Page 21 - Delaware Medical Journal - September 2017
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CASE REPORT
Two lumbar punctures alleviated symptoms, but the headaches returned and the patient was readmitted to the hospital four
months after his initial presentation. Of note, the patient remained on hydroxychloroquine, but his prednisone had been weaned to 12.5mg daily, and methotrexate had been stopped. Upon admission, an MRI of the brain was completed and showed new evidence
of enhancement in the supratentorial regions consistent with meningitis, with similar enhancement noted in the basal ganglia and thalami. A repeat lumbar puncture showed the following: opening pressure of 44 cm H20, 126 WBC, 12 RBC, 132 mg/
dl protein and 28 mg/dL glucose, cryptococcal antigen 1:512.
A fungal culture returned negative. The patient received serial lumbar punctures, and yet the patient’s CSF pressures remained persistently elevated. On hospital day 12, he developed new onset grand mal seizures. The patient was restarted on induction therapy shunt was placed. His headache initially improved with the shunt placement. However, beginning on day 20, he developed fevers, vomiting and altered mental status. Repeat CSF sampling during this time showed the following: 21 WBC (12 percent neutrophils and 68 percent lymphocytes), 1 RBC, 180 mg/dl protein, and 42 mg/dL glucose. Bacterial culture and fungal culture were negative. Repeat MRI showed multiple changes when compared to admission MRI (Figure 1), including interval increased enhancement
of the leptomeninges supratentorially and infratentorially,
new enhancement of the pachymeninges supratentorially, and basal ganglia. Due to concern for IRIS, the patient was started on IV dexamethasone. Within 72 hours, his mental status cleared to complete lucidity, with resolution of vomiting and fever. He was slow oral prednisone taper.
DISCUSSION
The HIV/AIDS epidemic brought to light many different opportunistic infections, including cryptococcal meningitis. Thankfully, the all-too common complicated cryptococcal infection from the 1990s is not as common now. A review of the incidence of hospitalization due to cryptococcal disease within the HIV-infected population during the 13-year period from 1997 to 2009 showed a decline of 53.6 percent by 2009.1 However, the same research also showed a minimal decline in in the HIV-uninfected population for those hospitalized with cryptococcal disease.
There is limited data on prognosis of cryptococcal IRIS in the HIV negative population, though studies from the HIV positive population suggest a high degree of morbidity and mortality. In those with HIV, cryptococcal meningitis related IRIS (CM-IRIS)
has 33-57 percent mortality, and delaying the initiation of highly active antiretroviral therapy (HAART) is recommended to reduce the risk of mortality.2
In CM-IRIS, the morbidity and mortality often comes from
that leads to increasing intracranial pressure (ICP). Complications from increased ICP range from visual and hearing loss, which could be permanent, up to brain herniation and death.3 Managing reaction that must be treated.
CM-IRIS is a syndrome that is a result of an unbalanced immune response to microorganisms and their antigens. It is hypothesized role of Th17, other regulatory T cells, and cytokines is also being studied.3-5 This dysregulation of the normal immune system leads 3 systems, resulting in various clinical manifestations depending on manifestations occur within the closed space of the CNS.
The shifting balance to a pathologic immune response can
be impacted by numerous factors. This phenomenon is well- known in those with HIV who start antiretroviral treatment, and have restoration of a functioning immune system. As immunosuppressive medications are more widely used, it is important to consider immune reconstitution when their use is stopped, which then permits a robust immune response.
As a clinical diagnosis and one of exclusion, the diagnosis of CM-IRIS can be challenging. It must be differentiated from
a relapse of meningitis with negative or sterile CSF cultures. Evolving diagnostic criteria for IRIS include the following:
1) initial improvement on appropriate antifungal therapy; 2)
new or worsening symptoms developing after antimicrobial treatment initiation that cannot be explained by a new diagnosis;
3) all other infectious workup is negative; and antigen titers are stable or decreased.3,6 Presenting symptoms of CM-IRIS may include headache, fever, malaise, altered mental status, cranial nerve palsies.7 MHC genotypes are being evaluated.2,7,8
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