Discussion
Cryptococcosis by C.neoformans, can be considered as a life-threatening condition in HIV-positive patients. There has an increase in the incidence of cryptococcal meningitis but its prevalence is reducing (7). The most common route of entry for cryptococcus in immunocompromised patients is through inhalation of spores or desiccated yeast cells (8). In patients with immunosuppression, cryptococcus can start causing symptoms and acute respiratory distress syndrome can rapidly appear as a consequence. After infecting the lungs, these fungi can spread hematogenously and reach the CNS (9). Available data propose that currently there are two mechanisms by which cryptoccocus can enter the CNS. One is to migrate directly through endothelium by transcytosis and other one is being carried inside macrophages. Their polysaccharide capsule has anti-phagocytic propreties (10). There can be several signs and symptoms for CNS involvement, however the rate of patients who develop them is low. These manifestations involve headache, nausea, fever, memory loss, altered level of consciousness, confusion, seizures, and hearing impairment (1). Cryptoccocal pneumonia manifests as fever, productive cough, and chest pain and it can radiologically mimic lung cancer or metastasis, lung tuberculosis, and bacterial pneumonia. It can also be asymptomatic and diagnosed coincidentally (11). The radiological findings in immunocompromised patients may include cavitation, lobar opacities, nodules, pleural effusion, and lymphadenopathy (12).
Patients who are positive for HIV infection specially with low CD4 cell count and with subacute or chronic headache should be considered as candidates for lumbar puncture to investigate cryptococcal meningoencephalitis. In addition to CSF cell count, CSF culture, and india ink, we can assess CrAg in CSF. We can also detect CrAg in serum. We can also use blood culture, chest X ray, head CT scan, and MRI (13). Lateral flow assay (LFA) with a sensitivity of more than 95% and a specificity of 100% is a new laboratory tool being used for detecting cryptococcal antigen (1).
The initial therapy should contain antifungal drugs. A two-week therapy with amphotericin B at 3 mg/kg/day and flucytosine at 100 mg/kg/day as induction phase. Afterwards, therapy should be continued with fluconazole for eight to 12 months as consolidation phase (12). Studies suggested that a combination of amphotericin B with flucytosine can have a better fungicidal effect with lower risk of failure in treatment rather than a combination of amphotericin B with fluconazole (14).
A better clinical outcome for patients with meningoencephalitis is related to the choice of initial therapy and handling raised intracranial pressure. An elevated opening pressure of more than 25 cm of CSF requires serial lumbar punctures to reduce the pressure to less than 20 cm of CSF (15).
As we can see in presented case ART should be delayed at least 2 weeks after the start of antifungal therapy, due to the occurrence of immune reconstitution inflammatory syndrome (IRIS) resulting in worsening symptoms and sometimes death as happened in our patient.