Evidence map›Paper›PMID 37814084›Full record

ArticleJournal of clinical immunology2023

Tocilizumab as a Potential Adjunctive Therapy to Corticosteroids in Cryptococcal Post-infectious Inflammatory Response Syndrome (PIIRS): a Report of Two Cases.

Jessica C Hargarten, Seher H Anjum, Kenneth Ssebambulidde, Yoon-Dong Park, Malcolm J Vaughan, Terri L Scott, Dima A Hammoud, Bridgette Jeanne Billioux, Peter R Williamson

Abstract readCase Reports
PubMed Publisher
In one paragraph

Article in Journal of clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. The International Immunotherapy Society for Fungal Diseases.Antimicrobial agents and chemotherapy · 2026
    Article
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  4. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Jessica C HargartenLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.ORCID 0000-0001-8724-9463
Seher H AnjumLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.
Kenneth SsebambuliddeLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.ORCID 0000-0002-8125-0698
Yoon-Dong ParkLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.ORCID 0000-0001-8649-7692
Malcolm J VaughanLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.ORCID 0009-0006-0645-6510
Terri L ScottLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA.ORCID 0009-0006-4578-6088
Dima A HammoudCenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-7406-7871
Bridgette Jeanne BilliouxSection of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-4208-7100
Peter R WilliamsonLaboratory of Clinical Immunology and Microbiology (LCIM), Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bldg 10, Rm 11C208, Bethesda, MD, 20892, USA. williamsonpr@mail.nih.gov.ORCID 0000-0002-7953-2178
National Institutes of Health · USNational Institutes of Health Clinical Center · US

Funding

Molecular Pathobiology of Cryptococcus neoformansZIAAI001123 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI WILLIAMSON, PETER · 2010 to 2025
$10.4M
Prospective Cohort Study of CryptococcosisU01AI109657 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARR, KIEREN A., WILLIAMSON, PETER RICHARD · 2013 to 2015
$1.9M
Division of Intramural Research, National Institute of Allergy and Infectious Diseases AI001123Division of Intramural Research, National Institute of Allergy and Infectious Diseases AI001124NIAID NIH HHS U01 AI109657
6 · The paper itself

Abstract

purposeNon-HIV cryptococcal meningoencephalitis (CM) in previously healthy individuals is often complicated by a post-infectious inflammatory response syndrome (c-PIIRS) characterized by neurologic deterioration after appropriate antifungal therapy with sterilization of CSF fungal cultures. c-PIIRS results from an excessive inflammatory response to fungal antigens released during fungal lysis, mediated by IFN-γ, IL-6, and activated T-helper cells, leading to immune-mediated host damage that responds to pulse-corticosteroid taper therapy (PCT). Typically, oral steroids may take up to a year to taper, and occasionally, patients will be refractory to steroid therapy or may demonstrate high-risk lesions such as those involving intracranial arteries. Also, patients can have problematic side effects from prolonged corticosteroids. Hence, appropriate adjunctive agents are needed to reduce corticosteroid doses in the treatment of c-PIIRS. Due to a possible role of IL-6 in pathogenesis, IL-6 receptor blockade by tocilizumab may be useful in the treatment of c-PIIRS.

methodsTwo previously healthy patients with non-HIV cPIIRS were seen at the NIH. Due to concerns for intracranial vascular rupture in an area of inflammation (Patient 1) and intractable symptoms on high-dose oral corticosteroids (Patient 2) with evidence of persistent CSF inflammation, patients were treated with 4-8 mg/kg tocilizumab every 2 weeks while maintained on a constant dose of prednisone.

resultsTwo patients exhibited rapid immunological improvement following treatment with tocilizumab. Patient 1 remained vascularly stable, and Patient 2 had near resolution of headaches with improvement in mental status as evidenced by improved MOCA score. The two had improved CSF inflammatory parameters and no significant side effects. Both CSF cultures remained negative throughout treatment.

conclusionsTocilizumab may be a safe adjunctive treatment for CM-related PIIRS suggesting further study.

Indexed as

CryptococcusMeningitis, CryptococcalMeningoencephalitisAdrenal Cortex HormonesAntibodies, Monoclonal, HumanizedHumansInflammationInterleukin-6Adrenal Cortex HormonesAntibodies, Monoclonal, HumanizedInterleukin-6tocilizumabcorticosteroidsCryptococcal meningoencephalitis (CM)post-infectious inflammatory response syndrome (c-PIIRS)previously healthytocilizumab

Identifiers

PMID37814084
OpenAlexW4387445075

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.