Syphilis Differential Diagnoses

  • Author: Brian Euerle, MD, FACEP; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 6, 2012
 
 

Diagnostic Considerations

Syphilis, a reportable disease, is tracked by the Centers for Disease Control and Prevention (CDC). Syphilis has an extensive differential diagnosis. In particular, the extremely variable manifestations of tertiary syphilis produce an extremely broad differential diagnosis, and care must be taken to consider syphilis in cardiac, dermatologic, and neurologic disorders as is relevant. Patients diagnosed with syphilis should also be tested for other sexually transmitted diseases (STDs), including chlamydia, gonorrhea, trichomoniasis, bacterial vaginosis, and HIV infection.

When making a primary diagnosis of a generalized rash or an STD, always include syphilis in the differential diagnoses because of its varying manifestations. Consider prophylactic treatment or serologic studies for syphilis.

Diagnosis of syphilis in pregnant women

Routinely screen all pregnant women for syphilis. Repeat tests in high-risk mothers and patients who live in high-risk areas for syphilis (eg, inner city) before delivery. The rate of stillbirths in mothers with untreated syphilis is as high as 33%. In pregnant patients with positive Venereal Disease Research Laboratory (VDRL) test results, perform monthly VDRL tests for the duration of the pregnancy. If test results are positive, the treatment of choice is parenteral benzathine penicillin G. Penicillin is safe to use while breastfeeding.

According to the 2010 CDC sexually transmitted diseases treatment guidelines, pregnant women who are seropositive should be considered infected unless there is evidence of adequate treatment in the medical records and sequential serologic antibody titers have decreased.[18]

In pregnant patients who are allergic to penicillin, current CDC recommendations are for desensitization and subsequent treatment with penicillin. Erythromycin has also been used in penicillin-allergic pregnant patients, although it is less effective than other treatment regimens. Ceftriaxone has been used for the treatment of syphilis, but data are still limited regarding efficacy.

Per CDC guidelines, any woman who delivers a stillborn infant after 20 weeks’ gestation should be tested for syphilis. No infant should leave the hospital without the maternal serologic status having been determined at least once during pregnancy.

For further information, see the 2010 CDC guidelines for syphilis and pregnancy.

Diagnosis of congenital syphilis

Consider congenital syphilis and sexual abuse in all children who present with syphilis.

Most infants with congenital syphilis are born to mothers with syphilis who either were not treated in pregnancy or were treated too late during pregnancy. Mothers with syphilis deliver infants with positive VDRL and fluorescent treponemal antibody absorption (FTA-ABS) test results secondary to passive transfer of immunoglobulin G (IgG) antibodies, which react with the reagents in these tests.

The 2010 CDC guidelines recommend serologic testing of the mother rather than the infant. They do not recommend screening of newborn sera or umbilical cord blood. An infant’s serum may be nonreactive to serologic testing if the mother was infected late in pregnancy or if her serologic results are of low titer. No infant or mother should be discharged from the hospital unless the mother’s serologic status has been documented at least once during pregnancy; in areas where the risk of congenital syphilis is high, documentation should also occur at delivery.[18]

Most infants are born without any clinical evidence of syphilis. Because infants may develop serious disease up to several weeks after delivery, it is important to monitor the care of these patients with serial serological tests. If the mother has been adequately treated for syphilis during pregnancy and the infant has no symptoms, serial VRDL tests for 2 months are adequate. A rising titer over a 2-month course is evidence of active syphilis, whereas falling titers indicate passive maternal antibody transfer.

Some clinicians empirically treat infants who have positive serologic tests with penicillin to avoid the inconvenience of serial testing and the risk of no follow-up care.

For more information, see the 2010 CDC guidelines for congenital syphilis treatment.

Other problems to consider include the following:

  • Brain tumors
  • Carcinoma
  • Congestive heart failure
  • Fungal infection (superficial and deep)
  • Lymphoma
  • Mycotic infection
  • Other CNS infections
  • Sarcoid
  • Seizures
  • Stroke
  • Trauma
  • Traumatic superinfected lesions
  • Venereal chlamydial infections

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Brian Euerle, MD, FACEP  Associate Professor, Department of Emergency Medicine, Director of Emergency Ultrasound Program, University of Maryland School of Medicine

Brian Euerle, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Pranatharthi Haran Chandrasekar, MBBS, MD  Professor, Department of Internal Medicine, Director of Infectious Disease Fellowship, Harper Hospital, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Maria M Diaz, MD  Staff Physician, Department of Emergency Medicine, Memorial Hospital

Maria M Diaz, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Daniel J Hogan, MD  Clinical Professor of Internal Medicine (Dermatology), Nova Southeastern University College of Osteopathic Medicine; Investigator, Hill Top Research, Florida Research Center

Daniel J Hogan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, and Canadian Dermatology Association

Disclosure: Nothing to disclose.

Paul Krusinski, MD  Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine

Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Timothy McCalmont, MD  Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology

Timothy McCalmont, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Dermatopathology, California Medical Association, College of American Pathologists, and United States and Canadian Academy of Pathology

Disclosure: Apsara Consulting fee Independent contractor

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.

Richard H Sinert, DO  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.

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Eric L Weiss, MD, DTM&H  Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center

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.

Specialty Editor Board

Daniel R Lucey, MD, MPH  Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences

Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

John L Brusch, MD, FACP  Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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Syphilis. These photographs depict the characteristic chancre observed in primary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. These photographs show the disseminated rash observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. These photographs show close-up images of gummas observed in tertiary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This is a dark-field micrograph of spirochetes. Used with permission from Murray P et al. Medical Microbiology. 2nd ed. Mosby; 1994.
Syphilis. This photograph depicts primary syphilis "kissing" lesions. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. Palmar lesions observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
These photographs illustrate examples of condylomata lata. The lesions resemble genital warts (condylomata acuminata). Fluids exuding from these lesions are highly infectious. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. These photographs illustrate typical facies of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
Syphilitic chancre
Secondary syphilis - Exanthem
empty para to satisfy content model
Condylomata lata
Lues hematoxylin and eosin stain. Histopathological examination shows a lichenoid infiltrate that is stereotypical of the secondary stage of syphilis. Note that vacuolar alteration of the superjacent epithelium can be seen much like a noninfectious form of lichenoid dermatitis. The subjunctional infiltrate is rich in histiocytes and plasmacytes. At times, an overtly granulomatous lichenoid infiltrate can be seen.
Lues TP stain. Immunoperoxidase staining for T pallidum highlights many slender coiled organisms residing in the perijunctional zone. Occasionally, organisms can also be found in the upper dermis or around adnexal structures.
 
 
 
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