Churg-Strauss syndrome is a pulmonary and systemic small-vessel necrotizing vasculitis, characterized by extravascular granulomas, eosinophilia, and tissue infiltration by eosinophils. It tends to occur in people with adult-onset asthma, allergic rhinitis, nasal polyposis, or a combination. Diagnosis is best confirmed by biopsy. Treatment is primarily with corticosteroids and, for severe disease, addition of other immunosuppressants.

Churg-Strauss syndrome occurs in about 3 people/million. Mean age at onset is 48.

Churg-Strauss syndrome is characterized by extravascular necrotizing granulomas (usually containing eosinophilic infiltrates), eosinophilia, and tissue infiltration by eosinophils. However, these abnormalities rarely coexist. The vasculitis typically affects pulmonary and systemic arteries and veins. Any organ can be affected, but the lungs, skin, cardiovascular system (eg, as coronary artery vasculitis), kidneys, peripheral nervous system, sinuses, joints, and GI tract are most commonly affected. Occasionally, pulmonary capillaritis may cause alveolar hemorrhage.

Etiology

The cause is unknown. However, an allergic mechanism, with tissue directly injured by eosinophils and neutrophil degranulation products, may be involved. Activation of T lymphocytes seems to help maintain eosinophilic inflammation. The syndrome occurs in patients who have adult-onset asthma, allergic rhinitis, nasal polyposis, or a combination. Antineutrophil cytoplasmic autoantibodies (ANCA) are sometimes present.

Symptoms and Signs

The syndrome has 3 phases, which may overlap:

• Prodromal: This phase may persist for years. Patients have allergic rhinitis, nasal polyposis, asthma, or a combination.
• 2nd phase: Peripheral blood and tissue eosinophilia is typical. Clinical presentation, which may resemble Löffler's syndrome, includes chronic eosinophilic pneumonia and eosinophilic gastroenteritis.
• 3rd phase: Potentially life-threatening vasculitis develops. Systemic symptoms (eg, fever, malaise, weight loss, fatigue) are common.

However, the phases do not necessarily follow one another consecutively, and the time interval between them varies greatly.

Various organs and systems may be affected:

• Respiratory: Asthma, often with onset during adulthood, occurs in most patients. Sinusitis is common, typically without severe necrotizing inflammation. Sinusitis causes facial pain and increases nasal discharge. Patients may be short of breath. Cough and hemoptysis, due to alveolar hemorrhage, may be present. Transient patchy pulmonary infiltrates are common.
• Neurologic: Neurologic manifestations are common. Mononeuritis multiplex occurs in up to three fourths of patients. CNS involvement is rare but can include confusion, seizures, and coma, with or without cranial nerve palsies or evidence of cerebral infarction.
• Cutaneous: The skin is affected in about one half of patients. Nodules and papules appear on extensor surfaces of extremities. They are caused by extravascular palisading granulomatous lesions with central necrosis. Purpura or erythematous papules, due to leukocytoclastic vasculitis with or without prominent eosinophilic infiltration, may develop.
• Musculoskeletal: Occasionally, arthralgias, myalgias, or even arthritis can occur, usually during the vasculitic phase.
• Cardiac: Heart failure, MI, coronary artery vasculitis (possibly with MI), valvular disorders, or pericarditis may develop. The predominant histopathologic finding is eosinophilic myocarditis.
• GI: Up to one third of patients present with GI symptoms (eg, abdominal pain, diarrhea, bleeding) due to eosinophilic gastroenteritis or mesenteric ischemia due to vasculitis.
• Renal: The kidneys are affected less often than in other vasculitic disorders associated with ANCA. Typically, pauci-immune (few if any immune complexes), focal segmental necrotizing glomerulonephritis with crescent formation is present; eosinophilic or granulomatous inflammation of the kidneys is rare.

Renal, cardiac, or neurologic involvement indicates a worse prognosis.

Diagnosis

• Clinical criteria
• Routine laboratory tests
• Biopsy

Criteria for classification from the American College of Rheumatology consist of the following:

• Asthma
• Eosinophilia of > 10% in peripheral blood
• Paranasal sinusitis
• Pulmonary infiltrates, sometimes transient
• Histologic evidence of vasculitis with extravascular eosinophils
• Mononeuritis multiplex or polyneuropathy

If ≥ 4 criteria are present, sensitivity is 85%, and specificity is 99.7%.

Testing aims to establish the diagnosis and the extent of organ involvement and to distinguish Churg-Strauss syndrome from other eosinophilic disorders (eg, parasitic infections, drug reactions, acute and chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, idiopathic hypereosinophilic syndrome). Diagnosis is suggested by clinical findings and results of routine laboratory tests but should usually be confirmed by biopsy of lung or other affected tissue.

Blood tests and chest x-rays are done, but results are not diagnostic. CBC with differential is done to check for eosinophilia. Peripheral blood eosinophilia is also a marker of disease activity. IgE and C-reactive protein levels and ESR are determined periodically to evaluate inflammatory activity. Electrolyte levels are measured and urinalysis is done to check for evidence of renal involvement and to follow its severity.

Serologic testing is done. It detects ANCA in up to 50%; if ANCA is detected, enzyme-linked immunosorbent assay (ELISA) is done to check for specific antibodies. Perinuclear ANCA (p-ANCA) with antibodies against myeloperoxidase is the most common result, but ANCA is not specific for Churg-Strauss syndrome.

Chest x-ray often shows transient patchy pulmonary infiltrates.

Biopsy of the most accessible affected tissue should be done if possible.

Treatment

• Corticosteroids

Systemic corticosteroids are the mainstay of treatment. When to add other immunosuppressants is not clear, but Churg-Strauss syndrome is generally treated the same way as Wegener's granulomatosis (see Vasculitis: Wegener's Granulomatosis) or microscopic polyangiitis (see Vasculitis: Microscopic Polyangiitis). Recombinant interferon alfa-2a 3 million units sc daily has been used when the syndrome is refractory to other drugs or when eosinophilic inflammation is difficult to control.

Last full review/revision May 2008 by Carmen E. Gota, MD