Treatment Options for SLE in Children

The treatment regimen depends on the affected target organs and disease severity. Sun exposure should be minimized and include use of a sunscreen. Patients are treated to promote clinical well-being, using serologic markers of disease activity as guidelines, including serum complement levels. Nonsteroidal anti-inflammatory agents, used to treat arthralgia and arthritis, are used with caution because patients with lupus are more susceptible to hepatotoxicity. Hydroxychloroquine is often used to treat mild manifestations including skin lesions, fatigue, arthritis, and arthralgia. Hydroxychloroquine may also reduce the risk of thromboembolic disease and lowers lipid levels.

Patients with thrombosis and antiphospholipid antibodies or a lupus anticoagulant should receive anticoagulant medication at least until lupus is in remission. The length of therapy is controversial. Low molecular weight heparin is the anticoagulant of choice; warfarin can also be used.

Corticosteroids control symptoms and autoantibody production in lupus. Treatment with corticosteroids has improved kidney disease and the rate of survival. Corticosteroids can make the diagnosis and treatment of tuberculosis difficult; all patients should have PPD and control skin tests, when possible, before corticosteroids are initiated. The optimal dose and route of administration of corticosteroids are controversial. Patients with systemic disease are often started on 1–2 mg/kg/24 hr of oral prednisone in divided daily doses. When complement levels increase to within the normal range, the dose is carefully tapered to the lowest effective dose. One method uses alternate-day high-dose corticosteroids once disease is controlled to prevent the adverse effects of daily corticosteroid administration. Severely ill patients may require pulse intravenous corticosteroid therapy (30 mg/kg/dose, maximum 1 g/day, given over 60 min, for 3 days). Intermittent high-dose intravenous therapy in combination with low-dose daily oral corticosteroids has been used as an alternative regimen in some centers. Adverse effects of corticosteroids include hypertension, gastritis, cataracts, osteopenia, and cushingoid body habitus.

Patients with severe disease may require cytotoxic therapy. Pulse intravenous cyclophosphamide has maintained renal function and prevented progression in patients with lupus nephritis, particularly diffuse proliferative glomerulonephritis; the optimal length of therapy remains controversial. Cyclophosphamide is used to treat vasculitis, pulmonary hemorrhage, and central nervous system involvement. Azathioprine has been used to prevent renal disease progression, although little is known about the long-term sequelae of cytotoxic medications, particularly in children with lupus. Adverse effects include secondary infections, gonadal dysfunction, and possibly increased risk of later malignancies. Prepubertal children, compared with those who have entered puberty, may be at less risk for subsequent gonadal dysfunction from cytotoxic agents.

Other interventions are being proposed for the treatment of lupus. Methotrexate, cyclosporine, and mycophenolate mofetil are used as steroid-sparing agents. Mycophenolate is an alternative to cyclophosphamide for some types of lupus nephritis. Autologous stem cell and allogeneic bone marrow transplantation for patients with severe, persistent disease are undergoing clinical trials in adult and pediatric patients with lupus. Biologic agents that target cytokine production, in particular, anti-CD20/22 monoclonal antibodies, are also being studied. Other potential therapies include rituximab (anti-CD20 monoclonal antibody), as well as blockade of interleukin 6 (IL-6), T cell co-stimulatory molecules and BlyS, a B-cell activating factor.

Management of Renal Involvement:
The extent of renal involvement may be out of proportion to findings on urinalysis; renal biopsy for staging can help determine whether an immunosuppressive agent such as cyclophosphamide needs to be added to a corticosteroid regimen. Biopsy findings according to the World Health Organization classification, which was modified in 2004, correlate with morbidity and mortality. 

• Class I is minimal mesangial change without proteinuria or hematuria. 
• Class II demonstrates mesangial proliferation. 
• Both Class I and Class II are associated with excellent prognosis. 
• Class III (focal proliferative glomerulonephritis) shows involvement of <50% of glomeruli having focal, segmental proliferation of cells near capillaries with necrosis and lymphocytic infiltration, and is often associated with chronic renal disease. 
• Class IV (diffuse segmental or global proliferative glomerulonephritis) exhibits a majority of each glomeruli affected by cellular infiltration, mesangial cellular proliferation, and crescent formation corresponding to scarring and has been correlated with increased risk for developing end-stage renal disease in adulthood; intravenous pulse cyclophosphamide can decrease this risk. 
• Class V disease (membranous glomerulonephritis) shows thickened capillary walls on light microscopy and subepithelial deposits on electron microscopy along the basement membrane. These changes have been associated with proteinuria, which can occur with the other types of lupus nephritis, and variable chronic renal disease that is often poorly responsive to treatment.
• Class VI is advanced sclerosing nephritis and demonstrates diffuse, chronic damage suggesting progression to renal failure.

Regular Monitoring:
The most important aspect of management of lupus is meticulous and frequent re-evaluation of clinical signs and laboratory data, especially for renal and serologic flares of disease. Prompt recognition and treatment of disease flare is essential to patient outcome. Lupus is a lifelong illness, and patients require monitoring indefinitely.