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Syphilis: Differential Diagnoses & Workup

Author: Maria M Diaz, MD, Staff Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center
Coauthor(s): Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Jul 17, 2009

Differential Diagnoses

Chancroid
Pityriasis Rosea
Condyloma Acuminata
Psoriasis
Herpes Simplex
Stevens-Johnson Syndrome
Lymphogranuloma Venereum
Warts, Genital

Other Problems to Be Considered

Primary genital syphilitic lesion 
Herpes simplex (primary and recurrent infection)
Chancroid
Traumatic superinfected lesions
Carcinoma
Mycotic infection 
Granuloma inguinale
Lichen planus
Psoriasis
Fungal infection
Venereal chlamydial infections

Cutaneous eruption of secondary syphilis
Drug eruptions
Pityriasis rosea
Psoriasis
Lichen planus
Viral exanthem

Tertiary syphilis
The extremely variable manifestations of tertiary syphilis produce a broad differential diagnosis, and care must be taken to consider syphilis in cardiac, dermatologic, and neurologic disorders as is relevant.

Workup

Laboratory Studies

  • T pallidum cannot be cultivated in vitro and is too small to be seen under the light microscope. Serologic testing is considered the standard method of detection for all stages of syphilis. 
  • Nontreponemal tests are used as initial screening tests. These include the Venereal Disease Research Laboratory (VDRL) and the Rapid Plasma Reagin (RPR) tests. Nontreponemal tests usually become nonreactive with time after treatment. However, in some patients, nontreponemal antibodies can persist, sometimes for the life of the patient.6
    • Sensitivity of the VDRL and RPR tests are estimated to be 78-86% for detecting primary syphilis, 100% for detecting secondary syphilis, and 95-98% for detecting tertiary syphilis.
    • Specificity ranges from 85-99% and may be reduced in individuals who have coexisting conditions (ie, collagen vascular disease, pregnancy, intravenous drug use, advanced malignancy, tuberculosis, malaria, viral and rickettsial diseases).7
  • Because of the possibility of false-positive results, confirmation for any positive nontreponemal test should follow with a treponemal test. The fluorescent treponemal antibody absorption test (FTA-ABS) has a sensitivity of 84% for detecting primary syphilis infection and almost 100% sensitivity for detecting syphilis infection in other stages. Its specificity is 96%.7
  • Diagnosis of neurosyphilis can be challenging. The VDRL-CSF is highly specific but has low sensitivity. Therefore, the diagnosis of neurosyphilis usually depends on a combination of reactive serologic test results, CSF cell count, CSF protein, and clinical manifestations with or without a reactive VDRL-CSF. Some specialists recommend performing an FTA-ABS test on CSF. The CSF FTA-ABS is less specific for neurosyphilis than the VDRL-CSF, but it is highly sensitive.6
  • Patients with confirmed syphilis infections should be tested for other sexually transmitted diseases, including HIV.

Imaging Studies

  • Imaging studies should be performed depending on the organ system involved. For example, granulomatous disease can be seen on CT.

Procedures

  • Lumbar puncture should be performed on patients suspected of having neurosyphilis with no contraindication.

More on Syphilis

Overview: Syphilis
Differential Diagnoses & Workup: Syphilis
Treatment & Medication: Syphilis
Follow-up: Syphilis
Multimedia: Syphilis
References
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References

  1. Primary and secondary syphilis--United States, 2003-2004. MMWR Morb Mortal Wkly Rep. Mar 17 2006;55(10):269-73. [Medline].

  2. Harrison LW. The Oslo study of untreated syphilis, review and commentary. Br J Vener Dis. Jun 1956;32(2):70-8. [Medline].

  3. Rockwell DH, Yobs AR, Moore MB Jr. The Tuskegee Study of Untreated Syphilis; the 30th year of Observation. Arch Intern Med. Dec 1964;114:792-8. [Medline].

  4. Sexually Transmitted Disease Surveillance, 2007. Atlanta, Georgia: Centers for Disease Control and Prevention; 2008. 33. [Full Text].

  5. [Guideline] Screening for syphilis infection in pregnancy: U.S. Preventive services task force reaffirmation recommendation statement. Ann Intern Med. May 19 2009;150(10):705-9. [Medline]. [Full Text].

  6. [Guideline] Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55:1-94. [Medline]. [Full Text].

  7. [Guideline] U.S. Preventive Services Task Force. Screening for Syphilis Infection. Recommendation Statement. 2004. [Full Text].

  8. Bai ZG, Yang KH, Liu YL, et al. Azithromycin vs. benzathine penicillin G for early syphilis: a meta-analysis of randomized clinical trials. Int J STD AIDS. Apr 2008;19(4):217-21. [Medline].

  9. [Guideline] Calonge N. Screening for syphilis infection: recommendation statement. Ann Fam Med. Jul-Aug 2004;2(4):362-5. [Medline]. [Full Text].

  10. Centers for Disease Control and Prevention. Primary and Secondary Syphilis -- United States, 2003-2004. MMWR Morb Mortal Wkly Rep. March 17, 2006;55(10):269-273. [Full Text].

  11. Csonka GW, Oates JK. Sexually Transmitted Diseases. WB Saunders; 1990:227-76.

  12. Department of Health and Human Services. Sexually Transmitted Diseases Surveillance 2004 Report. Syphilius Surveillance Report. 2005;[Full Text].

  13. Hoeprich PD, Jordan MC. Infectious Diseases. 4th ed. Lippincott-Raven; 1989:666-83.

  14. Isselbacher KJ, Braunwald E, Wilson JD. Harrison's Principles of Internal Medicine. 13th ed. McGraw-Hill: 1994:726-37.

  15. Kent ME, Romanelli F. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother. Feb 2008;42(2):226-36. [Medline].

  16. Rosahn PD. Autopsy studies in syphilis; a monograph. Washington: U.S. Dept. of Health, Education, and Welfare, Public Health Service, Bureau of State Services, Communicable Disease Center, Venereal Disease Branch; 1948. U.S. Public Health Service Publication.

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Further Reading

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Keywords

syphilis, syphilis treatment, syphilis symptoms, syphilis symptoms, STDs, sexually transmitted diseases, Treponema pallidum, T pallidum, primary syphilis, secondary syphilis, early latent syphilis, late latent syphilis, tertiary syphilis, gummatous syphilis, cardiovascular syphilis, neurosyphilis, advanced syphilis, chancre, genital chancre, inguinal adenitis, condylomata lata, the great impostor

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Contributor Information and Disclosures

Author

Maria M Diaz, MD, Staff Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center
Maria M Diaz, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Joseph J Sachter, MD, FACEP, Consulting Staff, Department of Emergency Medicine, Muhlenberg Regional Medical Center
Joseph J Sachter, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Medical Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eric L Weiss, MD, DTM&H, Director of Stanford Travel Medicine, Medical Director of Stanford Lifeflight, Assistant Professor, Departments of Emergency Medicine and Infectious Diseases, Stanford University School of Medicine
Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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