MILIARY TUBERCULOSIS

I. Epidemiology

Miliary or disseminated tuberculosis was the fifth most common type of extrapulmonary tuberculosis in the U.S. in 1991. Historically, miliary TB has been a disease of children, with more than a third of cases occurring in those under 3 years of age. Today, most cases occur in adults especially over the age of 65 years. Medical risk factors include immunosuppression, especially cancer and chemotherapy, alcoholism, starvation, chronic hemodialysis, and viral infections (measles, influenza). Predictors of mortality from dissemination are age greater than 60 years, lymphopenia, thrombocytopenia, hypoalbuminemia, elevated transminases, and delay in appropriate therapy. One of the most common forms of extrapulmonary tuberculosis in patients with HIV infection is disseminated disease.

II. Clinical

Disseminated TB is defined by the involvement of two or more noncontiguous tuberculous sites, i.e. lesions that range from miliae to larger nodules to tuberculomas, or the presence of bacteremia. Miliary tuberculosis may occur in three separate distinct forms: (1) acute (acute primary and late generalized), (2) chronic (chronic hematogenous or cryptic), and (3) nonreactive (typhobacillosis of Landouzy).

The acute form is a rapidly progressive process that is uniformly fatal if not treated. Signs and symptoms are nonspecific and frequently include fever, weight loss, malaise, anorexia, and fatigue. Physical signs include hepatomegaly and less commonly splenomegaly and lymphadenopathy. Chronic or cryptic miliary TB is miliary TB where the classical and radiological features of miliary TB are not present. The disease is insidious before it becomes acute, typically affects the elderly, presents as a fever of unknown origin, and the diagnosis is often delayed. The overall mortality is about 90%. Nonreactive miliary TB is a fatal form of the disease where many organs show areas of caseous necrosis surrounded by normal or near normal parenchyma. The clinical spectrum ranges from an acute and overwhelming illness to chronic persistent condition. In HIV positive patients disseminated TB is seen more commonly, and can be rapidly progressive and overwhelming requiring an aggressive diagnostic approach and early therapy. The majority (90%) of patients are anergic.





III. Diagnosis

The chest radiograph is the single most important way of detecting miliary tuberculosis. It may be normal in 25-50% of patients (Maartens et al, 1990, Am. J. Med.) and may remain that way for several weeks. It may also exhibit a vast array of abnormalities including pleural effusions, hilar adenopathy, interstitial infiltrates, and extensive parenchymal consolidation (ARDS). The sputum smear is positive in approximately 30% of patients with miliary TB, and increases with additional lesions, e.g. cavitation, in up to 70% of patients. Sputum cultures are positive in almost two-thirds of patients (Maartens et al, 1990). Histologic confirmation of disseminated TB is achieved best by biopsy of the lung, bone marrow, liver, lynph node, skin, or any other tissue that is clinically involved. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) remains an invaluable tool in the immediate diagnosis of miliary TB. The definitive diagnostic yield from transbronchial biopsy and bronchial washings or lavage is 73-86% (Maartens et al, 1990, Wilcox et al, 1986, Pant et al, 1989).

IV. Treatment

With acute and overwhelming disease, it is reasonable to start early empiric therapy with a 4-drug regimen including isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol. Even with appropriate therapy, the mortality rate may reach 16-24%.

V. Complications

The complications of miliary TB are numerous and may involve any organ. "Sepsis tuberculosis gravissima" is acute overwhelming septic shock with multiple complications such as repiratory failure, ARDS, cholestatic jaundice, acute pancreatitis, hepatic and renal failure, and DIC. Multisystem organ failure has a mortality of up to 90%.