I soniazid
(INH) has been rarely implicated in the causation of optic neuritis in
adults(1-4). An extensive literature search failed to locate any report of
such an association in the pediatric age-group. It is believed that
side-effects of INH are less common and less severe in children(5) and
hence, pyridoxine is not routinely prescribed to children receiving
INH(6). We report a case of acute loss of vision in a child receiving INH
as part of treatment for CNS tuberculosis.
Case Report
A 10-year-old boy born of non-consanguineous union was
brought to the pediatric emergency department with loss of vision in both
eyes for two days. It started as blurring of vision with an inability to
recognize faces and progressed to complete blindness. Physical examination
revealed no perception of light with a sluggish, ill-sustained pupillary
response to light in both eyes. Fundoscopy revealed bilateral hyperemic
optic discs and blurred nasal margins, venous engorgement, cup fullness
and a single flame-shaped hemorrhage in the right eye. No other
abnormalities were noted on physical examination. The child was receiving
four drug anti-tuberculous therapy (ATT); consisting of INH 5mg/kg/d,
rifampicin10 mg/kg/day, pyrazinamide 25 mg/kg/day daily, all taken once
daily per orally; and streptomycin 20 mg/kg/d once daily intramuscular)
for tuberculous meningitis and phenytoin (5mg/kg/d div three doses, per
oral) for the past one month. The disease was diagnosed on the basis of
prolonged fever, seizures, positive tuberculin test, hilar lymphadenopathy,
history of tuberculous contact and characterstic CSF picture suggestive of
tuberculous meningitis. CT brain was normal.
At presentation, MRI scan showed bilateral retrobulbar
neuritis (left > right). EEG showed generalized slow activity with 5-6 Hz
baseline frequency. HIV ELISA was negative. The child was managed with
discontinuation of INH, administration of vitamin B1
(500 mg IM), vitamin B6 (25 mg IM), vitamin B12 (0.5 mg IM) and
dexamethasone (2 mg once daily IM). The child was also given 100 mg of
vitamin B6 orally since admission. Methylprednisolone (30mg/kg/d once
daily for 5d; IV) was given after two days of dexamethasone therapy.
Visual perception improved gradually with resolution of disc swelling and
papilledema. No tubercles were seen on fundoscopy. At the time of
discharge (day 18), he was able to count fingers up to four feet using his
right eye though with his left eye he could only perceive hand movements.
The papillitis had resolved bilaterally and the fundoscopy was normal.
After two months, visual acuity was 6/9 in the right eye and was 6/18 in
the left eye. After 3 months, there was complete restoration of visual
acuity to 6/6 in both eyes. In view of withdrawal of INH, an important
first-line drug, the child was given ATT consisting of rifampicin,
pyrazinamide, ofloxacin, clarithromycin and streptomycin. After completing
the intensive phase he continued to receive rifampicin, ofloxacin and
clarithromycin. Prednisolone was given at full doses for 6 weeks and then
tapered over the next 6 weeks. The Naranjo algorithm for adverse drug
reaction causality assessment(7) yielded a score of 6, suggesting that the
adverse drug reaction was probably related to INH.
Discussion
Optic neuritis due to isoniazid has been described
sporadically among adult patients(2-4).
These reports indicate that the neurotoxic effects of isoniazid may be
enhanced by co-morbidities like end stage renal disease requiring
hemodialysis(8,9) or malnutrition(3). The onset of visual symptoms
generally occurs within ten days of starting anti-tubercular therapy(2,4)
but may occur even two to three months after initiation of therapy(2,3,8).
Detailed ophthalmoscopic examination reveals a bilateral and often an
unequal decrease in visual acuity, loss of color vision, bitemporal
hemianopsia(2) or centrocentral scotomata on perimetry(3). Fundo-scopy
generally shows bilateral disc hyperemia with blurred borders. Rarely, the
fundoscopy may be normal(2). Methylprednisolone is considered useful, as
was seen by the visual improvement in our patient. However, the recovery
is often incomplete without discontinuation of INH(8). Some reports
indicate that the use of oral prednisone is not useful(4). Discontinuation
of INH is associated with improvement of the visual dysfunction as early
as four days after discontinuation(4,9) with complete recovery usually
taking four weeks(1,4,9) but rarely may take up to six months(3,8). In
some cases a residual bitemporal hemianopsia may persist. Reintroduction
of isoniazid is associated with a quicker onset of optic neuritis but is
still reversible. Failure to stop INH may eventually lead to optic
atrophy(2-4).
The mechanism of optic neuritis due to INH can be
considered to be an extension of the etiology of peripheral neuritis,
postulated to be due to INH-induced loss of pyridoxine in the urine or
isoniazid-blockade of pyridoxal phosphate synthesis which depletes
neurotransmitters(3). However, there are reports of neuritis even in
patients receiving pyridoxine supplementation(3,9).
It is unlikely that the boy had tuberculous optic
neuritis, as this rare condition is usually associated with
chorioretinitis, uveitis or military tuber-culosis(10). Our case
underscores the fact that optic neuritis can occur in children receiving
INH. It is necessary that practitioners watch children receiving INH
carefully for visual symptoms and take prompt actions that include
discontinuation of INH and supplementation of pyridoxine in equimolar
doses. It is also vital that such cases are reported through active
pharmacovigilance programs and medical journals, so that recommendation of
not supple-menting ATT with pyridoxine can be reviewed on the basis of
fresh evidence.
Acknowledgment
We thank Dr Sanjay Oak, Director (Medical Education and
Major Hospitals) and Dean, Seth GS Medical College and KEM Hospital for
permitting us to publish this communication.
Contributors: HSK: Concept, collection of data,
literature search, preparation of first draft; SBB: Conceptualization,
intellectual inputs for revision; YG: Intellectual inputs for revision; VK:
Literature search. All authors approved the final draft. SBB shall stand
guarantor.
Funding: None.
Competing interests: None stated.
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