**Background:** Syphilitic hepatitis is a rare but established cause of acute hepatitis. Over the past two decades, syphilis incidence has risen, particularly among adolescents. The infection is caused by the spirochete *Treponema pallidum* and progresses through primary, secondary, latent, and tertiary stages. Diagnosis of syphilitic hepatitis is challenging because clinical presentation, laboratory abnormalities, and histologic features are nonspecific. The authors present this case to raise awareness among pediatric gastroenterologists about the importance of syphilis screening in sexually active adolescents with acute hepatitis.
**Methods:** This is a single case report of a 19-year-old patient admitted to the Hepatology service for acute hepatitis. The authors describe the clinical presentation, laboratory workup, imaging, serologic testing, treatment, and follow-up. Laboratory parameters including ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and INR were tracked at presentation (day 0), day 1, week 1, month 1, and month 4 following initiation of penicillin therapy.
**Key Results:** The patient presented with 1.5 weeks of generalized abdominal pain, weight loss, and jaundice. Initial labs showed ALT 2004 IU/L, AST 1594 IU/L, direct bilirubin 6.1 mg/dL, and INR 1.3. Abdominal ultrasound was normal. Extensive workup for viral hepatitis (A, B, C), EBV, CMV, autoimmune hepatitis, Wilson disease, thyroid disease, celiac disease, and alpha-1 antitrypsin deficiency was negative or not consistent with acute disease. Total serum IgG was elevated at 2190 mg/dL (reference: 613–1295 mg/dL). Further history revealed a self-resolving diffuse nonpruritic erythematous papular rash and an ulcerated penile lesion. RPR was positive at 1:128 titer, and T. pallidum particle agglutination was positive, confirming syphilis. HIV testing was negative. The patient received intramuscular benzathine penicillin (3 weekly doses for presumed latent syphilis). At 1-month follow-up, ALT had decreased to 220 IU/L (from 2023 IU/L at day 0) and direct bilirubin to 0.7 mg/dL (from 6.3 mg/dL). At 4-month follow-up, all laboratory parameters had normalized: ALT 18 IU/L, AST 28 IU/L, alkaline phosphatase 68 IU/L, total bilirubin 1.4 mg/dL, direct bilirubin 0.2 mg/dL, albumin 5.2 g/dL, and INR 1.10. Serum IgG also normalized after treatment. The authors note that the patient's ALT and AST were uncharacteristically high and alkaline phosphatase uncharacteristically low compared to prior reports of syphilitic hepatitis.
**Clinical Implications:** This case demonstrates that syphilitic hepatitis should be considered in the differential diagnosis of acute hepatitis in sexually active adolescents, even when transaminase elevations are extreme. The rising incidence of syphilis among adolescents — with 55% of reported STIs in 2019 occurring in 15–24 year olds, and a 179% increase in syphilis among women from 2015–2019 — makes provider awareness essential. Diagnosis relies on clinical suspicion and targeted serologic testing; liver biopsy is not required. Treatment with penicillin leads to rapid clinical and biochemical improvement. The authors emphasize that syphilis is an ideal candidate for public health eradication given its lack of an animal reservoir, availability of inexpensive diagnostic tests, and curative treatment, but this requires improved screening and provider education across general pediatric and subspecialty settings.