Eosinophilic granulomatosis with polyangiitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2] Raviteja Guddeti, M.B.B.S. [3]

Overview

Churg-Strauss syndrome (also known as allergic granulomatosis) is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs (it begins as a severe type of asthma), gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-heritable, non-transmissable and often mis-diagnosed. Churg-Strauss syndrome was once considered a type of Polyarteritis nodosa (PAN) due to their similar morphologies.

Associated Diseases

• Asthma

  • >95%
  • Usually precedes the vasculitic phase by 8-10 years (but can be coincident)

• Nasal and Sinus Disease
• Skin Disease

  • 66%
  • Subcutaneous nodules on the extensor surfaces of the arm

• Cardiovascular disease

  • Pericarditis (32%)
  • Constrictive disease
  • Heart failure (47%)
  • Myocardial infarction (MI)

• Neurologic Disease

  • 75% mononeuritis multiplex
  • If untreated may progress to polyneuropathy

• Kidney Disease

  • 85% with focal segmental glomerulonephritis (FSGN) on biopsy

    • Unclear total incidence of renal disease.

  • 70% p-anca positive

    • But renal failure rare (contrast Wegener’s)

• GI Disease

  • Eosinophilic gastroenteritis with abdominal pain (59%)
  • Diarrhea (33%)
  • GI bleeding (18%)

Microscopic Pathology

• Eosinophilic infiltrates with necrosis (sometimes quite extensive)
• Giant cell vasculitis with eosinophils
• Interstitial and perivascular necrotizing granulomas
• Eosinophilic lymphadenopathy

Necrotizing and granulomatous arteritis in the lung of a patient with Churg-Strauss syndrome.

Epidemiology and Demographics

The mean age at diagnosis is 50. The initial onset of symptoms may be 10-20 years earlier. There is no gender predominance.

Natural History, Complications and Prognosis

Natural History

Classically, three phases of the disease are described:

Stage 1: The Prodromal Phase

This stage occurs in the teenage years through the 20’s. The first stage often involves the sinuses and the new onset of allergies or the worsening of pre-existing allergies (e.g. atopic diseases, allergic rhinitis).

Stage 2: The Eosinophilic Phase

Peripheral blood eosinophilia is now present. There is eosinophilic infiltration of lung and gastrointestinal (GI) tract. The second stage involves the onset of acute asthma. Normally, the person would not have had asthma previously.

People can live for many years in the first two stages before progressing to stage three.

Stage 3: The Vasculitic Phase

The third phase occurs in the 40’s-50’s and involves multiple organ systems in a life-threatening systemic vasculitis of small and medium sized vessels. Stage three is by far the most life threatening and painful. Often the person will develop severe nerve pain in their legs, arms and hands. Purple marks will appear on the skin and often sores will appear in the mouth or nose. The disease will affect the heart and lungs or it will affect the kidneys and liver.

Diagnosis

The diagnosis of Churg-Strauss syndrome can be difficult to make clinically for the following reasons:

• Individual manifestations of the syndrome can occur in isolation
• 40% of patients present with pulmonary opacities, asthma, and eosinophilia prior to systemic vasculitis, and granulomatosis, vasculitis, and eosinophilia are features of other diseases as well
• Lung involvement is not universal
• Chronic eosinophilic pneumonia may be the presenting feature

American College of Rheumatology Diagnostic Criteria

The presence of 4 of the 6 criteria below is 85% sensitive and 99.7% specific:

1. Asthma (history of wheezing or diffuse high-pitched wheezes on expiration)
2. Eosinophilia (>10%)
3. Neuropathy (mono, mono-multiplex, or poly)
4. Migratory or transient pulmonary opacities on chest x-ray
5. Paranasal sinus abnormality
6. Biopsy containing a blood vessel with eosinophilia (eos) in extravascular areas

History and Symptoms

Symptoms can include:

• Fever
• Weight loss
• Malaise
• Asthenia

Laboratory Findings

Electrolyte and Biomarker Studies

Diagnostic markers include eosinophil granulocytes and granulomas in affected tissue and Anti-neutrophil cytoplasmic antibodies (ANCA) against neutrophil granulocytes. Differentiation from Wegener's granulomatosis can be difficult, though the increasing use of ANCA assays has made the distinction more routine. Wegener's is closely associated with c-ANCA, unlike Churg-Strauss which shows elevations of p-ANCA.

The findings on other laboratory studies is nonspecific. Eosinophilia (5K-9K/uL) may be present. Anemia, elevated erythrocyte sedimentation rate (ESR), leukocytosis, elevated immunoglobin E (IgE), hypergammaglobulinemia, and a low-positive rheumatoid factor (RF) may be present.

Imaging

X-ray

CXR in a patient with Churg-Strauss syndrome showing opacification, hilar adenopathy

• Interlobular septal thickening with or without associated peripheral ground glass opacities or consolodation
• Transient opacities
• Symmetrical opacities in axillary and peripheral distribution
• Hilar with hilar adenopathy
• Diffuse interstitial or miliary opacities
• Pulmonary hemorrhage
• Nodular disease (without cavitation)
• Pleural effusions (30%) – exudative and eosinophilic

Risk stratification

Prior to the steroid treatment, the disease was uniformly fatal. Now, 5 year survival tops 70%. In general, poor prognostic indicators include cardiac involvement, GI disease, renal insufficiency (Cr >1.6), proteinuria (>1 g/day) and central nervous system (CNS) involvement. A shorter duration of asthma before the onset of vasculitis also portends poorer prognosis. The role of anti-neutrophil cytoplasmic antibodies (ANCA) in predicting outcome is unclear.

The French Vasculitis Study Group has developed a five-point score ("five-factor score" or FFS) that predicts the risk of death in Churg-Strauss syndrome. These are

(1) reduced renal function (creatinine >1.58 mg/dL or 140 μmol/l),

(2) proteinuria (>1 g/24h),

(3) gastrointestinal hemorrhage, infarction or pancreatitis,

(4) involvement of the central nervous system or

(5) cardiomyopathy.

Presence of 1 of these indicates severe disease (5-year mortality 26%) and 2 or more very severe disease (mortality 46%), while absence of any of these 5 indicates a milder case (mortality 11.9%).

Treatment

Acute Pharmacotherapy

Treatment for Churg-Strauss syndrome includes glucocorticoids such as prednisone at a dose of 0.5-1.5 mg/kg per day x 6-12 weeks and other immunosupressive drugs such as azathioprine and cyclophosphamide. In many cases the disease can be put into a type of chemical remission through drug therapy, but the disease is chronic and life long.

A systematic review conducted in 2007 indicated that all patients should be treated with high-dose steroids, but that in patients with an FFS of 1 or higher cyclophosphamide pulse therapy should be commenced, with 12 pulses leading to less relapses than 6. Remission can be maintained with a less toxic drug, such as azathioprine or methotrexate.

The erythrocyte sedimentation rate (ESR) and eosinophil count can be followed to gauge the response to therapy. Late relapses are uncommon and refractory disease may require Cyclophosphamide, Azathioprine, intravenous immunoglobulin (IVIG) and plasmapheresis.

Eponym

It is named for Dr Jacob Churg and Dr Lotte Strauss, who described the condition in 1951.

Suggested Reading

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External links

• FAQ
• Churg-Strauss syndrome - MedLink Neurology Clinical Summary
• Template:GPnotebook
• One Person's Experience With The Disease
• Natural History of Churg-Strauss Syndrome
• (http://www.mlcss.com/ My Domestic Life A Blog That Focuses On My Everyday Life With Churg Strauss Syndrome)

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