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ID PMID Title PublicationDate abstract
26208921 Modeling rheumatoid arthritis using different techniques - a review of model construction 2014 Dec BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory disease with severe effects on the functional ability of patients. Due to the prevalence of 0.5 to 1.0 percent in western countries, new treatment options are a major concern for decision makers with regard to their budget impact. In this context, cost-effectiveness analyses are a helpful tool to evaluate new treatment options for reimbursement schemes. OBJECTIVES: To analyze and compare decision analytic modeling techniques and to explore their use in RA with regard to their advantages and shortcomings. METHODS: A systematic literature review was conducted in PubMED and 58 studies reporting health economics decision models were analyzed with regard to the modeling technique used. RESULTS: From the 58 reviewed publications, we found 13 reporting decision tree-analysis, 25 (cohort) Markov models, 13 publications on individual sampling methods (ISM) and seven discrete event simulations (DES). Thereby 26 studies were identified as presenting independently developed models and 32 models as adoptions. The modeling techniques used were found to differ in their complexity and in the number of treatment options compared. Methodological features are presented in the article and a comprehensive overview of the cost-effectiveness estimates is given in Additional files 1 and 2. DISCUSSION: When compared to the other modeling techniques, ISM and DES have advantages in the coverage of patient heterogeneity and, additionally, DES is capable to model more complex treatment sequences and competing risks in RA-patients. Nevertheless, the availability of sufficient data is necessary to avoid assumptions in ISM and DES exercises, thereby enabling biased results. Due to the different settings, time frames and interventions in the reviewed publications, no direct comparison of modeling techniques was applicable. The results from other indications suggest that incremental cost-effective ratios (ICERs) do not differ significantly between Markov and DES models, but DES is able to report more outcome parameters. CONCLUSIONS: Given a sufficient data supply, DES is the modeling technique of choice when modeling cost-effectiveness in RA. Otherwise transparency on the data inputs is crucial for valid results and to inform decision makers about possible biases. With regard to ICERs, Markov models might provide similar estimates as more advanced modeling techniques.
24949211 Possible association of etanercept, venous thrombosis, and induction of antiphospholipid s 2014 Tumor necrosis factor α (TNF α ) inhibitors are commonly used for treatment of aggressive rheumatoid arthritis and other rheumatic diseases. Etanercept is one of the medications approved for treatment of rheumatoid arthritis. Though many studies have documented the safety and efficacy of these medications, evidence for adverse effects is emerging including cancer, infections, and cardiovascular disease. There have been studies showing that these medications induce autoantibody production, including antinuclear antibodies and anti-dsDNA antibodies. Limited data exists, however, regarding induction of antiphospholipid antibodies (APLs) by TNF α inhibitors, including anticardiolipin antibodies (ACLs), lupus anticoagulant (LAC), and anti- β 2-glycoprotein I (anti- β 2 GPI), or an association between antibody development and clinical manifestations. In this case series, we describe five patients who developed venous thromboembolism (VTE) and APLs while receiving etanercept therapy. All five of our patients met the criteria for diagnosis of APS after receiving etanercept. Our case series supports the association between etanercept, APLs, and VTE. We believe that testing for APLs prior to initiation of anti-TNF therapy is reasonable, given this relationship and the risks associated with VTE.
24804191 A Promoter Region Polymorphism in PDCD-1 Gene Is Associated with Risk of Rheumatoid Arthri 2014 Objective. Programmed cell death 1 (PD-1) induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of autoimmune diseases such as rheumatoid arthritis (RA). Herein, we investigate the association of PDCD-1 polymorphisms with the risk of RA among Chinese patients and healthy controls. Methods. Using the PCR-direct sequencing analysis, 4 PDCD-1 SNPs (rs36084323, rs11568821, rs2227982, and rs2227981) were genotyped in 320 RA patients and 309 matched healthy controls. Expression of PD-1 was determined in peripheral blood lymphocytes by flow cytometry and quantitative real-time reverse transcriptase polymerase chain reaction. Results. We observed that the GG genotype of rs36084323 was associated with a increased risk for developing RA (OR 1.70, 95% 1.11-2.61, P = 0.049). Patients carrying G/G genotype displayed an increased mRNA level of PD-1 (P = 0.04) compared with A/A genotype and healthy controls. Meanwhile, patients homozygous for rs36084323 had induced basal PD-1 expression on activated CD4+ T cells. Conclusion. The PDCD-1 polymorphism rs36084323 was significantly associated with RA risk in Han Chinese population. This SNP, which effectively influenced the expression of PD-1, may be a biomarker of early diagnosis of RA and a suitable indicator of utilizing PD-1 inhibitor for treatment of RA.
24602812 Transcriptional and metabolic pre-B cell receptor-mediated checkpoints: implications for a 2014 Dec At the pre-B cell stage of lymphocyte development, immunoglobulin light-chains are not yet produced, and heavy-chains are covalently linked to surrogate light-chains composed of VpreB and λ5 to form the pre-B cell receptor (pre-BCR) in a non-covalent association with signal-transducing modules. Even tough the pre-BCR does not have the potential to bind conventional antigens, accumulating evidence indicates that pre-BCR-mediated checkpoints are important both for negative and positive selection of self-reactivity, and that defects in these regulatory nodes may be associated with autoimmune disease. Thus, the transcription factor BACH2, which represents a susceptibility locus for rheumatoid arthritis, has recently emerged as a crucial mediator of negative selection at a pre-BCR checkpoint. The lysosome-associated protein LAPTM5, which is highly expressed in an animal model of Sjögren's syndrome, plays a role in down-modulation of the pre-BCR. Studies of copy number variation in rheumatoid arthritis suggest that a reduced dosage of the VPREB1 gene is involved in disease pathogenesis. Notably, animal models of autoimmune disease exhibit defects in pre-B to naïve B cell checkpoints. Administration of a pre-BCR ligand, which also plays a role in anergy both in human and murine B lymphocytes, ameliorates disease in experimental models of autoimmunity. Further investigation is required to gain a better insight into the molecular mechanisms of pre-BCR-mediated checkpoints and to determine their relevance to autoimmune diseases.
24470758 Preferences of patients and health professionals for route and frequency of administration 2014 OBJECTIVES: To examine the preferences of rheumatoid arthritis (RA) patients and health professionals (HPs) for the route and frequency of administration of biologic drugs. METHODS: One hundred and seven RA patients treated with biological agents for intravenous or subcutaneous use, 35 biologic-naïve RA patients treated with a disease-modifying antirheumatic drug and 30 rheumatology HPs (physicians and nurses) were recruited from two outpatient clinics in Copenhagen, Denmark. All subjects filled out a questionnaire interrogating their choice of preferred route and frequency of administration of a biologic corresponding to current available options, given that effects, adverse effects, and financial costs were identical for the different choices. The subjects were also asked to justify their preferences. The chi-square goodness-of-fit test was used to examine the distributions over different preferences. Proportions were compared using Fisher's exact test. RESULTS: Forty-one patients were currently treated with subcutaneous self-injections at home (SCH) and 66 intravenously at the clinic (IVC). IVC was preferred by 85% of patients currently treated with IVC (P<0.0001). SCH was preferred by 71% of patients currently treated with SCH (P<0.001), by 77% of the biologic-naïve patients (P<0.01), and by 87% of HPs (P<0.0001). The proportion of patients favoring SCH was significantly higher for patients currently receiving SCH and for biologic-naïve RA patients than for those currently on IVC (P<0.0001). SCH once a month and IVC every 8 weeks were the most appealing treatment frequencies (P<0.01). The most frequent reason among patients for choosing IVC or SCH was a wish for safety, and a wish to minimize the time of transportation and treatment, respectively. CONCLUSION: The majority of RA patients treated with biologics preferred their current route of administration. Most patients, those inexperienced with biologics, and HPs favored SCH. Low treatment frequencies were generally preferred.
24440319 Primary and secondary intralymphatic histiocytosis. 2014 May BACKGROUND: Intralymphatic histiocytosis (IH) is a rare condition often associated with systemic disease. A benign condition, clinical presentations can vary greatly and its cause is largely unknown. Histologically, there are macrophages within distended lymphatic vessels, although this can be an incidental finding or the primary abnormality. OBJECTIVE: We present a series of 7 cases of IH with and without disease associations, and a review of the literature. We propose IH as either primary (without associated conditions) or secondary (associated with systemic disease). METHODS: This was a retrospective collection of patients whose skin biopsy specimens revealed intralymphatic collections of histiocytes. We reviewed their clinical presentation, disease associations, and staining of slides with CD68 in all cases, D2-40 in 5 cases, and HLA-DR in 4 cases. RESULTS: Clinical features were highly variable, and not all cases were associated with systemic disease. One case had admixed reactive angioendotheliomatosis. All 4 cases stained for HLA-DR showed strong expression by the intralymphatic macrophages. LIMITATIONS: Retrospective analysis and limited numbers are limitations. CONCLUSION: IH is not always associated with systemic disease although macrophage activation nevertheless implies immune activation.
23959753 IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid ar 2013 Aug 19 OBJECTIVES: To determine whether heterogeneity in interleukin-6 (IL-6), IL-6 receptor and other components of the IL-6 signalling pathway/network, at the gene, transcript and protein levels, correlate with disease activity in patients with rheumatoid arthritis (RA) and with clinical response to tocilizumab. DESIGN: Biomarker samples and clinical data for five phase 3 trials of tocilizumab were analysed using serum (3751 samples), genotype (927 samples) and transcript (217 samples) analyses. Linear regression was then used to assess the association between these markers and either baseline disease activity or treatment response. RESULTS: Higher baseline serum IL-6 levels were significantly associated (p<0.0001) with higher baseline DAS28, erythrocyte sedimentation rate, C reactive protein and Health Assessment Questionnaire in patients whose responses to disease-modifying antirheumatic drugs (DMARD-IR) and to antitumour necrosis factor (aTNF-IR) were inadequate and patients who were naive/responders to methotrexate (MTX). Higher baseline serum IL-6 levels were also significantly associated with better clinical response to tocilizumab (versus placebo) measured by cDAS28 in the pooled DMARD-IR (p<0.0001) and MTX-naive populations (p=0.04). However, the association with treatment response was weak. A threefold difference in baseline IL-6 level corresponded to only a 0.17-unit difference in DAS28 at week 16. IL-6 pathway single nucleotide polymorphisms and RNA levels also were not strongly associated with treatment response. CONCLUSIONS: Our analyses illustrate that the biological activity of a disease-associated molecular pathway may impact the benefit of a therapy targeting that pathway. However, the variation in pathway activity, as measured in blood, may not be a strong predictor. These data suggest that the major contribution to variability in clinical responsiveness to therapeutics in RA remains unknown.
23871638 Promotion and prevention of autoimmune disease by CD8+ T cells. 2013 Sep Until recently, little was known about the importance of CD8+ T effectors in promoting and preventing autoimmune disease development. CD8+ T cells can oppose or promote autoimmune disease through activities as suppressor cells and as cytotoxic effectors. Studies in several distinct autoimmune models and data from patient samples are beginning to establish the importance of CD8+ T cells in these diseases and to define the mechanisms by which these cells influence autoimmunity. CD8+ effectors can promote disease via dysregulated secretion of inflammatory cytokines, skewed differentiation profiles and inappropriate apoptosis induction of target cells, and work to block disease by eliminating self-reactive cells and self-antigen sources, or as regulatory T cells. Defining the often major contribution of CD8+ T cells to autoimmune disease and identifying the mechanisms by which they alter the pathogenesis of disease is a rapidly expanding area of study and will add valuable information to our understanding of the kinetics, pathology and biology of autoimmune disease.
23413282 Measurement invariance of the Illness Invalidation Inventory (3*I) across language, rheuma 2014 Mar OBJECTIVES: The Illness Invalidation Inventory (3*I) assesses patients' perception of responses of others that are perceived as denying, lecturing, not supporting and not acknowledging the condition of the patient. It includes two factors: 'discounting' and 'lack of understanding'. In order to use the 3*I to compare and pool scores across groups and countries, the questionnaire must have measurement invariance; that is, it should measure identical concepts with the same factor structure across groups. The aim of this study was to examine measurement invariance of the 3*I across rheumatic diseases, gender and languages. METHODS: Participants with rheumatic disease from various countries completed an online study using the 3*I, which was presented in Dutch, English, French, German, Portuguese and Spanish; 6057 people with rheumatic diseases participated. Single and multiple group confirmatory factor analyses were used to test the factorial structure and measurement invariance of the 3*I with Mplus. RESULTS: The model with strong measurement invariance, that is, equal factor loadings and thresholds (distribution cut-points) across gender and rheumatic disease (fibromyalgia vs other rheumatic diseases) had the best fit estimates for the Dutch version, and good fit estimates across the six language versions. CONCLUSIONS: The 3*I showed measurement invariance across gender, rheumatic disease and language. Therefore, it is appropriate to compare and pool scores of the 3*I across groups. Future research may use the questionnaire to examine antecedents and consequences of invalidation as well as the effect of treatments targeting invalidation.
23291737 Comparison of short- to medium-term results of Coonrad-Morrey elbow replacement in patient 2013 Jan 7 BACKGROUND: The aim of this study was to assess the utility of the Coonrad-Morrey elbow prosthesis in patients with severe elbow dysfunction secondary to rheumatoid arthritis (RA) or post-traumatic elbow dysfunction. MATERIAL/METHODS: The study involved 35 patients followed up for a mean of 36 months. The patients were divided into those with RA (Group I) and those with post-traumatic elbow dysfunction (Group II). Treatment outcomes were evaluated according to the Mayo Elbow Performance Score (MEPS) and the Disabilities of the Arm, Shoulder and Hand Score (Quick DASH). RESULTS: According to the MEPS, there were 20 (57.15%) excellent, 12 (34.3%) good, 1 (2.85%) fair, and 2 (5.7%) poor outcomes. The mean post-operative Quick-DASH score for the entire study group was 37.73 points. In subgroup analysis, the MEPS-based evaluation revealed: 14 (70%) excellent, 5 (25%) good, and 1 (5%) satisfactory outcome in Group I, versus 6 (40%) excellent, 7 (46.7%) good, and 2 (13.3%) poor outcomes in Group II. The mean Quick Dash scores were 78.64 points in Group I and 76.36 points in Group II. The final MEPS scores in Group I (p=0.000018) and Group II (p=0.00065) were most markedly influenced by reduction in elbow pain and improvement in the ability to perform activities of daily living (ADL): p=0.000018 in Group I and p=0.000713 in Group II. CONCLUSIONS: The treatment outcomes confirm the utility of arthroplasty for severe elbow dysfunctions; they were most strongly influenced by pain reduction and improved ability to perform activities of daily living.
25848582 Validation of Diagnostic and Procedural Codes for Identification of Acute Cardiovascular E 2013 OBJECTIVE: To assess the accuracy of International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes for identifying cardiovascular (CV) events (myocardial infarction [MI], stroke, coronary artery bypass graft [CABG], and percutaneous coronary intervention [PCI]) in enrollees of the Veterans Affairs Rheumatoid Arthritis (VARA) registry. DESIGN: We performed a validation study from VARA enrollment until 6/1/2010 to compare the accuracy of CV events in those with and without CV-event coding in inpatient and outpatient records to evaluate for CV events +/- 3 months of the coding. The positive predictive value (PPV) was calculated, and codes with a PPV ≥50% were included in a composite coding algorithm. RESULTS: We evaluated 107 individuals for 21 CV-event codes and 60 individuals without CV-event coding. The PPV varied between 0-100%. Composite coding algorithms' PPV ranged from 70-100%. CONCLUSIONS: Validation of these algorithms allows for identification of acute CV events with known accuracy. The sensitivity and PPV of coding algorithms for CABG and PCI exceed that of stroke and MI.
24656110 Cardiovascular comorbidity in rheumatic diseases: a focus on heart failure. 2014 Apr Rheumatic diseases are associated with an increased risk of cardiovascular (CV) mortality attributed to a higher incidence of heart failure (HF) and ischemic heart disease. Although traditional CV risk factors contribute to the increased incidence seen in this population, by themselves they do not account for the increased risk; in fact, obesity and hyperlipidemia may play a paradoxic role. Immune-mediated mechanisms and chronic inflammation likely play a role in the pathogenesis of CV disease in patients with rheumatic diseases. The usual clinical features of ischemic heart disease and HF are less likely to be seen in this patient population.
24169518 Peripheral education of the immune system by the colonic microbiota. 2013 Nov 30 There is growing interest in understanding the effects of host-microbial interactions on host physiologic processes. Much of the work in this arena is logically focused on the interaction at mucosal surfaces as this is a primary site of interaction. However, there is ample evidence to suggest that the effects of the microbiota have a much farther reach including the systemic immune system. While there are some similarities to effects at mucosal surfaces (i.e. reduced numbers of adaptive immune cells, diminished innate responses), there are some important differences that we highlight such as the response to immunogens and bacterial antigens. We propose that understanding the details of how specific components of the microbiota influence the systemic immune system likely will have significant impact on our understanding the pathophysiology of a variety of autoimmune diseases.
25376380 Risk factors for AA amyloidosis in Germany. 2015 Mar OBJECTIVE: To identify risk factors for serum amyloid-A (AA) amyloidosis in patients living in Germany. METHODS: Clinical and genetic data were obtained from 71 patients with AA amyloidosis. SAA1 genotypes were analyzed in 231 individuals. Control groups comprised 45 patients with long-standing inflammatory diseases without AA amyloidosis and 56 age-matched patients without any inflammatory disease. RESULTS: The most frequent underlying diseases of AA amyloidosis were familial Mediterranean fever (FMF) (n = 24, 34%) and inflammatory rheumatic diseases (n = 30, 42%). Patients without any known underlying disease (n = 11, 16%) were considered as having idiopathic AA amyloidosis. Patients with FMF were significantly younger at disease onset and younger at diagnosis of AA amyloidosis compared with patients with rheumatic diseases. Patients with idiopathic AA amyloidosis were older than patients with definite rheumatic diseases. Patients with FMF and high penetrance MEFV gene mutations had a relative risk of 1.73 for AA amyloidosis. Patients with FMF or a rheumatic disease and the SAA1 α/α genotype had a relative risk of 4.86 and 2.53, respectively, for developing an AA amyloidosis. The prevalence of this risk genotype was 36% in German patients without an inflammatory disease, 92% in German patients with AA amyloidosis and 100% in German patients with idiopathic AA amyloidosis. CONCLUSIONS: Risk factors for AA amyloidosis are the presence of a hereditary autoinflammatory or chronic rheumatic disease, elevated C-reactive protein and SAA serum levels, a long delay of a sufficient therapy, an advanced age and the SAA1α/α genotype.
24975478 Getting Syk: spleen tyrosine kinase as a therapeutic target. 2014 Aug Spleen tyrosine kinase (Syk) is a cytoplasmic protein tyrosine kinase well known for its ability to couple immune cell receptors to intracellular signaling pathways that regulate cellular responses to extracellular antigens and antigen-immunoglobulin (Ig) complexes of particular importance to the initiation of inflammatory responses. Thus, Syk is an attractive target for therapeutic kinase inhibitors designed to ameliorate the symptoms and consequences of acute and chronic inflammation. Its more recently recognized role as a promoter of cell survival in numerous cancer cell types ranging from leukemia to retinoblastoma has attracted considerable interest as a target for a new generation of anticancer drugs. This review discusses the biological processes in which Syk participates that have made this kinase such a compelling drug target.
23804809 Inhibition of pre-B cell colony-enhancing factor (PBEF/NAMPT/visfatin) decreases the abili 2013 Sep NAMPT, also known as PBEF and visfatin, can act extracellularly as a cytokine-like molecule or intracellularly as a NAMPT, regulating NAD biosynthesis in the NAD salvage pathway. Inhibitors of NAMPT have anti-inflammatory and anticancer activity and are finding use as therapeutic agents. In view of the importance of NAD metabolism in neutrophil function, we determined the effects of NAMPT inhibition on a variety of neutrophil functions associated with their role in host protection against infections. Incubation of human neutrophils with the NAMPT inhibitor APO866 decreased neutrophil NAD(P)/H levels in a dose- and time-dependent manner but without a concomitant change in cell viability. NAMPT inhibition did not affect the expression of a number of cell-surface receptors involved in adhesion and opsono-phagocytosis, but the respiratory burst was decreased significantly. Whereas opsono-phagocytosis of Staphylococcus aureus was unaffected by NAMPT inhibition, intraphagosomal oxidant production was decreased. However, the killing efficiency of neutrophils was unaffected. These data indicate that therapeutic NAMPT inhibition is unlikely to have deleterious effects on host protection against infections, in spite of this ability to down-regulate neutrophil respiratory burst activity significantly.
23703852 Usual interstitial pneumonia-pattern fibrosis in surgical lung biopsies. Clinical, radiolo 2013 Oct Pulmonary fibrosis in surgical lung biopsies is said to have a 'usual interstitial pneumonia-pattern' (UIP-pattern) of disease when scarring of the parenchyma is present in a patchy, 'temporally heterogeneous' distribution. These biopsies are one of the more common non-neoplastic specimens surgical pathologists encounter and often pose a number of challenges. UIP is the expected histopathological pattern in patients with clinical idiopathic pulmonary fibrosis (IPF), but the UIP-pattern can be seen in other conditions on occasion. Most important among these are the rheumatic interstitial lung diseases (RILD) and chronic hypersensitivity pneumonitis (CHrHP). Because theses entities have different mechanisms of injury, approach to therapy, and expected clinical progression, it is imperative for the surgical pathologist to correctly classify them. Taken in isolation, the UIP-pattern seen in patients with IPF may appear to overlap with that of RILD and CHrHP, at least when using the broadest definition of this term (patchy fibrosis). However, important distinguishing features are nearly always present in our experience, and the addition of a multidisciplinary approach will often resolve the critical differences between these diseases. In this manuscript, we review the distinguishing clinical, radiologic and histopathological features of UIP of IPF, RILD and CHrHP, based, in part, on the existing literature, but also lessons learned from a busy lung biopsy consultation practice.
25368616 Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. 2014 Discovery and characterization of the cytokine receptor-cytokine-decoy receptor triad formed by receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of NF-κB (RANK)-osteoprotegerin (OPG) have led not only to immense advances in understanding the biology of bone homeostasis, but have also crystalized appreciation of the critical regulatory relationship that exists between bone and immunity, resulting in the emergence of the burgeoning field of osteoimmunology. RANKL-RANK-OPG are members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, and share signaling characteristics common to many members of each. Developmentally regulated and cell-type specific expression patterns of each of these factors have revealed key regulatory functions for RANKL-RANK-OPG in bone homeostasis, organogenesis, immune tolerance, and cancer. Successful efforts at designing and developing therapeutic agents targeting RANKL-RANK-OPG have been undertaken for osteoporosis, and additional efforts are underway for other conditions. In this review, we will summarize the basic biology of the RANKL-RANK-OPG system, relate its cell-type specific functions to system-wide mechanisms of development and homeostasis, and highlight emerging areas of interest for this cytokine group.
24935354 Should we target patients with autoimmune diseases for human papillomavirus vaccine uptake 2014 Aug Human papillomavirus (HPV) is the cause of most cases of cervical cancer worldwide. Studies suggest that patients with autoimmune diseases (AD) may be at increased risk for persistent HPV infection, cervical dysplasia, and possibly, cervical cancer. Despite this heightened risk, and studies demonstrating the safety and efficacy of the HPV vaccine in this population, uptake among patients with AD, and in the overall population, remains low. A number of studies suggest that this may be attributed to lack of patient and provider awareness, no school-based requirement for vaccination, and a hesitancy to discuss sexually transmitted diseases with adolescents. Among patients with AD, access to preventive care in general may be reduced. Overall, heightened public health efforts are needed to improve HPV vaccination uptake in the entire population and among patients with AD who may be at increased risk for persistent infection and for cervical dysplasia.
24902509 Carpal pseudoerosions: a plain X-ray interpretation pitfall. 2014 Oct OBJECTIVE: To examine in detail images of pseudoerosion of the wrist and hand on plain radiographs. MATERIAL AND METHODS: The study was conducted with 28 cadaver wrists. During a single imaging session three techniques-plain radiography, tomosynthesis, and computed tomography-were used to visualize the wrist and hand specimens. For each technique, 20 radio-ulno-carpo-metacarpal sites known to present bone erosions in rheumatoid arthritis were analyzed by two radiologists using a standard system to score the cortical bone: normal, pseudoerosion, true erosion, or other pathology. Cohen's concordance analysis was performed to determine inter-observer and intra-observer (for the senior radiologist) agreement by site and by technique. Serial sections of two cadaver specimens were examined to determine the anatomical correlation of the pseudoerosions. RESULTS: On the plain radiographs, the radiologists scored many images as pseudoerosion (7.3%), particularly in the distal ulnar portion of the capitate, the distal radial portion of the hamate, the proximal ulnar portion of the base of the third metacarpal, the proximal radial portion of the base of the fourth metacarpal, the distal ulnar portion of the hamate, and the proximal portion of the base of the fifth metacarpal. The computed tomography scan revealed that none of these doubtful images corresponded to true erosions. The anatomical correlation study showed that these images could probably be attributed to ligament insertions, thinner lamina, and enhanced cortical bone transparency. CONCLUSION: Knowledge of the anatomical carpal localizations where pseudoerosions commonly occur is a necessary prerequisite for analysis of plain radiographs performed to diagnose or monitor rheumatoid arthritis.