Syphilitic hepatitis: an increasingly common presentation of an epidemic disease

To the Editor: The incidence of syphilis is dramatically rising in Australia. As such, previously rare sequelae like syphilitic hepatitis are occurring more frequently, supported by a growing number of case reports in the literature.1 We present a typical case of syphilitic hepatitis and review the evolving at‐risk populations, to raise awareness of this potentially fatal yet highly treatable disease.

A 34‐year‐old Caucasian man presented with a maculopapular rash over the trunk and limbs associated with abdominal discomfort, anorexia and fatigue. He had been treated for early syphilis 2 years previously, with serological evidence of response. He had no history of human immunodeficiency virus infection. He was married with children and denied other sexual relationships. Aside from the aforementioned rash, his examination was unremarkable. His alkaline phosphatase level was 684 U/L (reference interval [RI], 50–130 U/L), $\gamma$‐glutamyl transpeptidase was 942 U/L (RI, < 55 U/L), alanine aminotransferase was 429 U/L (RI, < 45 U/L), and aspartate aminotransferase was 181 U/L (RI, 5–35 U/L); bilirubin was 18 μmol/L (RI, < 20 μmol/L) and C‐reactive protein (CRP) was 55 mg/L (RI, < 5 mg/L). Abdominal ultrasound and extensive liver screen results were normal. Treponema pallidum particle agglutination assay and rapid plasma reagin test results were reactive at a 1:32 titre, prompting a diagnosis of syphilitic hepatitis. He was administered 2.4 million units of benzathine benzylpenicillin intramuscularly once‐weekly for 3 weeks. His rash, symptoms and liver function tests resolved within 6 weeks.

The Australian notification rate of syphilis increased from 5.0 to 18.3 per 100 000 population between 2010 and 2017. Women aged 15–19 years experienced a tenfold increase in incidence over this period. In 2017, women from remote areas were 27.3 times more likely to contract syphilis than those from major cities, while Aboriginal and Torres Strait Islander people were 6.6 times more likely to contract syphilis than non‐Indigenous Australians.2 Despite this disproportionate rise in vulnerable populations, rates remain highest among men who have sex with men and those with human immunodeficiency virus infection.3,4 Re‐infection is common, as was found in our patient.

Described as the “great imitator”, secondary syphilis can be difficult to diagnose; consequently, the true incidence of syphilitic hepatitis is not known. While our case illustrates a typical presentation, cases of fulminant liver failure have been described.5 Rash (78%), anorexia (57%) and fatigue (57%) are the most common presenting symptoms.1 Marked elevation of alkaline phosphatase and $\gamma$‐glutamyl transpeptidase, coupled with milder elevation of alanine aminotransferase and aspartate aminotransferase are the most common laboratory findings, with hyperbilirubinaemia present only in severe cases. A liver biopsy is not essential for diagnosis, but may reveal inflammatory infiltration of the bile duct, hepatic granulomas or, less commonly, intrahepatic spirochetes via immunohistochemical staining.1

It is imperative that clinicians consider ordering treponemal serology in high risk patients fitting this presentation, as prompt treatment with penicillin leads to rapid disease resolution and aversion of tertiary complications, including death.