Should I refer a patient with elevated anti-scleroderma (anti-Scl-70) antibodies to rheumatology?

Referral for Elevated Anti-Scleroderma Antibody

Yes, patients with elevated anti-scleroderma (anti-Scl-70) antibodies should be referred to rheumatology, even if they are currently asymptomatic, as this antibody is strongly associated with systemic sclerosis and may indicate early or developing disease requiring specialized evaluation and monitoring.

Clinical Significance of Anti-Scl-70 Antibodies

Anti-Scl-70 (anti-topoisomerase I) antibodies are highly specific for systemic sclerosis (SSc), with important diagnostic and prognostic implications:

• These antibodies have a specificity of approximately 99% for systemic sclerosis 1
• Anti-Scl-70 antibodies are associated with a higher risk of developing:
  • Diffuse cutaneous involvement (86% of patients) 2
  • Pulmonary involvement/interstitial lung disease (85% of patients) 2
  • Joint involvement (89% of patients) 2

Rationale for Rheumatology Referral

The 2017 Society for Immunotherapy of Cancer (SITC) guidelines explicitly state: "For other suspected rheumatologic manifestations (e.g. vasculitis, myositis, scleroderma, etc.), rheumatology referral is advisable even if the symptoms are mild, to ensure that appropriate diagnostic testing and optimal management can be coordinated to prevent permanent organ damage." 3

This recommendation is particularly important because:

1. Early detection of systemic sclerosis can prevent irreversible organ damage
2. Rheumatologists can conduct comprehensive evaluations to confirm or rule out systemic sclerosis
3. Even in asymptomatic patients, the presence of anti-Scl-70 antibodies warrants monitoring for future disease development

Potential for False Positives

It's important to note that false positive anti-Scl-70 results can occur:

• A 2022 study found that 92.3% of patients referred to a scleroderma center with positive anti-Scl-70 antibodies but without classifiable SSc tested negative when retested using the more specific immunodiffusion method 4
• These false positives led to unnecessary diagnostic evaluations, with 43.8% of these patients undergoing chest CT scans and 29.2% undergoing echocardiograms 4

Recommended Evaluation Process

When referring a patient with elevated anti-Scl-70 antibodies to rheumatology, the following should be considered:

1. Pre-referral assessment:

   • Check for Raynaud's phenomenon, which is present in most SSc patients
   • Look for any skin changes, especially sclerodactyly or skin thickening
   • Assess for symptoms of interstitial lung disease (dyspnea, cough)

2. Laboratory testing to consider:

   • Complete autoimmune profile including:
     • Antinuclear antibody (ANA) by immunofluorescence
     • Other scleroderma-specific antibodies (anti-centromere, anti-RNA polymerase III)
     • Inflammatory markers (ESR, CRP)

3. Rheumatology evaluation will likely include:

   • Detailed assessment of skin involvement
   • Pulmonary function testing (PFTs) as recommended by the 2023 ACR/CHEST guidelines for screening of ILD in patients at risk for systemic autoimmune rheumatic diseases 3
   • Consideration of high-resolution CT chest if pulmonary symptoms are present

Conclusion

The presence of anti-Scl-70 antibodies, even in asymptomatic individuals, warrants rheumatology referral for proper evaluation and monitoring. While false positives can occur, the potential consequences of missing early systemic sclerosis are significant, including irreversible organ damage and increased mortality. Rheumatologists can provide expert assessment, confirm the diagnosis with more specific testing methods if needed, and implement appropriate monitoring and early intervention strategies.