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Syphilis, Emergency Medicine

Basics

Description

- Secondary syphilis: - Replication and hematogenous spread - Begins 3 " 6 wk after primary lesion - Late latent secondary phase

- 21-day incubation period - No constitutional symptoms - Chancre: - Painless papule at site of inoculation - Clean-based, circular, sharply defined borders: - Solitary lesions - Commonly on penis, vulva, and rectum - Bilateral regional lymphadenopathy

- Occurs 3 " 6 wk after primary lesion - Disseminated stage - Rash (most common): - Symmetric, diffuse, polymorphous, papular, or maculopapular rash - Rash may be diverse and not fit a pattern - Starts on trunk and flexor extremities - Spreads to involve palms and soles: - Discrete, red/reddish-brown - 0.5 " 2 cm in diameter

- Condyloma lata: - Large raised gray/white lesions, painless, moist - Mucous membranes: - Oral cavity and perineum - Very contagious - Intertriginous areas - Flat rectal warts

- Less common: - "Moth-eaten " alopecia - Syphilitic meningitis - Scleritis

- Cardiovascular: - Thoracic aortic aneurysm (ascending most common): - Dilated aorta and aortic valve regurgitation - Aortic valve insufficiency - Coronary thrombosis - Destructive lesions of skeletal structures or skin

- Serology: - Nontreponemal test: - RPR - VDRL - Positive 14 days after chancre appears - Early false negatives, especially ≤7 days after primary chancre - Repeat negative test in 2 wk and correlate with disease activity - False positives in 1 " 2% of general population - 4-fold change in titer clinically significant - 100% sensitivity in secondary syphilis - Nonreactive after successful treatment

- Treponemal antibody test: - Fluorescent treponemal antibody absorption (FTA " ABS) - Hemagglutination assay for antibody to T. pallidum (MHA " TP) - More sensitive and specific - 1% false-positive rate - Confirmatory test - Reactive for patients lifetime - More costly and harder to perform

- Dark-field microscopy: - Identifies treponemes from primary and secondary lesions - Suspicious early lesions with negative serology (early primary syphilis) - False negatives with ointments, creams - Oral specimen unsuitable

- Lymphogranuloma venereum - Granuloma inguinale - Superficial fungal infection - Carcinoma

- Jarisch " Herxheimer reaction: - Transient febrile reaction to therapy - May be owing to antigen liberation from spirochetes or activation of complement cascade - Peaks at 8 hr, resolves in 24 hr - Symptoms: - Fever, headache, malaise, worsening rash

- Recommended testing: - Sexual partners - Concomitant sexually transmitted diseases including HIV - Repeat serology test in 6 and 12 mo.

- Early primary, secondary, early latent (<1 yr): - Benzathine penicillin G: 2.4 million U IM - Doxycycline: 100 mg PO BID for 14 days - Tetracycline: 500 mg PO QID for 14 days

  • Sexually transmitted disease
  • 12 million new cases diagnosed annually worldwide
  • Acquired via mucous membranes/disrupted skin
  • Divided into 3 stages:Primary syphilis:Painless chancre or ulcerSecondary syphilis:Replication and hematogenous spreadBegins 3 " 6 wk after primary lesionLate latent secondary phaseTertiary or late syphilis:Very uncommonCardiovascular and neurologic symptoms

Etiology

Treponema pallidum:

Diagnosis

Signs and Symptoms

Primary (Early) Syphilis

  • 21-day incubation period
  • No constitutional symptoms
  • Chancre:Painless papule at site of inoculationClean-based, circular, sharply defined borders:Solitary lesionsCommonly on penis, vulva, and rectumBilateral regional lymphadenopathyHeals spontaneously in 3 " 6 wk
  • Rectal chancre:Painful or painlessRectal irritation/dischargePainless enlargement of lymph nodes

Secondary (Early) Syphilis

  • Occurs 3 " 6 wk after primary lesion
  • Disseminated stage
  • Rash (most common):Symmetric, diffuse, polymorphous, papular, or maculopapular rashRash may be diverse and not fit a patternStarts on trunk and flexor extremitiesSpreads to involve palms and soles:Discrete, red/reddish-brown0.5 " 2 cm in diameter
  • Condyloma lata:Large raised gray/white lesions, painless, moistMucous membranes:Oral cavity and perineumVery contagiousIntertriginous areasFlat rectal warts
  • Systemic symptoms:Fever, headache, malaise, anorexia, sore throat, myalgias, and weight loss
  • Diffuse lymphadenopathy:Palpable nodes at inguinal, axillary, posterior cervical, femoral, and/or epitrochlear regionsPainless, firm, and rubbery
  • Less common: "Moth-eaten " alopeciaSyphilitic meningitisScleritis
  • Loss of lateral 3rd of eyebrows
  • Painless mucosal lesions (mucous patches)
  • Secondary stage resolves spontaneously in 1 " 2 mo

Latent Secondary Syphilis

  • Begins after primary and secondary symptoms resolve.
  • Period of no symptoms but positive serology:
  • Late latent stage not infectious except for fetal transmission in pregnant women
  • Persists for lifetime or develops into tertiary syphilis

Tertiary (Late) Syphilis

  • Occurs in about 15% of patients with untreated latent secondary syphilis
  • Can appear 10 " 20 yr after initial infection
  • Neurologic and cardiovascular involvement:Destructive stages of disease
  • Neurosyphilis (most common):Asymptomatic:Positive CSF " Venereal Disease Research Laboratories (VDRL)CSF pleocytosis (10 " 100 lymphocytes)Elevated CSF protein at 50 " 100 mg/dLMeningitis:Aseptic; CSF with positive VDRL, higher protein, and lower glucose (compared with above)Cranial nerve palsy, including isolated 8th nerve palsyGeneral paresis:Loss of cortical functionArgyll Robertson pupils (small fixed pupils that do not react to strong light, but do react to accommodative convergence)Tabes dorsalis (peripheral neuropathy)
  • Degeneration of posterior columns/posterior or dorsal roots of spinal cord
  • Dementia
  • Paresthesias, abnormal gait, and lightning (sudden, severe) pain of extremities/trunk
  • Progressive loss of reflexes, vibratory/position sensation
  • Positive Romberg sign
  • Vision: Optic atrophy
  • Pupils: Argyll Robertson pupils
  • Urinary incontinence
  • Gummas:Late benign syphilis of cutaneous skin/viscera:Bone, brain, abdominal viscera, etc.
  • Granulomatous, cellular hypersensitivity reaction:Round, irregular, or serpiginous shape "Great pox "
  • Cardiovascular:Thoracic aortic aneurysm (ascending most common):Dilated aorta and aortic valve regurgitationAortic valve insufficiencyCoronary thrombosisDestructive lesions of skeletal structures or skin
  • HIV-infected:Strong association with syphilis
  • Increased incidence of neurosyphilis

Congenital Syphilis

  • In utero infection:Age <2 yr:Hepatosplenomegaly, rash, condyloma lata, rhinitis (snuffles), jaundice (nonviral hepatitis), osteochondritis
  • Older children (syphilis stigmata):Interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, etc.

Essential Workup

Rapid plasma reagin (RPR)

Diagnosis Tests & Interpretation

Lab

  • Serology:Nontreponemal test:RPRVDRLPositive 14 days after chancre appearsEarly false negatives, especially ≤7 days after primary chancreRepeat negative test in 2 wk and correlate with disease activityFalse positives in 1 " 2% of general population4-fold change in titer clinically significant100% sensitivity in secondary syphilisNonreactive after successful treatmentTreponemal antibody test:Fluorescent treponemal antibody absorption (FTA " ABS)Hemagglutination assay for antibody to T. pallidum (MHA " TP)More sensitive and specific1% false-positive rateConfirmatory testReactive for patients lifetimeMore costly and harder to performDark-field microscopy:Identifies treponemes from primary and secondary lesionsSuspicious early lesions with negative serology (early primary syphilis)False negatives with ointments, creamsOral specimen unsuitableCSF analysis for tertiary neurosyphilis:Tertiary syphilisPositive VDRL/RPRLymphocytes >5/mLProtein >45 mg/dLDecreased glucose

Differential Diagnosis

  • Genital ulcer:Chancroid (painful)Genital herpes:Vesicular, multiple lesionsLymphogranuloma venereumGranuloma inguinaleSuperficial fungal infectionCarcinoma
  • Secondary and tertiary syphilis:Pityriasis roseaDrug-induced rashAcute febrile exanthemsPsoriasisLichen planusScabiesInfectious mononucleosisViral illnessBacteremiaTertiary syphilis:PsychosisDementiaMultiple sclerosisMeningitisEncephalitisDeliriumUnknown overdose

Treatment

Initial Stabilization/Therapy

Lower BP and establish IV access for aortic dissection.

Ed Treatment/Procedures

  • Treatment other than penicillin with increased relapse rate:Desensitize those allergic to penicillin.
  • Pregnancy:Treat with penicillin even in latent syphilis.If patient allergic to penicillin, admit for desensitization.
  • Jarisch " Herxheimer reaction:Transient febrile reaction to therapyMay be owing to antigen liberation from spirochetes or activation of complement cascadePeaks at 8 hr, resolves in 24 hrSymptoms:Fever, headache, malaise, worsening rashTreat with antipyreticsNo serious sequelae
  • Recommended testing:Sexual partnersConcomitant sexually transmitted diseases including HIVRepeat serology test in 6 and 12 mo.

Medication

  • Early primary, secondary, early latent (<1 yr):Benzathine penicillin G: 2.4 million U IMDoxycycline: 100 mg PO BID for 14 daysTetracycline: 500 mg PO QID for 14 days
  • Late latent (>1 yr) except neurosyphilis:Benzathine penicillin G: 2.4 million U IM 3 times over 2 wk on days 0, 7, and 14Doxycycline: 100 mg PO BID for 4 wkTetracycline: 500 mg PO QID for 4 wk
  • Neurosyphilis:Penicillin G: 3 " 4 million U IV q4h for 10 " 14 daysProcaine penicillin: 2.4 million U IM daily +Probenecid: 500 mg PO QID for 10 " 14 days
  • Congenital syphilis:Penicillin G: 50,000 U/kg IM q8 " 12h for 10 " 14 days; orProcaine penicillin: 50,000 U/kg IM daily for 10 " 14 days

Follow-Up

Disposition

Admission Criteria

  • Neurosyphilis requires IV antibiotics
  • Pregnant women allergic to penicillin requiring desensitization

Discharge Criteria

Follow-up care:

  • Measure for falling titers in 6 mo and 1 yr after treatment.
  • Tertiary/latent (>1 yr):Measure for falling titers in 3, 6, 12, and 24 mo after treatment.

Issues for Referral

Infectious disease consultation for secondary and tertiary syphilis as well as congenital and neurosyphilis

Followup Recommendations

Titers must be monitored.

Pearls and Pitfalls

  • Syphilis is known as the "great imitator. "
  • In patients presenting with unknown rash, think of syphilis and ask about history of genital lesions.
  • Be sure to examine mucous membranes of all patients presenting with rash.
  • Think of tertiary syphilis with neurologic symptoms of unknown etiology.

Additional Reading

  • Centers for Disease Control and Prevention (CDC). Primary and secondary syphilis " United States, 2003 " 2004. MMWR Morb Mortal Wkly Rep. 2006;55(10):269 " 273.
  • Domantay-Apostol GP, Handog EB, Gabriel MT. Syphilis: The international challenge of the great imitator. Dermatol Clin. 2008;26(2):191 " 201, v.
  • Grange PA, Gressier L, Dion PL, et al. Evaluation of a PCR test for detection of treponema pallidum in swabs and blood. J Clin Microbiol. 2012;50:546 " 552.
  • Hook EW 3rd, Peeling RW. Syphilis control " a continuing challenge. N Engl J Med. 2004;351:122 " 124.
  • Schacter J. Classification of latent syphilis. Sex Transm Dis. 2005;32:143.
  • Sparling PF. Diagnosis of neurosyphilis: New tools. Sex Transm Dis. 2010;37:288 " 289.
  • Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004;75:1727 " 1730.
  • Tramont EC. Treponema pallidum (syphilis). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennetts Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2009, Chapter 238.

Codes

ICD9

  • 091.2 Other primary syphilis
  • 091.9 Unspecified secondary syphilis
  • 097.9 Syphilis, unspecified
  • 097.1 Latent syphilis, unspecified
  • 097.0 Late syphilis, unspecified
  • 097 Other and unspecified syphilis

ICD10

  • A51.0 Primary genital syphilis
  • A51.49 Other secondary syphilitic conditions
  • A53.9 Syphilis, unspecified
  • A52.8 Late syphilis, latent
  • A52.9 Late syphilis, unspecified
  • A53.0 Latent syphilis, unspecified as early or late

SNOMED

  • 76272004 Syphilis (disorder)
  • 266127002 Primary syphilis (disorder)
  • 240557004 Secondary syphilis (disorder)
  • 444150000 Latent syphilis (disorder)
  • 402940004 Syphilitic chancre of penis (disorder)
  • 402944008 Condylomata lata of perianal skin (disorder)
  • 402946005 Condylomata lata of vulva (disorder)
  • 66887000 Late syphilis, latent (positive serology, negative cephalospinal fluid 2 years after) (disorder)
  • 72083004 Late syphilis (disorder)