Polyarteritis Nodosa

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 rare, with a prevalence of 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.

Diagnostic Essentials

• Medium-sized arteries are affected.
• Clinical findings depend on the arteries involved; lungs are spared.
• Common features include fever, abdominal pain, extremity pain, livedo reticularis, mononeuritis multiplex.
• Kidney involvement causes renin-mediated hypertension.
• Associated with hepatitis B (10% of cases).

Clinical Findings

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 (Figure 1–7ck), subcutaneous nodules, and skin ulcers—reflect the involvement of deeper, medium-sized blood vessels.

Digital gangrene is common.

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 frequent 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.

Newly acquired hypertension from renin-mediated kidney disease frequently occurs.

Subclinical cardiac involvement is common in polyarteritis nodosa, and overt cardiac dysfunction may occur (eg, MI secondary to coronary vasculitis, or myocarditis).

Laboratory Findings

Most patients with polyarteritis nodosa have 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.

Tests for active hepatitis B infection (HBsAg, HBeAg, hepatitis B viral load) should be performed.

Patients with childhood onset of polyarteritis nodosa should undergo genetic evaluation for mutations in the genes for adenosine deaminase 2.

Biopsy and Angiography

The diagnosis of polyarteritis nodosa requires confirmation with either a tissue biopsy or vascular imaging.

Biopsies of symptomatic sites such as skin and nerve and muscle (or both), are essential for diagnosis.

A deep biopsy, not a punch biopsy, of skin ulcers or nodules should be made to ensure a medium-size vessel is included in the sample.

Current guidelines recommend a biopsy of the nerve and muscle (instead of the nerve alone) in patients with neuropathic symptoms.

Patients in whom polyarteritis nodosa is suspected—eg, based on 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.

Differential Diagnosis

Genetic collagen vascular disorders (such as Ehlers-Danlos and Loey-Dietz syndromes), fibromuscular dysplasia, and segmental arterial mediolysis should be considered when imaging findings suggest polyarteritis nodosa in the absence of other clinical features of the disorder.

Treatment

High-dose pulse methylprednisolone (eg, 1 g IV daily for 3 days) is recommended as the initial treatment for severe polyarteritis nodosa.

Adding 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).

TNF inhibitors are first-line therapy for the polyarteritis associated with deficiency of adenosine deaminase 2.

Prognosis

Without treatment, the 5-year survival rate in this disorder 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 are CKD with serum creatinine > 1.6 mg/dL (141 mcmol/L), proteinuria > 1 g/day, GI ischemia, CNS disease, and 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.

Substantial morbidity and death may result from adverse effects of cyclophosphamide and corticosteroids (Table 26–17). These therapies require careful monitoring and expert management.

In contrast to many other forms of systemic vasculitis, disease relapses in polyarteritis following the successful induction of remission occur in only about 20% of cases.