Eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome is characterized by asthma, eosinophilia and small vessel necrotizing vasculitis and involves the lungs and other organs.

Epidemiology

The incidence typically peaks in middle age, 30-50 years of age with pediatric cases being rare ^2,16,24. The annual incidence rate of around 0.24-1.78 per 100,000 ^2,16. There is no gender predilection ²⁴.

Clinical presentation

Clinically, patients with EGPA pass through three phases. Although these do provide a general overview of progression, the phases do overlap ²⁴:

• allergic prodrome

  • marked by allergic symptoms typically asthma and sinusitis

  • may last years

• eosinophilic phase

  • eosinophilia

  • end-organ involvement

• vasculitic phase

  • small-vessel vasculitis with end organ damage

Almost all patients have symptomatic asthma and chronic sinusitis. Extrapulmonary signs and symptoms will vary depending on end-organ involvement and the phase of the disease and include diarrhea, skin purpura, arthralgias, renal impariment and neurological symptoms.

Diagnostic criteria

The 1990 American College of Rheumatology criteria requires a positive biopsy for vasculitis and at least four of the six criteria listed below (sensitivity 85% and specificity 99.7%) ¹⁶: 

• asthma: present in almost all patients ²

• blood eosinophilia (>10% of the total white blood cell count): present in almost all patients ^2,13

• mono/polyneuropathy

• transient pulmonary infiltrates

• paranasal sinus abnormalities: pain or radiographic abnormality

• presence of extravascular eosinophils on a biopsy specimen

Pathology

Can be histologically identical to classic polyarteritis nodosa or microscopic polyangiitis. Around 25% of patients will have renal disease, classically necrotizing crescentic glomerulonephritis ¹².

Biopsy of parenchymal opacities may show a mixture of necrotizing granulomas, eosinophilic pneumonia, and granulomatous vasculitis ¹⁶. 

Markers

Anti-neutrophil cytoplasmic antibodies (ANCA) is detected in approximarly half of patients, most often against myeloperoxidase (MPO) (pANCA) ²⁴.

The presence of ANCA has an impact on clinical phenotype, with skin rash, neurological involvement and glomerulonephritis more common in ANCA positive patients, whereas pulmonary, cardiac and gastrointestinal involvement is more common in ANCA negative patients ²⁴.

Radiographic features

Below are the respiratory and cardiac imaging features. Neurological manifestations of EGPA are discussed separately.

Plain radiograph

Chest radiographs are nonspecific but may show:

• peripheral consolidation: may be transient/migratory

• small pleural effusions: up to 50% of cases ¹⁶

CT

Imaging features include:

• peripheral or random parenchymal opacification (consolidation or ground glass)

  • tends to be the most frequent feature ¹; can be transient

  • often bilateral and can sometimes be symmetrical ¹⁴

  • parenchymal opacification is predominantly peripheral or random in distribution ¹

• less common features include

  • features related to eosinophilic infiltration of the bronchial wall and asthma ¹⁴

    • centrilobular nodules

    • bronchial wall thickening and/or dilatation ⁵

    • bronchiectasis ¹⁶

• regular and smooth interlobular septal thickening: may reflect the presence of edema secondary to cardiac involvement or eosinophilic septal infiltration ¹⁴

• cavitation: rare and if present other co-existing pathology should be considered, e.g. granulomatosis with polyangiitis, infection ⁶

• mediastinal lymphadenopathy: seen in less than 25% of cases ¹⁶

• paranasal sinus disease ^19-22

  • nasal polyposis ~75% ²²

  • chronic rhinosinusitis without polyps

MRI

Cardiac MRI

Cardiac involvement clinically manifests in about 66% of patients and can be found in up to 92% of autopsies ¹⁶. They include: 

• delayed myocardial enhancement: a commonly described finding; can be intramyocardial, subepicardial, or subendocardial ^9-10

  • not confined to one vascular territory (cf. myocardial infarction) ¹⁶

• myocardial edema: high T2 signal 

• reduced left ventricular ejection fraction 

Treatment and prognosis

Corticosteroids (most commonly prednisone) are the mainstay of treatment. Patients with cardiac, renal, gastrointestinal, or CNS involvement, require additional immunosuppression (e.g. cyclosporine, azathioprine).

The condition generally has a low mortality rate compared with other systemic vasculitides ¹¹. Cardiac involvement may, however, be a significant contributor to disease-related death and may occur in up to 60% of cases ^8,13.

History and etymology

Eosinophilic granulomatosis with polyangiitis was first described in 1951 by Jacob Churg (1910-2005), an American pathologist, subspecialising in renal and vascular diseases, and his long-term collaborator and friend Lotte Strauss (1913-1985), an American pediatric pathologist, who were both based at Mount Sinai Hospital in New York City ^4,18.

Differential diagnosis

• eosinophilic pneumonia

• granulomatosis with polyangiitis

  • usually has cavitating nodules

• other forms of pulmonary infection