Differential Diagnosis: Overlap Syndrome - Rheumatoid Arthritis with Axial Spondyloarthropathy
This 28-year-old female most likely has rheumatoid arthritis (RA) with coexisting axial spondyloarthropathy (axSpA), representing an overlap syndrome, given the combination of high anti-CCP antibodies (highly specific for RA), sacroiliac joint sclerosis on X-ray, elevated inflammatory markers, and the pattern of joint involvement.
Primary Diagnostic Considerations
Rheumatoid Arthritis (Most Likely Primary Diagnosis)
- Anti-CCP antibodies are 81-85% specific for RA and predict more aggressive disease with structural damage 1
- The presence of both high anti-CCP and elevated CRP strongly supports RA diagnosis, as anti-CCP is predictive of RA diagnosis and worse radiographic outcomes 1
- Hand pain (now resolved) with positive anti-CCP is characteristic of RA, even when RF status is unknown 1
Axial Spondyloarthropathy (Coexisting Condition)
- Radiographic sclerosis of sacroiliac joints indicates established structural changes consistent with axSpA 1
- Back pain in a young patient (<45 years) with sacroiliac joint involvement suggests axSpA 1
- The prevalence of SpA features in RA patients may be 15-18%, much higher than previously recognized 2
Critical Diagnostic Algorithm
Step 1: Confirm RA Diagnosis
- Verify anti-CCP levels are significantly elevated (>250 U/ml suggests more severe disease) 3
- Check rheumatoid factor (RF) status - 79-81% of RA patients are RF-positive 2, 4
- Document pattern of joint involvement (small joints of hands/feet typical for RA) 1
Step 2: Characterize Axial Involvement
- Determine if back pain meets inflammatory back pain (IBP) criteria: morning stiffness, improvement with exercise, pain in second half of night, alternating buttock pain 1
- Order HLA-B27 testing - positive in 90% of axSpA with sensitivity/specificity of 90%, yielding 32% post-test probability 1
- Obtain MRI of sacroiliac joints without contrast if diagnosis unclear, as this is the highest-rated second-line investigation with 79% sensitivity and 89% specificity 1, 5
Step 3: Additional Imaging
- X-rays of hands and feet should be performed at baseline to assess for RA-related erosions 1
- Spine radiographs (cervical and lumbar) complement sacroiliac imaging for complete axSpA assessment 5
- MRI of spine is NOT routinely recommended for initial diagnosis but may be considered if sacroiliac joints appear normal on imaging yet clinical suspicion remains high 1, 5
Important Clinical Pitfalls
Radiographic Interpretation Caveats
- Radiographic sacroiliitis has only 80% sensitivity and specificity, with fair to moderate interobserver agreement 1, 5
- Sclerosis represents chronic structural changes; early inflammatory disease may be radiographically occult for 3-7 years 5
- If X-rays show established sclerosis, this patient likely has longstanding axSpA that was previously undiagnosed 1
Overlap Syndrome Recognition
- 16.8% of RA patients have inflammatory back pain, and 5.3% meet ASAS criteria for axial SpA 2
- The coexistence of high anti-CCP with sacroiliitis is uncommon but well-documented 2
- Do not dismiss axial symptoms in anti-CCP positive patients as "just RA" 2
Treatment Implications
Therapeutic Approach
- TNF inhibitors are effective for both RA and axSpA, making them ideal for overlap syndromes 6, 7
- Higher anti-CCP concentrations at baseline predict better response to abatacept in RA patients 3
- NSAIDs at full dose should be considered for axial symptoms, as good response (within 48 hours) has diagnostic value 1
Monitoring Strategy
- Anti-CCP antibodies remain stable during treatment and do not reflect treatment response 4
- CRP and RF levels decrease with effective therapy, making them better markers for monitoring 4
- Repeat sacroiliac joint X-rays should not be performed more frequently than every 2 years for structural monitoring 1