Can Sjogren's Syndrome (SS) occur without sicca symptoms, such as dry mouth (xerostomia) and dry eyes (xerophthalmia), presenting instead with autonomic dysfunction, myopathic issues, and general dysautonomia, including fatigue and weight loss, years after symptom onset?

Sjögren's Syndrome Without Sicca Symptoms

Yes, Sjögren's Syndrome can present without sicca symptoms (dry eyes and dry mouth), manifesting instead with systemic features such as autonomic dysfunction, myopathic issues, fatigue, and weight loss, even years after symptom onset.

Atypical Presentations of Sjögren's Syndrome

Sjögren's Syndrome (SjS) is traditionally characterized by the sicca complex (dry eyes and dry mouth), but clinical presentations can vary significantly:

• The EULAR-SS Task Force recognizes that primary SjS may initially present with non-sicca (systemic) manifestations, referred to as "occult" SjS when these features appear before overt sicca syndrome 1
• Extraglandular manifestations can include:
  • Autonomic dysfunction
  • Myopathic issues
  • General dysautonomia
  • Fatigue
  • Weight loss
  • Musculoskeletal pain
  • Respiratory, renal, gastrointestinal, hematological, and cardiovascular symptoms 2

Diagnostic Considerations

When sicca symptoms are absent, diagnosis becomes more challenging but remains possible:

• According to the ACR-EULAR criteria, diagnosis requires a total score ≥4 based on five weighted criteria 2:

  • Anti-SSA/Ro antibody positivity (3 points)
  • Focal lymphocytic sialadenitis (3 points)
  • Abnormal ocular staining score (1 point)
  • Schirmer test ≤5 mm/5 minutes (1 point)
  • Unstimulated salivary flow rate ≤0.1 ml/minute (1 point)

• In patients without sicca symptoms, diagnosis may rely more heavily on:

  • Positive serologic markers (anti-SSA/Ro antibodies)
  • Salivary gland biopsy showing characteristic lymphocytic infiltration
  • Presence of systemic manifestations

• Even without classic anti-Ro/La antibodies, diagnosis remains possible:

  • 20-30% of SjS patients are "seronegative" for specific autoantibodies 3
  • Alternative antibodies like anti-salivary gland protein 1 may identify some seronegative patients 4

Clinical Implications for Non-Sicca Presentations

For patients presenting with autonomic dysfunction, myopathic issues, and fatigue without sicca symptoms:

• A thorough evaluation for SjS should be considered, including:

  • Serologic testing for autoantibodies (ANA, RF, anti-Ro/SSA, anti-La/SSB)
  • Consideration of minor salivary gland biopsy even in the absence of sicca symptoms
  • Evaluation for subclinical sicca features through objective tests (Schirmer, salivary flow)

• Pulmonary involvement should be assessed:

  • The American College of Chest Physicians recommends obtaining a detailed medical history inquiring about respiratory symptoms in all SjS patients 5
  • Baseline chest radiograph and pulmonary function tests may be considered even in asymptomatic patients 5

Management Approach

For patients with SjS presenting primarily with systemic manifestations:

• Co-management with a rheumatologist is essential for all SjS patients due to potential systemic complications 2, 5

• For systemic manifestations:

  • Hydroxychloroquine may be considered for fatigue and arthralgia 2
  • Systemic immunomodulatory/immunosuppressive therapies should be considered for patients with active systemic disease 2

• Regular monitoring for complications is crucial, including:

  • Lymphoproliferative disorders
  • Pulmonary function
  • Vasculitic manifestations 2

Important Caveats

• Delayed diagnosis is common in patients without typical sicca symptoms, potentially leading to complications such as salivary gland tumors 4

• Even in the absence of subjective sicca symptoms, objective tests may reveal subclinical glandular dysfunction

• The absence of classic autoantibodies does not rule out SjS, as alternative autoantibodies may be present in seronegative cases 3, 4