Basics
Description
- Systemic infection caused by the spirochete, Treponema pallidum
- Can be congenital or acquired
- Consider sexual abuse when syphilis is diagnosed in young children.
Epidemiology
- Congenital syphilis is defined as transmission from an infected mother to her unborn or newborn baby.
- Infection transmitted to the fetus at any stage of disease; during primary and secondary syphilis, rate of transmission is 60 " 100%.
- ’ Ό10.8 cases per 100,000 live births in 2008
- Acquired syphilis is sexually transmitted from an infected to an uninfected individual.
- Nasal secretions are highly infectious in congenital syphilis, and open, moist skin lesions are infectious in congenital and acquired syphilis.
Risk Factors
- Lack of prenatal care
- Maternal use of illicit drugs
- Sexual abuse
- Infection with HIV
Diagnosis
Signs and Symptoms
- Congenital syphilis
- Clinical manifestations range from clinically inapparent to stillbirth.
- Clinical signs include hepatosplenomegaly, periostitis, osteochondritis, persistent rhinorrhea, or maculopapular rash.
- Acquired syphilis
- Primary stage: painless, indurated ulcers (chancres), single or multiple, at the site of inoculation ’ Ό3 weeks after exposure (range 10 " 90 days); lesions usually resolve without treatment in 3 " 6 weeks.
- Secondary stage: generalized rash, which is often maculopapular and involves the palms and soles; condyloma lata, hypertrophic papular lesions; fever, malaise, lymphadenopathy; signs appear 3 " 6 weeks after initial chancre and may last 2 " 10 weeks.
- Relapse: Symptoms of secondary syphilis may recur 1 or more times before the latent period.
- Latent period: Untreated, illness may enter a latent stage; patients are asymptomatic, not contagious; lasts 1 " 40 years or more; patients seroreactive but without other evidence of disease.
- Early latent period: 1st year of latent period
- Late latent period: subsequent years
- Tertiary stage: Up to 1/3 of untreated secondary syphilis cases progress to tertiary or late disease; can occur many years after the primary infection; may see gummatous changes of the skin, bone, and/or viscera or cardiovascular syphilis
- Neurosyphilis: CNS involvement in 3 " 7% of untreated cases; can develop at any stage of disease; signs include changes in mood/behavior, hyperactive reflexes, impaired memory and/or judgment, and Argyll-Robertson pupils
History
- Newborn/infants
- Obtain a detailed prenatal history; inquire about all syphilis testing done on the mother; if mother has a history of syphilis, ensure documented treatment. The local department of health should have detailed records that include titers and treatment on all cases of syphilis.
- Newborns should be evaluated for congenital syphilis if the mother is not adequately treated for syphilis (treated with nonpenicillin regimen, such as erythromycin), mother treated adequately but less than 4 weeks before delivery, maternal syphilis treated prior to pregnancy with insufficient follow-up to assess serologic response to treatment, if the infant 's titer is 4-fold greater than the mother 's titer, or if the infant has clinical signs of infection.
- Older children/adolescents
- Ask about possible sexual abuse in children.
- Ask about sexual activity in adolescents, including experience, number of lifetime partners, ages of partners, history of other STDs, and use of barrier contraception.
- Ask about other risk behaviors.
- Ask about risk factors for HIV exposure.
Physical Exam
- Early congenital syphilis
- Intrauterine growth restriction; irritability, bulging fontanel, if neurosyphilis is present
- Alopecia (scalp and eyebrows)
- Fissures in the lips, nares, anus (rhagades); mucocutaneous lesions
- Rhinitis ( "snuffles " ) may occur at one to several weeks of age and may be blood-tinged and purulent.
- Lymphadenopathy
- Pneumonia alba: Check for tachypnea and/or respiratory distress.
- Myocarditis
- Hepatosplenomegaly with or without jaundice
- Pseudoparalysis of an extremity
- Rash: bullous ( "syphilitic pemphigus " ) and/or maculopapular ( "blueberry muffin " ) lesions symmetrically distributed on palms, soles, and other parts of the body
- Condyloma lata: flat, wartlike, moist lesions around the anus/vagina; chancres
- Late congenital syphilis
- Bony deformities, such as short maxilla, high-arched palate, saddle nose, mulberry molars, Higoumenakis sign (enlargement of the sternoclavicular portion of the clavicle), protuberance of the mandible, saber shins, scaphoid scapulae
- Rhagades, neurologic involvement
- Acquired syphilis
- Primary syphilis
- Chancre (painless ulcer), single, most commonly located on the genitalia, and/or
- Painless inguinal adenopathy
- Secondary syphilis: flulike illness with fever, headache, sore throat, nasal discharge, generalized arthralgias and myalgias, malaise, generalized painless and mobile lymphadenopathy; hepatosplenomegaly; maculopapular rash involving the palms and soles that may involve mucous membranes; condyloma lata (moist, papular lesions); alopecia; signs of meningitis, hepatitis, nephropathy, ocular involvement
Diagnostic Tests & Interpretation
- Pitfalls:
- False-positive nontreponemal test (e.g., rapid plasma reagin [RPR]) results may be seen with lab error, autoimmune disease, tuberculosis, lymphoma, viral infections (including Epstein-Barr, hepatitis, varicella, HIV, and measles viruses), endocarditis, malaria, and IV drug abuse.
- False-positive treponemal tests may be seen in other spirochetal diseases (i.e., Lyme disease, leptospirosis) and rarely in autoimmune disease (i.e., systemic lupus erythematosus) and viral infections.
- False-negative nontreponemal test (e.g., RPR) results may be seen with prozone phenomenon if titers are high.
- Mothers of infants with congenital syphilis should also be tested for gonorrhea, chlamydia, HIV, and hepatitis B virus infection.
- In newborns, cord blood testing may result in false-positive and false-negative results; therefore, serum from the infant is the preferred source of testing.
- Infants should not be discharged from the nursery until the results of maternal syphilis tests are known.
- "Reverse screening " algorithm refers to using treponemal test first, then confirming a positive result with nontreponemal test.
- Discordant results should be confirmed with a second, different treponemal test
- Unclear how to manage well-appearing infants born to mothers identified by reverse screening who have positive treponemal tests but nonreactive RPR (most experts recommend single IM dose of penicillin G, 50,000 U/kg)
Lab
- Nontreponemal tests
- VDRL (Venereal Disease Research Laboratory) or RPR test to measure nontreponemal antibodies
- Used for routine screening; quantitative serum titers generally correlate with disease activity; need to confirm positive results with a treponemal antibody test. 4-fold titer change (e.g., from 1:8 to 1:32) necessary to document clinically significant change. Titers for different nontreponemal tests are not equivalent; therefore, use same test (and preferably same lab) when following serial titers.
- VDRL (not RPR) is used on CSF to evaluate for neurosyphilis.
- Treponemal antibody tests
- Used for confirmation of positive nontreponemal test
- FTA-ABS (fluorescent treponemal antibody-absorption), TPPA (T. pallidum particle agglutination), MHA-TP (microhemagglutination assay for T. pallidum antibodies), or EIA (enzyme immunoassay for antitreponemal IgG)
- Treponemal tests usually remain positive for life once infected; not useful for measuring treatment effectiveness
- Dark-field microscopy
- CSF analysis
- Findings include mononuclear pleocytosis, moderately elevated protein, and normal glucose.
- Should be performed in all patients with acquired syphilis of >1 year 's duration
- Perform on infants when congenital syphilis suspected, if the physical examination is consistent with syphilis, if infant 's titer is 4-fold greater than that of mother, or if dark-field or fluorescent antibody test positive on body fluids
- Remember that CSF protein levels in normal newborns are higher than in older children; some are as high as 150 " 200 mg/dL.
Imaging
Long bone plain films: Rule out metaphyseal osteochondritis and/or diaphyseal periostitis.
Differential Diagnosis
- Congenital syphilis
- Herpes simplex virus (HSV)
- Toxoplasmosis
- Cytomegalovirus
- Rubella
- Neonatal hepatitis
- Osteomyelitis
- Acquired syphilis
- Chancroid (Haemophilus ducreyi)
- Granuloma inguinale
- Calymmatobacterium granulomatis
- Lymphogranuloma venereum (Chlamydia trachomatis)
- Scabies
- Mycotic infections
- Genital herpes (HSV)
- Venereal warts (human papillomavirus [HPV])
- Viral exanthem (e.g., enteroviruses may cause a maculopapular rash involving the palms and soles)
Treatment
Medication
- Infants <28 days of age
- Aqueous crystalline penicillin G (50,000 U/kg/dose) IV q12h for first 7 days of life, then q8h for a total of 10 days or procaine penicillin G (50,000 U/kg/dose) IM daily for 10 days
- If >1 day of treatment is missed, restart 10-day course.
- Infants >28 days of age
- Aqueous crystalline penicillin G (50,000 U/kg/dose) IV q4 " 6h for 10 days
- Primary, secondary, and early latent (<1 year duration) syphilis
- Infant/child: penicillin G benzathine 50,000 U/kg IM (maximum, 2.4 million units), single dose
- Adolescent/adult: doxycycline 100 mg PO b.i.d. or tetracycline 500 mg PO q.i.d. for 14 days for nonpregnant, penicillin-allergic patients
- Late latent syphilis (>1 year duration) or disease of unknown duration
- Infant/child: penicillin G benzathine, 50,000 U/kg IM (maximum 2.4 million U) weekly for 3 consecutive weeks
- Adolescent/adult: doxycycline 100 mg PO b.i.d. or tetracycline 500 mg PO q.i.d. for 4 weeks for nonpregnant, penicillin-allergic patients
- Pregnant women with penicillin allergy who require therapy for syphilis should be desensitized
- Alternative therapy can be found at www.cdc.gov/nchstp/dstd/penicillinG.htm.
Ongoing Care
Issues for Referral
All cases should be reported to the local department of (public) health.
Prognosis
- The prognosis is better the earlier syphilis is detected and treated.
- Following appropriate therapy, the disease usually is totally arrested.
- With late findings of syphilis involving the nervous and/or cardiovascular systems, there may not be clinical improvement.
- Untreated infection in the neonate progresses to neurosyphilis within 1 year.
- Osteochondritis and periostitis in the newborn are usually self-limited and heal in the first 3 " 6 months of life.
- Hemolytic anemia seen in congenital syphilis may persist for weeks.
Complications
- Stillbirth or spontaneous abortion
- Perinatal death in 40% of pregnancies in mothers with untreated early syphilis
- Prematurity
- Hydrops fetalis
- Nephrosis
- Pneumonia alba
- Intrauterine growth restriction and failure to thrive
- Disseminated intravascular coagulation
- Pseudoparalysis of Parrot: paralysis of one of the limbs of an infant affected by congenital syphilis; usually unilateral
- Acute syphilitic leptomeningitis
- Cranial nerve palsies
- Interstitial keratitis: 5 " 20 years after birth
- Cerebral infarction
- Seizure disorder, mental retardation
- Rhagades: cluster of scars radiating around the mouth
- Mulberry molars: maldevelopment of the cusps in the first molars
- Clutton joints: painless arthritis of the knees and, rarely, other joints
- Hutchinson triad: Hutchinson teeth (notched upper central incisors), interstitial keratitis, 8th-nerve deafness
- Saber shins: anterior bowing of the midportion of the tibia
Patient Monitoring
- Congenital syphilis:
- Clinical follow-up and serial nontreponemal serologic testing every 2 " 3 months until titer decreases 4-fold or test is nonreactive
- After adequate treatment, nontreponemal tests should be nonreactive after 6 months; infants with a history of abnormal CSF findings need serial CSF analyses every 6 months until CSF is normal.
- Treated infants, follow-up at 1, 2, 4, 6, and 12 months of age; serologic tests should be performed 2, 4, 6, and 12 months after therapy until they become nonreactive or the titer has decreased 4-fold.
- If titers have not shown a decline by 6 " 12 months, require reevaluation and treatment.
- Primary and secondary syphilis
- Clinical follow-up and serial nontreponemal titers at 6 and 12 months after treatment (more often, if at high risk for reinfection or treatment failure): Nontreponemal titers should drop 4-fold within 6 months of treatment of primary or secondary syphilis and within 12 " 24 months after treatment of latent or tertiary syphilis.
Additional Reading
- American Academy of Pediatrics. Syphilis. In: Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:690 " 703.
- Binniker MJ. Which algorithm should be used to screen for syphilis? Curr Opin Infect Dis. 2012;25(1):79 " 85. [View Abstract]
- Centers for Disease Control and Prevention. Congenital syphilis " United States, 2003 " 2008. MMWR Morb Mortal Wkly Rep. 2010;59(14):413 " 417. [View Abstract]
- Centers for Disease Control and Prevention. Primary and secondary syphilis " United States, 2003 " 2004. MMWR Morb Mortal Wkly Rep. 2006;55(10):269 " 273. [View Abstract]
- Chakraborty R, Luck S. Managing congenital syphilis again? The more things change. Curr Opin Infect Dis. 2007;20(3):247 " 252. [View Abstract]
- Chakraborty R, Luck S. Syphilis is on the increase. Arch Dis Child. 2008;93(2):105 " 109. [View Abstract]
- Hyman EL. Syphilis. Pediatr Rev. 2006;27(1):37 " 39. [View Abstract]
- Tobian AA, Serwadda D, Quinn TC, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009;360(13):1298 " 1309. [View Abstract]
- Wendel GD, Stark BJ, Jamison RB, et al. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med. 1985;312(19):1229 " 1232. [View Abstract]
Codes
ICD09
- 097.9 Syphilis, unspecified
- 090.9 Congenital syphilis, unspecified
- 092.9 Early syphilis, latent, unspecified
- 097.0 Late syphilis, unspecified
- 097.1 Latent syphilis, unspecified
ICD10
- A53.9 Syphilis, unspecified
- A50.9 Congenital syphilis, unspecified
- A51.5 Early syphilis, latent
- A52.9 Late syphilis, unspecified
- A53.0 Latent syphilis, unspecified as early or late
SNOMED
- 76272004 Syphilis (disorder)
- 35742006 Congenital syphilis (disorder)
- 240555007 Acquired syphilis
- 266130009 Acquired syphilis - early latent (disorder)
- 186867005 Latent early syphilis (disorder)
FAQ
- Q: Can an infant have congenital syphilis if the mother had a negative RPR during pregnancy?
- A: A mother with a negative RPR during pregnancy may have acquired syphilis late in pregnancy and transmitted it to her fetus. If the mother was not tested at delivery, then the diagnosis may have been missed.
- Q: What is the prozone phenomenon?
- A: When a nontreponemal test is falsely negative due to high concentrations of antibody to T. pallidum; diluting the serum will result in positive test results.