HomeDisseminated TB is defined as disease occurring in two or more noncontiguous organs or the isol. tion of M. tuberculosis in blood, bone marrow or liver biopsy.21 Miliary TB is a distinct subset of disseminated TB, one that comes with increased mortality.248 Hematogenous dissemination of TB in miliary disease causes formation of minute tubercles throughout multiple organs, often resulting in characteristic uniform micronodular (1-5 mm) changes on lung imaging and life-threatening systemic illness.95
The clinical presentation of disseminated TB is often nonspecific. Fever, night sweats, anorexia, weight loss and weakness are commonly reported, while respiratory or other organ-specific symptoms occur less frequently.94,96,249,250 Clinical presentation is often subacute or chronic, although acute fulminant deterioration (including shock and acute respiratory distress syndrome) has been described.251,252 In elderly patients, disseminated TB may mimic metastatic carcinoma, being characterized by progressive wasting alone. The absence of fever and chest radiograph changes in this setting can confound TB diagnostic work-up.253,254 Funduscopic exam demonstrating choroidal tubercles is a specific finding and occurs in up to 20% of cases among people with HIV.255,256 The nonspecific and often variable presentation of disseminated TB frequently leads to a delay or lack of diagnosis and a high mortality rate.96,257
Good practice statement
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In severely ill cases, or in those with significant immunocompromising conditions, empiric anti-TB treatment should be considered to prevent morbidity and death while waiting for mycobacterial culture confirmation.
Laboratory findings in disseminated TB are nonspecific, though hematologic abnormalities are common, and hypoalbuminemia, hypercalcemia and elevated ferritin portend a worse prognosis.95,96 Between 30 and 50% of cases do not have the classic discrete micronodular or “miliary” pattern on chest radiograph.95 High-resolution CT is more sensitive than chest radiograph, though not necessarily specific for miliary TB.258 Prompt examination of AFB smear, NAAT and culture of sputum and urine, along with clinical specimens from multiple sites where disease may be clinically or radiographically apparent (pleural, pericardial, peritoneal, CSF, liver, bone marrow, blood) increases the probability of a positive result and may obviate the need for more invasive tissue biopsy testing (Table 1).93,94,96,248 Positron emission tomography-computed tomography (PET-CT) scan may aid in the work-up of disseminated TB by accurately mapping involved lymph nodes to improve diagnostic yield of minimally invasive sampling.259 However, limited accessibility may make routine use of PET-CT impractical and delayed access should not delay other investigations or treatment. CNS involvement in disseminated TB may occur in 10-30% of cases, with increased prevalence among people with HIV. Thorough clinical assessment and a low threshold for neuroimaging and lumbar puncture, among those with objective neurologic findings, is advised when disseminated TB is suspected or confirmed.
3.6.1. Disseminated TB treatment
There are no clinical trials specifically evaluating optimal therapy for disseminated TB and observational studies are confounded by variable definitions. Existing guideline recommendations are largely expert opinion based on extrapolation from evidence on treatment of other forms of organ-specific EPTB.95,96,213,214
Recommendation
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For drug-susceptible disseminated TB without central nervous system involvement, we conditionally recommend treatment with six months of standard anti-TB therapy. Extension to 9-12 months can be considered in immune-compromised patients if the predisposing condition is not modified (eg, people with human immunodeficiency virus not receiving antiretroviral therapy, or continuation of immunosuppressive therapy) (poor evidence).
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