From the Guidelines
When screening patients with suspected connective tissue disease, clinicians should prioritize screening for interstitial lung disease (ILD) using pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT), as ILD is a major cause of morbidity and mortality in these patients 1. The screening process should include a comprehensive evaluation of both laboratory and clinical assessments.
- Begin with a complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and C-reactive protein to assess for inflammation.
- Specific autoantibody testing is crucial, including antinuclear antibody (ANA), which serves as an initial screening test with further specific antibodies based on clinical presentation:
- anti-dsDNA and anti-Smith for lupus;
- anti-Ro/SSA and anti-La/SSB for Sjögren's syndrome;
- anti-topoisomerase I (Scl-70) and anti-centromere for systemic sclerosis;
- and anti-Jo-1 for inflammatory myopathies.
- Complement levels (C3, C4) should be checked as they may be decreased in active lupus.
- Urinalysis is important to detect renal involvement.
- Muscle enzymes (CK, aldolase) are valuable when myositis is suspected.
- Imaging studies like chest X-ray or high-resolution CT may be needed to evaluate for interstitial lung disease. These tests help identify the specific connective tissue disease and assess organ involvement, guiding appropriate treatment. The pattern of clinical manifestations—such as skin rashes, joint pain, Raynaud's phenomenon, muscle weakness, or sicca symptoms—combined with laboratory findings will direct the diagnostic process and subsequent management 1. It is essential to note that the risk of ILD varies among patients with different connective tissue diseases, and screening should be focused on high-risk patients or those with symptoms suggestive of ILD 1. A risk-based approach is necessary for determining the need for HRCT and additional testing, and the frequency of testing should be guided by the patient's risk factors and clinical presentation 1.
From the Research
Screening Tests for Connective Tissue Disease
To screen for connective tissue disease in patients, several tests can be utilized:
- Antinuclear antibodies (ANAs) testing, as it has been shown that the presence of ANAs can precede the diagnosis of systemic lupus erythematosus (SLE) and other connective tissue diseases 2
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) tests, which are indicators of inflammation, with CRP being more sensitive and responsive to changes in the clinical situation than ESR 3
- Complete Blood Count (CBC) test, which can provide parameters such as Neutrophil-to-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), and red cell distribution width (RDW) that can assess disease activity and prognosis in rheumatic disorders 4
Specific Markers for Connective Tissue Disease
Specific markers that can be screened for in patients with suspected connective tissue disease include:
- ANAs, which have a positive predictive value (PPV) of 7% and a negative predictive value (NPV) of 98% for the development of a new connective tissue disease in undiagnosed symptomatic patients 2
- U1 small nuclear ribonucleoprotein particle antibodies, which are associated with mixed connective tissue disease (MCTD) 5
- CRP and ESR, which can show discordance in some cases, with high CRP/low ESR discordance often associated with infections and high ESR/low CRP discordance associated with connective tissue diseases such as systemic lupus erythematosus 6
Interpretation of Test Results
When interpreting test results, it is essential to consider the following:
- The presence of ANAs does not necessarily confirm a diagnosis of connective tissue disease, but rather indicates an increased risk of developing the disease 2
- CRP and ESR tests can show discordance, and the causes of this discordance should be investigated, as it can provide valuable information for diagnosis and treatment 6
- CBC-derived parameters such as NLR, MPV, and RDW can provide prognostic information and assess disease activity in rheumatic disorders 4