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Proportion of TB reported to Public Health England New developments in the diagnosis of extrapulmonary
2000-2011 tuberculosis
miliary CNS
bone 3% 3% genitourinary C Automated DNA tests (e.g. Xpert MTB/RIF) are rapid tests
6% 1% (w2 hours) that detect the presence of MTB DNA and test for
gastrointestinal mutations in the rpoB gene
4% C In extrapulmonary samples, the overall sensitivity is 77.3e95%
and specificity 99e100%, equivalent to tuberculosis (TB) liquid
pleural culture3,5
7% C rpoB mutations identify 95% of resistance to rifampicin
(taken as an indicator of multi-drug resistant TB). This
other extra- represents a huge advance in TB diagnostics
pulmonary
pulmonary C Urine enzyme-linked immunosorbent assay (dipstick) tests
51%
6% extra thoracic (Determine TB-LAM ) detect the mycobacterial cell wall
lymphadenitis lipopolysaccharide antigen, lipoarabinomannan (LAM).
19%
Although still in development, they have potential as a low-cost,
point-of-care test to detect disseminated TB in highly
immunosuppressed patients (advanced HIV with CD4
count <200 cells/mm3 e also those most likely to benefit
Figure 1 from prompt treatment)6,7
Specific extrapulmonary TB syndromes by disease site lymphadenitis may present with dysphagia or recurrent laryngeal
nerve involvement; abdominal/peritoneal disease, usually
Miliary TB affecting periportal, mesenteric or peri-pancreatic nodes, often
Miliary TB results from massive lympho-haematogeneous spread causes non-specific abdominal pain. Ultrasound or computerized
throughout the body. It accounts for 3% of EPTB cases and is tomographic (CT) imaging may show matted mesenteric lymph
associated with immunodeficiency. Infection is multi-bacillary, nodes with fat stranding and oedema. Rarely, enlarged lymph
with foci in many organs and mortality is high.9 The term nodes cause obstructive symptoms in the liver (presenting with
‘miliary’ (Manget, 1700) refers to the resemblance of pulmonary jaundice) or renal vasculature.
and hepatic nodules to millet seeds. Classically, these appear on Fine-needle aspiration (FNA) of the affected node is recom-
chest radiology as multiple small ("2 mm), discrete opacities. mended for mycobacterial molecular diagnostics and culture,
and to exclude differentials such as malignancy or other in-
TB lymphadenitis
fections (e.g. Bartonella, Toxoplasma) (Table 2).10 Excision bi-
Lymphadenitis is the most common presentation of EPTB in both
opsy may be considered if the diagnosis is in doubt. The yield of
children and adults (19% of UK TB cases). It usually represents
acid-fast bacilli (AFB) from a smear is poor but increases in pa-
reactivation from latent TB, although cervical disease may be
tients co-infected with HIV.10
caused by local spread from direct infection of tonsils or ade-
TB lymphadenitis often follows a waxing and waning course,
noids. The most common sites are the anterior or posterior cer-
even during treatment. Worsening on treatment may be attrib-
vical and submandibular nodes.
utable to paradoxical reactions (an enhanced immune response
TB lymphadenitis is usually painless. On palpation, nodes are
to dying mycobacteria). Aspiration of abscesses may relieve
firm but groups may become matted together with induration of
symptoms temporarily, although repeated aspiration carries a
overlying skin. Tissue necrosis with formation of fluctuant ab-
small risk of sinus or fistula formation. Treatment is with stan-
scesses is common and abscesses may discharge with sinus
dard quadruple therapy; the benefit of corticosteroids is debat-
formation. Symptoms depend upon site: mediastinal TB
able, although they do seem to expedite symptomatic
improvement.
Pleural TB
Risk factors for extrapulmonary tuberculosis Symptoms of pleural TB include pleuritic chest pain and breath-
C HIV infection lessness, associated with fevers and night sweats. Radiology may
C Tumour necrosis factor-a antagonists (e.g. Infliximab) show pleural effusions, even in the absence of lung parenchymal
C Corticosteroids changes. The pleural fluid is an exudate with high protein, low
C Malignancy glucose and often lymphocytosis. AFB are rarely visible but
C Female gender pleural fluid becomes culture positive in up to 75% of patients;
C Non-smoker adenosine deaminase analysis is useful, having an 88% sensi-
tivity for TB diagnosis.11 Diagnosis can also be aided by pleural
Table 1 biopsy (for histology and culture) and the use of video-assisted
thoracic surgery (VATS). The differential diagnosis for pleural symptoms. Plain X-rays may be deceptively normal and CT or
effusion is obviously wide, notably including para-pneumonic magnetic resonance (MR) imaging is often needed for diagnosis.
effusions, adenocarcinoma and malignant mesothelioma. Aspiration of collections and/or biopsy of the affected bone may
aid diagnosis and drainage may expedite recovery. TB treatment
Spinal and bone TB should be started immediately with standard quadruple therapy
TB affecting bones accounts for 12% of EPTB cases and 6% of all for 6e9 months. Adjuvant corticosteroids are recommended if
TB notifications in the UK.1 The most common site of infection is there is evidence of CNS or dural involvement. Joint manage-
the spine (9% of EPTB), followed by other large joints such as ment with orthopaedic or neurosurgeons experienced in the
the hip, knee and shoulder. Spinal TB comprises several patho- management of TB spine is essential to assess spinal stability and
logical entities including vertebral osteomyelitis, spondylitis and the need for external support or operative stabilization.
discitis (or spondylodiscitis, “Pott’s disease”) (Figure 2). The TB affecting other bones and joints is less common. Most
infection usually begins in the anterior aspect of the vertebral cases present with bone or soft tissue swelling, often with sinus
body adjacent to the subchondral plate, spreading to the adjacent formation. There is no clear evidence to support the role of
disc, although in children the sequence may be reversed, pro- surgery and drainage or sinus repair. Sinus formation can be
gressing from vascularized disc to bone. Progressive bone particularly troublesome and can take months if not years to
destruction may lead to vertebral collapse and kyphosis with heal, even with fully drug-sensitive organisms.
spinal gibbus formation (anterior angulation). Destructive cold
abscesses may form and commonly extend into adjacent liga- Abdominal TB
ments and soft tissues, especially the psoas muscle (psoas Gastrointestinal TB has a predilection for the terminal ileum;
abscess). Narrowing of the spinal canal by deformity, abscess- thickening or ulceration in this area may easily be mistaken for
formation, granulation tissue or direct dural invasion may result Crohn’s disease. Conversely, large bowel disease may be diag-
in spinal cord compression, a neurosurgical emergency.12,13 nosed radiologically as cancer. Complications include perforation
Typically there is a long history (#6 months) of fluctuating and TB peritonitis. Diagnosis is difficult as symptoms (abdominal
non-specific back pain, accompanied by constitutional pain, fevers, weight loss) are non-specific. Radiological findings
may include bowel thickening, lymphadenopathy, ascites, free
gas suggestive of perforation, and abscess-formation, but the
most important diagnostic aspect is a high index of suspicion in
patients with risk factors for TB.14 Laparoscopic or colonoscopic
biopsies are useful for histology and culture.
Urogenital TB
Urogenital TB comprises renal disease, ureteric disease and gen-
ital infection. The diagnosis of renal disease is easily missed, as
back or flank pain, dysuria or constitutional symptoms occur in
only 30% of patients.15 Renal TB is usually unilateral and rarely
causes renal failure; the exception is tuberculous interstitial
nephritis, which may affect both kidneys. Renal abscesses
(Figure 3) may destroy the entire renal parenchyma. Pelvo-
calyceal involvement may result in thickening of the collecting
system; more distally, ureteric fibrosis and stricture formation
may cause hydronephrosis,16 whereas TB of the bladder wall may
lead to fibrosis. Genital tract infection is unusual but most
commonly affects the prostate of men or endometrium of women.
Ovarian, tubal and testicular disease may result in infertility.
Depending on site, diagnosis depends on a combination of
early-morning urine samples (EMUs) (when the concentration of
AFBs in the urine is highest), biopsies and radiology. EMUs are
insensitive but molecular tests may improve diagnostic yield
(Table 2).6 Renal biopsy may show granulomatous interstitial
nephritis, often with multifocal caseous necrosis. Cystoscopy
with biopsies of bladder or ureteric/prostate tissue may also be
helpful. Imaging or the renal tract may show a characteristically
‘beaded’ ureter (ureteritis cystica).17
Pericardial TB
Although rare (accounting for <1% of EPTB), pericardial TB
Figure 2 MR imaging in TB spondylodiscitis. The lumbar spine is most
commonly affected, but involvement can occur at multiple sites, as seen merits consideration because it is potentially life-threatening. TB
here (arrows). Importantly, look for evidence of spinal cord compression, pericarditis can present either acutely, with massive pericardial
which is a neurosurgical emergency. fluid accumulation causing cardiac tamponade, or sub-acutely
Table 3
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13 Cormican L, Hammal R, Messenger J, Milburn HJ. Current difficulties in C Always perform an HIV test in anyone with TB
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J 2006; 82: 46e51. suspected renal TB
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