Clinical Aspects of Adult Tuberculosis

Downloaded from http://perspectivesinmedicine.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Clinical Aspects of Adult Tuberculosis Robert Loddenkemper1, Marc Lipman2, and Alimuddin Zumla3 1Charite´ Universita¨tsmedizin Berlin, Department of Pneumology, HELIOS-Klinikum Emil von Behring, 14165 Lungenklinik Heckeshorn, Berlin, Germany 2Respiratory & HIV Medicine, Royal Free London NHS Foundation Trust, University College London, London NW3 2QG, United Kingdom 3Division of Infection and Immunity, University College London, Consultant Infectious Diseases Physician, University College London Hospitals NHS Foundation Trust, London NW3 2PF, United Kingdom Correspondence: [email protected] Tuberculosis (TB) in adults can present in a large number of ways. The lung is the predominant site of TB. Primary pulmonary TB should be distinguished from postprimary pulmonary TB, which is the most frequent TB manifestation in adults (70%–80% cases). Cough is common, although the chest radiograph often raises suspicion of disease. Sputum sampling is a key step in the diagnosis of TB, and invasive procedures such as bronchoscopy may be necessary to achieve adequate samples for diagnosis. Extrapulmonary involvement, which may present many years after exposure, occurs in a variable proportion of cases (20%–45%). This reflects the country of origin of patients and also the frequency of associated human immunodefi- ciency virus (HIV) coinfection. In the latter case, the presentation of TB is often nonspecific, and care needs to be taken to not miss the diagnosis. Anti-TB therapy should be given in line with proven (or assumed) drug resistance. In extrapulmonary TB, adjunctive therapeutic measures may be indicated; although in all cases, support is often required to ensure that people are able to complete treatment with minimal adverse events and maximal adherence to the prescribed regimen, and so reduce risk of future disease for themselves and others. www.perspectivesinmedicine.org n parts of the world where tuberculosis (TB) is accentuated by the stigma associated with a po- Iendemic, symptomatic individuals and their tential diagnosis of TB (as well as HIV coinfec- health-care providers are likely to recognize and tion) (Courtwright and Turner 2010). Hence, consider TB early within the diagnostic algo- education for individuals, communities, and rithm (Aı¨t-Khaled et al. 2010). However, in social care providers about TB symptoms, countries with a declining or low prevalence, and where and how to get them investigated, the time to diagnosis and starting treatment is an important part of clinical management can be prolonged. This may be attributable to (Chowdhury et al. 2013; TB CARE 2014). both patient and health system factors (Millen Considering TB as the cause of a person’s et al. 2008, Migliori et al. 2012) and can be symptoms (or new signs in a child with a sig- Editors: Stefan H.E. Kaufmann, Eric J. Rubin, and Alimuddin Zumla Additional Perspectives on Tuberculosis available at www.perspectivesinmedicine.org Copyright # 2015 Cold Spring Harbor Laboratory Press; all rights reserved Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a017848 1 Downloaded from http://perspectivesinmedicine.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press R. Loddenkemper et al. nificant exposure), making a rapid and accu- CLINICAL PRESENTATION AND rate diagnosis and initiating effective treatment DIAGNOSIS OF TB promptly are central to good patient care and public health TB management. Not only does Pulmonary TB this alleviate symptoms and reduce mortality Pulmonary TB is defined as tuberculosis of for the individual, but it also decreases onward the lung parenchyma and the tracheobronchi- transmission to others and hence impacts on al tree only. Primary pulmonary TB should be the overall burden of TB. distinguished from postprimary pulmonary TB in adults can present in a variety of ways. TB, which is the most frequent TB manifesta- The lung is the predominant site of TB as in- tion in adults. The classic clinical features of fection with Mycobacterium tuberculosis (Mtb) pulmonary TB include chronic cough, sputum or other members of the TB complex arises production, appetite loss, weight loss, fever, almost exclusively from inhaling droplets con- night sweats, and hemoptysis (Lawn and Zumla taining the bacilli. This may result in sympto- 2011). Someone presenting with any of these matic, primary pulmonary TB disease (usually symptoms should be suspected of having TB. in children) and in adults, after a variable If they are or were known to be in contact amount of time in a clinically asymptomatic with infectious TB, they are even more likely state of latent TB infection (LTBI), generally as to be suffering from TB (Ait-Khaled et al. 2010.) postprimary pulmonary TB. Mtb may spread directly from the lungs, via the lymphatics, or Primary Pulmonary TB the bloodstream, to other body sites causing the various extrapulmonary TB manifestations de- In countries with a high TB prevalence, primary scribed in this review. pulmonary disease occurs usually in childhood, The location of disease should be docu- but where TB is less endemic, it occurs fairly mented in all patients. Given that there may be often also in adults. It is characterized by local multiple sites involved, it is recommended that granulomatous inflammation, usually in the at least two, a major and a minor site, when periphery of the lung (Ghon focus), and may applicable, be recorded. Here, the definitions be accompanied by ipsilateral lymph node in- used are those proposed by a Working Group volvement, termed the Ghon complex. The in- of the World Health Organization (WHO) and fection is usually asymptomatic but can present the European Region of the International as an acute lower respiratory tract infection. The Union Against Tuberculosis and Lung Disease most important clue to the diagnosis is a histo- (IUATLD) for uniform reporting of TB cases ry of close contact with an infectious TB case. www.perspectivesinmedicine.org (Rieder et al. 1996). The diagnosis is suspected when a tuberculin It is important to note that TB can be diag- skin test or a blood interferon-g release assay nosed via a number of different clinical path- (IGRA) converts to positive, usually 3–8 wk af- ways and settings. In a low incidence country ter infection. The chest radiograph may show such as Germany, among more than 25,000 TB the Ghon focus/complex (Fig. 1). cases studied between 1996 and 2000, almost Rare primary sites of TB are the alimentary 80% were diagnosed through passive case find- tract caused by swallowing Mtb, usually Myco- ing (62% had symptoms suggesting TB, 16% bacterium bovis, present in nonpasteurized milk were diagnosed during investigations for other products (de la Rua-Domenech 2006), or after medical causes, 1% at autopsy) and 19% by direct cutaneous infection (usually occurring active case finding in high-risk groups, partic- in laboratory personnel) (Menzies et al. 2003). ularly in close contacts of infectious patients Intravesical Bacillus Calmette–Gue´rin (BCG) (Forssbohm 2004). This further reinforces the vaccination used to treat localized bladder tu- importance of thinking of TB as a possible cause mors may occasionally disseminate and pre- of a patient’s symptoms or signs in clinical prac- sent as primary BCG disease (Fig. 2) (Lamm tice (Craig et al. 2009). 1992). 2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a017848 Downloaded from http://perspectivesinmedicine.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press Clinical Aspects of Adult Tuberculosis the skeletal or urogenital system and other or- gans may result (Wallgren 1948). Postprimary pulmonary TB may follow primary TB. In the generally immunocompetent, there is a lifetime chance of reactivation of the dormant primary complex of 5%–10% (Hors- burgh Jr 2004). These estimates were developed before the availability of molecular techniques that can distinguish reactivation from reinfec- tion with another strain of Mtb, and it may be that the overall risk is rather less in most people with latent TB infection not exposed again to Mtb. The first 2 yr following primary infection are the period of maximal risk of progression. This can be reduced significantly by treating Ghon complex. (Figure reprinted from Figure 1. LTBI, which is indicated particularly in high- Fuehner et al. 2007, with permission, from Springer, # 2007.) risk groups (Table 1) (Diel et al. 2013). It is not known why only 10% of individuals in- fected with Mtb develop active disease. Apart Local complications of primary pulmonary from diverse risk factors such as diabetes, smok- TB may result from lymph node enlargement ing, and chronic renal failure (Hu et al. 2014), leading to bronchial obstruction. Tuberculous several genes have been found to be associated pleurisy can arise early in the course of primary with increased susceptibility to, or resistance pulmonary TB, either by direct spread from the against, Mtb (Mo¨ller et al. 2010). pulmonary lesion or through hematogenous Erythema nodosum and other skin condi- dissemination. tions such as granulomatous panniculitis plus Rare, serious, early systemic complications forms of uveitis and polyarthritis (Poncet’s dis- caused by blood-borne spread of Mtb are mili- ease) are considered to reflect the host immune ary TB and meningitis. Many years later, TB of response to mycobacterial antigen. They can be www.perspectivesinmedicine.org Figure 2. Disseminated BCG disease. Computed tomography (CT) of the chest showing bilateral patchy ground glass shadowing and consolidation in a patient who developed fevers, cough, and positive blood cultures for BCG following treatment with intravesical BCG for bladder carcinoma. (Figure provided by Marc Lipman.) Advanced Online Article. Cite this article as Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a017848 3 Downloaded from http://perspectivesinmedicine.cshlp.org/ on October 1, 2021 - Published by Cold Spring Harbor Laboratory Press R.

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