Churg-Strauss syndrome

Synonyms: eosinophilic granulomatosis with polyangiitis, allergic granulomatosis angiitis, granulomatous small-vessel vasculitis, eosinophilic granulomatosis with polyangiitis

What is EGPA?

EGPA (eosinophilic granulomatosis with polyangiitis), formerly known as Churg-Strauss syndrome, is a rare diffuse vasculitic disease affecting coronary, pulmonary, cerebral, abdominal visceral and skin circulations. The vasculitis affects small- and medium-sized arteries and veins and is associated with asthma.

Causes of EGPA (aetiology)

The aetiology is unknown although autoimmune and genetic factors have been implicated¹ . Drug-induced EGPA has been reported. Drugs implicated have included mesalazine, propylthiouracil, methimazole, freebase cocaine and leukotriene receptor antagonists² .

Diagnosing EGPA (diagnostic criteria)

The American College of Rheumatology (ACR) identified six criteria for the diagnosis of EGPA³ :

• Asthma (wheezing, expiratory rhonchi).

• Eosinophilia of more than 10% in peripheral blood.

• Paranasal sinusitis.

• Pulmonary infiltrates (may be transient).

• Histological confirmation of vasculitis with extravascular eosinophils.

• Mononeuritis multiplex or polyneuropathy.

The presence of four out of six of these features was considered to have a high specificity and sensitivity for the diagnosis of EGPA.

However, the criteria did not take into account the subsequent development of antineutrophil cytoplasm antibody (ANCA) testing in the diagnostic process. The ACR therefore collaborated with the European League Against Rheumatism to produce updated criteria with a scoring system, viz⁴ :

i) Maximum eosinophil count ≥1x109/L (+5).

ii) Obstructive airway disease (+3).

iii) Nasal polyps (+3).

iv) cANCA or anti-PR3 ANCA positivity (-3).

v) Extravascular eosinophilic predominant inflammation (+2).

vi) Mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1).

vii) Haematuria (-1).

After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as EGPA with a cumulative score of ≥6 points.

Epidemiology⁵

• EGPA is a rare disease. The estimated prevalence is 10.7 to 14 per million adults worldwide.

• The reported mean age of onset is 38-54 years, with a median of 40. However, it has been reported in extremes of age as well, from as low as 4 to as high as 74.

• There is no gender difference in incidence.
  

EGPA symptoms (presentation)

EGPA symptoms will depend on which systems are involved. In any patient with asthma and/or nasal polyposis, any new or worsening general or constitutional symptoms - including fever, joint pain, diffuse muscle pain, major involuntary weight loss, chest pain, palpitations or abdominal pain - may be the first signs of a vasculitis, including EGPA⁵ .

The most prominent symptoms and signs include:

• Pulmonary: asthma, pneumonitis and haemoptysis.

• Upper respiratory tract: allergic rhinitis, paranasal sinusitis, nasal polyposis.

• Cardiac involvement is common⁶ . This includes heart failure, myocarditis and myocardial infarction⁷ .

• Skin: purpura, skin nodules, leukocytoclastic angiitis with palpable purpura, livedo reticularis, urticaria, necrotic bullae and digital ischaemia.

• Renal: glomerulonephritis, hypertension and advanced chronic kidney disease.

• Peripheral neuropathy: mononeuritis multiplex is the most frequent form. Less frequent symptoms include stroke and eye involvement.

• Gastrointestinal: vasculitis and bleeding, bowel ischaemia and perforation, appendicitis and pancreatitis.

• Cholestatic liver dysfunction has been reported⁸ .

• Malaise, fatigue, weight loss, fever, myalgia and arthralgia.

• Myositis following unaccustomed exercise has been reported⁹ .

Differential diagnosis¹⁰

There are many possible differential diagnoses to consider but include:

• Other causes of systemic vasculitis¹¹ :
  

  • Primary vasculitis - eg, polyarteritis nodosa, granulomatosis with polyangiitis.

  • Secondary vasculitis: a complication of a connective tissue disorder (eg, rheumatoid arthritis), infection, medication, or malignancy.

• Infections - eg, helminth/nematode.

• Primary eosinophilic syndrome.

• Malignancy - eg, leukaemias, lymphomas, myeloproliferative neoplasms, solid cancers (especially gastrointestinal, breast or lung).

• Myelodysplastic syndromes.

Investigations

• Antineutrophil cytoplasmic antibodies (ANCAs): 30-40% of patients are perinuclear staining (p-ANCA) positive (antimyeloperoxidase antibodies)¹⁰ .

• Other likely findings include eosinophilia and anaemia on the FBC; elevated ESR and CRP; elevated serum creatinine; increased serum IgE levels, hypergammaglobulinaemia; proteinuria, microscopic haematuria and red blood cell casts in the urine.

• CXR: pulmonary opacities, transient pulmonary infiltrates, pleural effusions.

• Pulmonary CT scan: peripheral areas of parenchymal consolidation with ground-glass attenuation similar to chronic eosinophilic pneumonia.

• Bronchiolar lavage may yield eosinophilia.

• Biopsy: the characteristic changes, found especially in the lung, include small necrotising granulomas, as well as necrotising vasculitis involving small arteries and venules.

• Other investigations are indicated for the complications of the disease and specific organ system involvement.

EGPA treatment and management¹²

• High-dose steroids are usually adequate for treatment.

• Cyclophosphamide is administered in patients with severe or life-threatening complications. Either azathioprine or methotrexate is also used.

• Other treatments include intravenous immune globulin, interferon-alpha and plasma exchange.

• Successful use of rituximab has been reported¹³ .

• Oral tacrolimus in combination with methylprednisolone and cyclophosphamide was used successfully in the treatment of a child severely ill with EGPA¹⁴ .

• Plasmapheresis, mepolizumab (an anti-IL-5 monoclonal antibody) and omalizumab (recombinant humanised monoclonal anti-IVIG E antibody) have been found to be useful in refractory cases⁵ .

• Gastrointestinal transplantation in a patient with severe gastrointestinal involvement has been reported¹⁵ .

Complications

• Complications of vasculitis depend on the specific organ system involvement.

• Cardiac and neurological complications are particularly serious and are more likely in patients with a delayed diagnosis¹⁶ .

Prognosis⁵

• Without treatment, the five-year survival rate is about 25%.

• However, patient outcomes have dramatically improved in recent years. With appropriate and timely treatment, the survival rate at five years is now 90%.

• Relapses are not uncommon¹² .

• Five features have been recognised as being associated with an increased risk of mortality:

  • Proteinuria (greater than 1 gm per day).

  • Renal insufficiency (Cr greater than 1.58 mg/dl).

  • Cardiomyopathy.

  • GI tract involvement.

  • CNS involvement.

One review found that, compared with adult EGPA patients, children had a predominance of cardiopulmonary disease, a lower rate of peripheral nerve involvement and a higher mortality¹⁷ .