A O S 1999

Unilateral papilloedema after

hepatitis B vaccination in a
migraine patient
A case report including forensic aspects

Hans C Fledelius
University Eye Department, Rigshospitalet, Copenhagen, Denmark
ABSTRACT.
Purpose: To report on a unilateral optic nerve reaction appearing 9–10 hours Right eye visual field findings were nor-
after vaccination against hepatitis B. mal throughout.
Methods: To describe the case and discuss the underlying mechanisms. There During the first week her left eye papil-
was a scintillating scotoma leaving a permanent inferior notch in the visual loedema changed from an engorged look
field, but central vision was left normal and with only a slight affection of (’choked’) to a relatively ischaemic ap-
colour perception. Shortly the optic nervehead appeared engorged, then slightly pearance. Fluorescence angiography on
ischaemic, but was hardly left with evidence of atrophy. day 5 showed a larger disc, but no vascu-
Results: Immune-based reactions could hardly be held responsible, multiple lar leakage or other abnormalities. After
2–3 months both optic discs appeared
sclerosis was unlikely, and ultrasonography excluded optic nervehead drusen.
normal, however, with a little more lam-
An optic nerve migraine mechanism is probable, possibly with the vaccination
ina cribrosa visible in the optic cup of the
having acted as the trigger.
left eye than in the right. Intraocular
pressures were normal.
Key words: hepatitis B vaccine – papilloedema – optic nerve migraine – visual field defect.
B-scan ultrasound showed normal and
symmetrical orbital patterns without evi-
Acta Ophthalmol. Scand. 1999: 77: 722–724 dence of optic nervehead drusen, and
Copyright c Acta Ophthalmol Scand 1999. ISSN 1395-3907 there was a normal CT-scan of orbits and
brain.
With a three year follow-up her visual
status has remained normal, with an acu-
ity ±1.0 of the previously sick left eye.

C ompared to the number of vacci-

nations given all over the world,
the number of reported adverse reactions
is small. In particular this is true, the
cleaner the vaccine, and the modern re-
combinant vaccines are generally re-
garded as very safe (WHO Drug Info
1990). The present discussion of a case of
unilateral papilloedema temporally as-
sociated with hepatitis B vaccination is
therefore considered of general interest.
Case History
A 55-year-old female general practitioner
had a vaccination against hepatitis B
with the Engerix B vaccine (Smith-
Kline & Beecham). Except for pollen al-
lergy and occasional migraine she had al-
ways enjoyed a good health. Paroxystic
headaches had occurred for years and
episodes of blurred vision lasting 15–20
minutes, like a wet window with running
water.
She woke up from sleep nine hours
after the vaccination with a scintillating
scotoma. The following morning there
was a persistent left eye visual peripheral
blurring downwards, of a character never
experienced before. Two days later her
ophthalmologist found papilloedema of
the eye.
When referred to our clinic on day 4
visual acuity was 1.2 and 1.0 in the right
and the left eye, respectively. Ishihara’s
plates were correctly identified, however,
with a paler tint when seen with the left
eye. Tangent screen examination was nor-
mal except for an enlarged blind spot of
the left eye and a slight lower margin in-
dentation for white object 5/1000. There
was no disturbance on Amsler charts. Re-
peated Goldmann perimetries of the left
eye over 21⁄2 years demonstrated per-
sistance of the peripheral field defect.
There is still a minimum difference re-
garding colour brightness by Ishihara.
Objectively, the minimum inferior visual
field defect appears as the only significant
permanent sequel.
There were no abnormal findings by
general and laboratory evaluation (X-ray
of chest, angiotension converting en-
zyme, haemoglobin and white cell counts
(no eosinophilia), bilirubine, basic phos-
phatase, se-creatinine, Borrelia, Tox-
oplasmosis). Marginally elevated values
were found for ESR (24 mm/h) and
plasma immunoglobulin G, but not A
and M. A positive titer for Herpes sim-
plex virus IgG antibodies has been con-
sidered without relevance for the case.
Discussion
In the present case the sequence of events
is beyond dispute. A vaccination was

722

given, and subsequently a unilateral
anteriorly located optic nerve disorder
was observed. Visual perception showed
only a minimum and transient reduction
of quality (visual acuity and colour
sense), and the permanent peripheral vis-
ual field defect of the left eye has not in-
fluenced her overall visual skills.
On behalf of the investigators, the be-
nign course explains why a supplemen-
tary scan by MRI and a lumbar puncture
were not considered. As for the patient,
with the initial anxiety gone and her pro-
fessionalism as an MD restored she asked
the company behind the vaccine for in-
formation about cases of a similar na-
ture. Her motives were later enforced due
to secondary economic losses. In nego-
tiating raised pension savings her up-
dated medical record was used against
her. The insurance company gave her
poorer terms than first scheduled under
referral to multiple sclerosis as ‘most
likely underlying her optic neuritis’.
Whatever the correct label, her common
sense still saw the vaccination as the in-
disputable trigger of the disease.
Though rare, significant adverse im-
mune reactions associated with various
vaccinations are documented in medical
literature. This includes CNS symptoms,
for instance Guillain-Barré-like entities
(Shaw et al. 1988), and bilateral optic
neuritis (Yen & Liu 1991, Ray & Dreizin
1996, van de Geijn et al. 1994). In particu-
lar, manifestations appeared in associ-
ation with the plasma-derived vaccines of
the past. As relevant for the present case,
with modern recombinant vaccines the
likeliness of such an occurrance is re-
garded to be minimal (WHO Drug Info
1990), but case stories have been published
(Brézin et al. 1993, Berkman et al. 1996).
As a common feature of vaccination-re-
lated neurological disease there is a la-
tency period of 1⁄2–3 weeks, however,
without specific temporal peaks. Usually,
it is preceded by systemic reactions (Fen-
ichel 1982, Shaw et al. 1988, Mancini et al.
1996), and a type III or IV immune reac-
tion is suggested.
In literature short latencies, of hours
only as in our patient, appeared in two
cases with generalized CNS reactions.
Encephalopathy developing 5–9 hours
after influenza vaccination was thus re-
garded as a ‘delayed anaphylactoid reac-
tion’ by Warren (1956). A similar case
was published by Gross et al. in 1978.
With an isolated optic nerve manifes-
tation and a lack of systemic reactions it
is hard to imagine a type 1 or other im-
A O S 1999
mune-based reaction in the present case,
and the medical company showed no
understanding for her views and claims.
Looking for other explanations, the
pension company’s suggestion of multiple
sclerosis should be addressed first. The
age of the patient and the lack of other
neurological manifestations over time
speak against a demyelinating disorder.
Nor is a peripheral visual field defect
typical. Further, the association between
vaccination-related optic neuritis and
multiple sclerosis seems to be a feature
pertaining almost exclusively to child-
hood or young adult age (Riikonen 1989;
Farris & Pickard 1990). Herroelen and
coworkers (1991) published 2 cases of
CNS disease after recombinant hepatitis
B vaccination. One of them was a
multiple sclerosis relapse in a patient
aged 28.
Considering migraine instead, usually
there will be normal vision after attacks.
Exceptional patients are, however, left
with persistent visual field defects, hemi-
anopic, for instance (Miller 1991). Like-
wise, the much rarer forms of optic nerve
migraine might leave a small infarction in
a ‘weak’ vessel zone, possibly leading to
papilloedema – and to the visual findings
as met in our patient. As relative support,
after 2–3 months the patient shortly ex-
perienced monocular zebra-stripes corre-
sponding to the visual field defect of the
sick eye, typically provoked by strong
light; later it has attained a permanent
more greasy appearance.
A brief mention also of vascular oc-
clusions on a retinal level with a possible
association to recombinant hepatitis B
vaccine, as reported by Geijn et al. (1994)
and Granel (1997). Webb and McCary
(1977) further discussed the association
between optic nerve drusen and perma-
nent visual field defects (Lorentzen 1966,
Borruat & Sanders 1996). None of these
mechanisms were of relevance in our case.
Concluding remarks: The indisputable
association between the vaccination and
the unilateral papilloedema that ap-
peared in our patient may have been
purely temporary and random. If on a
migrainoid basis, however, on biological
grounds it is hard quite to refute the
possibility of the vascular episode being
triggered by the vaccination.
The ultimate aim of the presentation
has been to direct attention to the clinical
picture described, possibly to raise alert-
ness regarding similar atypical and minor
cases if of a more general occurrence than
reflected by the literature so far. Prophy-
lactic vaccination programmes are still of
obvious value globally, but for pro-
fessional councelling a currently updated
knowledge regarding possibly associated
adverse reactions is also of importance.
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