**4. Clinical manifestations and natural course**

Tuberculous pleurisy may occur as an acute, subacute or rather chronic disease. At times the course is also surprisingly oligosymtomatic. Therefore duration of symptoms or major illness priortohospital admissionanddiagnosisvaries considerably from< 1 week (31 %)to < 1months (62%)or evenlonger(7%)[28].Thesedata refertothepre-HIVera andwouldnot applyforHIVseropositive patients and elderly populations, which both tend to have a particularly long symptomatic or else oligosymtomaticperiod.Aninfectious,i. e.febrile illness isnevertheless by far the most common clinical presentation. As a general rule, an acute febrile illness is the more likely to occur the younger and the more immunocompetent a given patient is. In developing, high-prevalence and high primary-TB-affected countries the age peak of incidence is in the mid thirties, whereas in industrialized countries with a major contribution of reactivated TB it has shifted to about 50 yrs [29]. But still the age-related incidence peak of tuberculous pleuritis is distinctly lower than of parenchymal pulmonary TB which used to peak around 55 yrs [30]. Implicitly by the same statement in Western populations TB-pleurisy was historically more symptomatic than is currently the case. In a representative series from the 1960-1970s ~ 60 % of patientsdevelopedanacute illnessmimickingbacterial(pleuro)-pneumoniawithcough(70%), chest pain (75 %) and low- to high-grade fever (86 %) as the most frequent symptoms [31, 32]. Other symptoms include those commonly occurring in various TB disease states such as weight loss,malaiseandnight sweat.Severeorevenlivethreateningdisease,definedaspersistenthighgrade fever > 38,3°C over > 2 weeks or respiratory distress has been in reported in a more recent series in only 7 % [31], whereas an oligosymptomatic or a febrile course is described in 14-33 % [32]. Tuberculous pleurisy usually involves one hemithorax only (90-95 %) and is of limited size (roughly up to one-half of the hemithorax volume). In a major series (n=254) effusions occupy‐ ing more than 2/3 of a hemithorax were noted in only 18 % [33]. Rarely effusion will occupy the entirehemithoraxandwillalmostneverrevealcompressiveordisplacingfeatures [31].Basically there are no specific clinical clues to tuberculous etiology in pleurisy unless some TB-contact is revealed or suspected. An HIV-related background may be suspected in a compatible clinical and history setting or when there is a long preclinical period, unusual additional symptoms like diarrhea and more hepato(spleno)-megaly or lymphadenopathy as might be attributed to the tuberculous condition. Untreated, lone pleuritis exudativa tuberculosa in the short term seems to be a self-limited inflammatory process in most instances, terminating in complete or incom‐ plete resolutionwithinweeksormonth.Frequentlyobservedotherwiseunexplaineddiaphrag‐ maticadhesionsmaybealatesequelofclinicalsilentoroligosymtomaticTBpleurisy.Importantly however progression or reactivation to active pleuropulmonary or extrapulmonary TB occurs inanimportantfraction.Inone follow-upstudythe recurrence ratewithin1yearwas 5%,where TBdidnotrelapseearlierthan8monthaftertheonsetofpleurisy.Withina4-5yrperiodhowever the rate was dramatically higher and in initially culture positive and culture negative subjects with 65 % and 60 % respectively roughly alike [27]. One major outcome determinant clearly is the presence and the extent of pulmonary involvement. At a similar therapeutic intensity in a very recent major clinical study from Taiwan, 51 (24,9 %) out of 205 hospitalised patients having beenidentifiedtohaveisolated(lone)pleuritishadasignificantlybetteroutcome,shorterhospital stay and less comorbidity than the patients with pleuropulmonary disease [34].

aetiology, but this observation holds also true for "plain" parapneumonic pleurisy. Usual signs of systemic infection, as mentioned above, that should be looked for, may alert to the possibility

Tuberculous Pleural Effusion http://dx.doi.org/10.5772/54955 273

Imaging techniques are engaged in the evaluation of tuberculous pleurisy following general diagnosticpathwayrecommendationsforeffusion.*Conventionalchestradiography(CRX)*requires fluid amounts of at least 150 ml to become clearly detectable as blunting of the costodiaphrag‐ matic angle in standard projections. Profuse effusion with opacification of an entire hemithor‐ ax wouldratherfavourdifferentialdiagnoses likemalignancyinthe elderly andafebrilepatient [35]. Free flowing effusion may be easily identified, but one should look specifically for signs of loculation, pleural thickening or adhesions and in profuse effusion for compressive signs interfering with the respiratory performance. Apart from pleural changes pulmonary infil‐ trates, nodules, lymphnodes and other suggestive signs of TB like encapsulated or cavitary lesions must be carefully looked for using routine *CT-imaging*. CT-based prevalence of lung perenchymal tuberculous lesions in mixed populations appears to be significantly higher than previously assessed based on conventional radiography. In one recent series from Korea comprising 106 patients with an age distribution from 16-89 yrs (mean 53) with 86% a remarka‐ ble high rate of parenchymal changes was found, presumed to represent active tuberculosis in 59 % [36]. Most of these lesions revealed features of reactivated rather than primary tuberculo‐ sis. *Sonography (Ultrasound, US)* using innovative technical achievements like high frequency (5-7.5 MHz) – US and convex or sector scanners allow extended exploration of the chest wall structures, the diaphragm and the anterior mediastinum up to a penetration depth of ~ 25 cm. Specific advantages of US are a more precise fluid volumetry than by CRX, precise localisation of septae, membranes and chambers as well as pleural thickening along with its particular versatility for bedside diagnosis. On demand guidance for interventions such as thoracentesis is a particular asset of US.. Examples are shown in figure 2, 3. *Magnetic-resonance imaging (MRI)* isahighlyrefined,notgenerallyavailabletechnique,whichwillrarelyberequiredbutdoeshave differential diagnostic merits in the analysis of critical borderline relationships i. e. distinguish‐ ingbetweeninflammatory-infiltrativeandmalignant-destructivepleuralprocessesviadifferent T-weighted sequences [37]. Very recently a role of PET-CT has also been described. PETimagingmayindeedprovidedifferentlyextensive focal andimpressinglaminar changeswhich

however remain indistinguishable from malignant lesions [38].

The tuberculin skin reaction is traditionally considered an indispensable tool in the diagnosis of tuberculosis in general and likewise in tuberculous pleurisy although it is less reliable than in pulmonary TB. The rate of false negative reactions to PPD has been given as high 30 % of cases but even figures up to < 41 % have been reported [31, 32, 33], the variability possibly reflecting non-standardised test doses. Still however there remains an amazing false negative rate. There is no absolutely satisfying hypothesis to explain this paradoxon, let alone unequiv‐

of a HIV-related background.

*5.1.2. Imaging studies*

**5.2. Immunologic tests**

*5.2.1. Tuberculin skin reaction*
