Diagnosis Of Seronegative Rheumatoid Arthritis Research Articles

Contribution of the Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis.

This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound. A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed. The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408. In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions.

Impact of anti-human IgG hinge peptide antibodies on identification of patients with early seronegative rheumatoid arthritis.

The early diagnosis of seronegative rheumatoid arthritis (SNRA), characterised by the absence of rheumatoid factor and anti-citrullinated antibody, involves a greater challenge compared to seropositive RA (SPRA). This study aimed to assess the discriminatory potential of anti-human IgG hinge antibodies (AHAs) for patients with early SNRA. DMARDs-naive patients with SPRA (n=43), SNRA (n=21), and non-RA (n=49), with disease duration < 2 years, were included. Antigens comprised IgG1 or IgG4 F(ab')2 cleaved by pepsin or MMP-3 and their hinge peptide analogues. Eight IgG anti-hinge antibodies (AHAs) against these antigens were measured in sera from the patients and 58 healthy controls (HCs) using ELISA. Serum CRP and MMP-3 levels, and clinical disease activity index (CDAI), were obtained from medical records. The area under the curve (AUC) obtained from logistic regression and receiver operating characteristic curve analyses were used as a discriminant indicator. The levels of the IgG AHAs were as follows: SPRA≥SNRA≈non-RA>HC. None of the AHAs were effective in discriminating SNRA from non-RA. However, the combination of MMP-3 and AHAs against IgG4 hinge peptide analogues demonstrated the utility (AUC=0.94). Furthermore, combination of MMP-3, AHAs against IgG1 hinge peptide analogues and CDAI maximally exerted discriminatory power (AUC=0.997). Specific AHAs in combination with MMP-3 and CDAI are potentially useful to discriminate SNRA from non-RA.

A novel diagnostic model based on lncRNA PTPRE expression, neutrophil count and red blood cell distribution width for diagnosis of seronegative rheumatoid arthritis

Diagnosis of seronegative rheumatoid arthritis (SNRA) is difficult due to the lack of diagnostic markers. The study aims to construct a novel diagnostic model based on long noncoding RNAs (lncRNAs) expression and laboratory indicators to provide a new idea for diagnostic methods of SNRA. Differentially expressed lncRNAs in peripheral blood cells of RA patients were screened through eukaryotic long noncoding RNA sequencing and validated by quantitative real-time PCR. Meanwhile, the correlation between lncRNAs expression and laboratory indicators was analyzed. The diagnostic value was evaluated by receiver operating characteristic curve analysis. Finally, combined with laboratory indicators, a diagnostic model for SNRA was constructed based on logistic regression and visualized by nomogram. Expression of ADGRE5, FAM157A, PTPN6 and PTPRE in peripheral blood was significantly increased in RA than healthy donors. Meanwhile, we analyzed the relationship between lncRNAs and erythrocyte sedimentation rate, C-reactive protein and CD4 + T cell-related cytokines and transcription factors. Results showed that FAM157A and PTPN6 were positively related to RORγt, and negatively related to GATA3. Moreover, PTPRE has potential discrimination ability between SNRA and healthy donor (AUC = 0.6709). Finally, we constructed a diagnostic model based on PTPRE, neutrophil count and red blood cell distribution width (RDW). The AUC of the model was 0.939 and well-fitted calibration curves. Decision curve analysis indicated the model had better predict performance in SNRA diagnosis. Our study constructed a novel diagnostic model based on PTPRE, neutrophil count and RDW which may serve as a potential tool for the diagnosis of SNRA.

Diagnosis of Sero-negative Rheumatoid Arthritis Depending on Pathology Associated with Clinical Picture

Objectives: This study was done to assess the role of synovial tissue analysis in rheumatoid arthritis (RA) patients.&#x0D; Methods: All data were recorded at baseline. All patients underwent clinical, radiologic, serologic, and histological assessments before treatment. Patients were divided into anti-citrullinated protein antibody (anti-CCP) positive and anti-CCP-negative and were compared according to different disease aspects. Correlations between clinical, laboratory, imaging, histological, and pathophysiological data were done for all patients.&#x0D; Results: There were no statistically significant differences in synovial cell infiltrates according to the serology.&#x0D; Conclusion: Both study groups had similar synovial cell infiltrates.

Diagnosis of Seronegative Rheumatoid Arthritis by 68Ga-FAPI PET/CT.

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis.

ITRAQ-based proteomic analysis of differentially expressed proteins in sera of seronegative and seropositive rheumatoid arthritis patients.

ObjectiveThe diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD).MethodsA total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism.ResultsUsing iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What's more, SAA1 was increased in the anti‐CCP or RF high‐level group in RA patients, and PSME1 was increased in the RF high‐level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators.ConclusionsiTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.

The validity of rheumatoid arthritis diagnoses in Finnish biobanks

Objective The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. Method We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients’ diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. Results The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. Conclusion These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.

Classification Criteria for Seronegative Rheumatoid Arthritis Based on Rheumatologist's Practice and Experience

Background: Diagnosis of seronegative rheumatoid arthritis (SNRA) remains difficult because chronic synovitis is nonspecific and is seen in a large number of diseases. Although the 2010 American college of Rheumatology (ACR)/European League Against Rheumatism criteria enable early detection of seropositive rheumatoid arthritis (RA), it is not much helpful in identifying seronegative patients. Objective: The objective of the study was to suggest classification criteria for SNRA. Methods: This was a questionnaire-based study. A validated questionnaire was sent to rheumatologists all over the country to collect data regarding the points which they consider for detecting SNRA. The data so collected were analyzed to identify priority given to each point. Weightage given to these points was used to suggest systematic criteria for classifying SNRA. Results: Total 50 rheumatologists participated in the survey. They reported using the presence of inflammatory polyarthritis (62%), elevated acute phase reactants (high erythrocyte sedimentation rate [ESR] - 86% and high C-reactive protein [CRP] - 78%), absence of spondyloarthropathy features (68%), absence of antibodies (rheumatoid factor [RF] – 82% and anticitrullinated protein antibodies [ACPA] – 74%), and chronic infections for detecting SNRA. Based on these results, chronic inflammatory polyarthritis or synovitis confirmed by ultrasonography or magnetic resonance imaging, raised ESR and/or raised CRP, and negative RF and negative RF and ACPA were identified as mandatory criteria, while the absence of SPA features including psoriasis, absence of clinical features of connective tissue diseases, negative Antinuclear antibodies (ANA) by Immunofluorescence assay (IFA), and absence of HCV, HBSAg, HIV, TB as well as leprosy (in endemic regions) were identified as supportive criteria. Conclusion: We propose classification criteria for SNRA. This needs further validation and could be used for studies and clinical practice in future.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

ObjectivesThe differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic...

Importance of 14-3-3eta, anti-CarP, and anti-Sa in the diagnosis of seronegative rheumatoid arthritis

Background/aimRheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation. The study aimed to assess serum 14-3-3eta, anti-CarP, and anti-Sa in seronegative RA (SNRA) patients who were treatment-naïve as well as in healthy subjects. This is the first study in the literature to examine these autoantibodies together in SNRA patients.Materials and methodsForty-five treatment-naïve SNRA patients and 45 healthy subjects were recruited. Drugs change the levels of autoantibodies; therefore, patients who took any medication had been excluded from our study. Anti-carbamylated protein, anti-Sa, and 14-3-3eta were measured by using three different ELISA kits.ResultsMedian serum concentration of healthy controls in 14-3-3eta was 0.02 (0.02–0.27) ng/mL. Median serum concentration of SNRA patients in 14-3-3eta was 1.00 (0.48–1.28) ng/mL. Data were analyzed with Mann–Whitney U tests; the P-value was <0.001 in 14-3-3eta. Receiver operating characteristic (ROC) curve analysis showed that 14-3-3eta in SNR compared to healthy controls had a significant (P < 0.001) area under the curve (AUC) of 0.90 (95% confidence interval, 0.83–0.96). At a cutoff of ≥0.33 ng/mL, the ROC curve yielded a sensitivity of 88.9%, a specificity of 82.2%, a positive predictive value of 83.3%, and a negative predictive value of 88.1%.ConclusionWe found that 14-3-3eta can be used as a diagnostic marker in SNRA.

Seronegative Rheumatoid Arthritis: A Case Control Study

Background : Seronegative Rheumatoid Arthritis (RA) is a disorder associated with considerable diagnostic, prognostic and therapeutic uncertainty for many clinicians. Objectives : The aim of this study is to elucidate clinical features at diagnosis, manifestations and treatment of patients with RA with negative serologies, as compared to a control group of patients presenting with similar polyarthralgias but diagnosed with alternative (non-RA) musculoskeletal disorders. Methods : The study was a retrospective chart review of electronic medical records from January 2003 to December 2012. Patients were identified using ICD-9 code Rheumatoid Arthritis 714.0 and at least two rheumatology clinic visits during the specified time. Charts were reviewed individually by two investigators. The inclusion criteria were a diagnosis of RA confirmed by a rheumatologist and normal values for both rheumatoid factor (RF) and anti-cyclic citrullinated protein antibodies (ACPA, third generation assay). Charts were also reviewed for eventual final diagnosis, either seronegative RA or alternate diagnosis (control group). Data were collected on demographics (sex, race, smoking status), family history of RA, and laboratory values (presence of anemia, inflammatory markers) at the time of diagnosis. The presence of erosions and synovitis identified by imaging studies was assessed. In addition, the presence of extra-articular manifestations of RA including nodules, pleural or parenchymal lung disease, eye involvement and osteoporosis was recorded. The therapies (disease modifying anti-rheumatic drug (DMARD), biologic) used to treat the seronegative RA were also reviewed. The family & smoking history and laboratory values of the seronegative RA patients were compared to the control group and analysis was done using Fisher’s exact test. Results : Charts from 107 patients were reviewed. Forty-four patients were eventually classified as having an alternate diagnosis and were considered the control group. Sixty-three patients were considered to have an established clinical diagnosis of seronegative RA. Among all patients at the time of diagnosis, 25% were smokers, 13% had a family history of RA, 54% were anemic, and 76% had abnormal ESR or CRP. The RA patients had statistically higher proportion with anemia compared to controls at presentation, and statistically lower proportion with ESR elevation compared to controls ( p =0.033 and p =0.013, respectively). Seven of the 59 (11%) patients who had hand/wrist films during their care had erosions on radiography, and 6 of 13 (46%) patients who had an MRI of an extremity had findings of synovitis. Extra-articular manifestations were infrequent in this group. Forty-eight of the 62 were initiated on a DMARD, most commonly hydroxychloroquine (16% patients) or methotrexate (29% patients) or a combination of methotrexate and hydroxychloroquine therapy (35%). Of the 63 patients, 17 (27%) patients required a biologic therapy during treatment course. Conclusions : This study supports the hypothesis that clinical history and physical examination can be important determinants in helping to diagnose seronegative RA and distinguish it from other polyarthopathies. In addition to characteristic symptoms, factors which might contribute to diagnosis of RA in a patient without seropositivity include presence of anemia, and results of imaging studies.

A Case of Methimazole-Induced Chronic Arthritis Masquerading as Seronegative Rheumatoid Arthritis

We report a 40-year-old woman with onset of oligoarthritis shortly after initiating treatment with methimazole for Graves disease. Over the course of 7 years, her arthritis became progressively severe, leading to a diagnosis of seronegative rheumatoid arthritis. Treatment with disease-modifying antirheumatic agents and surgical intervention was contemplated. Ultrasound and magnetic resonance imaging revealed exuberant synovitis, involving right elbow and knees. Upon withdrawal of methimazole, prompt resolution of all signs and symptoms of arthritis was observed within several weeks. Following a MEDLINE search of available literature concerning antithyroid drug-induced arthritis, it is evident that this case represents the lengthiest duration of inflammatory arthropathy ever described in a patient that nonetheless was rapidly reversible with discontinuation of methimazole.

Carpal Tunnel Syndrome with Paracoccidioidomycosis

Carpal Tunnel Syndrome with Paracoccidioidomycosis