16th January 2024

Background

Epidemiology

This rare condition was previously termed ‘Wegener’s disease’ and has also been referred to as necrotising respiratory granulomatosis. It is the most common of the above ANCA associated vasculitides, and the vasculitis involved affects small and medium-sized vessels. Incidence of GPA varies between countries, but in the UK, approximately 700 people are diagnosed with GPA annually. The condition is autoimmune in nature, with onset most commonly occurring in those aged between 40 and 60 years. It is rare for the condition to occur in children. People of any ethnicity or sex can develop GPA, although there is evidence the condition is more common in those of Caucasian descent.

Pathophysiology

The exact pathophysiology of GPA is unclear, although it has been suggested that exposure to an environmental agent, e.g., silica, or another agent such as infection, initiates excessive cytokine production, leading to granuloma formation, which can occlude vessels and cause necrosis. Alongside this, neutrophils are activated by ANCA, which release cellular products, resulting in vessel damage and inflammation. B cells are also thought to be involved in these processes. No immune complexes are deposited, which helps differentiate this condition from others with similar clinical presentations, e.g., Systemic Lupus Erythematosus (SLE).
Additionally, genetic factors may play a part in disease manifestation via association with genes such as HLA-DP and HLA-DQ. Currently, the condition is believed to be immune-mediated for a number of reasons. Firstly, it is associated with other immune-mediated conditions, and secondly, patients demonstrate good response to immunosuppressive treatment.