Rapid progression to gummatous syphilitic hepatitis and neurosyphilis in a patient with newly-diagnosed HIV

Case

A 34-year-old homosexual man presented with severe dull headaches, left eye scotomas and blurred vision. One month prior, he was diagnosed with human immunodeficiency virus (HIV), but had not started anti-retroviral therapy. He reported a penile lesion and an evanescent truncal rash three months prior to presentation, for which he did not seek medical attention. Physical examination showed an injected left eye conjunctiva, a supple neck, a healing lesion on the penis, inguinal lymphadenopathy and no hepatosplenomegaly or jaundice. Neurological examination revealed normal mental status, a normal cranial nerve, motor, sensory and gait examination.

Laboratory findings showed an absolute CD4 count of 305 cells/µL (22%), HIV viral load of 255,748 copies/mL, and a cholestatic pattern with total bilirubin 19.6 µmol/L, direct bilirubin 4.9 µmol/L, AST 49 U/L, ALT 81 U/L, alkaline phosphatase 434 U/L, GGT 128 U/L, albumin 30 g/L and INR 1.09. Serologies showed that he was immune to hepatitis A but non-immune for hepatitis B; hepatitis C antibody was negative. A syphilis EIA screen was positive, with RPR titre 1:256. A lumbar puncture revealed 52 white cells/mm ³ (84% lymphocytes), protein 0.81 g/L, glucose 2.0 mmol/L and a positive CSF VDRL (titre of 1:8).

CT head and brain MRI showed normal brain parenchyma without lepto-meningeal enhancement. Ophthalmological exam revealed left eye acute panuveitis. An abdominal ultrasound showed multiple hypoechoic liver lesions consistent with gummatous lesions (Figure 1). He was treated with penicillin G 3 million units intravenously every 4 h with dramatic symptomatic improvement. The patient completed 14 days of antibiotic treatment. OPEN IN VIEWER

Several months later, his liver enzymes normalized and RPR titre decreased to 1:4. Repeat abdominal ultrasound showed complete resolution of the hepatic lesions.

Discussion

Since 2000, the incidence of syphilis, caused by Treponema pallidum, has been on the rise, particularly in men who have sex with men (MSM). ¹ The development of tertiary syphilis, defined as the presence of cardiovascular syphilis, neurosyphilis or gummas, is rare in the immunocompetent host in the post-penicillin era. ² However, the natural history of syphilis is altered by co-infection with HIV. Patients with HIV and syphilis co-infection are at greater risk for neurosyphilis ³ and disease progression is accelerated, ⁴ especially when the CD4 count drop below 350 cells/mm³. ⁵ Several cases of cerebral and skin gummatous lesions and single cases of testicular, bone and pulmonary gummatous lesions have been reported in the HIV population.^6,7 Gummatous hepatic involvement has not been previously reported in HIV patients to date.

Syphilitic hepatitis, also called luetic jaundice, was first described in 1585. ⁸ Liver involvement can occur at two periods after infection: the secondary stage, weeks to months after the initial chancre, or the tertiary stage when, after a variable latency period, organ involvement can occur in up to 30% of untreated patients. ⁹ Gummatous involvement of the liver is rarely documented, with incidences of 4.9–16% reported in a post-mortem series. ⁹ Gummatous disease of the liver consists of foci of hepatocellular necrosis with elevated number of spirochetes, associated with a granulomatous infiltrate. ¹⁰ Gummas vary in size, are usually multiple and coexist at different stages of transition from active to healed. Hepar lobatum refers to the distorted anatomy of the liver created by the scars of healed gummas. ⁹

The incidence of syphilitic liver involvement is difficult to assess in patients with HIV because of multiple confounders. Elevation of liver enzymes in this population can be due to multiple aetiologies including alcoholism, viral hepatitis, hepatotoxic drugs, fatty liver disease, opportunistic infections and neoplastic diseases. ¹¹ One large cohort study and a more recent small observational study have both reported that 19% of HIV patients co-infected with syphilis had elevations in liver enzymes not attributable to another aetiology and resolved with syphilis treatment.^1,11 In a recent, multicenter study, up to 30.6% of HIV patients co-infected with syphilis had elevations in liver enzymes. ¹² None of these studies evaluated for the presence of gummas on imaging or biopsy, so the incidence of gummatous involvement of the liver remains uncertain.

Ocular involvement in syphilis, most commonly uveitis, remains rare but is seen with increasing frequency, especially among the MSM and HIV-positive populations. ¹³ Unexplained ophthalmological abnormalities in the HIV-positive patient should trigger investigations for syphilis with serologic testing and CSF examination. ¹² Ocular syphilis may occur with or without CSF abnormalities and should be treated with a neurosyphilis regimen.^13,14

Conclusion

The natural history of syphilis can be drastically altered in HIV patients. In this population, especially patients with CD4 counts below 350 cells/mm³, syphilis can progress rapidly from primary infection to tertiary syphilis, including neurosyphilis and gummatous disease. We believe that careful study of the natural history of syphilis in HIV patients and increased awareness of the different disease evolution in this population are needed.