Molecular Characterization of Treponema pallidum pallidum in an Adolescent With Syphilitic Hepatitis

To the Editors: In Argentina, an increase in the rate of syphilis has been observed over the past years in adolescents and young adults, raising the need for improved clinical awareness of this disease presentation.1 Concurrently, the availability of molecular biology techniques has significantly enhanced Treponema pallidum pallidum (TPA) detection in complex clinical contexts.2 Molecular epidemiology studies substantiate a global diversity of the TPA strains such as SS14 and Nichols, but little is known about the genetic patterns related to different organ susceptibility, especially in pediatric syphilis. Here we present a 14-year-old girl from Buenos Aires admitted at the Ricardo Gutierrez Children’s Hospital in July 2023 with a 4-week history of intermittent abdominal pain, jaundice and choluria. Physical examination was otherwise unremarkable. Initial labs revealed abnormal liver enzymes (total bilirubin: 11 mg/dL; conjugated bilirubin: 9.5 mg/dL, alanine aminotransferase: 870 IU/L, aspartate aminotransferase: 627 IU/L, alkaline phosphatase: 138 IU/L, gamma-glutamyl transferase: 96 IU/L) (Table 1). The patient was sexually active and anamnesis revealed a history of rash on the palms and trunk 2 weeks before admission. Hepatitis A, B, C and autoimmune hepatitis markers were negative. Rapid plasma reagin test (RPR) and a TPA chemiluminescence immunoassay were both reactive (RPR titer 1:64) confirming a diagnosis of syphilitic hepatitis (SH). The patient was treated with intravenous Penicillin G sodium at 300,000 IU/kg/d for 10 days. A Jarisch-Herxheimer reaction (body temperature of 37.6 ºC and generalized exanthema) was observed during the first day of treatment. TABLE 1. - Trend of Biochemical and qPCR Testing Determination At Diagnosis End of Treatment Four Weeks After Treatment RPR titers 1:64 ND 1:16 TPA CMIA signal to cutoff ratio (s/co) Positive s/co:30.62 ND Positive s/co:35.16 Total bilirubin, mg/dL 11 2.62 1.05 Conjugated bilirubin, mg/dL 9.5 2.31 0.71 ALT, IU/L 870 97 23 AST, IU/L 627 50 23 Alkaline phosphatase, IU/L 138 144 163 GGT,IU/L 96 52 31 Albumin, g/dL 5 4.1 4.6 INR 1.1 ND 1.1 ANA titers 1:640 ND 1:320 qPCR tpp47 on blood Positive Negative Negative qPCR tpp47 on oral samples Positive Negative ND ALT indicates alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate aminotransferase; CMIA, chemiluminescent microplate immunoassay; GGT, gamma-glutamyl transferase; INR, international normalized ratio; ND, not determined. Peripheral blood and oral swab samples were taken at diagnosis and 4 weeks after treatment for TPA real-time PCR (qPCR), gen tpp47. Both samples were positive at diagnosis. Additionally, multilocus sequence typing for TP0136, TP0548 and TP0705 TPA genes was performed.3 TP0548, TP0136, TP0705 and 23S rDNA locus were amplified and sequenced in blood and swab samples. The multilocus sequence typing scheme obtained allowed the identification of a 1.1.1 SS14-like strain profile of TPA. The analysis of 23S rDNA determined the absence of mutations associated with macrolide resistance. After treatment, clinical improvement of the patient was observed and liver enzymes decreased to normal values. In addition, a 2-fold decline in RPR titers and a negative TPA qPCR were registered 4 weeks after treatment. Few cases of SH have been reported in people younger than 18 years of age.4,5 Syphilis should be considered in the differential diagnosis of hepatitis in sexually active adolescents with liver dysfunction. As far as we know, this is the first case of TPA characterization by molecular biology techniques in SH. Further research is needed to better understand TPA strains’ relationship with organ compromise in patients with syphilis.