Ntatsaki E, Carruthers D, Chakravarty K, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014 Dec;53(12):2306-9. doi: 10.1093/rheumatology/ket445. Epub 2014 Apr 11. PubMed PMID: 24729399.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. PubMed PMID: 23045170.
Mukhtyar C, Guillevin L, Cid MC, et al; European Vasculitis Study Group. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009 Mar;68(3):310-7. doi: 10.1136/ard.2008.088096. Epub 2008 Apr 15. PubMed PMID: 18413444.
Microscopic polyangiitis (MPA) is a necrotizing vasculitis with few or no immunologic deposits, which usually affects small vessels (arterioles, capillaries, venules) and may involve small- and middle-sized arteries. It very frequently coexists with necrotizing glomerulonephritis and with pulmonary capillaritis. There is no inflammation extending beyond the blood vessels or granulomatous inflammation, distinguishing it from granulomatosis with polyangiitis.
Clinical Features and Natural HistoryTop
The course of MPA may be indolent, with recurring general symptoms of fever, weight loss, myalgia, and arthralgia persisting for many months or years prior to the onset of organ-specific symptoms. Organ specific manifestations include:
1) Cutaneous manifestations: Palpable purpura (observed at presentation in ~50% of patients). These tend to favor the feet, lower legs, and buttocks.
2) Renal manifestations: There can be mild renal involvement or rapidly progressive glomerulonephritis.
3) Nervous system manifestations: Mononeuritis multiplex (~60%).
4) Respiratory manifestations: Lung involvement can present as diffuse alveolar hemorrhage.
Diagnosis is based on clinical manifestations and histologic examination of the skin, kidney, or lung biopsies. A positive myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) (type of perinuclear ANCA [p-ANCA], present in ~70% of patients) or proteinase 3 (PR3) ANCA (type of cytoplasmic ANCA [c-ANCA], present in 45%) test result also suggests the diagnosis of microscopic polyangiitis.
Laboratory test results may reveal elevations in the erythrocyte sedimentation rate and C-reactive protein levels and features of glomerulonephritis. Chest radiographs, high-resolution computed tomography, and bronchoalveolar lavage reveal typical features of alveolar hemorrhage.
Polyarteritis nodosa (differences: only extraglomerular vessels of the kidneys are involved [no features of glomerulonephritis], pulmonary involvement usually does not occur, ANCA-negative); other causes of pulmonary-renal syndrome (see Granulomatosis With Polyangiitis), cutaneous leukocytoclastic angiitis.
Initial remission induction is recommended with cyclophosphamide and glucocorticoids.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). de Groot K, Adu D, Savage CO; EUVAS (European vasculitis study group). The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant. 2001 Oct;16(10):2018-27. PubMed PMID: 11572891. de Groot K, Harper L, Jayne DR, et al; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80. PubMed PMID: 19451574. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD003232. doi: 10.1002/14651858.CD003232.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;9:CD003232. PubMed PMID: 18646089. Harper L, Morgan MD, Walsh M, et al; EUVAS investigators. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012 Jun;71(6):955-60. doi: 10.1136/annrheumdis-2011-200477. Epub 2011 Nov 29. PubMed PMID: 22128076. Assuming the cost is acceptable, rituximab (with high-dose glucocorticoids) is preferred over cyclophosphamide in patients at increased risk of infection or in younger patients who are planning a pregnancy, with the efficacy equal to that of cyclophosphamide.Evidence 2Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Remark: strong rather than weak recommendation places high value on differences in efficacy and less value on cost. High Quality of Evidence (high confidence that we know true effects of the intervention). Applicable when comparing the efficacy of cyclophosphamide versus rituximab. Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905. PubMed PMID: 20647199; PubMed Central PMCID: PMC3137658. Jones RB, Tervaert JW, Hauser T, et al; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169. PubMed PMID: 20647198. The dosage and long-term maintenance is the same as in granulomatosis with polyangiitis. Some patients may require long-term renal replacement therapy including dialysis or renal transplantation.