Part 4 • Infectious Uveitic Conditions

Chapter 10 Spirochetal Diseases

Table 10-4  Treatment of syphilis

PRIMARY AND SECONDARY SYPHILIS

Procaine penicillin, 2.4 million units IM daily, and probenecid, 1 g PO qd × 14 days or benzathine penicillin G, 2.4 million units IM in a single dose (although treatment failures have been reported)

If penicillin allergies exist, treat with doxycycline, 100 mg PO bid × 15 days or tetracycline 500 mg PO qid for 15 days. (Ceftrizone and azithromycin have also been used)

LATENT AND TERTIARY SYPHILIS, INCLUDING NEUROSYPHILIS

Aqueous crystalline penicillin G, 3–4 million units IV q 4 h × 10–14 days or benzathine penicillin G, 2.4 million units IM given weekly × 3. (Ceftriaxone and amoxicillin also have been used)

CONGENITAL SYPHILIS IN THE INFANT

Procaine penicillin, 50 000 units/kg/day IM × 10 days, or aqueous crystalline penicillin G, 50 000 units/kg/day IV in two divided doses × 10 days.

these patients have one or more relapses with mucocutaneous lesions. Eventually, most untreated patients remain in a latent stage of the disease; however, about one-third go on to experience tertiary syphilis. Benign tertiary syphilis occurs in about 15% of untreated patients. Cardiovascular syphilis occurs in 10% of these, and CNS involvement is seen in about 8% of untreated patients.

Treatment

General recommendations.  Although guidelines for the treatment of syphilis exist, controversy persists. Before treating a patient with syphilis one should refer to the most current recommendations for therapy, and consultation with an infectious disease specialist may be helpful. Coinfection with HIV should be ruled out because standard therapy may be insufficient to eradicate disease in these patients. Recommendations for therapy are based on the stage of disease and are presented in Table 10-4.24 Riedner and colleagues evaluated the efficacy of treating primary or latent syphilis with a single oral dose of 2 g azithromycin or a single intramuscular dose of 2.4 million units of penicillin G benzathine.26 Cure rates were 97.7% for patients in the azithromycin group and 95.0% in the penicillin G benzathine group, achieving the prescribed criteria for equivalence.

Unfortunately, the ideal therapy for patients with uveitic syphilis has not been determined. Virulent T. pallidum infection has been reported to persist in the eye despite treatment with penicillin; therefore, many experts suggest that patients with any ocular inflammation secondary to syphilis be treated as for neurosyphilis, even if the CSF findings are normal.

In addition to treating the patient, the physician has a responsibility to report the disease to the local health department to ensure that all sexual contacts over at least the past 3 months are contacted, examined, and treated as necessary.

Patients with syphilis should have the VDRL test repeated at 3, 6, and 12 months after treatment because titers should become nonreactive within a year after successful therapy. In addition, patients with CSF involvement should have repeated CSF examinations at 6-month intervals for at least 3 years. Patients should be re-treated if clinical evidence of

syphilis occurs, if a previously nonreactive VDRL test again becomes reactive, or if an initially high-titer VDRL test does not decrease fourfold within a year.

Finally, patients receiving therapy for syphilis, especially intravenous therapy, should be monitored for a Jarisch– Herxheimer reaction. This is a hypersensitivity response to treponemal antigens. The reaction may exacerbate preexisting ocular inflammation, such as uveitis and interstitial keratitis; prophylaxis with corticosteroids may help in some cases.

Approach to Syphilis in Patients with AIDS

Recognition of concurrent infection with HIV in patients with syphilis is important to the clinician because the diagnostic and therapeutic approach to syphilis may differ in these patients. Numerous reports suggest that uncharacteristic clinical manifestations of syphilis may occur in patients with concomitant HIV infection.27,28 Unusual cases of ocular syphilis in HIV-infected patients with findings of panuveitis and retinal detachment have been reported, and some authors have stated that the incidence of ocular complications of syphilis may be increased in HIV-infected patients.29–31 In addition, acute retinal necrosis and acute retinitis have been associated with syphilis in patients coinfected with HIV.21,29 Despite some unique symptoms and signs, these patients usually also experience the characteristic clinical manifestations of syphilis. Patients with both HIV infection and syphilis may have an accelerated course with a greater likelihood of uveitis and progression to neurosyphilis.27,30,32 In the study by Berry and colleagues6 there was no difference in the detection of T. pallidum in the CSF in patients with or without concurrent HIV infection; nevertheless, it appears that treatment failures are more common in HIV-infected patients.6,33,34 In addition, serologic evidence of syphilis may be delayed. Hicks and colleagues35 reported on a patient with AIDS and skin manifestations consistent with secondary syphilis in whom the VDRL and FTA-ABS results were negative on two separate occasions. A skin biopsy demonstrated spirochetes with Warthin–Starry staining of the tissue, and the patient’s VDRL and FTA-ABS test results later became positive, suggesting a delayed immunologic response.

Although patients with HIV infection and syphilis have more symptoms of CNS involvement, such as acute syphilitic meningitis and hearing loss, many of them do not have positive CSF VDRL test results and may manifest only CSF leukocytosis or elevated CSF protein concentration, findings that are seen in HIV patients without syphilis.36 These findings have prompted some clinicians to treat all patients with concurrent HIV infection and syphilis with high-dose antibiotic therapy to cover the possibility of CNS involvement. The Centers for Disease Control and Prevention in Atlanta is currently studying the question of appropriate antibiotic therapy for patients with syphilis and concurrent HIV infection. For now, recommendations include the careful evaluation of all patients with syphilis for underlying HIV infection. Patients with AIDS should also be monitored for clinical signs of syphilis, and the diagnosis should be pursued despite negative serologic results early in the course of the disease.

Patients with syphilis and HIV infection should have a lumbar puncture to look for evidence of neurosyphilis.