Rheumatoid Arthritis: Bombardieri S

Mancarella L, Bobbio-Pallavicini F, Ceccarelli F, Falappone PC, Ferrante A, Malesci D, Massara A, Nacci F, Secchi ME, Manganelli S, Salaffi F, Bambara ML, Bombardieri S, Cutolo M, Ferri C, Galeazzi M, Gerli R, Giacomelli R, Grassi W, Lapadula G, Cerinic MM, Montecucco C, Trotta F, Triolo G, Valentini G, Valesini G, Ferraccioli GF, Anonymous00012. · Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy. · J Rheumatol. · Pubmed #17611987 No free full text.

Abstract: OBJECTIVE: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics. METHODS: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.2 were defined as having active disease and could start TNF-alpha blockers. All patients received one TNF-alpha blocker plus methotrexate (10-20 mg/wk). At the third month the patients were categorized as responders or nonresponders, based on improvement of at least 0.25 of the Health Assessment Questionnaire (HAQ). Those who had improved by at least 0.25 HAQ were analyzed for possible predictors of DAS28 remission at the sixth month. RESULTS: A total of 1257 patients started TNF-alpha blockers. Of these, 591 (46.7%) reached the sixth month with an improvement of HAQ of 0.25 at the third month. In the cohort of patients reaching HAQ of 0.25, DAS28 remission was seen in 24% of rheumatoid factor (RF)-positive and 36% of RF-negative patients (p = 0.03). Logistic regression analysis for predictors of remission identified age at baseline, HAQ < 1.63, and RF negativity as positive predictors of remission at 6 months along with sex (male). CONCLUSION: We show that only a minority of patients with longstanding RA achieve a good clinical response or remission at the outpatient community level. Predictors of remission identify characteristics commonly observed in subsets with less severe RA.

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.

Giusti L, Baldini C, Bazzichi L, Ciregia F, Tonazzini I, Mascia G, Giannaccini G, Bombardieri S, Lucacchini A. · Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. · Proteomics. · Pubmed #17436266 No free full text.

Abstract: Sjögren's syndrome (pSS) is a systemic disease that affects salivary glands directly, and is therefore expected to influence the composition of human whole saliva (WS) fluid. The aim of this study was to characterize the WS proteins of pSS patients using a proteomic approach to assess a valid procedure to examine the global changes of the salivary protein profiles in connective tissue disorders. The WS proteins expressed in patients affected by pSS and healthy volunteers were analyzed using the 2-DE technique. The WS protein pattern was altered in pSS patients compared to controls, with a decrease in some of the typical salivary proteins. Particularly, a remarkable alteration of carbonic anhydrase VI was observed. Moreover, a comparison of WS protein profile of pSS patients with the one obtained from controls revealed a set of differentially expressed proteins. These proteins were related to acute and chronic inflammation while some others were involved in oxidative stress injury. These findings are in line with the systemic immuno-inflammatory aspects of pSS and open the possibility for a systematic search of diagnostic biomarkers and targets for therapeutic intervention in pSS.

Michou L, Lasbleiz S, Rat AC, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Pierlot C, Glikmans E, Garnier S, Dausset J, Vaz C, Fernandes M, Petit-Teixeira E, Lemaire I, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Prum B, Bardin T, Dieudé P, Cornélis F, Anonymous00173. · GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France. · Proc Natl Acad Sci U S A. · Pubmed #17237219 links to  free full text

Abstract: The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.

Riente L, Delle Sedie A, Iagnocco A, Filippucci E, Meenagh G, Valesini G, Grassi W, Bombardieri S. · Cattedra di Reumatologia, Università di Pisa, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #17181916 No free full text.

Abstract: Ultrasonography (US) is a useful tool for imaging, which can be used for the assessment of joints and periarticular structures in all rheumatological disorders. In patients with pain and/or swelling of the ankle and foot, US provides information about the presence of joint effusion, synovitis, tenosynovitis, tendinosis, and tendons tears, helping in the differential diagnosis between joint or tendon/enthesis involvement. Moreover, US allows clinicians to monitor and guide needle positioning to inject pharmaceutical substances more safely and effectively even in hard-to-reach sites. US represents an accurate, safe and low-cost technique that can be used for the examination of the ankle and foot in rheumatic disorders.

Díaz-González F, Alten RH, Bensen WG, Brown JP, Sibley JT, Dougados M, Bombardieri S, Durez P, Ortiz P, de-Miquel G, Staab A, Sigmund R, Salin L, Leledy C, Polmar SH. · Service of Rheumatology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Canary Islands, Spain. · Ann Rheum Dis. · Pubmed #17170051 No free full text.

Abstract: BACKGROUND: Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA. METHODS: This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20. RESULTS: Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated. CONCLUSIONS: This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.

Antonelli A, Delle Sedie A, Fallahi P, Ferrari SM, Maccheroni M, Ferrannini E, Bombardieri S, Riente L. · From the Department of Internal Medicine and the Rheumatology Unit, University of Pisa, and the Endocrinological Laboratory, Azienda Ospedaliera Pisana, Pisa, Italy. · J Rheumatol. · Pubmed #17014017 No free full text.

Abstract: OBJECTIVE:To evaluate the prevalence of thyroid disorders in a group of patients with psoriatic arthritis (PsA). METHODS: A complete thyroid investigation was carried out in 80 patients with PsA, in gender- and age-matched subjects (1:5) drawn from the general population (controls), and in 112 patients with rheumatoid arthrtitis (RA) with similar iodine intake. RESULTS: Anti-thyroid peroxidase antibodies (AbTPO), a hypoechoic thyroid, and subclinical hypothyroidism were significantly more frequent in women with PsA than in control women, and their frequency was similar to that in patients with RA (positive AbTPO titer 28%, 12%, and 31%; hypoechoic thyroid 31%, 16%, and 36%; subclinical hypothyroidism 25%, 8%, and 12%, respectively). Among men, positive AbTPO titers and a hypoechoic thyroid were found more frequently in the patients with PsA and RA than in controls (positive AbTPO titer 14%, 5%, and 2%; hypoechoic thyroid 16%, 10%, and 3%, respectively). All patients with PsA with subclinical hypothyroidism had polyarticular involvement (p </= 0.05) and a longer disease duration (years 19 +/- 15 vs 11 +/- 8, p = 0.03) than patients with euthyroid PsA. The prevalence of subclinical hyperthyroidism, thyroid nodules, and thyroid enlargement was not significantly different among the 3 groups.CONCLUSION: Our results demonstrate a significantly higher prevalence of thyroid autoimmunity (positive AbTPO, hyoechoic thyroid) findings in men and women with PsA and of subclinical hypothyroidism in women with PsA than in the general population. Therefore, thyroid function tests, an AbTPO assay, and thyroid ultrasound should be performed as part of the clinical evaluation, particularly in women with PsA.

Iagnocco A, Filippucci E, Meenagh G, Delle Sedie A, Riente L, Bombardieri S, Grassi W, Valesini G. · Cattedra di Reumatologia, Università di Roma La Sapienza, Roma, Rome, Italy. · Clin Exp Rheumatol. · Pubmed #16870087 No free full text.

Abstract: Ultrasonography (US) is a reliable and useful diagnostic tool for the assessment of hip pathology. It depicts changes within the coxo-femoral joint (synovitis, erosions, osteophytes) and in the adjacent peri-articular tissues (calcifications, tendonitis, enthesitis, bursitis) in many rheumatic diseases (rheumatoid arthritis, spondyloarthritis, osteoarthritis, polymyalgia rheumatica ) and in some orthopaedic disorders (septic arthritis, trauma, abscess, painful hip after arthroplasty). It is commonly used both in adults and in children. In the assessment of hip joint pathology, US exerts considerable diagnostic supremacy over physical examination. In fact, by virtue of its size and position, reliable physical examination of the hip is often difficult thus making US particularly useful as a bedside tool for the evaluation of a painful hip. Hip US has also proven to be of great practical benefit when performing aspiration and injection within the joint and in the periarticular soft tissues. The relatively limited acoustic windows available to the US beam is the principal limitation to hip US thereby making detailed examination of some important structures impossible together with the interpretation of power Doppler signal sometimes unreliable. In addition, the deep location of the hip can confer further problems to US scanning in obese or particularly muscular subjects.

Piccinni A, Maser JD, Bazzichi L, Rucci P, Vivarelli L, Del Debbio A, Catena M, Bombardieri S, Dell'Osso L. · Department of Psychiatry, Pharmacology and Biotechnology, Psychiatry II Unit, University of Pisa, 56100 Pisa, Italy. · Compr Psychiatry. · Pubmed #16635649 No free full text.

Abstract: BACKGROUND: Previous studies suggested that rheumatoid arthritis (RA) is associated with depressive and anxiety symptomatology. The well-being and functioning of patients with RA may be significantly influenced by subthreshold psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with RA, compared with the Italian norms and patients with diabetes, was assessed by the influence of lifetime mood and panic-agoraphobic spectrum symptoms and demographic and clinical variables. METHODS: Ninety-two patients were consecutively recruited at the Department of Rheumatology at the University Hospital of Pisa, Italy. All patients met diagnostic criteria of RA according to the American College of Rheumatology. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire (MOS SF-36). Mood and panic-agoraphobic spectra were assessed by two different structured self-report instruments: the Mood Spectrum (MOODS-SR) and the Panic-Agoraphobic Spectrum (PAS-SR), respectively. RESULTS: Patients with RA were compared, as regards the MOS SF-36 scale scores, with the Italian normative population and patients with diabetes. Compared with the Italian population, patients with RA showed significantly lower MOS SF-36 scale scores, except for role emotional. Moreover, patients with RA scored significantly lower on the role physical, bodily pain, and social functioning scales compared with patients with diabetes and higher on role emotional and mental health. A significant worsening of all MOS SF-36 scale scores was related to higher scores of the depressive domains of MOODS-SR, except for social functioning and bodily pain. A statistically significant negative association was also found between PAS-SR total score and the MOS SF-36 scales physical functioning, vitality, role emotional, and mental health. There were no statistically significant correlations between MOS SF-36 scales and the manic MOODS spectrum. In the multivariate models, the negative correlations between depressive MOODS, role emotional, and mental health were confirmed and the severity of arthritis showed a significant impact on all MOS SF-36 areas with the exception for social functioning; moreover, manic MOODS was associated with better general health. CONCLUSIONS: The present report shows that lifetime depressive spectrum symptoms negatively affects HRQoL of patients with RA and subthreshold mania improves the perception of general health. Diagnosis and appropriate clinical management of depression, including subthreshold symptoms, might enhance HRQoL in these patients.

Bazzichi L, Maser J, Piccinni A, Rucci P, Del Debbio A, Vivarelli L, Catena M, Bouanani S, Merlini G, Bombardieri S, Dell'Osso L. · Department of Internal Medicine, Rheumatology Unit, University of Pisa, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #16396695 No free full text.

Abstract: OBJECTIVE: The aim of this study was to investigate the impact of disability and lifetime subthreshold depressive symptoms on Health-Related Quality of Life (HRQoL) among patients with rheumatoid arthritis (RA). METHODS: Ninety-two subjects with a diagnosis of RA according to the American College of Rheumatology (ACR) criteria were recruited at the Department of Rheumatology of the University Hospital, Pisa, Italy. Participants who met DSM-IV-TR diagnostic criteria for current or previous Axis I disorders were excluded. Assessments of functional status and disability was conducted using both the ACR classification and the Stanford Health Assessment Questionnaire (HAQ). Health-related Quality of Life was assessed using the Medical Outcomes Study Short Form 36 health survey questionnaire (MOS-SF36) and lifetime depressive spectrum symptomatology using the Mood Spectrum Questionnaire, Self-Report version (MOODS-SR). RESULTS: Comparison with MOS-SF36 Italian normative values indicated that RA patients were significantly impaired on mental and physical HRQoL areas. Correlations between MOODS-SR depressive scores and ACR severity (Spearman rho = 0.15, p = 0.07) and HAQ score (Spearman rho = 0.20, p = 0.05) were modest in absolute value and borderline significant. Lifetime mood depressive spectrum was related with impaired HRQoL levels, both in physical (except for bodily pain) and mental (except for social functioning) domains. Associations of mood depressive spectrum and general health, vitality, role emotional and mental health continued to be significant after controlling for functional status, duration of illness, age and gender. CONCLUSIONS: Because lifetime mood depressive symptoms significantly contribute to impairment in HRQoL in RA patients without a past psychiatric history, even after controlling for functional status, duration of illness and demographic characteristics, these symptoms should be assessed for an accurate clinical evaluation and appropriate clinical management of RA patients.

Salaffi F, Stancati A, Neri R, Grassi W, Bombardieri S. · Department of Rheumatology, Università Politecnica delle Marche, Ospedale A. Murri, ASL5, Via dei Colli, 52, 60035 Jesi, ANCONA, Italy. · Clin Exp Rheumatol. · Pubmed #16273783 No free full text.

Abstract: OBJECTIVE: Disability has been identified as a core outcome measure in rheumatoid arthritis (RA). The aim of this study was to test the Recent-Onset Arthritis Disability (ROAD) questionnaire for validity, reliability and responsiveness in Italian patients with early RA. METHODS: The psychometric properties of ROAD were tested in 159 patients with early RA, mean age 54.7 (+/- 8.8), 74.3% women, mean disease duration 14.5 months (+/- 1.9 months). All completed the ROAD, the Medical Outcomes Study SF-36 Health Survey (SF-36), the Health Assessment Questionnaire (HAQ) and the patient global assessment (PGA) of functional disability twice, in order to test for validity and responsiveness. Of the 159 patients who completed the health status instruments on two occasions, 121 were included in the responsiveness analyses. The test-retest reliability of the ROAD questionnaire was calculated using intraclass correlation coefficients (ICCs) and the Bland and Altman method on 77 patients who completed the questionnaire twice over an interval of one week. Construct validity was assessed using Spearman's correlations, while responsiveness was evaluated by 3 different methods: (1) effect size (the mean difference between the baseline scores and thefollow-up scores divided by the standard deviation of the baseline scores); (2) standardized response mean (the mean change in scores divided by the standard deviation of the change in scores); (3) receiver operating characteristics (ROC) curve analysis. RESULTS: ROAD fulfilled the established criteria for validity, reliability and responsiveness. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, thus supporting the convergent construct validity. Significant correlations were seen between ROAD scores and HAQ scores (rho = 0.372), SF-36 physical component summary (PCS) (rho = -0.413), PGA functional disability (rho = 0.417), pain (rho = 0.639), Ritchie index (rho = 0.357), number of swollen joints (rho = 0.387), patient and physician assessment of disease activity (rho = 0.467 and 0.323, respectively), and Disease Activity Score (rho = 0.476). Test-retest reliability was satisfactory, with ICCs of 0.927 (upper extremity function), 0.892 (lower extremity function), and 0.851 (activity of daily living/work). Bland-Altman plots confirmed this finding. The results of responsiveness analysis indicate that the ROAD subscales were slightly more sensitive to perceived change in functional disability than those of HAQ, SF-36 PCS, and PGA offunctional disability. CONCLUSION: Our data suggest that the ROAD index is a reliable, valid and responsive tool for measuring physical functioning in patients with early RA, and is suitable for use in clinical trials and daily clinical practice. Its generalizability and utility for assessing aggressive treatment and functional outcomes must now be evaluated in broader settings.

Merlini G, Anzilotti C, Chimenti D, Tommasi C, Bombardieri S, Migliorini P. · Clinical Immunology Unit, Department of Internal Medicine, Via Roma 67, 56126 Pisa, Italy. · Ann N Y Acad Sci. · Pubmed #16014539 No free full text.

Abstract: The data presented suggest that a deiminated viral peptide is specifically recognized by antibodies contained in rheumatoid arthritis (RA) sera. Antipeptide antibodies are not associated with the presence or severity of specific manifestations of RA, but are more frequent in subjects with erosive arthritis. Taking into account the association with rheumatoid factor and with erosive arthritis, we can conclude that antipeptide antibodies are markers of severe forms of RA. Our data also show familial aggregation of anticitrullinated peptide antibodies.

Riente L, Chimenti D, Pratesi F, Delle Sedie A, Tommasi S, Tommasi C, Bombardieri S, Migliorini P. · Rheumatology and Immunology Units, Department of Internal Medicine, University of Pisa, Pisa, Italy. · J Rheumatol. · Pubmed #15124251 No free full text.

Abstract: OBJECTIVE: Subclinical gut inflammation has been described in patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Joint involvement has also been reported related to celiac disease. We investigated IgA antibodies to bovine tissue tranglutaminase (tTg) and IgA and IgG antibodies to human tTg and to Saccharomyces cerevisiae (ASCA) in patients with AS and PsA. METHODS: We evaluated the frequency of IgA antibodies to bovine tTg, and of IgA and IgG antibodies to human tTg and to ASCA in 43 patients with AS and 75 with PsA. As control groups we considered 79 patients with rheumatoid arthritis (RA) and 78 healthy blood donors. RESULTS: We detected antibodies as follows: IgA antibodies to bovine tTg in 1/43 patients with AS, 3/75 with PsA, 1/79 with RA, and in 9/78 healthy controls; IgA antibodies to human tTg in 1/43 patients with AS, 1/75 with PsA, 1/79 with RA, and in 3/78 healthy controls; IgG antibodies to human tTg in 1/43 patients with AS, 4/75 with PsA, 5/79 with RA, and in 7/78 healthy controls. IgA ASCA were confirmed in 10/43 patients with AS, 7/75 with PsA, 14/79 with RA, and in 7/78 healthy controls; IgG ASCA were present in 5/43 patients with AS, 4/75 with PsA, 8/79 with RA, and in 8/78 healthy controls. No statistically significant difference was observed in the prevalence of IgA or IgG antibodies to bovine and human tTg and in the frequency and in mean level of IgA or IgG ASCA between the studied groups or between each group and healthy controls. CONCLUSION: Our data fail to show an increased prevalence of autoantibodies associated with celiac and Crohn's disease in patients with AS and PsA.

Bernacchi E, Amato L, Parodi A, Cottoni F, Rubegni P, De Pità O, Papini M, Rebora A, Bombardieri S, Fabbri P. · Department of Dermatological Sciences, University of Florence, Italy. · Clin Exp Rheumatol. · Pubmed #15005005 No free full text.

Abstract: OBJECTIVE: Various cutaneous manifestations have been described (xerosis, eyelid dermatitis, angular cheilitis, cutaneous vasculitis and annular erythema) in Sjögren's syndrome (SS), but so far only three studies on large numbers of SS patients have been carried out. The frequency of cutaneous manifestations and their association with specific clinical or immunological parameters have never been studied. The aim of the Italian Group of Immunodermatology was to evaluate these associations in a large number of SS patients. METHODS: A retrospective review was performed on 93 patients with SS followed over a ten-year period (1990-2000) at 6 Italian dermatological centers. They were subdivided into two groups, 62 with primary SS and 31 with secondary SS, and the frequency of cutaneous manifestations and specific antibodies was determined and compared between them. RESULTS: We found significantly higher levels of xerosis (p = 0.009) (56.4% versus 25.8%) and angular cheilitis (p = 0.017) (38.7% versus 16.1%) in primary SS patients than in those with secondary SS. A significant association of xerosis with anti-SSA + SSB (p = 0.033) antibodies was also demonstrated. Eyelid dermatitis and pruritus were common but less specific cutaneous symptoms. Annular erythema was found more often in primary (6.45%) than in secondary (3.2%) SS and was associated with SSA + SSB antibodies in 75% of the cases. Cutaneous vasculitis was present in 30.6% of primary SS (manifesting as palpable purpura in 84%) and in 29.3% of secondary SS cases. CONCLUSION: Xerosis is the most frequent and characteristic cutaneous manifestation of primary SS. It is not linked to decreased sebaceous or sweat gland secretion, but more probably to a specific alteration of the protective function of the stratum corneum. Angular cheilitis is a common but less specific skin lesion in SS and is associated with xerosis and xerostomia.

Giacomelli R, Matucci-Cerinic M, Bombardieri S. · Internal Medicine, University of L'Aquila, School of Medicine, Italy. · Ann Rheum Dis. · Pubmed #12429531 links to  free full text

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Mosca M, Neri R, Bencivelli W, Tavoni A, Bombardieri S. · Clinical Immunology Unit and Rheumatology Unit, University of Pisa, Pisa, Italy. · J Rheumatol. · Pubmed #12415590 No free full text.

Abstract: OBJECTIVE: Undifferentiated connective tissue disease (UCTD) refers to a cluster of systemic disorders characterized by a simple clinical and autoantibody profile. Previously, we had described a series of 91 patients with UCTD who were followed at our unit for a minimum period of one year; here we report the extended followup of these patients. METHODS: Of the original 91 patients, 8 were lost to followup; the remaining 83, with a minimum followup of 5 years, were included in our analysis. RESULTS: During the followup 18 patients developed systemic lupus erythematosus (SLE) and one developed Sjögren's syndrome within a mean period of 54 months after the onset of the disease (range 17-96 mo). On analysis the 18 patients with SLE showed a clinical profile similar to cohorts reported in the literature. In one patient the evolution to SLE occurred during puerperium, but no other triggering factors were observed in our series. The presence of anticardiolipin antibodies and of multiple antibody specificities was significantly correlated with the development of SLE (p < 0.05). CONCLUSION: This analysis confirms the findings of our one year followup study that UCTD comprises a distinct group of mild diseases and that the rate of evolution to defined connective tissue diseases is higher during the first years after its onset. Patients who maintain an undifferentiated profile during the followup seem to run a decreasing risk of developing a defined CTD.

Pratesi F, Moscato S, Sabbatini A, Chimenti D, Bombardieri S, Migliorini P. · Department of Internal Medicine, University of Pisa, Italy. · J Rheumatol. · Pubmed #10648026 No free full text.

Abstract: OBJECTIVE: To analyze the presence and specificity of anti-alpha-enolase antibodies in various systemic autoimmune diseases. METHODS: Sera from patients with systemic lupus erythematosus (SLE), mixed cryoglobulinemia (MC), systemic sclerosis (SSc), and rheumatoid arthritis (RA) were tested by immunoblot on partially purified a-enolase from human kidney and on beta- and gamma-enolase. The isotype of anti-enolase antibodies was determined by means of isotype-specific monoclonal antibodies. RESULTS: IgG anti-alpha-enolase antibodies were detected in 9/33 (27%) SLE sera (6/9 patients had active renal disease), in 6/19 sera from patients with MC and nephritis, in 0/15 sera from MC patients without renal involvement, in 6/20 (30%) SSc sera, in 2/35 (6%) disease controls with RA, and in 2/32 (6%) healthy controls. The antibodies were not species-specific, but in most cases were specific for the alpha isoform of enolase. The anti-enolase immune response was not isotypically restricted. In half of the patients with SLE the anti-alpha-enolase and anti-DNA antibodies constituted distinct antibody populations, while in the other half a partial overlap of the 2 antibody specificities was observed. CONCLUSION: Anti-alpha-enolase antibodies can frequently be detected in systemic autoimmune disorders. In SLE and MC they are associated with nephritis and in SSc they are associated with severe endothelial damage. Alpha-enolase is ubiquitous, but is highly expressed in the kidney and also on the membrane of several cell types including endothelial cells. Thus, anti-alpha-enolase antibodies could contribute to renal injury not only by the local formation of immune complexes, but also by direct damage to endothelial cells.

Tavoni A, Vitali C, Cirigliano G, Frigelli S, Stampacchia G, Bombardieri S. · University of Pisa, Italy. · Arthritis Rheum. · Pubmed #10524701 links to  free full text

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Teixeira VH, Dieudé P, Michou L, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Bardin T, Cornélis F, Anonymous00026, Petit-Teixeira E. · No affiliation provided · Ann Rheum Dis. · Pubmed #19213753 No free full text.

This publication has no abstract.

Bernacchi E, Bianchi B, Amato L, Giorgini S, Fabbri P, Tavoni A, Bombardieri S. · No affiliation provided · J Dermatol Sci. · Pubmed #15894462 No free full text.

This publication has no abstract.