gms | German Medical Science

Tumor necrosis factor alpha (TNF-α) stimulates systemic inflammation and acute phase reaction [1]. Infliximab binds to TNF-α and inhibits its action. Infliximab is widely used for the treatment of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, psoriasis and ankylosing spondylitis [2], [3]. Infliximab is generally well-tolerated by patients. Most common side effects include infusionrelated reactions like headache, rush and flushing. Demyelinating disorders are rarely seen due to the use of anti-TNF-α agents [4], [5], [6], [7]. Herein, we present a case of infliximab-induced retrobulbar optic neuritis in an ankylosing spondilitis patient.

A 58-year-old woman with a 25-year history of ankylosing spondylitis presented to our clinic with a blurred vision in her right eye for two days. Best-corrected visual acuity was counting fingers OD (right eye) and 20/25 OS (left eye). She identified 6 out of 21 Ishihara pseudoisochromatic color plates with the right eye and 21 of 21 with the left eye, and she had a right relative afferent pupillary defect. Her optic discs seemed healthy (Figure 1 [Fig. 1]). Fundus fluorescein angiography and optical coherence tomography findings did not point out any causative pathology (Figure 2 [Fig. 2]). Magnetic resonance imaging (MRI) of the brain and orbits revealed high signal intensity in the right optic nerve (Figure 3 [Fig. 3]). Her neurological examination was unremarkable. Detailed history of the patient revealed that she was receiving infliximab therapy for ankylosing spondylitis. Infliximab treatment was stopped and 1 g/day of intravenous methylprednisolone for five days was started, then switched to oral prednisone 1 mg/kg/day and tapered slowly. Her vision improved gradually. Her visual acuity improved to 20/20.

MRI of the brain and orbits revealed high signal intensity in the right optic nerve (Figure 3 [Fig. 3]). Her neurological examination was unremarkable. The detailed history of the patient revealed that she was receiving infliximab therapy for ankylosing spondylitis. Infliximab treatment was stopped and 1 g/day of intravenous methylprednisolone for five days was started, then switched to oral prednisone 1 mg/kg/day and tapered slowly. Her vision improved gradually. Her visual acuity improved to 20/20.

The patient’s clinical course was consistent with retrobulbar optic neuritis. Alternative diagnoses, such as compressive, infiltrative, and infectious optic neuropathies, were eliminated based on laboratory testing, neuro-imaging and clinical history. The clinical presentation of the patient started after taking three doses of medication. In a case series by ten Tusscher et al., after the third dose of infliximab infusion patients showed signs of anterior optic neuropathy, which was resistant to steroid therapy [8]. Simsek et al. reported a temporary link between the onset of symptoms and duration of drug use [9]. However, it is unclear from published case reports whether the anti-TNF-α agents, cumulative dose, or duration of therapy influences the clinical presentation. This article adds a new case of infliximab-induced optic neuritis to the literature. TNF-α inhibitors are used for rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis and psoriasis [2], [3]. TNF-α seems to have a role in the pathophysiology of demyelinating diseases [10], [11]. Human studies have demonstrated negative effects of TNF-α blocking in multiple sclerosis and precipitating of demyelination has even been described [4]. However, no clear explanation regarding the pathogenic mechanism is available.

Not only infliximab but also other TNF-α antagonists are thought to facilitate autoimmune reactions and demyelinating process [12], [13], [14]. On the other hand, Winthrop et al. evaluated patients in whom anti-TNF-α treatment or non-biologic disease-modifying anti-rheumatic drugs (DMARD) had recently been started [15]. A total of 61,227 patients’ records were analyzed and only six cases of optic neuropathy were noted. Half of the patients with optic neuritis were anti-TNF-α users and the other half were non-biologic DMARD users. They have found similar frequency of optic neuritis with anti-TNF-α agents and non-biologic DMARDs. TNF-α inhibitors are used for inflammatory diseases in gastroenterology, dermatology, neurology, and rheumatology with increasing frequency. In ophthalmology practice, anti-TNF-α agents can be used in ocular inflammation like scleritis and resistant uveitis [16]. Neurological deficits may occur during the treatment with TNF-α inhibitors. Patients who are on anti-TNF-α should be followed on a multidisciplinary basis and properly informed about potential side effects.

It is important to consider the possibility of optic neuritis in patients who experience sudden-onset visual loss while being treated with infliximab. If a patient using TNF-α blockers experiences visual abnormalities, he/she should present to an ophthalmologist immediately.

Consent has been obtained from the patient.

The authors declare that they have no competing interests.