Hemophagocytic Syndromes and Infection

, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Disclosures

Emerging Infectious Diseases. 2000;6(6) 

In This Article

Prognosis and Therapy

Because these disorders are rare, no controlled clinical trials of therapy have been performed. For patients with reactive HLH associated with pathogens other than EBV, supportive care and treatment of the underlying infection is associated with recovery in 60%-70%[20,64]. Among adults with HLH, age > 30 years appears to be associated with an increased risk for death[27].

Epstein-Barr virus-associated HLH is almost universally fatal if untreated, with death usually resulting from hemorrhage, infection, or multiorgan failure[64,65]. The poor prognosis of this syndrome suggests that patients should be treated initially with combination chemotherapy and immunotherapy, regardless of whether they are thought to have familial HLH. Chemotherapy with etoposide (which is toxic to macrophages) and dexamethasone is recommended, with the use of intrathecal methotrexate in patients with neurologic symptoms or persistent cerebrospinal fluid abnormalities[66,67,68,69]. In a group of children with EBV-associated HLH, investigators induced complete remission (median 15 months) in 15 of 17 patients[68]. The increasing recognition of the important role of T lymphocytes in HLH has led to the recommendation that chemotherapy be combined with cyclosporin A immunotherapy[60,61,62,67]. Antithymocyte globulin may also have a role in therapy[60].

HLH associated with viral infection may be difficult to distinguish from familial HLH triggered by a viral infection[39], although familial HLH should be considered more likely in infants even in the absence of a positive family history[19]. The distinction is important, as allogeneic bone marrow transplantation is the therapy of choice in patients with familial HLH who attain remission[67,70]. In patients without a clear diagnosis of familial HLH, bone marrow transplantation should be considered if remission is not attained by 8 weeks of chemotherapy and immunotherapy. Patients in remission without a clear diagnosis of familial HLH should be monitored closely for signs of relapse[67].

The role of intravenous immunoglobulin in the treatment of HLH is unclear. Remission after such therapy has been reported in adults and older children with underlying immune dysfunction[71,72]. However, Chen and colleagues noted remission in only two of nine children with virus-associated HLH treated with intravenous immunoglobulin alone[65].

Acyclovir does not appear to be useful in the treatment of EBV-associated HLH. However, resolution of HLH associated with other viral pathogens has been reported after antiviral chemotherapy. For example, adenovirus-associated HLH in a bone marrow transplant patient was reported to resolve with vidarabine[73], while human herpesvirus-8-associated HLH in a patient with HIV infection appeared to improve with the use of foscarnet[74].

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