Hyponatremia as a "red flag" for concurrent meningitis in pulmonary cryptococcosis: a risk stratification model

BACKGROUND: Pulmonary cryptococcosis (PC) is increasingly diagnosed in human immunodeficiency virus (HIV)-negative and apparently immunocompetent individuals. A critical complication of PC is dissemination to the central nervous system (CNS), leading to concurrent cryptococcal meningitis (CM). Identifying CNS involvement remains a clinical challenge due to insidious presentations and non-specific radiological findings. This study aimed to identify independent clinical and laboratory predictors of concurrent CM in patients presenting with PC. METHODS: We conducted a retrospective study of patients diagnosed with PC at a tertiary referral center. Patients were stratified into two groups based on the presence or absence of concurrent CM. Demographic data, clinical symptoms, laboratory parameters, and chest computed tomography (CT) findings were analyzed. Multivariable logistic regression was performed to identify independent risk factors, and a predictive model was constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 77 patients were included, of whom 23 (29.9%) were diagnosed with concurrent CM. In the multivariable analysis, neurological symptoms (adjusted odds ratio [aOR]: 24.69; 95% confidence interval [CI]: 3.66-166.57; P < 0.001) and hyponatremia (serum sodium < 135 mmol/L; aOR: 40.31; 95% CI: 3.80-427.17; P = 0.002) were identified as robust independent predictors of dissemination. The predictive model demonstrated excellent discrimination with an AUC of 0.898 (95% CI: 0.814–0.983). The predicted probability of concurrent meningitis increased from 8.2% in patients with no risk factors to 98.9% in those presenting with both hyponatremia and neurological symptoms. CONCLUSIONS: Concurrent meningitis is a frequent complication in patients with PC. Hyponatremia and neurological symptoms serve as critical “red flags” for CNS dissemination. The combination of these two readily available markers can effectively stratify patients into high-risk groups. Clinicians should consider immediate CNS screening, including lumbar puncture, for PC patients presenting with this high-risk profile, regardless of pulmonary imaging severity.