Macrophage Activation Syndrome

Recently it has been suggested that in patients unresponsive to the combination of steroids and CyA, particularly in those with renal and hepatic impairment, antithymocyte globulin (ATG) might be a safer alternative to etoposide.²¹ ATG depletes both CD4+ and CD8+ T cells through complement-dependent cell lysis. Mild depletion of monocytes is noted in some patients as well. Although in the reported cases this treatment was tolerated well, one must remember that infusion reactions are frequently reported with the use of ATG and adequate laboratory and supportive medical resources must be readily available if this treatment is used. The utility of biologic drugs in MAS treatment remains unclear. Although, tumor necrosis factor– (TNF-) inhibiting agents have been reported to be effective in occasional MAS patients, other reports describe patients in whom MAS developed while they were on TNF-inhibiting agents. Because, at least in systemic JIA, MAS episodes are often triggered by the disease flare, biologics that neutralize interleukin-1, a cytokine that plays a pivotal role in SJIA pathogenesis, have been tried by some authors. However, as with TNF-inhibiting agents, the results, however, have been conflicting. Based on some success of intravenous immunoglobin treatment in virus-associated reactive HLH, this treatment might be considered in MAS triggered by viral infection. If MAS, however, is driven by EBV infection, one might consider rituximab, a treatment that would eliminates B lymphocytes, the main type of cells harboring EBV virus. This approach has been successfully used in EBV-induced lymphoproliferative disease.²²

Prognosis

Although the reported mortality rates of MAS reach 20%, due to increasing awareness it is now diagnosed relatively early and the outcome is improving. A substantial proportion of MAS patients experience recurrent episodes and these patients may require closer monitoring.

Dr. Grom is associate professor of pediatrics in the division of rheumatology at Cincinnati Children’s Hospital Medical Center.

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