What is the definition of Disseminated Tuberculosis (TB)?

Definition of Disseminated Tuberculosis

Disseminated tuberculosis (TB) is defined as a severe form of TB characterized by hematogenous or lymphatic spread of Mycobacterium tuberculosis from a primary site of infection to multiple organs throughout the body. 1

Pathophysiology and Terminology

Disseminated TB results from massive lympho-hematogenous dissemination of Mycobacterium tuberculosis from a focal lesion that ruptures into the blood or lymphatic flow 1. This form is also known as miliary TB in many contexts, with the terms often used interchangeably in clinical practice.

The pathogenesis involves:

• Initial infection (typically pulmonary)
• Bacterial replication
• Spread through bloodstream or lymphatic system
• Seeding of multiple organs with tubercle bacilli

Clinical Manifestations

Disseminated TB presents with involvement of two or more non-contiguous sites, or evidence of widespread hematogenous spread. Common clinical features include:

• Systemic symptoms: fever, night sweats, weight loss, fatigue
• Multi-organ involvement: lungs, liver, spleen, bone marrow, meninges, lymph nodes
• Often misleading presentation with general signs predominating 1
• Possible absence of respiratory symptoms despite pulmonary involvement

Diagnostic Criteria

The diagnosis of disseminated TB is based on the following:

1. Microbiological evidence: Isolation of M. tuberculosis from blood or from specimens from at least two non-contiguous organs 2

2. Radiological findings:

   • Classic "miliary pattern" on chest radiograph (1-3 mm nodules resembling millet seeds)
   • Multiple small nodules on CT imaging of affected organs

3. Histopathological evidence: Demonstration of caseating granulomas in multiple tissue samples

4. Clinical presentation: Evidence of multi-system involvement with compatible symptoms

High-Risk Populations

Disseminated TB is more commonly found in:

• Children and young adults
• HIV-infected patients 1
• Severely immunocompromised individuals
• Patients with AIDS (disseminated MAC was estimated at 37,000 cases in the US in 1994) 2
• Individuals with impaired cell-mediated immunity

Prognosis and Mortality

Untreated disseminated TB is fatal 1. Even with treatment, it carries significant mortality:

• In pre-antiretroviral era, only 13% of AIDS patients with disseminated MAC survived 1 year without treatment 2
• Mortality rates remain high even with treatment, especially when diagnosis is delayed
• Prognosis depends on early diagnosis and prompt treatment initiation 1

Treatment Approach

Treatment of disseminated TB follows standard TB treatment protocols but may require:

• Longer duration of therapy (6-12 months)
• Combination drug therapy with at least 4 first-line drugs initially
• For disseminated MAC in AIDS patients: macrolide-based regimen (clarithromycin or azithromycin) plus ethambutol, with consideration of a third drug such as rifabutin 2
• Monotherapy is contraindicated due to high risk of resistance development 2

Clinical Implications

Disseminated TB represents a medical emergency requiring:

• Prompt diagnosis
• Early treatment initiation
• Comprehensive supportive care
• Monitoring for complications
• Assessment for underlying immunodeficiency

The diagnosis is often challenging due to clinical polymorphism and frequent lack of bacteriological proof in many cases 1. A high index of suspicion is essential, particularly in high-risk populations.