Can Wegener's granulomatosis with polyangiitis (GPA) cause schizophrenia-like symptoms?

Granulomatosis with Polyangiitis (GPA) and Schizophrenia-like Symptoms

Yes, Granulomatosis with Polyangiitis (GPA) can cause schizophrenia-like symptoms in rare cases due to central nervous system involvement. 1 While neuropsychiatric manifestations are not among the most common presentations of GPA, they can occur as part of the disease's multisystem involvement.

Neuropsychiatric Manifestations in GPA

GPA is a systemic vasculitis characterized by:

• Necrotizing granulomatous inflammation
• Small-to-medium vessel vasculitis
• Strong association with anti-neutrophil cytoplasmic antibodies (ANCA), particularly PR3-ANCA 2

Central Nervous System Involvement

• CNS involvement can occur in GPA, though less common than other organ systems
• A documented case report describes a 69-year-old man who presented with acute manic symptoms but was ultimately diagnosed with Wegener's granulomatosis (now called GPA) 1
• The vasculitic process can affect cerebral vessels, leading to various neuropsychiatric manifestations

Pathophysiological Mechanisms

Several mechanisms may explain the development of schizophrenia-like symptoms in GPA:

1. Direct CNS vasculitis: Inflammation of cerebral blood vessels can cause ischemic damage to brain regions involved in cognition and behavior
2. Granulomatous lesions: Formation of granulomas in the CNS can act as space-occupying lesions
3. Immune-mediated mechanisms: The autoimmune process may affect neural tissue directly

Diagnostic Considerations

When evaluating patients with schizophrenia-like symptoms and suspected GPA:

• Look for other systemic manifestations of GPA:

  • Upper respiratory tract involvement (70-100% of cases) 2
  • Pulmonary manifestations (nodules, infiltrates, hemorrhage)
  • Renal involvement (glomerulonephritis)
  • Ocular, cutaneous, or other organ involvement

• Laboratory testing:

  • ANCA testing (PR3-ANCA/c-ANCA is present in 80-90% of GPA cases) 2
  • Elevated inflammatory markers
  • Evidence of organ dysfunction (renal function tests)

• Imaging:

  • Brain MRI to detect CNS vasculitis or granulomatous lesions
  • Chest imaging for pulmonary manifestations
  • Sinus CT for upper respiratory involvement

Treatment Implications

For GPA patients with neuropsychiatric manifestations:

• First-line therapy: Rituximab plus glucocorticoids for remission induction 2
• Alternative: Cyclophosphamide plus glucocorticoids, particularly for severe disease 3, 4
• Maintenance therapy: Rituximab or azathioprine 2, 5
• Adjunctive treatment: May require psychiatric medications to manage acute psychotic symptoms

Important Considerations

• Psychiatric symptoms may be the presenting feature or develop during the course of GPA
• Early recognition and treatment are crucial to prevent permanent CNS damage
• Multidisciplinary management involving rheumatology, psychiatry, and neurology is essential 1
• Distinguishing primary psychiatric disorders from GPA-related neuropsychiatric manifestations requires thorough evaluation

Monitoring and Follow-up

• Regular assessment of disease activity using validated tools
• Monitoring for treatment response and medication side effects
• Vigilance for relapse of both systemic disease and neuropsychiatric symptoms

The association between GPA and schizophrenia-like symptoms highlights the importance of considering systemic vasculitides in the differential diagnosis of new-onset psychiatric symptoms, particularly when accompanied by other systemic manifestations.