Immunomodulation treatment for childhood virus‐associated haemophagocytic lymphohistiocytosis

Abstract

The Epstein-Barr virus (EBV), or human herpesvirus-6 (HHV-6) associated haemophagocytic lymphohistiocytosis, has been found prevalent in Taiwan; it affects previously healthy children and is always fatal when treated only supportively. Recognition of the underlying pathogenesis for this disease prompted adoption of an immunomodulatory regimen of intravenous immunoglobulin (IVIG) and/or etoposide on 17 such patients treated between 1990 and 1993. Remarkable improvement in patients' prognoses was demonstrated. Eight patients are still alive with a median follow-up of 1 year and 2 months post-treatment. Both IVIG and etoposide had positive immunomodulation effects such as alleviation of fever and normalization of haematological and hepatic parameters. Sustained complete response was obtained in two of nine cases of EBV-associated diseases treated with IVIG only. EBV transcripts became undetectable after etoposide and/or IVIG treatment without antiviral agents. Etoposide given by split-doses schedule appeared to be superior to conventional three-consecutive-days schedule for both remission induction and disease-free survival. Our preliminary trial apparently provides a promising improvement in the treatment of this previously fatal disease. IVIG or etoposide is effective in reversing the process of lymphohistiocytic dysregulation resulting from virus infection of immune cells in this syndrome and probably helps hosts to control active virus replication in certain cases, through immunomodulation.

Successful umbilical cord blood transplantation from an unrelated donor for a patient with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

“…14,15 In practice, allogeneic SCT might be required only when recurrent disease develops, since it is possible to control EBV-HLH in a high proportion of cases without resorting to SCT. 5,16 To our knowledge, this is the first case with EBV-HLH in which CBSCT was successfully performed. As previously reported for successful CBSCT for familial hemophagocytic lymphohistiocytosis (FEL) cases, 17,18 this approach has potential for control of HLH.…”

Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment

“…Success of intravenous immunoglobulin requires treatment early in the course of MAS. 82 Although often useful for the treatment of infection-triggered MAS 83,84 and a few children with sJIA, 72,85 children with MAS as part of sJIA are often refractory to intravenous immunoglobulin. 86 A more aggressive approach using anti-thymocyte globulin has been proposed for FHLH 87 and has been used successfully in two patients with probable MAS.…”

Neonatal Tuberculosis Associated With Shock, Disseminated Intravascular Coagulation, Hemophagocytic Syndrome, and Hypercalcemia: A Case Report

“…4,5 Abughali et al 3 reported a case of congenital tuberculosis with the onset of fever at 3 days of age. The disease was not diagnosed until 2 weeks of life.…”

“…Successful treatment of IAHS usually depends on a specific treatment for the known infectious agent and adequate supportive care. Treatment with intravenous immunoglobulin has been reported to improve the outcome of virus-associated hemophagocytic syndrome, 5 but no information has been reported for the treatment of IAHS associated with tuberculosis. Our patient did not respond to treatment with intravenous immunoglobulin, and the resolution of IAHS seemed to be the result of an adequate treatment for tuberculosis.…”