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Chapter 27 : Miliary Tuberculosis
Category: Clinical Microbiology; Bacterial Pathogenesis
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Miliary tuberculosis (TB) is a lethal form of disseminated TB that results from a massive lymphohematogenous dissemination from a Mycobacterium tuberculosis-laden focus. Diagnosis of miliary TB requires the presence of a diffuse miliary infiltrate on a chest radiograph or high-resolution CT (HRCT) or histopathological evidence of miliary tubercles in tissue specimens obtained from multiple organs. The majority of the patients in a study had chest radiographs consistent with miliary TB; in some, these classical radiographic changes evolved over the course of the disease. The diagnosis of miliary TB is easier when the patient presents with classical miliary shadowing on chest radiograph in an appropriate setting. Magnetic resonance imaging (MRI) of the brain and spine is very useful in the initial evaluation and follow-up of miliary TB patients with TB meningitis (TBM) or spinal TB and also protects from radiation exposure. Adenosine deaminase and gamma interferon level estimation in ascitic fluid and pleural fluid can be helpful in the diagnosis of miliary TB. Changes in the WHO revised recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system regarding the timing of starting of antiretroviral drugs, the choice of drugs, and the timing of initiation in relation to institution of anti-TB treatment, have been provided in this chapter. Assisted mechanical ventilation and other interventions may be required for the management of patients with miliary TB who develop acute respiratory distress syndrome (ARDS). BCG vaccination is effective in reducing the incidence of miliary TB, especially in children.
Pearl millet (Pennisetum typhoides) seeds are small grains that have an average diameter of <2 mm (A to C). These grains (D and E) correspond to the approximate size of lesions observed in miliary TB on HRCT of the chest.
Distribution of TB cases by anatomical site in immunocompetent (A) and immunosuppressed (B) adults. PTB, pulmonary TB; EPTB, extrapulmonary TB; GUTB, genitourinary TB; DTB, disseminated TB; MTB, miliary TB; ABD, abdominal TB; LNTB, lymph node TB. Reproduced with permission from Indian Journal of Medical Research ( 109 ).
Proportion of miliary TB cases among all reported TB cases and extrapulmonary TB (EPTB) cases. Reprinted with permission from the CDC ( 22 ).
Development of miliary TB. Small droplet nuclei (1 to 5 µm) containing Mycobacterium tuberculosis get deposited in the alveoli ( 1 ), where host-pathogen interactions occur. Seventy percent of individuals exposed do not get infected ( 2 ), whereas 30% develop infection ( 3 ). Infection is contained in 90% of those infected (latent TB infection) ( 4 ). The remaining 10% develop progressive primary TB ( 5 ). During this phase, extensive lymphohematogenous dissemination ( 6 ) to various organs can result in miliary TB. People with latent TB infection have a 10% lifetime risk of reactivation of the infection, resulting in postprimary TB ( 7 ). Fifty percent of reactivations occur during the first 2 years of primary infection. By contrast, in HIV-infected individuals with latent TB infection, the risk of reactivation is enormously high (approximately 10%/year). Massive lymphohematogenous dissemination during reactivation ( 8 ) can also result in miliary TB (progressive postprimary miliary TB). In areas with high transmission rates, reinfection with a new strain of Mycobacterium tuberculosis ( 9 ) can occur and the cycle is repeated. MTB, miliary TB; TNF, tumor necrosis factor. Reproduced with permission from Lancet Infectious Diseases ( 111 ).
Papulonodular skin lesions in a patient with miliary TB. Skin biopsy confirmed the diagnosis.
(A) Chest radiograph (postero-anterior view) of a 30-year old woman who presented with a 3-month history of fever with no other localizing clue; (B) HRCT of the same patient showing the classical miliary pattern. Bone marrow biopsy confirmed the diagnosis of miliary TB; Mycobacterium tuberculosis was grown on bronchoscopic aspirate culture.
Chest radiograph (antero-posterior view, done bedside with a portable machine) showing bilateral frontal opacities and air space consolidation suggestive of ARDS in an HIV-seropositive patient with miliary TB. Tracheal aspirate smear for AFB and bone marrow biopsy confirmed the diagnosis.
Guidelines on timing of antiretroviral treatment in patients with HIV-TB coinfection. ART, antiretroviral treatment; BHIVA, British HIV Association; EFV, efavirenz; HAART, highly active antiretroviral treatment. NNRTI, nonnucleoside reverse transcriptase inhibitor. Guidelines are based on references 83 and 139 .
Epidemiology of miliary TB
Conditions predisposing to or associated with miliary TB
Iatrogenic causes of miliary TB a
Organ system involvement in miliary TB a
Presenting symptoms and signs in miliary TB a
Atypical clinical manifestations and complications in miliary TB a
Method of confirmation of diagnosis in adults with miliary TB a
Laboratory abnormalities in miliary TB
Chest radiographic abnormalities in miliary TB a
Predictors of poor outcome in patients with disseminated or miliary TB