Eosinophilic Granulomatosis with Polyangiitis

An antineutrophil cytoplasmic antibody associated small to medium vessel vasculitis, historically termed Churg Strauss syndrome, characterised by the combination of asthma, marked peripheral eosinophilia and necrotising eosinophil rich granulomatous vasculitis, typically evolving through a recognisable sequence of clinical phases over years.

Pathophysiology and disease phases

A prodromal phase, often lasting years, is characterised by adult onset asthma, frequently severe and difficult to control, together with allergic rhinitis and nasal polyposis.

An eosinophilic phase follows, with marked peripheral blood and tissue eosinophilia causing eosinophilic pneumonia, gastrointestinal infiltration and other organ involvement.

A final vasculitic phase, sometimes but not always developing, produces the systemic vasculitis with its characteristic multisystem manifestations. The timing and degree of overlap between these phases varies considerably between patients.

Late onset, often severe asthma, frequently requiring escalating treatment in the years preceding overt vasculitis, together with chronic rhinosinusitis and nasal polyposis, characterises the prodromal respiratory phase.

Marked peripheral blood eosinophilia is a hallmark laboratory feature, often accompanying constitutional symptoms as the eosinophilic phase develops.

Pulmonary infiltrates, migratory and transient, reflect eosinophilic pneumonia, and cardiac involvement (eosinophilic myocarditis, pericarditis) represents a major cause of mortality in this condition and warrants active screening.

Peripheral neuropathy, characteristically mononeuritis multiplex, occurs in the majority of patients with established vasculitic phase disease and is often a presenting feature prompting recognition of the systemic vasculitis.

Cutaneous manifestations include palpable purpura and subcutaneous nodules, and gastrointestinal involvement (abdominal pain, bleeding) reflects eosinophilic and vasculitic bowel infiltration.

Renal involvement is generally less prominent and less severe than in the other antineutrophil cytoplasmic antibody associated vasculitides, though pauci immune glomerulonephritis can occur.

Full blood count showing marked peripheral eosinophilia is a key supportive feature, with the degree of eosinophilia often striking and disproportionate to that seen in uncomplicated asthma or allergic disease.

Antineutrophil cytoplasmic antibody testing is positive in a minority, typically with a perinuclear pattern and myeloperoxidase specificity when present, and its presence is associated with a higher likelihood of renal and peripheral nerve involvement, while antineutrophil cytoplasmic antibody negative disease tends to be associated with more prominent cardiac and pulmonary eosinophilic infiltration.

Tissue biopsy from an accessible affected site (skin, nerve, lung) demonstrating eosinophilic tissue infiltration, necrotising vasculitis and, characteristically, extravascular granulomata provides histological confirmation.

Chest imaging assesses for the characteristic migratory pulmonary infiltrates, and cardiac assessment (electrocardiogram, echocardiography, and cardiac magnetic resonance imaging where available) is essential given the substantial contribution of cardiac involvement to mortality.

Nerve conduction studies confirm and characterise the pattern of peripheral neuropathy where clinically suspected.

High dose corticosteroids form the foundation of induction treatment, with the addition of cyclophosphamide or rituximab for severe, organ or life threatening disease, particularly with significant cardiac, renal or gastrointestinal involvement.

Mepolizumab, an interleukin 5 inhibitor, is approved specifically for this condition and offers an effective, targeted, corticosteroid sparing option, particularly valuable given the frequent difficulty controlling the asthma and sinonasal components of the disease with corticosteroids alone, and its mechanism directly addresses the eosinophil driven pathophysiology.

Maintenance therapy following successful induction of severe disease uses azathioprine, methotrexate or rituximab, continued for an extended period given relapse risk.

Ongoing management of the underlying asthma and chronic rhinosinusitis, often requiring specific respiratory and otolaryngology input alongside the systemic vasculitis treatment, is an important and sometimes underappreciated component of full care.

Cardiac monitoring, given the disproportionate contribution of cardiac involvement to mortality in this condition, and long term surveillance for disease relapse across the full range of potential organ manifestations, underpins ongoing specialist follow up.