Granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a multisystem necrotising non-caseating granulomatous c-ANCA positive vasculitis affecting small to medium sized-sized arteries, capillaries and veins, with a predilection for the respiratory system and kidneys ³.

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

• granulomatosis with polyangiitis: pulmonary manifestations
• granulomatosis with polyangiitis: renal manifestations
• granulomatosis with polyangiitis: upper respiratory tract manifestations
• granulomatosis with polyangiitis: CNS manifestations
• granulomatosis with polyangiitis: orbital manifestations

Epidemiology

There is a slight male predilection and onset is typically at approximately 50 years of age ⁸.

Clinical presentation

Presentation depends on which organ systems are involved, however upper respiratory tract symptoms are most common ⁸. Cough and haemoptysis, proteinuria and haematuria as well as systemic symptoms such as anorexia, malaise and fever are also common ⁹.

Symptoms related to other organ systems are less frequent, due to a corresponding infrequency of involvement (musculoskeletal symptoms, ocular symptoms, skin changes) ⁹.

Pulmonary involvement 

Interstitial fibrosis at the bases is usually the first finding,manifestation but is usually asymptomatic. Multiple pulmonary nodules, cavitating in 50% cases isare the most common and characteristic manifestation. Pleural effusions and mediastinal nodal enlargement are also encountered. 

Renal involvement

Focal lesions can give proteinuria and haematuria while diffuse lesions can give acute renal failure.

Upper respiratory tract and paranasal sinus involvement

Causes mucosal ulceration and granulomatous masses within the nasal cavities with adjacent bony and cartilaginous destruction.

Splenic involvement

Can result in splenic infarction ^16-18

Pathology 

It results from an immune mediated-mediated vascular injury.

Histology

Histologically necrotising granulomas with an associated vasculitis isare the dominant feature.

Markers

In 90% of cases, cANCA(PR3) is positive and the levels correlate with disease activity ⁸.

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 ⁷
• widespread: additional organ involvement ¹⁴
  • skin (50%)
  • eyes (45%)
  • peripheral nervous system (35%)
  • occasionally also other organs, such as the heart and gastrointestinal tract

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 ⁷. Appropriate medical therapy has dramatically increased long term survival ⁷.

History and etymology

The former name "Wegener granulomatosis" comes from the German pathologist Friedrich Wegener who first described it in 1936 ¹¹. 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 ¹⁵.

Differential diagnosis

General imaging differential considerations include:

• eosinophilic granulomatosis with polyangiitis
• lymphomatoid granulomatosis
• sarcoidosis
• microscopic polyangiitis

See also

• pulmonary vasculitides