Eosinophilic Granulomatosis with Polyangiitis (EGPA) a.k.a Churg-Strauss Syndrome

Introduction

In 1951, Churg and Strauss described a syndrome with a relatively uniform clinical picture of severe asthma, fever, peripheral eosinophilia, and symptoms of “vascular embarrassment” in 13 patients initially diagnosed as having polyarteritis nodosa. Churg-Strauss syndrome (CSS) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an uncommon form of antineutrophil cytoplasmic antibody-associated necrotizing vasculitis affecting the small-to-medium sized blood vessels. Disease typically follows three phases.

Etiology

  • Although the etiology of this disease is not well known, both T- and B-cell mediated immunity have been considered.
  • Hyper-responsiveness to antigenic stimuli may be the etiologic factor in the development of CSS.
  • In 1998, Wechsler and colleagues reported eight patients with this syndrome after a decrease or withdrawal of oral steroids.
  • Also cases have been attributed to antibiotics such as erythromycin, azithromycin and roxithomycin and some metered dose inhalers (bamuterol, salmeterol and nedrocromil)

Clinical Manifestations

  • The prodromal phase presents as adult-onset asthma, atopic disease, and allergic rhinosinusitis. It precedes the vasculitic phase by 3 to 9 years but intervals as long as 30 years have also been described.
  • Next, is the eosinophilic phase which is usually a subclinical eosinophilic tissue infiltration without necrosis but can sometimes manifest as pulmonary infiltrates or nodules with or without pneumonitis, or as gastroenteritis.
  • The third and final phase is the vasculitic phase, where patients are usually diagnosed. The mean age at presentation varies from 38 to 52 years of age, but can range from 7 to 74.
  • The most common manifestations at the time of diagnosis were asthma (91.1%), weight loss (49.3%), mononeuritis multiplex (46%), sinusitis or polyposis (41.8%), skin lesions (39.7%), and lung infiltrates (38.6%).

Diagnosis

  • Laboratory Studies
    • Eosinophilia usually appears in the second phase of disease, but can also initially present in the prodromal or vasculitic phases.
    • The presence of ANCA is documented in approximately 40% of EGPA and appears to be associated with renal and upper respiratory tract involvement, alveolar hemorrhage, purpura, biopsy-proven vasculitis and peripheral neuropathy.
      • The absence of ANCA is associated with pulmonary disease, cardiomyopathy, and fever.
      • The origin of this dichotomy is uncertain but it is hypothesized that the tissue damage in ANCA-negative EGPA is directly related to the presence of tissue eosinophils, whereas the ANCA-positive patients are thought to have endothelial damage in the typical ANCA-associated vasculitis fashion.
  • Criteria
    • In 1990, the American College of Rheumatology established the classification criteria for EGPA with a sensitivity of 85% and specificity of 99.7%.
    • Fulfillment of 4 or more criteria is needed for classification as EGPA.
      1. Asthma
      2. Eosinophilia greater than 10% on differential white blood cell count
      3. Mononeuropathy or polyneuropathy
      4. Migratory or transient pulmonary infiltrates detected radiographically
      5. Paranasal sinus abnormality
      6. Biopsy with perivascular eosinophils.
  • Imaging
    • The most common radiological findings are lobular or centrilobular peripheral consolidation and nodularity, thickened bronchial walls, inter-lobular septum, and peri-cardial and pleural effusion.
    • On computed tomography, enlargement of or distortion of peripheral pulmonary arteries may be seen.
  • Pathology
    • Histological diagnosis is by demonstration of vasculitis that is necrotizing, tissue infiltration with eosinophils and extra-vascular granulomas are found in a few cases

Differential Diagnosis

  • The differential diagnosis includes polyarteritits nodosa, Wegener’s granulomatosis, drug reaction, bronchogenic granulomatosis, fungal and parasitic infections, and malignancy

Treatment

  • Regularly with prednisone starting at 40-60 mg a day
  • Cyclophosphamide or azathioprine can be added with the purpose to limit the disease or spare steroids.
  • In case of fulminant disease or multi-organ involvement, parenteral corticosteroid such as methylprednisolone is used.
  • If response to mentioned treatment is not seen, parenteral immunoglobulin is administered.
  • Newly experimental medications for unresponsive cases are mycophenolate mofetil and tumor necrosis factor (TNF)-α blockers (such as etanercept and infliximab).
  • Treatment is continued at least one month after remission

Modified from:

– BMC Musculoskeletal Disorders 2014, 15:388

– Journal of Medical Case Reports 2010, 4:188