Medicine – Churg–Strauss Syndrome

Churg–Strauss syndrome, now more commonly called eosinophilic granulomatosis with polyangiitis (EGPA), is a rare systemic small- to medium-vessel vasculitis characterised by asthma, eosinophilia, eosinophil-rich granulomatous inflammation, and necrotising vasculitis. It commonly affects the respiratory tract, peripheral nerves, skin, heart, gastrointestinal tract, and kidneys.

1. Classical Pathological Features

Churg and Strauss originally described the syndrome in patients with a combination of asthma, marked eosinophilia, granulomatous inflammation, necrotising systemic vasculitis, and glomerulonephritis.

The pathological hallmark is eosinophil-rich necrotising granulomatous inflammation, usually involving the respiratory tract, together with necrotising vasculitis of small and medium-sized vessels.

Renal involvement can occur, often as a pauci-immune necrotising glomerulonephritis, although kidney disease is generally less frequent and often less severe than in granulomatosis with polyangiitis.

2. ANCA Association

Approximately 30–50% of patients with EGPA are ANCA-positive. When ANCA is present, the usual pattern is p-ANCA with antibodies against myeloperoxidase (MPO-ANCA).

ANCA-positive patients tend to have more classic vasculitic manifestations such as glomerulonephritis and peripheral neuropathy, whereas ANCA-negative patients may have more eosinophilic tissue disease, including cardiac involvement.

3. Asthma

Asthma is one of the most characteristic features of EGPA and occurs in the great majority of patients.

It may develop many years before the systemic vasculitic phase, sometimes preceding vasculitis by up to a decade or more. The asthma is often persistent and may become increasingly difficult to control.

Because many patients receive corticosteroids for asthma, treatment can partially suppress eosinophilia and other inflammatory manifestations, potentially delaying recognition of the full syndrome.

4. Constitutional Symptoms

Systemic inflammation commonly produces malaise, fatigue, flu-like symptoms, fever, and weight loss.

Myalgias are also common and may occur as part of the systemic inflammatory phase. These symptoms can precede or accompany the onset of overt vasculitis.

5. Arthralgia

Arthralgia occurs in a substantial proportion of patients. Joint pain is usually non-erosive and may occur alongside myalgia and other constitutional symptoms.

True inflammatory arthritis can occur but is less characteristic than the respiratory, eosinophilic, neurological, and vasculitic manifestations.

6. Peripheral Neuropathy

Peripheral neuropathy is an important and characteristic manifestation of EGPA.

The classic pattern is mononeuritis multiplex, caused by vasculitic damage to the small blood vessels supplying peripheral nerves. Patients may develop sudden painful sensory loss, weakness, foot drop, or wrist drop involving individual peripheral nerves in an asymmetric distribution.

Over time, multiple nerves may become involved and produce a more confluent peripheral neuropathy.

7. Respiratory and Eosinophilic Features

In addition to asthma, patients often have allergic rhinitis, chronic sinusitis, nasal symptoms, and pulmonary infiltrates.

Pulmonary infiltrates may be transient or migratory and are related to eosinophilic inflammation. Marked peripheral blood eosinophilia is a central feature of the disease and may fluctuate with corticosteroid treatment.

8. Other Organ Involvement

The skin may be affected by palpable purpura, nodules, or other vasculitic lesions.

The heart is an especially important site of disease because eosinophilic myocarditis, pericarditis, or cardiomyopathy may occur and can be a major cause of morbidity.

The gastrointestinal tract may also be affected, causing abdominal pain, bleeding, or ischaemic complications.

Renal disease is less common than in some other ANCA-associated vasculitides but can present with haematuria, proteinuria, and glomerulonephritis.

Key Clinical Pattern

Think of eosinophilic granulomatosis with polyangiitis when a patient has adult-onset or difficult-to-control asthma, marked eosinophilia, sinus or pulmonary disease, constitutional symptoms, and systemic vasculitic manifestations such as mononeuritis multiplex.

A p-ANCA/MPO-ANCA may support the diagnosis, but a negative ANCA does not exclude EGPA because many patients are ANCA-negative.

1. Classical Pathological Features Churg and Strauss originally described the syndrome in patients with a combination of asthma, marked eosinophilia, granulomatous inflammation, necrotising systemic vasculitis, and glomerulonephritis. The pathological hallmark is eosinophil-rich necrotising granulomatous inflammation, usually involving the respiratory tract, together with necrotising vasculitis of small and medium-sized vessels. Renal involvement can occur, often as a pauci-immune necrotising glomerulonephritis, although kidney disease is generally less frequent and often less severe than in granulomatosis with polyangiitis. 

2. ANCA Association Approximately 30–50% of patients with EGPA are ANCA-positive. When ANCA is present, the usual pattern is p-ANCA with antibodies against myeloperoxidase (MPO-ANCA). ANCA-positive patients tend to have more classic vasculitic manifestations such as glomerulonephritis and peripheral neuropathy, whereas ANCA-negative patients may have more eosinophilic tissue disease, including cardiac involvement. 

3. Asthma Asthma is one of the most characteristic features of EGPA and occurs in the great majority of patients. It may develop many years before the systemic vasculitic phase, sometimes preceding vasculitis by up to a decade or more. The asthma is often persistent and may become increasingly difficult to control. Because many patients receive corticosteroids for asthma, treatment can partially suppress eosinophilia and other inflammatory manifestations, potentially delaying recognition of the full syndrome. 

4. Constitutional Symptoms Systemic inflammation commonly produces malaise, fatigue, flu-like symptoms, fever, and weight loss. Myalgias are also common and may occur as part of the systemic inflammatory phase. These symptoms can precede or accompany the onset of overt vasculitis. 

5. Arthralgia Arthralgia occurs in a substantial proportion of patients. Joint pain is usually non-erosive and may occur alongside myalgia and other constitutional symptoms. True inflammatory arthritis can occur but is less characteristic than the respiratory, eosinophilic, neurological, and vasculitic manifestations. 

6. Peripheral Neuropathy Peripheral neuropathy is an important and characteristic manifestation of EGPA. The classic pattern is mononeuritis multiplex, caused by vasculitic damage to the small blood vessels supplying peripheral nerves. Patients may develop sudden painful sensory loss, weakness, foot drop, or wrist drop involving individual peripheral nerves in an asymmetric distribution. Over time, multiple nerves may become involved and produce a more confluent peripheral neuropathy. 

7. Respiratory and Eosinophilic Features In addition to asthma, patients often have allergic rhinitis, chronic sinusitis, nasal symptoms, and pulmonary infiltrates. Pulmonary infiltrates may be transient or migratory and are related to eosinophilic inflammation. Marked peripheral blood eosinophilia is a central feature of the disease and may fluctuate with corticosteroid treatment. 

8. Other Organ Involvement The skin may be affected by palpable purpura, nodules, or other vasculitic lesions. The heart is an especially important site of disease because eosinophilic myocarditis, pericarditis, or cardiomyopathy may occur and can be a major cause of morbidity. The gastrointestinal tract may also be affected, causing abdominal pain, bleeding, or ischaemic complications. Renal disease is less common than in some other ANCA-associated vasculitides but can present with haematuria, proteinuria, and glomerulonephritis. 

Key Clinical Pattern Think of eosinophilic granulomatosis with polyangiitis when a patient has adult-onset or difficult-to-control asthma, marked eosinophilia, sinus or pulmonary disease, constitutional symptoms, and systemic vasculitic manifestations such as mononeuritis multiplex. A p-ANCA/MPO-ANCA may support the diagnosis, but a negative ANCA does not exclude EGPA because many patients are ANCA-negative.