eMedicine Specialties > Ophthalmology > Infectious Disease

Ocular Manifestations of Syphilis

Author: Manolette R Roque, MD, MBA, President and CEO, Service Chief of Ocular Immunology and Uveitis, Refractive Surgery, EYE REPUBLIC Ophthalmology Clinic; General Manager, Ophthalmic Consultants Philippines; Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Section Chief of Ocular Immunology and Uveitis, Department of Ophthalmology, St. Luke's Medical Center Global City; Senior Eye Surgeon, The LASIK Surgery Clinic; Senior Eye Surgeon, Precise Eye Laser Center
Coauthor(s): Barbara L Roque, MD, Full Partner, Ophthalmic Consultants Philippines Co, Chief of Service, Pediatric Ophthalmology and Strabismus, Consulting Staff, Orbit and Eye Plastics, Eye Republic Ophthalmology Clinic; C Stephen Foster, MD, FACS, FACR, FAAO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution
Contributor Information and Disclosures

Updated: Feb 19, 2010

Introduction

Background

Syphilis is caused by an infection with a spirochete, Treponema pallidum, a thin, tightly wound, relatively stiff, spiral-shaped parasite measuring 10-13 µm. Schaudinn and Hoffman of Hamburg discovered T pallidum in 1905.

This disease has been a source of social stigma, morbidity, and mortality for centuries, and it was notably notorious in the early 1900s for infectious chorioretinitis. The term "syphilis" came from a poem written in 1530 by the Italian poet Hiero Fracastor. His main character, in the poem, was an infected shepherd named Syphillus. Syphilis was first described at the end of the 15th century by an Italian physician, Nicolaus Leonicenus, at the same time of the return of the first European explorers from the New World. When Charles VIII of France invaded Naples with mercenaries from all over Europe, spread of this disease was noted on both war camps and was termed French Pox and Neopolitan Pox, respectively.

Syphilis can be congenital or acquired. The acquired form is usually sexually transmitted, chronic, and systemic. Although the introduction of penicillin in the 1940s decreased the epidemiology, there has been a resurgence of the disease, over the past two decades, especially among nonwhites, male homosexuals, and intravenous drug users. Bacterial resistance, poor socioeconomic backgrounds, increased high-risk sexual activity, and immunodepressing diseases have contributed to this resurgence.

Syphilis has been given titles, such as "the great imitator, the great mimic, and the great masquerader!" of ocular inflammatory conditions. It lacks pathognomonic signs and often presents similar to other ocular inflammatory conditions.

Syphilis is associated with the following ocular diseases: interstitial keratitis, episcleritis, scleritis, iritis, iris papules, chorioretinitis, papillitis, retinal vasculitis, and exudative retinal detachment. Examples of ocular manifestations of syphilis are shown in the images below.

Pathophysiology

Primary syphilis

The predominant lesion of primary syphilis is a chancre at the inoculation site, which is usually at the genitalia region. Chancres are erythematous papules at the inoculation site that later erode to form painless ulcers. They may occur at multiple sites. Spirochetes fill the serous fluid from these lesions. The lesions appear 4 weeks after the initial infection and heal spontaneously in 1-2 months.

After T pallidum penetrates the skin or mucous membrane, the organism enters the lymphatics and blood stream and disseminates shortly after contact. If left untreated, primary syphilis leads to secondary syphilis.

Secondary syphilis

The systemic treponemal load is largest in secondary syphilis. Generalized maculopapular (or pustular rash), and lymphadenopathy are the characteristic lesions in this stage. These lesions appear 4-10 weeks after the initial manifestation. Lesions usually present at the flexor and volar body surfaces (ie, palms, soles). Resolution occurs without scarring, although hyperpigmentation or hypopigmentation may occur. Papules (condylomata lata) at the mucocutaneous junctions, and in moist areas of the skin, appearing as dull pink or gray hypertrophic lesions, are common.

Constitutional symptoms of fever, malaise, headache, nausea, anorexia, and joint pains often are present. The liver, kidneys, and/or GI tract may or may not be involved. Ocular involvement has been reported in 10% of cases, and cerebrospinal fluid (CSF) pleocytosis has been seen in a few cases.

Latent syphilis

Latent syphilis follows secondary syphilis and is divided into 2 groups, early latent and late latent. These subgroups occur within and beyond 1 year after initial infection, respectively. Most cases have been reported to stay at the latent stage with 30% converting to the next stage.

Tertiary syphilis

Tertiary syphilis is divided into 3 groups (ie, benign tertiary, cardiovascular, neurosyphilis). Benign tertiary syphilis characteristically presents with gummatous lesions that are actually granulomas, histologically, in the skin and the mucous membranes. The lesions may occur in the choroid, ciliary body, and iris. Cardiovascular syphilis presents with involvement of the coronary arteries or the aorta. Neurosyphilis may manifest with tabes dorsalis or general paresis. The CNS is affected via the vascular pathways or via direct involvement of parenchyma.

Quaternary syphilis

Quaternary syphilis has been disregarded for some time now; however, with the advent of AIDS-related syphilis cases, this stage is being reintroduced. Some authors use it to describe an aggressive form of neurosyphilis in which necrotizing encephalitis is present in patients with AIDS.

Frequency

United States

Occurrence is higher in the southern and southwestern United States. It is higher in large urban populations.

In 1940, prior to the introduction of antibiotics, the incidence of primary and secondary syphilis was about 100,000 cases. In 1956, with antibiotic therapy, incidence declined steadily to 10,000 cases. In the early 1980s, the incidence of syphilis rose to about 35,000. In 1988, 40,275 new cases of primary and secondary syphilis were reported. In 1990, as a result of intravenous drug and crack cocaine abuse, as well as illegal prostitution, the incidence went up to more than 45,000 cases. In 1995, 16,500 cases were reported in the Summary of Notifiable Diseases.

International

In Seville, Spain, a report indicates that enhanced opportunity for spread accounts for clustering of syphilis in some towns. Syphilis has reemerged in developed countries.¹

In Singapore, special political and sociologic factors, including prostitution, reduced prescribing of penicillin for gonorrhea because of the emergence of penicillin-resistant strains of Neisseria gonorrhoeae, and loss of "herd" immunity, resulted in an increase of early infectious syphilis from 1980-1984.

Mortality/Morbidity

Morbidity from primary and secondary syphilis ranges from the irritation brought about by the primary lesion to the more significant symptoms of secondary syphilis.

Infant deaths resulting from syphilis and new admissions of patients with syphilitic psychoses have fallen 99% in the United States since 1940. The total number of cases of late and latent syphilis has fallen 98% in the United States since 1943. Congenital syphilitic cases have decreased by 98% since 1941.

Race

Incidence is greater among nonwhites.

Sex

Incidence is greater in males than in females. Garfinkel and colleagues noted that women are screened less frequently for syphilis among emergency department patients with suspected sexually transmitted diseases (STDs).² This raises a flag of concern about the underdiagnosis of women.

Age

Frequency is greater in young adults during the years of peak sexual activity. Most new cases occur in persons of both sexes aged 15-39 years, with the highest infection rates in individuals aged 20-29 years.

Clinical

History

Physicians must pay close attention to the patient's clinical history in suspected cases of syphilis. A high index of suspicion, combined with an excellent history, leads to a streamlined list of differentials prior to examination.

• Elicit a sexual history (ie, sexual intercourse, oral sex, anal sex).
  • Transmission of T pallidum is almost exclusively sexual.
  • Transmission through skin requires a break in the skin, but T pallidum can penetrate intact mucous membranes.
• Transplacental transmission from an infected mother to an infant accounts for infantile syphilis.
• Prior to modern donor screening procedures and blood banking, blood transfusions were another route for transmission. Spread by transfusion of fresh blood is still possible.
• Intravenous drug abuse contributes to the rising cases of syphilis.
• Syphilis can be spread by accidental contact with an infected lesion.
• The patient may complain initially of nonspecific symptoms, such as photophobia, eye redness, and blurring of vision.

Physical

Syphilis may be congenital or acquired.

• Congenital syphilis
  • Manifestations of the disease affect approximately 70% of infected newborn infants.
  • Congenital syphilis can present with various ocular findings that include the following:
    • Acute and chronic iritis
    • Characteristic corneal lesion (see interstitial keratitis)
    • Scleritis
    • Chorioretinitis
    • "Salt and pepper" fundus
    • Pseudo–retinitis pigmentosa (pseudo-RP)
    • Retinal periphlebitis
    • Optic neuritis
    • Optic nerve pallor
    • Secondary cataract
• Anterior uveitis
  • Unilateral in 56% of cases
  • Granulomatous with mutton-fat keratic precipitates on the corneal endothelium in 50% of cases
  • Iris nodules
    • Iritis roseata (small, dilated collections of capillaries in the iris)
    • Iritis papulosa (iritis roseata increasing in size to resemble a papule)
    • Iritis nodosa (iritis papulosa increasing in size forming a yellow-red nodule)
    • Treponemal emboli may cause vascular tortuosity and dilatation, which account for the iris nodules.
• Intermediate uveitis
• Posterior uveitis
  • Posterior uveitis occurs in 9-18% of cases.
  • Panuveitis occurs in 27-47% of cases.
  • Vitreal cells are typical.
  • Vasculitis with or without vascular occlusion, macular edema, stellate maculopathy, disciform macular detachment, serous macular/retinal detachment (pseudohypopyon), pseudo-RP, retinal detachment, neuroretinitis, papillitis, diffuse chorioretinitis, uveal effusion, central retinal vein occlusion (CRVO), subretinal neovascular membrane (SNVM) formation, and retinal necrosis (big blind spot syndrome)
  • Syphilitic posterior placoid chorioretinitis are present in individuals who are HIV positive
    • Large, flat, dry, yellowish, or gray (with baited centers); macular or juxtapapillary placoid lesions at the retinal pigment epithelium (RPE) layer
    • Leopard spot hypofluorescence on fluorescein angiography
    • Chen in Australia reported report a case of acute unilateral maculopathy, due to posterior placoid chorioretinitis associated with syphilis in an immunocompetent patient.³ Ophthalmoscopy showed a unilateral yellowish placoid lesion at the macula. Positive syphilis serology confirmed active infection. No other systemic signs of syphilis were noted. Treatment with intravenous benzylpenicillin 1.2 g every 4 hours for 2 weeks resulted in resolution of the lesions.
• Conjunctiva
  • Chancre in primary syphilis
  • Nonspecific conjunctivitis in secondary syphilis
  • Gumma in tertiary/late syphilis
• Scleritis/episcleritis
  • Nodular or diffuse
  • Usually present in secondary syphilis
• Interstitial keratitis
  • Nonulcerative and nonsuppurative inflammation of the corneal stroma
  • May form stromal neovascularization if untreated
  • Diffuse or localized
  • Congenital (90%): This commonly appears at age 6-12 years. Corneal edema and infiltrates are present with lacrimation and photophobia. Vascularization of the corneal stroma is characteristic and may give the cornea a pink salmon-patch appearance. The condition generally begins unilaterally and becomes bilateral in 90% of cases.
  • Acquired (10%): Active interstitial keratitis shows stromal inflammation, especially in the peripheral cornea. Marginal infiltrates of the anterior stroma may be present, usually in association with anterior uveitis. When the uveal inflammation subsides, corneal scarring appears. Evidence of stromal neovascularization just anterior to the Descemet membrane may be present.
• Neuro-ophthalmic manifestations
  • Papillitis
  • Optic neuritis
  • Optic perineuritis
  • Papilledema
• Lids/eyebrows
  • Chancre rarely occurs in the primary stage.
  • Brow loss at its temporal aspect has been reported in secondary and tertiary syphilis.
  • Tarsitis or lid abscess rarely occurs in the tertiary stage.
  • Pseudoepitheliomatous hyperplasia has also been reported, as a rare occurrence, related to the gumma of tertiary syphilis. These lesions are generally elevated, and they have an uneven surface that is either ulcerated or crusty, which appears similar to squamous cell carcinoma or basal cell carcinoma.
• Others
  • Cataract has been seen in syphilis cases; however, whether the development is caused by T pallidum or from the uveitis associated with the disease is unknown.
  • Glaucoma almost always is associated with uveitic inflammation. In congenital syphilis, interstitial keratitis is associated with adult secondary glaucoma in 15-20% of patients. The glaucoma develops an average of 27 years after the initial episode of interstitial keratitis has subsided. Clinical evidence has shown 2 different forms of late glaucoma, a deep-chamber, open-angle type, and a shallow-chamber, narrow-angle type. Both types occur with equal frequency and present with characteristic changes of congenital syphilis, such as corneal scarring with ghost vessels and chorioretinal atrophy.

Causes

• Spirochete T pallidum
  • The only known natural host is humans.
  • Its origin is unknown.
  • The entire genome of T pallidum has been determined; 1.1 million base pairs are present, containing 1041 open reading frames. The study of these open reading frames and their protein products help scientists study the virulence factors, develop a method of culture, develop a vaccine, and develop specific and sensitive diagnostic tests.

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