Syphilis medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
==Current | ==Current medical therapy== | ||
The first-choice treatment for all manifestations of syphilis remains [[penicillin]] in the form of [[Penicillin#Benzylpenicillin .28penicillin G.29|penicillin G]].<ref name=CDC>{{cite journal | author=Centers for Disease Control | title=Sexually Transmitted Diseases Treatment Guidelines, 2006 | journal=MMWR | volume=55 | date=08-04-2006 | issue=RR-11 | pages=24-32}}</ref> 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. | The first-choice treatment for all manifestations of syphilis remains [[penicillin]] in the form of '''[[Penicillin#Benzylpenicillin .28penicillin G.29|penicillin G]]'''.<ref name=CDC>{{cite journal | author=Centers for Disease Control | title=Sexually Transmitted Diseases Treatment Guidelines, 2006 | journal=MMWR | volume=55 | date=08-04-2006 | issue=RR-11 | pages=24-32}}</ref> 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 | ====Pencillin allergy: Non-pregnant individuals==== | ||
*No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women. | |||
*Of the adult U.S. population, 3%-10% have experienced an immunoglobulin E (IgE) mediated allergic response to penicillin such as urticaria, angioedema, or anaphylaxis (i.e., upper airway obstruction, bronchospasm, or hypotension). Re-administration of penicillin to these patients can cause severe, immediate reactions.[http://www.guideline.gov/content.aspx?id=25581&search=syphilis] | |||
*Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., [[anaphylaxis]]) may be treated with oral [[tetracycline]] or [[doxycycline]] although 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 [[cephalosporin]]s 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.<ref name=Azith>{{cite journal | author=Lukehart SA, Godornes C, Molini BJ, et al | title=Macrolide resistance in Treponema pallidum in the United States and Ireland | journal=N Engl J Med. | volume=351 | pages=154-8 | date=2004 | PMID=15247355}}</ref> | |||
*Because anaphylactic reactions to penicillin can be fatal, every effort should be made to avoid administering penicillin to penicillin-allergic patients. If compliance and follow-up cannot be ensured, the [[Centers for Disease Control and Prevention|CDC]] recommends [[Desensitization (medicine)|acute desensitization]] with penicillin followed by penicillin treatment to eliminate anaphylactic sensitivity. | |||
*Although an estimated 10% of persons who report a history of severe allergic reactions to penicillin continue to remain allergic to penicillin their entire lives, with the passage of time, most persons who have had a severe reaction to penicillin stop expressing penicillin-specific IgE. These persons can be treated safely with penicillin. | |||
====Pencillin allergy: Pregnant individuals==== | |||
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. | |||
====Pencillin allergy: Penicillin skin test==== | |||
*Penicillin skin testing with the major and minor determinants of penicillin can reliably identify persons at high risk for penicillin reactions. Although these reagents are easily generated and have been available for more than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen [i.e., the major determinant]) and penicillin G have been available commercially. These two tests identify an estimated 90%-97% of the currently allergic patients. However, because skin testing without the minor determinants would still miss 3%-10% of allergic patients and because serious or fatal reactions can occur among these minor-determinant-positive patients, caution should be exercised when the full battery of skin-test reagents is not available. | |||
*Patients with history of penicillin reaction and negative skin-test negative can receive conventional penicillin therapy. | |||
*Skin-test-positive patients should be desensitized before initiating treatment. | |||
*All patients with a history suggesting IgE- mediated reactions to penicillin (e.g., [[anaphylaxis]], [[angioedema]], [[bronchospasm]], or [[urticaria]]) should be desensitized in a hospital setting. In patients with reactions not likely to be IgE-mediated, outpatient-monitored test doses can be considered. | |||
====Late latent and infections of unknown duration==== | ====Late latent and infections of unknown duration==== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Current medical therapy
The first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G.[1] 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.
Pencillin allergy: Non-pregnant individuals
- No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women.
- Of the adult U.S. population, 3%-10% have experienced an immunoglobulin E (IgE) mediated allergic response to penicillin such as urticaria, angioedema, or anaphylaxis (i.e., upper airway obstruction, bronchospasm, or hypotension). Re-administration of penicillin to these patients can cause severe, immediate reactions.[2]
- Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be treated with oral tetracycline or doxycycline although 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.[2]
- Because anaphylactic reactions to penicillin can be fatal, every effort should be made to avoid administering penicillin to penicillin-allergic patients. If compliance and follow-up cannot be ensured, the CDC recommends acute desensitization with penicillin followed by penicillin treatment to eliminate anaphylactic sensitivity.
- Although an estimated 10% of persons who report a history of severe allergic reactions to penicillin continue to remain allergic to penicillin their entire lives, with the passage of time, most persons who have had a severe reaction to penicillin stop expressing penicillin-specific IgE. These persons can be treated safely with penicillin.
Pencillin allergy: Pregnant individuals
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.
Pencillin allergy: Penicillin skin test
- Penicillin skin testing with the major and minor determinants of penicillin can reliably identify persons at high risk for penicillin reactions. Although these reagents are easily generated and have been available for more than 30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen [i.e., the major determinant]) and penicillin G have been available commercially. These two tests identify an estimated 90%-97% of the currently allergic patients. However, because skin testing without the minor determinants would still miss 3%-10% of allergic patients and because serious or fatal reactions can occur among these minor-determinant-positive patients, caution should be exercised when the full battery of skin-test reagents is not available.
- Patients with history of penicillin reaction and negative skin-test negative can receive conventional penicillin therapy.
- Skin-test-positive patients should be desensitized before initiating treatment.
- All patients with a history suggesting IgE- mediated reactions to penicillin (e.g., anaphylaxis, angioedema, bronchospasm, or urticaria) should be desensitized in a hospital setting. In patients with reactions not likely to be IgE-mediated, outpatient-monitored test doses can be considered.
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 as 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.
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.
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.[3] 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 cases of unethical human medical experimentation in the twentieth century was the Tuskegee syphilis study. The study took place in Tuskegee, Alabama and was supported by the Tuskegee Institute and the U.S. Public Health Service (PHS).[4]
The study began in 1932 using a group of 600 black sharecroppers. Of these 600, 399 of the men had the disease and 201 were uninfected control patients. The PHS stated at first that treatment was supposed to be a part of the study, but they were unable to produce any useful data. It was then discovered that the PHS had decided to leave the men untreated and follow the course of the disease to these men's eventual deaths. They thought they were receiving experimental treatment for "bad blood" in exchange for free meals and a $50 death benefit. However, the study was designed to measure the progression of untreated syphilis and to determine whether syphilis caused cardiovascular damage more often than neurological damage, and to determine if the natural course of the disease was different in black men versus white men. By 1947 penicillin had become the standard treatment of syphilis. 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 last six to nine months, but continued for 40 years, ending in 1972, long after wives and children had been infected, and many of the men had died of syphilis. It was estimated that more than one hundred men and women died as a result of this study. The study ended because of a story printed in the Washington Star. A class-action lawsuit was then filed 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.
References
- ↑ Centers for Disease Control (08-04-2006). "Sexually Transmitted Diseases Treatment Guidelines, 2006". MMWR. 55 (RR-11): 24–32. Check date values in:
|date=(help) - ↑ Lukehart SA, Godornes C, Molini BJ; et al. (2004). "Macrolide resistance in Treponema pallidum in the United States and Ireland". N Engl J Med. 351: 154–8. PMID 15247355.
- ↑ Rolfs RT, Joesoef MR, Hendershot EF; et al. (1997). "A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group". N. Engl. J. Med. 337 (5): 307–14. PMID 9235493.
- ↑ "A A World . Reference Room . Articles . Tuskegee Syphilis Study". Text " PBS " ignored (help)