Churg–Strauss syndrome

EGPA is one of the three primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), along with granulomatosis with polyangiitis (GPA, Wegener) and microscopic polyangiitis (MPA), but has unique features due to its allergic and eosinophilic phenotype.

EGPA follows a typically triphasic clinical course:

1. Prodromal (Allergic) phase: Characterised by asthma and allergic rhinitis, often years before vasculitic manifestations.
2. Eosinophilic phase: Marked peripheral eosinophilia and eosinophilic infiltration of lungs, gastrointestinal tract, or myocardium.
3. Vasculitic phase: Systemic necrotizing vasculitis affecting multiple organs — commonly skin, peripheral nerves, lungs, kidneys, and heart.

Epidemiology

• Prevalence: ~10–14 cases per million; incidence 0.5–6.8 per million/year
• Typical age of onset: 30–50 years
• Sex ratio: Approximately equal; slight male predominance in some cohorts
• Asthma: Present in >90% of cases and often precedes vasculitis by years
• ANCA status: ~30–40% are ANCA-positive (typically perinuclear ANCA [p-ANCA]/anti-MPO); ANCA-positive cases more commonly have glomerulonephritis and peripheral neuropathy

Clinical Features

• Respiratory: Asthma, sinusitis, transient pulmonary infiltrates
• Dermatologic: Palpable purpura, subcutaneous nodules
• Neurologic: Mononeuritis multiplex (most common vasculitic manifestation)
• Cardiac: Eosinophilic myocarditis, pericarditis — major cause of mortality
• Gastrointestinal: Abdominal pain, bleeding, ischemia
• Renal: Usually milder than other AAV; focal segmental necrotising GN in ANCA+ patients

Diagnosis

• Eosinophilia: Absolute eosinophil count >1.5 ×10⁹/L
• Histology: Extravascular eosinophils, necrotizing vasculitis, and granulomatous inflammation
• Immunology: p-ANCA/anti-MPO antibodies in ~30–40%; negative ANCA does not exclude diagnosis
• Imaging: Pulmonary infiltrates on CXR/CT; cardiac MRI for myocarditis
• 1990 ACR Criteria for CSS (4 of 6 = sensitivity 85%, specificity 99.7%):
  1. Asthma
  2. Eosinophilia >10%
  3. Mononeuropathy or polyneuropathy
  4. Pulmonary infiltrates
  5. Paranasal sinus abnormality
  6. Biopsy with extravascular eosinophils

Treatment

• Mild disease: Oral glucocorticoids may suffice for non-organ-threatening manifestations
• Moderate–severe disease: Induction with glucocorticoids + immunosuppressants (cyclophosphamide, methotrexate, or azathioprine)
• Life-threatening disease: Cyclophosphamide + high-dose steroids
• Maintenance: Azathioprine or methotrexate
• Biologic agents: Mepolizumab (anti-IL-5) approved for relapsing/refractory EGPA; Rituximab may benefit ANCA-positive cases
• Supportive: Cardiac surveillance, infection prophylaxis, asthma optimisation

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History of Churg-Strauss

1951 – Jacob Churg (1910–2005) and Lotte Strauss (1913–1985) publish “Allergic Granulomatosis, Allergic Angiitis, and Periarteritis Nodosa“ in the American Journal of Pathology, describing 13 patients with asthma, hypereosinophilia, and necrotizing granulomatous vasculitis.

They introduced the concept of a distinct clinicopathological entity: “allergic granulomatosis”

The syndrome is characterized by fever, eosinophilia, cardiac involvement, and a clinical picture resembling periarteritis nodosa, but in allergic individuals

1960s–1970s – Increasing recognition as distinct vasculitis. Series and case reports begin to reinforce it as separate from classic polyarteritis nodosa (PAN)

1990 – American College of Rheumatology (ACR) classification criteria. ACR includes “Churg–Strauss Syndrome” as a distinct vasculitis, with 6-item criteria for research purposes (≥4 for classification).

1994 – CHCC first international consensus classification. The Chapel Hill Consensus Conference lists Churg–Strauss Syndrome among primary systemic vasculitides, distinguished by eosinophilia and granulomatous inflammation.

2012 – CHCC update: EGPA replaces “Churg–Strauss Syndrome” Formal renaming to Eosinophilic Granulomatosis with Polyangiitis (EGPA) to reflect pathophysiology and align with nomenclature of other vasculitides (e.g. GPA, MPA).

Defined as: “eosinophil-rich and necrotizing granulomatous inflammation involving the respiratory tract, and necrotizing vasculitis of small- to medium-sized vessels, associated with asthma and eosinophilia.”

2017 – Mepolizumab gains FDA/EMA approval for EGPA. First biologic (anti–IL-5) therapy approved for EGPA, based on MIRRA trial data by Wechsler et al

2022 – Revised ACR/EULAR classification criteria published. Introduced points-based criteria system combining clinical, serological, and histologic findings.

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Associated Persons

• Jacob Churg (1910–2005)
• Lotte Strauss (1913–1985)

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Alternative names

• Eosinophilic granulomatosis with polyangiitis (EGPA)
• Allergic granulomatosis
• Allergic granulomatous angiitis
• Churg–Strauss syndrome

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References

• Churg J, Strauss L. Allergic Granulomatosis, Allergic Angiitis, and Periarteritis Nodosa. Am J Pathol. 1951; 27(2): 277–301.
• Strauss L, Churg J, Zak FG. Cutaneous lesions of allergic granulomatosis: a histopathologic study. J Invest Dermatol. 1951; 17(6): 349-359.
• Jennette JC, Falk RJ et al 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11.
• Wechsler ME et al. EGPA Mepolizumab Study Team. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. 
• Grayson PC, Ponte C, Suppiah R, Robson JC, Craven A, Judge A, Khalid S, Hutchings A, Luqmani RA, Watts RA, Merkel PA; DCVAS Study Group. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis. Ann Rheum Dis. 2022 Mar;81(3):309-314