Diagnosis Of Connective Tissue Disease Research Articles

Computer-aided image analysis aids early diagnosis of connective-tissue diseases

Computer-aided image analysis aids early diagnosis of connective-tissue diseases

A 32‐year‐old woman with arthralgias and severe hypotension

A 32‐year‐old woman with arthralgias and severe hypotension

Outcome of high titer antinuclear antibody positivity in individuals without connective tissue disease: a 10-year follow-up

To ascertain the development of disease in a cohort of connective tissue disease (CTD)-negative patients 10 years after testing positive for antinuclear antibody (ANA) in high titer, a telephone survey and serological tests were conducted on a group of CTD-negative patients with high ANA titer identified in a previous study. Thirty-four out of 62 patients (55%) completed only the telephone survey and 27 completed both. The mean length of follow-up was 11.5 years. The ages ranged from 27 to 89 years with the mean being 58.9 years. The sex distribution included 4 (12%) men and 30 (88%) women. Twenty-one out of 27 patients (78%) remained ANA-positive. A total of five patients were diagnosed with CTD with two in the last 5 years. Common symptoms described, in order of frequency, were joint pain, Raynaud's phenomenon, and Sicca symptoms. This study shows that a considerable percentage of CTD-negative individuals with an initial high ANA titer continue to maintain their positivity even after an extended period. It is reassuring, however, that only a small number of these individuals go on to develop CTD. It confirms the fact that the ANA test, despite remaining a useful clinical tool, needs to be used in conjunction with other evidence and clinical judgement when attempting to validate the diagnosis of CTD.

Antibodies to Mitotic Spindle Apparatus: Clinical Significance of NuMA and HsEg5 Autoantibodies

The clinical associations of NuMA and HsEg5 antibodies, the main anti-mitotic spindle apparatus autoantibodies, remain unclear due to their extremely low prevalence. We have analysed the clinical data of 40 anti-NuMA- (0.87 per thousand) and 7 anti-HsEg5- (0.15 per thousand) positive patients detected during routine immunofluorescence examination of 45,804 sera. NuMA reactivity was further confirmed by immunoblotting. Antibodies to HsEg5 did not associate with any specific pathology. NuMA positivity associated with a diagnosis of connective tissue disease (CTD) in 18 patients (45%), primary Sjögren or sicca syndrome and undifferentiated connective tissue disease being the most represented. Seven patients (17.5%) were diagnosed with different organ-specific autoimmune diseases, whereas in the other 15 patients (37.5%), no autoimmune pathology could be documented. Therefore, although both anti-mitotic spindle apparatus antibodies are not associated to a defined autoimmune pathology, the presence of NuMA antibodies, mainly at high titers, may be an indication for a more extensive screening of CTD.

Undifferentiated connective tissue diseases-related hepatic injury

Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manifestations, laboratory findings, treatment and its short-term effect. The patient was admitted to the hospital with symptoms of fatigue, anorexia, low-grade fever and skin rashes. She had a past history of left knee joint replacement. Laboratory tests showed elevated levels of serum transaminase, IgG and globulin, accelerated erythrocyte sedimentation rate, eosinophilia and a high titer of antinuclear antibodies (1:320). Imaging studies showed interstitial pneumonitis and hydropericardium. Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis. After treatment with a low-dose of oral prednisone, both symptoms and laboratory findings were significantly improved. UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests. Low-dose prednisone may effectively improve both symptoms and laboratory tests.

Multiplex immunoassay could be valuable for the diagnosis of connective tissue diseases

Multiplex immunoassay could be valuable for the diagnosis of connective tissue diseases

Performance of Antinuclear Antibody Connective Tissue Disease Screen

Antinuclear antibodies (ANAs) have become routine laboratory parameters in clinical hospitals. However, ANA testing by indirect immunofluorescence (IIF) assays is not an automated laboratory test. Efforts are being made to develop easy and semi- or automated methods to screen for ANAs. We evaluated the clinical performance of a new ELISA developed to screen for connective tissue disease related ANAs. The presence of serum ANA was studied with a commercial ELISA (Varelisa ANA CTD Screen) in 472 patients (202 SLE, 41 Sjögren syndrome, 11 CREST, 59 rheumatoid arthritis, 30 seronegative spondyloarthropaties, 77 inflammatory bowel disease, 13 reactive arthritis, 11 giant cell arteritis, 28 ankylosing spondilitis). A hundred and five sera from healthy subjects were used as controls. Receiver operator characteristics (ROC) analysis was carried out in order to optimize the cutoff. At target specificities of 80/90%, sensitivities of 80.8/ 73.9% were achieved. At the manufacturer's cutoff (ratio >or=1.0) sensitivity/specificity of 71.4/91.2% was found. At that cutoff, a positive likelihood ratio of 8.11 was found. For helping in the diagnosis of connective tissue diseases a test employing a subset of the most prevalent specificities reveals a good compromise as indicated by a high-positive likelihood ratio. However, the presence of ANAs in pathologies other than connective tissue diseases, such as SLE or Sjögren syndrome, may be of clinical significance as well. In these cases an IIF assay test is still mandatory, especially in autoimmune laboratories.

Comparison of Survival Among Patients With Connective Tissue Disease and Cardiomyopathy (Systemic Sclerosis, Systemic Lupus Erythematosus, and Undifferentiated Disease)

Connective tissue disease (CTD) encompasses several disease or abnormal states characterized by inflammatory or degenerative changes in connective tissue. These disorders affect many organs, including the heart. However, the long-term survival of patients with cardiomyopathy and CTD is not known. The prognostic implications of different categories of CTD were studied in patients with cardiomyopathy. One thousand seven hundred patients with initially unexplained cardiomyopathy who underwent endomyocardial biopsy from 1983 to 2003 at The Johns Hopkins Hospital were evaluated. Seventy-one subjects were diagnosed with CTD. This cohort was followed for an average of 5.1 years. Among the different disorder categories within CTD, there was a significantly lower survival rate for subjects with undifferentiated CTD (adjusted hazard ratio for death 2.39, 95% confidence interval 1.27 to 4.48, p = 0.007) and a trend toward decreased survival in patients with systemic sclerosis (adjusted hazard ratio for death 1.75, 95% confidence interval 0.93 to 3.29, p = 0.081) compared with those with idiopathic dilated cardiomyopathy (DCM). No significant survival difference was observed between systemic lupus erythematosus and idiopathic DCM (p = 0.41). The long-term outcomes of subjects with CTD and myocarditis were not statistically different from the outcomes of those with CTD and no myocarditis (p = 0.71). In conclusion, the diagnosis of cardiomyopathy and either undifferentiated CTD or systemic sclerosis appears to be a poor prognostic indicator compared with the diagnosis of idiopathic DCM. Patients with systemic lupus erythematosus and cardiomyopathy have a similar prognosis to those with idiopathic DCM. Finally, the presence of myocarditis does not alter the survival of patients with CTD and cardiomyopathy.

Indirect immunofluorescent assay for antinuclear antibodies on McCoy-Plovdiv serum-free cell line substrate

Indirect immunofluorescent assay for antinuclear antibodies (IIFA-ANA) on HEp-2 cell substrate is a widely used test for diagnosis of connective tissue diseases. Recently, serum-free fibroblast cell line McCoy-Plovdiv has been developed to provide an alternative substrate. The aim of the present study was to evaluate the diagnostic performance of IIFA-ANA on McCoy-Plovdiv cell substrate for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and compare it with that of the standard HEp-2 cell substrate. Sera from 72 patients with RA and 23 patients with SLE were tested with IIFA-ANA on both substrates. The control group consisted of 100 sera from healthy individuals. The agreement (Cohen's kappa) and the diagnostic performance (ROC analysis) of both methods were evaluated. IIFA-ANA on McCoy-Plovdiv cells proved to be comparable with the standard IIFA-ANA on HEp-2 cell substrate.

Achados capilaroscópicos no lúpus eritematoso

FUNDAMENTOS: A capilaroscopia é método não invasivo e reprodutível capaz de analisar diretamente os capilares na região periungueal, auxiliando no diagnóstico diferencial das doenças do tecido conectivo. OBJETIVOS: Estudar, por meio da capilaroscopia periungueal, pacientes com lúpus eritematoso cutâneo crônico, lúpus eritematoso sistêmico e grupo controle. MÉTODOS: Foram analisados 70 pacientes pela capilaroscopia periungueal, sendo 37 com lúpus eritematoso cutâneo crônico e 33 com forma sistêmica, comparados a 32 indivíduos sadios. RESULTADOS: A presença de capilares ectasiados (p=0,027; p=0,001), enovelados (p=0,001; p=0,007) e em saca-rolhas (p=0,011;p=0,005), além de hemorragias capilares (p=0,004; p=0,001) foram parâmetros capazes de discriminar os dois grupos de pacientes do grupo controle. A variável capilar enovelado demonstrou ser preditiva para o diagnóstico de lúpus eritematoso sistêmico (OR=8,308). As variáveis independentes capilares ectasiados (OR=12,164) e hemorragias capilares (OR=5,652) foram preditoras para lúpus eritematoso cutâneo crônico. CONCLUSÃO: A capilaroscopia é útil na prática clínica, pois pacientes com alterações capilaroscópicas específicas parecem ter maior probabilidade de desenvolver lúpus eritematoso. As variáveis preditoras independentes para lúpus eritematoso sistêmico foram capilares enovelados e para lúpus eritematoso cutâneo crônico foram capilares ectasiados e hemorragias capilares.

Diffuse Alveolar Damage: Uncommon Manifestation of Pulmonary Involvement in Patients With Connective Tissue Diseases

Background Diffuse alveolar damage (DAD) is a relatively common finding on surgical lung biopsy and can result from a variety of causes. Methods We studied nine consecutive patients with connective tissue disease (CTD) and DAD diagnosed on surgical lung biopsy to examine this association and clinical implications. Results The median age was 63 years (range, 35 to 76 years), and seven of the patients were women (78%). Underlying CTDs included rheumatoid arthritis in five patients, polymyositis in two patients, and one patient each with systemic sclerosis and mixed CTD. In seven patients (78%), CTD had been diagnosed before the onset of DAD; six of these patients had a preexisting interstitial lung disease (ILD) related to their CTD. DAD was the presenting manifestation leading to a new CTD diagnosis in two patients (22%). CT of the chest revealed ground-glass opacities and/or consolidation bilaterally with or without honeycombing. In all patients, surgical lung biopsy revealed DAD for which no cause could be identified other than the underlying CTD. Seven patients (78%) were receiving mechanical ventilatory support at the time of the surgical lung biopsy. Four patients (44%) survived to hospital discharge and included one patient with preexisting ILD and all three patients without chronic ILD. Conclusion We conclude that DAD can complicate the clinical course of patients with CTD-related chronic ILD, or can occasionally occur as a presenting manifestation of CTDs. When DAD occurs in patients with CTDs, the outcome appears to be worse for those with preexisting chronic ILD compared to those without ILD. Diffuse alveolar damage (DAD) is a relatively common finding on surgical lung biopsy and can result from a variety of causes. We studied nine consecutive patients with connective tissue disease (CTD) and DAD diagnosed on surgical lung biopsy to examine this association and clinical implications. The median age was 63 years (range, 35 to 76 years), and seven of the patients were women (78%). Underlying CTDs included rheumatoid arthritis in five patients, polymyositis in two patients, and one patient each with systemic sclerosis and mixed CTD. In seven patients (78%), CTD had been diagnosed before the onset of DAD; six of these patients had a preexisting interstitial lung disease (ILD) related to their CTD. DAD was the presenting manifestation leading to a new CTD diagnosis in two patients (22%). CT of the chest revealed ground-glass opacities and/or consolidation bilaterally with or without honeycombing. In all patients, surgical lung biopsy revealed DAD for which no cause could be identified other than the underlying CTD. Seven patients (78%) were receiving mechanical ventilatory support at the time of the surgical lung biopsy. Four patients (44%) survived to hospital discharge and included one patient with preexisting ILD and all three patients without chronic ILD. We conclude that DAD can complicate the clinical course of patients with CTD-related chronic ILD, or can occasionally occur as a presenting manifestation of CTDs. When DAD occurs in patients with CTDs, the outcome appears to be worse for those with preexisting chronic ILD compared to those without ILD.

Pneumocystis carinii Pneumonia in Patients With Connective Tissue Disease

Although the association of Pneumocystis carinii pneumonia (PCP) with connective tissue disease (CTD) has been noted for a long time, there are few series reported. The objective of this study was to describe clinical features and prognosis of PCP infections in patients with CTD in China. We retrospectively reviewed the characteristics, clinical features, and prognosis of PCP in patients with CTD in a single hospital. A total of 7 cases were reviewed (systemic lupus erythematosus n = 2, microscopic polyangiitis n = 2, dermatomyositis n = 2, polymyositis n = 1). Eighty-six percent of patients developed PCP within 3 months of the diagnosis of CTD. All patients were receiving daily glucocorticoid therapy and cytotoxic drugs before the diagnosis of PCP. Most patients had fever, progressive dyspnea, and dry cough at onset of PCP. The mean duration of symptoms before PCP diagnosis was 7 days. Absolute lymphocyte counts ranged from 126 to 528/microL. The CD4 lymphocyte counts of all patients were 87 +/- 78/microL. One patient was diagnosed by induced sputum; 6 patients were diagnosed by bronchoalveolar lavage fluid. Complicating fungal infection was found in 4 of 7 patients at the time of diagnosis of PCP. All patients were treated by trimethoprim-sulfamethoxazole and corticosteroids. Six (86%) patients died. The mean duration of the time from diagnosis to death was 14 +/- 4 days. Our results suggest that PCP is an uncommon and fatal opportunistic infection in patients with CTD. When patients with CTD who are receiving immunosuppressive therapy have low lymphocyte counts and/or CD4 lymphocyte counts less than 250/microL develop fever, dry cough, dyspnea, and chest radiography shows diffuse interstitial infiltrate, the diagnosis of PCP should be highly suspected. Induced sputum or BAL must be quickly performed to confirm diagnosis. Further study is needed as to whether earlier treatment will improve prognoses or whether patients with CTD with low CD4 counts should receive PCP prophylaxis.

Nail unit in collagen vascular diseases: A clinical, histopathological and direct immunofluorescence study

Background: Abnormalities of the nail unit are common in patients with connective tissue diseases. Clinical examination of the nail unit, coupled with biopsy of proximal nail fold offers an additional advantage in the diagnosis. Purpose: Our aim was to record clinical changes of the nail unit in connective tissue diseases and to study the histopathological (both H and E and periodic acid Schiff and direct immunofluorescence (DIF) findings of nail-fold biopsy. Materials and Methods: Thirty-eight confirmed cases connective tissue diseases attending skin OPD were enrolled in the study. After detailed clinical examination of the nail unit, a crescentric biopsy was taken from the proximal nail fold (PNF). Histopathological and DIF studies were was carried out. Findings: Nail changes could be demonstrated in 65% connective tissue diseases. Specific histopathological (H and E) and immunofluorescence findings were also encountered in many patients. Conclusion: Clinical examination of the nail unit offers additional clue in the diagnosis of connective tissue diseases. Though DIF of PNF biopsy is useful in the diagnosis, it is not an ideal site for H and E study, as the yield is very low. Limitations: Lack of adequate comparison group and non-utilization of capillary microscopy for the detection of nail fold capillary abnormalities.

Evaluation of Nailfold Videocapillaroscopic Abnormalities in Patients With Systemic Lupus Erythematosus

Nailfold capillaroscopy (NFC) has been shown to have a remarkable value in the differential diagnosis of connective tissue diseases. In fact, NFC patterns reflect the microvascular changes that may play a significant role in pathogenesis. The aims of this study were to determine in patients with systemic lupus erythematosus (SLE) the prevalence of NFC patterns, to evaluate any association with clinical features and laboratory parameters. One hundred twenty-three patients with SLE were included in this retrospective study. Video NFC parameters were analyzed in each patient. In all cases, the following parameters were evaluated: capillary arrangement, density, size, and shape. In patients with SLE, major capillary abnormalities were frequently observed (44 of 123 = 35.8%); however, no specific pattern was noted. There was a significant correlation between the SLEDAI index and the severity of capillary abnormalities (P < 0.0001). Pathologic capillary abnormalities were also significantly increased in SLE with positive anti-U1-RNP antibodies (P < 0.05). NFC may be a useful method to evaluate the microvascular changes in patients with SLE, and the presence of major capillary abnormalities seems to herald a more severe clinical course of the illness.

Esophageal Manometry and pH Monitoring

To determine whether gastroenterologists use esophageal manometry (EM) and esophageal pH recording (pHR) in accordance with published guidelines. Questionnaires were mailed to 900 randomly selected gastroenterologists nationwide. Each questionnaire requested demographic information and contained 11 case scenario-based questions, followed by a choice of management options. A total of 275 completed questionnaires (30.6%) were returned. 63.6% and 64.4% of respondents were aware of published guidelines regarding the use of EM and pHR, respectively. The majority of respondents ordered EM appropriately: 1) to confirm a suspected diagnosis of achalasia (97.1%); 2) to establish a diagnosis of connective tissue disease (89.7%); 3) as part of the preoperative evaluation for anti-reflux surgery (74.6%); and 4) to ensure the proper placement of pH probes (69.4%). EM was rarely ordered for the initial workup of noncardiac chest pain. The majority of responding gastroenterologists would order pHR for the evaluation of: 1) endoscopy-negative patients being considered for anti-reflux surgery (79.1%); 2) patients with recurrent GERD symptoms after anti-reflux surgery (62.5%); 3) endoscopy-negative patients with GERD symptoms refractory to proton pump inhibitor (PPI) therapy; and 4) patients with extraesophageal manifestations of GERD that are refractory to PPI therapy (88.7%). The majority of gastroenterologists in our study order EM and pHR in accordance with published guidelines. However, EM appears to be used less than expected for preoperative evaluation before anti-reflux surgery and for ensuring the proper placement of pH probes. In addition, the use of pHR to evaluate persistent GERD symptoms after anti-reflux surgery was less than anticipated.

Pneumopathies infiltrantes diffuses des connectivites

Interstitial lung diseases (ILD) associated with connective tissue disorders differ from idiopathic ILD in several aspects, although most of them are comparable. In most patients, ILD occurs during the course, or at the time of diagnosis of connective tissue disease. Opportunistic pulmonary infections, together with adverse effects of treatment should always be discussed. The prevalence of ILD varies among the different connective tissue disorders. Thus, ILD is frequently encountered in patients with systemic sclerosis and to a lesser degree in patients with myositis. As compared to idiopathic ILD, histopathological aspects of ILD associated with connective tissue diseases are more frequently those of non-specific interstitial pneumonia, whereas usual interstitial pneumonia is rare. Other ILD, such as organized pneumonia, interstitial lymphoid pneumonia, diffuse alveolar damage and alveolar hemorrhage are occasionally encountered. ILD must be detected early in the course of collagen disorders by performing computed tomodensitometry and pulmonary function tests. The prognosis of connective tissue associated ILD is better than that of idiopathic ILD. The treatment requires corticosteroids and/or immunosuppressants, depending on the nature of the associated connective tissue disease and ILD progression.

Comparison of Different Test Systems for Simultaneous Autoantibody Detection in Connective Tissue Diseases

The serological diagnosis of connective tissue diseases (CTDs) is based on the analysis of circulating autoantibodies to cytoplasmic and nuclear proteins (extractable nuclear antigens [ENAs]). The determination of autoantibody specificities supports the clinical diagnosis of the type of CTD and also often the prognosis of the disease. The former indirect immunofluorescence (IIF) technique still provides a useful screening method that currently is supplemented by a range of different techniques allowing the exact determination of single autoantibody specificities. These ENA profiling techniques include ELISA, immunoblotting, line-blot assays, and flow cytometric bead-based multiplex assays. The novel line immunoassay (LIA) from Mikrogen has been introduced in a recent study as a suitable technique for the simultaneous detection of autoantibodies in a routine clinical laboratory, providing comparable results as ELISA and ELiA (both from Pharmacia Diagnostics) (see Damoiseaux et al., this volume). In this study, LIAs from three different manufacturers were performed in 30 serum samples from patients with dermatological manifestations and 27 samples from SLE patients with renal involvement. The line assays from Mikrogen (recomLine ANA/ENA), Innogenetics (Inno-Lia ANA Update), and Imtec (ANA-LIA) were compared for antigen composition, handling, and statistical analysis including sensitivity and concordance. Autoantibody frequencies detected by the Mikrogen, Innogenetics, and Imtec line assays were 14.0%, 19.3%, and 15.8% for RNP; 14.0%, 22.8%, and 14.0% for Sm; 26.3%, 31.6%, and 40.3% for SSA; 3.5%, 12.3%, and 14.0% for SSB; and 3.5%, 14.0%, and 10.5% for histones. Our studies show that the line assay format is an easy-to-use, sensitive, and specific method for ENA antibody detection in human sera.

Laboratory screening of connective tissue diseases by a new automated ENA screening assay (EliA Symphony) in clinically defined patients

Background The measurement of antinuclear antibodies (ANA) is used in the autoimmune laboratory for the screening of connective tissue diseases (CTD). ANA measurements are mainly performed by indirect immunofluorescence (IIF) on HEp-2 cells or by enzyme immunoassay (EIA). The objective of this study was to clinically evaluate an automated EIA for extractable nuclear antigens (ENA) which lacks anti-dsDNA for the screening of CTD. Methods The study involved a total of 170 serum samples, 54 from patients with CTD, 26 from patients with other autoimmune diseases, and 90 from patients with non-autoimmune diseases. For all sera, ANA detection was performed by IIF and by EliA™ Symphony (Pharmacia Diagnostics, Freiburg, Germany), an ENA screening which detects the following autoantibodies: SSA/Ro, SSB/La, U 1RNP (70 kDa, A, C), Scl-70, JO-1, centromere B and Sm. Also, anti-dsDNA (EliA™ dsDNA, Pharmacia Diagnostics, Freiburg, Germany) was measured on all samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), efficiency, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. Results Diagnostic efficiency was similar for IIF (82.6%) and EliA™ Symphony (82.3%), as well as PLR (6.5 for IIF, and 7.3 for EliA™ Symphony), and NLR (0.35 for IIF, and 0.41 for EliA™ Symphony). The combined measurement of EliA™ Symphony and dsDNA increased sensitivity but not PLR. Area under receiver operator characteristic (ROC) curve was similar for IIF (0.847) and EliA™ Symphony (0.823). Conclusions The results of the study demonstrate that EliA™ Symphony solely or combined with anti-dsDNA detection has an efficiency similar to HEp-2 cells IIF with a cut-off of 1:160 for the diagnosis of CTD.

Testing for anti-nucleosome antibodies in daily practice: a monocentric evaluation in 1696 patients.

The objective was to report our experience of the detection of anti-nucleosome (anti-Nuc) antibodies (Ab) in a large series of consecutive patients, and to compare these results with those of anti-nuclear and anti-dsDNA Ab. In total, 1696 consecutive patients with suspected or confirmed autoimmune disease were tested over a two-year period. The biological investigation included detection of anti-nuclear, anti-dsDNA and anti-Nuc Ab. Among 1696 sera, 382 (23%) were negative for all Ab tested (anti-nuclear, anti-dsDNA and anti-Nuc) and 1314 (77%) were positive for at least one Ab. Anti-Nuc Ab were positive in 350/1314 patients. In this group, 249/350 (71%) also had positive anti-nuclear and anti-dsDNA, 97/350 (28%) had only positive anti-nuclear Ab without anti-dsDNA Ab and 4/350 (1%) had both anti-dsDNA and anti-Nuc Ab without anti-nuclear Ab. No patient had 'isolated' anti-Nuc Ab. Clinical data were available for 307/350 anti-Nuc positive patients. Systemic lupus erythematosus (SLE) was diagnosed in 240/307 (78%) patients, including 43 SLE patients with negative anti-dsDNA Ab. In conclusion, this study extends the relevance of anti-Nuc Ab to routine use for the diagnosis of connective tissue diseases, mainly anti-dsDNA Ab negative SLE.

Análisis de las interconsultas de pacientes nuevos recibidas en un policlínico de reumatología de un hospital terciario

The prevalence of rheumatic diseases is approximately 15% in the general population. To assess the concordance between the original and final diagnosis of patients referred to a rheumatology unit. During 2000, all new patients referred to the rheumatology section of Temuco General Hospital were recorded. The concordance between the referral diagnosis given by general practitioners or general internists and the final diagnosis reached at the rheumatology unit was analyzed using the Kappa index. The modified version of the American College of Rheumatology nomenclature was used as reference. The clinical records of 787 outpatients, 83% females, aged 54.7 +/- 14 years old, were analyzed. Twenty seven percent of patients were referred with the diagnosis of connective tissue diseases, 26% with extra articular diseases and 24% with osteoarthritis. The concordance between referral and final diagnosis reached at the rheumatology unit had a kappa of 0.6 for general practitioners and 0.72 for general internists. Although the overall concordance between referral diagnosis, given by general practitioners or general internists, and final rheumatological diagnosis is good, there are still major discrepancies that should be improved.