What is the pathophysiology of miliary tuberculosis (TB)?

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From the Guidelines

Miliary tuberculosis is a severe form of TB characterized by widespread dissemination of Mycobacterium tuberculosis throughout the body, involving primary infection or reactivation of latent TB, followed by hematogenous spread of the bacteria to multiple organs. The pathophysiology of miliary TB begins with the entry of TB bacilli into the bloodstream from a primary focus, typically in the lungs, and their dissemination to various organs, including the lungs, liver, spleen, bone marrow, meninges, and adrenal glands 1. This process is facilitated by bacterial replication within macrophages, followed by cell lysis and release of bacilli that infect adjacent cells and tissues.

Key Factors in Pathophysiology

  • The immune system's attempt to contain the infection through cell-mediated immunity, with macrophages, T lymphocytes, and other immune cells surrounding the bacteria, leads to the formation of characteristic millet seed-sized (1-2 mm) granulomas in affected tissues.
  • Immunocompromised individuals, particularly those with HIV/AIDS, are at higher risk for developing miliary TB due to impaired cell-mediated immunity.
  • The extensive inflammation and organ involvement lead to systemic symptoms including fever, weight loss, and night sweats, as well as organ-specific manifestations depending on the sites affected.

Clinical Considerations

  • Prolonged treatment for 12 months is required to reduce the risk of reactivation in miliary tuberculosis, as indicated by guidelines for managing tuberculosis in various contexts 1.
  • Early detection and treatment are crucial to prevent the spread of the disease and reduce morbidity and mortality.
  • In endemic areas, routine screening for tuberculosis, such as the Mantoux test and chest X-ray, is recommended for individuals at high risk, including those with immunocompromised conditions.

From the Research

Pathophysiology of Miliary TB

  • Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli, characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance 2, 3, 4.
  • The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs have altered the epidemiology of miliary TB, making it increasingly encountered in adults as well 2, 3, 4.
  • Impaired cell-mediated immunity underlies the disease's development, leading to a potentially lethal form of tuberculosis 3.

Clinical Manifestations

  • The clinical manifestations of miliary TB are protean and nonspecific, often delaying the diagnosis 2, 3, 4.
  • Atypical presentations, such as cryptic miliary TB and acute respiratory distress syndrome, can also delay the diagnosis 3, 4, 5.
  • Fundus examination for detecting choroid tubercles offers a valuable clinical clue for early diagnosis, as their presence is pathognomonic of miliary TB 2, 4, 5.

Diagnosis and Treatment

  • Diagnosis of miliary TB is a challenge that can perplex even the most experienced clinicians, requiring a high index of clinical suspicion and early diagnosis 5.
  • Imaging modalities, such as high-resolution computed tomography (HRCT), ultrasonography, CT, and magnetic resonance imaging, are useful in discerning the extent of organ involvement by lesions of miliary TB 5.
  • GeneXpert MTB/RIF, line probe assay, mycobacterial culture, and drug-susceptibility testing must be carried out as appropriate and feasible to confirm the diagnosis and guide treatment 2, 4, 5.
  • Treatment of miliary TB should be started at the earliest, as this can be life-saving, with response to first-line anti-TB drugs being good 2, 4, 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Miliary Tuberculosis.

Microbiology spectrum, 2017

Research

Miliary tuberculosis: new insights into an old disease.

The Lancet. Infectious diseases, 2005

Research

Miliary tuberculosis: A new look at an old foe.

Journal of clinical tuberculosis and other mycobacterial diseases, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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