Pediatric Polyarteritis Nodosa Medication

Steroids and immunosuppressive drugs have been demonstrated to improve survival in polyarteritis nodosa (PAN). 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 is added to prednisone, survival improves.

Class Summary

Glucocorticoids are naturally occurring hormones that have anti-inflammatory properties and exert profound and varied metabolic effects. They prevent or suppress inflammation and immune responses when administered at pharmacologic doses (decreased lymphocyte volume and activity, decreased polymorphonuclear [PMN] cell migration, and decreased or reversed capillary permeability). In high doses, especially over periods longer than 2-3 weeks, they suppress adrenal function.

Prednisone

Prednisone is the most commonly prescribed oral corticosteroid. It is metabolized in the liver to its active form, prednisolone. Relative to hydrocortisone, prednisone is approximately 4 times as potent.

Prednisolone (Pediapred, Prelone, Orapred)

Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is a commonly used oral agent.

Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol)

Initial management of PAN should include high doses of corticosteroids. Methylprednisolone has been widely used as a first-line agent in patients with severe PAN. Its half-life is approximately 2 hours, which contributes to decreased short-term and long-term adverse effects and complications. Methylprednisolone may be used every week or every other week to facilitate rapid tapering of daily oral steroids.

Class Summary

Patients with immune dysregulation and autoimmunity often benefit from immunosuppression.

Cyclophosphamide

Cyclophosphamide is a cell cycle phase nonspecific antineoplastic agent and immunosuppressant. It is a prodrug that requires activation by the cytochrome P-450 system to be cytotoxic. Cyclophosphamide is chemically related to nitrogen mustards and is an alkylating agent. The mechanism of action of active metabolites may involve cross-linking of DNA and possible protein modification, which may interfere with growth of normal and neoplastic cells.

When cyclophosphamide is indicated for a 5-factor score (FFS) greater than 0, pulse therapy may be preferred to daily oral therapy because of the rapid clinical response. Even though pulse therapy increases acute adverse effects, fearsome long-term complications (eg, bladder cancer) are lesser issues. The low incidence of bladder cancer with pulse therapy has been linked to the lower cumulative dose. Adjust dose and frequency on the basis of disease severity, renal function, hematologic profile, and response to previous therapies.

Azathioprine (Azasan, Imuran)

Azathioprine is an oral and parenteral immunosuppressive agent that is a chemical analogue of endogenous purines (adenine, guanine, hypoxanthine) and is metabolized to 6-mercatopurine. It antagonizes purine metabolism and may inhibit synthesis of proteins, RNA, and DNA. It may interfere with mitosis and cellular division.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

Trimethoprim-sulfamethoxazole (Bactrim DS, Septra DS)

Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis of Pneumocystis carinii. It inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.