Granulomatosis with polyangiitis (Wegener’s granulomatosis)

Granulomatosis with polyangiitis (GPA) is a rare (<1/200.000 annual incidence) systemic small vessel vasculitis that affects primarily the respiratory system and kidneys. It is associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) in the majority of cases and it has many similarities with other vasculitis, particularly with microscopic polyangiitis (MPA).

CLINICAL PRESENTATION:

It can affect the ears, eyes, nose, sinuses, trachea, lungs, kidney, skin, joints and nerves.

SYMPTOMS:
Runny nose, stuffiness, sinus infections and nosebleeds
Coughing, sometimes with bloody phlegm
Fever
Fatigue and general aches and pains
Joint pain
Skin sores or bruising
Eye redness, burning or pain
Ear infections
Red eyes

SIGNS:
Ulcers in the nasal mucosa, sinuses or other parts of the respiratory tract
Hematuria
Weight loss
Fever
Pulmonary consolidation
Otitis
Uveitis
Hematuria and/or Proteinuria
Mononeuritis
Cutaneous manifestations (ulcers, urticaria, livedo reticularis, nodules).

DIAGNOSTIC CRITERIA:
American College of Rheumatology Criteria (1990):

Nasal or oral inflammation (painful or painless oral ulcers, or purulent or bloody nasal discharge)
Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
Abnormal urinary sediment (microscopic hematuria with or without red cell casts)
Granulomatous inflammation on biopsy of an artery or perivascular area

Two or more of these four criteria yields 88% sensitivity and 92% specificity.

TESTS TO CONSIDER ORDERING:

CBC, CMP, ESR and Urinalysis
ANCA (positive in up to 80% of the cases (pANCA 60%, cANCA 40%) )
Chest X-ray or CT-Scan (nodules, patchy or diffuse opacities, fleeting pulmonary infiltrates, hilar adenopathy).
Biopsy (affected organ such as lung, kidney or skin. In most patients, the glomerulonephritis is associated with few or no immune deposits in the glomeruli (pauci-immune glomerulonephritis)).
If there is suspicion of a different rheumatic disease, the relevant antibodies should be ordered as well.

TREATMENT:

Induce remission with: Cyclophosphamide or Rituximab (either associated with Glucocorticoids). PCP prophylaxis should be given (TMP-SMZ 160/800 mg 3 times weekly).
Maintenance: Azathioprine, mycophenolate mofetil, methotrexate or rituximab.

REFERENCES AND FURTHER READING: