Polyarteritis nodosa is 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. Polyarteritis nodosa is relatively rare, with a prevalence of about 30 per 1 million people. Approximately 10% of cases of polyarteritis nodosa are caused by hepatitis B. Most cases of hepatitis B–associated disease occur within 6 months of hepatitis B infection. Mutations in the gene for adenosine deaminase 2 have been identified in early-onset familial polyarteritis.
The exact cause of polyarteritis nodosa is not known. In the majority of patients no predisposing cause has been found. Unidentified bacterial and/or viral infections may be a cause. Polyarteritis nodosa has been observed in drug abusers, particularly those using amphetamines, and in patients with hepatitis B (infection of the liver). This disorder has also been linked to an allergic reaction to some drugs and vaccines.
Most scientists believe that polyarteritis nodosa is an autoimmune disease. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. Recent research suggests that a bacterial infection may initially trigger onset of polyarteritis nodosa causing an abnormal immune response to infection. Treatment of polyarteritis nodosa usually involves drugs that alter the immune system.
Symptoms and Signs
The clinical onset is usually insidious, with fever, malaise, weight loss, and other symptoms developing over weeks to months.
Pain in the extremities is often a prominent early feature caused by arthralgia, myalgia (particularly affecting the calves), or neuropathy.
The combination of mononeuritis multiplex (with the most common finding being foot-drop) and features of a systemic illness is one of the earliest specific clues to the presence of an underlying vasculitis. Polyarteritis nodosa is among the forms of vasculitis most commonly associated with vasculitic neuropathy.
In polyarteritis nodosa, the typical skin findings— livedo reticularis, subcutaneous nodules, and skin ulcers— reflect the involvement of deeper, medium-sized blood vessels.
Digital gangrene is not an unusual occurrence.
The most common cutaneous presentation is lower extremity ulcerations, usually occurring near the malleoli.
Involvement of the renal arteries leads to a renin-mediated hypertension (much less characteristic of vasculitides involving smaller blood vessels). For unclear reasons, classic polyarteritis nodosa seldom (if ever) involves the lung, with the occasional exception of the bronchial arteries.
Abdominal pain—particularly diffuse periumbilical pain precipitated by eating—is common but often difficult to attribute to mesenteric vasculitis in the early stages.
Nausea and vomiting are common symptoms. Infarction compromises the function of major viscera and may lead to acalculous cholecystitis or appendicitis.
Some patients present dramatically with an acute abdomen caused by mesenteric vasculitis and gut perforation or with hypotension resulting from rupture of a microaneurysm in the liver, kidney, or bowel.
Subclinical cardiac involvement is common in polyarteritis nodosa, and overt cardiac dysfunction occasionally occurs (eg, myocardial infarction secondary to coronary vasculitis, or myocarditis).
Most patients with polyarteritis nodosa have a slight anemia, and leukocytosis is common. Acute-phase reactants are often (but not always) strikingly elevated. A major challenge in making the diagnosis of polyarteritis nodosa, however, is the absence of a disease-specific serologic test (eg, an autoantibody). Patients with classic polyarteritis nodosa are ANCA-negative but may have low titers of rheumatoid factor or antinuclear antibodies, both of which are nonspecific findings. Appropriate tests for active hepatitis B infection (HBsAg, HBeAg, hepatitis B viral load) should be performed.
The diagnosis of 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 clinicians, tissue biopsies normally have high benefit-risk ratios because of the importance of establishing the diagnosis. Patients in whom polyarteritis nodosa is suspected—eg, on the basis of mesenteric ischemia or new-onset hypertension occurring in the setting of a systemic illness—may be diagnosed by the angiographic finding of aneurysmal dilations in the renal, mesenteric, or hepatic arteries. Angiography must be performed cautiously in patients with baseline kidney disease.
For polyarteritis nodosa, corticosteroids in high doses (up to 60 mg of oral prednisone 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. The addition of cyclophosphamide lowers the risk of disease-related death and morbidity among patients who have severe disease. Methotrexate or azathioprine are used to maintain remissions induced by cyclophosphamide.
For patients with polyarteritis nodosa associated with hepatitis B, the preferred treatment regimen is a short course of prednisone accompanied by anti-HBV therapy 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.