intramuscular therapy inadequate [67]. Therefore, a patient with primary, secondary, tertiary, or congenital syphilis and concurrent HIV infection needs intravenous antibiotic therapy.

7.1.3.2 Lyme Disease

Scleritis and episcleritis may be ocular manifestations of Lyme disease, a tick-borne illness caused by B. burgdorferi, a larger spirochete than

T. pallidum.

Epidemiology

Lyme disease was Þrst described in 1977 by Steere et al. [93], in three Connecticut communities. Since then it has been increasingly recognized in the USA, particularly in the northeast, upper midwest, and California, as well as in certain areas of the PaciÞc Northwest and midwest [94, 95]. Lyme disease has also been detected in Europe [96].

Pathogenesis and Clinical Features

Lyme disease is acquired by the bite of Ixodes dammini, a well-recognized tick vector for the spirochete B. burgdorferi [97, 98]. However, only approximately 30% of persons recall being bitten [99]. Lyme disease has three deÞned clinical stages [100Ð102]. Stage 1 appears within 1 month of an infected tick bite, usually in the summer, and is characterized by a skin macular rash of varying severity, often with a clear center at the area of the bite, known as erythema chronicum migrans. There may be associated stiff neck, fever, headache, malaise, fatigue, myalgias, and/or arthralgias [99].

Stage 2 begins several weeks to months after the tick bite and is characterized by neurological (meningitis, radiculoneuropathies, severe headache) and cardiac (atrioventricular block, myopericarditis) manifestations [103Ð109].

Stage 3 occurs up to 2 years after the tick bite and is characterized by a migratory oligoarthritis [103, 110Ð112]. Neurological manifestations (encephalopathy, seizure, dementia, myelitis, spastic paraparesis, psychiatric disturbances, ataxia) also may occur in this stage [113Ð118]. Other manifestations include fatigue, lymphadenopathy, splenomegaly, sore throat, dry cough, nephritis, hepatitis, or testicular swelling.

Ocular manifestations of Lyme disease may appear at any stage but are more common in the

last two stages. They include neuroophthalmic Þndings, such as involvement of third, sixth, and seventh cranial nerves, optic nerve (optic neuritis and perineuritis, papilledema, ischemic optic neuropathy, optic nerve atrophy), and retina (retinal hemorrhages, exudative retinal detachments, cystoid macular edema) [96, 114, 119Ð123]. Other ocular Þndings are anterior and posterior uveitis, endophalmitis, keratitis, conjunctivitis, blepharitis, scleritis, and episcleritis [124Ð133]. Keratitis may manifest as stromal opacities, punctate superÞcial keratitis, or peripheral ulcerative keratitis. Ocular manifestations also may indicate recrudescence of the Lyme disease after inadequate treatment of the infection [130, 132].

Scleritis and Episcleritis

Scleritis and episcleritis may occur in Lyme disease. Their pathogenesis may be related either with direct invasion of the Borrelia species or to an immune-mediated response to Borrelia or its metabolic products. Scleritis has not been previously reported in Lyme disease.

In our prior series of 172 patients with scleritis [13], one patient had Lyme disease (0.58%). The patient was a 57-year-old female who had been living in New England for the past 5 years. She had had recurrent episodes of diffuse scleritis in her left eye along with mild anterior uveitis, disk edema, and cystoid macular edema. The patient did not recall being bitten and no systemic clinical abnormalities were found. Laboratory tests revealed a Lyme titer of 1:640 by enzyme-linked immunosorbent assay (ELISA) and elevated circulating immune complexes by Raji cell assay; an FTA-ABS test was negative. No scleral biopsy for silver stains or immunostains was performed. Therapy with intravenous ceftriaxone (2 mg a day for 14 days) and topical steroids controlled the scleritis without further recurrences.

Lyme disease must always be considered in the differential diagnosis of scleritis associated with neuroophthalmological Þndings.

Episcleritis also may appear in Lyme disease [132, 133], usually after other ocular manifestations, such as follicular conjunctivitis or stromal keratitis. Episcleritis may indicate a recurrence of the infection after inadequate treatment for Lyme disease [132].