Abstract:
Cryptococcosis mainly affects immunocompromised hosts but can also occur in immunocompetent individuals, often presenting with non-specific pulmonary radiological lesions and asymptomatic clinical course, which frequently causes misdiagnosis and delayed treatment. Diagnostic challenges arise when central nervous system (CNS) involvement is suspected despite negative initial cerebrospinal fluid (CSF) microscopy findings. We present a 24-year-old previously healthy immunocompetent male with incidental left lung infection detected on chest CT, who remained completely asymptomatic. Empirical oral antibiotic treatment resulted in only minimal improvement of lung lesions. Laboratory tests showed positive serum cryptococcal polysaccharide antigen. Bronchoalveolar lavage mNGS detected Pneumocystis jirovecii and Klebsiella aerogenes, with elevated BAL galactomannan level. Lumbar puncture revealed elevated CSF protein, neutrophil-predominant pleocytosis and weakly positive Pandy’s test, while India ink staining and culture were negative for cryptococci.
The patient had normal CD4 count, confirming intact immune function. Induction therapy with liposomal amphotericin B plus flucytosine was initiated for presumed cryptococcal meningoencephalitis. Transient liver enzyme elevation and hypokalemia occurred during treatment, which were effectively corrected by symptomatic management, and the patient was discharged in stable condition. This case indicates that positive serum cryptococcal antigen in patients with pulmonary nodules requires mandatory CNS evaluation even without typical meningeal symptoms. Negative CSF India ink cannot exclude cryptococcal meningitis. Incidental detection of Pneumocystis jirovecii by mNGS in immunocompetent individuals raises concerns about colonization or subclinical infection. Clinicians should interpret mNGS results cautiously and determine the true pathogen based on comprehensive clinical information. Pulmonary cryptococcosis should be considered for persistent unexplained pulmonary lesions regardless of immune status; early serological screening, routine lumbar puncture to rule out occult CNS dissemination, and timely standardized antifungal therapy are essential to improve diagnostic accuracy and clinical prognosis.
