SIGNS AND SYMPTOMS
Syphilis is a multi-system, multi-symptom disorder that occurs primarily through sexual transmission, though the disease can be spread through blood transfusion and direct contact with an infected lesion. Patients tend to be younger, with a history of unprotected sex. Elderly patients may manifest late-stage syphilis left untreated many years before.

In cases of congenital syphilis, the patient may manifest Hutchinson's triad (interstitial keratitis, deafness and malformed teeth), osteochondritis (inflammation of both bone and cartilage), chorioretinitis, hepatosplenomegaly (enlargement of the liver and spleen), and anorexia.

In the primary stage of acquired syphilis, the patient develops a painless chancre at the site of inoculation, as well as regional lymphadenopathy. While primarily genital, chancres may develop on the eyelid and conjunctiva. Other ocular signs in the primary stage include conjunctivitis, blepharitis, and alopecia.

In the secondary stage of acquired syphilis, the patient will develop malaise, lymphadenopathy, fever, maculopapular skin lesions on the palms and soles, joint pain, headache, and loss of appetite. Ocular signs are most common in secondary syphilis and include episcleritis, anterior uveitis, uveitic glaucoma, neuroretinitis, chorioretinitis, ischemic retinal vasculopathy, and infectious optic neuropathy.

In the third stage of acquired syphilis, focal endarteritis causes the formation of gummas (granulomatous lesions), which can involve the eye and adnexa, and the central nervous and cardiovascular systems. At this stage, neurosyphilis can manifest with acute meningitis, cranial neuropathies, optic atrophy, pupil abnormalities, paresis, and tabes dorsalis (degeneration of the dorsal columns of the spinal cord resulting in loss of coordination, reflexes and sensation, and ataxic gait).

PATHOPHYSIOLOGY
Syphilis is caused by the spirochete bacteria, Treponema pallidum. It is transmitted through mucous membranes or open skin-to-skin contact, primarily through sexual intercourse. Transmission can also occur through blood transfusion.

After infection, a period of incubation ensues. The organism enters the lymphatic system and bloodstream and disseminates soon after contact. Shortly after infection, a chancre forms at the site of inoculation. The chancres spontaneously heal after two to eight weeks, and the patient enters the secondary stage of syphilis. In individuals with an intact immune system, the disease enters a period of latency. Inflammation and regional vasculopathy account for the signs and symptoms.

After a period of latency (which may extend four or more years in an untreated or undertreated individual), the patient enters the tertiary stage. Focal granulomatous lesions known as gummas develop and can affect virtually any organ system. The resultant dysfunction caused by these gummas accounts for the dysfunction seen in tertiary syphilis. Approximately 10 percent of untreated patients develop neurosyphilis. Since the organism has a predilection for the dorsal spinal cord and intercalated neurons, these patients can develop an ataxic gait and loss of sensation from the lower limbs, and light-near dissociated pupils, which are often miotic (Argyll Robertson pupils). If left untreated, dysfunction of the central nervous and cardiovascular systems can lead to progressive dementia and death.

MANAGEMENT
Serologic testing to detect host antibodies is the mainstay of diagnosis. Tests that detect cardiolipin-lecithin-cholesterol antibodies but are non-specific for Treponema pallidum include the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) which indicate current activity of disease. False-positive results are possible on these tests.

Tests specific for antibodies to Treponema pallidum include the fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination assay for Treponemal pallidum (MHA-TP). These tests indicate whether or not antibodies are present from a previous syphilitic infection, but do not indicate current disease activity. There is a lower incidence of false-positive results with these specific tests. When you suspect syphilis, order both a specific and a non-specific test. In cases where serologic results are uncertain, these tests can be performed using cerebrospinal fluid.

Treatment of syphilis involves systemic IV or IM penicillin. Alternatives for penicillin-sensitive patients include doxycyline, tetracycline, ceftriaxone, and chloramphenicol. In neurosyphilis, there is no acceptable substitute, and patients must be desensitized to penicillin prior to treatment.

CLINICAL PEARLS

• Syphilis is a great mimic. Always keep this condition in mind when encountering patients with cranial neuropathies, optic neuropathies, anterior uveitis, chorioretinitis, retinal vascular occlusion, and chronic anterior segment inflammation.
• Manifestations of syphilis can be complicated by concurrent HIV infection. Always consider HIV infection in patients with syphilis. Further, concurrent infections with gonorrhea and chlamydia frequently occur, and should also be investigated.
• Nearly 45 percent of males manifesting bilateral tonic pupils will test positive for syphilis.
• Lyme disease, another spirochetal disease, is also a great mimic and behaves very similar to syphilis. In fact, Lyme disease can cause false-positive readings on both specific and non-specific tests for syphilis. Always consider Lyme disease as a possibility when testing for syphilis, particularly in cases where a history of sexual contact is absent. In these cases, particularly in endemic areas, try to elicit a history of tick bite.
• Stromal interstitial keratitis is a manifestation of primarily congenital syphilis, but may exist in acquired syphilis. When encountering stromal interstitial keratitis, consider testing for syphilis if the cause does not seem to be congenital. Interstitial keratitis is treated with high doses of potent topical steroids, as this is inflammatory in nature and not actual stromal infection.

Other reports in this section

• Giant Cell Arteritis
• Myasthenia Gravis
• Sarcoidosis
• Sickle Cell Disease
• Syphilis
• Albinism
• Diabetes Mellitus
• Hypertension
• Thyroid Ophthalmopathy (Graves’ Disease)
• Acquired Immune Deficiency Syndrome (AIDS)