ETIOLOGY OF ISCHEMIC STROKE / VASCULITIS
Churg-Strauss syndrome
Eosinophilic Granulomatosis with Polyangiitis
David Goldemund M.D.
Updated on 19/06/2024, published on 19/06/2024
Updated on 19/06/2024, published on 19/06/2024
- Churg-Strauss Syndrome (CSS, now more commonly referred to as Eosinophilic Granulomatosis with Polyangiitis or EGPA) is a rare systemic vasculitis that primarily affects small-sized vessels
- CSS accounts for only 20% of patients with the systemic necrotizing vasculitis of the polyarteritis nodosa group
- CSS typically affects middle-aged individuals
- peripheral nervous system involvement is common, but cerebral infarction or hemorrhage may also occur
- involvement of the CNS is associated with an increased risk for mortality and requires aggressive treatment with steroids and immunosuppressants
- neuroimaging of CSS-related stroke is nonspecific
- the diagnostic evaluation involves a combination of clinical, laboratory, imaging, and histopathological criteria; the condition should be considered in any patient who has asthma and develops eosinophilia and peripheral and/or CNS signs
Pathology and pathophysiology
- medium- to small-vessel vasculitis that preferentially affects capillaries, arterioles, and venules
- in some patients, the larger vessels can be affected, but this is uncommon
- pathologically, CSS consists of three classical features:
- necrotizing vasculitis
- the presence of ANCA is associated with a “vasculitic” clinical picture and more frequent CNS involvement than in ANCA-negative patients
- eosinophilic inflammation
- eosinophils are linked to the release of their cytotoxic enzymes, which can lead to tissue damage
- extravascular granulomas
- necrotizing vasculitis
- the triggering events and cause of CSS remain unclear
Clinical presentation
- characterized by a wide range of symptoms due to its systemic involvement
- systemic symptoms – fever, malaise, weight loss
- asthma, typically severe and adult-onset
- allergic rhinitis and nasal polyps, chronic sinusitis with nasal obstruction, pulmonary infiltrates (nonfixed)
- palpable skin purpura and subcutaneous nodules
- mononeuritis multiplex – common, causing asymmetric pain, weakness, and sensory loss
- cardiovascular symptoms – myocarditis (heart failure, arrhythmias), pericarditis (chest pain)
- gastrointestinal symptoms – abdominal pain, diarrhea, and gastrointestinal bleeding
- glomerulonephritis
Cerebrovascular complications of CSS
- CNS is less often involved (< 10%) compared with peripheral lesions
- cerebrovascular disease related to CSS has no specific pattern that could be used for diagnostic purposes
- infarcts are typically small and multiple, and patients often present with diffuse encephalopathy; large cerebral infarcts are rare
- occlusions of the dural sinuses, cerebral veins, and ophthalmic arteries have also been reported
- there have been several reports of CSS presenting with intracranial hemorrhage
- ICH probably due to uncontrolled hypertension
- intraventricular hemorrhage from a necrotizing vasculitis of the choroid plexus
Diagnostic evaluation
Clinical evaluation
- presence of adult-onset asthma and chronic sinusitis
- mononeuritis multiplex or polyneuropathy
- palpable skin purpura and nodules
Laboratory tests
- Complete Blood Count (CBC):
- eosinophilia – elevated eosinophil count (usually >10% or count >1.5 x 10^9/L)
- elevated ESR and CRP
- ↑ serum IgE levels
- Antineutrophil Cytoplasmic Antibodies (ANCA) positivity
- positive p-ANCA/MPO-ANCA in 40-60% of cases
- tissue biopsy (skin, lung, nerve, or other affected tissues)
- eosinophilic infiltration, granulomatous inflammation, and vasculitis of small to medium-sized vessels
Imaging studies
- chest X-ray and high-resolution CT (HRCT) – pulmonary infiltrates, nodules, or ground-glass opacities
- echocardiogram – assess for cardiac involvement such as myocarditis or pericarditis
- standard stroke imaging (CT+CTA/MRI+MRA, ultrasound, etc.)
Other methods
- EMG – detection of mononeuritis multiplex, etc.
Diagnostic criteria of the American College of Rheumatology
Diagnosis is established if ≥ 4 of the following six criteria are present:
- asthma
- eosinophilia >10%
- mononeuritis multiplex or polyneuropathy
- nonfixed pulmonary infiltrates
- paranasal sinus abnormality
- biopsy containing a blood vessel with extravascular eosinophils
Treatment
- glucocorticoids are the mainstay of therapy (pulse prednisolone 15 mg/kg for 1-3 days, followed by prednisone 1 mg/kg per day)
- in some patients, other immunosuppressive drugs are added to the steroid regimen (steroid-sparing effect)
- cyclophosphamide bolus should be considered in severe cases
- rituximab has proven useful in the treatment of steroid-resistant cases, as well as in the prevention and treatment of relapse (however, efficacy is greatly reduced in ANCA-negative patients)
- interleukin-5 (IL-5) antagonist monoclonal antibody
- mepolizumab – approved by the FDA for use in adult patients with EGPA
- benralizumab
- plasma exchange has been studied in EGPA and other ANCA-positive vasculitides without a clear benefit
Prognosis
- negative prognostic factors include:
- renal insufficiency with serum Cr >1.58 mg/dL
- CNS involvement
- cardiomyopathy
- presence of proteinuria (>1 g/d)
- gastrointestinal tract involvement
- the more factors, the higher the mortality
