Diagnosis Of Systemic Rheumatic Diseases Research Articles

Characteristics and outcome of critically ill patients with systemic rheumatic diseases referred to the intensive care unit

ObjectivesPatients with systemic rheumatic diseases (SRDs) are at risk of admission to the intensive care unit (ICU). Data concerning these critically ill patients are limited to few retrospective studies.MethodsThis is...

Significance of serum procalcitonin for differentiating infections from rheumatic diseases

Differentiation between flare of a rheumatic disease (RD) and the development of infectious process is often extremely difficult due to the similarity of clinical and laboratory manifestations, as well as their lack of specificity.Objective of the study: to assess the significance of procalcitonin (PCT) test as a specific marker of generalized and local infection in patients with RD, and also to determine its role in assessing the inflammatory process activity in various RDs.Material and methods: The case records of 145 patients (101 women , 44 men, age of 3–79 years), who were undergoing inpatient examination and treatment at Nasonova Research Institute of Reumatology, were examined during the retrospective study. The serum PCT level was determined by the quantitative electrochemiluminescence method using the Cobas E 411 analyzer (Roshe, Switzerland).Results: The infectious process was diagnosed in 85 patients, the generalized one in 13 and the local one in 72. Local infections were divided into those with the light course – 41 and with the severe course – 31. In patients with generalized infection, the PCT level exceeded 2.0 ng/ml in 77% of cases and in 10.0 ng/ml in 46.2% of cases. Median (Me) PCT was 3.6 [2.26; 10.5] in the group with generalized infection. Me PKT exceeded the threshold values and amounted to 0.49 [0.19; 1.5] ng/ml in the case of a local infection with the severe course, PCT indices did not significantly differ from those of the group without infection (Me = 0.13 [0.08; 0.25] and 0.09 [0.06; 0.18 ] ng / ml, p> 0.05).with a local infection of the lungs, The maximum values of PCT in the absence of infection and with a high activity of the rheumatic process were detected in patients with Adult-onset Still’s Disease (AOSD) – Me = 0.26 [0.10; 0.61] ng/ml, moderate increase was detected in patients with systemic-onset juvenile idiopathic arthritis (JIA)– Me = 0.2 [0.14, 0.24] ng/ml, juvenile rheumatoid arthritis (JRA) – Me = 0.2 [0.1; 0.26] ng/ml, systemic lupus erythematosus (SLE) – Me = 0.19 [0.11, 0.39] ng/ml.Conclusions: Determining PCT level undoubtedly contributes to the diagnosis of generalized infections, and differential diagnosis of systemic RD from the infectious process. Further research is required to determine the PCT threshold value for various RDs.

PROCALCITONIN TEST IN RHEUMATIC DISEASES

Estimation of serum procalcitonin (PCT) levels is of great interest in rheumatology in both the diagnosis of coinfections and the differential diagnosis between rheumatic disease activity and the current infectious process. Objective: to estimate the value of PCT as a specific marker for generalized and local infection in rheumatic patients. Subjects and methods. A retrospective study investigated the case histories of 100 inpatients examined and treated at the V.A. Nasonova Research Institute of Rheumatology. Serum PCT concentrations were determined by a quantitative electrochemiluminescence assay using a Cobas E 411 analyzer (Roche, Switzerland). Results. Infectious diseases were diagnosed in 41 of the 100 patients. The infectious process was generalized and local in 11 and 30 cases, respectively. In the patients with generalized infection, the level of PCT was more than 2.0 ng/ml in 81.8% of the cases. In the local infection and non-infection groups, it was below 0.5 mg/ml in 70 and 84.7% of cases, respectively. In the generalized infection group, the content of PCT was significantly higher (3.6 [2.3; 10.5]) than in the local infection (0.24 [0.15; 0.7]; р = 0.004) and non-infection (0.15 [0.09; 0.26]; р = 0.0001) groups. It did not depend on rheumatic disease activity. C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) correlated with PCT concentrations in different patient groups. ROC analysis showed the optimal sensitivity (82%) and specificity (98%) of PCT as a marker of systemic infection only in the rheumatic patients with its concentration of ≥2.3 ng/ml. Conclusion. The determination of PCT is certain to contribute to the diagnosis of generalized infections and the differential diagnosis of systemic rheumatic diseases and infectious ones.

Predictive value of antinuclear antibodies in autoimmune diseases classified by clinical criteria: Analytical study in a specialized health institute, one year follow-up

Introduction: Determination of antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) is usually the initial test for the diagnosis of systemic rheumatic diseases (SRD). Assigning predictive values to positive and negative results of the test is vital because lack of knowledge about ANAs and their usefulness in classification criteria of SRD leads to inappropriate use. Methods: Retrospective study, ANA tests requested by different specialties, correlation to patients' final diagnosis. Results: The prevalence of autoimmune disease was relatively low in our population yielding a low PPV and a high NPV for the ANA test. 40% of the patients had no clinical criteria applied prior to test. Coexistence of two or more autoimmune disorders affects prevalence and predictive values. Conclusion: Application of the test after careful evaluation for clinical criteria remarkably improves the positive likelihood ratio for the diagnosis.

Detection of antinuclear antibodies by automated indirect immunofluorescence analysis

BackgroundTesting for antinuclear antibodies is useful for the diagnosis of systemic rheumatic diseases. Automated systems for image acquisition and interpretation of indirect immunofluorescence-based tests are increasingly used. The diagnostic performance of such automated approach in untreated patients has not been reported. MethodsAntinuclear antibodies were measured by automated indirect immunofluorescence using Zenit G. Sight on HEp2 and HEp2000 substrate in 268 consecutive samples submitted to the laboratory for antinuclear antibody testing, and in 231 patients with a systemic rheumatic disease at the time of diagnosis, 143 blood donors, 134 patients with chronic fatigue syndrome, and 133 diseased controls. ResultsImage acquisition by G-Sight was of high quality. The accuracy of pattern assignment was limited. There was a significant correlation between automated estimation of fluorescence intensity (probability index of positivity) and end-point titer. Probability index interval specific likelihood ratios for systemic rheumatic disease increased with increasing level of positivity probability. With the HEp-2 substrate, the likelihood ratio for systemic lupus erythematosus was 0.06, 0.4, 6.8, 12.1, and 43.9 for a probability measure of positivity of ≤10, 11–≤30, 31–≤50, 51–≤85, and >85, respectively. ConclusionQuantitative data generated by automated image acquisition facilitates standardized interpretation.

Multiplex assessment of non‐organ‐specific autoantibodies with a novel microbead‐based immunoassay

Advances in immunofluorescence assay development paved the way for the simultaneous detection of several antibodies in one sample, for the serological diagnosis of systemic rheumatic diseases. Standardized automated screening of such antibodies can be achieved by HEp-2 cell-based indirect immunofluorescence (IIF) using a multicolor fluorescence imaging technical platform. To create a common platform for both screening and specific antibody assessment, multiplex measurement of antibodies using fluorescence-coded immobilized microbeads was employed on the same platform. The multicolor fluorescence detection system VideoScan (AKLIDES®) was used for the fluorescence analysis of a multiplex microbead-based immunoassay (MIA). First, immunoglobulin G (IgG) was covalently coupled to one microbead population in duplicate and in three independent experiments. The coupled IgG was detected by a Cy™5-conjugated secondary antibody. Thus, intra- and interassay coefficients of variation (CV) were obtained. Second, a multiplex determination of antinuclear autoantibodies (ANA) to Scl-70, Sm, dsDNA, SS-A (Ro60), CENP-B, and La/SS-B by solid-phase MIA was investigated, using 72 sera from patients with autoimmune diseases such as systemic lupus erythematosus and systemic sclerosis (SS). The reproducibility study revealed intra-assay CVs ranging from 3.2% to 9.9%, and interassay CVs ranging from 9.6% to 14.7%. The detection of Scl-70-, Sm-, CENP-B-, and La/SS-B-ANA with MIA showed very good agreement with the ELISA results (kappa = 1.0). The resulting relative sensitivities and specificities for Scl-70-, Sm-, CENP-B-, dsDNA-, and La/SS-B-ANA were 100%, respectively, with the exception of dsDNA (specificity 97%). Multiplex detection by immobilized fluorescence-coded microbeads using multicolor fluorescence is a reliable method for the assessment of rheumatic-disease-specific antibodies. Multicolor fluorescence analyses with pattern detection algorithms provide a common platform technique for both the screening of ANA by cell-based IIF and specific antibody assessment by multiplex detection.

Diagnostic Tests for Rheumatic Disease: Clinical Utility Revisited

Establishing a diagnosis of systemic rheumatic disease requires an integration of a patient's symptoms, physical examination findings, and the results of diagnostic testing. There is often a temptation by clinicians to rely heavily on objective measures such as the presence or absence of an autoantibody. Medical textbooks and the medical literature may overestimate the diagnostic utility of many commonly ordered tests for rheumatic disease because the tests are usually analyzed among patients with established rheumatic disease rather than among patients with an uncertain cause of symptoms as is common in practice. Few diagnostic tests are highly sensitive, though the antinuclear antibody in systemic lupus erythematosus (SLE) and the erythrocyte sedimentation rate in temporal arteritis are notable exceptions. Conversely, few diagnostic tests are highly specific; anti-proteinase-3 and antimyeloperoxidase antibodies (types of antineutrophilic cytoplasmic antibodies) among patients with Wegener granulomatosis (and related vasculitides) and anti-double-stranded and anti-Smith antibodies among patients with SLE may be particularly helpful in the proper clinical settings due to their high specificity. Anticitrullinated cyclic protein (anti-CCP), a newly described autoantibody that may be highly specific for rheumatoid arthritis, requires additional study as its utility in clinical practice is uncertain.

Autoantibodies in the diagnosis of systemicrheumatic diseases

Distinct profiles of autoantibodies directed to intracellular antigens can be detected in the systemic connective tissue diseases. They aid in establishing the correct diagnosis and are included in many sets of diagnostic criteria, such as the ones developed for systemic lupus erythematosus (anti-Smith antigen and anti-double-strand DNA antibodies), mixed connective tissue disease (anti-U1-nuclear ribonucleoprotein antibodies), and Sjögren's syndrome (SS) (anti-SS A/Ro and anti-SS-B/La antibodies). They are useful prognostic markers in some situations and facilitate clinical and treatment follow-up. Autoantibodies have also been used as probes to gain insights into cell biology, helping to isolate and purify intracellular proteins involved in key cellular functions. We give detailed information on two of the most useful techniques for the detection of autoantibodies in the clinical and research laboratory settings, indirect immunofluorescence and immunoblotting. We also discuss several of the antigen -autoantibody systems found in systemic lupus erythematosus (Smith antigen, U1-nuclear ribonucleoprotein, SS-A/Ro, SS-B/La, proliferating cell nuclear antigen ribosomal ribonucleoprotein, double-strand DNA, histones, antiphospholipids, Ku, Ki/SL), systemic sclerosis (centromere, topo I, RNA polymerases, fibrillarin, polymyositis-Scl, Th/To), polymyositis/dermatomyositis (transferRNA synthetases, signal recognition particle, and others), and SS (SS-A/Ro, SS-B/La, nucleolar organizing region-90, p80-coilin), addressing their clinical significance, common detection methods, immunogenetic associations, and the molecular and cellular biology of the cognate antigens.

Concurrent Linear Scleroderma and Systemic Lupus Erythematosus: A Report of Two Cases

Two patients with linear scleroderma (en coup de sabre) developed systemic lupus erythematosus (SLE). This association has been well documented in only one previous case. The presence of high titer antibodies to ribonucleoprotein (RNP) initially led to the diagnosis of the mixed connective tissue disease. Development of more serious clinical involvement and antibodies to Sm (case 1) or native deoxyribonucleic acid (nDNA) (case 2) helped establish a diagnosis of SLE. Use of these studies in the differential diagnosis of systemic rheumatic diseases is disucssed briefly. The presence of anti-RNAP antibodies in patients with localized scleroderma may herald a more serious rheumatic disease.