Eosinophilic Granulomatosis with Polyangiitis – EGPA (Churg–Strauss Syndrome)

, David G. I. Scott² and Chetan Mukhtyar²

(1)

Department of Rheumatology, Ipswich Hospital NHS Trust, Ipswich, UK

(2)

Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK

8.1 Introduction

EGPA, also known as allergic granulomatous angiitis, is a rare, anti-neutrophil cytoplasmic antibody (ANCA) associated small vessel vasculitis. It was first described in 1951 by Churg and Strauss and is a multisystem disorder, characterized by allergic rhinitis and asthma, eosinophilia, and extravascular granulomata.

8.2 Definition and Classification

EGPA is defined using the Chapel Hill consensus definitions (2012) “Eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium vessels, and associated with asthma and eosinophilia. ANCA is more frequent when glomerulonephritis is present [1].”

There are three main classification schemes for EGPA. The Chapel Hill Consensus Conference definition (above) is based on clinical and histopathological features, Lanham’s criteria (Table 8.1) put emphasis on clinical presentation [2] and the ACR criteria (Table 8.2) developed in 1990 [3]. The presence of four or more out of six criteria yields a sensitivity of 85 % and a specificity of 99.7 %.

Table 8.1

Lanham criteria for EGPA

Asthma

Peripheral eosinophilia >1 × 10⁹/L

Systemic vasculitis involving two or more extrapulmonary organs

From Lanham et al. [2]

Table 8.2

ACR criteria for EGPA

Asthma

History of wheezing or diffuse high-pitched rales on expiration

Eosinophilia

Greater than 10 % of white blood cell differential count

Mononeuropathy or polyneuropathy

Development of mononeuropathy, multiple mononeuropathies, or polyneuropathy

(i.e., glove/stocking distribution) attributable to vasculitis

Pulmonary infiltrates, nonfixed

Migratory or transitory pulmonary infiltrates on radiographs (not including fixed infiltrates), attributable to systemic vasculitis

Paranasal sinus abnormality

History of acute or chronic paranasal sinus pain or tenderness or radiographic opacification of the paranasal sinuses

Extravascular eosinophils

Biopsy including artery, arteriole or venule, showing accumulations of eosinophils in extravascular areas

From Masi et al. [3]. With permission from John Wiley and Sons

8.3 Epidemiology

Among the three ANCA-associated vasculitides (EGPA, GPA and MPA), EGPA is the rarest with an annual incidence of 1–3 cases/million [4]. The median age at diagnosis is 50 years and there is a slight a male preponderance.

8.4 Etiology

The exact etiology of the condition is unknown, but the prominence of allergic features, the pronounced T-cell immunity with granuloma formation along with the increased globulin level, especially IgE and immune complex formation, all suggest an autoimmune process. It is thought that environmental and genetic factors (HLA-DRB4) may also play a role [5].

EGPA has been associated with the use of leukotriene therapies for asthma and anti-IgE monoclonal antibodies (omalizumab) [6]. In most instances, it is thought that the occurrence of EGPA reflects masking of previously undiagnosed EGPA in asthmatic patients taking glucocorticoids.

8.5 Clinical Manifestations

EGPA is believed to evolve through three clinical phases [2]:

Prodromal phase

This phase may last for years and is characterized by asthma, with or without atopic features (e.g., allergic rhinitis, nasal polyposis).

Eosinophilic phase

Peripheral blood eosinophilia and eosinophilic tissue infiltration often of the lung and gastrointestinal tract.

Vasculitic phase

This is the most severe phase and may only become apparent several years after the initial or prodromal phase.

Symptoms of malaise, lethargy, weight loss, and fevers are often experienced during the vasculitic phase of the disease.

8.5.1 Pulmonary

Asthma, usually late-onset (mean age 50 years), is a cardinal feature of the disease and seen in the majority of cases (>95 %). Corticosteroid use in asthma often masks the onset of vasculitis for many years. The asthma may worsen just before the onset of vasculitis, leading to hospital admissions.

8.5.2 Cutaneous

Skin involvement is seen in 40–70 % of patients and is one of the most common features of the vasculitic phase of EGPA (Fig. 8.1). It reflects the predilection for small vessels. Palpable purpura (50 %) commonly occurs on the lower extremities. Cutaneous or subcutaneous nodules (30 %) are the most distinctive skin lesions of EGPA, but not pathognomonic. These red or violaceous lesions occur primarily on the scalp and the limbs or hands and feet and are often bilateral and symmetrical.