Connective Tissue Disorder Laboratory Workup

Initial Laboratory Evaluation

A comprehensive laboratory workup for connective tissue disorders should include baseline inflammatory markers, autoantibody testing, and targeted additional testing based on clinical presentation and suspected specific disorders, as recommended by the European Respiratory Society and the European League Against Rheumatism 1, 2
Inflammatory markers, such as Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), should be performed at baseline for both diagnosis and prognosis of undifferentiated inflammatory conditions, according to the Annals of the Rheumatic Diseases 2
A basic metabolic panel, including serum creatinine, liver function tests, should be performed to assess for organ involvement, as suggested by the European Respiratory Review 1

Antinuclear antibodies (ANA) are an essential screening test for most connective tissue diseases, as recommended by the European Respiratory Review and the Annals of the Rheumatic Diseases 1, 2
Rheumatoid factor (RF) is important for evaluation of rheumatoid arthritis and other connective tissue diseases, according to the Annals of the Rheumatic Diseases 2
Anti-citrullinated cyclic peptide antibodies (anti-CCP) are a specific marker for rheumatoid arthritis, as suggested by the Annals of the Rheumatic Diseases 2

If ANA positive or clinical suspicion warrants, proceed with more specific autoantibody testing, including anti-SSA/Ro and anti-SSB/La for Sjögren's syndrome, as recommended by the European Respiratory Review and PM&R 1, 3
Anti-centromere, anti-topoisomerase-1 (Scl-70), and anti-U3RNP should be tested for systemic sclerosis, according to the European Respiratory Review 1
Anti-synthetase antibodies should be tested for myositis, as suggested by the European Respiratory Review 1
Anti-thyroid antibodies should be tested for autoimmune thyroid disease, according to the European Respiratory Review 1
Anti-dsDNA and anti-Smith should be tested for systemic lupus erythematosus, as recommended by PM&R 3

For suspected vasculitis, ANCA profile and cryoglobulins should be tested, as suggested by PM&R 3
For suspected mixed connective tissue disease, anti-U1-RNP antibodies should be tested, according to Autoimmunity Reviews and the European Respiratory Review are not preferred sources, however Praxis Medical Insights is also not preferred, the fact will be kept as it is the only one available 4
For interstitial lung disease evaluation, pulmonary function tests including diffusing capacity (DLCO) and high-resolution CT scan should be performed, as recommended by Autoimmunity Reviews 5

For patients with interstitial lung disease risk, pulmonary function tests should be performed every 6 months, and annual HRCT for the first 3-4 years after diagnosis, however this fact is from Praxis Medical Insights, and will be replaced with a similar fact from a more preferred source, in this case there is no other source, so the fact will be kept as it is the only one available 4

Laboratory results should always be interpreted in the context of clinical presentation, as no single test is diagnostic for connective tissue disorders, according to the Annals of the Rheumatic Diseases 2
Avoid over-testing, and tailor additional testing based on clinical presentation and initial test results, as recommended by the Annals of the Rheumatic Diseases 2
Remember that negative tests do not exclude disease, especially early in the disease course, according to the Annals of the Rheumatic Diseases 2