Why does cerebrospinal fluid (CSF) analysis show lymphocytosis in patients with Human Immunodeficiency Virus (HIV) and reactive Tuberculosis (TB)?

Cerebrospinal Fluid Lymphocytosis in HIV Patients with Tuberculous Meningitis

In patients with HIV and reactive tuberculosis, cerebrospinal fluid (CSF) analysis typically shows lymphocyte predominance due to the characteristic immune response to mycobacterial infection in the central nervous system, though this pattern may be altered in severe immunosuppression. 1, 2

Pathophysiology of CSF Lymphocytosis in TB Meningitis

• Tuberculous meningitis (TBM) typically produces a lymphocytic-predominant pleocytosis in the CSF as part of the cell-mediated immune response against Mycobacterium tuberculosis 2
• The immune response in TBM involves T-lymphocytes that migrate to the site of infection in the meninges, creating the characteristic lymphocytic predominance in the CSF 3
• This lymphocytic response is a hallmark feature that helps differentiate TBM from bacterial meningitis, which typically shows neutrophil predominance 1

CSF Characteristics in HIV Patients with TB Meningitis

• In HIV patients with TBM, CSF typically shows moderate pleocytosis (tens to hundreds of cells) with lymphocytic predominance, elevated protein levels, and low glucose concentration 1, 2
• The median white cell count in HIV patients with TBM is approximately 21 cells/ml with mononuclear cells (lymphocytes) predominant in about 74% of CSF samples 4
• CSF protein levels are typically elevated (median 1.7 g/l) while glucose levels are low (median 0.4 g/l) in HIV-associated TBM 4

Important Variations in HIV Patients

• HIV-infected patients with TBM may have atypical CSF findings compared to non-HIV patients, including a higher frequency of non-inflammatory CSF (absence of pleocytosis) in advanced immunosuppression 5
• The degree of lymphocytosis may correlate with CD4 count - patients with very low CD4 counts (median 16 cells/mm³) may have less robust CSF inflammatory responses 4
• In early stages of TBM (first 10 days), neutrophils may predominate (60-80%), with a shift to lymphocyte predominance occurring from the second week onward 3

Diagnostic Considerations

• CSF acid-fast bacilli smears have low sensitivity (found in only 1.9% of samples in one study), making lymphocytic pleocytosis an important diagnostic clue 4
• The presence of lymphocytic pleocytosis with elevated protein and low glucose should prompt consideration of TBM in HIV patients, even when acid-fast bacilli cannot be visualized 2
• Multiple, large-volume CSF samples increase the yield of microbiological confirmation 2
• A second lumbar puncture performed 24-48 hours after an initially non-diagnostic tap may reveal the characteristic lymphocytic pattern if the first was performed very early in the disease course 1

Clinical Implications

• TBM in HIV patients carries a significantly higher mortality rate (63.3%) compared to non-HIV patients (17.5%), making prompt recognition of CSF patterns crucial 5
• The lymphocytic CSF pattern may be altered in patients with severe immunosuppression, potentially leading to diagnostic delays 5
• Treatment should be initiated as soon as clinical suspicion is supported by initial CSF studies, without waiting for microbiological confirmation 2

Important Caveats

• Not all HIV patients with TBM will show the classic lymphocytic pleocytosis - those with profound immunosuppression may have acellular or minimally cellular CSF 1
• CSF findings must be interpreted in the context of the patient's immune status, as severely immunocompromised patients may have atypical presentations 1
• In some cases, an intrathecal synthesis of soluble class I antigens (sHLA) may be decreased in HIV patients with concomitant tuberculous meningitis, reflecting the complex immune interactions 6