Retrobulbar optic neuritis in a patient with enteropathic
spondyloarthritis treated with tumor necrosis factor inhibitors
Ben Ayed H, Fazaa A, Ouenniche K, Miladi S, Sellami M, Souabni L, Kassab
S, Chekili S, Ben Abdelghani K, Laatar A
Abstract: We report a case of a 62-year-old-woman with a 17
year-history of axial and peripheral spondyloarthritis associated to a
crohn disease, treated with tumor necrosis alpha inhibitors, who
developed an asymetric retrobulbar optic neuritis that promptly
responded to a high dose of steroids.
Key Words: optic neuritis, crohn disease,
spondyloarthritis.
Key Clinical Message: Optic neuritis is a rare ocular
manifestation of inflammatory bowel diseases and spondyloarthritis. It
should be suspected in case of painful loss of central visual field. The
incrimination of tumor necrosis alpha inhibitors reminds possible.
Introduction: Retrobulbar optic neuritis (RBON) is an
inflammatory condition of the optic nerve in which the disease process
occurs behind the lamina cribrosa (1). It is frequently associated to
demyelinating diseases as Multiple Sclerosis (MS) (2), autoimmune
disorders and infections (3). However, many other rare causes were
identified. We report the case of a patient with enteropathic
spondyloarthritis treated with tumor necrosis alpha inhibitors (TNF
alpha inhibitors) presenting a RBON.
Case Presentation: Our patient was a 62-year-old-woman with a
family medical history of MS, a 17 year-history of axial and peripheral
spondyloarthritis associated to a Crohn disease (CD), with no previous
neurologic or ocular manifestation. She was initially treated with a
20mg/week of oral Methotrexate which failed to bring her symptoms under
control. Then, she received Infliximab, discontinued after 8 courses for
secondary non-response, Etanercept, discontinued for lymphopenia, and
lastly 40 mg/2 weeks of Adalimumab. One year after the switch to
Adalimumab, anti-nuclear anti-double stranded and anti-histone
antibodies were positive, consistent with a drug induced lupus.
Adalimumab was discontinued for 6 months then reintroduced after an
immunologic remission.
Two years later she presented with an occipital headache, blind spots
and pain with her left eye movement. At the time of presentation, the
neurologic physical examination found a quadripyramidal syndrom, a
convergent strabism on the left eye and a normal accommodation reflex.
Her visual acuity was 20/20 in the two eyes. Formal visual field showed
a central scotoma in the left eye and full field in the right eye.
Dilated fundoscopic examination was unremarkable.
Laboratory tests demonstrated normal levels for complete blood count and
no B12 vitamin deficiency was detected. The Neuromyelitis optica (NMO)
antibodies were negative. A visual evoked potential showed a prolonged
latencies consistent with bilateral demyelinating RBON. Non-specific
frontal white matter hyperintensities (wMH) lesions were found on the
T2/FLAIR brain magnetic resonance imaging (MRI).
The diagnosis of an asymetric bilateral RBON was made. Both anti-TNF
therapy and inflammatory diseases (CD and spondyloarthritis) were
incriminated. The patient received 1 g intravenous Methylprednisolone
per day on 3 successive days with a dramatic improvement of blind spots
and eye pain. The decision was to discontinue Adalimumab.
An ophthalmic and a neurologic follow-up were recommended. No signs of
relapse were noted during follow-up visits.
Discussion: The frequency of ophthalmic involvement in
CD features 6.8% (4). It is more frequently seen in the first year of
the following-up, during activity of the bowel disease, in colonic
localisation and in the case of coexistence of articular manifestations
(entheropathic arthritis)(5).
Episcleritis and acute anterior uveitis are the most frequent ocular
complications (5). This latter is also reported as the most common
extra-articular manifestation of Spondyloarthritis, affecting more than
20% of the patients (6). Many other ophthalmic manifestations have been
described in relation to inflammatory bowel disease (IBD) such as
glaucoma, keratitis and dry eyes(5). However, the reported incidence of
posterior segment involvement ranges between less than 1% to 30%,
depending upon the series (4). Optic neuritis (ON), which is an
inflammation or demyelination or a degeneration of the optic nerve, may
be present in up to 4% of adult IBD patients(4). To our knowledge, only
6 documented cases of ON with CD were reported in the literature (7)(
table 1). The co-existence of ankylosing spondylarthritis (AS) and ON
were only reported in three cases(8) (Table 2).
On the other hand, a possible association between IBD and MS was
hypothesized and an approximately 3-fold increased risk of MS in IBD
patients was suggested (9). A retrospective study performed to examine
the relation between the two diseases in the era before TNF alpha
inhibitors showed a small but a significant association(9). Patients
with CD and ulcerative colitis were 54% and 75% more likely than
community controls to have been diagnosed with MS, ON or other
demyelinating conditions(4). ON was recorded in 6 of 7988 CD patients
(0.08%) and in 17 of 12 185 ulcerative colitis patients (0.14%), in
comparison with 50 of 80 666 controls (0.06%) (9).
TNF alpha inhibitors which are commonly used for the treatment of IBD
and refractory rheumatic diseases are incriminated in increasing the
risk of developing MS and ON. By 2001, the Food and Drug Administration
had received more than 20 reports of MS or other demyelinating
conditions in patients treated with these medications. In 2004,
clinician and patient warnings were updated on 3 major anti-TNF α
therapies: Etanercept, Adalimumab, and Infliximab (9). The mechanism of
this complication is not still well elucidated. A hypothesis suggests
that systemically administered anti-TNF agents may inhibit the apoptosis
of self-reactive T cells but fail to penetrate and reach the central
nervous system, inducing an autoimmune demyelinating process(10). The
other hypothesis suggests an activation of infecting microorganisms
which may result in a demyelinating process(11).
In our case, the incrimination of anti-TNF α therapy remained possible,
but it is less likely to be the sole cause of the RBON.
Conclusion: ON is rarely the ocular manifestation of AS
or CD. To date, the reported cases of demyelination after anti-TNF
therapy suggest a possible causal relationship. Further research should
be conducted to elucidate the mechanism of this complication which is a
serious adverse event.
Table 1: cases of co-existence of crohn disease and optic
neuritis in the absence of anti-TNF therapy reported in the
literature