Naidus RM, Rodvien R, Mielke CH Jr. Colchicine toxicity. A multisystem disease. Arch Intern Med 137: 394, 1977.

Stapczynski JS, et al. Colchicine overdose: report of two cases and review of the literature. Ann Emerg Med 10: 364, 1981.

Vignes S, Vidailhet M, Dormont D, et al. Pseudotumorous presentation of neuro-Behçet: role of the withdrawal of colchicine. Revue de Medecine ­Interne 19(1): 55–59, 1998.

Class: Antirheumatic Agents

Generic name: 1. Adalimumab; 2. etanercept; 3. infliximab.

Proprietary name: 1. Humira; 2. Enbrel; 3. Remicade.

Primary use

These agents block the activity of tumor necrosis factor (TNF). These drugs are primarily used in the management of various arthritic diseases and Crohn’s disease.

Ocular side effects

Systemic administration

Certain

1. Optic or retrobulbar neuritis

2. Visual field defects

a.Peripheral vision loss

b.Various scotomas

Possible

1. Uveitis (etanercept)

2. Ocular sicca

3. Systemic lupus erythematous

Conditional/Unclassified

1. Orbit

a.Cellulitis

b.Myositis

2. Activation of toxoplasmosis (infliximab)

3. Retinal hemorrhage

Clinical significance

These relatively new agents have few clear-cut ocular side effects­ but there are areas of concern, with causation yet to be determined. Smith et al (2001) reported 60 cases of etanercept and optic neuritis. Symptoms develop within 1 to 14 months after starting therapy with a mean development time of 9.5 months. Nine patients had positive dechallenges and three had positive rechallenges. Tauber et al (2005) and NogueraPons et al (2005) also reported an association of this drug with optic neuritis. Fooroozan et al (2002), Mejico (2004), ten Tusscher et al (2003), Strong et al (2004), and Tran et al (2005) suggested an association of optic or retrobulbar neuritis with infliximab usage. Chung et al (2006) report two cases of optic neuritis associated with adalimumab use. There are five cases in the WHO database, making this whole class of drugs suspect as to an association with optic nerve disease. There are three cases in the National Registry showing uveitis. Some have suggested that these drugs cause or exacerbate systemic demylenating disease. This was postulated as the possible­ cause of a third nerve palsy with infliximab use (Farukhi et al 2006).

The question of whether or not these agents cause intraocular ­inflammation is confused by the fact that the diseases the drugs

are used to treat may also cause uveitis. There are two cases in the literature (Reddy and Backhouse 2003) and a case in the National­ Registry showing uveitis occurring each time etanercept was started and clearing each time the drug was stopped. Taban et al (2006) reported a case of positive double rechallenge of etanercept exacerbating anterior uveitis. Hashkes and Shajrawi (2003) reported sarcoid related uveitis occurring during etanercept therapy. De Vos et al (1995) have shown exacerbation of uveitis with anti-tumor necrosis factor in animals. It is possible one may find a subset of patients for which entanercept may cause or aggravate uveitis. Infliximab seems to be free of causing uveitis.

While some suggest etanercept as a treatment for scleritis there are three cases in the National Registry where this drug is implicated as causing or exacerbating scleritis. Since the disease these drugs are used to treat can also cause scleriis, at this time a drug-induced effect is suspect. Since these drugs can cause a dry mouth, they may aggravate ocular sicca. Reports of these drugs causing systemic vasculitis and suppression of the hemopoetic systems possibly supports occasional reports of retinal vascular abnormalities and vitreous hemorrhage.

Single cases of possible retinal toxicity causing visual field changes with etanercept (Clifford and Rossiter 2004), orbital myositis (Caramaschi et al 2003) and orbital cellutitis (Roos and Ostor 2006) have been reported. We have no cases of either of these in the National Registry.

References and Further Reading

Bleumink BS, terBorg EJ, Ramselaar CG, et al. Etanercept-induced subacute cutaneous lupus erythematosus. Rheumatology 40: 1317–1319, 2001.

Caramaschi P, Carletto A, Biasi D, et al. Orbital myositis in rheumatoid arthritis patient during etanercept treatment. Clin Exp Rheumotol 21: 136–137, 2003.

Chung JH, Van Stavern GP, Frohman LP, et al. Adalimumab-associated optic neuritis. J Neurol Sci 244: 133–136, 2006.

Clifford LJ, Rossiter JD. Peripheral visual field loss following treatment with etanercept. Br J Ophthalmol 88: 842, 2004.

De Vos AF, Van Haren MAC, Verhagen C, et al. Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat. Exp Eye Res 61: 667–675, 1995.

Farukhi FI, Bollinger K, Ruggieri P, et al. Infliximab-associated third nerve palsy. Arch Ophthalmol 124: 1055–1057, 2006.

Foroozan R, Buono LM, Sergott RC, et al. Retrobulbar optic neuritis associated with infliximab. Arch Ophthalmol 120: 985–987, 2002.

Hashkes PJ, Shajrawi I. Sarcoid-related uveitis occurring during etanercept therapy. Clin Exp Rheumatol 21: 645–646, 2003.

Hernandez-Illas M, Tozman E, Fulcher AFA, et al. Recombinant human tumor necrosis factor receptor fc fusion protein (etanercept): experience as a therapy for sight-threatening scleritis and sterile corneal ulceration. Eye Contact Lens 30: 2–5, 2004.

Koizumi K, Poulaki V, Doehmen S, et al. Contribution of TNF-alpha to leukocyte adhesion, vascular leakage, and apoptotic cell death in endotoxin-induced uveitis in vivo. Invest Ophthalmol Vis Sci 44: 2184–2191, 2003.

Mejico LJ. Infliximab-associated retrobulbar optic neuritis. Arch Ophthalmol 122: 793–794, 2004.

Noguera-Pons R, Borrás-Blasco J, Romero-Crespo I, et al. Optic neuritis with concurrent etanercept and isoniazid therapy. Ann Pharmacother 39: 2131–2135, 2005.

Rajaraman RT, Kimura Y, Li S, et al. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology 113: 308–314, 2006.

Reddy AR, Backhouse OC. Does etanercept induce uveitis? Br J Ophthalmol 87: 925, 2003.

Reiff A, Takei S, Sadeghi S, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum 44: 1411–1415, 2001.

arthritis treat to used agents and antagonists narcotic Analgesics, • 3 Section