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Chapter 27 : Miliary Tuberculosis

Authors: Surendra K. Sharma1, Alladi Mohan2
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Affiliations: 1: Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 029, India; 2: Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, India
Content Type: Monograph
Publication Year: 2011

Category: Clinical Microbiology; Bacterial Pathogenesis

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Abstract:

Miliary tuberculosis (TB) is a lethal form of disseminated TB that results from a massive lymphohematogenous dissemination from a -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.

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27

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Acute Respiratory Distress Syndrome
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Highly Active Antiretroviral Therapy
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Major Histocompatibility Complex
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Miliary Tuberculosis
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Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27fig01
Figure 1.
Pearl millet () 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.
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Image of Figure 1.
Figure 1.

Pearl millet () 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.

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 2.
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 ( ).
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Image of Figure 2.
Figure 2.

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 ( ).

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 3.
Proportion of miliary TB cases among all reported TB cases and extrapulmonary TB (EPTB) cases. Reprinted with permission from the CDC ( ).
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Image of Figure 3.
Figure 3.

Proportion of miliary TB cases among all reported TB cases and extrapulmonary TB (EPTB) cases. Reprinted with permission from the CDC ( ).

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 4.
Development of miliary TB. Small droplet nuclei (1 to 5 µm) containing get deposited in the alveoli ( ), where host-pathogen interactions occur. Seventy percent of individuals exposed do not get infected ( ), whereas 30% develop infection ( ). Infection is contained in 90% of those infected (latent TB infection) ( ). The remaining 10% develop progressive primary TB ( ). During this phase, extensive lymphohematogenous dissemination ( ) 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 ( ). 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 ( ) can also result in miliary TB (progressive postprimary miliary TB). In areas with high transmission rates, reinfection with a new strain of ( ) can occur and the cycle is repeated. MTB, miliary TB; TNF, tumor necrosis factor. Reproduced with permission from ( ).
10.1128/9781555817138/f0418-01_thmb.gif
10.1128/9781555817138/f0418-01.gif
Image of Figure 4.
Figure 4.

Development of miliary TB. Small droplet nuclei (1 to 5 µm) containing get deposited in the alveoli ( ), where host-pathogen interactions occur. Seventy percent of individuals exposed do not get infected ( ), whereas 30% develop infection ( ). Infection is contained in 90% of those infected (latent TB infection) ( ). The remaining 10% develop progressive primary TB ( ). During this phase, extensive lymphohematogenous dissemination ( ) 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 ( ). 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 ( ) can also result in miliary TB (progressive postprimary miliary TB). In areas with high transmission rates, reinfection with a new strain of ( ) can occur and the cycle is repeated. MTB, miliary TB; TNF, tumor necrosis factor. Reproduced with permission from ( ).

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 5.
Papulonodular skin lesions in a patient with miliary TB. Skin biopsy confirmed the diagnosis.
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Image of Figure 5.
Figure 5.

Papulonodular skin lesions in a patient with miliary TB. Skin biopsy confirmed the diagnosis.

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 6.
(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; was grown on bronchoscopic aspirate culture.
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Image of Figure 6.
Figure 6.

(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; was grown on bronchoscopic aspirate culture.

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 7.
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.
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Image of Figure 7.
Figure 7.

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.

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Figure 8.
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 and .
10.1128/9781555817138/f0430-01_thmb.gif
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Image of Figure 8.
Figure 8.

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 and .

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
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Tables

Miliary Tuberculosis
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Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table01
Table 1.
Epidemiology of miliary TB
Generic image for table
Table 1.

Epidemiology of miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table02
Table 2.
Conditions predisposing to or associated with miliary TB
Generic image for table
Table 2.

Conditions predisposing to or associated with miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table03
Table 3.
Iatrogenic causes of miliary TB
Generic image for table
Table 3.

Iatrogenic causes of miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table04
Table 4.
Organ system involvement in miliary TB
Generic image for table
Table 4.

Organ system involvement in miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table05
Table 5.
Presenting symptoms and signs in miliary TB
Generic image for table
Table 5.

Presenting symptoms and signs in miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table06
Table 6.
Atypical clinical manifestations and complications in miliary TB
Generic image for table
Table 6.

Atypical clinical manifestations and complications in miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table07
Table 7.
Method of confirmation of diagnosis in adults with miliary TB
Generic image for table
Table 7.

Method of confirmation of diagnosis in adults with miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table08
Table 8.
Laboratory abnormalities in miliary TB
Generic image for table
Table 8.

Laboratory abnormalities in miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table09
Table 9.
Chest radiographic abnormalities in miliary TB
Generic image for table
Table 9.

Chest radiographic abnormalities in miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27
/content/10.1128/9781555817138.ch27.ch27table10
Table 10.
Predictors of poor outcome in patients with disseminated or miliary TB
Generic image for table
Table 10.

Predictors of poor outcome in patients with disseminated or miliary TB

Citation: Sharma S, Mohan A. 2011. Miliary Tuberculosis, p 415-435. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch27

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