Depart. Of Pulmonology R4 백승숙

Miliary tuberculosis In 1700, John Jacob Manget Latin word miliarius, meaning related to millet seed Resemblance of gross pathological findings to that of innumerable millet seeds in size and appearance Haematogenous, generalised, disseminated tuberculosis Lungs  distant blood-borne spread  extrapulmonary tuberculosis Intense systemic dissemination from the rupture of a Mycobacterium tuberculosis-laden focus into a vascular channel

Miliary tuberculosis accounts for about 1–2% of all cases of tuberculosis and about 8% of all forms of extrapulmonary tuberculosis in immunocompetent

Demographic shift The HIV/AIDS pandemic and widespread use of immunosuppressive The modulating effect of BCG vaccination Increasing use of CT scans and invasive diagnostic methods Presently two peaks Adolescents and young adults Later in life among elderly people

Gross examination Organs with high blood flow eg, the spleen, liver, lungs, bone marrow, kidneys, adrenals Small, punctate, grey to reddish brown coloured, rounded lesions of more or less uniform size are discernible various organs In advanced HIV infection Poor granuloma formation with minimal cellular reaction Severe necrosis, and abundant acid-fast bacilli Foci of acute tuberculosis pneumonia involve airspaces rather than the interstitium

In adult Protean and non-specific Most often the involvement is asymptomatic Fever, anorexia, weight loss, lassitude, and cough is frequent Apyrexial presentation with progressive wasting (older people) Tuberculosis meningitis has been described in 10–30% In children Peripheral lymphadenopathy and hepatosplenomegaly >> Chills, night sweats, haemoptysis, productive cough Tuberculosis meningitis has been described in 20–40%

(CD4+ cell counts >500 cells/L) ; Similar to that observed in immunocompetent individuals (CD4+ cell counts <200 cells/L) ; Disseminated and miliary tuberculosis are seen more (CD4+ cell counts <100 cells/L) ; Cutaneous involvement Immune reconstitution disease (IRD) Paradoxical worsening of lesions in patients with tuberculosis HIV-negative individuals with tuberculosis (32–36%) HIV/tuberculosis co-infection within days to weeks of the initiation of highly active antiretroviral therapy (HAART)

Choroidal tubercles Pathognomonic of miliary TB Valuable clue to the diagnosis

 Not useful as a diagnostic test in miliary tuberculosis A higher proportion of tuberculin anergy Cross reactivity with environmental mycobacteria Tuberculin positivity due to BCG vacination Typical of interstitial lung disease Impairment of diffusion ; most frequent and severe abnormality Mild reduction in flow rates ; peripheral airways involvement Arterial hypoxaemia, hypocapnia (acute stage)

Newer in-vitro T-cell based interferon assays Early Secretory Antigenic Target 6, Culture Filtrate Protein 10 Major targets of the T-cell response to M. tuberculosis Commercially available in the ELISA and ELISPOT formats Less affected by malnutrition, HIV infection, and BCG vaccination  Useful in detecting latent tuberculosis infection, especially in children with suspected tuberculosis in developing countries

Classic miliary pattern even when the chest radiograph looks apparently normal Contrast-enhanced CT scan ; Better for detecting intrathoracic lymphadenopathy, calcification, and pleural lesions

Figure 2. Thin-section CT scan obtained in a 29-year-old man with AML Eisenhuber E Radiology 2002;222:771-772 Figure 2. Thin-section CT scan obtained in a 29-year-old man with AML

Useful in the detection of associated lesions such as loculated ascites, focal hepatic and splenic lesions, and cold abscess Useful tool to assess the activity of various infectious lesions including pulmonary tuberculosis

Wherever possible, efforts should be directed at procuring tissue/fluid for mycobacterial culture and sensitivity testing Criteria Clinical presentation consistent with a diagnosis of tuberculosis and responding to antituberculosis treatment eg, pyrexia with evening rise of temperature, night sweats, anorexia, and weight loss of greater than 6 weeks in duration Typical miliary pattern on chest radiograph And/or bilateral, diffuse reticulonodular lung lesions on a background of miliary shadows either on chest radiograph or HRCT scan Microbiological and/or histopathological evidence of tuberculosis

that there is no consensus regarding the optimum duration of treatment Critical evaluation of published clinical series on miliary tuberculosis reveals that there is no consensus regarding the optimum duration of treatment

* BTS guidelines - All patients with miliary tuberculosis undergo In the absence of associated meningeal involvement ATS, CDC, IDSA, BTS guidelines 6 months of treatment - 2-month intensive phase with isoniazid, rifampicin, pyrazinamide, and ethambutol or streptomycin - 4-month continuation phase with isoniazid and rifampicin In the presence of associated tuberculosis meningitis At least 12 months of treatment * BTS guidelines - All patients with miliary tuberculosis undergo a lumbar puncture

No study has specifically evaluated the role of adjunct corticosteroid treatment in patients with miliary tuberculosis Absolute indication Associated adrenal insufficiency Adjunctive corticosteroid treatment Miliary tuberculosis with - tuberculosis meningitis, large pericardial or pleural effusion, - dyspnoea and/or disabling chest pain, IRD, ARDS, - immune complex nephritis, and histiocyticphagocytosis syndrome

At times bilateral, may be the presenting feature or may develop while the patient is receiving treatment Most dreaded complications of miliary tuberculosis and is usually seen at the time of initial presentation May develop at any time during the course of disease Renal failure may occur due to direct renal parenchymal involvement Can develop as a manifestation of IRD in HIV-infected patients

A unique form of hepatitis where widespread liver cell necrosis ; extrapulmonary focus has discharged into the portal circulation  hepatic miliary tuberculosis Drug-induced hepatitis ; standard guidelines should be followed in its management Life-threatening complications eg, myocarditis, congestive heart failure, infective endocarditis, pericarditis, intracardiac mass, mycotic aneurysm, sudden cardiac death

The mortality related to miliary tuberculosis 15–20% in children 25–30% in adults Delay in the diagnosis or commencement of treatment ; important cause of high mortality

BCG vaccination Effective in reducing the incidence of miliary tuberculosis Not effective in individuals who are already infected Should not be administered to immunosuppressed hosts Targeted tuberculin testing Treatment of latent tuberculosis infection Effort to develop a more effective vaccine

The national tuberculosis control programmes The reasons for the severely cmpromised local T-cell response The new interferon assays in the diagnosis of miliary tuberculosis The proposed diagnostic criteria are strictly adhered to The cause of death in patients with miliary tuberculosis The optimum regimen and duration of treatment The role of adjunctive corticosteroid therapy