scholarly journals Immune Reconstitution Inflammatory Syndrome with Recurrent Paradoxical Cerebellar HIV-Associated Progressive Multifocal Leukoencephalopathy

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 813
Author(s):  
Paola Frattaroli ◽  
Teresa A. Chueng ◽  
Obinna Abaribe ◽  
Folusakin Ayoade
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
People Living With Hiv ◽  
Rare Presentation ◽  
Diagnosis And Management ◽  
Art Initiation ◽  
Cerebellar Lesions ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML), presenting as immune reconstitution inflammatory syndrome (IRIS), is a known complication of antiretroviral therapy (ART) in people living with HIV (PLWH). Typically preceded by ART initiation, IRIS may appear simultaneously/unmasked (PML-s-IRIS) or as a delayed/worsening/paradoxical (PML-d-IRIS) presentation of known PML disease. Primary cerebellar tropism continues to be a rare presentation, and paradoxical cerebellar involvement of PML-IRIS syndrome can be a challenge for both diagnosis and management. Steroids have been suggested as a possible therapy in severe cases but the duration of steroid therapy remain elusive. Our case is that of a 34-year-old man with newly diagnosed HIV simultaneously found to have cerebellar PML. His PML lesions however worsened after initiation of ART (PML-d-IRIS) with evidence of increased intracranial pressure. Despite initial favorable response to a short duration of steroids, he had multiple recurrence of his PML lesions after steroids were discontinued. The presence of predominant cerebellar lesions and the question of how long steroids should be provided to prevent or minimize PML recurrence is the highlight of our case. This report emphasizes the need for more controlled studies to assist clinicians in the optimal diagnosis and management of PML-IRIS in PLWH.

scholarly journals Systemic Inflammation Associated with Immune Reconstitution Inflammatory Syndrome in Persons Living with HIV

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Caian L. Vinhaes ◽  
Mariana Araujo-Pereira ◽  
Rafael Tibúrcio ◽  
Juan M. Cubillos-Angulo ◽  
Fernanda O. Demitto ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Inflammatory Responses ◽  
Morbidity And Mortality ◽  
People Living With Hiv ◽  
Art Initiation ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Antiretroviral therapy (ART) has represented a major advancement in the care of people living with HIV (PLWHH), resulting in significant reductions in morbidity and mortality through immune reconstitution and attenuation of homeostatic disruption. Importantly, restoration of immune function in PLWH with opportunistic infections occasionally leads to an intense and uncontrolled cytokine storm following ART initiation known as immune reconstitution inflammatory syndrome (IRIS). IRIS occurrence is associated with the severe and rapid clinical deterioration that results in significant morbidity and mortality. Here, we detail the determinants underlying IRIS development in PLWH, compiling the available knowledge in the field to highlight details of the inflammatory responses in IRIS associated with the most commonly reported opportunistic pathogens. This review also highlights gaps in the understanding of IRIS pathogenesis and summarizes therapeutic strategies that have been used for IRIS.

scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome in seven patients with sarcoidosis: a critical discussion of treatment and prognosis

2021 ◽  
Vol 14 ◽  
pp. 175628642110355
Author(s):  
Maike F. Dohrn ◽  
Gisa Ellrichmann ◽  
Rastislav Pjontek ◽  
Carsten Lukas ◽  
Jens Panse ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Opportunistic Infections ◽  
Jc Virus ◽  
Immunosuppressive Treatment ◽  
Interleukin 2 ◽  
Cerebral Magnetic Resonance Imaging ◽  
Virus Load ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML) is a subacute brain infection by the opportunistic John Cunningham (JC) virus. Herein, we describe seven patients with PML, lymphopenia, and sarcoidosis, in three of whom PML was the first manifestation of sarcoidosis. At onset, the clinical picture comprised rapidly progressive spastic hemi- or limb pareses as well as disturbances of vision, speech, and orientation. Cerebral magnetic resonance imaging showed T2-hyperintense, confluent, mainly supratentorial lesions. Four patients developed punctate contrast enhancement as a radiological sign of an immune reconstitution inflammatory syndrome (IRIS), three of them having a fatal course. In the cerebrospinal fluid, the initial JC virus load (8–25,787 copies/ml) did not correlate with interindividual severity; however, virus load corresponded to clinical dynamics. Brain biopsies ( n = 2), performed 2 months after symptom onset, showed spotted demyelination and microglial activation. All patients had lymphopenia in the range of 270–1150/µl. To control JC virus, three patients received a combination of mirtazapine and mefloquine, another two patients additionally took cidofovir. One patient was treated with cidofovir only, and one patient had a combined regimen with mirtazapine, mefloquine, cidofovir, intravenous interleukin 2, and JC capsid vaccination. To treat sarcoidosis, the four previously untreated patients received prednisolone. Three patients had taken immunosuppressants prior to PML onset, which were subsequently stopped as a potential accelerator of opportunistic infections. After 6–54 months of follow up, three patients reached an incomplete recovery, one patient progressed, but survived so far, and two patients died. One further patient was additionally diagnosed with lung cancer, which he died from after 24 months. We conclude that the combination of PML and sarcoidosis is a diagnostic and therapeutic challenge. PML can occur as the first sign of sarcoidosis without preceding immunosuppressive treatment. The development of IRIS might be an indicator of poor outcome.

scholarly journals Cardiovascular Biomarker Profile on Antiretroviral Therapy Is Not Influenced by History of an IRIS Event in People With HIV and Suppressed Viremia

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Aurelie Gouel-Cheron ◽  
Martha Nason ◽  
Adam Rupert ◽  
Virginia Sheikh ◽  
Greg Robby ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Antiretroviral Therapy ◽  
Chronic Inflammation ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Art Initiation ◽  
History Of ◽  
Cardiovascular Biomarker ◽  
Inflammatory Syndrome

Abstract Immune reconstitution inflammatory syndrome (IRIS) is characterized by release of proinflammatory cytokines and tissue inflammation occurring early after antiretroviral therapy (ART) initiation. The role of previous IRIS events in persistent chronic inflammation in people with HIV is currently unclear. In this retrospective analysis of 143 participants who maintained suppression of HIV viremia, we compared biomarkers related to inflammation, coagulation, and cardiovascular risk after 3 years on ART in participants with and without a history of IRIS. There was no evidence of higher levels of persistent chronic inflammation in people with HIV who had a history of an IRIS event. ClinicalTrials.gov Identifier . NCT00286767.

Progressive Multifocal Leukoencephalopathy Syndrome and Immune Reconstitution Inflammatory Syndrome

2013 ◽  
Author(s):  
Aaron E. Miller ◽  
Teresa M. DeAngelis
Keyword(s):  
Monoclonal Antibody ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Jc Virus ◽  
Radiographic Findings ◽  
Life Threatening ◽  
The Central Nervous System ◽  
Immunosuppressant Medications ◽  
Inflammatory Syndrome

Progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system caused by the JC virus, typically manifests in severely immunocompromised conditions, ranging from HIV/AIDS to lymphoproliferative malignancies to the consequence of immunosuppressant medications such as natalizumab, a monoclonal antibody approved for the treatment of relapsing forms of MS. In this chapter, we discuss the typical symptomatology and radiographic findings of PML and how to distinguish it from those of MS. In addition, we review the management of PML in natalizumab-treated MS patients as well as the features of immune reconstitution inflammatory syndrome (IRIS), the potentially life-threatening consequence of natalizumab withdrawal in patients with PML.

scholarly journals Clinical and immunologic predictors of Mycobacterium avium complex immune reconstitution inflammatory syndrome in a contemporary cohort of patients with HIV

2020 ◽  
Author(s):  
Kimberly F Breglio ◽  
Caian L Vinhaes ◽  
María B Arriaga ◽  
Martha Nason ◽  
Gregg Roby ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
T Cell Activation ◽  
Mycobacterium Avium ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Mycobacterium Avium Complex ◽  
Subsequent Development ◽  
Art Initiation ◽  
Increased Risk ◽  
Inflammatory Syndrome

Abstract Background Patients with HIV (PWH) can present with new or worsening symptoms associated with Mycobacterium avium complex (MAC) infection shortly after antiretroviral therapy (ART) initiation as MAC immune reconstitution inflammatory syndrome (MAC-IRIS). In this study, we assessed the utility of several laboratory tests as predictors of MAC-IRIS. Methods PWH with clinical and histologic and/or microbiologic evidence of MAC-IRIS were identified and followed up to 96 weeks post-ART initiation within a prospective study of 206 ART-naïve patients with CD4 <100 cells/µL. Results Fifteen (7.3%) patients presented with MAC-IRIS within a median interval of 26 days after ART initiation. Patients who developed MAC-IRIS had lower BMI, lower hemoglobin levels, a higher alkaline phosphatase and increased CD38 frequency and MFI on CD8 + T-cells, at the time of ART initiation compared to non-MAC IRIS patients. A decision tree inference model revealed that stratifying patients based on levels of alkaline phosphatase and D-dimer could predict the likelihood of MAC-IRIS. A binary logistic regression demonstrated that higher levels of alkaline phosphatase at baseline were associated with increased risk of MAC-IRIS development. Conclusions High alkaline phosphatase levels and increased CD8 + T-cell activation with low CD4 counts at ART initiation should warrant suspicion for subsequent development of MAC-IRIS.

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