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

Post-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull’s rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44hiCD62loCD4+effector CD4+T-cells and MHC II+inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR+CD4+and CD8+cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK/STAT in PIIRS as well as further study of JAK/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.

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A Case Report of Cryptococcal Meningitis Presenting with Psychiatric Abnormalities

Wo,

Zhu,

Jiang

et al. 2024

Jundishapur J Microbiol

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Introduction: Cryptococcal infection is a significant pathogen causing meningitis, often manifesting early with psychiatric abnormalities. Due to the lack of other specific symptoms, these behavioral changes are frequently misattributed to other mental disorders or overlooked, leading to delays in diagnosis. This article reports on the diagnosis and treatment process of a patient with cryptococcal meningitis and summarizes the abnormal behavior in terms of mental and behavioral aspects of cryptococcal meningitis patients, providing a reference for the diagnosis and treatment of cryptococcal meningitis. Case Presentation: We present a case of cryptococcal meningitis where the initial abnormal behaviors were attributed to stress, resulting in a lack of emphasis on cryptococcal treatment and subsequent failure of standard anti-infective therapy. Ultimately, we discovered abnormalities through cerebrospinal fluid examination and conducted targeted tests for Cryptococcus, resulting in a clear diagnosis and timely adoption of appropriate treatment measures. The patient's condition improved, and they were discharged. Conclusions: It is crucial for clinicians to deepen their understanding of cryptococcal meningitis. When encountering patients with unexplained fever accompanied by psychiatric and behavioral changes, a high suspicion for cryptococcal infection should be maintained.

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

Cited by 3 publications

References 30 publications

Cryptococcal Disease in Diverse Hosts

Cryptococcal Disease in Diverse Hosts

JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome

A Case Report of Cryptococcal Meningitis Presenting with Psychiatric Abnormalities

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