Syphilitic Hepatitis

Abstract

40 year-old woman with a history of Guillain-Barré syndrome, Bell's Palsy, hypertension, and migraines presented with jaundice with aspartate aminotransferase (AST) 172 U/L, alanine aminotransferase (ALT) 230 U/L, total bilirubin 6.0 mg/dL, direct bilirubin 3.6 mg/dL, and alkaline phosphatase 412 U/L. Full viral hepatitis serologies and anti-smooth muscle Ab were negative, anti-nuclear antibodies (ANA) was positive at 1:640 with a normal IgG level. MRI/MRCP demonstrated a normal appearing liver with a few prominent retroperitoneal lymph nodes. Labs on follow-up six weeks later demonstrated AST 144 U/L, ALT 222 U/L, total bilirubin 15.0, direct bilirubin 9.1, alkaline phosphatase 866 U/L with a positive Antimitochondrial Antibody (AMA) at 1:320. Percutaneous liver biopsy demonstrated organizing microabscesses, mild mixed portal inflammation with bile duct damage, endotheliitis of portal veins, and mild lobular mixed inflammation. After biopsy, she developed a hyperpigmented papulosquamous rash affecting bilateral palms and forearms. Serum rapid plasma regain (RPR) was 1:32768 with positive serum syphilis IgG Ab and negative HIV testing. She was treated with a two-week course of continuous IV Penicillin G 24 million units daily, with resolution of liver chemistries one-month later. While Warthin Starry stain of her liver biopsy at our institution was negative for spirochetes, the Centers for Diseases Control (CDC) reported positive Treponema spp. immunohistochemistry confirming syphilitic hepatitis. Liver abnormalities characterized by a disproportionally elevated alkaline phosphatase and normal or mildly increased bilirubin and aminotransferases are reported in 30-40% of early syphilis cases, and typically rapidly normalize with antibiotic treatment. However, severe cholestasis, jaundice, and one episode of acute liver failure has been reported. As in our patient, AMA positivity has been reported with syphilitic hepatitis. There are nine mitochondrial autoantigens (M1-9), of which M2 is specific for primary biliary cholangitis (PBC). In syphilis, antibodies to cardiolipin (M1) can form which explains the positive result. M1 and M2 can be distinguished by M2-specific ELISA testing. Early syphilis is on the rise in the US, and must remain on the differential for clinicians evaluating acute cholestatic liver injury. Furthermore, clinicians must be aware of the potential false-positive AMA, as the pattern of liver injury could be confused with PBC.Figure: Histologic sections of the liver demonstrate organizing microabscesses, composed of numerous neutrophils, lymphocytes, plasm cells, and histiocytes. H&E stain, original magnification 400x.Figure: Histologic sections of the hepatic portal tracts demonstrate mild mixed inflammation with bile duct damage (larger arrows) and endothelitis of portal veins (smaller arrows). Periportal hepatocytes show intracytoplasmic cholestasis (arrowheads). H&E stain, original magnification 400x.Figure: Hyperpigmented papulosquamous rash affecting the patient's bilateral palms and forearms.