May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?

Abstract

BackgroundArthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins.DiscussionTo our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels.SummaryAnalogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible.

Unusual presentation of Epstein–Barr virus encephalitis in an older patient with a dramatic clinical response to intravenous immunoglobulin

“…IVIg has been reported to treat successfully encephalitides of other viral aetiologies. 5 Our patient displayed delayed EBV seroconversion. It is possible the IVIg could have resulted in a positive IgG titre.…”

“…4 Urine creatinine excretion has been shown to be decreased in those requiring longer hospital stay suggesting the presence of decreased creatinine production. 5 We hypothesise that creatinine generation decreases post-cardiac arrest. The pCrdecrease group can then be explained by clearance with near-normal glomerular filtration rate (GFR).…”

Clinical Outcomes of Japanese Encephalitis after Combination Treatment of Immunoglobulin, Ribavirin, and Interferon-α2b

“…Even though the mechanisms by which JEV causes encephalitis are not completely understood, possible models of the immune response to viral infection have been suggested for the damage caused to the CNS and for the disease progression. 11 The best known effects of immunoglobulin are immunomodulation in general via blocking the Fc receptors of macrophages and complement activation, reducing inflammatory cytokines, and suppressing T-cell responses, and it has been applied to several inflammatory autoimmune diseases and infectious conditions. 11 Several factors including antibody replacement, enhanced neutralization, and an augmented opsonocytophagic function have been suggested to contribute to the antimicrobial efficacy of immunoglobulin.…”

Two Cases of Severe Tick-Borne Encephalitis in Rituximab-Treated Patients in Germany: Implications for Diagnosis and Prevention

“…There is currently no specific antiviral treatment for TBE. However, the early administration of high-dose IVIG has been considered [ 12 ]. Particularly, in cases of significant viral replication in the CNS and concomitant absence of endogenous TBEV antibodies, passively transferred neutralizing antibodies may improve the outcome.…”

“…Particularly, in cases of significant viral replication in the CNS and concomitant absence of endogenous TBEV antibodies, passively transferred neutralizing antibodies may improve the outcome. However, therapeutic administration of IVIG requires a risk-benefit analysis as antibody-dependent enhancement of infection has been suspected in children after postexposure prophylaxis with TBEV-specific hyperimmune serum [ 12 ]. High-dose IVIG has been used in RTX-treated patients with West Nile Virus infection, another neurotropic flavivirus, but did not show a clear clinical benefit [ 13 ].…”