Drug-Induced Uveitis

Kara C. LaMattina

Nehali V. Saraiya

Debra A. Goldstein

Uveitis is usually a result of immune or infectious causes; however, certain systemic or local drugs may also precipitate intraocular inflammation. In general, the pathogenesis of drug-induced inflammation is not well understood. It is hypothesized that direct and/or indirect mechanisms are involved. Direct mechanisms are thought to play a role with topically or intracamerally administered drugs and are usually observed soon after medication use. Indirect mechanisms result from immune complex deposition in uveal tissues, immune reactions to antigens liberated from antibiotic-induced death of a microorganism, or drug-induced alteration of melanin’s ability to scavenge free radicals. These mechanisms may result in intraocular inflammation weeks to months after initial use of the drug.

The most common medications implicated in drug-induced uveitis are discussed in the following sections.

ANTIMICROBIALS

RIFABUTIN

Rifabutin is prescribed for the treatment and prophylaxis of Mycobacterium avium complex infection in HIV-positive patients. Symptoms of acute anterior uveitis may present 2 weeks to more than 7 months following initiation of therapy. Uveitis has been reported to occur with rifabutin alone as well as in combination with other antimicrobial agents, such as azithromycin, erythromycin, clarithromycin, ethambutol, and fluconazole. It has been reported with doses as low as 300 mg/day. It recurs with rechallenge and increases in severity with dose escalation.

Treatment and Prognosis

• Discontinue rifabutin.

• Treat inflammation with topical steroids and cycloplegic agents.

• Uveitis generally resolves within 1 to 2 months of discontinuation of rifabutin and administration of topical corticosteroids, often with complete resolution of symptoms and recovery of vision.

REFERENCES

Jacobs DS, Piliero PJ, Kuperwaser MG, et al. Acute uveitis associated with rifabutin use in patients with human immunodeficiency virus infection. Am J Ophthalmol. 1994;118(6):716-722.

Moorthy RS, London NJ, Garg SJ, Cunningham ET Jr. Drug-induced uveitis. Curr Opin Ophthalmol. 2013;24(6):589-597.

CIDOFOVIR

Cidofovir has been used intravenously (IV) and intravitreally for the treatment of cytomegalovirus (CMV) retinitis. Anterior uveitis has been reported to occur in 26% to 59% of patients receiving IV cidofovir after a median of 4 to 11 doses. Hypotony and uveitis have also been reported following IV cidofovir in a patient with nonocular CMV infection (encephalitis) and an otherwise normal fundus exam, suggesting a direct effect of the drug on the ciliary body. Anterior uveitis also occurs with intravitreal cidofovir for the treatment of CMV retinitis. One cases series reported anterior uveitis in 26% of patients after a single intravitreal cidofovir injection. Concomitant use of systemic probenecid decreased the frequency of inflammation. Because of its association with immune recovery uveitis, cidofovir should be used only as a last resort if immune recovery is expected.

Treatment and Prognosis

• Aggressive topical steroid and cycloplegic agents

• Cessation of cidofovir is usually required.

• Outcome is variable with potential for permanent structural complications, such as posterior synechiae and hypotony.

REFERENCES

Ambati JK, Wynne KB, Angerame MC, Robinson MR. Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis. Br J Ophthalmol. 1999;83(10):1153-1158.

Kempen JH, Min YI, Freeman WR, et al; Studies of Ocular Complications of AIDS Research Group. Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis. Ophthalmol. 2006;113(4):684-694.

Moorthy RS, London NJ, Garg SJ, Cunningham ET Jr. Drug-induced uveitis. Curr Opin Ophthalmol. 2013;24(6):589-597.

SULFONAMIDES

Sulfonamide derivatives are a mainstay for the treatment of many gram-positive and gram-negative bacterial infections, including urinary tract infections, otitis media, bronchitis, sinusitis, and pneumonia. Visual disturbances, keratitis, conjunctivitis, and periorbital edema have been reported with their use. Inflammation may occur within 24 hours of starting the medication and often recurs with rechallenge.

Signs and Symptoms

• Unilateral or bilateral

• Pain

• Redness

• Photophobia

• Conjunctival or scleral injection

• Anterior chamber cell and flare

• Other autoimmune dysfunction such as erythema multiforme minor, diffuse macular vesicular rash, stomatitis, glossitis, or granulomatous hepatitis may be present concurrently. The most serious complication is Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) (Figs. 12-1, 12-2, 12-3, 12-4 and 12-5).

SJS/TEN are acute hypersensitivity reactions of the skin/mucous membranes that are usually drug induced.
Affected patients are mostly young adults.
Patients typically have a flu-like prodrome of malaise, fatigue, and headache followed by diffuse erythematous patches that can coalesce to form blisters with full-thickness epidermal necrosis.
There is risk of bacterial superinfection.
Mucosal involvement, including the conjunctiva, occurs in

nearly all patients.

Treatment and Prognosis

• Discontinue the offending agent.

• Treat iritis with topical steroids and cycloplegic agents as necessary.

• Patients have guarded visual prognosis because of associated corneal scarring.

• Patients with SJS may need hospitalization and care in an intensive care or burn unit. Patients may develop hypotension, renal failure, and respiratory failure.

REFERENCES

Moorthy RS, London NJ, Garg SJ, Cunningham ET Jr. Drug-induced uveitis. Curr Opin Ophthalmol. 2013;24(6):589-597.

Shifera AS, Kopplin L, Lin P, Suhler EB. Drug-induced uveitis. Int Ophthalmol Clin. 2015;55(2):47-65.

FIGURE 12-1. Stevens-Johnson syndrome. This patient with Stevens-Johnson syndrome has dry eye and extensive symblepharon formation. (Courtesy of Charles Bouchard, MD, at Loyola University.)

FIGURE 12-2. Stevens-Johnson syndrome. This patient with Stevens-Johnson syndrome has conjunctivitis and sloughing of the conjunctival epithelium. (Courtesy of Charles Bouchard, MD, Loyola University.)

FIGURE 12-3. Stevens-Johnson syndrome. A 3-year-old girl developed Stevens-Johnson syndrome and suffered a desquamative eruption. Note the extensive mucositis (conjunctivitis and stomatitis) characteristic of Stevens-Johnson syndrome. Her medication was changed, and she was successfully treated with intravenous immunoglobulin (IVIG). (Courtesy of Vanessa A. London, MD.)

FIGURE 12-4. Stevens-Johnson syndrome. The palms of a 59-year-old man diagnosed with Stevens-Johnson syndrome. Note the sharp demarcation of erythema at the edges of the palms and the classic targetoid lesions with dusky centers along his wrists. His medication was discontinued, and he was treated with 60 mg prednisone for 3 days with resolution of his symptoms. (Courtesy of Vanessa A. London, MD.)

FIGURE 12-5. Stevens-Johnson syndrome. A. A 48-year-old man with AIDS presented with a diffuse morbiliform eruption that evolved into blistering with prominent palm and sole involvement. B. He also had conjunctivitis, stomatitis, and involvement of the glans penis. Skin biopsy confirmed a diagnosis of Stevens-Johnson syndrome. With discontinuation of trimethoprim/sulfamethoxazole, his rash eventually resolved. (Courtesy of Vanessa A. London, MD.)

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