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Syphilis: Differential Diagnoses & Workup
Updated: May 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Primary syphilis
Genital herpes
Chancroid
Lymphogranuloma venereum
Granuloma inguinale
Drug eruptions
Carcinoma
Lichen planus
Superficial fungal infections
Psoriasis
Trauma
Secondary syphilis
Hepatitis
Infectious mononucleosis
Drug eruptions
Viral exanthemas (eg, pityriasis rosea)
Febrile exanthemas
Scabies
Lichen planus
Psoriasis
Oral candidiasis
Condylomata acuminata
Tertiary syphilis
Tuberculosis
Sarcoid
Leprosy
Deep fungal infections
Carcinoma
Lymphoma
Congestive heart failure
Myocardial infarction
HIV infection
Stroke
Multiple sclerosis
Seizures
Brain tumors
Other CNS infections
Workup
Laboratory Studies
- Immunofluorescence staining of mucocutaneous lesions or dark-field microscopy demonstrates the spirochete in primary, secondary, and early congenital syphilis.
Syphilis. This is a dark-field micrograph of spirochetes. Used with permission from Murray P et al. Medical Microbiology. 2nd ed. Mosby; 1994.
- Serologic reaginic tests for syphilis include the following:
- Screening tests include the rapid plasma reagin (RPR) test and the Venereal Disease Research Laboratory (VDRL) test.
- Sensitivities are 70%-80% for primary syphilis and approach 99%-100% for secondary syphilis, although these tests yield high false-positive rates. Other factors (eg, lupus, concomitant viral or bacterial infection, recent immunization, pregnancy) may result in false-positive readings.
- Serological tests cannot be used to differentiate the different species of the treponeme family (eg, yaws).
- Use VDRL titers to monitor treatment efficacy.
- The VDRL test results turn positive 1-2 weeks after chancre formation. After a positive VDRL test finding, follow up with a more specific test.
- VDRL test findings are persistently positive in a small percentage of adequately treated individuals. See Further Outpatient Care for more information.
- The fluorescent treponemal antibody absorption (FTA-ABS) test is reactive in 85% of primary syphilis cases, 99-100% of secondary syphilis cases, and 95% of latent or late syphilis cases. FTA-ABS should be used as a confirmatory test following positive VDRL or RPR test findings.
- The T pallidum hemagglutination (TPHA) test and the T pallidum particle agglutination (TPPA) test are generally used for screening.
- Treponemal enzyme immunoassay (EIA/immunoglobulin G [IgG], immunoglobulin M [IgM]) tests may be performed.
- Testing must be performed more than once in patients diagnosed with latent syphilis in order to exclude laboratory error.
- Infants with congenital syphilis and positive VDRL or FTA-ABS test results can undergo IgM FTA-ABS testing (maternal IgM is not passed to the fetus in utero). However, the false-negative rate is 35%, and the false-positive rate is 10%. See the congenital syphilis testing section in Special Concerns for more information.
Imaging Studies
- Obtain chest radiography in patients with tertiary syphilis to screen for aortic dilatation.
- CT scanning and MRI of the head and body may be used to document the complications of tertiary syphilis.
Other Tests
- Slit-lamp examination and ophthalmic assessment can be used to differentiate between acquired and congenital syphilis (presence of interstitial keratitis) in patients with latent infection of uncertain duration.
Procedures
- Lumbar puncture
- CNS invasion by treponemes occurs in 30-40% of patients with primary or secondary syphilis; however, no studies show this to be a predictor of poor neurologic outcome.
- Lumbar puncture (LP) is not indicated for patients with early syphilis. Current guidelines in clinical infectious diseases state that physicians should evaluate cerebrospinal fluid (CSF) in individuals with latent syphilis of unknown duration or with late latent syphilis if (1) treatment fails, (2) neurologic or ocular symptoms are present; or (3) the patient has underlying HIV infection. LP is only relatively indicated in patients with high titers on serological tests (³ 1:32).
- Examination of the CSF should include the VDRL test, cell count, and protein level. Abnormalities of any of these measurements combined with a suggestive history and examination strongly indicate the presence of neurosyphilis. Derangements of these values are consistently found in neurosyphilis. A positive VDRL test result indicates active syphilis. A positive polymerase chain reaction (PCR) test finding is sensitive in detecting past invasion of the CNS but does establish whether the T pallidum organisms are still alive.
Histologic Findings
The primary lesion of syphilis is a chancre. Histologically, it is characterized by mononuclear leukocytic infiltration, macrophages, and lymphocytes.
The inflammatory reaction of secondary syphilis is histologically similar to that of the primary chancre but is less intense.
In tertiary syphilis, histological examination shows palisaded macrophages and fibroblasts, as well as plasma cells surrounding the margins. Treponemes are rare in these lesions and typically cannot be cultured or visualized.
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References
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CDC. Penicillin Allergy-STD Treatment Guidelines 2006. Department of Health and Human Services. Available at http://www.cdc.gov/std/treatment/2006/penicillin-allergy.htm.
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Ernst AA, Romolo R, Nick T. Emergency department screening for syphilis in pregnant women without prenatal care. Ann Emerg Med. May 1993;22(5):781-5. [Medline].
Hibbs JR, Ceglowski WS, Goldberg M. Emergency department-based surveillance for syphilis during an outbreak in Philadelphia. Ann Emerg Med. Aug 1993;22(8):1286-90. [Medline].
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Further Reading
Keywords
syphilis, primary syphilis, secondary syphilis, latent syphilis, congenital syphilis, tertiary syphilis, venereal disease, Treponema pallidum, T pallidum, syphilemia, syphilid, syphiloderm, syphiloderma, syphiloma, syphilitic infection, sexually transmitted disease, STD, yaws, pinta, chancres, gumma, lues venerea, malum venereum, great imitator, gummatous syphilis, cardiovascular syphilis, meningovascular syphilis, paretic syphilis, late congenital syphilis, early congenital syphilis, late syphilis, early syphilis, acquired syphilis
