http://dx.doi.org/10.4046/trd.2015.78.2.

47
REVIEW ISSN: 1738-3536(Print)/2005-6184(Online) • Tuberc Respir Dis 2015;78:47-55

Diagnosis and Treatment of Extrapulmonary

Tuberculosis

Ji Yeon Lee, M.D.

Department of Internal Medicine, National Medical Center, Seoul, Korea

Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB
remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus
decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate
specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-
affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase
chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB
drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently
occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required
mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not
available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment.

Keywords: Tuberculosis; Diagnosis; Therapeutics; Surgical Procedures, Operative

Introduction intrathoracic lymphadenitis (mediastinal and/or hilar) or

tuberculous pleural effusion, without radiographic abnormali-
The two types of clinical manifestation of tuberculosis (TB) ties in the lungs, constitutes a case of EPTB1.
are pulmonary TB (PTB) and extrapulmonary TB (EPTB).
The former is most common. EPTB refers to TB involving or-
gans other than the lungs (e.g., pleura, lymph nodes, abdomen, Epidemiology
genitourinary tract, skin, joints and bones, or meninges). A
patient with both pulmonary and EPTB is classified as a case According to the TB notification data, there were 36,089
of PTB. For example, miliary TB is classified as PTB because reported cases of TB (71.4 cases per 100,000 people) in Ko-
there are lesions in the lungs. On the other hand, tuberculous rea in 2013. Of these, 7,369 cases were EPTB (14.6 cases per
100,000) which comprised 20.4% of all cases of TB. The most
Address for correspondence: Ji Yeon Lee, M.D. commonly affected sites of EPTB in Korea were pleura, fol-
Department of Internal Medicine, National Medical Center, 245 Eulji-ro, lowed by lymph nodes, gastrointestinal organs, bones and
Jung-gu, Seoul 100-799, Korea joints, central nervous system (CNS), and genitourinary or-
Phone: 82-2-2260-7536, Fax: 82-2-2260-7281 gans. The reported proportion of EPTB among total TB cases
E-mail: [email protected] from 2005 to 2007 was about 14%, but increased to more than
Received: Feb. 3, 2015
20% from 2010 to 20132. The reason for the increase remains
Revised: Feb. 12, 2015
Accepted: Mar. 3, 2015 unclear. Considering lower voluntary reporting, diagnostic
difficulty of EPTB, and missed cases, it is likely that actual
cc It is identical to the Creative Commons Attribution Non-Commercial proportion of EPTB was much higher than reported. Various
License (http://creativecommons.org/licenses/by-nc/3.0/). factors associated with EPTB have been reported in the litera-
ture. Young age, female gender, Asian and African origin, and
Copyright © 2015 human immunodeficiency virus (HIV) infection are indepen-
The Korean Academy of Tuberculosis and Respiratory Diseases. dent risk factors for EPTB3.
All rights reserved.

47
 JY Lee

Diagnosis quires a long time for M. tuberculosis to become evident dur-

ing culture. As a result, the diagnosis of EPTB mostly depends
1. Mycobacterial stain and culture on histological evidence. For histopathological diagnosis,
presence of granulomas, caseation, and demonstration of AFB
A definitive diagnosis of TB can only be made by culturing have been commonly used to define a positive test. However,
Mycobacterium tuberculosis organisms from a specimen ob- loss of host immune function can result in histopathologic
tained from the patient. However diagnosing EPTB remains findings demonstrating greater suppurative response and less
challenging because clinical samples obtained from relatively well-formed granulomas10. Additionally, the granulomas can
inaccessible sites may be paucibacillary, decreasing the sen- be seen also in nontuberculous mycobacteria disease, fungal
sitivity of diagnostic tests. Since the conventional smear mi- infections, brucellosis, or syphilis, so cautious interpretation is
croscopy has a low sensitivity with a range of 0%–40%, nega- required11.
tive results cannot exclude the presence of TB4. The reported In general, tissue biopsy yields positive culture results more
yields of mycobacterial culture vary from 30% up to 80%, but often than fluid aspiration. The diagnostic accuracy could
it usually takes 2–8 weeks to receive the results, which is too increase further when the results of the biopsy histology and
slow to help treatment decisions4. polymerase chain reaction (PCR) assays are combined with
About 10%–50% of EPTB patients have concomitant pul- those of culture. In one study of tuberculous pleurisy patients,
monary involvement. Therefore, all suspected cases of EPTB diagnostic success of 91% was achieved when the pleural
should be assessed for concomitant PTB to determine wheth- biopsy and culture results were combined12. Likewise, both
er the case is infectious and to assist with diagnosis. Some sensitivities (82.4%–100%) and specificities (94%–100%) were
EPTB patients have positive sputum culture results despite increased when fine needle aspiration (FNA) cytology and
normal chest radiography findings5. The sensitivity of sputum PCR were combined in the diagnosis of TB lymphadenitis13,14.
culture varied in previous studies by site of EPTB: 28%–50% The selection of the diagnostic procedures depends on the
for abdominal TB, 10%–11% for tuberculous pericarditis, organ of involvement in EPTB. Various methods that include
24%–29% for tuberculous meningitis, and 5%–14% for tuber- needle biopsy, excision, endoscopy, laparoscopy, and biopsies
culous lymphadenitis4. Bronchoscopic evaluation or sputum under guidance of ultrasound, computed tomography (CT),
induction with nebulized hypertonic saline can increase diag- or endoscopic ultrasound have been employed to ascertain
nostic sensitivity6,7. In one prospective study of patients with the diagnosis. The relative sensitivities of different procedures
suspected pleural TB, the yield of sputum culture in induced and the potential therapeutic benefits should be considered
samples approached 52%7. in making the choice of diagnostic approach. In superficial
If possible, repeating tests may improve diagnostic perfor- TB lymphadenitis, FNA biopsy of affected lymph nodes is
mance. In patients with urinary tract TB, three to six first-void the first-line diagnostic technique. Excisional biopsy has the
morning urine specimens can improve the likelihood of a pos- highest sensitivity, whereas FNA is less invasive and may be
itive acid-fast bacilli (AFB) culture result with approximately useful14. Thus, if the FNA examination results are inconclusive,
80%–90% (only 30%–40% of single specimens are positive)4. excision biopsy may need to be done. Laparoscopy with tar-
Repeated lumbar punctures and cerebrospinal fluid (CSF) get peritoneal biopsy is the current investigation of choice in
examination also increase diagnostic yield. A previous study the diagnosis of peritoneal TB. Previous studies of peritoneal
reported that AFB smears and culture positivity approached biopsy performed by laparoscopic guidance, minilaparotomy,
87% and 83%, respectively, in four serial CSF samples8. Stool or exploratory laparotomy reported a diagnostic yield of 85%–
cultures for tubercle bacilli are not recommended for diag- 95% for TB peritonitis15. When bone TB is being considered,
nosis of gastrointestinal TB because positive results are more CT-guided needle biopsy is the recommended first approach
likely to occur in patients with active pulmonary disease who to obtain tissue for assessment. If that assessment is non-di-
are swallowing infected sputum9. agnostic, a surgical biopsy should be performed for definitive
Drug susceptibility testing (DST) should be performed on diagnosis and to assess for etiologies other than TB.
the first isolate of M. tuberculosis from all patients. A paradoxi- Histopathologic examination requires the specimen to be
cal reaction during anti-TB therapy occurs more frequently in placed in formalin, which destroys the mycobacteria and pre-
EPTB patients as compared to those with PTB. Therefore, DST vents further culture confirmation. Therefore, biopsy material
can have important treatment implications to distinguish the for mycobacterial culture should be submitted fresh or in a
paradoxical reaction from the treatment failure due to drug small amount of sterile saline.
resistance.
3. Body fluid examination
2. Biopsy
Although tissue biopsy is the most effective method of diag-
Conventional AFB smears have low sensitivity and it re- nosing EPTB, it is invasive and sometimes inaccessible. Con-

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Extrapulmonary tuberculosis

sequently, more easily accessible body fluids, such as pleural, mean sensitivity and specificity of the IFN-γ assay of 89% and
peritoneal, and pericardial fluids, can often provide valuable 97%, respectively28. A study of 30 consecutive patients with di-
diagnostic clues in EPTB patients. verse causes of pericardial effusion demonstrated a sensitivity
As body fluid analysis can show atypical features, the ab- and a specificity of 100%, using a cut-off level of >200 pg/L of
sence of typical findings cannot rule out EPTB. Tuberculous IFN-γ for the diagnosis of TB pericarditis29. However, INF-γ is
pleural fluid is invariably an exudate, with lymphocytic pre- not commonly used in clinical practice compared with ADA,
dominance in about 90% of cases. However, polymorpho- because it is expensive to acquire and complicated to use,
nuclear cells may predominate in patients with symptoms of and because there is lack of evidence that INF-γ is more useful
<2-week duration, though a shift towards lymphocytic pre- than ADA.
dominance is observed at repeat thoracentesis16. The lympho-
cyte percentage in pleural fluid was negatively associated with 4. Nucleic acid amplification test
the probability of a positive effusion culture17,18. Examination
of the CSF typically reveals a leucocytosis (10-1000×103 cells/ The major advantage of nucleic acid amplification test
mL; mostly lymphocytes), raised protein (0.5–3.0 g/L), and (NAAT), such as PCR, is rapid diagnosis. The greatest prom-
CSF:plasma glucose <50%. However, atypical CSF findings are ise is the early diagnosis of life-threatening disease such as
well described, particularly in immune-suppressed patients, TB meningitis. Because EPTB is a paucibacillary disease, the
and the CSF can be acellular or contain a predominance of sensitivity could be improved by PCR, as it can detect as few
neutrophils19. Pericardial fluid assessment typically demon- as 10 mycobacteria30. A systematic review suggested that the
strates a bloody, exudative effusion that is often predominant- NAAT has a relatively high specificity in EPTB, while sensitiv-
ly neutrophilic and not lymphocytic4. ity is generally lower and highly variable among sample types
Measurement of adenosine deaminase (ADA) activity is and test methods31-33. Therefore, a positive NAAT result can
one of the most studied and widely used biomarkers in body be considered a presumptive case, whereas a negative NAAT
fluids for the diagnosis of EPTB. ADA is an enzyme involved cannot be relied upon to exclude the diagnosis31.
in purin metabolism that is found in many tissues, particularly Xpert MTB/RIF assay, a novel, automated, cartridge-based
in T-lymphocytes from the lymphoid tissue. Activity of this NAAT, is considered useful for rapid molecular diagnosis of
enzyme increases in TB patients because of the stimulation EPTB34,35. A recent meta-analysis reported that Xpert MTB/
of T-cell lymphocytes by mycobacterial antigens20. It has been RIF has an overall sensitivity of 83.1% and a pooled specificity
proposed to be a useful surrogate marker for TB in body flu- of 98.7% for the diagnosis of EPTB35. Xpert sensitivity differed
ids, such as pleural, pericardial, and peritoneal fluid, although substantially between sample types. While Xpert was highly
possible false-negative and false-positive results should be sensitive for TB detection in lymph node samples and mod-
considered21-23. erately sensitive for the detection of TB meningitis (80.5% and
Different cut-off values for ADA activity have been sug- 83.1%, respectively), lower sensitivity was shown (46.4%) for
gested as being indicative of disease. For diagnosing TB pleu- testing pleural fluid35. Based on this systematic review, the
risy, sensitivity and specificity are reportedly 92% and 89%, World Health Organization now recommends Xpert over con-
respectively, using a cut-off value of 40 IU/L20. There is a wide ventional tests for diagnosis of TB in lymph nodes and other
range of CSF ADA activity in TB meningitis24,25. An ADA cut- tissues, and as the preferred initial test for diagnosis of TB
off value of 8 IU/L showed a sensitivity of 59% and a specificity meningitis36. The consequences of TB meningitis may be life-
of 96% in the diagnosis of TB meningitis25. The sensitivity and threatening. Thus timely diagnosis and initiation of appropri-
specificity for diagnosing TB peritonitis have been reported to ate therapy are crucial. Given this urgency for rapid diagnosis,
be 100% and 97%, respectively, using cut-off values from 36 to Xpert is recommended as the initial diagnostic test for CSF
40 IU/L, with the optimal cut-off point of 39 IU/L26. Liao et al.23 specimens from patients suspected of having TB meningitis,
suggested that lowering cut-off value to 27 IU/L could increase in preference to conventional microscopy and culture. Also,
the sensitivity and specificity to 100% and 93.3%, respectively, Xpert is conditionally recommended as a replacement test for
in patients with liver cirrhosis, in whom false-negative results usual practice in specific non-respiratory specimens (lymph
are a concern. In the diagnosis of TB pericarditis, the sensitiv- nodes and other tissues) for EPTB. Though Xpert has a low
ity was 88% and specificity was 83%, using an ADA cut-off sensitivity in pleural fluid, a positive Xpert result in pleural
value of 40 IU/L27. fluid can be treated as TB. However, a negative result should
Interferon-gamma (IFN-γ) is a major macrophage-activating be followed by other tests, as it cannot rule out the disease.
cytokine during M. tuberculosis infection. Many studies have The data on the utility of Xpert MTB/RIF for ascitic fluid, peri-
investigated the usefulness of IFN-γ measurements in pleural cardial fluid, urine, blood, or stool are limited.
or pericardial fluid for the early diagnosis of TB. A meta-analy-
sis of 22 studies that included 782 patients with TB and 1,319
patients with nontuberculous pleural effusion reported a

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 JY Lee

5. Immunological tests ficult to generalize due to lack of data.

Tuberculin skin test (TST) and IFN-γ releasing assay (IGRA)

may be the supportive method for diagnosing EPTB, but it has Treatment
a limited diagnostic value.
Interpretation of TST reactivity can be complicated by 1. Anti-TB drugs
cross-reactivity with previous bacille Calmette–Guerin vac-
cination or latent TB infection in countries where TB is preva- Anti-TB treatment is the mainstay in the management of
lent. Factors like HIV infection, poor nutritional status, recent EPTB. However, the treatment regimen is one of the contro-
viral or bacterial infections, or vaccination with live virus can versial aspects of the management of EPTB. Most current
reduce response to the TST. guidelines recommend the same regimen for both EPTB and
Like the TST, IGRA cannot distinguish between latent infec- PTB, but the data for the recommendation for most other
tion and active pulmonary TB or EPTB, and negative results forms of EPTB is not based on studies as robust as those for
cannot entirely exclude the disease. A recent meta-analysis PTB.
evaluating the accuracy of commercially available IGRAs on In addition, the ability of the blood-brain barrier to limit
blood reported that pooled sensitivity and specificity for the intracerebral concentrations of anti-TB drugs is an important
diagnosis of EPTB was 72% and 82%, respectively, for Quan- consideration in the treatment of TB meningitis. While isonia-
tiFERON-TB Gold or QuantiFERON-TB Gold in-tube assay zid, pyrazinamide, protionamide, and cycloserine penetrate
and 90% and 68%, respectively, for T-SPOT.TB37. The diagnos- well into CSF, ethambutol and p-aminosalicylic acid have poor
tic performance of IGRA on blood samples varies according to or no penetration. Rifampicin, streptomycin, and kanamycin
the site of infection. In a prospective study, the T-SPOT.TB was penetrate the CSF well only in the presence of meningeal in-
more sensitive in patients with chronic forms of EPTB, such as flammation. The fluoroquinolones have variable CSF penetra-
lymph node or osteoarticular TB (89% and 100%), than in pa- tion, with excellent penetration seen in later generation drugs,
tients with acute forms of EPTB, such as TB meningitis (74%)38. such as levofloxacin and moxifloxacin48. In a recent phase 2
In another retrospective study, the sensitivity and specificity clinical trial, treatment incorporating high-dose intravenous ri-
of QuantiFERON-TB Gold in-tube in patients with TB lymph- fampicin with the addition of moxifloxacin led to a three-times
adenitis was 81.8% and 80.0%, but 38.5% and 50.0% in patients increase in the plasma and CSF area under the concentration-
with TB pleurisy39. In patients with suspected lymph node time curve and was associated with a survival benefit in TB
or osteoarticular TB, the negative result of blood IGRA may meningitis patients49.
be useful to exclude EPTB. However, the diagnostic value of The optimal duration of therapy is debatable. Although 6
blood IGRA is more limited in TB meningitis or TB pleurisy, months of standard anti-TB medical therapy is generally con-
given the relatively low sensitivities of the tests. sidered adequate for most forms of EPTB, longer treatment is
Several studies have investigated the diagnostic value of suggested for TB meningitis and for bone and joint TB. In case
IGRA on body fluid from infected site for the diagnosis of of bone and joint TB, some guidelines recommend 6 months
EPTB. In a prospective study including 74 patients with TB regimens, because these frequently achieve microbiologic and
serositis, both the sensitivity and specificity of T-SPOT.TB on clinical cure4. However, many experts still prefer a duration
serous effusion (91.9% and 87.1%) were significantly higher of more than 12 months or until radiological or pathological
than the test on peripheral blood (73.0% and 73.1%)40. Pre- evidence of regression of disease occurs, due to the difficulties
viously, the sensitivities of IGRAs using pleural fluid as test of both assessing treatment response and defining the cure. In
samples were inconsistent, ranging from 86.4%–100% for T- this respect, Korean guidelines also recommend 9–12 months
SPOT.TB, and 44.4%–96.4% for QuantiFERON-TB Gold40. In a of treatment for bone or joint TB. In TB meningitis, treatment
meta-analysis of 7 publications, the sensitivity and specificity extension to 12 months has been promoted given the serious
of pleural fluid IGRAs for diagnosing TB pleurisy were 75% risk of disability and mortality and the lack of randomized
and 82%, respectively41. Based on the evidence so far, the controlled studies comparing different treatment durations.
IGRAs are not recommended to diagnose TB pleurisy. The Korean guidelines recommend the regimen consisting of 2
CSF IGRAs show comparatively high specificity (70%–90%) to months of isoniazid, rifampin, pyrazinamide, and ethambutol
make a useful rule-in test, but have low sensitivity (50%–70%) followed by 7–10 months of isonazid and rifampin50.
for the diagnosis of TB meningitis42,43. Because indetermi- On the one hand, 6-month regimens are recommended
nate results are common unless CSF volumes of 5–10 mL for both lymphatic and intestinal TB, because previous ram-
are tested, the advantage of IGRAs compared with NAATs is domized controlled studies on these forms of EPTB showed
unclear44. Limited studies suggest the diagnostic potential of no significant difference in treatment outcome between the
IGRA for TB peritonitis and pericarditis45-47. Overall, the diag- 6-month and the 9-month regimens51,52.
nostic utility of IGRAs according to each site of infection is dif- There is scant information regarding drug-resistant EPTB

50 Tuberc Respir Dis 2015;78:47-55 www.e-trd.org

Extrapulmonary tuberculosis

in the medical literature. A recent study of EPTB in Korea re- positive AFB stain in 17.4%, and positive TB-PCR in 47.8%, but
ported that the overall resistance rate to at least one anti-TB all samples were sterile (no microbiological recurrence) and
drug was 8.9%, and multidrug resistance rate was 1.8%, which most of the patients with lymphadenopathy improved spon-
were similar to or slightly lower than those in the entire TB taneously without further TB medication60. It is complicated
patients53. EPTB that is drug-resistant is treated with the same to differentiate post-therapy paradoxical response from post-
strategy and duration as drug-resistant PTB. If the patient has chemotherapy relapse. Comprehensive assessment consider-
symptoms suggestive of CNS involvement and is infected with ing the clinical findings, previous TB treatment history and
drug-resistant TB, the regimen should use drugs that have ad- DST results is needed.
equate penetration into the CNS48. Treatment of paradoxical reaction remains controversial.
The usefulness of corticosteroids is not well established. Nev-
2. Paradoxical reaction ertheless, in selected patients who continue to have severe
systemic symptoms, the use of corticosteroids may be ben-
A paradoxical reaction is generally defined as the clinical eficial. Occasionally, additional treatment, such as aspiration
or radiological worsening of preexisting TB lesions or the de- of lymph nodes, surgery, or drainage of pleural fluid, may be
velopment of new lesions in a patient who initially improves helpful despite the lack of data.
with anti-TB therapy. A paradoxical reaction occurs more
frequently in EPTB than in PTB. It is rarely reported in <3% 3. Corticosteroids
of HIV-negative PTB patients, whereas in about 16%–50% of
those patients with EPTB54,55. The diagnosis is made by exclu- Despite the availability of effective antimycobacterial
sion. Investigations should be performed to rule out other treatment, adverse outcomes are common in patients with
causes of clinical deterioration such as secondary infections, EPTB, such as death and neurological disability, and fibrotic
treatment failure, multidrug-resistance, poor compliance, or sequelae like pleural fibrosis/loculations and constrictive
drug toxicity. DST is important to distinguish between a para- pericarditis, and strictures of hollow viscera, such as the in-
doxical reaction and treatment failure due to drug resistance. testine and ureter. Corticosteroids often have been used as
In patients with a paradoxical reaction, an anti-TB regimen an adjunctive in the treatment of EPTB for the prevention of
can be administered without any alteration56. these complications. However, there is uncertainty regarding
The most common sites involved in paradoxical reactions the role of adjunctive corticosteroids for EPTB. Currently, the
are lymph nodes, pleura, and CNS54. In a retrospective study available evidence indicates meaningful clinical benefits only
of 459 patients with isolated TB pleurisy, paradoxical reaction in patients with TB meningitis or TB pericarditis.
developed in 16% of the patients approximately 2 months after In TB meningitis, recent randomized controlled trials and
initiation of anti-TB treatment, mostly presenting with aggra- meta-analysis revealed that corticosteroids significantly de-
vation of preexisting pleural effusion57. A number of different crease the mortality and improve the disability-free survival.
paradoxical reactions have been reported in patients with TB Thus adjunctive corticosteroids (either dexamethasone or
meningitis including expansion of existing cerebral tubercu- prednisolone) are recommended to all patients, regardless of
lomas and appearance of new tuberculomas, hydrocephalus, disease severity61,62. The recommended dosage regimens of
vasculitic infarcts, and optochiasmatic and spinal arachnoidi- corticosteroids are dexamethaxone 12 mg/day or 0.4 mg/kg/
tis. Although corticosteroids are routinely used in all patients day for the first 3 weeks in adults, with tapering over the next
with TB meningitis, there are conflicting reports about the 3–5 weeks with monitoring of the improvement19,50.
role of corticosteroids in preventing the development of para- The effectiveness of treatment with corticosteroids in TB
doxical worsening58. Reported outcomes were not generally pericarditis remains controversial. Previous randomized con-
different between the patients with and without paradoxical trolled trials showed that corticosteroids increase the rate of
reaction58. However, for some severe forms of paradoxical clinical improvement and reduce the need for repeated peri-
reaction, like optochiasmatic and spinal arachnoiditis pre- cardiocentesis. In addition, there tends to be lower mortality
senting as vision loss and paraplegia, more aggressive forms and progression to constrictive pericarditis in patients receiv-
of treatment, like immuno-modulatory drugs and surgery ing steroids, but the trials and the meta-analysis did not reach
could be required. In TB lymphadenitis, paradoxical reaction statistical significance63,64. Although published trials are incon-
has been observed in 20%–30% of the patients, usually within clusive, it seems that corticosteroids show a potentially large
3 months after therapy59. Moreover, the worsening of lymph beneficial effect on the mortality and morbidity associated
node lesion has also been observed after the completion of with pericarditis. Therefore, most guidelines recommend cor-
anti-TB therapy, that is post-therapy paradoxical response, as ticosteroids as adjunctive therapy for TB pericarditis during
well as during the therapy. According to a recent prospective the initial weeks of anti-TB therapy. The recommended adult
study, re-biopsy performed in 23 of the 36 patients with post- steroid (prednisone) dosage is 1 mg/kg/day (60 mg/day) for 4
treatment lymphadenopathy revealed granuloma in 52.2%, weeks, tapered slowly over the following 8 weeks (30 mg/day

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 JY Lee

for 4 weeks, 15 mg/day for 2 weeks, and finally 5 mg/day for 2 be unavoidable for sepsis or abscesses. Nephrectomy is not
weeks)50,56. routinely required in those patients without complications,
In pleural TB, corticosteroids hasten the resolution of but is indicated for a non-functioning kidney or extensive
pleural effusion as well as clinical symptoms, but there is no disease involving the whole kidney, together with hyperten-
beneficial influence on the development of pleural thickening, sion and ureteropelvic junction obstruction. Reconstructive
or residual lung function65. There are insufficient data to rec- surgery, mainly the repair of ureteral strictures, and bladder
ommend adjunctive corticosteroid therapy in the treatment of augmentation for a small fibrotic bladder, is frequently re-
peritoneal TB or genitourinary TB. For those forms of TB, the quired. Early ureteral stenting or percutaneous nephrostomy
use of corticosteriods does not significantly reduce the devel- in patients with tuberculous ureteral strictures may increase
opment fibrotic complications like intestinal obstruction or the opportunity for later reconstructive surgery and decrease
ureteric stenosis56. the likelihood of renal loss69.

4. Surgery 5. Monitoring during treatment

With the advent of effective chemotherapeutic agents, the For patients with EPTB, bacteriological evaluation of the re-
need for surgical treatment in TB patients has largely revolved. sponse to treatment is often limited by the difficulty in obtain-
Nevertheless, surgery is often required in EPTB patients, ing follow-up specimens. Response often must be judged on
mainly to obtain valid diagnostic specimens (biopsies) and as the basis of clinical and radiographic findings. The frequency
a therapeutic option under certain circumstances to deal with and kinds of evaluations will depend on the sites involved,
complications or sequelae arising from the disease. severity of disease, and the ease with which specimens can be
Therapeutic lymph node excision is not indicated except obtained. In contrast with PTB treatment, cure for EPTB is dif-
in unusual circumstances. For patients who have discomfort ficult to define. Moreover, there are no established criteria for
from tense, large lymph nodes that are fluctuant and appear the end of treatment.
to be about to drain spontaneously, aspiration or incision and In case of studies on TB lymphadenitis, residual lymph
drainage appears to be beneficial, although this approach has nodes at the end of treatment have usually been used for as-
not been examined systematically14. sessing treatment outcomes. However, residual nodes do not
Although most spinal TB with or without functional impair- always mean an unfavourable outcome. The size of the nodes
ment often responds to chemotherapy, surgery appears to be during follow-up could decrease more after completion of
beneficial and may be indicated in some circumstances. Such treatment. Furthermore, 11%–13% of patients may be left with
situations include severe kyphosis, persistence or recurrence residual nodes in the long term51,70. In bone and joint TB, ra-
of neurological deficit, instability of the spine or clinical dete- diologic markers have been used to assess the cure. However,
rioration while on anti-TB therapy56. plain X-rays may never return to baseline, and recent studies
In TB pleurisy, routine complete drainage of pleural fluid at in spinal TB have shown that 50% of patients had magnetic
the time of diagnosis is not needed because it does not appear resonance imaging evidence of tuberculous activity even at
to decrease the amount of residual pleural thickening66. How- the end of 12 months of treatment71,72. In intestinal TB, most
ever, if the patient is dyspneic from a large pleural effusion, a patients seem to improve within 2 months after therapy initia-
therapeutic thoracentesis should be performed. The admin- tion. Youn et al.73 reported that considerable colonoscopic im-
istration of a fibrinolytic may decrease the degree of residual provement was noted in 93% of patients with intestinal TB at 3
pleural thickening in patients with loculated tuberculous pleu- months of therapy. Based on these results, Korean guidelines
ral effusions67. recommend the follow-up colonoscopy after 2–3 months of
Pericardiectomy is advised in the setting of persistent con- anti-TB therapy74. However, prolongation of therapy may be
strictive pericarditis despite anti-TB therapy for TB pericardi- considered in patients with complicated conditions because
tis. However, the timing is controversial, and data are limited68. of the difficulty in defining a cure.
Placement of a ventriculo-peritoneal shunt for treatment of
hydrocephalus is the most frequent surgical intervention per-
formed in patients with TB meningitis. Also, urgent surgical Conflicts of Interest
decompression should be considered in patients with tuber-
culomas producing obstructive hydrocephalus or compress- No potential conflict of interest relevant to this article was
ing the brainstem, and extra-dural lesions causing parapare- reported.
sis19.
In urinary system TB, surgery is more frequently required
than in other organs. Although chemotherapy is the mainstay
of treatment, ablative surgery as a first-line management may

52 Tuberc Respir Dis 2015;78:47-55 www.e-trd.org

Extrapulmonary tuberculosis

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