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Miliary Tuberculosis

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  • Authors: Surendra K. Sharma1, Alladi Mohan2
  • Editor: David Schlossberg3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Infectious Diseases, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110 029, India; 2: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati 517 507, India; 3: Philadelphia Health Department, Philadelphia, PA
  • Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
  • Received 01 October 2016 Accepted 09 January 2017 Published 10 March 2017
  • Surendra K. Sharma, sksharma.aiims@gmail.com
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  • Abstract:

    Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well. The clinical manifestations of miliary TB are protean and nonspecific. Atypical clinical presentation often delays the diagnosis. Clinicians, therefore, should have a low threshold for suspecting miliary TB. Focused, systematic physical examination helps in identifying the organ system(s) involved, particularly early in TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles offers a valuable clinical clue for early diagnosis, as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, defining the extent of organ system involvement. Examination of sputum, body fluids, image-guided fine-needle aspiration cytology or biopsy from various organ sites, needle biopsy of the liver, bone marrow aspiration, and biopsy should be done to confirm the diagnosis. Cytopathological, histopathological, and molecular testing (e.g., Xpert MTB/RIF and line probe assay), mycobacterial culture, and drug susceptibility testing must be carried out as appropriate and feasible. Miliary TB is uniformly fatal if untreated; therefore, early initiation of specific anti-TB treatment can be lifesaving. Monitoring for complications, such as acute kidney injury, air leak syndromes, acute respiratory distress syndrome, adverse drug reactions such as drug-induced liver injury, and drug-drug interactions (especially in patients coinfected with HIV/AIDS), is warranted.

  • Citation: Sharma S, Mohan A. 2017. Miliary Tuberculosis. Microbiol Spectrum 5(2):TNMI7-0013-2016. doi:10.1128/microbiolspec.TNMI7-0013-2016.

Key Concept Ranking

Acute Respiratory Distress Syndrome
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/content/journal/microbiolspec/10.1128/microbiolspec.TNMI7-0013-2016
2017-03-10
2017-11-20

Abstract:

Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well. The clinical manifestations of miliary TB are protean and nonspecific. Atypical clinical presentation often delays the diagnosis. Clinicians, therefore, should have a low threshold for suspecting miliary TB. Focused, systematic physical examination helps in identifying the organ system(s) involved, particularly early in TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles offers a valuable clinical clue for early diagnosis, as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, defining the extent of organ system involvement. Examination of sputum, body fluids, image-guided fine-needle aspiration cytology or biopsy from various organ sites, needle biopsy of the liver, bone marrow aspiration, and biopsy should be done to confirm the diagnosis. Cytopathological, histopathological, and molecular testing (e.g., Xpert MTB/RIF and line probe assay), mycobacterial culture, and drug susceptibility testing must be carried out as appropriate and feasible. Miliary TB is uniformly fatal if untreated; therefore, early initiation of specific anti-TB treatment can be lifesaving. Monitoring for complications, such as acute kidney injury, air leak syndromes, acute respiratory distress syndrome, adverse drug reactions such as drug-induced liver injury, and drug-drug interactions (especially in patients coinfected with HIV/AIDS), is warranted.

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Figures

Image of FIGURE 1
FIGURE 1

Pearl millet () seeds are small grains that have an average diameter of <2 mm , , and . These grains and correspond to the approximate size of lesions observed in miliary TB on HRCT of the chest.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 2
FIGURE 2

Distribution of tuberculosis cases by anatomical site in immunocompetent and immunosuppressed 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 reference 18 .

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 3
FIGURE 3

The development of miliary TB. Small droplet nuclei (1 to 5 μm) containing 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 post-primary TB (7). Fifty percent of reactivations occur during the first 2 years of primary infection. In 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 post-primary miliary TB). In areas with high transmission rates, reinfection with a new strain of (9) can occur and the cycle is repeated. *, important in areas of endemicity; , organ-restricted TB with adequate host immunity. MTB, miliary TB; TNF, tumor necrosis factor. Reproduced with permission from reference 2 .

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 4
FIGURE 4

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

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 5
FIGURE 5

Chest radiograph (postero-anterior view) for a 30-year-old woman who presented with a 3-month history of fever with no other localizing clue. HRCT of the same patient showing a classical miliary pattern. Bone marrow biopsy confirmed the diagnosis of miliary TB; was grown on bronchoscopic aspirate culture.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 6
FIGURE 6

Chest radiograph (antero-posterior view, done bedside with a portable machine) showing bilateral frontal opacities and airspace consolidation suggestive of ARDS in a HIV-seropositive patient with miliary TB. Tracheal aspirate smear for AFB and bone marrow biopsy confirmed the diagnosis.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 7
FIGURE 7

Chest radiograph (poster-anterior view) and chest CT (lung window) and showing predominance of miliary lesions on the right side. F-labeled 2-deoxy--glucose PET-CT of the same patient showing increased activity in the coalesced pulmonary lesions, which is evident more prominently on the right side. Reproduced with permission from reference 4 .

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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FIGURE 8

Algorithm for the diagnostic workup of a patient with suspected miliary TB. The clinical and imaging diagnostic workup should also aim at accurately assessing the extent of extrapulmonary involvement to facilitate monitoring and ensure adequate duration of treatment. All laboratory testing, especially anti-TB DST, must be carried out in quality-assured, periodically accredited laboratories. *, often used in children; †, FNAC/excision biopsy; ‡, radiologically guided FNAC/biopsy; §, mediastinoscopic/video-assisted thoracoscopic surgery, biopsy; ||, laparoscopic biopsy; ¶, useful in advanced HIV infection. TST, tuberculin skin test; CECT, contrast-enhanced CT; L-J, Lowenstein-Jensen medium; MGIT, mycobacterial growth inhibitor tube; BACTEC, radiometric culture method; Xpert MTB/RIF, GeneXpert MTB/RIF assay (Cepheid, Sunnyvale, CA); LPA, line probe assay. Reproduced with permission from reference 4 .

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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Image of FIGURE 9
FIGURE 9

Guidelines on timing of antiretroviral treatment in patients with HIV and TB coinfection. *, although the data suggest a cutoff of 50 cells/μl, because of the daily variability in CD4, a cutoff of 100 cells/μl may be more appropriate. ART, antiretroviral treatment; BHIVA, British HIV Association; EFV, efavirenz; HAART, highly active antiretroviral treatment; NNRTI, nonnucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor; TDF, tenofovir disoproxil fumarate; 3TC, lamivudine; FTC, emtricitabine. Data are from references 144 and 145 .

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Tables

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TABLE 1

Epidemiology of miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 2

Proportions of miliary TB cases among all reported TB cases and extrapulmonary TB cases in the United States, 2012 to 2014

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 3

Conditions predisposing to or associated with miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 4

Iatrogenic causes of miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 5

Organ system involvement in miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 6

Presenting symptoms and signs in miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 7

Atypical clinical manifestations and complications in miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 8

Method of confirmation of diagnosis in adults with miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 9

Laboratory abnormalities in miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 10

Chest radiographic abnormalities in miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016
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TABLE 11

Predictors of poor outcome in patients with disseminated or miliary TB

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0013-2016

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