Letters To The Editor
In high-prevalence countries, the diagnosis may be different.
Catherine Anne Curley, MD
Division Director, Hospital Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH; Medical Director, Cuyahoga County TB Program; Associate Professor of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH
Address: Catherine Anne Curley, MD, Department of Medicine, MetroHealth Medical Center, 2500 Metrohealth Drive, Cleveland, OH 44109; e-mail: Ccurley@metrohealth.org
As tuberculosis rates decline in the United States, clinicians are less likely to consider it early in a patient’s illness. Certain clinical and radiographic features increase the likelihood of tuberculosis. This review covers the clinical and radiographic features of tuberculosis, the initial evaluation of the patient, the use of airborne infection isolation, and the utility of new molecular techniques in diagnosing tuberculosis.
Tuberculosis rates in the United States are at an all-time low, which is good news for public health. However, as clinicians see fewer cases of tuberculosis, their skill at making this diagnosis rapidly diminishes.
In 2012, for the first time, fewer than 10,000 tuberculosis cases were reported in the United States to the Centers for Disease Control and Prevention (CDC),1 for a case rate of 3.2 per 100,000. This is in sharp contrast to the worldwide burden of tuberculosis: the World Health Organization2 estimated that there were 8.6 million new cases of tuberculosis in 2012. As a result of travel and immigration, clinicians in the United States will continue to see sporadic cases of active tuberculosis in their hospitals and clinics.
This review describes the clinical and radiographic clues to the diagnosis of pulmonary tuberculosis, discusses the use and discontinuation of respiratory isolation, and reviews the use of new diagnostic technologies.
CASE 1: A COLLEGE STUDENT WITH FATIGUE
A 23-year-old graduate student presents to the student health clinic with vague symptoms of fatigue and several pounds of weight loss over the past 3 months. When asked about coughing, he says he thinks he has had a mild, nonproductive cough for about a month. On examination he is thin, appears comfortable, and has faint rales in the right middle lung zone.
The clinician thinks that the symptoms are likely related to stress, lack of sleep, and difficulty adapting to graduate school life. However, in view of the pulmonary finding on examination, the physician obtains a complete blood cell count (CBC) and a chest radiograph. The CBC is normal. The radiograph (Figure 1) reveals a patchy, somewhat nodular infiltrate in the right upper lobe. The radiologist reviews the results, noting that tuberculosis is high on the list of possible diagnoses. The clinician calls the student and obtains the following additional history.
The patient was born in Thailand and arrived in the United States 3 months ago. Soon after his arrival, he had a tuberculin skin test with purified protein derivative in the student health department, which produced an induration 18 mm in diameter. The patient dismissed this finding as a false-positive result, attributing it to having received BCG vaccine in his native country, and he therefore did not follow up as recommended for a chest radiograph. He denies having fever, night sweats, or hemoptysis.
Since the patient lives in a college dormitory and has four roommates, the clinician admits him to the hospital for further evaluation and for airborne infection isolation. Sputum smears are positive for acid-fast bacilli, and samples ultimately grow Mycobacterium tuberculosis. He is started on standard antituberculosis treatment with isoniazid, rifampin, ethambutol, and pyrazinamide and discharged about 1 week later. He does well. Approximately 50 of his classmates are tested for possible exposure to tuberculosis.
CASE 2: A MAN WITH ACUTE-ONSET SYMPTOMS
A 35-year-old man presents to the emergency department for evaluation of cough with sputum production, fever, nausea, vomiting, and diarrhea. The symptoms began suddenly 1 week previously. He has no medical history, was born in the United States, and works in computer sales. On examination he looks uncomfortable, is slightly tachypneic, and has a temperature of 101°F (38.3°C).
Given his complaint of cough, chest radiography and a CBC are ordered. The white blood cell count is 18.0 × 109/L (reference range 4.5–11.0), with 50% bands (reference range 3%–5%). The chest radiograph (Figure 2) shows a dense infiltrate in the right upper lobe, with air bronchograms and possible right hilar fullness.
The patient is diagnosed with community-acquired pneumonia, and because his oral intake is poor, he is admitted to the hospital and started on azithromycin and ceftriaxone. Blood cultures the next day grow Streptococcus pneumoniae. He fully recovers. A follow-up radiograph is performed 6 weeks later because of the right hilar fullness, and it is normal.
These two cases demonstrate the importance of clinical, demographic, laboratory, and radiographic clues to raise or lower our suspicion for pulmonary tuberculosis. Both patients had right-upper-lobe infiltrates on radiography, yet the diagnosis of tuberculosis was considered only in the first patient.
CLINICAL CLUES TO PULMONARY TUBERCULOSIS
Symptoms of tuberculosis are generally indolent in onset, often so much so that the patient does not realize that he or she is sick until after starting treatment and beginning to improve. In addition, the symptoms can be vague, including only mild fatigue and cough. The classic symptoms of prolonged nonproductive cough, hemoptysis, weight loss, and fever often do not appear until the disease is quite advanced in the lung and the patient has been sick for months.
Since the symptoms of tuberculosis can be nonspecific, the patient’s social and demographic characteristics are important in assessing the likelihood that his or her current illness is tuberculosis.
Almost two-thirds of all reported tuberculosis cases in the United States are in people who were born outside of the United States.1 The highest risk of reactivation appears to be within the first 5 years after immigration to the United States.3
Certain medical conditions predispose to reactivation of tuberculosis and should be considered when evaluating someone for active tuberculosis. These include human immunodeficiency virus infection and immunosuppression from tumor necrosis factor inhibitors, steroids, and medications used in organ transplantation. Other risk factors include diabetes requiring insulin, end-stage renal disease, and hematologic malignancies.4 Absence of these risk factors does not exclude tuberculosis, but it decreases the likelihood.
Findings on physical examination and laboratory testing are generally nonspecific in active tuberculosis. In particular, fever is present in 40% to 80% of patients. The white blood cell count is generally normal or only slightly elevated.
While the presenting symptoms and physical findings can be nonspecific, there are definite clues to the diagnosis of tuberculosis on chest radiography. In adults, most cases of tuberculosis are reactivation-type, which means the patient was exposed to tuberculosis many months to years in the past.
Reactivation-type tuberculosis usually occurs in the upper lobes, classically in the apical and posterior segments. The infiltrates tend to be patchy rather than densely consolidated. Cavitation, when present, increases the likelihood of tuberculosis. Intrathoracic lymphadenopathy, which occurs in primary tuberculosis, is generally not seen in adults with typical reactivation pulmonary tuberculosis.
However, adults who are highly immunosuppressed, such as those with advanced human immunodeficiency virus infection, organ transplant recipients, or those taking tumor necrosis factor inhibitors, may have radiographic features that are atypical for tuberculosis. For example, they may present with hilar adenopathy or lower-lobe infiltrates.5
Because tuberculosis rates have been declining and most hospitals have a limited number of rooms for airborne infection isolation, several studies have evaluated clinical prediction rules for diagnosing pulmonary tuberculosis.
Reactivation-type tuberculosis usually occurs in the upper lobes
In general, the signs and symptoms that predict tuberculosis are similar to those discussed above, including chronic symptoms, immunosuppression, birth in a region with a high incidence of the disease, a chest radiograph showing upper-zone findings, a positive tuberculin skin test, and fever.6–8 The studies that identified these factors are limited in generalizability as they were performed and validated in single institutions, and the prediction rules have not been widely adopted. Yet they provide a straightforward way to determine which patients should be prioritized for isolation.
RETURN TO THE CASES
The student in case 1 had several features suggesting tuberculosis: indolent and nonspecific symptoms, normal CBC, patchy upper-lobe infiltrates, birth in a country that has a high incidence of tuberculosis, and a positive skin test.
In contrast, the man in case 2 had features that made tuberculosis much less likely: acute symptoms, markedly elevated white blood cell count, and densely consolidated infiltrate. He was also born in the United States and had no additional risk factors for tuberculosis exposure.
In high-prevalence countries, the diagnosis may be different.
Purified protein derivative testing and the interferon-gamma-release assay are more useful in low-prevalence countries like the United States.