Granulomatosis with Polyangitis (GPA)

Question 1

pathogenesis

Answer 1

granulomatous inflammation of respiratory tract, small and medium vessels
necrotizing glomerulonephritis common

Question 2

who gets it

Answer 2

more common in northern Europe (90%)
m:f 1.5:1
35-55yrs

Question 3

how does it present?

Answer 3

constitutional symptoms & arthralgia are common
American college of rheumatology 1990 criteria for the classification of GPA - 2 or more criteria (88.2% sensitivity, 92% specificity)
o Nasal / oral inflammation: painful/painless oral ulcers or purulent/bloody nasal discharge
o Abnormal chest radiograph: nodules, fixed infiltrates or cavities
o Urinary sediment: microhematuria (>5 RBC/high power field) or red cell casts in urine
o Granulomatous inflammation on biopsy: Histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular / extravascular area (artery or arteriole)

Question 4

ENT symptoms

Answer 4

o	sinusitis
o	nasal crusting
o	epistaxis
o	mouth ulcers
o	sensorineural deafness
o	otitis media and deafness
o	“saddle nose” due to cartilage ischaemia

Question 5

Respiratory symptoms

Answer 5

o	pulmonary infiltrates
o	cough
o	haemoptysis
o	diffuse alveaolar hemorrhage
o	cavitating nodules on CXR

Question 6

Cutaneous symptoms

Answer 6

o palpable purpura

o cutaneous ulcers

Question 7

renal symptoms

Answer 7

necrotising glomerulonephritis

Question 8

nervous symptoms

Answer 8

o mononeuritis multiplex
o sensorimotor polyneuropathy
o cranial nerve palsies

Question 9

ocular symptoms

Answer 9

o	conjunctivitis
o	episcleritis
o	uveitis
o	optic nerve vasculitis
o	retinal artery occlusion
o	proptosis

Question 10

how is it investigated?

Answer 10

ESR, PV, CRP raised 
anaemia of chronic disease 
U&E for renal involvement 
urinalysis 
CXR 
biopsy of affected area - skin, kidney 
immunology - ANCA

Question 11

how is it classified?

Answer 11

Localized – Upper/Lower respiratory tract disease without any other systemic involvement or constitutional symptoms
Early systemic - any, without organ or life threatening
Generalized – renal (creatinine < 500) or other organ threatening
Systemic – renal (creatinine > 500) or other vital organ failure
Refractory – progressive disease unresponsive steroids + cyclo

Question 12

How is it managed?

Answer 12

Localized/early systemic – Methotrexate + steroids (?Azathioprine + steroids)
Generalised/systemic
o Cyclophosphamide + steroids (1st line)
o Rituximab + steroids (alternative)
o plasma exchange if creatinine > 500
o Followed by azathioprine with alternatives being methotrexate. mycophenolate mofetil or leflunomide
• Refractory – IV immunoglobulins, Rituximab