Treatment-resistant granulomatosis with polyangiitis and microscopic polyangiitis
- Ronald J Falk, MD
Ronald J Falk, MD
- Nan and Hugh Cullman Eminent Professor of Nephrology
- Chair, Department of Medicine
- Director, UNC Kidney Center
- University of North Carolina-Chapel Hill
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
In January 2011, the Boards of Directors of the American College of Rheumatology (ACR), the American Society of Nephrology (ASN), and the European League Against Rheumatism (EULAR) recommended that the name "Wegener's granulomatosis" be changed to "granulomatosis with polyangiitis," abbreviated as GPA [1-3].
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related systemic vasculitides. Both are associated with antineutrophil cytoplasmic autoantibodies (ANCA), have similar features on renal histology (eg, a focal necrotizing, pauci-immune, crescentic glomerulonephritis), and have somewhat different clinical features and outcomes (including different patterns of pulmonary involvement and relapse rates) (see "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis", section on 'Clinical presentation'). These entities are closely related to renal-limited necrotizing and pauci-immune necrotizing and crescentic glomerulonephritis.
Cyclophosphamide or rituximab in combination with glucocorticoids are usually used for initial immunosuppressive therapy [4,5]. Patients who continue to have active vasculitis, despite at least six months of treatment with one of these optimal initial therapies, have treatment-resistant disease.
Treatment-resistant GPA and MPA will be reviewed here. Initial and maintenance immunosuppressive therapy, the clinical manifestations and diagnosis of these diseases and renal-limited disease, the identification and treatment of relapsing disease, and the prognosis of patients with GPA and MPA are discussed elsewhere. (See "Initial immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis" and "Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis" and "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis" and "Identification and management of relapsing disease in granulomatosis with polyangiitis and microscopic polyangiitis" and "Prognosis in granulomatosis with polyangiitis and microscopic polyangiitis, and management of those who develop end-stage renal disease".)
IDENTIFICATION OF TREATMENT RESISTANCE
Treatment resistance in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) is defined as the presence of active disease affecting a major organ despite optimal initial immunosuppressive therapy with glucocorticoids plus either cyclophosphamide or rituximab for an adequate period of time. (See "Initial immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis".)
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- NEW TERMINOLOGY
- IDENTIFICATION OF TREATMENT RESISTANCE
- Differential diagnosis
- - Unresponsive but not resistant
- INCIDENCE AND RISK FACTORS
- MANAGEMENT OF TREATMENT-RESISTANT DISEASE
- Our approach
- - Rituximab in patients with cyclophosphamide resistance
- - Cyclophosphamide in patients with rituximab resistance
- - Mycophenolate mofetil in cyclophosphamide- and rituximab-resistant patients
- Therapies of unproven efficacy
- - Anti-TNF-alpha therapy
- - Anti-T cell antibodies
- - Intravenous immune globulin
- - Intravenous azathioprine
- - 15-deoxyspergualin
- - Radiation therapy
- - Stem cell transplantation
- SUMMARY AND RECOMMENDATIONS