Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 20-19: Polyarteritis Nodosa For further information, see CMDT Part 20-21: Microscopic Polyangiitis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis +++ POLYARTERITIS NODOSA ++ Medium-sized arteries are affected Clinical findings depend on the arteries involved; lungs are spared Common features Fever Abdominal pain Extremity pain Livedo reticularis Mononeuritis multiplex Anemia Elevated acute phase reactants (erythrocyte sedimentation rate [ESR] or C-reactive protein or both) Kidney involvement causes renin-mediated hypertension Associated with hepatitis B (10% of cases) +++ MICROSCOPIC POLYANGIITIS ++ Necrotizing vasculitis of small- and medium-sized arteries and veins Most common cause of pulmonary-renal syndrome: diffuse alveolar hemorrhage and glomerulonephritis Associated with antineutrophil cytoplasmic antibody (ANCA) in 75% of cases, usually anti-myeloperoxidase antibodies (MPO-ANCA) (that cause a P-ANCA pattern on immunofluorescence testing) ANCA directed against proteinase-3 (PR3-ANCA) (that cause a C-ANCA pattern on immunofluorescence testing) can also be observed +++ General Considerations +++ POLYARTERITIS NODOSA ++ A necrotizing arteritis of medium-sized vessels that has a predilection for involving the skin, peripheral nerves, mesenteric vessels (including renal arteries), heart, and brain but spares the lungs Relatively rare, with a prevalence of about 30 cases per 1 million people Approximately 10% of cases are caused by hepatitis B; most cases of hepatitis B–associated disease occur within 6 months of onset of hepatitis B infection +++ MICROSCOPIC POLYANGIITIS ++ A pauci-immune nongranulomatous necrotizing vasculitis that Affects small blood vessels (capillaries, venules, or arterioles) Often causes glomerulonephritis and pulmonary capillaritis Often is associated with ANCA on immunofluorescence testing (directed against MPO, a constituent of neutrophil granules) Appears in a spectrum overlapping with both polyarteritis nodosa and granulomatosis with polyangiitis (formerly Wegener granulomatosis) because it May involve medium-sized as well as small blood vessels Tends to affect capillaries within the lungs and kidneys Rarely medications induce a systemic vasculitis associated with high titers of p-ANCA and features of microscopic polyangiitis, particularly Propylthiouracil Hydralazine Allopurinol Penicillamine Minocycline Sulfasalazine + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs +++ POLYARTERITIS NODOSA ++ Fever, malaise, weight loss, and other symptoms develop over weeks to months Pain in the extremities Vasculitic neuropathy Livedo racemosa, subcutaneous nodules, and skin ulcers reflect involvement of deeper, medium-sized blood vessels Digital gangrene is common Lower extremity ulcerations, usually occurring near the malleoli Renin-mediated hypertension due to involvement of renal arteries Acalculous cholecystitis or appendicitis caused by compromised function of major viscera Dramatic presentation in some cases Acute abdomen caused by mesenteric vasculitis and gut perforation Hypotension resulting from rupture of a microaneurysm in the liver, kidney, or bowel Subclinical cardiac involvement is common; overt cardiac dysfunction occurs occasionally Lungs are seldom (if ever) involved +++ MICROSCOPIC POLYANGIITIS ++ "Palpable" (or "raised") purpura and other signs of cutaneous vasculitis (ulcers, splinter hemorrhages, vesiculobullous lesions) Pulmonary-renal syndromes (eg, anti-glomerular basement membrane disease) Interstitial lung fibrosis that mimics usual interstitial pneumonitis; conveys poor prognosis Pulmonary hemorrhage may occur Pathologic findings in the lung are typically those of capillaritis The renal lesion is a segmental, necrotizing glomerulonephritis, often with localized intravascular coagulation and the observation of intraglomerular thrombi upon renal biopsy Vasculitic neuropathy (mononeuritis multiplex) +++ Differential Diagnosis ++ Genetic collagen vascular disorders (such as Ehlers-Danlos, Loey Dietz syndromes) Fibromuscular dysplasia Segmental arterial mediolysis + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests +++ POLYARTERITIS NODOSA ++ Slight anemia and leukocytosis are common Acute phase reactants (ESR, CRP) are often (but not always) strikingly elevated Patients are ANCA-negative Rheumatoid factor or antinuclear antibodies may be present in low titers Tests for active hepatitis B infection (HBsAg, HBeAg, hepatitis B viral load) should be performed +++ MICROSCOPIC POLYANGIITIS ++ Microscopic hematuria, proteinuria, and red blood cell casts may be present in the urine Careful scrutiny of the urine sediment is essential to assess for active renal disease 75% of patients are ANCA-positive Elevated acute phase reactants are also typical of active disease +++ Diagnostic Procedures +++ POLYARTERITIS NODOSA ++ Requires confirmation with either a tissue biopsy or an angiogram Biopsies of symptomatic sites such as skin (from the edge of an ulcer or the center of a nodule), nerve, or muscle have sensitivities of approximately 70% The least invasive tests should usually be obtained first, but biopsy of an involved organ is essential If performed by experienced physicians, tissue biopsies normally have high benefit-risk ratios because of the importance of establishing the diagnosis Angiographic finding of aneurysmal dilations in the renal, mesenteric, or hepatic arteries is diagnostic when PAN is suspected based on mesenteric ischemia or new-onset hypertension occurring in the setting of a systemic illness Angiography must be performed cautiously in patients with baseline kidney disease + Treatment Download Section PDF Listen +++ +++ Medications +++ POLYARTERITIS NODOSA ++ Corticosteroids in high doses (up to 60 mg of prednisone orally daily) may control fever and constitutional symptoms and heal vascular lesions Pulse methylprednisolone (eg, 1 g intravenously daily for 3 days) may be necessary for patients who are critically ill at presentation Immunosuppressive agents, especially cyclophosphamide, appear to improve the survival of patients when given along with corticosteroids Methotrexate or azathioprine are used to maintain remissions induced by cyclophosphamide For cases associated with hepatitis B, the treatment of choice is a short course of prednisone accompanied by antiviral therapy (eg, entecavir) and plasmapheresis (three times a week for up to 6 weeks) Inhibitors of TNF are first-line therapy for the polyarteritis associated with deficiency of adenosine deaminase 2 +++ MICROSCOPIC POLYANGIITIS ++ Treated in the same way as granulomatosis with polyangiitis Patients with severe disease, typically involving pulmonary hemorrhage and glomerulonephritis, require urgent induction treatment with corticosteroids and either cyclophosphamide or rituximab If cyclophosphamide is chosen, it may be administered either in an oral daily regimen or via intermittent (usually monthly) intravenous pulses Following the induction of remission, treatment with azathioprine, rituximab, or methotrexate (provided the patient has normal kidney function) should be continued In cases of drug-induced MPO-ANCA-associated vasculitis, The offending medication should be discontinued Significant organ involvement (eg, pulmonary hemorrhage, glomerulonephritis) requires immunosuppressive therapy + Outcome Download Section PDF Listen +++ +++ Complications ++ Mesenteric vasculitis can cause bowel ischemia with bleeding or perforation +++ Prognosis +++ POLYARTERITIS NODOSA ++ Without treatment, the 5-year survival rate in these disorders is about 10% With appropriate therapy, remissions are possible in many cases and the 5-year survival rate has improved to 60–90% Poor prognostic factors Chronic kidney disease with serum creatinine > 1.6 mg/dL (> 141 mcmol/L) Proteinuria > 1 g/day Gastrointestinal ischemia CNS disease Cardiac involvement In the absence of any of these five factors, 5-year survival is nearly 90% Survival at 5 years drops to 75% with one poor prognostic factor present and to about 50% with two or more factors Relapses following the successful induction of remission occur in only about 20% of cases +++ MICROSCOPIC POLYANGIITIS ++ Early diagnosis is key to a good outcome Patients with microscopic polyangiitis are more likely than those with granulomatosis with polyangiitis (formerly Wegener granulomatosis) to have significant fibrosis on renal biopsy The likelihood of disease recurrence following remission is about 33% +++ When to Refer ++ Refer to a rheumatologist to assist with establishing the diagnosis and planning therapy +++ When to Admit ++ Admit for therapy whenever new visceral complications, such as bowel ischemia, cardiomyopathy, or rapidly progressive neuropathy, develop + References Download Section PDF Listen +++ + +Forbess L et al. Polyarteritis nodosa. Rheum Dis Clin North Am. 2015;41(1):33–46. [PubMed: 25399938] + +Gibson KM et al; PedVas Investigators Network. Identification of novel adenosine deaminase 2 gene variants and varied clinical phenotype in pediatric vasculitis. Arthritis Rheumatol. 2019 Oct;71(10):1747–55. [PubMed: 31008556] + +Jardel S et al; French Vasculitis Study Group (FVSG). Mortality in systemic necrotizing vasculitides: a retrospective analysis of the French Vasculitis Study Group registry. Autoimmun Rev. 2018 Jul;17(7):653–9. [PubMed: 29730524] + +Karadag O et al. Polyarteritis nodosa revisited: a review of historical approaches, subphenotypes and a research agenda. Clin Exp Rheumatol. 2018 Mar–Apr;36 Suppl 111(2):135–42. [PubMed: 29465365] + +Lhote R1 et al. Spectrum and prognosis of ANCA-associated vasculitis-related bronchiectasis: data from 61 patients. J Rheumatol. 2019 Dec 1. [Epub ahead of print] [PubMed: 31787599] + +Maillet T et al; French Vasculitis Study Group (FVSG). Usual interstitial pneumonia in ANCA-associated vasculitis: a poor prognostic factor. J Autoimmun. 2020 Jan;106:102338. [PubMed: 31570253]