Can Venereal Disease Research Laboratory (VDRL)-positive syphilis and Human Immunodeficiency Virus (HIV) infection cause transaminitis?

Can Syphilis and HIV Cause Transaminitis?

Yes, both syphilis (particularly secondary syphilis) and HIV can cause transaminitis, with syphilitic hepatitis being a well-recognized manifestation that presents with a characteristic cholestatic pattern of liver injury, especially in patients co-infected with both conditions. 1

Syphilitic Hepatitis as a Cause of Transaminitis

Clinical Presentation

• Syphilitic hepatitis is a recognized manifestation of secondary syphilis that presents with elevated liver enzymes in a cholestatic pattern 1
• The typical pattern includes disproportionately elevated alkaline phosphatase (ALP) relative to transaminases, though both AST and ALT are elevated 1, 2
• In documented cases, ALP can reach 648 unit/L, AST 251 unit/L, and ALT 409 unit/L in the setting of secondary syphilis 1

Association with HIV Co-infection

• Syphilitic hepatitis is more commonly seen in patients co-infected with both syphilis and HIV 1
• The combination of HIV and syphilis appears to increase the likelihood of hepatic involvement compared to syphilis alone 1
• A case series demonstrated that 29.8% of syphilis patients were HIV co-infected, highlighting the frequency of this dual diagnosis 3

Diagnostic Approach to Unexplained Transaminitis

Key Laboratory Findings

• Patients with syphilitic hepatitis typically have reactive RPR with titers often ≥1:64 and positive treponemal tests (TPPA or FTA-ABS) 1
• The cholestatic pattern (elevated ALP out of proportion to transaminases) is the characteristic biochemical signature 1, 2
• Liver biopsy can confirm syphilitic hepatitis when the diagnosis is uncertain 2

Critical Clinical Pitfall

• Primary care physicians must include infectious etiologies—specifically syphilis and HIV—in the differential diagnosis of any patient presenting with unexplained liver dysfunction in a cholestatic pattern 1
• This is particularly important given the rising incidence of syphilis in the United States over the past 15 years 1

HIV-Specific Considerations

Atypical Presentations in HIV

• HIV-infected patients may have atypical serologic responses with unusually low, high, or fluctuating titers 4, 5
• Concomitant uveitis and meningitis might be more common among HIV-infected patients with syphilis 4
• False-negative serologic tests have been reported among HIV-infected patients with documented T. pallidum infection, though this is rare 4

Screening Recommendations

• All patients diagnosed with syphilis must be tested for HIV infection 5, 6
• HIV-infected patients require more frequent monitoring at 3-month intervals rather than 6-month intervals 5
• HIV-infected patients with late-latent syphilis require CSF examination to rule out neurosyphilis 5, 6

Treatment and Resolution

Response to Therapy

• Syphilitic hepatitis responds to standard penicillin therapy for the appropriate stage of syphilis 2
• A 14-day course of penicillin for neurosyphilis resulted in near full biochemical recovery in documented cases 2
• The rate of cure with three-dose benzathine penicillin regimen is excellent (92.2%) even in HIV co-infected patients 3

Monitoring Treatment Response

• Treatment success is defined by a fourfold decline in nontreponemal test titers (RPR/VDRL) within 6-12 months for early syphilis 5
• HIV patients with CD4 count <500 cells/μL may have slower serological response to treatment, particularly in primary syphilis 7

Clinical Bottom Line

When evaluating transaminitis with a cholestatic pattern, always obtain syphilis serology (both nontreponemal and treponemal tests) and HIV testing, as syphilitic hepatitis is a treatable cause that is increasingly common, particularly in HIV-positive patients 1. The diagnosis is often missed because clinicians fail to consider infectious etiologies in the differential diagnosis of liver dysfunction 1.