European Journal of Cardiovascular Medicine

RA usually affects synovial joints, destroying them over time, making it hard to function, and lowering quality of life. This inflammatory arthritis, one of the most common forms, affects 0.5–1% of the world's population, predominantly women, and usually appears between 30 and 60 years old [1]. RA is caused by genes, environment, immune dysregulation, and hormones. RA aetiology involves synovial inflammation induced by autoreactive T-cells, B-cells, and pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, leading to pannus formation, cartilage degradation, and bone erosion. Rapid diagnosis and treatment of RA are essential to prevent joint damage and disability [2]. Traditional diagnostics include clinical assessment, serological testing for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP), and measurement of systemic inflammatory markers like CRP and ESR. Disease activity and systemic inflammation are assessed using these markers in diagnostic and therapeutic monitoring [3]. Their association with joint inflammation is questioned due to individual responses and non-specific increases in other inflammatory or viral illnesses. CRP, an acute-phase reactant generated in the liver in response to interleukin-6, is a rapid and sensitive indicator of inflammation [4]. ESR simply measures the rate at which erythrocytes settle in plasma and indirectly reflects inflammation-induced plasma protein changes. Age, sex, and anaemia can alter it. Regularly employed serological criteria may miss subclinical disease activity or structural joint degeneration since they may not indicate joint inflammation [5].

Due to its high sensitivity and specificity, magnetic resonance imaging (MRI) can detect early RA changes before clinical symptoms or radiographic indicators occur. Magnetic resonance imaging (MRI) shows synovial hypertrophy, joint effusions, bone marrow oedema, and early erosions with high resolution, unlike radiographs, which only reveal later erosions [6]. Magnetic resonance imaging (MRI) can assess therapy response, guide treatment, and predict joint deterioration in addition to early detection. Standardised scoring systems like RAMRIS make radiological disease activity measurement more objective and reproducible [7]. This improved longitudinal illness tracking and inter-observer agreement. Bone marrow oedema is now recognised as a precursor to erosive damage and a predictor of structural progression, and MRI-detected synovitis matches histopathologic results, making it a sensitive indicator of disease activity. The complexity or misleadingness of clinical symptoms in early RA or seronegative presentations makes these imaging properties clinically significant. Recent studies have combined imaging data with clinical, serological, and functional parameters to produce composite disease activity markers based on MRI findings. Some studies show a good association between MRI characteristics and inflammatory indicators like CRP and ESR, whereas others find a large discrepancy [8]. This is especially true when individuals have increased markers but no MRI abnormalities, or when MRI shows active synovitis and bone oedema when inflammation is present. Given the prominence of treat-to-target approaches and biologic drugs, this disparity makes one wonder if we trust serological markers too much to follow disease progression or remission.

RA therapy is changing, and biochemical indicators and imaging data are becoming more significant. Despite being a straightforward, non-invasive, and inexpensive technique to assess systemic inflammation, inflammatory markers frequently lack the anatomical resolution needed to assess disease localisation, severity, and responsiveness to treatment [9]. Despite its high resource requirements, MRI provides the finest view of intra-articular pathology and can detect subclinical inflammation in otherwise healthy persons. To properly assess a condition, one must understand the pros and cons of each method. CRP/ESR levels and MRI changes may differ, resulting in patients with active illness receiving too little medication and those with elevated markers from other sources receiving too much [10]. Understanding how much CRP and ESR reflect MRI-detected synovitis, bone marrow oedema, and erosions helps monitor disease activity and customise treatment. Surrogate endpoints are becoming more important in clinical trials and real-world studies to assess therapy efficacy. Academics and clinicians should study this correlation in real-world patients since it may affect treatment decisions and long-term outcomes [11].

Considering the aforementioned, the current study examined MRI scans and inflammatory markers (particularly CRP and ESR) in RA patients at the Rheumatology Clinic at Gouri Devi Institute of Medical Sciences. The study's main objective is to determine if these common laboratory indicators properly predict MRI-visible joint inflammation, especially in early or active disease. This year-long observational study uses standardised grading to find associations between serological and radiographic indices on illness monitoring. This study aims to expand the literature on RA multimodal disease evaluation and help doctors make better imaging, treatment escalation or de-escalation, and follow-up decisions. This work seeks to identify blood marker-imaging characteristic concordance or discordance to inform future changes to disease activity scoring systems like DAS28 and SDAI, which rely heavily on CRP and ESR. The relationship between inflammatory markers and MRI may enable more accurate, personalised patient therapy and better long-term RA outcomes.

Study Design and Duration

This was a prospective observational study conducted over a duration of one year.

Study Setting

The study was carried out at the Department of Rheumatology and Radiodiagnosis, Gouri Devi Institute of Medical Sciences, with collaborative input from both clinical and radiological teams.

Inclusion Criteria

• Adults aged 18 to 70 years
• Diagnosed with rheumatoid arthritis (RA) according to the 2010 ACR/EULAR classification criteria
• Underwent both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) testing
• Had MRI imaging of affected joints (preferably hand/wrist) during the study period

Exclusion Criteria

• Presence of co-existing autoimmune diseases (e.g., lupus, psoriatic arthritis) or infectious diseases that could elevate CRP/ESR
• Received intra-articular steroids, systemic corticosteroids, or biologic therapies in the last 3 months
• Were pregnant or lactating

Sample Size Calculation

The sample size was calculated to determine the correlation between inflammatory markers and MRI findings. Assuming a moderate correlation coefficient (r = 0.4), and using:

• Alpha (α) = 0.05
• Power (1-β) = 0.80

The sample size formula used was:

Plugging the values into the formula gave a required sample size of approximately 47 participants. To account for possible dropouts or data loss, the final sample size was rounded up to 50 patients.

Data Collection Protocol

CRP and ESR measurements were taken at baseline and at regular follow-up intervals of every 3 months during the study period. MRI of the affected joints (primarily hand and wrist) was performed using a standard protocol. MRI scans were assessed using the RAMRIS (Rheumatoid Arthritis MRI Scoring) system, which quantifies:

• Synovitis
• Bone marrow edema
• Erosions

MRI interpretations were performed by radiologists blinded to the clinical and laboratory findings to reduce bias.

Statistical Analysis

Data was entered and analyzed using SPSS or an equivalent statistical software. Descriptive statistics (mean, standard deviation, frequency) were used for demographic variables. The relationship between CRP, ESR, and MRI scores was assessed using either: Pearson’s correlation coefficient for normally distributed data. Spearman’s rank correlation coefficient for non-parametric data. A p-value < 0.05 was considered statistically significant.

Table 1: Baseline Characteristics of Study Participants (n = 44)

The study population had a mean age of 48 years, with a female predominance (70%), which is consistent with known RA demographics. A high proportion of patients had elevated inflammatory markers: 84% had raised CRP and 90% had raised ESR at the time of enrollment, indicating active systemic inflammation in most participants.

Table 2: MRI Findings in Study Participants

MRI revealed active synovial inflammation (synovitis) in 82% of patients, bone marrow edema in 66%, and joint erosions in 54%. This demonstrates that a significant number of patients had both active inflammation and structural joint changes, underlining MRI’s utility in detecting early and ongoing disease pathology, often beyond what clinical or serologic findings can capture.

Table 3: Correlation between Inflammatory Markers and MRI Scores

There was a moderate positive correlation between CRP and ESR with MRI-detected synovitis, indicating that higher inflammatory marker levels are generally associated with increased synovial inflammation. A milder correlation was seen between these markers and bone marrow edema, suggesting that systemic inflammation contributes to, but doesn't fully account for, marrow involvement. No meaningful correlation was found between inflammatory markers and erosion scores, indicating that erosive damage may not align with current inflammation levels and is likely a result of past, untreated disease activity. Notably, CRP showed a slightly stronger correlation than ESR across the board.

Key Findings

This study examined the connection between inflammatory markers—CRP and ESR—and magnetic resonance imaging (MRI) outcomes in rheumatoid arthritis (RA) patients and found important insights. Many of the 44 trial participants had elevated C-reactive protein (84%) and serum redness (ESR) levels (90%) indicating ongoing systemic inflammation. MRI findings of synovitis (82%), bone marrow oedema (66%), and bone erosions (54%), reveal the predominance of inflammatory and structural joint pathology in this cohort. The correlation analysis revealed a moderate positive correlation (r = 0.52 and r = 0.47, respectively; p < 0.01) between CRP, ESR, and MRI synovitis scores. CRP was somewhat stronger (r = 0.44) and ESR was slightly weaker (r = 0.41), with p-values less than 0.05. The lack of a correlation between CRP, ESR, and erosion scores suggests that structural deterioration may not always indicate systemic inflammation. Even with normal CRP and ESR, some individuals had prolonged synovitis and oedema on MRI. Even though systemic indicators are normal, joint inflammation may still be present. The findings suggest that CRP and ESR can screen and measure inflammation, however they may not be able to assess joint inflammation in RA patients.

Previous Research

This study confirms past findings on RA's MRI features and serological markers. [12] & [13] showed moderate associations between CRP levels and MRI-detected synovitis and bone marrow oedema, like us. Clinical inspection and blood tests may miss subclinical inflammation, however MRI is more sensitive, as shown in these studies. We discovered that CRP and ESR predict synovitis disease activity, but not conclusively. There is no assurance, however moderate correlations demonstrate that elevated markers imply synovial joint inflammation. Historical research also suggests no strong erosion score connections. Erosion is usually seen as a long-term result of chronic inflammation rather than a symptom of disease. Many persistent joint injury patients have normal CRP/ESR levels if the systemic inflammatory response has decreased or they are in partial remission. Note that other studies has found this disparity.  [14] & [15] found that MRI can detect erosive progression in people believed to have low disease activity using traditional composite criteria like DAS28. Our data support these findings and demonstrate that serological markers alone cannot monitor illnesses.

This study contributes to the growing body of data challenging standard inflammatory indicators' ability to describe all RA symptoms. As treat-to-target (T2T) and biologic medications become more common, disease activity must be precisely and sensitively measured. MRI can identify active disease in patients with normal C-reactive protein and elevated serum ferritin, which helps doctors reconcile clinical observations and lab results. MRIs may show synovial inflammation in patients with joint stiffness, pain, or decreased function despite normal CRP and ESR values, requiring treatment adjustments. Avoiding overtreatment may assist non-rheumatologic systemic inflammation patients with increased CRP or ESR but no significant MRI abnormalities. Combining clinical, serological, and imaging data supports a more tailored, evidence-based RA care strategy.

Limitations and Suggestions for Future Research

Despite its strengths, this study has numerous drawbacks. First, the small sample size (n = 44) limited statistical power and generalisability. The sample was large enough to find moderate correlations, but a larger cohort would reveal age, gender, disease duration, and treatment status subgroup differences. Second, this single-center study at Gouri Devi Institute of Medical Sciences may have introduced center-specific biases in patient selection, clinical care, and MRI interpretation. A multicenter strategy would improve patient representation and validate these findings. Third, while one year is sufficient for assessing relationships, it may not be long enough to determine long-term consequences like erosion progression or therapy response. Multi-year longitudinal studies could better explain the temporal link between inflammatory markers, MRI findings, and clinical outcomes. Fourth, MRI only examined the hand and wrist joints, which are often inflamed in RA, but not the knees, ankles, or shoulders. MRI of the whole body or additional joints may identify illness tendencies. Fifth, while CRP and ESR are commonly used, other biomarkers like interleukin-6, TNF-α, or MBDA scores may offer a more complex picture of systemic inflammation and should be considered in future research.

In ordinary clinical practice, MRI cost and accessibility remain practical hurdles, especially in resource-limited countries. This study recommends using MRI in cases of diagnostic doubt or discordant data, however not all patients can utilise it. Thus, more research should develop clinical algorithms or prediction tools to identify patients who will benefit from MRI screening. Although proven, RAMRIS scoring is semi-quantitative and operator-dependent. Standardising scoring methodologies and using AI-driven picture analysis could improve objectivity and reproducibility. Consider ultrasound imaging, which is less sensitive than MRI but more accessible and can identify synovitis and power Doppler signs in real time.

This study underlines the moderate but significant relationship between MRI results and inflammatory indicators like CRP and ESR in RA patients. CRP had a somewhat higher connection with MRI-detected synovial inflammation and bone marrow oedema than ESR, supporting its role as a systemic inflammation measure. Since neither signal corresponds with erosion scores, imaging is crucial for long-term disease surveillance. This suggests structural joint deterioration may occur without systemic inflammation. MRI showed subclinical inflammation in several patients with normal CRP and ESR values, revealing chronic synovitis and bone marrow oedema that serological assays missed. This finding supports the use of sophisticated imaging techniques in routine clinical practice and highlights the limitations of blood-based biomarkers for disease activity evaluation in circumstances of diagnostic doubt or contradictory clinical and laboratory data. Multimodality is utilised to better assess disease activity, make appropriate treatment decisions based on patient-specific information, and enhance patient outcomes while preventing permanent joint damage. Clinical evaluation and MRI are used in this method. In some clinical scenarios, magnetic resonance imaging (MRI) can improve diagnosis accuracy and treatment planning. However, it is still resource-intensive. The study also emphasises broadening imaging availability and employing modern technology like AI in image analysis to standardise. Future multicenter trials with larger, more diverse cohorts and longer follow-up durations are needed to confirm these findings, assess disease progression, and improve the use of MRI and serological indicators in rheumatoid arthritis treatment.

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