Churg-Strauss Syndrome

Churg-Strauss Syndrome (CSS)

Churg-Strauss Syndrome, also known as Eosinophilic Granulomatosis with Polyangiitis (EGPA), is a rare systemic vasculitis characterized by hypereosinophilia and necrotizing vasculitis affecting small to medium-sized vessels. It primarily affects individuals with a history of asthma and allergic rhinitis.

Key Points:

  • Rare autoimmune condition affecting 2-5 per million people annually
  • Typically occurs in adults aged 30-50 years
  • Characterized by eosinophilic inflammation, necrotizing vasculitis, and extravascular granulomas
  • Associated with ANCA (Anti-Neutrophil Cytoplasmic Antibody) in about 40% of cases
  • Multisystem disorder with a predilection for the respiratory tract

Pathophysiology

The exact pathogenesis of Churg-Strauss Syndrome is not fully understood, but it involves complex immunological mechanisms:

  1. Eosinophilic Inflammation:
    • Increased production and activation of eosinophils
    • Release of cytotoxic granule proteins and pro-inflammatory mediators
  2. T-cell Dysregulation:
    • Imbalance between Th1 and Th2 responses, with Th2 predominance
    • Increased production of IL-4, IL-5, and IL-13
  3. B-cell Activation:
    • Production of ANCA (particularly p-ANCA with anti-MPO specificity)
    • Hypergammaglobulinemia and increased IgE levels
  4. Vascular Inflammation:
    • Endothelial cell activation and damage
    • Infiltration of vessel walls by eosinophils and other inflammatory cells
  5. Granuloma Formation:
    • Extravascular accumulation of eosinophils, lymphocytes, and histiocytes
    • Formation of necrotizing granulomas in affected tissues

Clinical Presentation

Churg-Strauss Syndrome typically progresses through three phases, although not all patients experience all phases:

1. Prodromal Phase:

  • Allergic rhinitis
  • Adult-onset asthma (often severe and requiring steroids)
  • Nasal polyps
  • Sinusitis

2. Eosinophilic Phase:

  • Peripheral blood eosinophilia
  • Eosinophilic pneumonia
  • Gastroenteritis

3. Vasculitic Phase:

  • Constitutional symptoms (fever, weight loss, fatigue)
  • Skin lesions (purpura, nodules, livedo reticularis)
  • Peripheral neuropathy (mononeuritis multiplex)
  • Cardiac involvement (myocarditis, pericarditis, coronary vasculitis)
  • Renal involvement (focal segmental glomerulonephritis)
  • Pulmonary infiltrates or nodules
  • Gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding)

Diagnosis

Diagnosis of Churg-Strauss Syndrome is based on a combination of clinical features, laboratory findings, and histopathology:

Diagnostic Criteria (American College of Rheumatology):

Four or more of the following six criteria suggest CSS with 85% sensitivity and 99.7% specificity:

  1. Asthma
  2. Eosinophilia > 10% on differential WBC count
  3. Mononeuropathy or polyneuropathy
  4. Migratory or transient pulmonary opacities on chest radiographs
  5. Paranasal sinus abnormalities
  6. Biopsy containing blood vessels with extravascular eosinophils

Laboratory Tests:

  • Complete blood count (CBC) with differential (eosinophilia)
  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
  • ANCA testing (p-ANCA/MPO-ANCA in about 40% of cases)
  • Serum IgE levels (often elevated)
  • Urinalysis (to assess renal involvement)
  • Rheumatoid factor and ANA (may be positive)

Imaging Studies:

  • Chest X-ray and CT scan (pulmonary infiltrates, nodules)
  • Sinus CT (chronic sinusitis, nasal polyps)
  • Cardiac MRI (if cardiac involvement suspected)

Tissue Biopsy:

Biopsy of affected organ (e.g., skin, nerve, lung) showing:

  • Eosinophilic tissue infiltration
  • Necrotizing vasculitis
  • Extravascular granulomas

Treatment

Treatment of Churg-Strauss Syndrome is tailored to disease severity and organ involvement:

1. Glucocorticoids:

  • Cornerstone of initial therapy
  • High-dose prednisone (1 mg/kg/day) for induction of remission
  • Gradual tapering over months to years

2. Immunosuppressants:

  • Used in severe cases or as steroid-sparing agents
  • Cyclophosphamide for life-threatening disease
  • Azathioprine, methotrexate, or mycophenolate mofetil for maintenance therapy

3. Biological Agents:

  • Rituximab: Effective in ANCA-positive patients
  • Mepolizumab: IL-5 inhibitor, useful for eosinophilic asthma and refractory CSS

4. Plasma Exchange:

  • Considered in cases with severe organ involvement (e.g., rapidly progressive glomerulonephritis)

5. Supportive Care:

  • Management of asthma and allergic rhinitis
  • Cardiac monitoring and treatment of cardiac complications
  • Physical therapy for neuropathy
  • Pneumocystis jirovecii prophylaxis in patients on high-dose immunosuppression

6. Monitoring:

  • Regular follow-up with clinical assessment, CBC, ESR/CRP, and organ-specific tests
  • Monitoring for treatment-related side effects
  • Assessment of disease activity using validated tools (e.g., Birmingham Vasculitis Activity Score)


Further Reading
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