An Atypical Case of Chronic Cryptococcal Meningoencephalitis in a Patient with Subclinical Sarcoidosis

Background: CNS cryptococcosis is classically seen in immunocompromised patients and is often rapid in onset. Sarcoidosis can manifest variably and signify immune dysfunction. We present a case of cryptococcal meningoencephalitis in a patient with a history of dormant sarcoidosis. Case presentation: A 66 year-old woman began experiencing headaches, generalized weakness, and ambulatory dysfunction over a period of months. Her medical history was notable for distant ductal carcinoma in situ (DCIS) and pulmonary sarcoidosis. Her sarcoidosis was diagnosed at least one decade prior, considered inactive, and the patient was not taking medications. She was HIV-negative and not otherwise immunocompromised. CT head showed calvarial lesions, and MRI demonstrated communicating hydrocephalus and vertebral, iliac and calvarial osteolytic lesions. Malignancy was ruled out through biopsy of iliac and vertebral lesions and negative CSF cytology. The patient continued to deteriorate, with worsening headaches and ambulation, mild confusion, and weight loss. Two years after initial symptoms, she was hospitalized with disorientation, paucity of speech, and an inability to stand. MRI brain revealed worsened hydrocephalus with transependymal flow, areas of cortical edema, and leptomeningeal and subependymal enhancement. Due to concern for neurosarcoidosis, lumbar puncture was initially deferred due to risk of herniation and the patient was given high-dose IV steroids. However, she continued to worsen and ultimately required a ventriculoperitoneal shunt. CSF from the shunt revealed a positive Cryptococcal antigen (1:4) and she was started on anti-fungal therapy. Subsequent lumbar puncture yielded CSF with a Cryptococcal antigen (1:512), lymphocytic pleocytosis, and an elevated protein level. Unfortunately, the patient continued to worsen and eventually passed away from presumed CNS cryptococcosis. Discussion: This case describes chronic cryptococcal meningoencephalitis in the background of inactive sarcoidosis and absence of other immunocompromise. The immune paradox of sarcoidosis refers to excessive inflammation found at granulomatous lesions coupled with development of peripheral T lymphocyte anergy. Given that immunity against cryptococcal infection is primarily T lymphocyte-mediated, this immune paradox may account for our patient's development of disseminated cryptococcosis (evidenced by her numerous bone lesions) and ultimately fatal CNS cryptococcosis. Conclusion: Awareness of the association between sarcoidosis, active or inactive, and CNS cryptococcosis is essential for early diagnosis and potentially adequate treatment of the infection. CNS cryptococcosis may manifest subacutely or chronically, rather than fulminantly. This should not deter the clinician from considering the diagnosis, as prompt treatment is imperative for improved outcomes.