The term "Immune reconstitution inflammatory syndrome" (IRIS) was originally introduced to describe the phenomenon of paradoxical clinical deterioration in HIV-infected patients despite the successful virological and immunological recovery after treatment with antiretroviral therapy. This condition has actually been described even in the central nervous system (CNS) when immunosuppressed patients experience an opportunistic infection, as a result of an aberrant response of the immune function. Since new immunosuppressant therapies for autoimmune diseases or graft rejection in transplanted patients have been established, IRIS has become much more frequent, as a consequence of sudden immunosuppressive drug removal. In Natalizumab treated multiple sclerosis (MS) patients, there is a well known risk of developing progressive multifocal encephalopathy (PML), a rare demyelinating disease of the subcortical white matter, requiring the reactivation of latent JCV reservoirs and the subsequent invasion of the CNS. PML typically presents with subacute neurological symptoms that mainly affect cognitive functions, with a progressive course sometimes leading to severe neurological deficits. When PML takes place the standard treatment is plasma exchange (PLEX) or immunoabsorption (IA). The drug removal from bloodstream restores lymphocyte trafficking into the CNS, leading to a massive infiltration into PML lesions. Evidence from literature describes in nearly all cases of Natalizumab-associated PML the occurrence of IRIS, presenting as a subacute progression and exacerbation of earlier symptoms of PML within days to a few weeks after PLEX. PML-IRIS is the consequence of an enhanced immune response to disease-specific antigens, likely leading to an overproduction of inflammatory mediators. This condition is differentiated in early or late PML-IRIS by the time course relative to PLEX/IA and contrast enhancement at the brain MRI. There is a variety of patterns of clinical presentation and evolution, ranging from asymptomatic to catastrophic. The two major factors which contribute to the severity of IRIS are the degree of immune suppression and the rapidity of immune recovery. It has become routine so far to observe that a strong reactivation of the disease, in terms of inflammatory response, is a risk after the suspension of Natalizumab therapy in MS patients. The scientific community is now trying to differentiate the classical IRIS, typically occurring in the setting of PML, from the typical MS rebounds following Natalizumab suspension. Reports of outcomes after discontinuation of therapy suggested an eventual return of disease activity to pretreatment levels in terms of the degree of inflammatory response, which eventually increases with duration of therapy interruption. In this chapter, we will focus on epidemiology, pathogenesis and treatment of IRIS with particular attention to cases following Natalizumab-associated PML.
|Title of host publication||Progressive Multifocal Leukoencephalopathy: Risk Factors, Management Strategies and Prognosis|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||21|
|ISBN (Print)||9781634829205, 9781634828895|
|Publication status||Published - Jul 1 2015|
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