29th January 2024

Granulomatosis with polyangiitis (Wegener’s granulomatosis)

Background 

Epidemiology

Granulomatosis with polyangiitis, which was formerly known as Wegener’s granulomatosis, affects equal numbers of males and females. The peak incidence is around 40-60 years of age. Prevalence is approximately 3 per 100,000 population.

Aetiology

Idiopathic.

Pathophysiology

Aberrant epigenetic expression of PR-3 on the cell membranes of neutrophils binds to c-ANCA. This activates neutrophils to release neutrophilic inflammatory markers. This process damages the endothelial cells of the small blood vessels. 

Clinical features

Granulomatosis with polyangiitis can affect virtually any site in the body with predisposition to certain organs such as the upper respiratory tract, lungs and kidneys. Constitutional features such as fever, night sweats, weight loss and arthralgia will commonly occur.

Ear, nose and throat involvement are often the first clinical manifestation of disease. Commonly, patients have chronic rhinitis or sinusitis, which are slow to resolve. This causes nasopharyngeal ulcerations and nasal septum perforation, leading to depression of the nasal dorsum (saddle nose deformity). Others can present with chronic otitis (decreased hearing), mastitis, oral ulcers or gingival hyperplasia (strawberry gingivitis). 

Skin lesions such as papules, vesicles and ulcers may occur. Palpable purpura of the lower extremities may lead to Raynaud’s phenomenon, necrotising vasculitis and dry gangrene of digits. Ocular involvement includes conjunctivitis, episcleritis, retinal vasculitis and corneal ulcerations. 

Life-threatening complications of the disease include those with renal involvement causing pauci-immune glomerulonephritis. This can progress to rapidly progressive (crescentic) glomerulonephritis with possible pulmonary-renal syndrome if not aggressively managed. These patients have proteinuria, haematuria, and red cell casts in the urine. 

Patients can also present with pneumonia-like symptoms caused by pulmonary fibrosis, pulmonary hypertension and pulmonary haemorrhage. Cardiac involvement can lead to pericarditis and myocarditis. Disease in the coronary arteries are complicated by myocardial infarction and death. 

Image Source: Wikipedia (2021). Granulomatosis with polyangiiti, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Granulomatosis_with_polyangiitis (Accessed:16 February 2022).

Diagnosis

Blood tests can demonstrate an acute kidney injury with a rise in urea and creatinine. Inflammatory markers are typically raised. PR3, c-ANCA is highly sensitive and positive in around 90% of patients. Patients can also have normocytic normochromic anaemia. Urinalysis typically shows microscopic haematuria and mild to moderate proteinuria, with urine sediments of dysmorphic RBC and RBC casts (nephrotic sediment) with sterile pyuria. 

CXR or CT chest are done to look for bilateral cavitating nodule lesions and pulmonary haemorrhage. 

Diagnosis of condition is typically by biopsy of the affected tissue (primarily lung or kidney), which can show necrotic, partially granulomatous vasculitis of small and medium-sized vessels with necrotising granulomas.

Treatment 

Urgent treatments with glucocorticoids along with immunosuppressive agents such as methotrexate, cyclophosphamide or rituximab are required to initiate remission. In severe disease such as those with pulmonary haemorrhage, intravenous immunoglobulins and plasmapheresis may be used. Remission maintenance requires immunosuppressive drugs such as azathioprine, rituximab and methotrexate. 

Without adequate treatment, the 1-year survival rate is < 20%. 5-year survival with adequate treatment is approx. 80%. 

References

• Granulomatosis with Polyangiitis, Johns Hopkins Vasculitis Center. Available at: https://www.hopkinsvasculitis.org/?s=polyarteritis [Accessed 16th January 2022].
• Vasculitides, Amboss. Available at: https://www.amboss.com/us/knowledge/Vasculitides/ [Accessed 17th January 2022].
• Vasculitis, Versus Arthritis. Available at: https://www.versusarthritis.org/about-arthritis/conditions/vasculitis/[Accessed 15th January 2022].
• Wallace, Z.S. and Miloslavsky, E.M., 2020. Management of ANCA associated vasculitis. BMJ, 368.