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.