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Original article

Spinal tuberculosis in children

Sarah Eisen,1 Laura Honywood,2 Delane Shingadia,2 Vas Novelli2
1Department

of Infectious
Diseases and Microbiology,
Institute of Child Health,
London, UK
2Department of Infectious
Diseases, Great Ormond
Street Hospital for Children,
London, UK
Correspondence to
Sarah Eisen, Department
of Infectious Diseases and
Microbiology, Institute of Child
Health, 30 Guilford St, London
WC1N 1EH, UK; saraheisen@
hotmail.com
Received 19 December 2011
Accepted 18 May 2012
Published Online First
25 June 2012

ABSTRACT
Objectives To review our experience of spinal
tuberculosis (TB) at a major UK paediatric tertiary
referral centre.
Methods The authors performed a retrospective case
survey of 21 patients admitted to Great Ormond Street
Hospital over a 15-year period (19952010) with confirmed
or presumed spinal TB. Data were collected concerning
demographics, clinical, laboratory and radiological
characteristics, treatment and clinical outcome.
Results Only one patient was of Caucasian origin.
Four (19%) had a previous diagnosis of TB, 11 (52%) a
known contact, 10 (48%) had received BCG vaccine
and none were HIV-positive. Clinical presentations
included systemic symptoms (18 patients), back pain
(16 patients), deformity (five patients) and neurological
deficits (12 patients). Mycobacterium tuberculosis was
isolated from 14 patients (67%) including one multidrug resistant strain. Spinal cord compression or critical
stenosis was demonstrated in eight patients (38%).
All received TB treatment for at least 12 months; six
patients received treatment for a longer period. Seven
(33%) underwent surgical intervention. Seventy-five
per cent showed clinical and radiological resolution
after treatment. No patients died or suffered long-term
neurological deficit.
Conclusions Spinal TB in children needs a high index of
suspicion for diagnosis. Early referral to an expert centre
allows a multidisciplinary approach to management.
The authors recommend that treatment should be
individually tailored and may need to exceed 12 months
in cases of poor adherence, extensive disease or drug
resistance.

INTRODUCTION
Tuberculosis (TB) is the most common infectious disease worldwide, and, in 2009, affected
four per 100 000 UK-born children under 5 years
old in the UK.1 Spinal TB refers to infection of
one or more vertebral bodies with Mycobacterium
tuberculosis, with or without involvement of the
spinal cord.2 3 This condition is believed to arise
by haematogenous dissemination, often without an obvious primary focus in children, who
may be vulnerable to discitis because of the
persisting anastomosis between the vertebral
endplate and disc. Septic embolus may result in
thrombosis and bony necrosis, often with extension to adjacent vertebral bodies, vertebral endplate destruction, subligamentous spread and
cord involvement.4 There is limited evidence to
guide treatment of spinal TB in children, which
remains controversial. This review of our experience of childhood spinal TB over 15 years is, to
our knowledge, the only paediatric case series
reported from the UK.
724

What is already known on this topic

There is no consensus on the management

of paediatric spinal tuberculosis and little
evidence upon which to base guidelines.
Controversy exists regarding duration of
therapy and the role of surgery in treatment.

What this study adds

Presenting features of spinal tuberculosis

in children are back pain and/or systemic
symptoms (fever, night sweats, anorexia,
weight loss).
Helpful investigations include tuberculin
skin test (positive in 90%), Mycobacterium
tuberculosis culture (67% positive), MRI
(abnormal in all cases).
Treatment may need to exceed 12 months in
cases of poor adherence, extensive disease or
drug resistance.

PATIENTS AND METHODS

We performed a retrospective study of patients
treated at Great Ormond Street Hospital, London
(19952010) with a diagnosis of spinal TB. Patients
were identied by review of the database of cases of
TB maintained by the hospital since 1995. Hospital
records were reviewed to obtain demographic,
clinical, laboratory and radiological data relating
to characteristics, treatment and outcome.
Patients were included if diagnosed with spinal
TB based on microbiological con rmation from
vertebral tissue or paravertebral abscess, or on a
combination of clinical, radiological and/or histological ndings.
Relapse was diagnosed during or after treatment
when a patient showed clinical or radiological
deterioration consistent with active TB following
initial clinical improvement, or reverted to culturepositivity (where multiple cultures were available).

RESULTS
Demographics and clinical characteristics
Twenty-one patients were identied. Median
age was 9.7 years (range 3.415.9 years). Eleven
patients were Black African, seven Asian, two
Middle Eastern and one Caucasian. Nine were
born in the UK, one in the Netherlands and the
remainder outside Europe. Ten patients reported
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Original article
travel to a country where TB is endemic within the year preceding diagnosis. Four (19%) had a previous diagnosis of TB
disease (three of whom had been diagnosed within the previous 3 years in the UK, only one of whom had completed a
full treatment course), while 11 (52%) had a history of recent
active TB disease in a relative. Ten patients (48%) had received
BCG. None were known to be HIV-positive (although only
seven were tested). Of 14 patients with data available, four
(29%) were <0.4th centile for weight.
Table 1 shows the symptoms and signs recorded in each of
the 21 patients on admission.
Eighteen patients presented with systemic and 12 with neurological symptoms, and ve with spinal deformity. Back pain
was common and associated with systemic symptoms in all
but three (night sweats in 11, weight loss in nine, fever in eight
and anorexia in ve). The ve patients without back pain all
reported one or more systemic symptoms. Median symptom
duration before diagnosis was 6 weeks (range 216 weeks).

Vitamin D was measured in seven patients, ve of whom were

found to be insufcient (<50 ng/ml) or decient (<25 ng/ml).
A QuantiFERON-TB Gold test was performed in all 14
patients admitted since 2003 and was positive in nine (64%),
negative in four (29%) (two of whom were culture-positive)
and indeterminate in one (7%).

Microbiological and histological data

Diagnosis was con rmed microbiologically in 14 patients
(67%) by growth of M tuberculosis from vertebral biopsy or paraspinal abscess. Radiological guidance achieved tissue samples
in nine cases (four CT and ve ultrasound-guided), thus avoiding open surgical biopsy. Of these culture-positive patients,
only three stained positive for acid fast bacilli (20%) from the
same sample and two tested positive on PCR for M tuberculosis.
None had M tuberculosis isolated from sputum. Of the seven
patients without microbiological con rmation, four were
diagnosed based on clinical and radiological features and three
underwent biopsy with histology suggestive of mycobacterial
infection, despite persistently negative cultures. Three further patients with positive culture also showed characteristic
biopsy changes.
Drug resistant isolates were identied in three of the 14
con rmed cases of M tuberculosis (20%): two to isoniazid and
one to isoniazid, rifampicin, streptomycin and pyrazinamide
(multi-drug resistant: (MDR)-TB; the father of this child was
also MDR-TB culture-positive).

Skin tests
Tuberculin test results (before 2003: 10TU Evans tuberculin; after 2003: 2TU Statens Serum Institut tuberculin) were
recorded for 20 patients, of whom 18 (90%) were positive and
two (10%) negative (both in patients without microbiological
diagnosis and with a negative QuantiFERON-TB Gold test but
histology suggestive of TB). All positive results were >10 mm
(widest diameter); 17 were >15 mm (eight of these patients had
previously received BCG).

Radiology
Laboratory data

Spinal radiographs and MRI scans were performed in all

patients and were abnormal in seven and all 21 cases, respectively. The thoracic spine was most commonly affected (13
cases). Three patients (14%) had non-contiguous multiple foci,
and in one (with fully sensitive isolate, previous incompletely
treated TB and extensive extra-spinal disease) the entire spine
was affected. Vertebral collapse was evident in 13 (62%),

The C reactive protein and erythrocyte sedimentation rate

were raised (>20 mg/l and >10 mm/h, respectively) in 11
and 17, respectively, of the 18 patients in whom they were
documented. Neutrophilia (>8.0109/l) and lymphopaenia
(<1.5109/l) were each seen in four patients, and anaemia (haemoglobin <11.5 g/dl) in 15 of 19 documented results (79%).

Table 1

The presenting features on admission in 21 children with spinal tuberculosis, shown in decreasing order of frequency
Patient

Presenting features

Back pain
Night sweats
Fever
Weight loss
Cough
Anorexia
Limp
Weakness/reduced
power
Lymphadenopathy
Deformity
Sensory change
Abdominal pain
Hyperreflexia
Discharging sinus
Features relating to
extra-spinal site*
Identified through
contact tracing

Y
Y

Y
Y
Y
Y
Y

Y
Y
Y
Y
Y
Y

Y
Y
Y
Y
Y

10

11

Y
Y

Y
Y
Y
Y
Y
Y

Y
Y

Y
Y
Y
Y

Y
Y
Y
Y

Y
Y

14

15

16

17

18

19

Y
Y

Y
Y
Y
Y
Y

Y
Y
Y
Y

Y
Y

Y
Y
Y

Y
Y
Y
Y
Y

Y
Y
Y

Y
Y

Y
Y

13

Y
Y

Y
Y
Y

12

Y
Y

Y
Y
Y

Y
Y

Y
Y

20

21

Total

16
15
12
11
10
9
7
7

Y
Y
Y
Y
Y
Y
Y
Y

7
5
5
2
1
1
1

Y
Y
Y

*Thumb pain, later confirmed to be due to tuberculous osteomyelitis of the thumb.

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paraspinal abscesses in 15 (71%) and disc involvement in 12
(57%). Cord compression or critical stenosis was demonstrated
in eight (38%), although none showed actual involvement of
the spinal cord. Figure 1 shows a spinal MRI demonstrating
vertebral collapse, compression, discitis and subligamentous
spread at the level of T11.
Chest x-ray was abnormal in eight patients (38%) (two
showed pleural effusions, three mediastinal lymphadenopathy
and three consolidation). Twelve patients (57%) had co-existent
extra-spinal TB disease (pulmonary, osteoarticular, pericardial
or TB meningitis) of whom two had multiple extra-spinal disease foci. Five patients (24%) had coexisting psoas abscess.

Treatment
Table 2 summarises treatment and outcome for each patient.
All patients received inpatient care (median duration 12
days, range 242) and antituberculous drugs. Ten (48%)
received standard quadruple therapy for fully sensitive TB
(rifampicin, isoniazid, pyrazinamide, ethambutol). The three
patients with isoniazid-resistant isolates (or contacts) received
rifampicin and ethambutol (one also received ciprooxacin).
The patient with an MDR isolate received ethambutol, ciprooxacin, cycloserine, prothionamide and intravenous amikacin. Six patients changed drugs during treatment, two due
to clinical or radiological deterioration (moxioxacin added),
one due to side effects (clarithromycin substituted for ethambutol following a documented reduction in visual acuity) and
three based on subsequently available sensitivities.

Table 2

Figure 1 Spinal MRI showing vertebral collapse, compression,

discitis and subligamentous spread at the level of T11.

Summary of the treatment and outcome for each patient

Patient

Treatment

1
2
3
4
5
6
7
8
9
10
11

RHZ, streptomycin
E, ciprofloxacin*, cycloserine,
prothiamide, amikacin
RHZ
RE
RHZE
RHZ, streptomycin
RHZE
RE, ciprofloxacin*
RHZE
RE
RZE

12

RHZE, moxifloxacin

13

RHZE

14
15

RHZE
RHZE, clarithromycin,
ciprofloxacin*, streptomycin

16
17
18
19
20
21

RHZE
RHZE
RHZE
RHZE
RHZE
RHZE, moxifloxacin

Corticosteroids

Treatment
duration
(months)

Adherence
difficulties

N
N

N
N

12
48

Y
Y

Y
N
N
Y
N
N
N
Y
N

N
N
Y
Y
Y
N
N
N
N

12
24
12
12
12
12
12
16
12

N
N
N
N
N
N
N
Y
N

18

18

Y
N

Y
Y

12
12

N
N

N
N
N
N
N
Y

N
N
Y
Y
N
Y

12
12
12
12
12
18

N
N
Y
N
N
N

Reason for deviation from standard

regime (RHZE)

Surgery

Unknown
MDR-TB
Unknown
H resistance
Unknown
H resistance, ciprofloxacin sensitive
H resistant contact
Unknown
Failure to resolve with further lumbar
vertebral collapse

E stopped (reduced visual acuity); ciprofloxacin and streptomycin added due to

failure to resolve

Wound breakdown, suspected MDR-TB

Outcome
Resolved
Two relapses on
treatment
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved
Resolved
Residual deformity
and pain
Resolved
Two relapses then
resolved
Resolved
Relapse and
deafness
Resolved
F/u
F/u
F/u
F/u
F/u

E, ethambutol; F/u, follow-up ongoing; H, isoniazid; MDR, multi-drug resistant; R, rifampicin; Z, pyrazinamide.
*It should be noted that ciprofloxacin has the weakest anti-TB activity of all quinolones and is no longer recommended for the treatment of drug resistant TB.

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Fifteen patients (71%) received therapy for 12 months only.
Those with isoniazid-resistant strains or extensive extraspinal disease received longer treatment courses (16 and 24
months and 18 months, respectively), as did those whose condition deteriorated on treatment (18 months). The patient with
MDR-TB received 4 years of treatment. None received directly
observed therapy, but adherence difculties are documented in
six patients, including those who deteriorated on treatment.
Nine patients (43%) received steroid therapy, of whom eight
had radiologically demonstrated cord compression and one
associated raised intracranial pressure (with co-existent tuberculous meningitis con rmed on lumbar puncture).
Seven patients underwent surgical intervention (33%).
Debridement and decompression was performed to resolve
cord compression in the four patients with neurological manifestations. Spinal instrumented stabilisation was performed in
three patients with instability. There were no surgical complications or failures of procedure. Time from diagnosis until
surgery was a median of 7 days (range 125 days), determined
by clinical severity, and all surgery was performed after initiation of medical therapy (median 7 days after treatment started,
range 022 days).

Outcome
All patients were alive at the end of follow-up (median duration 24 months; ve ongoing). Twelve of the 16 discharged
cases (75%) resolved fully, three relapsed (one off and two on
treatment, of whom one had MDR-TB). One patient is known
to have suffered long-term disease or treatment-related morbidity (deafness following streptomycin therapy).

DISCUSSION
Certain features should raise suspicion of spinal TB
Diagnosis of spinal TB is notoriously difcult. 5 Our ndings
indicate key features which should alert the clinician in primary, secondary or tertiary care. The demographics of our
cohort reect those seen locally and nationally, 5 the majority
originating from immigrant families, reecting higher prevalence in country of origin.6 A history of TB contact or travel
should be sought (and probably accounts for the nine affected
UK-born children in our cohort) as should a history of previous
TB, present in 19% of our group. Systemic symptoms were
present in almost all patients, consistent with other paediatric studies7 and over half presented with neurological symptoms. Rates of neurological features at presentation quoted in
the paediatric literature vary.7 8 It is clear from our cohort that
the association of back pain with systemic symptoms should
raise alarm. Likewise, long symptom duration is suspicious,
also reported elsewhere in both adults 5 and children.7 This is
likely to result from insidious onset of non-specic symptoms9
and is important as delayed presentation results in increased
complications.10

When to investigate and how?

Early and judicious investigation is needed to diagnose spinal
TB in children. The tuberculin skin test was positive in almost
all cases in which it was performed, but is notoriously unreliable in the context of immunosuppression, severe disease or
prior BCG.11 The QuantiFERON-TB Gold test, although positive in nine of the 14 tests performed, was negative in two
culture-positive cases, suggesting limitations of the assay. As
expected, low-grade in ammation and anaemia were common and may be useful warning signs.
Arch Dis Child 2012;97:724729. doi:10.1136/archdischild-2011-301571

National Institute for Health and Clinical Excellence guidelines12 recommend bacteriological con rmation of disease,
which can be challenging where infective foci may be inaccessible and biopsy invasive. Microbiological diagnosis was
con rmed in two thirds of our patients, with a culture con rmation rate (where biopsy specimens were obtained) of 77%,
consistent with the published literature. 5 9 Histology can be
useful and allowed diagnosis in the absence of positive microbiology in three cases. Of note, the use of radiological guidance
to obtain specimens avoided open surgical biopsy in several
patients and may facilitate rapid treatment, avoid invasive
diagnostic procedures and decrease hospitalisation time.13
Single, multi and extensive drug resistance is increasing
nationally and globally. Identication of resistant strains is
vital for effective treatment and disease control. The rate of
single drug resistance in our cohort appears higher than in
published data,14 but our sample size is small. There are, as
yet, no data specically relating to resistance rates in isolates
in spinal TB in the UK, but adult data from India suggest that
this is an increasing concern.15 History of contact with drug
resistant TB, as with two patients here, should result in a high
index of suspicion of drug resistant TB in the patient.16
Radiological investigation remains crucial in diagnosis,
determining the extent of disease and the risk of complications. According to the Medical Research Council de nition,17
18 active disease is diagnosed on plain radiograph by loss of
cortical outline and rarefaction of affected vertebral bodies.
The disc is frequently affected, as in more than half of our
patients. The role of plan radiographs has been largely superseded by MRI to identify early soft tissue abnormality, spinal
cord compression, epidural involvement and subligamentous
spread.19 Cord compression was demonstrated radiologically
in nine patients (ve without clinical neurological abnormality), allowing identication of those in whom corticosteroids
or surgical intervention may be benecial. 5 Disease distribution (predominantly thoracic) is consistent with limited reports
within the adult literature, 5 although higher rates of lumbar
involvement have been shown in children.7

A lack of evidence for management

Treatment aims to eradicate infection and prevent sequelae.
There may also be a requirement to decompress or stabilise
the spine. Considerable controversy exists regarding duration
of therapy, role of corticosteroids, surgical intervention and
follow-up. There is no consensus in the absence of paediatric
evidence-based data. 20 21 Table 3 summarises recommendations from current guidelines.
Existing guidelines, based on multicentre randomised controlled trials, 3 22 23 vary in their recommendations regarding
treatment duration from 6 to 12 months. 2 12 16 24 A further
study by van Loenhout-Rooyackers recently concluded that
6 months is probably sufcient for all, but notes that no guidelines are based on data from randomised controlled trials in
children. 25 In our centre, standard treatment is for at least
1 year, as described elsewhere.7 Apart from two cases with
known poor adherence, all but one showed disease resolution after treatment for this duration or longer. This practice
is not evidence-based and treatment duration is determined
on an individual basis, considering disease severity, treatment
response and microbiological sensitivities of isolates. Choice of
therapeutic drug in the case of resistance or treatment failure
is determined by the responsible clinician and microbiologist.
In the absence of sufcient evidence to support any single
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Table 3

Summary of recommendations from guidelines relating to management of spinal TB

Guideline

Drug treatment for fully

sensitive organism

Use of steroids

Role of surgery

Follow-up

In some circumstances surgery appears to be

beneficial and may be indicated. These
circumstances include failure to respond to
chemotherapy, relief of cord compression in
patients with persistence or recurrence of
neurological deficits or spinal instability
No comment

No comment

American Thoracic Society,

CDC, Infectious Disease
Society of America, 200324

Standard combination
(RHZE; ethambutol may be
omitted) for 69 months.
DOT should always be
used in children

Not recommended

WHO, 200616 (specifically

paediatric)

Standard regimen (RHZE)

for 69 months

No comment

NICE, 201112

Standard regimen (RHZE)

for 6 months. If direct cord
involvement, treat as for
meningeal TB (12 months).
DOT not required
Standard regimen (RHZE)
for 12 months

No comment

No indication for routine anterior spinal

fusion, except in the case of cord instability or
compression

Not recommended
routinely but may be
useful if symptoms
worsen on therapy or if
spinal cord compression

Decompression for extradural lesions causing

paraparesis

British Infection Society, 20092

None after treatment

completion except in the
case of resistance
Not routine after treatment completion except
in the case of resistance

No comment

CDC, Centers for Disease Control and Prevention; DOT, directly observed therapy; E, ethambutol; H, isoniazid; NICE, National Institute for Health and Clinical Excellence;
R, rifampicin; Z, pyrazinamide.

recommendation, this individualised, exible approach, with

monitoring for deterioration, seems sensible. Compliance is
critical: two thirds of patients with relapse reported adherence
difculties. Directly observed therapy is not routinely offered
in the UK but merits consideration in a disease with potential
for long-term morbidity in the context of high rates of nonadherence as demonstrated here, where a third of poorly adherent patients showed disease relapse.
There are no data to underpin the use of steroids in spinal TB in children. Their use is not recommended by some
guidelines, 24 26 but is advocated elsewhere2 27 where cord compression is suspected, as was the case in our cohort, in which
almost half received steroids for clinical or radiological cord
compression.
As with most aspects of this condition, there is no clear evidence to direct surgical intervention, which occurred in a third
of our cohort and usually comprises decompression, debridement or excision of infected material, or instrumented spinal
stabilisation. Disadvantages include need for hospitalisation
and general anaesthesia, and risk of complications. A recent
systematic review28 examined randomised control trials to
compare chemotherapy alone to chemotherapy with additional surgery. Only two trials met inclusion criteria, neither
recent nor specically paediatric.17 18 23 2932 The review stated
that too few patients were included to provide conclusions
and that routine surgery cannot be recommended without
a large randomised controlled trial, not conducted to date.
Practice, therefore, must rely on the judgment and collaboration of paediatric and surgical specialists. Many guidelines2 12 16
concur that, despite little evidence, surgery may be appropriate if there is failure of medical therapy, cord compression in
patients with neurological decits, 2 4 spinal instability,12 or to
enable drainage of paraspinal abscesses. 33 Some advocate prophylactic surgery34 35 to prevent kyphosis. 36
As with duration of medical therapy, the role and timing
of surgical intervention in our patients was, in the absence
of evidence-based guidelines, determined on an individual
basis. Prospective studies are needed to provide evidence to
dictate the role of surgical intervention in paediatric patients.
728

Appropriate imaging, vigilance for complications requiring

surgery and early discussion with surgeons are crucial.

How should we follow-up these patients?

We show rates of disease resolution in our study comparable
with those described elsewhere. 37 38 All were followed up
clinically for at least 15 months after discontinuing treatment.
Certain therapies may be associated with long-term impairment (in particular streptomycin, which may cause deafness)
and long-term monitoring for such iatrogenic complications is
important. An adult case series suggests that signs of radiological instability appear early in disease (and probably in relapse),
so routine radiological investigation may be useful to identify
those children at risk for late progressive vertebral collapse39
and spinal deformity,40 highlighting a possible role for radiological follow-up until growth is complete.

CONCLUSIONS
There is a need for further evidence from multi-site prospective studies to guide treatment in paediatric patients with
spinal TB. In the absence of this evidence, we recommend a
exible individualised approach, with careful follow-up, as
demonstrated in this case series. It is crucial that a high index
of suspicion for the diagnosis of spinal TB is maintained, with
early referral to an expert centre where liaison between infectious diseases specialists, radiologists, microbiologists and
surgeons is possible. Identication of drug resistant or extensive disease, complications which may benet from steroids or
surgical intervention, or adherence difculties, with monitoring for relapse, must inform appropriate management in the
absence of a robust evidence base.
Acknowledgements The authors are grateful to the patients and their families
Contributors SE analysed the data and wrote the paper. SE and LH acquired
and collated the data from original sources. DS and VN assisted in data analysis,
determining content and writing up the paper.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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Spinal tuberculosis in children

Sarah Eisen, Laura Honywood, Delane Shingadia, et al.
Arch Dis Child 2012 97: 724-729 originally published online June 25,
2012

doi: 10.1136/archdischild-2011-301571

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