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## Complete Summary

#### GUIDELINE TITLE

Syphilis.

#### BIBLIOGRAPHIC SOURCE(S)

Finnish Medical Society Duodecim. Syphilis. In: EBM Guidelines.
Evidence-Based Medicine \[Internet\]. Helsinki, Finland: Wiley
Interscience. John Wiley & Sons; 2006 Jul 25 \[Various\].

#### GUIDELINE STATUS

**Note**: This guideline has been updated. The National Guideline
Clearinghouse (NGC) is working to update this summary.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [September 11, 2007, Rocephin (ceftriaxone
    sodium)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin):
    Roche informed healthcare professionals about revisions made to the
    prescribing information for Rocephin to clarify the potential risk
    associated with concomitant use of Rocephin with calcium or
    calcium-containing solutions or products.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

**Syphilis, including**:

-   Primary, secondary, and latent syphilis

-   Neurosyphilis

-   Syphilis in pregnancy

-   Congenital syphilis (*prevention*)

-   Neonatal syphilis (*diagnosis*)

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Internal Medicine\
Obstetrics and Gynecology\
Pediatrics

#### INTENDED USERS

Health Care Providers\
Physicians

#### GUIDELINE OBJECTIVE(S)

Evidence-Based Medicine Guidelines collect, summarize, and update the
core clinical knowledge essential in general practice. The guidelines
also describe the scientific evidence underlying the given
recommendations.

#### TARGET POPULATION

Patients with suspected or confirmed syphilis and patients exposed to
syphilis

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis**

1.  Assessment of history of exposure and signs and symptoms of syphilis

2.  Microscopic assessment of lesion discharge for spirochetes

3.  Serologic testing (cardiolipin test, Treponema pallidum
    haemagglutination test \[TPHA\], fluorescent treponemal antibody
    absorption \[FTA-abs\] test as indicated for special cases)

4.  Gene amplification methods for screening

**Management/Treatment/Prevention**

1.  Penicillin for the treatment of primary, secondary and latent
    syphilis, neurosyphilis, and syphilis in pregnancy, and the
    prevention of congenital syphilis

2.  Ceftriaxone injections as alternative for patients who are allergic
    to penicillin

3.  After completion of antibiotic treatment, follow-up testing with the
    cardiolipin and Treponema pallidum haemagglutination tests at
    specified intervals

4.  Identification and screening of partners with cardiolipin test

#### MAJOR OUTCOMES CONSIDERED

-   Accuracy of diagnostic tests

-   Incidence of congenital syphilis

-   Rate of referral of sex partners

-   Signs and symptoms of syphilis

-   Syphilis serology titers

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

The evidence reviewed was collected from the Cochrane database of
systematic reviews and the Database of Abstracts of Reviews of
Effectiveness (DARE). In addition, the Cochrane Library and medical
journals were searched specifically for original publications.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

A.  Strong research-based evidence. Multiple relevant, high-quality
    scientific studies with homogeneous results.

B.  Moderate research-based evidence. At least one relevant,
    high-quality study or multiple adequate studies.

C.  Limited research-based evidence. At least one adequate scientific
    study.

D.  No research-based evidence. Expert panel evaluation of other
    information.

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not stated

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**Note**: This guideline has been updated. The National Guideline
Clearinghouse (NGC) is working to update this summary. The
recommendations that follow are based on the previous version of the
guideline.

The levels of evidence \[A-D\] supporting the recommendations are
defined at the end of the \"Major Recommendations\" field.

**Aims**

-   Suspected syphilis should be verified with the appropriate clinical
    and serological tests and the patient should be treated with the
    most efficient antibiotics.

-   Syphilis is a dangerous infectious disease that should be prevented
    and treated effectively.

**Aetiology and Transmission**

-   The pathogen is the spirochete Treponema pallidum.

-   Easily transmitted by sexual intercourse and also from the mother to
    the foetus.

-   Contagiousness is highest (30--60%) in the primary and secondary
    phases. After 2 years, the patient ceases to spread the disease.

**Clinical Picture**

-   Asymptomatic incubation period lasts for 3 to 4 weeks after which
    two thirds of the patients (not all) have visible symptoms

    1.  Primary symptoms (local infection)

        -   An ulcer, the \"primary lesion,\" with a clean, hard base
            (see picture 1\*) appears in the genital region, sometimes
            also in anus or the oral region.

        -   There is local lymphadenopathy without tenderness.

    ```{=html}
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    ```
    2.  Secondary stage 6 to 8 weeks after exposure (general infection).

        -   General symptoms include indisposition, fever and enlarged
            lymph nodes.

        -   Roseola eczema (see picture 2\*) resembles widely spread
            viral eczema or drug eruption.

            -   Syphilids (i.e., formations of papules) are found in the
                hands and feet or spread all over the body. May be
                large, cauliflower-like formations (condylomata latum)
                around the anus or necrotic in patients with a poor
                immune response (e.g. human immunodeficiency virus
                \[HIV\])

        -   Alopecia syphilitica, typical \"moth-eaten\" spotty baldness
            in some patients

    ```{=html}
    <!-- -->
    ```
    3.  Late symptoms occur in about one third of untreated patients in
        10 to 30 years. The most important are neurological (atypical
        psychosis, paralytic dementia) and vascular symptoms (aortic
        aneurysm, valvular regurgitation).

**Differential Diagnosis**

-   Primary syphilis

    -   Genital herpes. Incubation time is short in primary infection,
        lesions occur in groups and they are painful. Lymphadenopathy is
        less pronounced; however, the nodes are tender.

    -   Ulcus molle (soft chancre)

    -   Infected coital or other traumas

-   Secondary syphilis

    -   Roseola may resemble pityriasis rosea, drug eruption, measles
        (rubeola), German measles (rubella), or scarlet fever
        (scarlatina).

    -   Syphilids may resemble papular lichen ruber planus, psoriasis,
        scabies or infectious eczema of the feet (e.g., tinea).
        Condyloma latum may resemble condyloma acuminate.

**Diagnosis**

1.  History of exposure (unprotected sex) and/or clinical picture.

2.  Plain specimen. A dark field microscope may reveal spirochetes in
    lesion discharge and confirm the diagnosis.

3.  Serology

    -   The cardiolipin test becomes positive 3 to 4 weeks after
        infection. It is the primary test for screening. High titres
        (\>16) are almost always specific. A low titre is in many cases
        a false positive result (pregnancy, connective tissue disease,
        infection) or a serological scar of an earlier treated infection
        or latent syphilis.

    -   Treponema pallidum haemagglutination test (TPHA) is the test of
        choice for verifying syphilis. The result becomes positive
        slightly later than that of the cardiolipin test, but it is
        specific (almost 100%) and suitable for following up response to
        treatment.

    -   Fluorescent treponemal antibody absorption test (FTA-abs) is a
        specific syphilis test used in special cases (neurosyphilis,
        suspicion of neonatal syphilis) as it detects also
        immunoglobulin M (IgM) antibodies.

    -   Gene amplification methods are already being used for screening.

**Treatment**

-   Procaine penicillin 1.2 million IU x 1 intramuscular (i.m.) for 10
    days (primary and secondary syphilis; in latent syphilis treatment
    is received for three weeks), in neurosyphilis intravenous (i.v.)
    penicillin.

-   For patients allergic to penicillin, ceftriaxone injections (1
    g/day) are an alternative.

**Follow-up and Identification of Partners**

-   After antibiotic therapy the cardiolipin and treponema pallidum
    haemagglutination tests are performed at 3 and 6 months and one
    year. In primary stage infection, the tests become negative in most
    cases; in other recent infections the titre falls by at least two
    dilutions when the treatment has been successful.

-   All sexual partners who have been exposed to infection should be
    screened with the cardiolipin test. If the result is negative, the
    test should be repeated after 3 months.

**Related Evidence**

-   Patient assistance at facilitating patient referral and provider
    referral may increase partner notification for sexually transmitted
    diseases (Oxman et al., 1994) \[**C**\].

-   Penicillin is effective in the treatment of syphilis in pregnancy
    and in the prevention of congenital syphilis (Walker, 2001 )
    \[**B**\].

\***Note**: All pictures identified in this summary can be found in the
original guideline document (see \"Guideline Availability\" field).

**Definitions**:

**Levels of Evidence**

A.  Strong research-based evidence. Multiple relevant, high-quality
    scientific studies with homogeneous results.

B.  Moderate research-based evidence. At least one relevant,
    high-quality study or multiple adequate studies.

C.  Limited research-based evidence. At least one adequate scientific
    study.

D.  No research-based evidence. Expert panel evaluation of other
    information.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### REFERENCES SUPPORTING THE RECOMMENDATIONS

[References open in a new
window](http://www.guideline.gov/summary/select_ref.aspx?doc_id=9851)

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

Concise summaries of scientific evidence attached to the individual
guidelines are the unique feature of the Evidence-Based Medicine
Guidelines. The evidence summaries allow the clinician to judge how
well-founded the treatment recommendations are. The type of supporting
evidence is identified and graded for select recommendations (see the
\"Major Recommendations\" field).

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Appropriate use of clinical and serological tests for the
    verification of suspected syphilis

-   Effective prevention and treatment of syphilis

#### POTENTIAL HARMS

The cardiolipin test is the primary test for screening. High titres
(\>16) are almost always specific. A low titre is in many cases a false
positive result (pregnancy, connective tissue disease, infection) or a
serological scar of an earlier treated infection or latent syphilis.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Staying Healthy

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Finnish Medical Society Duodecim. Syphilis. In: EBM Guidelines.
Evidence-Based Medicine \[Internet\]. Helsinki, Finland: Wiley
Interscience. John Wiley & Sons; 2006 Jul 25 \[Various\].

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2001 Nov 22 (revised 2006 Jul 25)

#### GUIDELINE DEVELOPER(S)

Finnish Medical Society Duodecim - Professional Association

#### SOURCE(S) OF FUNDING

Finnish Medical Society Duodecim

#### GUIDELINE COMMITTEE

Editorial Team of EBM Guidelines

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Primary Author*: Timo Reunala

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

**Note**: This guideline has been updated. The National Guideline
Clearinghouse (NGC) is working to update this summary.

#### GUIDELINE AVAILABILITY

This guideline is included in \"EBM Guidelines. Evidence-Based
Medicine\" available from Duodecim Medical Publications, Ltd, PO Box
713, 00101 Helsinki, Finland; e-mail: <info@ebm-guidelines.com>; Web
site: [www.ebm-guidelines.com](http://www.ebm-guidelines.com/).

#### AVAILABILITY OF COMPANION DOCUMENTS

None available

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on December 17, 2002. The information
was verified by the guideline developer on February 7, 2003. This NGC
summary was updated by ECRI on October 4, 2004 and on December 22, 2006.
This summary was updated by ECRI Institute on October 3, 2007 following
the U.S. Food and Drug Administration (FDA) advisory on Rocephin
(ceftriaxone sodium).

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008