A case of ocular neurosyphilis in a patient with HIV
In the modern era, neurosyphilis in immunocompetent individuals is very rare compared to pre-antibiotic era. However, the incidence is still a few folds higher in immunodeficient individuals, especially in patients with human immunodeficiency virus (HIV) infection. The cases we found, involved mostly the brain with eye involvement was found in only five other instances. Ocular syphilis is a type of neurosyphilis that can threaten vision leading to blindness if not treated promptly. Its diagnosis can be challenging but it should be considered if the neuro-ophthalmological findings cannot be explained by any other commonly encountered disease and diagnosis by serology should be considered as it is a potentially treatable condition (1).
We present a 27 years old male with HIV, not on any therapy who came to the hospital with complete loss of vision in the right eye for 4 months and partial loss of vision in the left eye for 5 weeks. He also had 6-month history of maculopapular rash over his trunk that extended to involve the entire body including the palms prior to presentation. He denied any redness, watering, or itchiness of the eyes, or focal neurological deficits. He also denied a history of diabetes, sexually transmitted infections (STIs), or recent trauma to the eyes.
On physical exam, he was cachectic. His visual acuity was less than 20/200 in right eye and 20/100 in left eye. There was desquamative rash in his palms, but not in the trunk or genitals, and had no lymphadenopathy.
Figure 1: Desquamative rash on the palms
Normal lab included complete blood count, hepatic, renal, thyroid function tests, fasting blood glucose, electrolytes, erythrocyte sedimentation rate, C-reactive protein. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, low glucose and high protein level. A diagnosis of neurosyphilis was confirmed with reactive serum rapid plasma Reagin (RPR) test and positive CSF venereal disease research laboratory (VDRL) test. His CD4 count was 418/mcL and viral load was 289,000/mcL. He tested negative for other STIs including genital herpes, Tuberculosis (TB), Hepatitis and gonorrhea. Intravenous penicillin G was administered for 10 days. HIV treatment was held to avoid immune reconstitution inflammatory syndrome (IRIS).
He was discharged with better vision to follow-up with ophthalmology and primary care in order to initiate anti-retroviral therapy. He was advised to observe safe sex practices.
Outpatient ophthalmology workup with B-scan, fundoscopy, and optical coherence tomography (OCT) of the macula showed panuveitis, vitritis and disc hyperemia without signs of raised intraocular pressure. In 3 months, he completely regained vision in his left eye and had partial recovery of vision in the right eye.
Painless vision loss without accompanying symptoms or trauma in a young individual without any obvious cause like diabetes presents a wide differential diagnosis that can be categorized into compressive, mitochondrial, vascular, infectious versus noninfectious optic neuritis, and infiltrative etiologies. Accordingly pituitary lesions, meningioma, slowly-growing aneurysm, leukemia, and lymphoma were considered but were less likely due to absence of raised intraocular pressure. Noninfectious causes including sarcoidosis and infectious causes like TB were considered, but were not likely given absence of constitutional symptoms. Bilateral anterior ischemic optic neuropathy was also considered, but our patient lacked the typical acute onset of vision loss commonly consistent with this disease.
Our patients’ HIV history pointed towards an infectious etiology. A reactive serum RPR and CSF VDRL confirmed neurosyphilis while disc hyperemia on ophthalmoscopy and the positive response to IV antibiotic eventually validated the diagnosis.
Ocular syphilis commonly causes posterior uveitis and panuveitis though may occasionally cause anterior uveitis, optic neuropathy, retinal vasculitis and interstitial keratitis. It may lead to decreased visual acuity and could eventually cause permanent blindness. It can occur at any stage of syphilis, including primary and secondary syphilis (2).
Diagnosis requires a high suspicion as a negative CSF VDRL does not rule out neurosyphilis and only 35% cases of ocular syphilis have neurosyphilis. The recommended adult regimen is IV aqueous crystalline penicillin G 18-24 million units per day (either as continuous infusion or 3-4 million units every 4 hours) for 10-14 days. Alternative regimen for adults is procaine penicillin 2.4 million units IM per day and oral probenecid 500mg four times per day, also for 10-14 days (3). Co-administration of corticosteroids or immunosuppressants along with antibiotics is controversial. Oral steroids, along with supplements, are often required to control ocular inflammation. The use of intravitreal dexamethasone implant for refractory macular edema in syphilitic uveitis has also been reported (4). However, steroids should not be started before starting antibiotics as it could worsen disease to a life and/or sight-threatening degree (5). Patients treated for syphilis should have the VDRL test repeated every three months for a period of 1-year post-treatment as titers should become nonreactive within a year after therapy. Patients should be retreated, if an initially high-titer VDRL test does not decrease fourfold within a year, or if a previously non-reactive VDRL test becomes reactive again (6).
Factors associated with poor visual prognosis include the time between onset of uveitis and treatment (>12 weeks), longer duration of ocular symptoms (>28 days) as seen with our patient, presence of macular edema or long-standing optic neuropathy, coinfection with HIV, and poor initial visual acuity. Factors associated with higher success rates included the presence of vasculitis (as detected by fundus fluorescence angiography), anterior uveitis, or neurosyphilis.
Common long-term complications of syphilitic uveitis include glaucoma, cataract, epiretinal membrane and macular edema. Choroidal neovascularization and widespread chorioretinal scarring can occur in some patients. The Jarisch-Herxheimer reaction following initiation of antibiotic therapy, may result in fever, malaise and headache, as well as a worsening of ocular manifestations and may be prevented by administration of systemic corticosteroids concurrent with antibiotic treatment (7).
Ocular syphilis, although a rare entity, if overlooked in the early stages, can lead to irreversible damage to eyes. Early diagnosis and treatment can prevent permanent blindness.
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