Case Presentation: A 33-year-old Kenyan male school teacher presented to the hospital with a 3-day history of a gradually worsening diffuse headache, nausea and vomiting, and fevers. His past medical history was notable for liver cirrhosis of unknown etiology (Child-Pugh class B), complicated by portal hypertension. He had no known history of tuberculosis. His vital signs on admission included a temperature of 102.2°F, BP 110/76, HR 115, RR 22, and normal oxygen saturation. On general examination, the patient was restless and appeared unwell. On neurological examination, he had nuchal rigidity, a positive Kernig’s sign, and confusion. Cardiac and respiratory examinations were normal except for tachycardia and tachypnea. A CT head was normal. Cerebrospinal fluid (CSF) studies showed a total WBC of 3/uL erythrocytes 5/uL, total protein 115.3 mg/dL (high), glucose 0.04 mmol/L (low). CSF India ink was positive, CSF cryptococcus antigen positive, and CSF PCR was positive for mycobacteria tuberculosis. CSF culture grew Cryptococcus spp (neoformans/gatti). CBC revealed WBC of 3.2 10^9/L, hemoglobin 12.0 g/dL, and platelets 52 10^9/L. The metabolic panel was normal. Liver function tests revealed normal AST, normal ALT, elevated total bilirubin 3.33 mg/dL, elevated direct bilirubin 2.04 mg/dL, total protein 6.4 g/dL, albumin 5 g/dL. The coagulation panel revealed INR 2 and APTT 54 secs. ANA was 1:80, Anti-dsDNA antibodies were negative. HIV serology (combination immunoassay) was negative on admission. The patient was diagnosed with cryptococcal and tuberculous meningitis and was started on amphotericin B, fluconazole, dexamethasone, rifampin, isoniazid, pyrazinamide, and ethambutol and underwent a therapeutic lumbar puncture. The patient’s course was complicated by meningitis-induced sensorineural hearing loss, drug-induced liver injury, and death on hospitalization day thirty-four due to hemorrhagic shock from bleeding esophageal varices.
Discussion: Concurrent cryptococcal meningitis (CM) and tuberculosis meningitis (TBM) is a rare co-infection that may arise in immunocompromised patients. In a study of HIV-infected patients in Uganda, Ellis et al. (2018) found that concurrent TBM co-infections were prevalent in 0.8% of 586 cryptococcal meningitis patients, and the in-hospital mortality of this population was 60%. Our patient was immunocompromised due to liver cirrhosis, which imparted a high risk of hepatotoxicity from concurrent anti-tuberculosis drugs and fluconazole. Cirrhosis has been associated with an increased risk of developing extra-pulmonary cryptococcosis; the greatest risk was in Child-Pugh class C. To our knowledge, this is the first case report of concurrent TBM and CM in a cirrhotic patient. There can be marked overlap in the clinical presentation and the CSF profiles of CM and TBM, which can mask the diagnosis of concurrent infection. Further research is needed regarding the use of adjunctive corticosteroids in this co-infection in different patient populations. Guidelines recommend the use of steroids in the treatment of TBM, but there is evidence of more adverse events and disability with the use of adjuvant dexamethasone in the treatment of CM in the HIV- infected population.
Conclusions: Concurrent cryptococcal meningitis and tuberculosis meningitis must be considered as a cause of meningitis in immunocompromised patients, including those with cirrhosis. Further research is needed on the benefit of steroids in non-HIV populations with concurrent TBM/CM infection.