Clinical manifestations and diagnosis of polyarteritis nodosa in adults
- Peter A Merkel, MD, MPH
Peter A Merkel, MD, MPH
- Section Editor — Vasculitis
- Chief, Division of Rheumatology
- University of Pennsylvania
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that typically affects medium-sized muscular arteries, with occasional involvement of small muscular arteries [1,2]. Unlike some other vasculitides (eg, microscopic polyarteritis, granulomatosis with polyangiitis [Wegener’s]), polyarteritis nodosa is not associated with antineutrophil cytoplasmic antibodies (ANCA) . (See "Overview of and approach to the vasculitides in adults".)
Patients typically present with systemic symptoms. The kidneys, skin, joints, muscles, nerves, and gastrointestinal tract are commonly involved, usually in some combination and sometimes all at once by the time of diagnosis. PAN can affect virtually any organ but has a striking tendency to spare the lungs. Clinical variants or subsets of PAN include single-organ disease and cutaneous-only PAN.
The spectrum of disease known as PAN has evolved and narrowed substantially due to the identification and classification of other forms of vasculitis that had previously been considered PAN. Most importantly, the establishment and acceptance of microscopic polyangiitis as a distinct disease, and the routine availability and recognition of ANCA testing as critical to diagnosing vasculitides other than PAN, have led to more patients with vasculitis being classified as not having PAN. Patient cohorts of PAN included in case series and other research studies published prior to the 1990s almost certainly included a mixture of the newer definition of PAN with microscopic polyangiitis and possibly other forms of vasculitis. Thus, case series of PAN published after this time period that specifically exclude patients with MPA provide important updated information about this disease . (See "Overview of and approach to the vasculitides in adults" and "Clinical spectrum of antineutrophil cytoplasmic antibodies".)
The clinical manifestations and diagnosis of PAN will be reviewed here. Treatment is presented separately. (See "Treatment and prognosis of polyarteritis nodosa".)
Microscopic polyangiitis and other ANCA-associated systemic vasculitides (eg, granulomatosis with polyangiitis [Wegener’s] and eosinophilic granulomatosis with polyangiitis [Churg-Strauss]) that characteristically affect small vessels such as arterioles, capillaries, and venules, as well as muscular arteries, are discussed separately. (See "Overview of and approach to the vasculitides in adults" and "Pathogenesis of granulomatosis with polyangiitis and related vasculitides" and "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis" and "Clinical spectrum of antineutrophil cytoplasmic antibodies".)
- Balow JE. Renal vasculitis. Kidney Int 1985; 27:954.
- Sato O, Cohn DL. Polyarteritis and microscopic polyangiitis. In: Rheumatology, Klippel JH, Dieppe PA (Eds), Mosby, St Louis 2003.
- Kallenberg CG, Brouwer E, Weening JJ, Tervaert JW. Anti-neutrophil cytoplasmic antibodies: current diagnostic and pathophysiological potential. Kidney Int 1994; 46:1.
- Pagnoux C, Seror R, Henegar C, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 2010; 62:616.
- Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheum 2004; 51:92.
- Reinhold-Keller E, Zeidler A, Gutfleisch J, et al. Giant cell arteritis is more prevalent in urban than in rural populations: results of an epidemiological study of primary systemic vasculitides in Germany. Rheumatology (Oxford) 2000; 39:1396.
- Haugeberg G, Bie R, Bendvold A, et al. Primary vasculitis in a Norwegian community hospital: a retrospective study. Clin Rheumatol 1998; 17:364.
- Watts RA, Lane SE, Scott DG, et al. Epidemiology of vasculitis in Europe. Ann Rheum Dis 2001; 60:1156.
- Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum 2000; 43:414.
- Watts RA, Gonzalez-Gay MA, Lane SE, et al. Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe. Ann Rheum Dis 2001; 60:170.
- Guillevin L, Mahr A, Callard P, et al. Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients. Medicine (Baltimore) 2005; 84:313.
- Ramos-Casals M, Muñoz S, Medina F, et al. Systemic autoimmune diseases in patients with hepatitis C virus infection: characterization of 1020 cases (The HISPAMEC Registry). J Rheumatol 2009; 36:1442.
- Hasler P, Kistler H, Gerber H. Vasculitides in hairy cell leukemia. Semin Arthritis Rheum 1995; 25:134.
- Carpenter MT, West SG. Polyarteritis nodosa in hairy cell leukemia: treatment with interferon-alpha. J Rheumatol 1994; 21:1150.
- Navon Elkan P, Pierce SB, Segel R, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med 2014; 370:921.
- Zhou Q, Yang D, Ombrello AK, et al. Early-onset stroke and vasculopathy associated with mutations in ADA2. N Engl J Med 2014; 370:911.
- Stockigt JR, Topliss DJ, Hewett MJ. High-renin hypertension in necrotizing vasculitis. N Engl J Med 1979; 300:1218.
- Ng WF, Chow LT, Lam PW. Localized polyarteritis nodosa of breast--report of two cases and a review of the literature. Histopathology 1993; 23:535.
- Gibson LE, Su WP. Cutaneous vasculitis. Rheum Dis Clin North Am 1995; 21:1097.
- Karlsberg PL, Lee WM, Casey DL, et al. Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Arch Dermatol 1995; 131:1119.
- Leavitt RY, Fauci AS. Polyangiitis overlap syndrome. Classification and prospective clinical experience. Am J Med 1986; 81:79.
- Ohkoshi N, Mizusawa H, Oguni E, Shoji S. Sural nerve biopsy in vasculitic neuropathies: morphometric analysis of the caliber of involved vessels. J Med 1996; 27:153.
- Tervaert JW, Kallenberg C. Neurologic manifestations of systemic vasculitides. Rheum Dis Clin North Am 1993; 19:913.
- Moore PM. Neurological manifestation of vasculitis: update on immunopathogenic mechanisms and clinical features. Ann Neurol 1995; 37 Suppl 1:S131.
- Provenzale JM, Allen NB. Neuroradiologic findings in polyarteritis nodosa. AJNR Am J Neuroradiol 1996; 17:1119.
- Cohen RD, Conn DL, Ilstrup DM. Clinical features, prognosis, and response to treatment in polyarteritis. Mayo Clin Proc 1980; 55:146.
- Reichart MD, Bogousslavsky J, Janzer RC. Early lacunar strokes complicating polyarteritis nodosa: thrombotic microangiopathy. Neurology 2000; 54:883.
- Pagnoux C, Mahr A, Cohen P, Guillevin L. Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore) 2005; 84:115.
- Zizic TM, Classen JN, Stevens MB. Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa. Am J Med 1982; 73:525.
- Levine SM, Hellmann DB, Stone JH. Gastrointestinal involvement in polyarteritis nodosa (1986-2000): presentation and outcomes in 24 patients. Am J Med 2002; 112:386.
- Flaherty J, Bradley EL 3rd. Acute pancreatitis as a complication of polyarteritis nodosa. Int J Pancreatol 1999; 25:53.
- Kastner D, Gaffney M, Tak T. Polyarteritis nodosa and myocardial infarction. Can J Cardiol 2000; 16:515.
- Plumley SG, Rubio R, Alasfar S, Jasin HE. Polyarteritis nodosa presenting as polymyositis. Semin Arthritis Rheum 2002; 31:377.
- Fort JG, Griffin R, Tahmoush A, Abruzzo JL. Muscle involvement in polyarteritis nodosa: report of a patient presenting clinically as polymyositis and review of the literature. J Rheumatol 1994; 21:945.
- Teichman JM, Mattrey RF, Demby AM, Schmidt JD. Polyarteritis nodosa presenting as acute orchitis: a case report and review of the literature. J Urol 1993; 149:1139.
- Akova YA, Jabbur NS, Foster CS. Ocular presentation of polyarteritis nodosa. Clinical course and management with steroid and cytotoxic therapy. Ophthalmology 1993; 100:1775.
- Hsu CT, Kerrison JB, Miller NR, Goldberg MF. Choroidal infarction, anterior ischemic optic neuropathy, and central retinal artery occlusion from polyarteritis nodosa. Retina 2001; 21:348.
- Boki KA, Dafni U, Karpouzas GA, et al. Necrotizing vasculitis in Greece: clinical, immunological and immunogenetic aspects. A study of 66 patients. Br J Rheumatol 1997; 36:1059.
- Jennette JC, Falk RJ. The pathology of vasculitis involving the kidney. Am J Kidney Dis 1994; 24:130.
- Kato T, Fujii K, Ishii E, et al. A case of polyarteritis nodosa with lesions of the superior mesenteric artery illustrating the diagnostic usefulness of three-dimensional computed tomographic angiography. Clin Rheumatol 2005; 24:628.
- Schmidt WA. Use of imaging studies in the diagnosis of vasculitis. Curr Rheumatol Rep 2004; 6:203.
- Hellmann DB, Laing TJ, Petri M, et al. Mononeuritis multiplex: the yield of evaluations for occult rheumatic diseases. Medicine (Baltimore) 1988; 67:145.
- Lightfoot RW Jr, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum 1990; 33:1088.
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65:1.
- Watts RA, Suppiah R, Merkel PA, Luqmani R. Systemic vasculitis--is it time to reclassify? Rheumatology (Oxford) 2011; 50:643.
- CLINICAL FEATURES
- Skin disease
- Renal disease
- Neurologic disease
- Gastrointestinal disease
- Coronary artery disease
- Muscle disease
- Physical examination
- Laboratory testing
- Arteriography and cross-sectional imaging
- DIFFERENTIAL DIAGNOSIS
- Classification criteria
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS