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ID PMID Title PublicationDate abstract
22241902 Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection i 2012 Jul OBJECTIVES: To explore the relationship of serious infection risk with current and prior oral glucocorticoid (GC) therapy in elderly patients with rheumatoid arthritis (RA). METHODS: A case-control analysis matched 1947 serious infection cases to five controls, selected from 16207 RA patients aged ≥ 65 between 1985-2003 in Quebec, Canada. Adjusted odds ratios for infection associated with different GC patterns were estimated using conventional models and a weighted cumulative dose (WCD) model. RESULTS: The WCD model predicted risks better than conventional models. Current and recent GC doses had highest impact on current risk. Doses taken up to 2.5 years ago were also associated with increased risk, albeit to a lesser extent. A current user of 5mg prednisolone had a 30%, 46% or 100% increased risk of serious infection when used continuously for the last 3 months, 6 months or 3 years, respectively, compared to a non-user. The risk associated with 5mg prednisolone taken for the last 3 years was similar to that associated with 30 mg taken for the last month. Discontinuing a two-year course of 10mg prednisolone six months ago halved the risk compared to ongoing use. CONCLUSIONS: GC therapy is associated with infection risk in older patients with RA. The WCD model provided more accurate risk estimates than conventional models. Current and recent doses have greatest impact on infection risk, but the cumulative impact of doses taken in the last 2-3 years still affects risk. Knowing how risk depends on pattern of GC use will contribute to an improved benefit/harm assessment.
21337318 Rituximab treatment induces the expression of genes involved in healing processes in the r 2011 May OBJECTIVE: Rituximab displays therapeutic benefits in the treatment of patients with rheumatoid arthritis (RA) resistant to tumor necrosis factor (TNF) blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. We undertook this study to investigate the global molecular effects of rituximab in synovial biopsy samples obtained from anti-TNF-resistant RA patients before and after administration of the drug. METHODS: Paired synovial biopsy samples were obtained from the affected knee of anti-TNF-resistant RA patients before (time 0) and 12 weeks after (time 12) initiation of rituximab therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time reverse transcriptase-polymerase chain reaction experiments were performed to confirm the differential expression of selected transcripts. RESULTS: According to Student's paired t-tests, 549 of 54,675 investigated probe sets were differentially expressed between time 0 and time 12. Pathway analysis revealed that genes down-regulated between time 0 and time 12 were significantly enriched in immunoglobulin genes and genes involved in chemotaxis, leukocyte activation, and immune responses (Gene Ontology annotations). In contrast, genes up-regulated between time 0 and time 12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (Gene Set Enrichment Analysis). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy. CONCLUSION: Rituximab displays unique effects on global gene expression profiles in the synovial tissue of RA patients. These observations open new perspectives in the understanding of the biologic effects of the drug and in the selection of patients likely to benefit from this therapy.
21542893 The role of the central nervous system in the generation and maintenance of chronic pain i 2011 Apr 28 Pain is a key component of most rheumatologic diseases. In fibromyalgia, the importance of central nervous system pain mechanisms (for example, loss of descending analgesic activity and central sensitization) is well documented. A few studies have also noted alterations in central pain processing in osteoarthritis, and some data, including the observation of widespread pain sensitivity, suggest that central pain-processing defects may alter the pain response in rheumatoid arthritis patients. When central pain is identified, different classes of analgesics (for example, serotonin-norepinephrine reuptake inhibitors, α2δ ligands) may be more effective than drugs that treat peripheral or nociceptive pain (for example, nonsteroidal anti-inflammatory drugs and opioids).
22522087 The perioperative use of biologic agents in patients with rheumatoid arthritis. 2012 Dec Biologic drugs have gained an important place in the treatment of rheumatic diseases. These medications may, however, pose a higher risk of infections in rheumatic patients who a priori are prone to infections. The potential consequences of the immunosuppressive effects of the biologics raise concern about their safety in the perioperative setting. This article reviews the scientific literature that examines the influence of biologic drugs on post-surgical complications. According to these studies, it is apparently safe to use tumor necrosis factor-α blockers and the IL-6 receptor blocker, although a few study limitations, such as small sample size, retrospective design and differences in the comparison groups weaken the conclusions. In addition, the recommendations for some of the biologic drugs are based solely on pharmacological parameters due to the absence of trials, and larger randomized controlled studies are needed to establish the safety of their use by patients with rheumatic diseases.
22440823 Genetic variants in IL15 associate with progression of joint destruction in rheumatoid art 2012 Oct BACKGROUND: Interleukin (IL)-15 levels are increased in serum, synovium and bone marrow of patients with rheumatoid arthritis (RA). IL-15 influences both the innate and the adaptive immune response; its major role is activation and proliferation of T cells. There are also emerging data that IL-15 affects osteoclastogenesis. The authors investigated the association of genetic variants in IL15 with the rate of joint destruction in RA. METHOD: 1418 patients with 4885 x-ray sets of both hands and feet of four independent data sets were studied. First, explorative analyses were performed on 600 patients with early RA enrolled in the Leiden Early Arthritis Clinic. Twenty-five single-nucleotide polymorphisms (SNPs) tagging IL-15 were tested. Second, SNPs with significant associations in the explorative phase were genotyped in data sets from Groningen, Sheffield and Lund. In each data set, the relative increase of the progression rate per year in the presence of a genotype was assessed. Subsequently, data were summarised in an inverse weighting meta-analysis. RESULTS: Five SNPs were significantly associated with rate of joint destruction in phase 1 and typed in the other data sets. Patients homozygous for rs7667746, rs7665842, rs2322182, rs6821171 and rs4371699 had respectively 0.94-, 1.04-, 1.09-, 1.09- and 1.09-fold rate of joint destruction compared to other patients (p=4.0×10(-6), p=3.8×10(-4), p=5.0×10(-3), p=5.0×10(-3) and p=9.4×10(-3)). DISCUSSION: Independent replication was not obtained, possibly due to insufficient power. Meta-analyses of all data sets combined resulted in significant results for four SNPs (rs7667746, p<0.001; rs7665842, p<0.001; rs4371699, p=0.01; rs6821171, p=0.01). These SNPs were also significant after correction for multiple testing. CONCLUSION: Genetic variants in IL-15 are associated with progression of joint destruction in RA.
22490583 Impaired brachial artery flow-mediated dilation and increased carotid intima-media thickne 2012 Mar BACKGROUND: Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are common parameters used for detecting subclinical atherosclerosis. This study compared subclinical atherosclerosis of the carotid and brachial arteries in rheumatoid arthritis (RA) patients and healthy controls using high resolution ultrasonography. We also investigated their correlation with clinical factors and the association between FMD% and CIMT. METHODS: One hundred and two RA patients and 46 age-gender matched healthy controls were included in the study. FMD of the brachial artery and CIMT were measured ultrasonographically. Patients with diabetes mellitus, hypertension, renal failure, history of cardiovascular or cerebrovascular disease were excluded. Subjects who were receiving or used high dose steroids were also excluded. RESULTS: The CIMT was significantly higher in patients than that in the control group ((0.697±0.053) vs. (0.554±0.051) mm, P<0.001), whereas brachial artery FMD% was lower in patients than that in the controls ((5.454±2.653)% vs. (8.477±2.851)%, P<0.001). CIMT was related to age, disease duration, tender and swollen joint score, C-reactive protein, systolic blood pressure and high-density lipoprotein. However, FMD% was only association with systolic blood pressure. There was no significant correlation between CIMT and FMD%. CONCLUSIONS: Compared with the healthy control subjects, RA patients without clinically evident cardiovascular disease had subclinical atherosclerosis in terms of impaired FMD% and increased CIMT. FMD% and CIMT may measure a different stage of subclinical atherosclerosis in RA patients.
21952924 Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone deacetyl 2012 Feb OBJECTIVE: To characterize the role of histone deacetylase (HDAC) activity in rheumatoid arthritis (RA) and to evaluate the effects of MI192, a novel HDAC-3-selective inhibitor, compared with the established nonselective HDAC inhibitor trichostatin A (TSA), on proinflammatory cytokine production. METHODS: Activity of HDAC and histone acetyltransferase was measured in peripheral blood mononuclear cells (PBMCs) from RA patients by spectrophotometric assay, prior to and after 12 weeks of etanercept therapy. The effects of HDAC inhibitor treatment on cytokine production in both RA and healthy PBMCs were assessed by enzyme-linked immunosorbent assay. RESULTS: RA PBMCs exhibited significantly increased HDAC activity (P = 0.007) compared to PBMCs from healthy individuals, and the increase was unaltered after 12 weeks of etanercept therapy. TSA was a potent inhibitor of tumor necrosis factor (TNF) and interleukin-6 (IL-6) production in both RA and healthy PBMCs and of interferon-γ (IFNγ) production in healthy PBMCs; IFNγ was not produced by RA PBMCs. MI192 inhibited TNF production at high concentrations and dose-dependently inhibited IL-6 in RA PBMCs but not healthy PBMCs, across a dose range of 10 μM-5 nM. CONCLUSION: HDAC activity is dysregulated in RA PBMCs and is a potential target for therapeutic intervention, as it is not affected by conventional anti-TNF treatment with etanercept. Both the selective and the nonselective HDAC inhibitors (MI192 and TSA, respectively) were found to regulate cytokine production from PBMCs, but their effects were cell type and compound specific. HDAC inhibitors have potential in the treatment of RA, and HDAC-selective inhibition may improve the therapeutic margin of safety; however, further clinical characterization and evaluation for adverse effects is needed.
22045976 Psychiatric disorders in patients with immune-mediated inflammatory diseases: prevalence, 2011 Nov There has been much speculation on the importance of emotional factors in patients with immune-mediated inflammatory disease (IMID); it is only in the past 10 years that well designed, large-cohort studies have been able to clarify this relationship. This article provides an overview of evidence on the occurrence of depression and anxiety in IMID, and the role of these comorbidities as risk factors for onset of IMID, as well as the degree to which they affect the course of disease and treatment outcomes.
21502386 Science to practice: Can inflammatory arthritis be monitored by using MR imaging with inje 2011 May In providing a new tool for imaging inflammation, the study by MacKenzie et al may enable more effective treatment plans for inflammatory arthritis by allowing early, noninvasive monitoring of response to therapy.
21450355 Detection of preclinical impairment of myocardial function in rheumatoid arthritis patient 2012 Sep 20 BACKGROUND: Subclinical cardiac involvement diagnosis is important for long term management of rheumatoid arthritis (RA) patients. Recently, 2D speckle tracking echocardiography (STE) allows non invasive and angle-independent measurement of left ventricular (LV) dimensions and regional myocardial strain (ε). The aim of this study was to assess whether STE can be useful to detect subclinical cardiac involvement in RA patients. METHODS: We studied 22 RA patients (10 M, 12 F, aged 46 ± 12 years) without clinical evidence of coronary artery disease (CAD) and 20 healthy controls matched for age and sex by STE. LV end-systolic longitudinal and radial ε from apical 4-chamber view were analyzed using available software (QLAB 6.0). RESULTS: Standard echo and Doppler parameters did not differ between the 2 groups. Tissue Doppler Imaging (TDI) showed a significant reduction of S', E' and E'/A' ratio from the basal septum and lateral mitral annulus in RA patients. LV end-systolic radial and longitudinal ε of basal-lateral, basal- and mid-septal, mid-lateral and apical segments were significantly reduced compared to controls. CONCLUSIONS: Our data indicate that LV end-systolic radial and longitudinal ε are reduced in RA patients without CAD despite normal standard echo. Non invasive evaluation of LV function by STE appears to be useful to detect subclinical cardiac involvement in comparison to conventional 2D echoDoppler, representing a promising new modality to follow-up RA patients for cardiac involvement.
22956167 Comparison of patient satisfaction with two different etanercept delivery systems. A rando 2012 Dec The objective of this study was to investigate patients' perceptions of the acceptability of two devices delivering etanercept for rheumatoid arthritis (RA) treatment and to explore whether specific patients' attributes are associated with device preferences. Two similar multicenter, open-label, randomised, parallel-design studies were conducted in a total of 13 European countries. A total of 640 adult patients with RA were randomised to receive etanercept 50 mg once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a pre-filled pen (PFP). Patient satisfaction at week 12 was measured on a 0- to 10-point Likert scale (primary endpoint). The study was powered to demonstrate non-inferiority of a PFP over PFS for the primary endpoint. At week 12, mean patient satisfaction was 8.3 (± 2.4) points in the pen group and 7.2 (± 2.6) points in the syringe group. Non-inferiority and even superiority of the pen over the syringe was demonstrated. In conclusion, this study showed higher patient satisfaction in the group of patients injecting etanercept with a PFP compared with the group of patients using a PFS.
22872428 Detection of gene expression signatures related to underlying disease and treatment in rhe 2013 Jul OBJECTIVES: Gene expression signatures can provide an unbiased view into the molecular changes underlying biologically and medically interesting phenotypes. We therefore initiated this study to identify signatures that would be of utility in studying rheumatoid arthritis (RA). METHODS: We used microarray profiling of peripheral blood mononuclear cells (PBMCs) in 30 RA patients to assess the effect of different biologic agent (biologics) treatments and to quantify the degree of a type-I interferon (IFN) signature in these patients. A numeric score was derived for the quantification step and applied to patients with RA. To further characterize the IFN response in our cohort, we employed type-I IFN treatment of PBMCs in vitro and in reporter assays. RESULTS: Profiling identified a subset of RA patients with upregulation of type-I IFN-regulated transcripts, thereby corroborating previous reports showing RA to be heterogeneous for an IFN component. A comparison of individuals currently untreated with a biologic with those treated with infliximab, tocilizumab, or abatacept suggested that each biologic induces a specific gene signature in PBMCs. CONCLUSIONS: It is possible to observe signs of type-I IFN pathway activation in a subset of clinically active RA patients without C-reactive protein elevation. Furthermore, biologics-specific gene signatures in patients with RA indicate that looking for a biologic-specific response pattern may be a potential future tool for predicting individual patient response.
22709494 Adverse drug events in rheumatoid arthritis and osteoarthritis ambulatory patients. 2012 Jun AIM: We aimed to determine the prevalence and characteristics of adverse drug events (ADE) in rheumatoid arthritis (RA) and (osteoarthritis) OA patients. METHOD: A cross-sectional study at rheumatology clinics, was performed by random selection of RA and OA out-patients by a research pharmacist. All suspected ADEs occurring during the last hospital visit and the subjects were identified by retrospective chart review and direct patient interview. ADE characteristics, including causative drug groups, affected organ severity and patient outcomes, were recorded. RESULTS: One hundred and forty-three patients consisting of 129 RA and 14 OA were recruited. The patients' mean ages were 54.3 ± 14.3 years and 121 (84.6%) patients were female. A total of 68 ADEs were detected in 51 patients. The prevalence and rate of ADE were 35.7% and 47.6 events per 100 patients, respectively. Thirty out of 68 ADEs (44.1%) were preventable. Disease-modifying anti-rheumatic drugs and non-steroidal anti-inflammatory drugs resulted in ADEs by 41 (59.4%) and 10 (14.5%) events, respectively. Common affected organs were skin, gastrointestinal tract and eyes which accounted for 20 (29.4%), 18 (26.5%) and eight events (11.6%), respectively. Continuation of the suspected drug was noted in 42 ADEs (61.8%), classified as severity level 1 and 2a-b, and 43 ADEs (63.2%) were completely or partially resolved during the study period. CONCLUSION: ADEs are common in RA and OA patients with prevalence of 35.7%. High exposure to potentially harmful drugs might explain the higher rate of ADE in these patients.
20219786 The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosi 2011 Jan OBJECTIVES: Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP). METHODS: DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated. RESULTS: Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score. CONCLUSION: Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets.
22489073 Correlates and predictors of disability in vulnerable US Hispanics with rheumatoid arthrit 2012 Sep OBJECTIVE: US Hispanics with rheumatoid arthritis experience worse functional outcomes compared to whites. The determinants of disability, however, are not well established in large Hispanic cohorts. In the present report, we identified factors associated with disability in a cross-sectional design, and evaluated their individual contributions to disability over time. METHODS: Two hundred fifty-one Hispanic subjects from a single center were evaluated. Disease activity, serologies, radiographs, treatments, irreversible articular damage (defined as subluxation, arthrodesis, fusion, or prosthesis), and joint replacement surgeries were recorded. Self-reported disability (Health Assessment Questionnaire disability index), patient pain by a visual analog scale, and depression assessments were collected. Cross-sectional factors associated with disability were identified, and their effects on future disability were evaluated in a subgroup of 114 patients assessed 6 months later. RESULTS: Six parameters were independently related to disability cross-sectionally: pain was the strongest (P < 0.0001), followed by irreversible articular damage, disease activity, depression, age, and fibromyalgia (P < 0.03 for all). Baseline parameters predicting disability 6 months later included, in decreasing significance, irreversible articular damage (P = 0.004), depression, disease activity, age, and pain (all P < 0.04). CONCLUSION: In cross-sectional analysis, self-reported pain had the strongest relationship with disability; however, factors such as irreversible articular damage, depression, and disease activity were more important in predicting future disability. Most of these factors are amenable to targeted interventions and should be addressed in an effort to improve functional outcomes.
22901865 Early menopause and severity of rheumatoid arthritis in women older than 45 years. 2012 Aug 17 INTRODUCTION: We aimed to investigate whether recognized hormonal predictors of rheumatoid arthritis (RA) also influence the severity of RA. METHODS: One hundred thirty-four incident RA cases identified by four different local and national registers, who had participated in a community-based health survey between 1991 and 1996, were included. By a retrospective structured review of the medical records, information on the use of disease-modifying antirheumatic drugs (DMARDs), erosions on radiographs, rheumatoid factor (RF) status, and disability measured by using the health assessment questionnaire (HAQ) were collected. The variables were added to the SPSS TwoStep Cluster Analysis to reveal natural groupings of RA severity. Known hormonal predictors analyzed were breastfeeding history, history of oral contraceptive (OC) use, and menopausal age. RESULTS: The mean age at RA diagnosis was 63.4 years; 72% were RF positive, and 28% had received biological treatment. Three clusters were identified, one with severe RA, one with mild/moderate RF-positive RA, and one with mild/moderate RF-negative RA. A significant difference (P = 0.005) was found in the distribution of clusters between patients with a history of early menopause compared with those with menopause after 45 years, with a higher proportion with mild/moderate RF-negative RA in the early-menopause subset. No major difference in severity of the disease was noted depending on OC use or history of breastfeeding. CONCLUSIONS: Early menopause was associated with a milder form of RA. Hormonal changes may influence pathways that are distinct from those leading to severe, progressive disease.
22228465 Association between chronic periodontitis and rheumatoid arthritis: a hospital-based case- 2013 Jan Rheumatoid arthritis (RA) and chronic periodontitis are the most common chronic inflammatory diseases with remarkable pathological and clinical similarities. A lot of similarities exist between RA and periodontitis at cellular and molecular levels. The relationship between these two chronic inflammatory diseases is still unclear. This case-control study was undertaken to determine the possible association between chronic inflammatory diseases like RA and periodontitis. The case group consisted of 100 patients attending the Rheumatology clinic who have rheumatoid arthritis (RA group). Age- and gender-matched 112 patients without RA attending the Outpatient wing of Department of General Medicine formed the control group (NRA group). The number of missing teeth, gingival index (GI), oral hygiene index-simplified (OHI-S), probing pocket depth (PPD) and clinical attachment levels (CAL) were evaluated in both the groups. Rheumatoid disease activity was assessed by DAS-28 score system. Systemic markers of inflammation like erythrocytic sedimentation rate (ESR) and serum levels of C-reactive protein (CRP) were assessed. There was a statistically significant difference in GI, OHI-S, PPD, CAL, ESR and CRP levels between cases (RA group) and controls (NRA group) (P < 0.05). Among subjects with RA, there was no association between the rheumatoid disease activity and the severity of periodontal disease. The occurrence and severity of periodontitis was found to be higher in RA subjects as compared to subjects without RA, suggesting a positive relation between these two chronic inflammatory diseases.
22470803 Spontaneous talar and calcaneal fracture in rheumatoid arthritis: a case report. 2011 Rheumatoid arthritis (RA) leads to a progressive weakening of the skeleton which may result in bone fractures. However, spontaneous fractures (exclusive of stress fractures, vertebral collapse, and superficial articular fragmentation) in patients with rheumatoid arthritis have been only occasionally reported in the medical literature. A case of spontaneous talar and calcaneal fracture in rheumatoid arthritis is described. Bone lesions were identified on radiographs, MR images and scintigraphy in a patient with right ankle pain. The absence of episodes of acute trauma, and the presence of acute clinical manifestations should guide the clinical suspicion.
22111841 Profile and course of early rheumatoid arthritis in Morocco: a two-year follow-up study. 2011 Nov 23 BACKGROUND: This study aimed to establish the profile and the evolution of an early Rheumatoid arthritis (RA) cohort in the Moroccan population and also to search possible predictor factors of structural progression. METHODS: Patients with early RA (< 12 months) were enrolled in a 2-year follow-up study. Clinical, biological, immunogenetic, and radiographical data were analyzed at study entry and at 24 months. Presence of radiographic progression was retained when the total score was superior to the smallest detectable difference (SDD) calculated to be 5.4 according the Sharp/van der Heijde (SVDH) method. RESULTS: Fifty one patients (88.8% women, mean age of 46.9 [ 24-72 ] ± 10.8 years, mean disease duration of 24 [ 6-48 ] ± 13.9 weeks) were enrolled in this study. 68.6% were illiterate and 19.6% reported at least one comorbid condition. The mean delay in referral for specialist care was 140 [ 7-420 ] ± 43 days.Thirteen patients (62.5%) were IgM or IgA RF positive. HLA-DRB1*01 and DRB1*04 alleles were present respectively in 11.8% and 45.1% of patients.At baseline, 35.3% patients were taking corticosteroids and 7.8% were under conventional DMARDs.At 24 months, 77.2% received a median dose of 5 mg/day of prednisone. Methotrexate (MTX) was the most frequently prescribed DMARD, being taken by 65.2% of patients. 13.6% of patients had stopped their DMARD because of socioeconomic difficulties.Comparison of clinical and biologic parameters between baseline and 24 months thereafter revealed a significant global improvement of the disease status including morning stiffness, pain score, swollen joint count, DAS 28 and HAQ scores, ESR and CRP.Sixteen patients (34.8%) were in remission at 2 years versus no patients at baseline; P < 0.001.Forteen patients (27.5%) had at least one erosion at baseline. Radiographic progression occurred in 33.3% of patients and was associated in univariate analysis to swollen joint count (p = 0.03), total SVDH score (P = 0.04) and joint space narrowing score (P = 0.03). No independent factors of radiographic progression were shown by logistic regression. CONCLUSIONS: These study reports, provided for the first time in Morocco, a developing African country, a large amount of information concerning the profile and the course of early RA.Patients who were receiving, for most of them, Methotrexate in monotherapy and low doses of corticosteroids, showed an improvement of all clinic and biologic disease parameters. Moreover, DAS remission was obtained in one third of patients and two thirds of the cohort had no radiographic progression at 2 years. No predictor factors of radiographic progression were found out.These results should be confirmed or not by a large unbiased RA cohort which will give more relevant information about early RA characteristics and its course and will constitute a major keystone of its management.
22152116 Rheumatoid arthritis in Cardinal Carlo de' Medici (1595-1666): a confirmed macroscopic, ra 2012 Jan OBJECTIVES: The paleopathological study of the skeletal remains belonging to Cardinal Carlo de' Medici (1595-1666), son of Ferdinando I (1549-1609) and Cristina of Lorena (1565-1637), has been presented previously. A diagnosis of Klippel-Feil syndrome, tuberculosis and a polyarthopathy, interpreted as rheumatoid arthritis, was suggested. A revision of this case based on the analysis of the historical documents and of some radiological images of Carlo's bones has been proposed recently; according to the Authors, the Cardinal was affected by the 'Medici syndrome', a combined Psoriatic-DISH arthropathy. This revision offers us the opportunity to discuss this complex case, comparing different points of view, and to present the results of the molecular analyses carried out on Carlo's bone samples. We looked for the genetic risk factors of rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We also searched for the primary candidate genes of RA and PsA, i.e. DR4 or DR1 and Cw6 or DR7 respectively, the latter predisposing also for psoriasis. METHODS: An original molecular protocol was applied to achieve an aDNA uncontaminated by exogenous sources and almost intact, starting from one of the Cardinal's rib pieces. The allele risk factors for both diseases were identified by PCR-SSP assay as HLA genotyping methodology. RESULTS: Our data assigned Carlo the genotype DRB1*04/*11 for HLA-DRB locus and Cw*04/*12 for HLA-C locus. CONCLUSIONS: Since Carlo was infected by M. tuberculosis during infancy and was carrying the DR4 variant but not the Cw6, he surely had a predisposition to RA, not to PsA and/or psoriasis. The diagnosis of RA is thus confirmed.