Granulomatosis with Polyangiitis (formerly Wegener Granulomatosis)
Key Points
Granulomatosis with polyangiitis is a systemic necrotizing, mostly small vessel vasculitis of unknown etiology that manifests as granulomatous lesions of the upper respiratory tract, lungs and kidneys.
-Formerly known as Wegener Granulomatosis, it was renamed because of the eponymous individual’s association with Nazism
-GPA is the most common form of vasculitis to involve the lung.
-It’s a disease of triads
Classic Clinical Triad: Upper respiratory tract disease, lung disease, and glomerulonephritis
Classic Pathologic Triad: necrotizing granulomas in the upper respiratory tract and lungs, vasculitis involving both arteries and veins, and glomerulonephritis.
Immunofluorescence triad: C-ANCA, P-ANCA, and Atypical patterns
Epidemiology: a predilection for whites, men and women are similarly affected, typical age of onset 45 – 60 years
Symptoms & Signs
The most frequently involved sites are the upper airways, lungs, and kidneys, but other systems can also get affected.
Upper respiratory tract:
Nose: Rhinorrhea, nasal obstruction, epistaxis, bloody nasal crusts, perforation of the nasal septum, collapse of the nasal bridge (saddle-nose deformity)
Mouth: gum inflammation, gingival hyperplasia (strawberry gums), oral ulcers, tongue ulcers, sialadenitis
Sinuses: Sinusitis
Lower respiratory tract:
Trachea: subglottic stenosis, hoarseness and stridor
Lungs: Cough, dyspnea, hemoptysis, pleuritic chest pain
Kidneys: focal/segmental rapidly progressive glomerulonephritis, hematuria, proteinuria
Eyes: unilateral proptosis from orbital pseudotumor, optic nerve ischemia, corneal ulcerations (corneal melt), scleritis, episcleritis, uveitis, keratitis, loss of vision , nasolacrimal duct obstruction, central retinal artery occlusions
Ear: hearing loss, otitis media, mastoiditis, seventh cranial nerve damage in the middle ear leading to facial palsy, nausea, vertigo, tinnitus
Joints: Arthralgias, arthritis, migratory, pause- or monoarticular syndrome of lower or upper extremity joints, polyarthritis of the small joints of the hands, digital ischemia, gangrene
Skin: Round, palpable purpura, ulcers, pyoderma gangrenosum-like lesions, nodules of cutaneous extravascular necrotizing granulomas (Churg-Strauss granulomas) typically on the extensor surfaces of the elbows, splinter hemorrhages
Heart: Pericarditis, myocarditis, conduction disorder
Vascular: venous thromboembolism
Nervous system: Severe headaches, cranial neuropathies, Mononeuritis multiplex with peroneal nerve most often involved, distal symmetric polyneuropathy, meningitis
General: Fever, malaise, weight loss
Diagnosis
Serum tests: C-ANCA directed against antigens that reside within the primary granules of neutrophils and monocytes – proteinase-3 (PR3) (90% of cases) and myeloperoxidase (MPO); P-ANCA in a minority of patients; Elevated erythrocyte sedimentation rate, serum C-reactive protein level
Urinalysis: Proteinuria, hematuria, red cell casts
Imaging: Pulmonary infiltrates, nodules, cavities, alveolar hemorrhage, subglottic stenosis on Chest X ray and CT.
Tissue biopsy: Necessary for diagnostic confirmation; Necrotizing granuloma, vasculitis, multinucleated giant cells, palisading histiocytes, clusters of neutrophils within the blood vessel wall (microabscesses), coalescence of neutrophilic microabscesses (geographic necrosis), relatively sparse immunoglobulin and complement depositions (pauci-immune), segmental necrotizing glomerulonephritis with multiple crescents
Treatment
Induction of remission: rituximab (particularly anti-PR3 positive), cyclophosphamide, glucocorticoids, Avacopan (an oral C5a receptor inhibitor), and methotrexate
-Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole when Cyclophosphamide or rituximab is used
Maintenance of remission:
Azathioprine, methotrexate, mycophenolate mofetil, or rituximab
Rhinoplasty for saddle-nose deformity
Prognosis: 5 year mortality of untreated GPA is 90%
Beware of Sound Alikes!
Churg-Strauss syndrome and Churg-Strauss granulomas: Churg-Strauss syndrome is eosinophilic granulomatosis with polyangiitis while Churg-Strauss granulomas are cutaneous extravascular necrotizing granulomas.
Beware of Look Alikes!
Cocaine use: Cocaine can destroy nose and palate, can cause drug-induced positive results for C-ANCA, vasculitis. But it does not cause pulmonary or kidney disease.
Rheumatoid arthritis & GPA: Both can overlap and coexist in a patient; Both can cause vasculitis, arthritis, skin nodules and interstitial lung disease. Both can have positive Rheumatoid factors. Both can respond to rituximab. Use biopsy to differentiate the two.