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Middle-age man presents with bilateral painless loss of vision
OCT of the macula demonstrated vitelliform lesions in the right eye and a small subretinal cyst in the left eye.
A 52-year-old male chronic smoker with a medical history of coronary artery disease and ocular hypertension presented for evaluation of bilateral painless progressive blurred vision of 2 weeks’ duration.
The patient denied diplopia, headache or pain with eye movements. Family history was unknown. He had four lifetime male sexual partners and currently reported being in a monogamous relationship with a man. He lived in a Lyme-endemic area of Maine, although he denied a recent tick bite. He reported a penicillin allergy. He denied recent illness, rash, joint pain, respiratory symptoms, fevers, weight loss or neurological symptoms.
Examination
On initial presentation, the patient’s best corrected visual acuity was 20/30 in the right eye and 20/50 in the left eye. Pupils were round and reactive to light with an afferent pupillary defect in the left eye. Extraocular movements and IOPs were within normal limits. Color vision was full in both eyes. On slit lamp biomicroscopy, the anterior segment was quiet without presence of anterior segment inflammation. Posterior segment examination revealed bilateral optic nerve swelling with a superior disc hemorrhage in the right eye. Optical coherence tomography of the macula demonstrated vitelliform lesions, which corresponded to photoreceptor inner segment/outer segment junction disruption, in the right eye and a small subretinal cyst in the left eye (Figure 1). Humphrey visual field testing in both eyes demonstrated peripheral constriction that may have been a testing artifact, as it was of decreased reliability due to false negative errors. Additional testing revealed an enlarged blind spot on the right.
Figure 1. A: Color fundus photograph of the right eye. Note the prominent optic nerve head swelling, disc hemorrhage and yellow macular lesion. B: Color fundus photograph of the left eye with optic nerve head swelling and yellow macular lesion. Bottom: OCT retinal nerve fiber layer analysis demonstrating thickening of the retinal nerve fiber layer in both eyes.
Images: Branchini L, Athappilly G
Figure 2. Coronal (a) and axial (b) MRI orbit fat saturated T1 MRI revealing bilateral optic nerve sheath enhancement.
A lumbar puncture was performed with an opening pressure of 12 mm Hg and pleocytosis (26 white blood cells of lymphocytic predominance) with normal protein and glucose count. The venereal disease research laboratory (VDRL) test was negative. MRI with gadolinium demonstrated bilateral enhancement of the optic nerve sheath consistent with a diagnosis of bilateral optic perineuritis (Figure 2).
Diagnostic laboratory workups, including hemoglobin A1c, complete blood count, anti-nuclear antibody, HIV, Quantiferon gold, angiotensin-converting enzyme, Bartonella antibody, neuromyelitis optica antibody and an MRI of the spine, were all within normal limits. However, the patient had a positive treponema pallidum immune globulin G with a rapid plasma reagin titer of 1:128. Of note, he had a positive Lyme screen but negative confirmatory test.
What is your diagnosis?
Bilateral painless vision loss
The diagnosis of optic perineuritis due to syphilis was made clinically based upon examination and positive diagnostic findings. Cross-reactivity of treponemal antibody in serologic tests for Lyme disease has been well described, making the diagnosis of Lyme optic neuritis/perineuritis less likely.
In addition to infectious etiologies, the differential diagnosis of bilateral disc edema includes papilledema from meningitis, optic neuritis/perineuritis from inflammatory disorders such as sarcoidosis, neuromyelitis optica, and infectious agents such as Lyme or Cryptococcus. Rarely, leukemic or lymphoma infiltration may present with bilateral disc edema. All of the aforementioned were ruled out. In cases of sequential, profound vision loss in a man with bilateral disc edema, Leber’s hereditary optic neuropathy should be also considered.
Discussion
The most common manifestation of ocular syphilis is uveitis, which develops in 2.5% to 5% of patients with tertiary or secondary syphilis. Uveitis may be chronic or acute and may involve the anterior segment, although most often it involves the posterior segment. Posterior uveitis may present as chorioretinitis, retinal vasculitis, serous and exudative retinal detachments, and optic nerve changes. Anterior segment changes include stromal keratitis, episcleritis and scleritis. The number and variety of reported cases continue to rise. Doris et al reported six cases of syphilitic uveitis, one with papillitis and three with cutaneous symptoms including palmar eruption. A series published by Chao et al described four cases of ocular neurosyphilis, two with placoid retinal lesions and three with optic nerve involvement, suggesting overlap of disease presentation. O’Connell et al reported a case of bilateral ocular perineuritis.
Because close to 40% of patients with syphilis develop neurosyphilis, it is important that they are specifically tested for this if presenting with neurologic or ocular symptoms. Diagnosis of neurosyphilis is predominantly based on cerebrospinal fluid studies and imaging results. Cerebrospinal fluid analysis in neurosyphilis will most often show leukocytosis and elevated protein levels, IgG indices or oligoclonal bands. These indices may remain elevated for more than 1 year in symptomatic patients. If clinical suspicion is high, these findings alone warrant treatment. Positive VDRL testing of the cerebrospinal fluid may be confirmative but is not necessary for diagnosis. In this case, the cerebrospinal VDRL test result was negative.
Treatment consists of intravenous crystalline penicillin (18 million units to 24 million units daily) for 10 to 14 days or intramuscular procaine penicillin (2.4 million units) with the addition of probenecid by mouth for 10 to 14 days. The use of intravenous ceftriaxone also has reported success in a few cases of patients with penicillin allergy. However, this alternative has not been well studied for its long-term effects and is not recommended. It is currently recommended to perform allergy testing and, if necessary, desensitization if a patient is truly penicillin allergic. In this case, the patient reported a history of penicillin allergy and underwent skin testing, which was nonreactive.
There is debate in the literature as to whether or not to initiate systemic steroids in conjunction with antibiotic therapy. Steroids should never be used as the sole or initial treatment of syphilis. There has been subjective reported success in aiding in visual recovery of patients with syphilitic panuveitis with count fingers vision or worse. There may be also a theoretical benefit of possibly avoiding or mitigating a Jarisch-Herxheimer immune reaction after spirochete death from antibiotic treatment. However, there are no randomized control trials to support this practice.
In a retrospective analysis of 100 cases of neurosyphilis reported to Los Angeles County, the most common presenting symptom was visual changes (42%), underscoring the importance of ophthalmology in the identification and management of this disease. Of the 100 cases, 60% of subjects were infected with HIV and 52% of subjects were men who have sex with men. HIV should be tested for in all patients who test positive for syphilis. Concomitant infection with HIV will affect the likelihood, severity and management of neurosyphilis.
Follow-up
The patient received a 14-day course of intravenous crystalline penicillin without complication. His vision improved to 20/20- in the right eye and 20/30+ in the left eye with improvement of bilateral disc edema.