From the Guidelines
A comprehensive workup for connective tissue disorders should begin with a detailed history and physical examination, focusing on joint hypermobility, skin elasticity, and family history, as well as screening for organ involvement such as pulmonary arterial hypertension, interstitial lung disease, and scleroderma renal crisis, as recommended by recent guidelines 1. The workup should include initial laboratory testing with complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody (ANA), and rheumatoid factor.
- If ANA is positive, further testing for specific antibodies like anti-dsDNA, anti-Smith, anti-RNP, anti-Ro/SSA, and anti-La/SSB should be conducted.
- Complement levels (C3, C4) are important to assess immune system activity. Some key points to consider in the workup include:
- Screening for interstitial lung disease (ILD) in patients with systemic sclerosis, particularly those with diffuse cutaneous systemic sclerosis (dcSSc) and anti-topoisomerase 1 (Scl-70) antibodies 1.
- Screening for pulmonary arterial hypertension (PAH) in high-risk patients, such as those with longer disease duration, older age, and low diffusing capacity 1.
- Regular blood pressure checks and home blood pressure monitoring in patients with early dcSSc, especially those positive for anti-RNA polymerase III antibodies (anti-RNAPIII) 1. Imaging studies may include:
- X-rays of affected joints
- Echocardiography to evaluate cardiac involvement, particularly in disorders like Marfan syndrome or Ehlers-Danlos syndrome
- High-resolution CT of the lungs to screen for ILD Genetic testing is valuable for hereditary disorders such as:
- Marfan syndrome (FBN1 gene)
- Ehlers-Danlos syndrome (COL5A1, COL5A2, COL3A1 genes)
- Osteogenesis imperfecta (COL1A1, COL1A2 genes) Skin or tissue biopsies may be necessary in certain cases to examine collagen structure. This systematic approach helps differentiate between various connective tissue disorders like systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and hereditary disorders, enabling appropriate management strategies, as supported by recent research 1.
From the Research
Connective Tissue Disorder Workup
- The workup for connective tissue disorders involves a combination of clinical evaluation, laboratory tests, and genetic testing 2, 3, 4, 5, 6
- A complete rheumatological and medical history, and a thorough physical examination are essential in making a diagnosis of connective tissue disease 2
- Laboratory tests such as complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody can aid in the diagnosis of connective tissue disorders 3, 4, 6
- Genetic testing, including next-generation sequencing panels, can help identify novel variants causing disease in heritable connective tissue disorders (HCTDs) 5
Laboratory Tests
- CBC-derived inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet-to-lymphocyte ratio (PLR) can assess disease activity and prognosis in rheumatic disorders 3
- ESR and CRP tests can be used to monitor disease activity, but may not have sufficient specificity to appraise disease activity 3, 4
- RF and anti-CCP antibody tests can be used to diagnose rheumatoid arthritis (RA), with anti-CCP antibody being more specific than RF 6
Genetic Testing
- Genetic testing can help identify pathogenic, likely pathogenic, and potentially pathogenic variants in genes known to play a role in HCTDs 5
- Patients with potentially pathogenic variants may exhibit similar symptom profiles to those with pathogenic or likely pathogenic variants in the same genes 5
- Latent class analysis can help identify distinct groups of patients based on symptomatology, which can guide future diagnosis and disease monitoring 5