Diseases (27)

Screening/Initial Testing (7)


Should be performed on both maternal and infant samples


If syphilis is suspected by history


Rule out syphilis.

Diagnostic Testing (14)


Rule out syphilis in patients with patchy alopecia


If T. pallidum serology is positive.


Rule out syphilis.


Should be ordered with VDRL as VDRL is usually positive and RPR negative.


Treponema pallidum, the etiological agent of syphilis, induces the production of at least two types of antibodies in human infection: anti-treponemal antibodies that can be detected by fluorescence treponemal antigen assay (FTA-ABS), and anti-nontreponemal antibodies (reagin) that can be detected by RPR antigen. RPR is a latex flocculation based test that uses a cardiolipin-lecithin-cholesterol carbon-containing antigen reagent. If antibodies are present, black carbon clumps are produced by flocculation indicating a positive test for RPR. It is a rapid test used as a screening test and in suspected primary and secondary syphilis. It is not specific for syphilis and false positives can occur with disorders such as malaria, systemic lupus erythematosus, infectious mononucleosis, viral pneumonia as well as the status of being pregnant.  Positive results must be confirmed by IFA antibody testing or by PCR. The test is also used for treatment monitoring and disease management. After treatment with antibiotics, the levels of syphilis antibodies should fall. These levels can be monitored with the RPR titer.  Successful therapy is indicated by a 4 fold decrease in titer within 6 months after initiation of therapy for primary and secondary stages.  Unchanged or rising levels can mean a persistent infection.

Syphilis is a sexually transmitted infection (STI) caused by the bacterial spirochete Treponema pallidum. Syphilis can be divided into three infectious stages: primary, secondary, and early latent, and two non-infectious disease stages: late latent and tertiary. Untreated syphilis during pregnancy can lead to miscarriage, premature or stillbirth, and birth defects. Testing of the mother is very important during the early stages of pregnancy so that treatment can be administered and the fetus can remain unaffected. It is estimated that approximately 12 million new cases of venereal syphilis occur each year.

Clinical Utility

  • Diagnosis of syphilis
  • Screening test for syphilis
  • Therapy monitoring


Increased in:

  • Syphilis: primary in about 80%
  • Secondary >95%
  • Symptomatic late syphilis in about 75%

False positives:

  • Leprosy
  • Malaria
  • Intravenous Drug Abuse
  • Infectious Mononucleosis
  • HIV infection (15%)
  • Autoimmune Diseases such as SLE and Rheumatoid Arthritis
  • Occasional false positives in elderly and pregnancy

Reference Ranges

Negative (Non-reactive)




Macroscopic agglutination.

Specimen Collection

Serum (Red top) preferred, Serum gel (SST) acceptable


  • Ambient: 4 days
  • Refrigerated: 7 days
  • Frozen: 30 days

Additional Testing

Treponemal antibody by IFA or ELISA, T. pallidum by PCR testing, MHA-TP.

Turnaround Time

1-3 days.





A50Congenital syphilis
A50.1Early congenital syphilis, latent
A50.4Late congenital neurosyphilis [juvenile neurosyphilis]
A50.40Late congenital neurosyphilis, unspecified
A50.49Other late congenital neurosyphilis
A50.6Late congenital syphilis, latent
A50.7Late congenital syphilis, unspecified
A50.9Congenital syphilis, unspecified
A51Early syphilis
A51.0Primary genital syphilis
A51.3Secondary syphilis of skin and mucous membranes
A51.32Syphilitic alopecia
A51.39Other secondary syphilis of skin
A51.4Other secondary syphilis
A51.41Secondary syphilitic meningitis
A51.42Secondary syphilitic female pelvic disease
A51.49Other secondary syphilitic conditions
A51.5Early syphilis, latent
A52Late syphilis
A52.1Symptomatic neurosyphilis
A52.10Symptomatic neurosyphilis, unspecified
A52.19Other symptomatic neurosyphilis
A52.3Neurosyphilis, unspecified
A52.7Other symptomatic late syphilis
A52.79Other symptomatic late syphilis
A52.8Late syphilis, latent
A53Other and unspecified syphilis
A53.0Latent syphilis, unspecified as early or late
A53.9Syphilis, unspecified
A56Other sexually transmitted chlamydial diseases
A56.11Chlamydial female pelvic inflammatory disease
A56.8Sexually transmitted chlamydial infection of other sites
A60Anogenital herpesviral [herpes simplex] infections
A60.0Herpesviral infection of genitalia and urogenital tract
A60.00Herpesviral infection of urogenital system, unspecified
A60.01Herpesviral infection of penis
A60.02Herpesviral infection of other male genital organs
A60.03Herpesviral cervicitis
A60.04Herpesviral vulvovaginitis
A60.09Herpesviral infection of other urogenital tract
A60.1Herpesviral infection of perianal skin and rectum
A60.9Anogenital herpesviral infection, unspecified
B00Herpesviral [herpes simplex] infections
B00.0Eczema herpeticum
B00.1Herpesviral vesicular dermatitis
B00.3Herpesviral meningitis
B00.4Herpesviral encephalitis
B00.5Herpesviral ocular disease
B00.53Herpesviral conjunctivitis
B00.81Herpesviral hepatitis
B00.82Herpes simplex myelitis
B00.89Other herpesviral infection
B00.9Herpesviral infection, unspecified
B02.23Postherpetic polyneuropathy
D68.61Antiphospholipid syndrome
D68.62Lupus anticoagulant syndrome
F01Vascular dementia
F02Dementia in other diseases classified elsewhere
F03Unspecified dementia
F03.90Unspecified dementia without behavioral disturbance
F03.91Unspecified dementia with behavioral disturbance
F10.27Alcohol dependence with alcohol-induced persisting dementia
F18.17Inhalant abuse with inhalant-induced dementia
G31.84Mild cognitive impairment, so stated
G58.9Mononeuropathy, unspecified
G60Hereditary and idiopathic neuropathy
G60.0Hereditary motor and sensory neuropathy
G60.3Idiopathic progressive neuropathy
G60.8Other hereditary and idiopathic neuropathies
G61Inflammatory polyneuropathy
G61.1Serum neuropathy
G62Other and unspecified polyneuropathies
G62.9Polyneuropathy, unspecified
G63Polyneuropathy in diseases classified elsewhere
G90.0Idiopathic peripheral autonomic neuropathy
G99Other disorders of nervous system in diseases classified elsewhere
G99.0Autonomic neuropathy in diseases classified elsewhere
I32Pericarditis in diseases classified elsewhere
I39Endocarditis and heart valve disorders in diseases classified elsewhere
I40Acute myocarditis
I40.0Infective myocarditis
I40.1Isolated myocarditis
I40.8Other acute myocarditis
I40.9Acute myocarditis, unspecified
I73.0Raynaud's syndrome
I73.00Raynaud's syndrome without gangrene
I73.01Raynaud's syndrome with gangrene
J99Respiratory disorders in diseases classified elsewhere
L63Alopecia areata
L63.0Alopecia (capitis) totalis
L63.1Alopecia universalis
L63.8Other alopecia areata
L63.9Alopecia areata, unspecified
L64Androgenic alopecia
L64.0Drug-induced androgenic alopecia
L64.8Other androgenic alopecia
L64.9Androgenic alopecia, unspecified
L65Other nonscarring hair loss
L65.2Alopecia mucinosa
L66Cicatricial alopecia [scarring hair loss]
L66.8Other cicatricial alopecia
L66.9Cicatricial alopecia, unspecified
L93Lupus erythematosus
L93.0Discoid lupus erythematosus
L93.1Subacute cutaneous lupus erythematosus
L93.2Other local lupus erythematosus
M32Systemic lupus erythematosus (SLE)
M32.0Drug-induced systemic lupus erythematosus
M32.10Systemic lupus erythematosus, organ or system involvement unspecified
M32.8Other forms of systemic lupus erythematosus
M32.9Systemic lupus erythematosus, unspecified
N08Glomerular disorders in diseases classified elsewhere
N16Renal tubulo-interstitial disorders in diseases classified elsewhere
N70Salpingitis and oophoritis
N72Inflammatory disease of cervix uteri
N73Other female pelvic inflammatory diseases
N73.0Acute parametritis and pelvic cellulitis
N73.3Female acute pelvic peritonitis
N73.9Female pelvic inflammatory disease, unspecified
N74Female pelvic inflammatory disorders in diseases classified elsewhere
N88Other noninflammatory disorders of cervix uteri
N89Other noninflammatory disorders of vagina
N90Other noninflammatory disorders of vulva and perineum
O09Supervision of high risk pregnancy
O26Maternal care for other conditions predominantly related to pregnancy
O36.01Maternal care for anti-D [Rh] antibodies
O98.1Syphilis complicating pregnancy, childbirth and the puerperium
O98.51Other viral diseases complicating pregnancy
O98.52Other viral diseases complicating childbirth
O98.53Other viral diseases complicating the puerperium
O99.01Anemia complicating pregnancy
O99.280Endocrine, nutritional and metabolic diseases complicating pregnancy, unspecified trimester
O9A.41Sexual abuse complicating pregnancy
O9A.42Sexual abuse complicating childbirth
Q84.0Congenital alopecia
R41Other symptoms and signs involving cognitive functions and awareness
T74.2Sexual abuse, confirmed
T74.21Adult sexual abuse, confirmed
T74.21XAAdult sexual abuse, confirmed, initial encounter
T74.22Child sexual abuse, confirmed
T76.2Sexual abuse, suspected
T76.21Adult sexual abuse, suspected
T76.21XAAdult sexual abuse, suspected, initial encounter
T76.21XDAdult sexual abuse, suspected, subsequent encounter
T76.21XSAdult sexual abuse, suspected, sequela
T76.22Child sexual abuse, suspected
T76.22XAChild sexual abuse, suspected, initial encounter
T76.22XDChild sexual abuse, suspected, subsequent encounter
T86.4Complications of liver transplant
T86.40Unspecified complication of liver transplant
T86.41Liver transplant rejection
T86.42Liver transplant failure
T86.43Liver transplant infection
T86.49Other complications of liver transplant
Z04.4Encounter for examination and observation following alleged rape
Z04.41Encounter for examination and observation following alleged adult rape
Z04.42Encounter for examination and observation following alleged child rape
Z34Encounter for supervision of normal pregnancy
Z34.8Encounter for supervision of other normal pregnancy
Z48.23Encounter for aftercare following liver transplant
Z94.4Liver transplant status


  • Sex Transm Dis. 1998;25:569. [PMID:9858355]
  • Int J STD AIDS. 1995 Jul-Aug;6(4):241-8. [PMID:7548285]
  • J Emerg Med. 2000;18:361. [PMID:10729677]
  • Dermatol Clin .2006;24:497. [PMID:17010778]
  • Stevens CD. Clinical Immunology & Serology: A Laboratory Perspective 3rd edition. Philadelphia: F.A. Davis Company (2010).