Challenges and knowledge gaps with immune checkpoint inhibitors monotherapy in the management of patients with non-small-cell lung cancer: a survey of oncologist perceptions.

BACKGROUND: Immune checkpoint-inhibitors (ICIs) are changing outcomes in different cancer settings, notably for patients with non-small-cell lung cancer (NSCLC). There are, however, still important gaps of evidence for clinical practice when using these novel treatments. In this study, we assessed physicians' opinion and experience on challenges for clinical practice with ICIs monotherapy in NSCLC. METHODS: A survey was conducted on experienced physicians treating patients with NSCLC with ICIs. Two rounds of pilot tests were carried out for validation among a group of experts. Topics under analysis were in relation to treatment of elderly populations, performance status, brain metastases, use of steroids or antibiotics, the effects of gut microbiome, autoimmune diseases, human immunodeficiency virus infection, solid organ transplants, use of anti-programmed cell death protein 1 versus anti-programmed death-ligand 1 drugs, atypical tumour responses, predictors of response, duration of treatment and a final open question on additional relevant challenges. RESULTS: Two hundred and twenty-one answers were collected, including 106 (48%) valid answers from experts for final analysis (physicians who have treated at least 20 patients with NSCLC with ICIs). The vast majority agreed that the selected topics in this study are important challenges ahead and more evidence is needed. Moreover, predictors of response, treating brain metastasis, shorter duration of treatment, the effects of gut microbiome and concomitant use of steroids were voted the most important topics to be further addressed in prospective clinical research. CONCLUSIONS: This survey contributed to understanding which are the main challenges for clinical practice with ICIs monotherapy in NSCLC. It can also contribute to guide further clinical research, considering the opinions and experience of those who regularly treat NSCLC patients with ICIs.

Smoking and response to rituximab in rheumatoid arthritis: results from an international European collaboration.

OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Overactive bladder symptom bother and health-related quality of life in patients with systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). METHODS: We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. RESULTS: We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient -3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. CONCLUSIONS: Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

2016 update of the Portuguese recommendations for the use of biological therapies in children and adolescents with Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide evidence-based guidance for the rational and safe prescription of biological therapies in children and adolescents with juvenile idiopathic arthritis (JIAs) considering the latest available evidence and the new licensed biologics. METHODS: Rheumatologists and Pediatricians with expertise in Pediatric Rheumatology updated the recommendations endorsed by the Portuguese Society of Rheumatology and the Portuguese Society of Pediatrics based on published evidence and expert opinion. The level of agreement with final propositions was voted using an online survey. RESULTS: In total, 20 recommendations to guide the use of biological therapy in children and adolescents with JIAs are issued, comprising 4 general principles and 16 specific recommendations. A consensus was achieved regarding the eligibility and response criteria, maintenance of biological therapy, and procedures in case of non-response, for each JIA category. Specific recommendations concerning safety procedures were also updated. CONCLUSIONS: These recommendations take into account the specificities of each JIA category and are intended to continuously improve the management of JIA patients.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Musculoskeletal ultrasound in Paediatric Rheumatology: a retrospective analysis.

OBJECTIVES: Musculoskeletal Ultrasound (MSK-US) has become increasingly important in the diagnosis and follow-up of children with rheumatic diseases. We describe the experience of a large Portuguese centre and study the added value of MSK-US in the clinical assessment of paediatric rheumatic diseases. MATERIAL AND METHODS: Patients were observed by assistant Rheumatologists, a clinical diagnosis was assigned and MSK-US requested. 330 MSK-US exams were performed to 222 children with rheumatic inflammatory diseases. The children's ages were between 1 and 18 years (mean=11.7±4.7 years) and 67.6% were female. Synovial membrane proliferation, intra-articular effusion, cartilage abnormalities, erosions and periarticular affections were searched in each joint. Clinical and ultrasonography data were compared. RESULTS: MSK-US detected synovitis in 100 of 194 exams (51.5%) of patients with that clinical information and in 36 of 136 exams (26.5%) of patients who presented other clinical findings. In those in which MSK-US did not confirm the clinical information of synovitis (94; 48.5%), we detected tenosynovitis/tendinopathy in 13 cases (13.8%) and synovial cyst in four (4.3%). The remaining patients had no ultrasonography changes and MSK-US helped to exclude synovitis. The sensitivity for arthritis clinical assessment was good (73.5%), with modest specificity (51.5%), an accuracy of 60.6% and precision of 51.5%. Ultrasonography synovitis was mostly found in the knee (37.5%), followed by the ankle (22.8%) and hip (10.3%). Overall, 39 exams showed ultrasonographic tenosynovitis/tendinopathy, 15 of which had the same clinical diagnosis. Tenosynovitis/tendinopathy was mostly found in the ankle (59.0%) and knee (23.1%) areas. CONCLUSIONS: MSK-US is an important aid to clinical evaluation, allowing both the detection and exclusion of joint pathology in children, contributing to a better assessment.

Position paper on tuberculosis screening in patients with immune mediated inflammatory diseases candidates for biological therapy.

UNLABELLED: Chronic immunosuppression is a known risk factor for tuberculosis. Our aim was to reach a consensus on screening and prevention of tuberculosis in patients with immune mediated inflammatory diseases candidates to biologic therapy. METHODS: Critical appraisal of the literature and expert opinion on immunosuppressive therapies and risk of tuberculosis. RESULTS AND CONCLUSION: The currently recommended method for screening is the tuberculin skin test and the interferon gamma assay, after exclusion of active tuberculosis. Positively screened patients should be treated for latent tuberculosis infection. Patients may start biological therapy after 1 to 2 months, as long as they are strictly adhering to and tolerating their preventive regimen.

Bone histomorphometry revisited.

Bone histomorphometry is defined as a quantitative evaluation of bone micro architecture, remodelling and metabolism. Bone metabolic assessment is based on a dynamic process, which provides data on bone matrix formation rate by incorporating a tetracycline compound. In the static evaluation, samples are stained and a semi-automatic technique is applied in order to obtain bone microarchitectural parameters such as trabecular area, perimeter and width. These parameters are in 2D, but they can be extrapolated into 3D, applying a stereological formula. Histomorphometry can be applied to different areas; however, in recent decades it has been a relevant tool in monitoring the effect of drug administration in bone. The main challenge for the future will be the development of noninvasive methods that can give similar information. In the herein review paper we will discuss the general principles and main applications of bone histomorphometry.

Reuma.pt - the rheumatic diseases portuguese register.

INTRODUCTION: Since June 2008, Portuguese rheumatologists have been collecting on a routine basis, data into the nationwide Reuma.pt, the Rheumatic Diseases Portuguese Register from the Portuguese Society of Rheumatology (SPR), which includes rheumatic patients (rheumatoid arthritis - RA, ankylosing spondylitis - AS, psoriatic arthritis - PsA and juvenile idiopathic arthritis - JIA) receiving biological therapies or patients receiving synthetic disease modifying anti-rheumatic drugs (DMARDs). The aim of this publication is to describe the structure of Reuma.pt and the population registered since June 2008. METHODS: Demographic and anthropometric data, life style habits, work status, co-morbidities, disease activity and functional assessment scores, previous and current therapies, adverse events codified by the Medical Dictionary for Regulatory Activities (MedDRA), reasons for discontinuation and laboratory measurements are registered at each visit. The platform is based on a structured electronic medical record linked to a SQL Server database. All Rheumatology Departments assigned to the Portuguese National Health Service (n=21), 2 Military Hospitals (Lisboa and Porto), 1 public-private Institution and 6 private centers adhered to the Register. Until now, 18 centers have entered data into Reuma.pt. RESULTS: By January 2011, 3438 patients and 16130 visits had been registered. 2162 (63%) were RA patients, 700 of them treated with biological agents and 1462 with synthetic DMARDs. From the 515 (15%) AS patients, 297 were medicated with biological and 218 with non-biological therapies. 293 (8%) were PsA patients, 151 treated with biological drugs and 142 with other treatment strategies. 368 (11%) had the diagnosis of JIA, 68 were under biological treatment and 300 were managed with other treatment options. The register also includes 100 (3%) patients with other rheumatic diseases, submitted to treatments that required hospital day care infusions including 18 exposed to biological therapies. CONCLUSIONS: Registers are crucial to ensure correct clinical use, adequate assessment of post-marketing biological therapies' efficacy and safety, thus contributing for a better cost-benefit ratio. Reuma.pt, is a powerful and accurate tool to answer to these unmet needs. It presents a national coverage of the rheumatology centers and constitutes an invaluable resource for scientific research and to improve rheumatic patients care.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

BioRePortAP, an electronic clinical record coupled with a database: an example of its use in a single centre.

AIMS: To evaluate the efficacy and safety of the treatment of psoriatic arthritis (PsA) patients with tumor necrosis factor (TNF) antagonists in the Rheumatology Department of Hospital de Santa Maria using the BioRePortAP. METHODS: The Portuguese Society of Rheumatology (SPR) developed an electronic medical chart coupled with a database for the follow up of PsA patients, the BioRePortAP, which was launched in May 2009. This evaluation was based on all the PsA patients that were on active treatment with TNF antagonists in September 2009 and were registered in the BioRePortAP. All the previous data on these patients were introduced in BioRePortAP using the prospective paper based follow up protocol that this Department was using since 1999. Only patients with more than 9 months of treatment were analyzed. RESULTS: Forty-two patients with PsA, actively treated with anti-TNF agents in September 2009, for at least 9 months, were analyzed in BioRePortAP. Twenty-three patients were male (55%) and nineteen were female (45%). The average age of these patients was 49.8+/-10.9 years old, the average disease duration was of 10.7+/-5.6 years and the mean duration of biological therapy was of 37.8+/-27.8 months. For the 81% of patients with peripheral joint disease there was a mean reduction of more than 80% in the swollen and tender joint counts, and almost 50% in the health assessment questionnaire (HAQ) value. In the 19% of the patients with axial involvement the reduction of BASDAI and BASFI was not statistically significative. On top of that, PASI score suffered a reduction of 64%. Fourteen patients (33.3%) had to switch their TNF antagonist treatment. 58.8% of the switches were due to adverse effects and 41.2% due to therapy failure. Regarding the 56 adverse reactions registered, only one was a severe reaction. The remaining adverse reactions were not severe and 67% of them were due to infections. DISCUSSION: The results of this first report of the use of the BioRePortAP in clinical practice confirm the efficacy and safety of TNF antagonist treatment in PsA. The results shown here elucidate the potential applications of BioRePortAP as a tool for efficacy and safety assessment of PsA patients treated with biotechnological drugs.

Evaluation of bone mechanical strenght and fracture risk assessment (Frax) in patients with hip joint replacement surgery.

BACKGROUND: Fracture risk assessment tools are useful to calculate the long term probability of osteoporotic fracture. However, how it reflects bone quality is unknown. The aim of this study was to correlate the WHO clinical fracture risk assessment tool, FRAX, with bone mechanical properties. METHODS: Six patients submitted to hip replacement surgery, either due to osteoporotic fractures or to osteoarthritis, were evaluated. Bone samples were collected and the mechanical properties assessed by compression tests. Patients' data regarding the presence of clinical risk factors for fracture were registered. Laboratorial assessment of bone metabolic parameters and a dual X-ray absorptiometry(DXA) were done. RESULTS: Analysis of the load-displacement curves showed that patients with fragility fractures (n=4) had low values of elastic modulus, yield load and energy absorbed until yield point. Osteoarthritis patients tend to have a better biomechanical performance.Femoral neck DXA scan was also performed in 3 patients. Fragility fracture patients had a lower bone mineral density than the patients with osteoarthritis. FRAX algorithm was applied and a positive relation was found between FRAX results and biomechanical parameters. Blood bone metabolic markers were within the normal range for all the subjects. CONCLUSIONS: The worse mechanical properties observed in the fragility fracture patients were related to high probability of fracture given by FRAX. These observations, in a very small sample, need further confirmation. However, they suggest that the fracture risk assessment tool, FRAX, may reflect the current mechanical bone behavior of the patient.

Interleukin-6 as a key player in systemic inflammation and joint destruction.

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.

Osteoimmunology--the hidden immune regulation of bone.

Osteoimmunology is an emerging field of research dedicated to the investigation of the interactions between the immune and skeletal systems. These interactions are not only mediated by the release of cytokines and chemokines but also by direct cell-cell contact. Recently, it was proposed that immunoreceptors found in the immune cells are also an essential signal for osteoclasts activation, along with receptor activator NF-kappaB (RANK) ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). In addition, adipose tissue also produces several factors (adipokines) that are known to interfere with the immune system and bone homeostasis. Chronic inflammation strongly influences osteoimmunology determining profound metabolic, structural and functional changes in bone.

Factors influencing calcaneus quantitative ultrasound measurements in an urban population.

OBJECTIVE: To estimate the effect of demographic, social, behavioural and anthropometric factors on quantitative ultrasound (QUS) parameters in an urban population. METHODS: Cross-sectional evaluation of consecutive subjects selected as part of the EPIPorto study, Portugal. Information was obtained on demographic, social, clinical and behavioural characteristics using a standard protocol. Calcaneus QUS parameters (Broadband Ultrasound Attenuation-BUA, and Speed of Sound-SOS) were obtained for men and women, stratified by age group. Comparisons according to exposure levels were made using the Kruskal-Wallis test and the multivariate effect on QUS parameters was estimated by linear regression. RESULTS: 1482 consecutive subjects (1010 females and 472 males), aged from 18 to 92 years. Higher levels of QUS parameters were found in the younger groups and progressive decrease with age were reported. Men showed higher values as compared to women in all parameters and differences between them increased with age. Differences were significant for BUA after the age of 39 and for SOS after the age of 59. In women, the multivariate model showed that age, body mass index (BMI) and smoking status were independent predictors of BUA and SOS. In men, age, BMI and calcium intake were significantly associated with BUA and SOS. CONCLUSION: The reference values in our Portuguese population are similar to others obtained in Southern European countries. In the Portuguese population, QUS parameters have age, sex and BMI as its major determinants. In addition, BUA and SOS may reflect specific bone characteristics influenced by a different set of independent determinants.

Inflammatory cell infiltrate and RANKL/OPG expression in rheumatoid synovium: comparison with other inflammatory arthropathies and correlation with outcome.

OBJECTIVES: To evaluate if the immunofluorescence analysis of synovial tissue (ST) using antibodies against RANKL/OPG, conjugated with the immunophenotyping of lymphocytes and macrophages, could be of diagnostic and prognostic value in rheumatoid arthritis (RA) patients. METHODS: 3-year prospective study of 103 consecutive patients submitted to closed needle biopsy for diagnostic purposes. ST was analyzed with routine histologic techniques and immunofluorescence, using monoclonal antibodies against RANKL, OPG, CD163, CD68, CD4, CD8, interferon-gamma and CD19. Patients were prospectively evaluated with a clinical, laboratorial and radiological protocol. At the end of the follow-up patients were divided according to the final diagnosis. Results of the initial histologic evaluation were compared between the main diagnostic groups and in RA patients histologic data was correlated with clinical and radiologic outcome measures. RESULTS: The RANKL/OPG ratio and the inflammatory infiltrate were significatively higher in RA (n = 25) as compared to the same ratio observed in other inflammatory joint diseases (OIJD, n = 48) and in osteoarthritis (n = 17). The difference between RA and OIJD was specifically confirmed when the comparison involved spondyloarthropathy (n = 26). Final HAQ score and radiologic outcome were correlated with the density of intimal CD68+ macrophages. Radiologic progression was correlated with subintimal CD4+ lymphocytes and CD68+ macrophages and intimal CD68 and CD163+ macrophages. CONCLUSION: The quantification of the RANKL/OPG ratio and of the number of lymphocytes in the ST might be useful to differentiate RA from other inflammatory joint diseases. The ST number of CD4+ lymphocytes and macrophages are probable predictors of radiologic progression in RA patients.

Histology of the synovial tissue: value of semiquantitative analysis for the prediction of joint erosions in rheumatoid arthritis.

OBJECTIVE: Routine histologic techniques are still the main procedure in the study of the synovial biopsy. The relationship between the typical histological changes of rheumatoid synovium and clinical manifestations has not been studied in detail. METHODS: With the aim of determining whether a simple semiquantitative method of evaluating the changes in closed synovial biopsies was of clinical value in assessing both the diagnosis and prognosis of rheumatoid arthritis (RA) patients, we evaluated retrospectively 72 synovial biopsy specimens (26 RA patients, 30 patients with other inflammatory diseases and 16 osteoarthritis patients). Scores (0-10) were assigned to each biopsy specimen for each of 6 histologic features: synoviocyte hyperplasia; fibrosis in the subsynovial layer; proliferating blood vessels; perivascular infiltrates of lymphocytes; focal aggregates of lymphocytes; and diffuse infiltrates of lymphocytes. Scores were compared between the 3 groups and also between the RA subgroups with early and late disease; positive and negative rheumatoid factor; with and without joint erosions; and with and without systemic disease. RESULTS: Significant differences in the mean global score (mean of the 6 scores) were found both between RA and osteoarthritis and between other inflammatory diseases and osteoarthritis (p < 0.01). The mean global score for RA was higher than the mean global score obtained for the other inflammatory diseases, but the difference was not significant. We found a significantly higher mean global score in the RA patients with erosions in comparison to the RA patients without erosions, this difference being particularly evident for the lymphocyte perivascular infiltrate (p < 0.05). There were no significant differences between the other RA subgroups. CONCLUSION: In this study we have identified differences, using routine histologic techniques, between the rheumatoid synovial membrane of patients with and without erosions. Based on our present observations we suggest that the intensity of inflammatory histological features and, in particular, a high percentage of vessels with perivascular lymphocyte infiltrate might be of prognostic value in RA.