What are the symptoms and treatment of syphilis?

Symptoms and Treatment of Syphilis

Syphilis is a systemic disease caused by Treponema pallidum that progresses through distinct clinical stages with varied manifestations, requiring stage-specific treatment with parenteral penicillin G as the preferred therapy for optimal outcomes.

Clinical Stages and Symptoms

Primary Syphilis

• Characterized by a painless ulcer or chancre at the site of infection, typically accompanied by regional lymphadenopathy 1, 2
• The chancre is usually single, painless, indurated, and appears at the site of sexual contact 1, 2
• Multiple or atypical chancres may occur in HIV-infected individuals, and primary lesions might be absent or missed 1
• The primary lesion heals spontaneously within 3-6 weeks even without treatment 2

Secondary Syphilis

• Occurs 2-8 weeks after primary infection when T. pallidum disseminates throughout the body 1, 2
• Characterized by:
  • Skin eruptions (macular, maculopapular, papulosquamous, or pustular) that typically begin on the trunk and spread peripherally, involving palms and soles 1, 3
  • Generalized lymphadenopathy 1
  • Constitutional symptoms including fever, malaise, headache, anorexia, and arthralgias 1
  • Condyloma lata (moist, flat, papular lesions in warm intertrigenous regions) 1
  • Mucocutaneous lesions including mucous patches in the oral cavity 2, 4
• Secondary syphilis can mimic acute primary HIV infection with constitutional symptoms and CSF abnormalities 1
• Symptoms resolve spontaneously after several weeks, even without treatment 2

Latent Syphilis

• Characterized by positive serologic tests without clinical manifestations 1, 5
• Early latent syphilis: infection within the preceding year 5
• Late latent syphilis: infection of more than one year's duration 5
• Relapses of secondary manifestations may occur, most commonly during the first 1-4 years 1

Tertiary Syphilis

• Occurs in approximately 25% of untreated patients after 3-12 years of latency 2
• Manifestations include:
  • Gummatous lesions (granulomatous lesions affecting skin and internal organs) 1, 2
  • Cardiovascular syphilis (aortic aneurysm, aortic regurgitation) 1, 6
  • Neurologic involvement (tabes dorsalis, general paresis) 1, 2
  • Ophthalmic, auditory, or other organ system involvement 1

Neurosyphilis

• Can occur at any stage of infection 1
• Asymptomatic neurosyphilis: CSF abnormalities without clinical symptoms 1
• Symptomatic neurosyphilis: meningitis, meningovascular disease, or parenchymatous involvement 1
• May present with cranial nerve palsies, uveitis, or other ocular manifestations 1

Diagnosis

• Darkfield examination and direct fluorescent antibody tests of lesion exudate or tissue are definitive methods for diagnosing early syphilis 1
• Serologic testing involves two types of tests 1:
  • Nontreponemal tests (VDRL, RPR) - correlate with disease activity and should be reported quantitatively
  • Treponemal tests (FTA-ABS, MHA-TP) - remain positive for life in most cases
• Use of only one type of test is insufficient for diagnosis due to potential false positives 1
• A fourfold change in nontreponemal test titer (equivalent to two dilutions) is considered clinically significant 1
• HIV-infected patients may have atypical serologic responses 5

Treatment

Primary and Secondary Syphilis

• Recommended regimen: Benzathine penicillin G 2.4 million units IM in a single dose 1, 5
• Alternative for penicillin-allergic non-pregnant adults: Doxycycline 100 mg orally twice daily for 14 days 5, 7

Early Latent Syphilis

• Recommended regimen: Benzathine penicillin G 2.4 million units IM in a single dose 5
• Alternative for penicillin-allergic non-pregnant adults: Doxycycline 100 mg orally twice daily for 14 days 5, 7

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Recommended regimen: Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals 1, 5
• Alternative for penicillin-allergic non-pregnant adults: Doxycycline 100 mg orally twice daily for 28 days 5, 7

Tertiary Syphilis

• Recommended regimen: Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals 1, 5

Neurosyphilis

• Recommended regimen: Aqueous crystalline penicillin G 18-24 million units a day, administered as 3-4 million units IV every 4 hours for 10-14 days 1, 5
• Alternative regimen: Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg orally four times a day, both for 10-14 days 1

Special Considerations

HIV Co-infection

• HIV-infected patients may have more apparent clinical lesions and accelerated progression of syphilitic disease 1
• Treatment regimens are the same as for non-HIV-infected patients 5
• All patients with syphilis should be tested for HIV 1

Pregnancy

• Pregnant women should be treated with penicillin regimens appropriate for their stage of syphilis 5
• Pregnant women with penicillin allergy should undergo desensitization and receive penicillin 5

Jarisch-Herxheimer Reaction

• An acute febrile reaction that may occur within 24 hours after treatment, especially in early syphilis 1, 5
• Characterized by fever, headache, myalgia, and other symptoms 1
• May induce early labor or cause fetal distress in pregnant women 1

Management of Sex Partners

• Partners exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 1, 5
• Partners exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 1, 5

Follow-Up

• Quantitative nontreponemal tests should be repeated at regular intervals (3,6,12, and 24 months) 5
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis 5
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 5

Common Pitfalls to Avoid

• Do not use oral penicillin preparations for syphilis treatment as they are ineffective 5
• Do not rely solely on treponemal test antibody titers to assess treatment response 1, 5
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response 1, 5
• Do not miss the diagnosis of neurosyphilis in patients with neurological symptoms 1
• Do not overlook syphilis in patients with uveitis, sudden deafness, or aortic aneurysm 4