Blood Work for Suspected Connective Tissue Disorder
For suspected connective tissue disorder, order antinuclear antibodies (ANA) as the essential screening test, along with inflammatory markers (CRP preferred over ESR), complete blood count with differential, comprehensive metabolic panel including liver and renal function, and rheumatoid factor (RF). 1
Initial Laboratory Panel
Essential First-Line Tests
- Antinuclear antibodies (ANA) are the cornerstone screening test for connective tissue disorders, with positive results in 10-20% of patients with associated complications like interstitial lung disease 1
- C-reactive protein (CRP) is preferred over ESR as it is more reliable, not age-dependent, and provides better correlation with disease activity 1, 2
- Complete blood count with differential to assess for cytopenias, anemia, and other hematologic abnormalities commonly seen in connective tissue disorders 1, 3
- Comprehensive metabolic panel including liver function tests, renal function, glucose, and electrolytes for baseline assessment and to detect organ involvement 1
- Rheumatoid factor (RF) to help differentiate between different connective tissue disorders, though it is nonspecific 1, 2
Additional Baseline Tests
- Erythrocyte sedimentation rate (ESR) for baseline inflammatory marker assessment, though CRP is preferred for monitoring 1, 3
- Quantitative immunoglobulin levels to assess for immune dysregulation 4
- Urinalysis to screen for renal involvement, which is common in several connective tissue disorders 1
Conditional Testing Based on Clinical Presentation
If ANA is Positive
- Anti-double-stranded DNA antibodies are highly specific for systemic lupus erythematosus 2, 3
- Anti-Smith antibodies are specific for SLE and useful as prognostic markers 3
- Anti-Ro (SSA) and anti-La (SSB) antibodies are associated with Sjögren's syndrome, neonatal lupus, and congenital heart block 2, 3
- Anti-centromere antibodies are specific for CREST syndrome variant of scleroderma 2
- Anti-histone antibodies suggest drug-induced lupus 2
- Anti-U1 RNP antibodies show high specificity for mixed connective tissue disease 3
If Systemic Sclerosis is Suspected
- Anti-Scl-70 (anti-topoisomerase I) antibodies for diffuse cutaneous systemic sclerosis 1
- Anti-RNA polymerase III antibodies associated with diffuse disease and renal crisis risk 1
If Vasculitis is Suspected
- Anti-neutrophil cytoplasmic antibodies (ANCA) are essential for diagnosing Wegener's granulomatosis and other vasculitides 2, 3
If Antiphospholipid Syndrome is Suspected
- Antiphospholipid antibodies including anticardiolipin antibodies, lupus anticoagulant, and anti-beta-2-glycoprotein I antibodies if there is history of thrombosis or recurrent pregnancy loss 3
Screening for Associated Conditions
- Hepatitis B, hepatitis C, and HIV serologies to exclude these as associated diagnoses or confounding factors 4
- Complement levels (C3 and C4) are useful in SLE for diagnosis and monitoring disease activity 3
Critical Clinical Pearls
- Do not dismiss connective tissue disorder based on normal inflammatory markers alone - approximately 20% of patients with active disease may have normal CRP/ESR 4, 1
- ANA testing should be interpreted in clinical context - positive ANA occurs in healthy individuals and requires correlation with specific antibody subtypes for diagnosis 2
- Repeat inflammatory markers (CRP and ESR) when clinically relevant to monitor disease activity and treatment response 1
- Order specific autoantibody panels based on clinical suspicion rather than ordering all tests indiscriminately, as this improves diagnostic yield and cost-effectiveness 5, 6
Multi-System Assessment
Look for these clinical features that suggest connective tissue disease and guide further testing 1:
- Joint pain, swelling, or morning stiffness
- Raynaud's phenomenon
- Photosensitivity or skin rashes
- Dry eyes and dry mouth (sicca symptoms)
- Muscle weakness or pain
- Pleuritis or pericarditis
- Unexplained fever or fatigue