In Reply: Caution in Diagnosing Congenital Syphilis

To the Editors: We read with concern the article “Are We Playing It Fast and Loose With the Serofast” by Nelson et al.1 The authors describe four infants (1 singleton and a set of triplets) who they state have congenital syphilis, born to mothers who had received several courses of benzathine penicillin G before pregnancy but whose RPRs had remained serofast at 1:4. In 1 mother, the RPR titer was reported as 1:2 and then 1:4, 10 days, and 9 days before delivery, and so was started on a fourth course of treatment for discrepant results. However, RPR titers within 1 doubling dilution are considered normal variation of the test and should not be considered discrepant or indicative of active infection. As the authors point out, guidelines for the management of syphilis recommend that infants born to mothers with clearly documented treatment and serofast titers do not need full evaluation for congenital syphilis, and so cases such as those described here could be missed. However, we question whether these infants did in fact have congenital syphilis. The authors suggest that both mothers failed multiple courses of benzathine penicillin G. In our role as members of the NHS Infectious Diseases in Pregnancy Screening Programme’s Congenital Syphilis Expert Review Panel, we have reviewed the cases of all 55 children born with congenital syphilis in England between 2015 and 2023; there were no cases in which the mother had been adequately treated before delivery.2 In England, the cases described above would not have received these additional investigations, and to date, no cases have subsequently presented having been missed at birth. The diagnosis in 3 of the 4 infants described here was based solely on radiographic findings, with one triplet additionally having laboratory abnormalities and a rash. Of note, there were no cases in England in which the only abnormal findings were radiologic. The radiological images in the paper are of slightly suboptimal quality, and in the view of our pediatric radiologist with specialist expertise in bone infection, the bony changes are nonspecific and not pathognomonic of syphilis, indeed, definitive syphilitic osteitis was not seen in any of the images. Radiologic findings in keeping with syphilis are extremely valuable but need to be confirmed by the clinical and laboratory findings. The rash and bone marrow suppression described in the third triplet was certainly not pathognomonic for congenital syphilis and could have multiple causes, but if the hearing loss was confirmed, then congenital cytomegalovirus infection should have been excluded. Unfortunately, the diagnostic investigations, which could have confirmed a diagnosis of congenital syphilis, including treponemal IgM serology, treponemal PCR and placental histology,3 were not reported in these cases. In our view, the evidence for congenital syphilis in these four infants is weak. While we welcome vigilance for congenital syphilis, other clinical diagnoses can be missed if presentations are attributed to syphilis based on nonspecific findings and may cause unnecessary distress for parents.