Granulomatosis with Polyangiitis
Granulomatosis with polyangiitis is a necrotizing granulomatous vasculitis of small vessels. It affects men and women equally, and the peak age of onset is between the age of 60 and 70.
It most commonly affects respiratory tract and kidneys, but many other organs can be involved. Clinical manifestations by organ system include the following:• Upper respiratory tract: rhinitis, sinusitis, oral/nasal ulcers, nasal septum perforation, saddle nose deformity, recurrent otitis, sensorineural hearing loss, subglottic stenosis
• Lower respiratory tract: cough, hemoptysis, pulmonary infiltrates, nodules, diffuse pulmonary hemorrhage, pleurisy
• Renal: rapidly progressive glomerulonephritis
• Ocular: scleritis, episcleritis, orbital pseudotumor, uveitis
• Musculoskeletal: arthralgias or migratory arthritis
• Neurologic: mononeuritis multiplex, symmetric polyneuropathy and less commonly cranial neuropathies
• Cutaneous: palpable purpura, ulcers, subcutaneous nodules, livedo reticularis
• Abdominal vasculitis can manifest with abdominal pain, gut ulceration, or infarction
DIAGNOSIS
• Laboratory findings include anemia of chronic disease, elevated ESR/CRP, elevated creatinine, hematuria, proteinuria, and positive ANCA (commonly PR3).
• Imaging studies may show lung nodules, infiltrates, or cavities. Biopsy of kidney, lung, or skin can be done if affected.
• Nasal biopsies usually have low specificity. Kidney biopsy often shows pauci-immune glomerulonephritis. Lung biopsies may show capillaritis or necrotizing granulomatosis.
TREATMENT
• Treatment includes induction therapy followed by maintenance therapy. The use of glucocorticoid alone is inadequate and should always be used in combination with a DMARD.
î Induction therapy is usually the combination of IV methylprednisolone 1 g for 3 days followed by oral prednisone 1 mg/kg daily plus rituximab or cyclophosphamide or both. Based on the RAVE study, rituximab is as effective as cyclophosphamide and favored in relapsing disease.25
î Maintenance treatment options, once remission is achieved, include azathioprine, methotrexate, and mycophenolate mofetil. Low-dose rituximab can also be used for maintenance. For patients with limited GPA, only upper airway involvement, induction, and maintenance therapy with oral DMARDs alone can be considered.
î PEXIVAS trial showed that plasmapheresis does not reduce the risk of end-stage renal disease or death in patients with ANCA vasculitis, but it demonstrated that a rapid steroid taper was equally effective, and patients had less side effects.26 Thus, steroid taper protocol used in the trial is recommended. TMP/SMX should be considered for all patients for PCP prophylaxis.