Optometry - Journal of the American Optometric Association
Volume 79, Issue 11 , Pages 687-691, November 2008

Ocular syphilis associated with syphilitic resurgence in a human immunodeficiency virus–infected man

  • Tiffenie Harris, O.D.

      Affiliations

    • Corresponding Author InformationCorresponding author: Tiffenie Harris, O.D., Indiana University School of Optometry, Community Eye Care Center, 803 N. Monroe St., Bloomington, Indiana 47404.
    • ,
  • Edwin C. Marshall, O.D.

Indiana University School of Optometry, Community Eye Care Center, Bloomington, Indiana

Article Outline

Optometrists provide an important service to the community, often acting as the first health care provider a patient consults. Many patients will present with ocular complaints that have systemic associations. In addition to diabetes, hypertension, and rheumatologic disorders, optometrists can encounter the ocular manifestations of sexually transmitted diseases such as syphilis. Syphilis is a chronic systemic infection caused by the spirochete Treponema pallidum, which is transmitted primarily through sexual contact. A recent rise in the prevalence and clinical manifestation of syphilis increases the likelihood of its presence in the optometric office.

 

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Background 

Multiple stages of syphilis exist, often interrupted by periods of latency (see Table 1). Primary syphilis is characterized by a single, nonpainful chancre at the site of sexual contact with an infected individual. The lesion will heal, treated or nontreated, within 6 to 8 weeks. However, the organism will then disseminate through the body via the blood and lymphatic systems. The spirochetes remain in the body for a lifetime. The amount of systemic spirochetes is greatest during the secondary stage, which most commonly involves a skin rash that presents 1 to 6 months after the primary infection. The rash surfaces on the trunk as macules and becomes maculopapular or papulosquamous as it spreads to the extremities. It also characteristically appears on the palms of the hands and soles of the feet. The rash is present in 90% of secondary syphilis cases, affecting the hands and/or soles in 50% to 80% of cases. In addition to the body rash, spirochetes can involve the hair follicles, producing a patchy alopecia of the scalp. The most severe stage of syphilis is neurosyphilis. Ocular syphilis is a form of neurosyphilis and must be treated as such, regardless of when it develops after primary infection.1, 2, 3, 4, 5

Table 1. Systemic manifestations of syphilis
StageClinical Finding
Primary:Chancre
Secondary:Diffuse rash (trunk, extremities, hands, feet), fever, malaise, arthralgias, lymphadenopathy, genital/anal condyloma latum, alopecia, glomerulonephritis, hepatitis
Latent: early v. lateNo clinical manifestations
Tertiary:Cardiovascular disease, gummatous disease-granulomatous-like lesions affecting any organ
Neurosyphilis:Seizures, headaches, ataxia, aphasia, paresis, hearing loss, neuropathy, tabes dorsalis, meningitis

Note: Case report patient findings in bold.

Diagnosis of infection with T pallidum is based on the clinical presentation of physical and ocular findings (see Table 1, Table 2). Serologic diagnosis is confirmed by positive results of a nontreponemal test, such as the venereal disease research laboratory (VDRL) test or the rapid plasma regain (RPR) test, and treponemal tests, such as the fluorescent treponemal antibody absorption FTA-ABS test or the T pallidum particle agglutination (TP-PA) test. The RPR and VDRL will indicate if the patient has an active case of syphilis, whereas the FTA-ABS and TP-PA will test for lifetime exposure to syphilis. Exposure to or past treatment for syphilis will result in reactive FTA-ABS and TP-PA tests.

Table 2. Ocular manifestations of syphilis
Ocular structureClinical Finding
Conjunctiva:Granulomatous conjunctivitis
Sclera:Episcleritis, scleritis
Cornea:Interstitial keratitis (congenital and tertiary stages)
Lens:Cataract
Uveal tract:Iridocyclitis, focal or multifocal chorioretinitis, anterior and/or posterior uveitis, panuveitis
Retina:Cystoid macular edema, chorioretinitis necrotizing retinitis, neuroretinitis, vasculitis, serous retinal detachment, ASPPC
Optic nerve:Disc edema, papilledema, optic atrophy
Pupils:Argyll Robertson pupil with neurosyphilis
Extraocular muscles:Cranial nerve palsies with neurosyphilis

Note: Case report patient findings in bold.

Patients with syphilis are frequently co-infected with human immunodeficiency virus (HIV).1, 2, 6, 7, 8 The current therapy for HIV-infected individuals includes highly active antiretroviral therapy (HAART). HAART has resulted in immunologic reconstitution, which has lowered the risk of opportunistic infections and altered the clinical presentation of syphilis, making conventional syphilis staging questionable.1, 6 The prevalence of syphilitic complications in the United States began to decrease significantly with the advent of penicillin and the initiation of public health controls. However, after a steady decline in the 1990s and a record low rate in 2000, the number of syphilis cases is on the rise.1, 6, 7, 8, 9 The recent increase in the incidence of syphilis is especially noticeable in the HIV-positive population, irrespective of highly active antiretroviral therapy or the patient's CD4 count. From 2001 to 2004, the primary and secondary (P&S) syphilis rate increased largely as a result of increases in cases among men who have sex with men (MSM).7, 8 In 2004, the Centers for Disease Control and Prevention (CDC) estimated that approximately 64% of all P&S syphilis cases were among MSM.9 Although the outbreaks among MSM have been reported mostly in the metropolitan areas of the United States, MSM activity and the consequent health risks can occur in any area of the country. In addition, the United Kingdom and New Zealand are experiencing a similar trend of a 15-fold increase in the incidence of syphilis over the last 5 years.10, 11

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Case report 

In Bloomington, Indiana, a 44-year-old HIV-positive white man presented with symptoms of flashes and floaters as well as a black “spot” inferiorly in the left eye for 2 weeks. He reported that he has been HIV-positive for 4 years and started HAART at the time of his diagnosis. Ocular history was unremarkable. He denied a bad cough, exposure to tuberculosis, fever, or malaise. A review of systems history revealed a rash that spread from the torso to the extremities, which was healing over the previous 6 weeks. Physical examination showed scaly papules that were present on the palms and soles of his feet. The patient reported that he had not seen his infectious disease doctor for the rash. In addition, he presented with patchy alopecia of the scalp. The alopecia had begun over the previous month, along with joint pain of the left knee (see Figure 1).

Entering visual acuities were 20/20 in each eye. Slit-lamp examination found a moderate degree of bilateral cells and flare in the anterior chamber of both eyes (OU) with mutton-fat keratic precipitates (KPs) on the endothelium of the left eye (O.S.), indicative of bilateral granulomatous uveitis. Humphrey visual field testing displayed an inferior defect O.S. The dilated fundus examination was remarkable for retinitis, along the superior and inferior vascular arcades with 1+ vitritis O.S. (see Figure 2). The dermatologic and ocular findings were strongly suggestive of syphilitic manifestations. Tests were ordered to confirm the working diagnosis. The tests included a complete blood count with differential to rule out anemia or leukemia. A chest x-ray and purified protein derivative (PPD) was ordered to rule out tuberculosis. The chest x-ray in addition to angiotensin-1–converting enzyme (ACE) test screen for sarcoidosis. To rule out an autoimmune disorder, the antinuclear antibodies and rheumatoid factor were ordered, both of which were normal. Given his HIV-positive status, a CD4+ count, HIV viral load, and cytomegalovirus (CMV) titer were ordered. To confirm the working diagnosis of syphilis, the RPR and FTA-ABS were ordered.

  • View full-size image.
  • Figure 2. 

    In the figure on the left, note the grayish areas of retina edema off the superior and inferior arcades. The retina returned to a normal appearance after antibiotic treatment as seen in the figure on the right.

The bilateral granulomatous uveitis was treated with 2 drops of homatropine hydrobromide 5% instilled OU in the office. In addition, the patient was treated aggressively with prednisolone acetate and, with a tentative diagnosis of acute retinal necrosis (ARN), he was started on valacyclovir, 1,000 mg 3 times a day for 7 days. The chest x-ray was normal as were the PPD and ACE. His CD4+ count was 339/mm3 (normal CD4+ count is >500s/mm3).12 His viral load was undetectable, and the CMV titer was normal. The FTA-ABS was reactive and RPR positive at 1:512, which confirmed the diagnosis of syphilis. In addition, his ocular findings were consistent with ocular syphilis, presenting as uveitis OU and retinitis O.S. The patient was co-managed with his infectious disease specialist. The physician recommended that the patient continue the treatment course of valacyclovir, and the syphilis was treated with intravenous ceftriaxone for 3 weeks. After the antibiotic treatment, the patient no longer reported flashes and floaters. The visual field defect was resolved subjectively and clinically. The palmar-plantar rash and alopecia resolved within 4 weeks as did the retinitis (see Figure 2). The uveitis resolved over the next 4 weeks with a slow topical steroid taper.

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Discussion 

CDC officials attribute the rise in syphilis to an increase in risky sexual behavior among men who have sex with men.1, 7, 9 In 1999, the National Plan to Eliminate Syphilis began with a focus on African-American heterosexual men living in the South. Today, this traditional population at risk has shown a significant reduction in reported cases of P&S syphilis. However, in 2006, the CDC expanded its elimination efforts with the Syphilis Elimination Effort (SEE) to meet new changes in the epidemiology of the disease, specifically the resurgence among MSM.13 Among the Healthy People 2010 targets for sexually transmitted diseases is the elimination of the transmission of syphilis and the reduction of its primary and secondary prevalence from the 1997 baseline of 3.2 cases per 100,000 population to 0.2 cases per 100,000 population by 2010.14

Primary eye care encompasses more than simply examining the eye. It is important for the optometrist to assess all aspects of the patient's systemic health in addition to assessment of the eye and its related structures. The comprehensive history is the most important diagnostic tool for the eye care practitioner, along with gross observation of the patient. This is most significant when a patient presents with a bilateral granulomatous uveitis, as the history can aid in the differential diagnosis and problem-focused approach to the examination. Ocular syphilis lacks pathgnomonic signs3; there is no true clinical finding in the eye that reveals the diagnosis. Therefore, all of the differential diagnoses must be explored to guide the clinician to the appropriate diagnosis.

The ocular manifestations of syphilis mimic a host of infectious and noninfectious conditions, thus giving it the nickname of the “Great Imposter.” Consequently, many associated ocular and dermatologic findings of syphilis often present similar to various other disorders.1, 2, 4, 15 The examination of a patient suspicious for syphilis must include a physical assessment to find the characteristic palmar and plantar rash. In addition, the patient should provide a positive history of a concurrent rash on the trunk. The physical assessment will also help rule out the various differential diagnoses, along with information provided in the history regarding duration of the rash. The patient should be assessed for any fever, headache, and neurologic deficits. In addition, a slit lamp examination, as well as a dilated fundus examination, will aid in the decision as to which laboratory testing and imaging studies are needed.

The bilateral granulomatous uveitis in combination with the pattern recognition of this patient's physical findings was most consistent with syphilis. However, this type of uveitis can be seen in tuberculosis, sarcoidosis, toxoplasmosis, Lyme disease, and Vogt-Koyanagi-Harada syndrome.4, 16, 17 In addition, significant differential diagnoses for this case were CMV and herpes zoster virus (the potential cause of ARN). The skin rash of the trunk, along with the palms and soles, can be seen in an assortment of systemic conditions. The key differentials for this case included drug/chemotherapy-induced rash and Rocky Mountain spotted fever. A similar rash can also be seen with Coxsakie A virus, also known as hand-foot-mouth disease, endocarditis, gonoccocal infection, meningococcemia, and psoriasis.4, 15, 18, 19, 20

In the prepenicillin era, ocular syphilis was the most common cause of uveitis.4, 21 Today, it is still a common ocular finding in secondary and tertiary syphilis, occurring in 2.5% to 5% of cases.2, 8 The uveitis is typically bilateral with predominantly granulomatous versus nongranulomatous presentations.2, 4, 10 However, it has been proposed that acute syphilitic posterior placoid chorioretinitis (ASPPC) is specific to ocular syphilis among HIV-positive individuals.8, 21, 22 The ASPPC fundus findings are described as large, placoid, yellowish lesions with faded centers at the level of the pigment epithelium in the macular and juxtapapillary areas.21, 22

Co-infection with HIV can accelerate the natural course of syphilis and alter its clinical presentation with a greater frequency of ocular involvement, neurosyphilis, treatment failure, and relapse.1, 6, 21 The preferred treatment for ocular syphilis is a neurosyphilis regimen. According to the CDC guidelines, the treatment of neurosyphilis is with intravenous penicillin G benzathine (BPG) for 14 days.23 The patient in this case was treated with intravenous ceftiaxone 2 g/d for 21 days. Ceftriaxone is a reasonable alternative to BPG for the treatment of HIV-infected patients with ocular/neurosyphilis.24 The CDC also recommends that all patients with neurosyphilis be tested for HIV, and that HIV-positive patients be monitored for treatment failure. Long-term ocular and systemic follow-up is required because relapses may occur in HIV-positive patients, despite antiretroviral therapy and intravenous antibiotic treatment. The patient in this case was co-managed with the infectious disease specialist and monitored at 3-month intervals with no apparent relapse at the 9-month post-treatment follow-up.

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Summary 

Ocular involvement is a diagnostically significant manifestation of syphilis, as it represents the severity of the disease. This case highlights the clinical presentation of a patient in the secondary stage of syphilitic disease with ocular involvement and presumed neurosyphilis. Optometrists will encounter conditions with systemic physical findings such as this case, which presented to a primary eye care facility. Historically, HIV-positive patients suffered from CMV retinitis. With the return of P&S syphilis, a diagnosis of ocular syphilis should be suspected in patients who present with bilateral uveitis. The prevalence of ocular syphilis may become the more frequent HIV-associated finding in patients medically managed with HAART.

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References 

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PII: S1529-1839(08)00470-3

doi:10.1016/j.optm.2008.01.022

Optometry - Journal of the American Optometric Association
Volume 79, Issue 11 , Pages 687-691, November 2008

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