Small Vessel Vasculitides without Immune Complexes

Snapshot

A 34-year-old man presents to his doctor’s office for a rash of several weeks. He reports also having allergic rhinitis in the past few weeks, which was strange given that he normally has allergic rhinitis in the spring. Additionally, he reports having had childhood asthma, but in the past few months, he has had to use his inhaler for episodes of asthma. On physical exam, there is palpable purpura and urticarial plaques on the lower extremities and several skin nodules. Wheezes are heard on lung exam. Additional laboratory tests reveal peripheral eosinophilia with elevated IgE levels. (Eosinophilic granulomatosis with polyangiitis)

Introduction

Clinical definition
- vasculitis mediated by neutrophils, rather than immune complexes
  - referred to as “pauci-immune” vasculitides
Pathogenesis
- neutrophils directly damage vessel walls
  - ANCA antigens, proteinase 3 and myeloperoxidase, are proteins inside neutrophils that become expressed on the cell surface when activated
  - ANCA antibodies attach to these antigens and activate neutrophils, leading to vessel wall damage
- affects small and medium-sized vessels of the skin and organs
- cytoplasmic ANCA (c-ANCA) are directed against antigen proteinase 3 (PR3)
- perinuclear ANCA (p-ANCA) are directed against antigen myeloperoxidase (MPO)
Studies
- a biopsy may be needed to establish a diagnosis
direct immunofluorescence of skin biopsy is usually negative

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Clinical definition
- necrotizing granulomatous vasculitis with eosinophilia affecting multiple organs
Presentation
- skin involvement
  - palpable purpura
  - urticaria
  - skin nodules
- upper respiratory involvement
  - chronic sinusitis
  - allergic rhinitis
  - nasal polyps
- lung involvement
  - asthma
- neurologic involvement
  - peripheral neuropathy
    - foot or wrist drop
- can also affect the heart, gastrointestinal system, and kidneys
Studies
- histology
  - necrotizing vasculitis
  - granulomas
  - eosinophilia
- laboratory studies
  - peripheral eosinophilia
  - ↑ IgE
  - + MPO-ANCA/p-ANCA (anti-myeloperoxidase)
Treatment
- systemic glucocorticoids
cyclophosphamide for severe, multi-organ disease

Granulomatosis with Polyangiitis (Wegener Granulomatosis)

Clinical definition
- necrotizing granulomatous c-ANCA-associated vasculitis affecting the upper respiratory tract, lungs, kidneys, and skin
Presentation
- skin and mucosal involvement
  - palpable purpura and ulcers
  - friable, red gingivae
    - “strawberry gums”
  - oral ulcers
- upper respiratory tract involvement
  - nasal ulcers
  - perforation of the nasal septum
  - chronic sinusitis, otitis media, or mastoiditis
- lung involvement
  - hemoptysis
  - cough
  - dyspnea
- renal involvement
  - hematuria
Studies and imaging
- urine studies
  - hematuria
  - red cell casts
- histology
  - focal necrotizing vasculitis
  - necrotizing granulomas in the respiratory tract
  - necrotizing glomerulonephritis
- laboratory studies
  - + PR3-ANCA/c-ANCA (anti-proteinase 3)
- chest radiography
  - large nodular densities
Treatment
- cyclophosphamide
- corticosteroids
mepolizumab, a humanized monoclonal antibody, approved by FDA in 2017

Microscopic Polyangiitis

Clinical definition
- necrotizing p-ANCA-associated vasculitis affecting the lungs, kidneys, and skin
Presentation
- skin involvement
  - palpable purpura
  - ulcers
- no upper respiratory involvement (in contrast to granulomatosis with polyangiitis)
- pulmonary involvement
  - hemoptysis
  - dyspnea
- renal involvement
  - hematuria
Studies
- urine studies
  - hematuria
  - red cell casts
- histology
  - necrotizing vasculitis
  - no granulomas
- laboratory studies
  - + MPO-ANCA/p-ANCA (anti-myeloperoxidase)
Treatment
- cyclophosphamide
- corticosteroids