- Brief Report
- Open Access
A case report of adalimumab-associated optic neuritis
© The Author(s) 2012
- Received: 25 July 2011
- Accepted: 28 December 2011
- Published: 24 January 2012
To describe a case of retrobulbar optic neuritis that presented within 3 weeks of adalimumab treatment initiation.
This index case was evaluated with visual field testing, brain magnetic resonance imaging, lumbar puncture, and laboratory evaluation, and treated with intravenous methylprednisolone followed by a steroid taper.
Our patient made a full visual recovery, but was found to have extensive T2/FLAIR foci of hyperintensities that enhanced and had restricted diffusion on magnetic resonance imaging (MRI). Six months later, these demyelinating lesions still persisted and our patient was initiated on immunomodulatory treatment.
With the extensive burden of disease at presentation and persistence of lesions on follow-up MRI, this unusual case seems to suggest an unmasking of an underlying demyelinating process by adalimumab. The clinician should be mindful of this association and monitor for any manifestations and treat appropriately.
- Tumor necrosis factor
- Optic neuritis
- Multiple sclerosis
This report describes a case of adalimumab associated retrobulbar optic neuritis, of which two cases have been reported thus far in the literature . Adalimumab is a recombinant monoclonal antibody that binds to the cytokine tumor necrosis factor (TNFα). Various demyelinating disorders such as optic neuritis, multiple sclerosis, transverse myelitis, and Guillain–Barré have been reported in association with TNFα antagonist therapy [2–4].
The patient is a 42-year-old African-American female with a 20-year history of a chronic idiopathic non-granulomatous anterior uveitis. Her medical history includes hypertension and genital and oral herpes, for which she was maintained on valcyclovir. Her previous evaluations for the uveitis included non-reactive FTA-ABS and RPR, negative tuberculin skin test, negative serologies of ANCA, ANA, anti-double stranded DNA, rheumatoid factor, Lyme EIA, and normal ACE level, gallium scan and chest X-ray.
Within a few weeks, she experienced complete resolution and subsequent follow-up visual fields have been full. Six months afterwards, repeat imaging demonstrated no significant interval change in the multiple T2/FLAIR foci of hyperintensities. Several of the lesions still had faint restricted diffusion. Our patient has remained symptom free and has started on immunomodulatory therapy.
Since the introduction of TNFα antagonists into clinical use in 1998, three TNFα antagonists have been approved: two recombinant human monoclonal antibodies adalimumab and infliximab and a soluble receptor etanercept. TNFα antagonists have been found to be efficacious in the treatment of many immune mediated inflammatory diseases, including rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, Crohn's disease, psoriatic arthritis, and ankylosing spondylitis.
TNFα is a cytokine secreted by T-cells and macrophages that is an important component in the immune-mediation of demyelination. In vivo and in vitro experiments have suggested a correlative relationship between elevated TNFα and the severity of demyelinating disease . The effect of TNF inhibition was investigated in murine experimental autoimmune encephalitis (EAE) and the initial results were promising [6–9]. However, neutralization of TNFα in humans did not result in an improvement in demyelinative disease in multiple sclerosis, but rather it seemed to exacerbate it [10, 11]. Several explanations of its failure in humans include the inability of the TNFα inhibitor to penetrate the blood brain barrier and the complex role that TNFα plays in remyelination and regulation of other cytokines and lymphocytes .
Chung et al.  first described two cases of adalimumab associated optic neuritis. Subsequently, Simsek et al.  reviewed 15 cases of all TNFα antagonist associated optic neuritis in the literature. The interval from the initial administration to presentation ranged from 2 months to 1.5 years (median 7.5 months). All but one were treated with pulse steroids followed by oral steroids. Nine of the 15 patients had a complete visual recovery. Of the eight patients who had a brain MRI reported, only two had findings suggestive of demyelination. After 4 to 6 months, the two with significant MRI findings had only partial visual recovery.
It has been postulated that TNFα antagonists may induce demyelinating events or even unmask an underlying demyelinating process in those who are predisposed. Our patient with her short temporal proximity to therapy initiation and full recovery without recurrence would suggest a causal association. The large burden of radiographic disease at presentation so quickly after treatment initiation and its persistence would give credence to the theory that an underlying demyelinating process was unmasked by adalimumab.
The occurrence of a demyelinating event with TNFα antagonist treatment is rare; however, the clinician should be aware of the need to observe their patients closely for any manifestations and to institute appropriate therapy.
Conflicts of interest
No authors have any financial/conflicting interests to disclose.
- Chung JH, Van Stavern GP, Frohman LP, Turbin RE (2006) Adalimumab-associated optic neuritis. J Neurol Sci 244:133–136PubMedView ArticleGoogle Scholar
- Mohan N, Edwards ET, Cupps TR et al (2001) Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 44:2862–2869PubMedView ArticleGoogle Scholar
- Thomas CW Jr, Weinshenker BG, Sandborn WJ (2004) Demyelination during anti-tumor necrosis factor alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 10:28–31PubMedView ArticleGoogle Scholar
- Shin IS, Baer AN, Kwon HJ et al (2006) Guillain–Barre and Miller Fisher syndromes occurring with tumor necrosis factor alpha antagonist therapy. Arthritis Rheum 54:1429–1434PubMedView ArticleGoogle Scholar
- Sharief MK, Hentges R (1991) Association between tumor necrosis factor alpha and disease progression in patients with multiple sclerosis. N Engl J Med 325:467–472PubMedView ArticleGoogle Scholar
- Selmaj K, Raine CS, Cross AH (1991) Anti-tumor necrosis factor therapy abrogates auto-immune demyelination. Ann Neurol 30:694–700PubMedView ArticleGoogle Scholar
- Ruddlen H, Bergman CM, Mcgrath ML (1990) An antibody to lymphotoxin and tumor necrosis factor prevents transfer of xperimental allergic encephalomyelitis. J Exp Med 172:1193–1200View ArticleGoogle Scholar
- Selmaj K, Papierz W, Glabinski A, Kohn OT (1995) Prevention of chronic relapsing experimental autoimmune encephalomyelitis by soluble TNF receptor 1. J Neuroimmunol 56:135–141PubMedView ArticleGoogle Scholar
- Probert L, Akassoglou K, Pasparakis M et al (1995) Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor-α. Neurobiology 92:11294–11298Google Scholar
- van Oosten BW, Barkhof F, Truyen L et al (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47:1531–1534PubMedView ArticleGoogle Scholar
- The Lenercept Multiple Sclerosis Study Group and the University of British Columbia/MRI Analysis Group (1999) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 53:457–465View ArticleGoogle Scholar
- Magnano MD, Robinson WH, Genovese MC (2004) Demyelination and inhibition of tumor necrosis factor (TNF). Clin Exp Rheumatol 22(suppl 35):S134–S140PubMedGoogle Scholar
- Simsek I, Erdem H, Pay S et al (2007) Optic neuritis occurring with anti-tumour necrosis factor α therapy. Ann Rheum Dis 66:1255–1258PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.