Cryptococcus gattii infection complicated by immune reconstitution syndrome in a patient with common variable immunodeficiency

Cryptococcosis is a fungal disease caused by Cryptococcus sp¹. C. neoformans mainly affects immunocompromised patients, whereas C. gattii affects immunocompetent patients¹. We present the case of a 51-year-old man with common variable immunodeficiency, a hypogammaglobulinemia with reduced serum concentrations of IgG, IgA, or IgM, which led to susceptibility to infections. He was diagnosed with C. gattii infection in the central nervous system (CNS) presenting with immune reconstitution syndrome (IRIS), headache, and recurrent episodes of paresthesia and seizures. Brain magnetic resonance imaging (MRI) revealed multiple cystic lesions with peripheral gadolinium enhancement (Figure 1A and 1B). During treatment, he developed IRIS (Figure 1C), a paradoxical worsening of radiologic and clinical features, which is a relevant complication of cryptococcosis treatment commonly described in HIV-infected patients. Therefore, dexamethasone therapy (16 mg/dL) was initiated to treat the IRIS-like presentation. A repeat MRI after 20 days showed improvements.

FIGURE 1:
(A) MRI shows small peripheral lesions on FLAIR. (B) MRI shows small peripheral lesions with annular contrast enhancement on T1WI post-contrast. (C) The new MRI shows increased expansive mass effect and vasogenic edema on FLAIR. FLAIR: fluid attenuated inversion recovery. T1WI: T1-weighted image.

The radiologic and clinical deterioration following 2 weeks of treatment, despite mycological evidence of effective antifungal therapy in the CSF, had a paradoxical IRIS-like response. IRIS-like syndrome was first described in patients with HIV after initiating antiretroviral therapy and was also reported in C. gattii infections^2,3. It results from an initial Th2 cytokine response that transitions to an excessive Th1 response during therapy³. Corticosteroids are not part of the treatment for cryptococcosis; however, in this case, they may minimize CNS inflammation and reduce symptoms.

Initially, the patient recovered clinically and radiologically following amphotericin B, fluconazole, and dexamethasone therapy with no neurological deficits; however, he later died of complications during hospitalization.

ACKNOWLEDGMENTS

We offer our deepest thanks to the institutions that provided technical support for the development and implementation of this study. We thank Eduardo Cots and Lorenzo Nico Gavazza for their valuable help in conducting this case.

REFERENCES

• ¹
  Rosa Júnior M, Cots E, Biasutti C. Teaching NeuroImage: Cryptococcosis in the Central Nervous System Mimicking Neurocysticercosis. Neurology. 2022;98(12):e1302-3.
• ²
  Chen SC, Slavin MA, Heath CH, Playford EG, Byth K, Marriott D, et al. Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. Clin Infect Dis. 2012;55(6):789-98.
• ³
  Haddow LJ, Colebunders R, Meintjes G, Lawn SD, Elliott JH, Manabe YC, et al. Cryptococcal immune reconstitution inflammatory syndrome in HIV-1-infected individuals: proposed clinical case definitions. Lancet Infect Dis. 2010;10(11):791-802.

• Financial Support: None.

Publication Dates

• Publication in this collection
  16 Dec 2022
• Date of issue
  2022

History

• Received
  28 Aug 2022
• Accepted
  19 Oct 2022