Bem-vindo à SPR - Sociedade Portuguesa de Reumatologia
Artigos Publicados por Reumatologistas Portugueses - 2009
Nesta secção encontra-se uma lista de artigos publicados por reumatologistas portugueses, em diversas publicações, ao longo do ano de 2009.
Interleukin-6 as a key player in systemic inflammation and joint destruction
Autoimmun Rev. 2009 Jan 31. [Epub ahead of print]
Fonseca JE, Santos MJ, Canhão H, Choy E
Interleukin-6 (IL-6) is a cytokine that can facilitate autoimmune phenomena, amplify acute inflammation and promote the evolution into a chronic inflammatory state. In addition, it is a major promoter of bone resorption in pathological conditions. In particular, IL-6 has a pivotal role in synovitis, bone erosions and in the systemic features of inflammation. This cytokine specifically binds to IL-6 receptor (IL-6R), forming the IL-6/IL-6R complex that binds to gp130, a membrane-bound protein, which is involved in non-ligand-binding signal transduction. Targeting IL-6R in both animal models of arthritis and in rheumatoid arthritis patients with a humanized anti IL-6R monoclonal antibody (tocilizumab) effectively controls local and systemic inflammatory manifestations and blocks cartilage and bone destruction. Given the pleiotropic function of IL-6 it can be anticipated that other inflammatory diseases and bone metabolic conditions might benefit from selective IL-6 signaling inhibition.
Tumor Necrosis Factor-{alpha} -308 Genotypes Influence Inflammatory Activity and TNF-{alpha} Serum Concentrations in Children with Juvenile Idiopathic Arthritis.
J Rheumatol. 2009 Jan 22. [Epub ahead of print]
Mourão AF, Caetano-Lopes J, Costa P, Canhão H, Santos MJ, Pinto P, Brito I, Nicola P, Cavaleiro J, Teles J, José AS, Gomes M, Branco J, da Costa JT, Pedro JG, de Queiroz MV, Fonseca JE
OBJECTIVE: Considering the relevance of tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-alpha serum concentrations were associated with TNF-alpha -308 genotypes.
METHODS: Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-alpha gene promoter polymorphisms at position -308 by restriction fragment-length polymorphism.
RESULTS: One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the -308 GA/AA genotypes and 76% the -308 GG genotype, similar to findings in controls. Patients with the -308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-alpha levels compared to those with the -308 GG genotype.
CONCLUSION: TNF-alpha -308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.
Prevalence of Fibromyalgia: A Survey in Five European Countries
Semin Arthritis Rheum. 2009 Feb 26. [Epub ahead of print]
Branco JC, Bannwarth B, Failde I, Abello-Carbonell J, Blotman F, Spaeth M, Saraiva F et al
OBJECTIVE: A survey was performed in 5 European countries (France, Germany, Italy, Portugal, and Spain) to estimate the prevalence of fibromyalgia (FM) in the general population.
METHODS: In each country, the London Fibromyalgia Epidemiological Study Screening Questionnaire (LFESSQ) was administered by telephone to a representative sample of the community over 15 years of age. A positive screen was defined as the following: (1) meeting the 4-pain criteria alone (LFESSQ-4), or (2) meeting both the 4-pain and the 2-fatigue criteria (LFESSQ-6). The questionnaire was also submitted to all outpatients referred to the 8 participating rheumatology clinics for 1 month. These patients were examined by a rheumatologist to confirm or exclude the FM diagnosis according to the 1990 American College of Rheumatology classification criteria. The prevalence of FM in the general population was estimated by applying the positive-predictive values to eligible community subjects (ie, positive screens).
RESULTS: Among rheumatology outpatients, 46% screened positive for chronic widespread pain (LFESSQ-4), 32% for pain and fatigue (LFESSQ-6), and 14% were confirmed FM cases. In the whole general population, 13 and 6.7% screened positive for LFESSQ-4 and LFESSQ-6, respectively. 3The estimated overall prevalence of FM was 4.7% (95% CI: 4.0 to 5.3) and 2.9% (95% CI: 2.4 to 3.4), respectively, in the general population. The prevalence of FM was age- and sex-related and varied among countries.
CONCLUSION: FM appears to be a common condition in these 5 European countries, even if data derived from the most specific criteria set (LFESSQ-6) are considered.
Assessment of salivary gland function in Sjögren's Syndrome: The role of Salivary Gland Scintigraphy
Autoimmun Rev. 2009 Feb 23. [Epub ahead of print]
Vinagre F, Santos MJ, Prata A, Silva JC, Santos AL
Salivary Gland Scintigraphy (SGS) is a non invasive method of salivary gland function assessment. This technique is easy to perform, reproducible and well tolerated by the patients. Additionally, an abnormal salivary gland scintigraphy result is accepted by the American-European consensus group as a criterion for the diagnosis of Sjögren's Syndrome. Scintigraphic evaluation of salivary gland function also plays an important role in therapeutic decision and patient follow-up. Schall's categorical classification is usually considered the standard method for salivary scintigraphy interpretation, though subjective and with limited capacity to discriminate borderline results. In order to improve the diagnostic accuracy of SGS, there has been an increasing interest in the quantification of glandular function. However, the debate on the most reliable and suitable parameters for the diagnosis of SS persists.
Biomechanical effects of inflammatory diseases on bone- rheumatoid arthritis as a paradigm
Autoimmun Rev. 2009 Feb 14. [Epub ahead of print]
Abdulghani S, Caetano-Lopes J, Canhão H, Fonseca JE
Inflammatory diseases, such as rheumatoid arthritis (RA), influence the bone remodelling process and increase the risk of fracture. Bone can be viewed as a composite material comprising of two phases: the organic phase, constituted predominantly by collagen type I, and the mineral phase, composed primarily by calcium phosphate, in the form of mineral crystals. The mineral component confers bone with strength and stiffness while the organic phase is responsible for bone toughness and ductility and acts as a scaffold for the mineralisation process. The efficacy of bone as a structural material depends on the balance between these different bone components and their biomechanical properties. The main determinants of mechanical properties of bone are the amount of mineral, the collagen content, the orientation of the collagen fibers and minerals and the accumulation of microcracks in the bone matrix. In a mice model of arthritis mechanical testing has shown that arthritic femurs have a significantly lower Young's modulus, yield stress and work until ultimate stress. This evidence suggests that one of the major explanations for the increased fracture risk in RA is related to the changes on bone components induced by inflammation that result in compromised biomechanical properties.
Undifferentiated connective tissue disease: a seven-center cross-sectional study of 184 patients
Clin Rheumatol. 2009 Apr 24. [Epub ahead of print]
Vaz CC, Couto M, Medeiros D, Miranda LC, Costa J, Nero P, Barros R, Santos MJ, Sousa E, Barcelos A, Inês L
The purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients-94.5%; mean age at time of evaluation-47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease.
Increased prevalence of allergic sensitisation in rheumatoid arthritis patients treated with anti-TNFalpha
Joint Bone Spine. 2009 May 19. [Epub ahead of print]
Machado P, Santos A, Pereira C, Loureiro C, Silva J, Chieira C, Malcata A
INTRODUCTION: Tumour necrosis factor alpha (TNFalpha) has emerged as a therapeutic target in chronic inflammatory disorders characterised by a Th1 type immune response, such as rheumatoid arthritis (RA). The presence of allergic disease in these patients could be influenced both by the presence of RA and anti-TNFalpha therapy. Our aim was to evaluate the prevalence of sensitisation to airborne allergens and allergic disease in RA patients, with and without anti-TNFalpha treatment.
METHODS: RA patients with (N=20) and without (N=20) anti-TNFalpha therapy (groups T and R) were enrolled. Healthy controls (N=60, group C) were randomly selected from the general population. All participants answered a standardised questionnaire to assess the prevalence of allergic disease and had skin prick tests (SPT) with a standard panel of airborne allergen extracts.
RESULTS: Significant differences were found in the prevalence of positive SPT between groups T and R (70% vs 35%, p=0.027) and groups T and C (70% vs 36.7%, p=0.009), but not between groups R and C. The prevalence of allergic disease was similar in the three groups. Groups T and R had similar gender and age distribution, disease duration, disease activity score (DAS28), erythrocyte sedimentation rate and serum C-reactive protein.
CONCLUSIONS: Increased prevalence of sensitisation to airborne allergens in RA patients treated with anti-TNFalpha was found. The clinical impact of the positive SPT following anti-TNFalpha initiation has now to be assessed.
Competencies in rheumatology: a European framework
Best Pract Res Clin Rheumatol. 2009 Apr;23(2):145-60
Faarvang KL, da Silva J A
The aims, structure, methods and educational experiences employed in the training of rheumatologists vary from one national programme to another, according to traditions, rules and resources. Mutual recognition of titles, the free movement of labour and the striving towards for high-quality standards in medical care in Europe demand that efforts and progress are made to ensure that similar competencies are achieved by different programmes. The European Rheumatology Curriculum Framework, developed by the European Board of Rheumatology, is meant to be a step towards the harmonization of rheumatology specialist training within the European Union, by providing a reference framework to the development and benchmarking of national curricula for the specialist training of rheumatologists. The European Rheumatology Curriculum Framework has now been endorsed by scientific and educational bodies in 17 member countries. It has been provided with a contextualized review of good practice in curriculum planning and development - the European Board of Rheumatology Educational Guide.
Persistent low grade synovitis without erosive progression in magnetic resonance imaging of rheumatoid arthritis patients treated with infliximab over 1 year
Clin Rheumatol. 2009 Jun 6. [Epub ahead of print]
Canhão H, Fonseca JE, Tavares NJ, Cruz M, Branco JC, Queiroz MV
Disease remission is only reached by a minority of rheumatoid arthritis (RA) patients treated with infliximab. Radiological assessment reported in clinical trials support the view that even under persistent inflammatory activity there is no further structural damage. Magnetic resonance imaging (MRI) allows a highly accurate detection of synovitis, bone edema, and erosions, constituting the ideal instrument for the evaluation of treatment response. The goal of this study was to evaluate MRI changes over 1 year in RA patients treated with infliximab. Four RA patients refractory to methotrexate (MTX) therapy were treated with infliximab 3 mg/kg 8/8 weeks and followed up for 1 year. Disease Activity Score (DAS28) was measured in the day of each infliximab administration. MRI was performed at baseline, 3 months, and 1 year. A simplified OMERACT RA MRI scoring (RAMRIS) was applied to the dominant wrist: synovitis (0-3) was measured in the intercarpal-carpometacarpal joints (CMTJ); bone edema (0-39) and erosions (0-130) in the base of the metacarpal and wrist bones. Baseline DAS28 was superior to 3.2 in all patients (ranging from 4.8 up to 6.2). At 14 weeks, DAS28 was still superior to 3.2 (ranging from 3.5 up to 4.6) and at 46 weeks all patients have responded, however without having achieved clinical remission, as DAS28 was still above 2.6 (ranging from 2.6 up to 3.4). MRI showed that synovitis was reduced in all patients to a score of 1, bone edema was slightly reduced (10% reduction), and erosive score was unchanged (baseline values ranging from 2 up to 20). Despite persistent low disease activity, these four RA patients treated with infliximab had stable simplified RAMRIS erosive scores over 1 year. These results support the view that there might be an uncoupling process between inflammation and bone erosions when tumor necrosis factor alpha is targeted in RA.
Systemic lupus erythematosus and ulcerative colitis
Lupus. 2009;18(8):762-763
Medeiros D, Isenberg D
Chronic arthritis directly induces quantitative and qualitative bone disturbances leading to compromised biomechanical properties
Clinical and Experimental Rheumatology 2009; 27: 475-482.
J. Caetano-Lopes, A.M.Nery, R. Henriques, H. Canhão, J. Duarte, P.M. Amaral, M. Vale, R.A. Moura, P.A. Pereira, P. Weinmann, S. Abdulghani, M. Souto-Carneiro, P. Rego, J. Monteiro, S. Sakagushi, M.V. Queiroz, Y.T. Konttinen, L. Graça, M.F. Vaz, J.E. Fonseca
Objectives: Rheumatoid arthritis (RA) is associated with an increased risk of fragility fractures. In RA patients, the direct effect of inflammation on bone is difficult to study because their skeleton is also affected by medication with corticosteroids and other drugs as well as aging and menopause, which contribute to bone fragility. This study used an animal model of chronic arthritis to evaluate the direct impact of chronic inflammation on biomechanical properties and structure of bone.
Methods: In the SKG mouse chronic arthritis model three point bending tests were performed on femoral bones and compression tests on vertebral bodies. Collagen structure was analysed using second-harmonic generation (SHG) imaging with a two-photon microscope, ultramorphology by scanning electron microscopy (SEM) coupled with energy dispersive x-ray spectroscopy (EDS) and bone density using water pycnometer.
Results: Arthritic bones had poor biomechanical quality compared to control bones. SHG, SEM and pycnometry disclosed variable signs of impaired collagen organization, poor trabecular architecture and low bone density.
Conclusion: Present data demonstrate for the first time that chronic inflammation per se, without confounding influence of drugs and aging, leads to impairment of bone biomechanics in terms of stiffness, ductility and ultimate strength (fracture).
Key words: Rheumatoid arthritis, SKG mice, osteoporosis, bone, mechanical tests, multiphoton microscopy.
Treating lupus: from serendipity to sense, the rise of the new biologicals and other emerging therapies
Best Practice & Research Clinical Rheumatology 23 (2009) 563–574
Elsa Sousa, MD, Rheumatology Trainee, David Isenberg, MD, FRCP, Professor
During the last 10 years our increasing understanding of the immunopathogenesis of systemic lupus erythematosus (SLE) has led to the introduction of several new biological therapies. SLE treatment has moved from the use of conventional drugs such as hydroxychloroquine, corticosteroids, and non-specific immunosuppressants to targeting selective components of the immune system in the hope that they can be more effective and reduce undesired side-effects. These new treatments include B-cell-depleting therapies, antibodies and fusion proteins that block interleukins or the cross-talk between B and T cells, and tolerogens. However, although there are great expectations about new agents, double-blind controlled trials demonstrating safety and efficacy are still awaited, and better instruments for evaluating disease activity need to be developed.
Keywords: systemic lupus erythematosus, new biologics, B-cell depletion
Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study
Arthritis Res Ther. 2009;11(3):R69
Suarez-Gestal M, Calaza M, Endreffy E, Ordi-Ros J, Domenico Sebastiani G, Santos MJ, Papasteriades C, Suarez A, Carreira P, Gomez-Reino JJ, Gonzalez A
INTRODUCTION: We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci.
METHODS: We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of allele frequencies between cases and controls was done with the Mantel-Haenszel approach to account for heterogeneity between sample collections.
RESULTS: A previously controversial association with a SNP in the TYK2 gene was replicated (odds ratio (OR) = 0.79, P = 2.5 x 10-5), as well as association with the X chromosome MECP2 gene (OR = 1.26, P = 0.00085 in women), which had only been reported in a single study, and association with four other loci, 1q25.1 (OR = 0.81, P = 0.0001), PXK (OR = 1.19, P = 0.0038), BANK1 (OR = 0.83, P = 0.006) and KIAA1542 (OR = 0.84, P = 0.001), which have been identified in a genome-wide association study, but not found in any other study. All these replications showed the same disease-associated allele as originally reported. No association was found with the LY9 SNP, which had been reported in a single study.
CONCLUSIONS: Our results confirm nine SLE loci. For six of them, TYK2, MECP2, 1q25.1, PXK, BANK1 and KIAA1542, this replication is important. The other three loci, ITGAM, STAT4 and C8orf13-BLK, were already clearly confirmed. Our results also suggest that MECP2 association has no influence in the sex bias of SLE, contrary to what has been proposed. In addition, none of the other associations seems important in this respect.
Macroscopic features of knee synovitis in early untreated Behçet disease and psoriatic arthritis
Clin Rheumatol. 2009 Sep;28(9):1053-7
Moll C, Bogas M, Gómez-Puerta JÁ, Celis R, Vázquez I, Rodríguez F, Kanterewicz E, Sanmarti R, Cañete JD
In a previous study, we found that synovial immunopathology differs between Behçet disease (BD) and psoriatic arthritis (PsA). The objective of this study is to describe the macroscopic features of early untreated knee synovitis in BD and PsA. Fourteen consecutive patients with active early knee synovitis (seven BD and seven PsA) undergoing rheumatologic arthroscopy were assessed. The following macroscopic synovial features were evaluated and scored by analyzing the video recordings of each procedure: capillary hyperaemia, morphology of synovitis, vascular pattern, fibrinoid membranes, and topographic distribution of these features. Video-recording of 35 early untreated arthritis patients with different diagnoses were also studied looking for BD-like macroscopic features. Six out of seven BD patients had extensive fibrinoid membranes and large areas of erythematous synovitis without villi or a distinctive vascular pattern, while PsA patients had diffuse erythematous villous synovitis with a tortuous vascular morphology. None of the 35 patients with early untreated arthritis exhibited all the characteristic features of BD synovitis. This exploratory study shows some distinctive features between BD and PsA knee synovitis that confirm macroscopic differences in patients with previously reported immunopathological differences.
Respiratory manifestations of systemic lupus erythematosus: old and new concepts
Best Pract Res Clin Rheumatol. 2009 Aug;23(4):469-80
Pego-Reigosa JM, Medeiros DA, Isenberg DA
The respiratory system is commonly involved in systemic lupus erythematosus. Lung disorders are classified as primary (due to lupus) and secondary to other conditions. Pleuritis and pulmonary infections are the most prevalent respiratory manifestations of each type. Other infrequent manifestations include interstitial lung disease, acute lupus pneumonitis, diffuse alveolar haemorrhage, pulmonary arterial hypertension, acute reversible hypoxaemia and shrinking lung syndrome. Even when current diagnostic tests contribute to an earlier diagnosis, the treatment of these manifestations is based on clinical experience and small series. Larger controlled trials of the different therapies in the treatment of those lung manifestations of lupus are needed. Overall malignancy is little increased in lupus, but lung cancer and non-Hodgkin's lymphoma are among the most frequent types of cancer found in these patients. As survival in lupus patients has improved over recent decades, avoiding pulmonary damage emerges as an important objective.
Concomitant diseases in a cohort of patients with idiopathic myositis during long-term follow-up
Clin Rheumatol. 2009 Aug;28(8):947-53
Ng KP, Ramos F, Sultan SM, Isenberg DA
This study aims to report the concomitant diseases observed and damage outcome in a cohort of patients with adult idiopathic inflammatory myositis (IIM) during long-term follow-up. All patients with IIM were identified from a single centre (follow-up between 1979 and 2006) and fulfilled at least three of the four Bohan and Peter criteria. Patients with inclusion body myositis, juvenile-onset myositis and overt overlap syndromes were excluded. Medical notes were retrospectively reviewed. Concomitant diseases identified were divided into 12 different organ systems (bone, cardiac, respiratory, gastrointestinal, renal, central nervous, malignancy, infection, endocrine, eyes, dermatological and haematological). Patient damage index was calculated using the Myositis Damage Index tool. Fifty-five patients (31 polymyositis, 24 dermatomyositis) were identified. The most prevalent organ system involved was lung with 40 events per 1,000 patient years follow-up. There was significant steroid-related complications with 17/18 patients with bone involvement having osteopenia/osteoporosis. Sjogren's syndrome (n = 3) was the most frequent concomitant auto-immune disease observed. Patients with a higher number of organ systems involved had a significantly higher damage index (r = 0.48, p = 0.001). White patients showed a significant trend to develop more than three other organ system involvement (p < 0.0001) and myositis-related lung disease (p < 0.0001) compared to other races. There is significant steroid-related morbidity in adult IIM patients under long-term follow-up. The prevalence of another concomitant auto-immune disease unlike patients with lupus or Sjogren's syndrome is low.
Pharmacological management of osteoporosis and concomitant calcium supplementation in a Portuguese urban population: the EpiPorto study (2005-2007)
Clin Exp Rheumatol. 2009 Jan-Feb;27(1):47-53
Lucas R, Rocha O, Bastos J, Costa L, Barros H, Lunet N
INTRODUCTION: We aimed to describe the pharmacological management of osteoporosis in the general population, with emphasis on the inclusion of calcium supplementation.
METHODS: We interviewed 1511 participants in an evaluation of a cohort of Portuguese adults. Antiresorptive therapy and calcium supplementation in the previous year were recorded. Socio-demographic characterisation included education, occupation, marital status and source of medical care. The participants' osteoporosis history and menopause age were noted. Dietary calcium intake was quantified using a food frequency questionnaire and a calcaneus quantitative ultrasound was conducted.
RESULTS: Antiresorptive drugs had been used by 11.4% of women and 1.2% of men in the previous year. Bisphosphonates were the most referred subgroup (88% of all therapies), followed by raloxifen, and calcitonin. Overall, 43% of women reported using calcium in combination with bone-sparing drugs. Combination therapy was more frequent among older women (> or =70 years old: 63%), those with the highest educational level (>12 schooling years: 49%), blue-collar occupations (55%) and private healthcare (43%). Women with longer postmenopausal periods (>10 years: 42%) and those with the highest spontaneous calcium intakes (highest tertile: 44%) reported combination therapy more frequently.
CONCLUSION: Although treatment with bone-sparing drugs is frequent, the management of osteoporosis does not systematically include the recommended calcium supplementation.
Association study of the RANK locus in white European rheumatoid arthritis families
Ann Rheum Dis. 2009 Mar;68(3):448-9
Lopes-Vaz A, Teixeira VH, Dieudé P, Michou L, Migliorini P, Balsa A, Barrera P, Alves H, Fernandes M, Vaz C, Pascual-Salcedo D
Selecting men for bone densitometry: performance of osteoporosis risk assessment tools in Portuguese men
Osteoporos Int. 2009 Sep 2. [Epub ahead of print]
Machado P, Coutinho M, Pereira da Silva JA
Clinicians need tools to identify patients most likely to benefit from bone mineral density (BMD) testing, for which cost-effectiveness does not allow generalized screening. This study supports the utility of osteoporosis risk assessment tools in selecting men for BMD testing. Different cutoff values may be appropriate for different countries and/or ethnic origins.
INTRODUCTION: Our aim was to evaluate the utility of three osteoporosis (OP) risk assessment tools in a large group of Portuguese men aged 50 or more and to determine the best cutoff value to be used for selecting men for bone densitometry.
METHODS: We assessed the performance of three simple tools in 202 randomly selected men: body weight criterion (BWC), osteoporosis self-assessment tool for Asians (OSTA), and a modified version of the OSTA equation (OST). Previously published cutoff values (validated in postmenopausal women) and three additional cutoff values were tested. Sensitivity (SE), specificity (SP), predictive values, and area under the receiver operating characteristic (AUROC) curve for correctly selecting men with OP (defined by BMD testing) were determined.
RESULTS: Mean age of the cohort was 63.8 years. According to the World Health Organization diagnostic categories, 16.8% had osteoporosis. The best performing cutoffs for correctly selecting men with OP for BMD testing were OST < 3 (SE = 75.5%, SP = 50.0%, AUROC = 0.632), OSTA < 3 (SE = 73.5%, SP = 58.3%, AUROC = 0.659), and BWC < 75 kg (SE = 73.5%, SP = 61.3%, AUROC = 0.674).
CONCLUSIONS: OP risk assessment tools seem to be useful in men aged 50 or more. Best cutoff values are different from those recommended for postmenopausal women. Different cutoff values may be appropriate for different countries and/or ethnic origins.
Rituximab use in pediatric autoimmune diseases: four case reports
Ann N Y Acad Sci. 2009 Sep;1173:712-20
Polido-Pereira J, Ferreira D, Rodrigues AM, Nascimento C, Costa P, Almeida M, Esteves da Silva JE, Simão C, Stone R, Ramos F, Neto A, da Costa JC, Melo-Gomes J, Gomes-Pedro J, Viana-Queiroz M, Canhão H, Fonseca JE
Rituximab (RTX) is currently used in many diseases, but its efficacy and safety in juvenile systemic lupus erythematosus (SLEj) is still unknown. In this chapter we present four case reports of children treated with RTX: three SLE and one immune thrombocytopenic purpura (ITP). Two of the three SLEj patients had class IV lupus nephritis (LN) and hematologic manifestations (pancytopenia), both reaching complete recovery of blood counts and improvement of LN with RTX treatment. Our third SLE patient had a severe onset with generalized microangiopathic manifestations in association with antiphospholipid antibodies and has been in remission for almost 1 year after RTX. However, our fourth case, a patient with ITP and renal failure, was treated with RTX without either hematologic or renal response.
Ankylosing spondylitis susceptibility and severity--contribution of TNF gene promoter polymorphisms at positions -238 and -308
Ann N Y Acad Sci. 2009 Sep;1173:581-8
Sousa E, Caetano-Lopes J, Pinto P, Pimentel dos Santos F, Teles J, Canhão H, Rodrigues A, Resende C, Mourão AF,Ribeiro C, Pinto TL, Rosa CM, da Silva JA, Branco J, Ventura F, Queiroz MV, Fonseca JE
Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPs were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position -238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the -308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions -238 and -308 could have a small influence on AS susceptibility and prognosis.
Predictors of damage progression in Portuguese patients with systemic lupus erythematosus
Ann N Y Acad Sci. 2009 Sep;1173:822-8
Santos MJ, Vinagre F, Nero P, Barcelos A, Barcelos F, Rodrigues AM, Matos AA, Silva C, Miranda L, Capela S, Marques A, Branco J, da Silva JC
Patients with systemic lupus erythematosus (SLE) have a longer life expectancy. The occurrence of irreversible damage has become a major concern. The present study assessed damage progression in patients with SLE over a 2-year period and identified baseline features associated with damage accrual. Two hundred and twenty-one patients that fulfilled criteria for SLE and had a follow-up longer than 6 months were enrolled. Demographic, clinical, and immunological data were collected at baseline. Accumulated organ damage was scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Patients were prospectively followed and SDI assessment repeated at 2 years. At baseline 72 patients (33%) presented some irreversible damage, and after 2 years 53 had accrued new damage. The mean SDI for the whole cohort increased from 0.582 to 0.980. Damage progression was higher in ocular, cardiovascular, and musculoskeletal systems. Older age [OR = 1.045; 95% confidence interval (CI) 1.021-1.069; P = 0.03], presence of antiphospholipid antibodies (OR = 3.047; 95% CI 1.169-7.941; P = 0.02), steroid use (OR = 6.401; 95% CI 1.601-25.210; P = 0.008), azathioprine use (OR = 3.501; CI 1.224-10.012; P = 0.01), and hypertension (OR = 3.825; 95% CI 1.490-9.820; P = 0.005) were predictors of damage progression in multivariate analysis. Overall SDI increased over time, with some systems being affected more frequently. Demographic and clinical characteristics, co-morbidity, and treatment options may contribute to irreversible damage. It is necessary to determine whether the control of modifiable factors (e.g., hypertension and judicious use of medications) might prevent damage progression in SLE patients.
Association of IL23R and ERAP1 genes with ankylosing spondylitis in a Portuguese population
Clin Exp Rheumatol. 2009 Sep-Oct;27(5):800-6
Pimentel dos Santos F, Ligeiro D, Matos M, Mourão AF, Sousa E, Pinto P, Ribeiro A, Sousa M, Barcelos A, Godinho F, Cruz M, Fonseca JE, Guedes-Pinto H, Trindade H, Evans DM, Brown MA, Branco JC
OBJECTIVE: Association between ankylosing spondylitis (AS) and two genes, ERAP1 and IL23R, has recently been reported in North American and British populations. The population attributable risk fraction for ERAP1 in this study was 25%, and for IL23R, 9%. Confirmation of these findings to ERAP1 in other ethnic groups has not yet been demonstrated. We sought to test the association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to AS among a Portuguese population. We also investigated the role of these genes in clinical manifestations of AS, including age of symptom onset, the Bath Ankylosing Spondylitis Disease Activity, Metrology and Functional Indices, and the modified Stoke Ankylosing Spondylitis Spinal Score.
METHODS: The study was conducted on 358 AS cases and 285 ethnically matched Portuguese healthy controls. AS was defined according to the modified New York Criteria. Genotyping of IL23R and ERAP1 allelic variants was carried out with TaqMan allelic discrimination assays. Association analysis was performed using the Cochrane-Armitage and linear regression tests of genotypes as implemented in PLINK for dichotomous and quantitative variables respectively. A meta-analysis for Portuguese and previously published Spanish IL23R data was performed using the StatsDirect(R) Statistical tools, by fixed and random effects models.
RESULTS: A total of 14 nsSNPs markers (8 for IL23R, 5 for ERAP1, 1 for LN-PEP) were analysed. Three markers (2 for IL23R and 1 for ERAP1) showed significant single-locus disease associations, confirming that the association of these genes with AS in the Portuguese population. The strongest associated SNP in IL23R was rs1004819 (OR=1.4, p=0.0049), and in ERAP1 was rs30187 (OR=1.26, p=0.035). The population attributable risk fractions in the Portuguese population for these SNPs are 11% and 9.7% respectively. No association was seen with any SNP in LN-PEP, which flanks ERAP1 and was associated with AS in the British population. No association was seen with clinical manifestations of AS.
CONCLUSION: These results show that IL23R and ERAP1 genes are also associated with susceptibility to AS in the Portuguese population, and that they contribute a significant proportion of the population risk for this disease.
Prediction of Vertebral Fractures Is Specific for Gender and Site of Bone Mineral Density Measurement
J Rheumatol. 2009 Nov 16. [Epub ahead of print]
Jacobs JW, da Silva JA, Armbrecht G, Bijlsma JW, Verstappen SM
OBJECTIVE: To investigate basic assumptions of prediction models for future vertebral fractures.
METHODS: Lateral radiographs of the spine were obtained from 314 Portuguese individuals aged 60 years or older (205 women and 109 men) with bone mineral density (BMD) measurements at several sites. Associations between BMD at various sites, participant characteristics, and vertebral fractures were investigated. For men and women separately, logistic regression analyses and analyses of areas under the receiver-operating characteristic (ROC) curves were performed to determine the accuracy of BMD measurment at predicting the presence of vertebral deformities.
RESULTS: BMD measurements at all sites significantly predicted the presence of osteoporotic vertebral deformities in women but not in men. Similarly, in analyses of areas under ROC curves, BMD assessments were statistically significantly related to vertebral deformities in women but not in men. In multivariate analyses, BMD measurements of the lumbar spine and of the forearm, adjusted for gender, age, and body mass index, significantly predicted the presence of vertebral deformity, but BMD of the hip sites did not.
CONCLUSION: Prediction of fractures is specific for gender and site of BMD measurement. This challenges the use of similar algorithms for men and women as well as the use of hip BMD data to accurately estimate future vertebral fracture risk.
Exuberant calcinosis and acroosteolysis. A diagnostic challenge.
Clin Exp Rheumatol. 2009 May-Jun;27(3 Suppl 54):55-8
Saavedra MJ, Ambrosio C, Malcata A, Matucci-Cerinic M, Silva JA
A case of exuberant acroosteolysis and subcutaneous tissue calcinosis in the absence of skin involvement is presented. Different hypotheses are discussed following the clinical unfolding of the case in practice.
©2001-2012 Sociedade Portuguesa de Reumatologia ©2001-2012 ALERT Life Sciences Computing, S.A. Desenvolvido por ALERT Life Sciences Computing, S.A.