Syphilis Treatment

The first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G. The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience. Parenteral penicillin G is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient.

Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracycline or doxycycline; however, data to support this is limited. Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined. However, cross-reactions in penicillin-allergic patients with cephalosporins such as ceftriaxone are possible. Azithromycin was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas. If compliance and follow-up cannot be ensured, the CDC recommends desensitization with penicillin followed by penicillin treatment. All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.

Azithromycin has been used to treat syphilis in the past because of easy once-only dosing. However, in one study in San Francisco, azithromycin-resistance rates in syphilis, which were 0% in 2000, were 56% by 2004.

Late latent and infections of unknown duration

Late latent syphilis is defined as latency for greater than one year. If CSF examination yields no evidence of neurosyphilis, then penicillin G is recommended in weekly doses for 3 weeks. If allergic, then tetracycline or doxycycline may also be used for this stage, but for 28 days instead of the normal 14. As with before, the data to support use of tetracycline and ceftriaxone are limited.

Treatment of neurosyphilis

For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice. The recommended regimen is intravenous treatment every 4 hours or continuously for 10–14 days. If intravenous administration is not possible, then procaine penicillin is an alternative (administered daily with probenecid for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure. To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis. No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular ceftriaxone daily for 14 days. Neurosyphilis dementia is also a psychiatric diagnosis where as a multitude of atypical anti-psychotic medications are used to help control the patient's irrational behaviors with limited success.

Also used in traditional classification of Organic Disorders in the brain. Also commonly called Brain Syphilis.

Alternative regimens

Alternative regimens such as tetracyclines are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy.

HIV-infected patients with early syphilis may have a higher risk of neurological complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small. Skin testing or desensitization is recommended in latent syphilis and neurosyphilis in other patients with HIV infection.

Jarisch-Herxheimer reaction

Before administering any treatment, clinicians should warn all patients about the possibility of a Jarisch-Herxheimer reaction, which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients. This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with acetaminophen (paracetamol) and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.

Tuskegee syphilis study

One of the best-documented US cases of unethical human medical experimentation in the twentieth century was the Tuskegee syphilis study. The study took place in Tuskegee, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute.

The study began in 1932, when syphilis was a widespread problem, especially in poor communities, and when there was no effective treatment or cure. Study researchers recruited a group of 600 black male sharecroppers in the rural area of Tuskegee. Of these 600, 399 of the men had the disease in the latent, asymptomatic stage. 201 men were uninfected control patients. The PHS intended to study the progress of the disease and the effects of current treatments at different stages. Available treatments had such severe side effects that doctors questioned whether treatment provided the best outcome for the patient, or whether a man might do as well with no treatment. Patients were misled about the diagnosis of their disease, and about aspects of treatment, such as a painful lumbar puncture for evaluation. During the crisis of the Great Depression, in a segregated state with underfunded services for blacks, patients were recruited in exchange for physical exams, free health care of minor illnesses, free meals and transportation the day of exams, and a $50 death benefit. The study was designed to measure the progression of untreated syphilis. It also was to determine whether syphilis caused cardiovascular damage more often than neurological damage, as untreated disease led to effects in numerous body systems. Researchers hoped to determine whether the natural course of the disease was different in black men versus white men; historically, researchers had by then accumulated more information on the disease in white men.

By 1947 penicillin had been validated as an effective cure for syphilis and was becoming widely used by doctors and public health centers to treat the disease. PHS study directors continued the study, denying patients treatment by penicillin, and actively discouraging them from having penicillin administered by other sources. The men were never advised that they had syphilis, nor were they offered a treatment including Salvarsan or the other arsenical drugs that were in use at the beginning of the study.

The original study was meant to study patients in phases, with treatment after six to nine months. It continued to follow the original members and their families for 40 years. The study ended in 1972, long after 40 wives and 19 children had been infected, and many men had died of syphilis. During the study, 28 men died directly from syphilis, and 100 from other complications. The study ended because a PHS scientist leaked information about it to the ''Washington Star''.

Survivors and patients' families filed a class-action lawsuit against the federal government for the study. This lawsuit was settled out of court and the living subjects and their descendants were awarded a total of ten million dollars. After the settlement was awarded, the government passed the National Research Act, which required the government to review and approve all medical studies involving human subjects.