CHAPTER

Tuberculosis
Amy J. Behrman

31

Tuberculosis (TB) is a major global health problem, infecting one-third of the worlds population and causing approximately 2 million deaths annually. In the United States, TB is an important public health problem, particularly among immigrants whose active TB case rate is 11 times higher than that of nonimmigrants. Other risk factors include HIV infection; living or working in prison, shelters, and long-term care facilities; caring for TB patients; and alcohol/drug abuse.

CLINICAL FEATURES
Primary TB Primary TB infection is usually asymptomatic in immune-competent adults, generally presenting with only a new positive reaction to TB skin testing. When present, symptoms often include fever, cough, weight loss, malaise and chest pain. Some patients may present with active pneumonitis (which may be mistaken for community-acquired pneumonia) or extrapulmonary disease. Children are more likely to present with active early disease, although the presenting symptoms may be subtle even when chest radiographs (CXRs) are abnormal. Presenting symptoms may include fever, cough, wheezing, poor feeding, and fatigue. TB meningitis and military TB (see descriptions below) are more common in children than adults. Immunocompromised patients are much more likely to develop rapidly progressive primary infections. (All patients with active TB should be evaluated for immune-compromising conditions.) Symptoms may be pulmonary (fever, cough, dyspnea, hemoptysis) or may be extrapulmonary, reflecting early hematogenous spread to the central nervous system or other sites. Reactivation TB Latent tuberculosis infections are asymptomatic with positive tuberculin skin tests (TSTs) and/or positive interferon-gamma release assays (IGRAs). Latent tuberculosis infections will progress to active disease (ie, reactivation TB) in 5% of cases within 2 years of primary infection; an additional 5% will reactivate over their lifetimes. Reactivation rates are much higher in the very young, the elderly, persons with recent primary infection, those with immune compromise (in particular, HIV), and those with chronic diseases such as diabetes and renal failure. Most patients with reactivation TB present subacutely with fever, malaise, weight loss, fatigue, and night sweats. Most patients with active TB will have pulmonary involvement characterized by subsequent development of productive cough. Hemoptysis, pleuritic chest pain, and dyspnea may develop. Rales and rhonchi may be found, but the pulmonary examination is not usually diagnostic. TB should be considered in any HIV patient with 177

178 SECTION 5: Pulmonary Emergencies respiratory symptoms, even if chest radiographs are normal (see Chapter 92 HIV and AIDS). Extrapulmonary TB develops in up to 20% of cases. Lymphadenitis, with painless enlargement and possible draining sinuses, is the most common presentation. Patients may also present with symptomatic pleural effusion, pericarditis, peritonitis, or meningitis. Additional sites of reactivation TB after hematogenous spread include bones, joints, adrenals, GI tract and GU tract. Extrapulmonary reactivation TB is more common and often more severe in young children and immune-compromised patients as noted for primary TB infection above. Miliary TB is a multisystem disease caused by massive hematogenous dissemination. It is also more common in immune-compromised patients and young children. Symptoms are systemic with fever, weight loss, adenopathy and malaise. Patients may present with multiorgan failure or ARDS.

DIAGNOSIS AND DIFFERENTIAL

Variable presentations and limited testing options make TB diagnosis particularly challenging in the ED. Consider the diagnosis of active TB in any patient with respiratory or systemic complaints, in order to facilitate early diagnosis and treatment and to reduce exposure risks. Differential diagnoses may include other infectious causes of pulmonary and extrapulmonary lesions as well as malignancy. Imaging CXR is still the most useful ED diagnostic tool for TB. Active primary pulmonary TB usually presents with parenchymal infiltrates in any lung area. Hilar and/or mediastinal adenopathy may occur with or without infiltrates. Effusions, usually unilateral, may be seen with or without infiltrates. Reactivation TB classically presents with lesions in the upper lobes or superior segments of the lower lobes (Fig. 31-1). Cavitation, calcification, scarring, atelectasis, hilar adenopathy, and effusions may be seen. Cavitation is associated with increased infectivity. Miliary TB may cause diffuse, small (1 to 3 mm) nodular infiltrates. Patients coinfected with HIV and TB are particularly likely to present with atypical chest radiographs. Scarring, volume loss, and calcified or noncalcified nodules may be identified (often as incidental findings) in patients with asymptomatic latent TB infection; these patients do not require urgent treatment or isolation. Comparison with prior films may be very useful in determining the likelihood of active TB infection. Laboratory Studies Acid-fast staining of sputum can detect mycobacteria in 60% of patients with pulmonary TB, although the yield is lower in HIV patients. Results may be available within several hours, which increases potential ED utility, but there are serious limitations. Many patients will have false negatives on a single sputum sample. Microscopy of nonsputum samples (eg, pleural fluid, cerebrospinal fluid) is even less sensitive. Microscopy cannot differentiate between TB and nontuberculous mycobacteria.

CHAPTER 31: Tuberculosis 179

FIGURE 31-1. Cavitary tuberculosis of the right upper lobe.

Culture of sputum (or other specimens) is the gold standard for diagnosing active TB. Unfortunately, definitive culture results generally take 4 to 6 weeks. When available, newer technologies such as TBspecific nucleic acid amplification can produce results within 24 hours (thus rendering these tests potentially applicable to ED management). These tests have better positive predictive value than acid-fast staining and may also enable more cost-effective utilization of isolation, treatment, and contact-tracing resources. Tuberculin skin tests (TST), identify most patients with latent, prior, or active TB. Results are read 48 to 72 hours after placement, limiting the ED utility of this approach. Patients with HIV or other immunosuppressive conditions, and patients with disseminated TB, may have false negative TSTs. Immigrants who received BCG vaccine in childhood may have false positive TSTs. Finally, the TST may become paradoxically negative during active TB infection. Interferon-gamma release assays (IGRA) of whole blood may become more useful than TST for ED evaluation of suspected TB, since these tests may produce results within hours. IGRAs appear to be equally sensitive to, and more specific than, TST. The fact that prior BCG vaccination should not cause false positive results makes IGRA particularly useful when evaluating immigrants from high-prevalence countries.

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SECTION 5: Pulmonary Emergencies

EMERGENCY DEPARTMENT CARE AND DISPOSITION

1. ED and prehospital staff should be trained to identify patients at risk for active TB early in their evaluation and isolation protocols should be enacted (see parent chapter). 2. Therapy should include at least 4 drugs until susceptibility profiles are available for a patient. The initial regimen usually includes: isoniazid, INH (5 milligrams/kilogram up to 300 milligrams PO daily in adults, 10 to 15 milligrams/kilogram up to 300 milligrams PO daily in children), rifampin (10 milligrams/kilogram up to 600 milligrams PO daily in adults, 10 to 20 milligrams/kilogram up to 600 milligrams PO daily in children), pyrazinamide (20 to 25 milligrams/kilogram up to 2 grams PO daily in adults, 15 to 30 milligrams/kilogram up to 2 grams PO daily in children), and ethambutol (15 to 20 milligrams/kilogram up to 1.6 grams PO daily in adult, 15 to 20 milligrams/kilogram up to 1 gram PO daily in children) for 2 months. Give pyridoxine 10 to 50 milligrams/day with INH. At least 2 drugs (usually INH and rifampin) are continued for 18 to 31 months. An alternative to rifampin in adults is rifabutin (5 milligrams/kilogram up to 300 milligrams PO daily). Directly observed therapy (DOT) may improve outpatient compliance with these complex regimens (see parent chapter for DOT recommendations and more treatment options, or see the Centers for Disease Control and Prevention website http://www.cdc.gov/tb/). Patients with immune compromise or multidrug resistant (MDR) TB may require more drugs for longer periods. When available, culture and sensitivity results are used to tailor the antimicrobial regimen. 3. Concern for MDR TB should be high in patients with history of birth in or travel to endemic areas. MDR TB is also more likely in patients who have previous TB treatment, HIV infection, cavitary disease, or known acid-fast positive sputum smears. Treatment of known or suspected MDR TB begins with at least 4 oral drugs plus an injectable agent (eg, spectinomycin, amikacin, capreomycin). ID consultation is appropriate for MDR TB. 4. Admission is indicated for clinical instability, hypoxia, dyspnea, diagnostic uncertainty, unreliable outpatient follow-up or compliance, and suspected or known MDR TB. ED physicians should know local laws and resources regarding involuntary hospitalization and treatment (including DOT). Patients with suspected TB should wear masks during all transport, and these cases should be admitted to airborne-isolation single rooms. 5. Patients with active TB who are discharged from the ED must have documented immediate referral to a physician or local public health department for long-term treatment and contact tracing. Most TB can be treated in the outpatient setting with closely monitored daily or intermittent regimens. TB treatment should usually be initiated by the ambulatory providers who will be monitoring compliance and adverse events, rather than by the ED physician. Persons with latent TB infection should be referred to primary care or public health clinics for INH treatment (to prophylax against reactivation TB).
For further reading in Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 70, Tuberculosis, by Vu D. Phan and Janet M. Poponick.