Introduction
Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory mediator involved in the pathogenesis of many chronic immunologic conditions, including chronic plaque psoriasis.1 To target TNF-alpha in psoriasis treatment, several drugs have been developed, such as infliximab, adalimumab, and etanercept.1
Infliximab has been approved by the Food and Drug Administration for dermatologic use since 2005 for the treatment of psoriatic arthritis, followed by approval for chronic plaque psoriasis in 2006.2,3 Aside from its dermatologic applications, infliximab has been approved for the treatment of Crohn’s disease, ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis.4 While it is generally considered safe, side effects include headache, rash, myalgia, hepatotoxicity, and in rare cases, optic neuropathy.4 To date, only 4 cases of anterior ischemic optic neuropathy have been reported with infliximab use, all involving non-dermatologic conditions like rheumatoid arthritis and Crohn’s esophagitis.5,6 Herein, we report the first case of bilateral nonarteritic anterior ischemic optic neuropathy (NAION) following infliximab treatment for chronic plaque psoriasis.
Case report
A 76-year-old Ashkenazi Jewish female presented to our outpatient clinic with a 10-year history of chronic plaque psoriasis. Her condition had previously been managed with topical steroids, narrowband UVB phototherapy, and methotrexate. However, due to her disease progression and inadequate response to these treatments, biologic therapy was recommended, and she was initiated on infliximab. While not the current first-line biologic for psoriasis, at that time, infliximab was used because of its high efficacy and availability of in-office infusions.
After the second infusion, the patient showed significant improvement with a marked reduction in psoriatic plaques. However, within a few days of her third infusion of infliximab, she experienced gradual vision loss in the inferior visual field of her right eye. Over the next 3 weeks, this loss of vision extended to the entire visual field of her right eye and began to affect her left eye, with sudden vision loss in the superior visual field of her left eye.
She was seen by a neuro-ophthalmologist who diagnosed her with bilateral NAION. Despite treatment with systemic steroids, her vision showed minimal improvement. As a result of her ocular complications, infliximab was immediately discontinued. One year later, the patient had only slight improvement in visual acuity and remained on no active treatment for her ocular condition. Her psoriasis was subsequently well controlled with narrowband UVB phototherapy and topical steroids.
Discussion
TNF-alpha inhibitors, including infliximab, have significantly improved the management of chronic inflammatory diseases like psoriasis. While generally safe and effective, these biologics are associated with a range of adverse effects, including infusion-related reactions, gastrointestinal upset, and tuberculosis or hepatitis B reactivation.4 Though ocular complications are rare, cases of NAION have been documented, with an annual incidence of 0.54 per 100,000 persons in the general population and 5 reported cases linked to infliximab use, including this one.4,7,8 Aside from its rarity, the potential for irreversible vision loss necessitates dermatologists to recognize and screen for this serious complication.
Infliximab, in particular, has been linked to a higher incidence of ocular adverse events, including anterior uveitis, endophthalmitis, optic neuritis, and NAION.5, 6, 7 Compared to other TNF-alpha inhibitors, etanercept has a higher incidence of uveitis but no direct links to NAION, while adalimumab has similar uveitis incidence as infliximab but fewer overall ocular adverse events.7 However, there have been reports of NAION associated with adalimumab.9 Infliximab is more frequently associated with inflammatory demyelinating central nervous events, like optic neuritis, and only rare cases of NAION have been documented.7 Optic neuritis and NAION have overlapping features but can be clinically distinguished by the presence of optic disc edema, which is characteristic of NAION but typically absent in optic neuritis.8 NAION also presents with sudden vision loss due to infarction of the optic nerve head, as seen in our patient, while optic neuritis usually causes gradual vision loss due to demyelination.8
To date, we report the first case of NAION associated with infliximab for the treatment of a dermatologic condition, and the fifth case overall (Table I). The previous 4 cases included 3 patients with rheumatoid arthritis, and one patient with Crohn’s esophagitis.5,6 All 3 rheumatoid arthritis patients experienced NAION symptoms after the third infusion, similarly to our patient, suggesting there may be cumulative toxicity effects of infliximab.6 Although all patients diagnosed with NAION were treated with systemic steroids, none exhibited improvement in their condition.5,6 While establishing causality for rare adverse events is not absolute, the consistent timing of symptom onset and treatment outcomes strongly supports an association with infliximab.
Table I.
Cases of nonarteric anterior ischemic optic neuropathy associated with TNF-alpha inhibitors
| Case | Ocular disease | Medication | Age/gender | Diagnosis for TNFα treatment | Time until onset | Sequelae | Reference |
|---|---|---|---|---|---|---|---|
| 1 | Anterior ischemic optic neuropathy | Infliximab | 68 M | Crohn’s esophagitis | During third infusion | No improvement of visual acuity | 5 |
| 2 | 54 M | Rheumatoid arthritis | 1 mo after third infusion | No improvement of visual acuity | 6 | ||
| 3 | 62 F | Rheumatoid arthritis | 40 d after third infusion | No improvement of visual acuity | 6 | ||
| 4 | 54 M | Rheumatoid arthritis | After third infusion | No improvement of visual acuity | 6 | ||
| 5 | 76 F | Chronic Plaque Psoriasis | After third infusion | Minimal improvement of visual acuity | This case |
Bolded entries indicate data from the current study. Italics are used for emphasis to denote “this case” within the table.
TNF-α, Tumor necrosis factor-alpha.
The precise mechanism by which infliximab induces NAION is not well understood given the limited number of cases. The disease itself is thought to result from a temporary reduction in blood flow to the short posterior ciliary arteries, leading to ischemia of the optic nerve head.8 This ischemia causes swelling and further restricts blood flow, creating a damaging cycle that results in the death of retinal ganglion cells essential for vision.8 Although it is unknown how infliximab contributes to this pathophysiology, there are hypotheses regarding the mechanism by which TNF-alpha inhibitors exacerbate demyelinating diseases, including optic neuritis.10 The primary hypothesis involves the inability for TNF-alpha inhibitors to penetrate the blood brain barrier, leading to anti-inflammatory effects in peripheral areas like the skin and joints, but possible exacerbation of inflammation in the central nervous system, resulting in demyelination and optic neuritis.10 This mechanism may also apply to NAION, where increased inflammation could further restrict blood flow, leading to tissue damage and infarction.
Although ocular complications are rare with TNF-alpha inhibitors, it is important for physicians to be aware of potential treatment-related adverse effects. Given the risk of irreversible vision loss, dermatologists should consider baseline ophthalmic evaluations, particularly for patients with risk factors such as diabetes, hypertension, or a crowded optic disc. Patients should also be educated on NAION symptoms, including sudden, painless vision loss, and advised to seek immediate ophthalmologic care if they occur. Increased awareness and early intervention can help mitigate permanent damage while allowing patients to continue benefiting from the therapeutic effects of infliximab.
Conflicts of interest
Dr Murakawa is an investigator for the following companies: AbbVie, Amgen, Apollo Therapeutics Ltd, Arcutis Biotherapeutics, Bristol-Myers Squibb, Castle Biosciences, Inc, Eli Lilly and Company, Galderma Research & Development, LLC, Incyte, Janssen Pharmaceuticals, Inc, Kiniksa Pharmaceuticals, Ltd, Pfizer Inc, Regeneron Pharmaceuticals, Inc, Sun Pharmaceutical Industries, Ltd, UCB; Speaker for the following companies: Regeneron Pharmaceuticals, Inc, Sanofi Genzyme, and Sun Pharmaceutical Industries, Ltd; Data Safety Monitoring Board member for Numab Therapeutics; Advisory Board member for the following companies: Castle Biosciences, Inc and Zerigo Health; Stockholder in Astellas Pharma US, Inc, and Valeant Pharmaceuticals North America LLC. Authors Currier and Abraham have no conflicts of interest to declare.
Footnotes
Funding sources: None.
Patient consent: The authors obtained written consent from patients for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors.
IRB approval status: Not applicable.
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