evaluated the efficacy of Infliximab in the treatment of adult Still's disease (ASD) refractory to conventional therapy. Three patients with chronic and active ASD unresponsive to corticosteroids and methotrexate were given intravenous Infliximab infusions at a dosage of 3 mg/kg at weeks 0, 2, 6 and then once every 8 weeks. Methotrexate was maintained in all cases at a dosage of 15 mg/week, whereas the prednisone dose was modified according to disease activity. The follow-up lasted 50 weeks and disease activity improved in all cases during Infliximab therapy. Two patients presented arthralgias and sore throat at 20 and 28 weeks, that was rapidly controlled by Infliximab reinfusion every 4 weeks. One patient relapsed at 18 weeks and dropped out at 22 weeks due to an urticarioid rash after the beginning of the fifth infusion. Infliximab may be effective in the treatment of relapse of ASD refractory to conventional therapy and requiring continuous high dose corticosteroid medication. Further studies are needed to evaluate the long-term safety, efficacy and the optimal schedule of infusion.

Belfiore N, Rossi S, Bobbio-Pallavicini F, Epis O, Caporali R, Montecucco C. · Servizio di reumatologia, Policlinico S. Matteo, Pavia, Italy. · Joint Bone Spine. · Pubmed #10875315 No free full text.

Abstract: Autoantibodies to Ro(SS-A) may recognize two different polypeptides, of 52 kDa and 60 kDa, respectively. We used an ELISA with purified human recombinant antigens to conduct a detailed analysis of the specificities of anti-Ro(SS-A) antibodies from 170 patients with definite diagnoses (systemic lupus erythematosus [SLE], n = 55; primary Sjögren's syndrome [PSS], n = 39; systemic sclerosis, n = 9; rheumatoid arthritis [RA], n = 10) or undifferentiated connective tissue disease (UCTD, n = 57). Most of the patients with SLE or PSS had both anti-52 kDa and -60 antibodies; isolated anti-60 kDa antibodies were found in 13% of the SLE patients and in none of the PSS patients, whereas high titers of anti-52 kDa were more common in the PSS than in the SLE patients. In the UCTD patients, the anti-Ro(SS-A) profile showed no significant correlations with clinical features but was associated with the clinical outcome. Over the mean follow-up of five years, definite SLE developed in four of the five UCTD patients with isolated anti-60 kDa vs only one of the remaining 52 patients (P < 0.0001); progression to PSS was seen in seven of the 34 patients with both anti-52 kDa and anti-60 kDa vs none of the remaining 23 patients (P = 0.03); none of the 12 patients with isolated anti-52 kDa developed a definite connective tissue disease. CONCLUSION: Our study suggests that analysis of anti-Ro(SS-A) specificity may provide useful information for predicting the course of UCTD.

Caporali R, Epis O, Negrini R, Scirè CA, Solcia E, Montecucco C. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #12747290 No free full text.

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Caporali R, Rossi S, Epis O, Montecucco C. · No affiliation provided · J Rheumatol. · Pubmed #10685833 No free full text.

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Montecucco C, Caporali R, Rossi S, Epis O. · No affiliation provided · Rheumatology (Oxford). · Pubmed #10534560 links to  free full text

This publication has no abstract.