A Case of Immune Reconstitution Inflammatory Syndrome in AIDS-related Progressive Multifocal Leukoencephalopathy after Antiretroviral Therapy

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.

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

Pathogens ◽

10.3390/pathogens10070813 ◽

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.

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Immune reconstitution inflammatory syndrome in a patient treated with natalizumab presenting progressive multifocal leukoencephalopathy

Diagnostic and Interventional Imaging ◽

10.1016/j.diii.2012.10.004 ◽

2013 ◽

Vol 94 (1) ◽

pp. 101-103 ◽

Cited By ~ 2

Author(s):

D. Métivier ◽

F.-X. Arnaud ◽

F. Dutasta ◽

B. Nguema ◽

C. Teriitehau ◽

...

Keyword(s):

Progressive Multifocal Leukoencephalopathy ◽

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

Inflammatory Syndrome

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Immune Reconstitution Inflammatory Syndrome

Advances in Dental Research ◽

10.1177/0022034511399915 ◽

2011 ◽

Vol 23 (1) ◽

pp. 90-96 ◽

Cited By ~ 11

Author(s):

A.R. Tappuni

Keyword(s):

Antiretroviral Therapy ◽

Immune Reconstitution Inflammatory Syndrome ◽

Immune Reconstitution ◽

T Regulatory Cells ◽

Clinical Presentation ◽

Early Recognition ◽

Clinical Intervention ◽

Suppressor Cell ◽

Life Threatening ◽

Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon observed in patients recovering from immunodeficiency. The clinical presentation of IRIS involves the unmasking of covert infections or the worsening of overt conditions. Several causes and pathways have been suggested, most recognizing an inflammatory flare component occurring in the context of rapid immune reconstitution. In HIV-infected patients, IRIS inadvertently occurs as the consequence of successful antiretroviral therapy, and it is affiliated with improvement of the immune function, complicating the course of the disease and presenting treatment challenges to clinicians. The pathogenesis of IRIS is poorly understood, but in recovering HIV patients, its initiation and progression seem to be primarily linked to an increase in CD4+ T-helper and CD8+ T-suppressor cell count and a reduction in T-regulatory cells, all endorsed by exaggerated cytokine release and activity. The clinical presentation of IRIS is usually atypical. The manifestations depend on the trigger antigen, which can be an infective agent (viable or nonviable), a host antigen, or a tumor antigen. Most IRIS cases are self-limiting, but a few cases can be overwhelming and life-threatening; hence, early recognition is important. In most cases, there is no need to discontinue the antiretroviral therapy, although in the more severe cases, other clinical intervention may be necessary.

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Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652012000400009 ◽

2012 ◽

Vol 54 (4) ◽

pp. 231-233 ◽

Cited By ~ 3

Author(s):

Walter de Araujo Eyer-Silva ◽

Maria Cecília da Fonseca Salgado ◽

Jorge Francisco da Cunha Pinto ◽

Fernando Raphael de Almeida Ferry ◽

Rogério Neves-Motta ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Immune Reconstitution Inflammatory Syndrome ◽

Highly Active Antiretroviral Therapy ◽

Immune Reconstitution ◽

Gouty Arthritis ◽

Infected Male ◽

Acute Gouty Arthritis ◽

Highly Active ◽

History Of ◽

Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

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