TREATMENT ISSUES: Special Edition - Volume 6, Number 7, Summer/Fall 1992; The Gay Men's Health Crisis Newsletter of Experimental AIDS Therapies
Janet L. Mitchell, M.D., M.P.H.

In both HIV and syphilis epidemics, women are hit particularly hard. In fact, the rate per 100,000 adults increased 36% for black men, 43% for black women, 7% for hispanic men, and 24% for hispanic women. Although rates for white women increased 22%, the absolute rates were approximately 10 to 30 times lower than those in black or Hispanic women.[1] Complicating the general situation is the fact that symptoms, tests, and treatment for syphilis may be altered in people who are HIV-positive.

PRIMARY SYPHILIS

Syphilis develops in several stages. In the first stage (primary syphilis), a woman may get painless, hard, red sores on or around the skin of her genitals, anus, or mouth. Most of these lesions (chancres) are found on the labia, fourchette, or cervix in women and usually occur about two to three weeks after infection. However, the chancres can go unnoticed.

SECONDARY SYPHILIS

Untreated, the disease proceeds to the second stage within six weeks to three months. This stage can cause hair loss, sore joints, widespread rashes, swollen lymph nodes, and weight loss. The syphilis rash may occur all over the body, but it is usually pale and may not be very noticeable. It tends to occur as spots on the hands and feet bottoms. Because second-stage symptoms are somewhat vague, they often are misdiagnosed. After a period of 3 to 12 weeks, secondary syphilis gets better on its own, leaving the patient free of all symptoms, and leading into a stage of latency, when no symptoms occur.

TERTIARY OR LATE-STAGE SYPHILIS

The third stage (tertiary syphilis) may not occur until much later, after a latent period when the infection is not active and the person is free of symptoms. This stage only occurs if earlier stages of syphilis go untreated or inadequately treated. The third stage can cause very serious disease of the heart, the eyes, or the nervous system and brain (neurosyphilis).

NEUROSYPHILIS

Neurosyphilis is an advanced form of syphilis that can cause serious problems in the brain and nervous system. A lumbar puncture (spinal tap) is recommended to confirm diagnosis. Recent reports suggest that patients with HIV infection who acquire syphilis may be more likely to progress to neurosyphilis and may do so more quickly than expected.[2] There are also reports of individuals treated for early syphilis with recommended regimens of benzathine penicillin who seem to get better, but then relapse with syphilis of the brain.[3] Neurosyphilis may result in headache, stiffness of the neck, and confusion. It can also lead to blurred vision, blindness, abnormal eye movements, facial weakness, hearing loss, or loss of balance. There seems to be a consensus that treatment of neurosyphilis is with ten days of intravenous aqueous penicillin at 2 to 4 million units every four hours. Comparative studies may eventually show that ceftriaxone is preferable to penicillin because it is easier to administer and may more effectively penetrate the nervous system.[4] In one case of asymptomatic neurosyphilis, a cure was reported by using ceftriaxone, 1 g/d for two weeks.[5]

CONGENITAL SYPHILIS

It is important to know that a pregnant woman with syphilis, regardless of the stage of disease, can pass it on to her unborn infant (congenital syphilis). The number of congenital syphilis cases reported in 1988 was the highest since the early 1950s, and in New York City alone that number increased more than 500%.[6] Symptoms in infants who have contracted congenital syphilis (passed from mother to child during some stage of pregnancy or delivery) may develop as follows: distorted bones, misformed teeth, inflamed and clouded eyes, deafness, blindness, and retardation. Pregnant women should be tested for syphilis at least twice during their pregnancy, especially if they are HIV-positive.

DETECTING SYPHILIS

Historically, syphilis may be the most often misdiagnosed illness, mistaken for everything from hemorrhoids, cancer, and lymphoma, to incarcerated hernia, hepatitis, and multiple sclerosis. Tests to detect syphilis can be done either on blood or on fluid from the spinal cord (cerebrospinal fluid). There are two kinds of tests: one which measures levels of antibodies produced by the immune system to combat syphilis ((RPR) and one that directly measure the presence of the organism which causes syphilis (FTA). That organism is called Treponema pallidum.

Although these tests are standard for detecting syphilis, they are far from perfect. Syphilis has been called the "Great Masquerader" because of its vague symptoms, and many physicians have little experience detecting or even suspecting it in patients with symptoms. This is a problem for all persons with syphilis regardless of their serostatus. Because suppression can keep the immune system from responding in order to get rid of the infection, there is some possibility that tests may not be reliable in diagnosing syphilis in HIV-infected persons.

TREATMENT

HIV-infected persons should be treated with the most effective antibiotic. The best chance for a cure depends upon enough antibiotic entering and staying in the blood. A lot of drug is needed in order for it to enter the central nervous system. While there is consensus about treating neurosyphilis with the aggressive regimen suggested above, there is much debate about treatment for other stages of syphilis.

In 1988, the Centers for Disease Control (CDC) published guidelines for treatment of people (by which is meant men) infected with both syphilis and HIV.[7] These guidelines suggest treating HIV-infected patients in the same way as non-HIV-infected patients (namely, with 2.4 million units of benzathine penicillin). Research, however, suggests that higher doses of penicillin must be given to men with HIV in order to reduce the likelihood of a relapse of syphilis to neurosyphilis and, perhaps, to control lesions. While current doses may be adequate for most women (possibly because most women are smaller and may have lower blood levels), pregnancy may be different.

TREATMENT OF SYPHILIS IN PREGNANT WOMEN

Normal biological changes during pregnancy produce an increased amount of water in women's bodies. This increase is greater in multiple pregnancies (twins, triplets). Therefore, an increase in blood flow to the kidneys results in increased urination and increased elimination of medication taken to control infection. Additionally, the growth of the uterus and fetal compartments (fetus, placenta, and amniotic fluid) creates additional tissue to absorb the drug. Thus, the doses calculated for men may in fact be too low for pregnant women.

This concern has led many obstetricians and infectious disease specialists to suggest that HIV-infected pregnant women be treated with a regimen for neurosyphilis, especially if the duration of syphilis is unknown. No empiric data exists to support this approach, and it is based on a public health perspective. Congenital syphilis is rampant in certain areas, especially areas with high rates of HIV. The consequences of inadequate treatment are far greater than the consequences of over-treatment. However, in none of the articles reviewed is over-treatment raised as a concern. Of greater concern to obstetricians and pediatricians is the lack of information on pregnant women who are allergic to penicillin. Prior to HIV the alternate therapies were problematic in pregnancy. Tetracycline, for instance, a common alternative therapy, can cause developmental problems in the teeth and bone of developing fetuses. Erythromycin, another alternative, is associated with treatment failures because it does not cross the placenta very well. The best approach seems to be desensitization to penicillin. In this process, pregnant women with penicillin allergies are given a little drug at a time, in increasing doses. This technique has been used during pregnancy for almost a decade.

CONCLUSION

The controversy surrounding appropriate treatment for syphilis in HIV-infected persons is yet to be resolved. While changes in the recommended treatment regimen may be indicated in the future, the present CDC recommendations are used in most treatment facilities today. Providers, however, need to be aware that treatment failures have been reported using the recommended doses and that patients treated following those guidelines may need closer follow-up observation.

FOOTNOTES ---------

1. CDC. Syphilis and congenital syphilis--U.S. 1985-1988. MMWR 37:486-489 1988.

2. Johns DR et al. Alteration in the natural history of neurosyphilis by concurrent infection with HIV. N Engl J Med 316:1569-1572, 1987.

3. Barry et al. Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 316:1587-89, 1987.

4. Musher DM et al. Effect of HIV infection on the course of syphilis and on the response to treatment. Ann Intern Med 113:872-881,1990.

5. Hook EW et al. Ceftriaxone therapy for asymptomatic syphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy. Sex Transm Dis 13:185-8, 1986.

6. CDC. Congenital Syphilis--New York City, 986-1988. MMWR 38:825-889,1989.

7. Centers for Disease Control. Recommendations for diagnosing and treating syphilis in HIV-infected patients. MMWR 37:600-608,1988.

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