The development of cryptococcal infection in the setting of sarcoidosis is a rarely described phenomenon. Even more uncommon is the development of cryptococcal meningoencephalitis in a patient who has a distant history of sarcoidosis and is otherwise immunocompetent.

A 66 year-old woman presented with acute worsening of headaches, generalized weakness, and ambulatory dysfunction which had been slowly progressing over ~one year. She had a distant history of sarcoidosis from fifteen years prior, and was not on any immunosuppression at the time of presentation. She had no significant travel history and was HIV-negative. Workup in the months prior to admission revealed communicating hydrocephalus and multifocal osteolytic lesions, and there was concern for underlying malignancy.

Brain MRI at the time of hospitalization revealed transependymal flow, areas of suspected cortical edema, and leptomeningeal and subependymal enhancement. Other workup was negative for malignancy. The patient was initiated on steroids due to suspicion for neurosarcoidosis given her past history. However she continued to worsen and her hydrocephalus required shunting. Lumbar puncture had initially been deferred due to family preference, however was ultimately performed. CSF revealed elevated protein, a lymphocytic pleocytosis, and a cryptococcal antigen titer of 1:512. She was initiated on antifungal therapy, but unfortunately had a poor outcome.

This case demonstrates an atypical presentation of cryptococcal infection in the setting of a history of sarcoidosis but no active immunocompromise. CNS cryptococcal infection is often thought of as fulminant and rapid in onset, and vulnerable patients often have HIV/AIDS or another clear cause of immunosuppression. Our patient’s disease course may be explained by the “immune paradox” of sarcoidosis, where T-cell anergy resulting from excessive inflammation at the granulomatous lesions, even years after clinical symptoms, leads to a state of immune dysfunction. This immune dysfunction renders the patient aberrantly susceptible to indolent infections.