How do miliary tuberculosis and primary tuberculosis differ in clinical presentation, radiographic findings, diagnosis, and treatment?

Miliary Tuberculosis vs. Pulmonary Tuberculosis: Key Differences

Miliary tuberculosis and pulmonary tuberculosis (PTB) differ fundamentally in their pathogenesis, clinical presentation, radiographic patterns, diagnostic challenges, and prognosis—with miliary TB representing massive lymphohematogenous dissemination requiring urgent recognition due to its uniformly fatal outcome if untreated. 1, 2

Pathogenesis and Epidemiology

Miliary TB results from massive lymphohematogenous dissemination of M. tuberculosis bacilli throughout the body, characterized by tiny tubercles resembling millet seeds on gross pathology. 1, 2 This represents a failure of immune containment with widespread organ seeding. 3

Primary pulmonary TB (PTB) typically develops as a complication of initial infection, particularly in children, and is characterized by intrathoracic lymphadenopathy with mid- and lower lung zone infiltrates without cavitation. 4 In contrast, reactivation PTB presents with upper lobe infiltration and cavitation associated with sputum production. 4

The HIV/AIDS pandemic and widespread immunosuppressive drug use have dramatically altered miliary TB epidemiology, making it increasingly common in adults rather than just infants and children. 1, 2

Clinical Presentation

Miliary TB

• Protean and nonspecific manifestations that often delay diagnosis 1, 2
• Fever (80%), night sweats (35%), weight loss (25%) 1
• May present with acute respiratory distress syndrome (ARDS)—a life-threatening complication with high mortality 5
• Cryptic presentations are common, particularly in immunocompromised patients 1
• Fundus examination revealing choroid tubercles is pathognomonic and offers a valuable early diagnostic clue 2

Primary PTB

• Intrathoracic adenopathy, mid- and lower lung zone infiltrates, absence of cavitation 4
• Paucibacillary disease with fewer organisms than adult-type PTB 4
• May present with lymph node enlargement causing airway compression, hyperinflation, or lobar collapse 4

Radiographic Findings

Miliary TB

• Classic miliary pattern may not appear until late in disease course 1, 6
• HRCT shows randomly distributed miliary nodules (more sensitive than chest X-ray) 6
• Chest radiograph may be normal early in disease, even in severely ill patients 3
• Ultrasonography, CT, and MRI useful for detecting extrapulmonary organ involvement 6

Primary PTB

• Intrathoracic lymphadenopathy with or without lung opacities 4
• Mid- and lower lung zone infiltrates 4
• Absence of cavitation (unlike reactivation PTB which shows upper lobe cavitation) 4
• Chest X-ray is first-line imaging (rated 9/9 appropriateness) 4

Diagnostic Approach

Miliary TB: Major Diagnostic Challenges

Diagnosis is notoriously difficult because sputum cultures may be negative even with abnormal chest radiographs. 3 This represents a critical pitfall that distinguishes miliary TB from typical PTB.

Diagnostic strategy for miliary TB:

• Bronchoscopic sampling with bronchial brushings and/or transbronchial biopsy (TBB) is preferred when induced sputum is AFB smear-negative 4
• TBB has diagnostic yield of 32-75%, while bronchial washings yield only 14% 4
• Transbronchial biopsy is the preferred diagnostic method and permits rapid presumptive diagnosis via histopathology 3, 4
• Examination of body fluids, image-guided fine-needle aspiration, liver biopsy, and bone marrow biopsy should be pursued 2
• Molecular testing (Xpert MTB/RIF) and culture with drug susceptibility testing are critical 2

Primary PTB: Diagnostic Approach

Diagnosis relies on collecting at least three sputum specimens 8-24 hours apart, with at least one early morning specimen. 7 In children, this is more challenging due to paucibacillary nature. 4

For children unable to produce sputum:

• Three early morning gastric aspirations (optimally during hospitalization) 4
• Sputum induction 4
• Bronchoalveolar lavage or tissue biopsy 4

Critical difference: Primary PTB has higher organism burden in respiratory specimens compared to miliary TB, making microbiological confirmation more feasible. 4

Treatment Considerations

Miliary TB

Standard 6-month anti-TB regimen is recommended without routine corticosteroids for disseminated/miliary tuberculosis, though expert opinion suggests corticosteroids may be useful for respiratory failure. 8

Miliary TB is uniformly fatal if untreated; therefore, early empiric treatment initiation is lifesaving even before microbiological confirmation. 2 This contrasts with the approach to uncomplicated PTB where waiting for confirmation is more acceptable.

Monitor closely for:

• ARDS development (associated with high fatality rate) 5
• Drug-induced hepatotoxicity 6
• Acute kidney injury 2
• Drug-drug interactions in HIV/AIDS patients 6, 2

Prognostic factors predicting ARDS and mortality include platelet count, serum albumin, and liver enzyme levels at admission. 5

Primary PTB

Six-month therapy with INH, RIF, and PZA has >95% success rate with <2% adverse effects in children. 4

Treatment failure, relapse, and secondary resistance are rare in primary PTB due to paucibacillary nature, unlike adult-type cavitary disease. 4

In infants and children <4 years, treatment should start immediately upon suspicion due to higher risk of dissemination. 4

Critical Clinical Pitfalls

For miliary TB:

• Never rely on negative sputum cultures to exclude miliary TB—proceed to invasive sampling 3
• Do not wait for classic miliary pattern on chest X-ray before initiating treatment in critically ill patients 1, 6
• Maintain high index of suspicion in immunocompromised patients with nonspecific symptoms 1, 2
• Always perform fundus examination—choroid tubercles are pathognomonic 2

For primary PTB:

• Choosing appropriate treatment drugs often requires drug susceptibility testing from the presumed source case 4
• Do not confuse primary PTB (lymphadenopathy, lower lobe disease) with reactivation PTB (upper lobe cavitation) 4
• In children, diagnosis is microbiologically confirmed in only 15-50% of cases—clinical case definitions are important 4