What is Miliary Tuberculosis?
Miliary tuberculosis is a potentially fatal form of disseminated tuberculosis that results from massive lymphohematogenous spread of Mycobacterium tuberculosis bacilli throughout the body, characterized by tiny tubercles resembling millet seeds in size and appearance on gross pathology. 1, 2
Pathophysiology and Epidemiology
Miliary TB develops from rupture of a focal tuberculous lesion into the bloodstream or lymphatic system, leading to widespread dissemination of bacilli throughout multiple organ systems 1, 2
The disease is almost always secondary to hematogenous spread from chronic latent TB infection, with a lifetime reactivation risk estimated at up to 15% 3
The HIV/AIDS pandemic and widespread use of immunosuppressive drugs have fundamentally altered the epidemiology of miliary TB, shifting it from predominantly a pediatric disease to one increasingly seen in adults 2, 4
Miliary TB is commonly found in children, young adults, HIV-infected patients, and those with impaired cell-mediated immunity 1, 5
Risk factors include primary TB and latent TB infection, diabetes, advanced age, low body mass index, oncological comorbidities, immunosuppression (including HIV), renal failure, and poor socioeconomic conditions 3
Clinical Presentation
The clinical manifestations are protean and nonspecific, often leading to diagnostic delays that can be fatal. 2, 6
Patients typically present with general constitutional symptoms including fever, weight loss, and malaise, with poor localizing physical examination findings 1, 6
Respiratory symptoms may include cough, dyspnea, and hemoptysis, though these are not always prominent 4
Atypical presentations include cryptic miliary TB (insidious onset with minimal symptoms) and acute respiratory distress syndrome (ARDS), both of which frequently delay diagnosis 6, 5
Fundoscopic examination revealing choroid tubercles is pathognomonic of miliary TB and provides a valuable early diagnostic clue 2, 4
The disease can affect all genitourinary organs and other extrapulmonary sites, with symptoms varying based on organ involvement 3
Diagnostic Approach
Because miliary TB is uniformly fatal if untreated, clinicians must maintain a low threshold for suspicion and pursue aggressive diagnostic evaluation. 2, 4
Imaging Studies
Chest radiography may not show classical miliary changes early in the disease course, and typical findings may appear late 6, 5
High-resolution computed tomography (HRCT) is more sensitive than plain radiography and demonstrates randomly distributed miliary nodules throughout the lungs 6
For extrapulmonary involvement, ultrasonography, CT, and MRI help define the extent of organ involvement 6
Microbiological and Histopathological Diagnosis
For patients with suspected miliary TB whose induced sputum is AFB smear-negative or from whom respiratory samples cannot be obtained, flexible bronchoscopic sampling is recommended 3
Bronchoscopic sampling should include bronchial brushings and/or transbronchial biopsy (TBB), as the diagnostic yield from washings alone is substantially lower 3
Bronchial brushings have a diagnostic yield of 27-78% and TBB yields 32-75% 3, 7
Postbronchoscopy sputum specimens should be collected from all patients undergoing bronchoscopy, with AFB smear yields of 9-73% and culture yields of 35-71% 3
Examination of sputum, body fluids, image-guided fine-needle aspiration cytology or biopsy from various organ sites, liver needle biopsy, and bone marrow aspiration should be performed to confirm diagnosis 2, 4
Molecular testing including Xpert MTB/RIF and line probe assay, along with mycobacterial culture and drug susceptibility testing, must be carried out as appropriate 2, 4
Treatment
A standard daily 6-month regimen is adequate for miliary tuberculosis without CNS involvement. 3
Standard Regimen
The treatment consists of isoniazid, rifampicin, pyrazinamide, and ethambutol for the first 2 months (intensive phase), followed by isoniazid and rifampicin for at least 4 additional months 3, 7
This regimen applies when the disease is caused by drug-susceptible organisms 8
Special Considerations
When there is clinical or laboratory evidence of CNS involvement, treatment duration must be extended to 12 months following the meningitis protocol 3
Because of the high rate of blood-borne spread to the meninges in miliary TB, lumbar puncture is required to determine appropriate treatment duration 3
Adjunctive corticosteroid therapy with dexametasone or prednisolone tapered over 6-8 weeks is recommended for patients with tuberculous meningitis 3, 7
Some experts believe concurrent corticosteroid therapy is indicated for severe respiratory failure or adrenal insufficiency caused by disseminated tuberculosis, though the role in miliary TB without these complications remains unclear 3
Monitoring
Clinical follow-up should occur at least monthly, including evaluation for symptoms of hepatitis and education about adverse effects 7
Liver function tests should be performed every 2-4 weeks during antituberculosis treatment 7
Monitoring for complications including acute kidney injury, air leak syndromes, ARDS, and drug-induced liver injury is warranted 2
Drug-drug interactions require particular attention, especially in HIV-coinfected patients 2, 4