Granulomatosis with polyangiitis

Disease class: lung diseases, Interstitial

Systemic vasculitis

Formerly known as Wegener's granulomatosis.
This is a small vessel vasculitis.

 

Physiology

• In health, tissue macrophages have the capability to form granulomas (giant cells) to envelop pathogens and ‘wall off’ an infection inside the body. 
• Neutrophils contain latent NADPH oxidase. This enzyme generates superoxide and subsequent free radicals (reactive oxygen species). This enables the destruction of bacteria inside the phagosome. 
•  There is a group of rare immunodeficiency disorders, called chronic granulomatous diseases (CGD), in which patients have defective neutrophils. These are unable to produce reactive oxygen species and unable to clear ingested pathogens. Granulomata form in many organs. 

 

Pathophysiology

• Affected tissues contain granulomas 
• Studies have shown that anti-neutrophil cytoplasmic antibodies (ANCAs) can bind to proteinase 3 in neutrophils 
• ANCAs can activate neutrophils, increasing adherence and degranulation of neutrophils 
• This causes widespread damage to vessel walls and vasculitis

Symptoms

• Pyrexia of unknown origin
• Fatigue
• Arthritis
• Myalgia
• Haematuria
• Nasal congestion
• Rhinitis
• Epistaxis
• Nasal pain
• Rash 
• Dyspnoea
• Haemoptysis
• Teeth loosening
• Mouth ulcers
• Blurred vision
• Ocular pain 
• Hearing loss
• Numbness
• Paraesthesia
• Chronic pain
• Weakness 

 

Signs

• Saddle-nose deformity
• Septal perforation
• Splinter haemorrhages
• Nail-fold infarcts
• Mucosal ulceration
• Rash
• Strawberry gingivitis 
• Subcutaneous nodules (granulomas) on the elbow
• Conductive hearing loss
• Sensorineural hearing loss
• Signs of neuropathy
• Neuropathic pain
• Sensory neuropathy 
• Motor neuropathy
• Signs of kidney disease 
• Anasarca

 

Complications

• Rapidly progressive glomerulonephritis (75%)
• Subglottal stenosis 
• Bronchial stenosis 
• Pulmonary nodules, infiltrates 
• Cavitatary lung lesions
• Pulmonary haemorrhage 
• Mononeuritis multiplex 
• Sensory neuropathy
• Pseudotumors
• Scleritis
• Conjunctivitis
• Uveitis
• Episcleritis 

 

Epidemiology

• Typically affects older adults.
• More common in Caucasians.

 

Investigations

Initial immunology screening

• ANA
• ANCA
• C3, C4
• CRP
• RF
• Immunoglobulins and Cryoglobulins 

Monitoring

• CRP and ANCA at each visit.

 

Diagnosis

• Classic presentation: microscopic haematuria in a patient with non-specific malaise/ myalgia
• Bloods
• c-ANCA is usually positive with elevated PR3 antibodies.
• Urinalysis
• Evidence of glomerulonephritis should be sought on urinalysis.
• Imaging
• Thoracic imaging characteristically shows multiple nodules that often cavitate, areas of consolidation and ground-glass opacification (which may be due to pulmonary haemorrhage).
• Biopsy
• Diagnosis should be confirmed with biopsy of the active site.

 

Management

• It is sometimes necessary to initiate empirical treatment in acutely unwell patients.
• Initial immunosuppressant therapy is with a combination of glucocorticoids and cyclophosphamide, rituximab or methotrexate.