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CASE REPORT
Milliary Tuberculosis with Unusual Paradoxical Response
at 3 Weeks of Antituberculous Treatment
Liaqat Ali Chaudhry1, Ebtesam Ba-Essa2 and Shehab Al-Solaiman2
ABSTRACT
Milliary Tuberculosis (TB) occurs through lymphohaematogenous dissemination of M. tuberculosis and paradoxical response
(PR) is a recognized feature. Respiratory failure, choroid tubercles and brain tuberculomas are some of the complications.
Brain tuberculomas mainly occur in the cerebrum, cerebellum, where as involvement of the brainstem is rare. A 31 years
old female presented with history of ill health, easy fatigability, excessive sweating and fever of one month duration, dry
cough for one week and shortness of breath for 3 days. Provisional diagnosis was disseminated TB complicated by
hypoxemic respiratory failure and bilateral choroid tubercles. She was started on anti-TB treatment with adjuvant steroids.
The initial response to treatment was remarkable but after about 3 weeks of anti-TB therapy, she suddenly deteriorated
developing spastic ataxia. After exclusion of other possible causes she was successfully treated under the impression of
having PR.
Key words:
Disseminated tuberculosis. Pyrexia of unknown origin (PUO). Choroid tubercles. Tuberculomas. Paradoxical reaction (PR).
Paraparesis. AFB -Acid fast bacteria.
INTRODUCTION
Disseminated tuberculosis is defined as tuberculous
infection caused by Mycobacterium tuberculosis bacilli
spreading via lymphohaematogenous route to more
than two non-contiguous sites. PR is a recognized
feature in about 25% patients of TB with or without HIV,
defined by a clinical or radiological worsening of preexisting tuberculous lesions or the development of new
lesions in patients receiving anti-TB drugs who initially
improved on treatment. Central nervous system is the
commonest system affected.1-4
We present a case of disseminated TB who manifested
severe spastic ataxia as a manifestation of PR at
3 weeks of anti-TB treatment despite being on 2 weeks
adjuvant steroids from day one.
CASE REPORT
A previously healthy Indonesian female aged 31 years
presented with fatigability, excessive sweating and fever
especially in the afternoons of one month duration, dry
cough for one week and shortness of breath for 3 days.
There was no history of contact with infectious patient.
Department of Medicine and Chest Diseases1 / Medicine2,
Dammam Medical Complex (MOH), Dammam, Kingdom of
Saudi Arabia.
Correspondence: Dr. Liaqat Ali Chaudhry, Consultant
Pulmonologist and Acting Chairman of Internal Medicine,
Sultan Bin Abdulaziz Humanitarian City and Medical Centre,
P.O. Box 64399, Riyadh 11536, Qasim Highway, North Exit 6,
Banban, Kingdom of Saudi Arabia.
E-mail: [email protected]
Received September 24, 2010; accepted November 28, 2011.
She denied family history of tuberculosis, surgery, blood
transfusion, or high risk behaviour.
At the time of admission she was alert and ambulant
with blood pressure of 116/77 mmHg, 110/minute,
o
temperature of 38 C, respiratory rate of 26 breaths/
minute O2 saturation 87% at room air and weighing 42.2
kg. On chest auscultation, she had occasional bilateral
fine crackles, and bilateral choroid lesions on fundoscopy (Figures 1 and 2).
Patient denied any visual complaints, and rest of the
systemic examination was unremarkable.
Sputum Zeihl Nelson direct smear was AFB positive.
Arterial blood gas (ABG) analysis at room air showed pH
of 7.4, PaCO2 of 32 mmHg, PaO2 was 51.7 mmHg,
HCO3 was 23 and O2 saturation was 86.4. Sputum
culture sensitivity reported M. tuberculosis sensitive to all
drugs. Blood chemistry and haematology was normal.
ESR was 65 mm after first hour. Hepatitis B, C and
HIV serology were negative. CSF showed lymphocytic
predominance (78%) and raised proteins (2.3 mg/dl)
and low glucose (41 mg/dl). CSF PCR +ve for
M. tubercolosis but culture was AFB negative. Chest X-ray
showed bilateral miliary shadows.
Having disseminated TB involving lungs, complicated
with respiratory failure and bilateral choroid eye lesions,
she was started “DOTS” with INH 200 mg once daily,
Pyridoxine 20 mg once daily, Rifampicin 450 mg once
daily, Pyrazinamide 1250 mg once daily, Ethambutol
600 mg once daily, Injection Methylprednisolone 40 mg
I/V 12 hourly, Pantoprazole 20 mg HS, Paracetamol 500
mg 2 tablets 8 hourly only. She required 1-2 L/min of O2
by nasal cannula only.
Journal of the College of Physicians and Surgeons Pakistan 2012, Vol. 22 (1): 43-45
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Liaqat Ali Chaudhry, Ebtesam Ba-Essa and Shehab Alsolaiman
Figure 1: Choroid lesions in the left eye.
Figure 2: Choroid lesions in the right eye .
She tolerated treatment well and after one week her
ABG’s at room air became normal. Steroids were now
switched to oral prednisolone 40 mg /day. After 10 days
of treatment her temperature subsided. Prednisolone
was tapered off. After 22 days of treatment, she
complained of feeling heaviness of her feet and difficulty
in walking. Within 2 days she became bed bound and
neurological examination revealed spastic paraparesis.
Coordination and sensations were normal, bowel and
bladder control was intact, while upper limbs were
normal. An urgent MRI of brain and spine (Figure 3)
revealed multiple tuberculomas of the brain involving
cerebral cortex, cerebellum and brainstem. Her sputum
culture being positive for typical Mycobacterium and
sensitive to all first line drugs. She was treated by DOTS
method.
Initial clinical, radiological and finally bacteriological
response to initial 4 drug anti-TB and adjuvant steroids
treatment was remarkable, thus her ataxia was due to
PR. She improved in response to the same anti-TB
drugs with re-introduction of steroids. She received
Dexamethasone 4 mg IV 8 hourly in the first week, and
4 mg IV 12 hourly during the second week. Afterwards,
it was changed to oral Prednisolone 40 mg once daily.
After 41 days of treatment, her sputum direct AFB was
reported negative 3 times. On completion of 46 days of
treatment patient showed signs of improvement and
was able to walk with Zimmer's frame. Prednisolone
was tapered off and rest of the treatment continued
including physiotherapy. After she completed 54 days of
treatment and her sputum direct smear AFB was
reported 3 times negative, she was discharged home on
the request of her sponsor. She left for her home country
and could not be followed.
DISCUSSION
Paradoxical reaction (PR) in tuberculosis (TB) is
common and may affect upto 25% of patients. Among
patients having tuberculosis with HIV negative status in
Taiwan the reported incident of PR has been 2.4%.5 PR
has the potential to cause significant morbidity and, on
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Figure 3: Sagittal contrast enhanced MRI showing
enhancing lesions in brainstem.
rare occasions, death. Although PR has been recognised
for some time, the pathophysiology, especially in HIVnegative patients, is not well understood. Central
nervous system is the commonest system affected in
about 75% of cases. Diagnosis of PR is based on
excluding various secondary causes like poor
compliance, drug resistance, HIV status, anti-retroviral
therapy, drug fever and progression of original disease.
The incidence, timing and clinical spectrum of PR vary
widely. Associated risk factors and predisposition to PR
has not been well understood. A rise in lymphocyte
count, tuberculin conversion during treatment and
disseminated disease may all be associated with the
development of PR.6
This patient was active, ambulant and her neurological
examination was unremarkable at the time of admission.
She responded very well to initial treatment. But after
completion of 3 weeks of anti-TB treatment she
developed spastic ataxia of both lower limbs, it was an
unusual manifestation of paradoxical deterioration
despite 2 weeks adjuvant steroids from day one.
Diagnosis of PR is mainly by exclusion of various
causes like non-compliance, unexpected drug
resistance, malabsorption, immunodeficiency and antiretroviral therapy which was absent in this patient. The
clinical picture was also contrary to a drug fever, as this
patient remained afebrile and had evidence of central
nervous system involvement, which refuted drug fever.
The picture was that of a paradoxical reaction which
responded to same anti-TB drugs with re-introduction of
adjuvant steroids. PR is due to detonation of existing
lesions in large majority of patients but in minority of
patients it could be due to development of new lesions.
Response to steroids is typical as observed in this case.
Standard therapeutic guidelines on corticosteroids for
tuberculosis do not exist, but Dexamethasone (adults
12-16 mg/day for 3 weeks, tapered over next 3 weeks)
or Prednisolone (for adults 60 mg/day for 3 weeks and
tapered over 3 weeks) is recommended.7 In this case
intravenous Dexamethasone was used at a dose of 12
mg/day for the first week, and tapered over as twice
Journal of the College of Physicians and Surgeons Pakistan 2012, Vol. 22 (1): 43-45
Milliary tuberculosis with unusual paradoxical response
REFERENCES
daily (8 mg/day) for the second week. Afterwards oral
Prednisolone was continued at 40 mg/day.
1.
This case was unique in the sense that despite having
disseminated tuberculosis involving lungs, eyes and
brain she did not present with any neurological
complaints initially. Other feature was brainstem lesions
which is a rare finding. Above all, it is interesting to note
that she received anti-TB drugs and adjuvant steroids in
the first 2 weeks of treatment from day one for having
respiratory failure, but soon after her steroids were
tapered she manifested PR at 3 weeks of treatment.
This is unusual and exceptional. We would like to share
this observation for further debate to reach a consensus
on the dose and duration of adjuvant steroids once they
are started in a particular patient having disseminated
TB. Moreover, this observation has given rise to an
interesting question regarding the place for prophylactic
adjuvant steroid treatment in anticipation of PR in
patients having disseminated TB.
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