In morning report, we discussed a case of a patient with a history of poorly controlled asthma, requiring frequent courses of steroids, who presented with eosinophilia and multisystem disease including colitis and myocarditis. ANCA was negative, yet a biopsy confirmed extravascular eosinophilic infiltration, in keeping with a diagnosis of Eosinophilic Granulomatosis with Polyangiitis (EGPA). EGPA is formerly known as Churg-Strauss syndrome.
1. Clinical Manifestations of EGPA
- EGPA is a rare and potentially life-threatening vasculitis involving the small and medium-vessels that is associated with asthma and eosinophilia.
- It almost invariably involves the respiratory system, but may present with extra-pulmonary manifestations (e.g., polyneuropathy, eosinophilic colitis and glomerulonephritis).
- The diagnosis is based on the American College of Rheumatology or Lanham criteria
- Although classified as an ANCA-associated vasculitis, ANCA is detected in only 40-60% of cases.
- The three stages of EGPA (allergic prodromal phase; eosinophilic infiltrative phase and the vasculitis phase) are described below
2.Differential Diagnosis for Eosinophilia
Eosinophilia may be due to:
- Drug Hypersensitivity including DRESS
- Autoimmune Disorders (e.g., sarcoidosis, RA, IBD, IgG4 disease and other connective tissue diseases)
- Infections (e.g., parasitic, fungal, HIV)
- Neoplastic disorders
- Other: Idiopathic hypereosinophilic syndrome; immunodeficiencies; Loeffler’s syndrome, hypoadrenalism, cholesterol emboli
- The degree of eosinophilia may help to narrow the differential diagnosis.
- If absolute eosinophil count >1.5x 10^9/L, usually warrants further work up
3. Diagnosis of EGPA
- Suspect if:
- Eosinophils >1.5x 10^9/L
- Late onset asthma
- Not very sensitive, as p-ANCApositive only in 40-60% of patients
- Skin, nerve and muscle commonly biopsied but may biopsy kidney, GI tract or myocardium.
- Biopsies strongly supportive if shows:
- Extravascular eosinophilic infiltration
- Necrotizing Vasculitis
- Perivascular Granulomas
- ACR Criteria are below The presence of 4 or more is 85% sensitive, 99.7% specific for EGPA
4. Investigations in Suspected EGPA
- Diagnosis straightforward when all diagnostic criteria met
- But may mimic other diseases!
- See Consensus Guidelines for details of full investigations to be ordered depending on the presenting symptoms
5. Management of EGPA
- Immunosuppression is key
- 1 mg/kg/day prednisone for organ-threatening manifestations
- Methylprednisolone pulse x 3 days first if there are life-threatening manifestations
- If severe manifestations:
- Will receive another immunosuppressant (e.g. cyclophosphamide) in addition to steroids
- Maintenance therapy:
- Azathioprine or MTX after remission induction
- PLEX not generally recommended
6. Cardiac Manifestation and Treatment in EGPA
- Cardiac involvement (myopericarditis, CHF etc) described in 20-50% of cases
- More common if ANCA-negative
- Myocarditis may result from microvascular ischemia and myocardial eosinophilic infiltration
- Early detection and treatment of myocarditis essential- 50% risk of mortality (leading cause of death in EGPA)
- Important investigations: chest imaging, ECG, TTE, BNP, troponin
- Cardiac PET and/or MRI are more specific for myocarditis (MRI sensitivity of 88%, specificity 72%)
- Treatment: prevent myocardial fibrosis with immunosuppression
7. Take Home Points:
- EGPA can present with pulmonary and extra-pulmonary manifestations including eosinophilic myocarditis and colitis
- EGPA can present with a normal ANCA in up to 60% of patients and a high index of clinical suspicion is required to make the diagnosis
- Cardiac involvement contributes to morbidity and mortality in EGPA, emphasizing the need for early detection and treatment
- Cereda, A. F., Pedrotti, P., De Capitani, L., Giannattasio, C., & Roghi, A. (2017). Comprehensive evaluation of cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) with cardiac magnetic resonance. European journal of internal medicine, 39, 51-56.
- Groh, M., Pagnoux, C., Baldini, C., Bel, E., Bottero, P., Cottin, V., … & Humbert, M. (2015). Eosinophilic granulomatosis with polyangiitis (Churg–Strauss)(EGPA) Consensus Task Force recommendations for evaluation and management. European journal of internal medicine, 26(7), 545-553.