granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a multisystem necrotizing non-caseating granulomatous c-ANCA positive vasculitis affecting small to medium-sized arteries, capillaries, and veins, with a predilection for the respiratory system and kidneys.

This article discusses GPA in general. For organ-specific radiographic features, please refer to individual articles:

Epidemiology

There is a slight male predilection and onset is typically at approximately 50 years of age .

Clinical presentation

Presentation depends on which organ systems are involved:

  • cough and hemoptysis
  • subacute to chronic history of nasal obstruction, rhinitis, and epistaxis 
  • proteinuria and hematuria 

Symptoms related to other organ systems are less frequent, due to a corresponding infrequency of involvement (musculoskeletal symptoms, ocular symptoms, skin changes) .

Systemic symptoms such as anorexia, malaise and fever are also common .

Diagnostic criteria

The 1990 American College of Rheumatology criteria requires at least two of the four listed below (sensitivity 88.2% and specificity 92%)

  • positive biopsy for granulomatous vasculitis
  • urinary sediment with red blood cells 
  • abnormal chest radiograph 
  • oral or nasal inflammation 

Pathology 

It results from an immune-mediated vascular injury.

Histology

Histologically necrotizing granulomas with an associated vasculitis are the dominant feature.

Markers

In 90% of cases, cANCA (PR3) is positive and the levels correlate with disease activity .

Classification

The classic triad of organ involvement consists of:

  • lungs: involved in 95% of cases
  • upper respiratory tract / sinuses: 75-90%
  • kidneys: 80%

In terms of extent, granulomatosis with polyangiitis can be classified as:

  • classical: full triad
  • limited: not having the full triad
    • usually respiratory tract involvement only
    • renal only involvement has been described but is uncommon
  • widespread: additional organ involvement

Treatment and prognosis

Treatment is typically with cyclophosphamide, methotrexate and/or steroids. More recently agents such as Rituximab are also used.

Without treatment, granulomatosis with polyangiitis is rapidly progressive with death usually occurring within a year of diagnosis, with only 10% of patients surviving 2 years . Appropriate medical therapy has dramatically increased long term survival .

History and etymology

The former name "Wegener granulomatosis" comes from the German pathologist Friedrich Wegener who first described it in 1936 . Wegener was a member of the Nazi party and it is suspected that he took part in experiments on concentration camp inmates. Following the discovery of his past history, the current name "granulomatosis with polyangiitis" has been proposed .

Differential diagnosis

General imaging differential considerations include: