Central nervous system–immune reconstitution inflammatory syndrome in resource-limited settings

Mateen, Farrah J.; Nath, Avindra

doi:10.1097/qad.0b013e3283574e1a

Cited by 8 publications

(13 citation statements)

References 25 publications

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“…The differences in the incidence of cryptococcal IRIS reported across different studies probably reflect the typology of the study (retrospective versus prospective), different clinical definitions employed, and different settings (resource-limited countries versus high-income countries). However, what is undoubted is the fact that cryptococcal IRIS is a true problem with an high expected burden especially in sub-Saharan Africa, Southeast Asia and Latin America [143]. The pathogenesis of cryptococcal IRIS is complex and not fully understood but is mainly attributable to the severe immunodeficiency that is unable to clear the foreign antigens and the subsequent cytokine storm induced by the restored inflammatory response [144].…”

Section: Cryptococcal Immune Reconstitution Inflammatory Syndromementioning

confidence: 99%

New Insights into HIV/AIDS-Associated Cryptococcosis

Antinori

2013

ISRN AIDS

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Cryptococcal meningitis is a life-threatening opportunistic fungal infection in both HIV-infected and HIV-uninfected patients. According to the most recent taxonomy, the responsible fungus is classified into a complex that contains two species (Cryptococcus neoformans and C. gattii), with eight major molecular types. HIV infection is recognized worldwide as the main underlying disease responsible for the development of cryptococcal meningitis (accounting for 80–90% of cases). In several areas of sub-Saharan Africa with the highest HIV prevalence despite the recent expansion of antiretroviral (ARV) therapy programme, cryptococcal meningitis is the leading cause of community-acquired meningitis with a high mortality burden. Although cryptococcal meningitis should be considered a neglected disease, a large body of knowledge has been developed by several studies performed in recent years. This paper will focus especially on new clinical aspects such as immune reconstitution inflammatory syndrome, advances on management, and strategies for the prevention of clinical disease.

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Section: Cryptococcal Immune Reconstitution Inflammatory Syndromementioning

confidence: 99%

New Insights into HIV/AIDS-Associated Cryptococcosis

Antinori

2013

ISRN AIDS

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“…CNS-IRIS stands of high clinical relevance mainly because it contributes to the bulk of IRIS mortality [21] and its prevalence is most probably underestimated since diagnosis is hampered by the heterogeneous manifestations, CNS poor access to clinical investigation, absence of specific biomarkers and the need to exclude other conditions. CNS-IRIS diagnosis is presently based on a multi-parametrical assessment, including: 1) high pathogen load; 2) positive response to HAART with evidence of controlled HIV replication; 3) short temporal gap between HAART onset and disease worsening (usually up to 3 months); 4) inflammatory reaction associated with the worsening of previous lesions or the appearance of new lesions; 5) exclusion of differential diagnosis and; 6) clinical and radiological improvement without specific empiric therapies.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

et al. 2017

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BackgroundHIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed.Case presentationA 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+ T cells and higher percentage of activated CD4+ T cells at HAART initiation. The percentage of memory CD4+ T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+ T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset.ConclusionAlthough both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2159-x) contains supplementary material, which is available to authorized users.

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“…IRIS is a particularly salient topic in developing world settings since HIV disease may be treated late, and opportunistic infections more often precipitate the initiation of HIV therapy. 8 …”

Section: Immune Reconstitution Inflammatory Syndrome (Iris)mentioning

confidence: 99%

Neurological immune reconstitution inflammatory response

Clifford

2015

Current Opinion in Neurology

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Purpose of review This manuscript reviews current reports about clinical aspects of immune reconstitution inflammatory responses (IRIS), with particular emphasis on IRIS in the setting of progressive multifocal leukoencephalopathy (PML) and to a lesser extent on cryptococcal meningitis (CM) and human immunodeficiency virus (HIV). Recent findings PML prognosis has been radically improved as it has become possible to provide immune reconstitution, while some remaining morbidity and mortality results from excess inflammation. Similar pathologic responses are seen less often, but remain clinically important in CM, and HIV. Early diagnosis and active management of PML results in optimal outcomes with survival of 75% or higher in multiple recent series. These finding apply both to natalizumab and HIV associated PML. CM is frequently complicated by IRIS, and early treatment with antifungal therapy preceding HIV therapy provides optimal outcomes. HIV IRIS is reduced by early therapy which is now recommended, but even on therapy, chronic dysregulated immune responses may play important roles in ongoing HAND which is common, as well as rare but more dramatic subacute encephalopathies. Summary The clinician must actively monitor and treat both OI and the inflammatory response that is essential to recovery but may itself augment pathology and injury.

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Central nervous system–immune reconstitution inflammatory syndrome in resource-limited settings

Cited by 8 publications

References 25 publications

New Insights into HIV/AIDS-Associated Cryptococcosis

New Insights into HIV/AIDS-Associated Cryptococcosis

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Neurological immune reconstitution inflammatory response

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