Pediatric Polyarteritis Nodosa Treatment & Management

The choice of agents to treat polyarteritis nodosa (PAN) depends on the severity of the disease. Severity and outcome of PAN has been demonstrated to be dependent on the following 5 factors, known as the 5-factor score (FFS):

1. Proteinuria greater than 1 g/day
2. Renal insufficiency (creatinine concentration higher than 140 µmol/L)
3. Cardiomyopathy
4. Gastrointestinal (GI) manifestations
5. Central nervous system (CNS) involvement

Although it has not been definitively established that treatment should be chosen on the basis of the FFS, these criteria probably should be considered in the therapeutic strategy. Patients without poor prognostic factors can be treated with prednisone alone. Cyclophosphamide can be administered as a second-line medication in the presence of persistent disease activity or relapse despite steroid therapy.

Surgery is necessary during diagnostic evaluation to perform biopsies. Surgery is required therapeutically in patients with peripheral gangrene and acute abdomen. Unexplained abdominal pain may indicate silent bowel infarction.

Transfer to a tertiary care center is indicated for patients who require renal replacement therapy. Transfer to an emergency department (ED) is warranted if patients present with any of the following:

• Respiratory distress
• Acute abdomen
• Disseminated infection
• Acute CNS insult (eg, stroke or intracranial hemorrhage)

No dietary restriction is necessary, except as indicated for patients with hypertension, cardiac failure, and renal failure. Low sodium intake is recommended during courses of high-dose steroids. Activity is unrestricted, except in patients with joint and cardiac involvement, for whom appropriate activity restrictions apply.

Steroids and immunosuppressive medications form the backbone of therapy. These agents have been demonstrated to improve survival in PAN. In one study, the 5-year survival rate improved from 10% to 55% with steroids as monotherapy.^[9] Steroids can induce complete remission in many patients, but insidious progression to end-organ damage may result when activity is suppressed only partly. When cyclophosphamide was added to prednisone, the survival rate increased to 82%.

If no bad prognostic factors are present (ie, FFS = 0), prednisone can be administered as a single agent. As the patient’s clinical status improves and the erythrocyte sedimentation rate (ESR) returns to normal (usually within 1 month), progressive tapering of the dosage can begin. In the absence of relapses, steroids can be stopped after 9-12 months. For severe systemic disease, it is prudent to start “pulse” methylprednisolone at 30 mg/kg (not to exceed 1 g) intravenously (IV) over 60 minutes, repeated in 24-hour intervals for 1-3 days.

If poor prognostic factors are present (ie, FFS >0), cyclophosphamide is indicated. Daily oral dosing remains the established approach. The IV route may provide a more rapid clinical response with less toxicity than the oral route. To date, however, studies of comparative efficacy have included too few patients to allow any conclusions in favor of either route.

IV pulse cyclophosphamide increasingly is being used to treat systemic vasculitis. Use intense hydration and mesna to prevent hemorrhagic cystitis during both oral and pulse cyclophosphamide therapy.

If the initial therapy is with IV pulse cyclophosphamide, initiate oral cyclophosphamide if the IV regimen fails to control disease activity or if relapse occurs within the first 6 months of treatment.

Treatment duration with corticosteroids and cyclophosphamide usually does not exceed 1 year.

Plasma exchange is not recommended as a first-line therapy for individuals with PAN who do not have hepatitis B virus (HBV) infection; however, plasma exchange is useful as a second-line treatment of PAN refractory to conventional therapy. It is also useful for patients with renal failure (creatinine >500 µmol/L), patients dependent on dialysis, or patients with lung hemorrhage.

In view of the high frequency of renal involvement, all patients with microscopic polyangiitis (MPA) should be considered to have poor prognostic factors and thus should be treated with high-dose steroids and cyclophosphamide.

Cyclophosphamide pulse has been demonstrated as superior to azathioprine in inducing remission. Once remission is induced, azathioprine can be used for maintenance.

In patients with symptoms refractory to these treatments, IV immunoglobulin (IVIg) may be considered.

Chronic hepatitis B

In individuals with chronic hepatitis B, corticosteroids and immunosuppressive agents have deleterious effects and have been demonstrated to enhance viral replication. Accordingly, combination therapy involving antiviral drugs and steroids is used in patients with HBV infection.

Initially, corticosteroids are used to rapidly control the most severe life-threatening manifestations of PAN, which are common during the first weeks of the disease; plasma exchanges are then used to control the subsequent course of PAN. Antiviral drugs used include vidarabine and interferon alfa-2b. In most patients, antiviral treatment can be stopped after 3 months.

Other associated conditions

Because of maximal immunosuppression at the beginning of therapy for PAN treatment, measures to prevent opportunistic infections, such as P carinii infection, may be necessary. Typically, oral trimethoprim-sulfamethoxazole is given.

Angiotensin-converting enzyme (ACE) inhibitors can be used to control hypertension.

Consultations with the following specialists should be considered:

• Nephrologist, in the presence of renal involvement
• Surgeon, for severe GI bleeding,^[10] bowel perforation, and vascular catastrophes
• Cardiologist, for cardiac involvement in the form of atrioventricular block, pericarditis, and myocarditis
• Rheumatologist, for short-term and long-term follow-up care

Look for evidence of relapse, using both physical examination and laboratory evaluation. Look for adverse effects of drugs. Advise patients to avoid exposure to contagious disease. Prevent opportunistic infections that may emerge during therapy. Avoid abrupt cessation of drugs, especially steroids.Continue or taper the steroids and immunosuppressive drugs according to the response. Consider therapy to inhibit platelet aggregation.