Eosinophilic Granulomatosis with Polyangiitis - EGPA

Diagnosis

Indications for Testing

Asthma with multiorgan systemic disease

Criteria for Diagnosis

Laboratory Testing

• No reliable biomarkers to distinguish disease from similar eosinophil-associated diseases or for use in monitoring of therapeutic response
• Nonspecific testing –  helpful in excluding other diagnoses or identifying organ dysfunction (most likely abnormal during acute disease)
  • CBC – may have hypereosinophilia (>10% or 1500 cells/µL) (Valent, 2012)
    • Eosinophilia heralds relapse in established disease – may rapidly disappear with steroid initiation
  • Urinalysis – may have hematuria
  • C-reactive protein (CRP)
    • Preferred test to detect inflammatory processes (Choosing Wisely: 20 Things Physicians and Patients Should Question, 2017; American Society for Clinical Pathology)
    • Usually increases in vasculitic phase
    • If CRP not available, order erythrocyte sedimentation rate (ESR)
• Immunoglobulins
  • Serum IgG levels – may be increased, but lack specificity
    • IgG4 often increased in active disease
    • EGPA is being considered as belonging to the list of IgG4-related diseases (Greco, 2014)
  • IgA – recent data suggest elevations in up to 75% of patients with acute disease
• ANCA
  • Perinuclear ANCA (pANCA) with myeloperoxidase (MPO)+ – most common, but <50% are positive
    • Does not correlate with disease activity
  • Cytoplasmic ANCA (cANCA) with serine proteinase 3 (PR3) – uncommon
  • MPO and PR3 are enzymes to which ANCA antibodies are directed

Histopathology

• Tissue biopsy of involved organ site – small-to-medium sized artery vasculitis, extravascular eosinophilic necrotic  granulomas, eosinophilic infiltration of arterial and venous walls
  • Skin, nerve, and muscle biopsies have highest yields (Mouthon, 2014)

Imaging Studies

Chest radiograph (roentgenograph) – infiltrates common (often migratory); pleural effusion may be present

Prognosis

• Relapses are common, especially if maintenance treatments are fully withdrawn
  • May be heralded by increasing eosinophilia
• Flare-ups may follow reductions of corticosteroid doses

Differential Diagnosis

• Vasculitis
  • Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
  • Microscopic polyangiitis
  • ​Polyarteritis nodosa
  • Eosinophilic vasculitis
• Malignancy
  • Myeloid or lymphoid neoplasm associated with eosinophilia
  • Chronic eosinophilia leukemia
• Parasitic infection
  • Toxocara spp
  • Schistosoma spp
  • Trichinella spiralis
  • Strongyloides stercoralis
  • Wuchereria bancrofti
  • Paragonimus westermani
• Eosinophil-associasted syndromes
  • Bronchopulmonary aspergillosis
  • Hypersensitivity pneumonitis
  • Hypereosinophilic syndrome
  • Eosinophil-associasted pneumonia (acute or chronic)
  • Bronchocentric granulomatosis
• Drug reactions – most common
  • Antibiotics
  • Antiasthmatics
  • Anticonvulsants

Background

Epidemiology

• Incidence – 1-3/1,000,000 in U.S.
  • In asthma patients, may be as high as 67/1,000,000 (Greco, 2014)
• Age – 40-50 years
• Sex – M>F (minimal)

Pathophysiology

• Small and medium vessel necrotizing vasculitis/angiitis – involves arteries and veins
  • Dependent on site of tissue sampling and stage of disease
• Extravascular necrotizing granulomas and eosinophilic infiltration
  • Observation of granulomas less common than in the past due to recognition of disease in earlier stage
  • Vasculitis may not always be necrotizing

Clinical Presentation

• 3 phases of disease
  • Prodromal phase
    • Characterized by asthma and allergic rhinitis, +/- nasal polyposis
    • Typically occurs when individual is 20-30 years and persists for many years
  • Eosinophilic infiltrative phase
    • Peripheral eosinophilia, eosinophilic tissue infiltration of various organs, including lungs, cardiac, and GI tract
  • Vasculitic phase
    • Constitutional – fever, fatigue, malaise, weight loss
    • Pulmonary – asthma (~100%); migratory pulmonary infiltrates
    • Cardiovascular – myocarditis, endocarditis, pericarditis, coronary vasculitis, arrhythmias
      • Prominent cause of disease-related mortality
    • Neurologic – peripheral neuropathy (typically mononeuritis multiplex), polyneuropathy, confusion, seizures, cranial nerve palsies, coma
    • Dermatologic – nodules, papules, petechial rash, palpable purpura 
    • Gastrointestinal – abdominal pain, nausea, emesis, diarrhea
    • Renal – glomerulonephritis
    • Ophthalmologic – uveitis, retinopathy
    • Otorhinologic – paranasal sinus disease