June 2025

RHEUMATOLOGY

EARLY CLINICAL MANIFESTATIONS OF SYSTEMIC SCLEROSIS

Read time: 90 seconds

Recognizing early symptoms associated with systemic sclerosis (SSc) is crucial for timely diagnosis and treatment. Carrie Richardson, MD, and Duncan Moore, MD, highlight the variability of SSc's early presentation, specifically in cases where the initial clinical manifestation is not Raynaud’s phenomenon (RP).

​Key Takeaways
  • Over 30% of patients in two large SSc cohorts presented with initial symptoms other than RP; puffy fingers/hands were the most common.
  • A higher percentage of Black patients exhibited non-RP symptoms prior to the onset of RP.
  • Patients with non-RP initial symptoms were more likely to show greater skin and musculoskeletal severity and a higher rate of positivity for the RNA Polymerase III antibody, emphasizing the importance of early recognition and testing.

Common Non-RP Symptoms
  • Puffy fingers/hands were the most frequently reported non-RP initial symptom in both cohorts (40.4% in GENISOS, 52.9% in CONQUER).
  • Other skin and musculoskeletal symptoms (skin tightening, arthralgia/arthritis, or hypo- or hyperpigmentation) accounted for initial symptoms in 32.0% of GENISOS and 20.4% of CONQUER patients.
  • Within both cohorts, nearly half of Black patients reported a non-RP symptom preceding RP.

Clinical Implications of Non-RP Symptoms
Patients with non-RP initial symptoms showed:
  • Higher prevalence of diffuse cutaneous involvement.
  • Increased likelihood of joint contractures.
  • Greater RNA Polymerase III antibody positivity.
 
Guidelines for Clinicians
  • Various non-RP symptoms, especially puffy fingers/hands, can be the first signs of SSc.
  • Use ANA screening via the HEp-2 immunofluorescence assay (IFA) for its high sensitivity. Follow positive ANA results with tests for SSc-specific autoantibodies, particularly RNA Polymerase III if the initial reflex panel comes back negative.
  • Although RP is common, other symptoms can precede RP by months. Some patients may develop classifiable SSc without ever experiencing RP.
  • Patients with non-RP symptoms are more likely to progress to diffuse cutaneous disease and irreversible joint contractures. Early intervention is crucial.
Carrie L. Richardson, MD, co-director of the Scleroderma Program and Assistant Professor of Rheumatology at Northwestern Medicine.
Duncan F. Moore, MD, Assistant Professor of Rheumatology at Northwestern Medicine.

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