What is the interpretation and management plan for a 16-year-old female with a palmar rash, suspected secondary syphilis, elevated liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (Gamma GT)), and elevated ferritin?

Lab Interpretation for 16-Year-Old Female with Palmar Rash and Suspected Secondary Syphilis

Key Laboratory Findings

Your patient's labs show a hepatitic pattern strongly suggestive of syphilitic hepatitis, which is a well-documented but often overlooked manifestation of secondary syphilis. 1, 2

Abnormal Results Consistent with Syphilitic Hepatitis:

• Elevated transaminases: ALT 82 U/L (normal <36) and AST 63 U/L (normal <36) 1, 2
• Markedly elevated Gamma GT: 52 U/L (normal 7-21) - this disproportionate elevation is characteristic of syphilitic hepatitis 1, 2
• Elevated ferritin: 171 ug/L (normal 12-95) - reflects acute phase response 1
• Lymphocytosis: 5.9 x10^9/L (normal 1.0-3.6) with relative neutropenia 1.6 x10^9/L (normal 1.8-6.8) - this pattern is typical of secondary syphilis 1, 3

Normal Results That Are Reassuring:

• Normal bilirubin (10 umol/L) - indicates hepatitis without significant cholestasis 2
• Normal alkaline phosphatase (109 U/L) - though some cases show disproportionate ALP elevation 1, 2
• Negative pregnancy test - excludes pregnancy-related considerations 4
• Normal renal function - no systemic complications 1

Clinical Interpretation

The combination of palmar rash, elevated liver enzymes (particularly Gamma GT), and lymphocytosis with neutropenia creates a highly specific pattern for secondary syphilis. 1, 2, 3

Why This Pattern Matters:

• Syphilitic hepatitis occurs during secondary syphilis and presents with cholestatic enzyme elevation (Gamma GT) more prominently than transaminases 1, 2
• The hepatitic pattern typically shows AST/ALT elevation with disproportionately elevated alkaline phosphatase or Gamma GT 1, 2
• Hepatomegaly may be present clinically even when not documented 1
• This presentation is often misdiagnosed as viral hepatitis or alcoholic liver disease 5

Immediate Management Plan

1. Complete Syphilis Serologic Testing (If Not Already Done):

• Nontreponemal test (RPR or VDRL) - will be positive in secondary syphilis with titers typically ≥1:8 4, 6
• Treponemal test (FTA-ABS or TP-PA) - confirms true infection versus false-positive 4, 6
• Both tests should be positive in secondary syphilis with high titers 4

2. Mandatory HIV Testing:

• All patients with syphilis must be tested for HIV - this is non-negotiable 4, 6
• HIV coinfection affects monitoring frequency (every 3 months instead of 6 months) and increases neurosyphilis risk 4, 7
• HIV-infected patients may have atypical presentations and more severe manifestations 8, 3

3. Clinical Examination for Systemic Involvement:

• Examine all mucosal surfaces (oral cavity, perianal area, vagina) for mucous patches or condyloma lata 8
• Assess for lymphadenopathy - generalized adenopathy is common in secondary syphilis 8, 3
• Screen for neurologic symptoms: headache, vision changes, hearing loss, cranial nerve deficits 4, 7
• Screen for ocular symptoms: uveitis, optic neuritis 4, 7

4. Consider CSF Examination If:

• Any neurologic or ocular symptoms are present 4, 7
• Patient is HIV-positive 8, 4
• Some specialists recommend CSF examination before treatment in HIV-infected persons with early syphilis 8

Treatment Recommendation

Treat immediately with benzathine penicillin G 2.4 million units IM as a single dose without waiting for confirmatory serology if clinical suspicion is high. 4, 6, 9

Treatment Rationale:

• The CDC recommends empiric treatment for suspected secondary syphilis in high-risk patients or those at risk for loss to follow-up 4
• Standard treatment for secondary syphilis is benzathine penicillin G 2.4 million units IM single dose 8, 4, 9
• Administer by deep intramuscular injection in the upper outer quadrant of the buttock 9

Expected Response:

• Jarisch-Herxheimer reaction may occur within 24 hours - warn the patient about fever, headache, and myalgia 8
• Liver enzymes should normalize within 3 months after appropriate antibiotic treatment 2
• Rash should resolve with treatment 1, 2

Penicillin Allergy Alternative:

• If truly penicillin-allergic: doxycycline 100 mg orally twice daily for 14 days 8
• However, penicillin desensitization is preferred if compliance or follow-up is uncertain 8

Follow-Up Plan

Serologic Monitoring:

• Recheck RPR at 6 and 12 months after treatment for secondary syphilis 4, 6
• Use the same nontreponemal test (RPR or VDRL) by the same laboratory for all follow-up 4, 6
• Treatment success: fourfold decline in RPR titer within 6-12 months 4, 6

If HIV-Positive:

• More frequent monitoring required: at 3,6,9,12, and 24 months 8, 4
• Consider CSF examination 6 months after therapy 8

Liver Enzyme Monitoring:

• Recheck liver enzymes at 3 months to confirm normalization 2
• Persistent elevation suggests treatment failure or alternative diagnosis 2

Partner Notification

Identify and notify all sexual contacts from the past 6 months plus duration of symptoms. 4

• Partners should be examined, tested, and treated presumptively 8, 4
• Partners exposed within 90 days should be treated presumptively even if seronegative 8

Critical Pitfalls to Avoid

• Do not delay treatment waiting for serologic confirmation if clinical presentation is classic 4
• Do not miss HIV testing - this is mandatory for all syphilis cases 4, 6
• Do not overlook neurosyphilis screening - ask specifically about neurologic and ocular symptoms 4, 7
• Do not assume viral hepatitis - syphilitic hepatitis is often misdiagnosed as viral or alcoholic hepatitis 5, 10
• Do not use alternative antibiotics without close follow-up - penicillin remains the gold standard 8