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Tocilizumab as a Potential Adjunctive Therapy to Corticosteroids in Cryptococcal Post-infectious Inflammatory
Jessica C Hargarten1, Seher H Anjum1, Kenneth Ssebambulidde1
1Laboratory 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.
Purpose:
Non-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.
Methods:
Two 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.
Results:
Two 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.
Conclusions:
Tocilizumab may be a safe adjunctive treatment for CM-related PIIRS suggesting further study.
Insights
Tocilizumab shows promise as an adjunctive therapy for cryptococcal meningoencephalitis-related post-infectious inflammatory response syndrome (c-PIIRS). This treatment may reduce corticosteroid dependence and improve patient outcomes in previously healthy individuals.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Pharmacology
Background:
- Non-HIV cryptococcal meningoencephalitis (CM) can lead to a severe inflammatory complication, cryptococcal-PIIRS, marked by neurological decline despite antifungal treatment.
- This syndrome arises from an overactive immune response to fungal antigens, causing host damage and often requiring prolonged corticosteroid therapy.
- Current treatments face challenges, including lengthy steroid tapers, refractory cases, and significant side effects, necessitating novel adjunctive therapies.
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