From the Guidelines
C-reactive protein (CRP) testing alone cannot reliably determine if elevated levels are specifically due to inflammatory arthritis versus other causes. While CRP is a valuable marker of inflammation, it is non-specific and can be elevated in many conditions including infections, cardiovascular disease, cancer, and various inflammatory disorders. To determine if elevated CRP is related to inflammatory arthritis, clinicians typically use a combination of approaches including comprehensive clinical evaluation, additional blood tests like rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, erythrocyte sedimentation rate (ESR), and specific imaging studies such as X-rays, ultrasound, or MRI of affected joints. Joint fluid analysis may also be performed to examine for inflammatory cells and crystals. The pattern and timing of CRP elevation, along with its response to treatment, can provide additional diagnostic clues when interpreted in the context of other clinical findings. Serial CRP measurements are often more valuable than a single reading, as they can track disease activity and treatment response over time. For definitive diagnosis of inflammatory arthritis as the cause of elevated CRP, these multiple assessment methods must be used together rather than relying on CRP testing alone, as supported by recent studies 1. In fact, a study published in 2024 found that elevated CRP levels were present in both systemic juvenile idiopathic arthritis and adult-onset Still's disease, highlighting the need for a comprehensive diagnostic approach 1. Other studies have also emphasized the importance of considering multiple factors, including clinical evaluation, laboratory tests, and imaging studies, to accurately diagnose the cause of elevated CRP levels 1. Therefore, a comprehensive diagnostic approach, rather than relying solely on CRP testing, is essential for determining the cause of elevated CRP levels and guiding appropriate treatment. Some key laboratory findings to consider in the diagnosis of inflammatory arthritis include:
- Elevated ESR
- Elevated CRP
- Anaemia
- Leucocytosis
- Neutrophilia
- Elevated ferritin
- Elevated transaminases
- RF positive
- ANA positive These findings, in combination with clinical evaluation and imaging studies, can help to determine the cause of elevated CRP levels and guide appropriate treatment. It is also important to note that the interpretation of CRP results can be influenced by various factors, including the presence of underlying inflammatory conditions, infections, or other diseases, and therefore requires careful consideration of the clinical context 1.
From the Research
Reliable Testing for Elevated CRP
To determine if elevated C-reactive protein (CRP) is related to inflammatory arthritis or other causes, several tests and markers can be used in combination.
- CRP is a sensitive biomarker of inflammation, but not specific to a single disease state 2
- The combination of CRP with other markers such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody can be beneficial in confirming a diagnosis of rheumatoid arthritis (RA) 3, 4
- Elevated CRP levels have been implicated in various conditions, including cardiovascular disease, certain cancers, and autoimmune diseases, making it essential to consider multiple factors when interpreting CRP results 2, 5, 6
Diagnostic Implications of CRP
The level of circulating CRP correlates with endovascular disease and may serve to identify otherwise asymptomatic patients at sufficient cardiovascular risk to warrant aggressive therapy 5
- CRP has been associated with the risk for cardiovascular disease, diabetes, metabolic syndrome, pulmonary diseases, and depression in patients with rheumatoid arthritis 6
- The relationship between systemic inflammation, CRP, and comorbidities in RA is complex, and it is challenging to determine how changing CRP levels may affect the risk or progression of these comorbidities 6
Combination of Markers for Diagnosis
A diagnostic criterion including anti-CCP2 assay in combination with RF, CRP, and/or swollen joints is less sensitive but highly specific, and accurately predicts future development of RA among those with arthritic symptoms 4
- The sensitivity, specificity, and accuracy of RF, anti-CCP antibody, and CRP in the diagnosis of RA have been reported to be significant, with anti-CCP being more specific than the other parameters 3
- The combination of these markers can help differentiate between inflammatory arthritis and other causes of elevated CRP 3, 4