Untreated Late Latent Syphilis of Both Spouses with Observation of Kassowitz Law: Adverse Pregnancy Outcomes in the Postpenicillin Era

Sir,

Syphilis “the great imitator” was defined by Stokes as an infectious disease caused by Treponema pallidum,[1] systemic from the outset, characterized by florid manifestations on one hand and years of complete asymptomatic latency on the other hand, capable of involving practically every organ in its course, simulating almost every disease in the field of medicine and surgery, transmissible to the offspring in man, transmissible to certain laboratory animals, and treatable to the point of presumptive cure.[2] The disease is broadly classified into infectious or early syphilis and noninfectious or late syphilis with cut-off being 2 years. Early syphilis is a disease of considerable public health importance.[3] This importance particularly relates to untreated pregnant women with series of adverse pregnancy outcomes such as miscarriage, preterm delivery, stillbirth, low birth weight, and normal child (Kassowitz law).[4] After 2 years, late syphilis begins with a continuation of the early latent phase which is termed as late latent syphilis.[5] Without treatment, a third of patients would have a spontaneous cure. A further third of patients maintain a positive venereal disease research laboratory (VDRL) but no signs of disease. The remaining third of patients would develop signs and symptoms of the disease. The clinical relevance of distinguishing early and late latent stage is with respect of infectiousness and duration of treatment.[6] We report a rare case of untreated late latent syphilis of both spouses with observation of Kassowitz law in the postpenicillin era.

A 41-year-old man, smoker and alcoholic, diagnosed as hypertensive and chronic kidney disease Stage IV on antihypertensives and hemodialysis thrice weekly for the last 2 years was sent to sexually transmitted diseases out patient (OP) for routine screening. He was planned for renal transplant surgery later. The patient was married 18 years back. History of promiscuity was present. Last premarital contact was 19 years back with unknown female, unprotected, penovaginal and paid which was followed by genital ulcer 2 months later. He was treated with oral medications by a private practitioner. Last marital contact was 2 years back. He denied any extramarital contact.

Clinical examination revealed pallor and bilateral pedal edema. General and local examination did not show any evidence of primary, secondary, and tertiary syphilis. Ocular and neurological examination were normal. Investigations revealed raised renal parameters. Serum VDRL was found to be reactive in 1:4 dilution. Serum Treponema pallidum hemagglutination assay (TPHA) was found to be positive. Enzyme-linked immunosorbent assay for human immunodeficiency virus, hepatitis B surface antigen, and anti-hepatitis C virus were negative. Chest radiograph, electrocardiogram (ECG), echocardiography, and cardiologist opinion were normal. Cerebrospinal fluid (CSF) examination was done. It showed 2 white blood cells/mm³, protein 29 mg%, and sugar 54 mg%. CSF-VDRL and TPHA were negative. No significant abnormalities were detected in magnetic resonance imaging (MRI) brain and spinal cord. He was diagnosed as late latent syphilis and treated with injection benzathine penicillin 2.4 million units deep intramuscularly after test dose weekly once for 3 weeks except on the days of hemodialysis.

On partner screening, his spouse had no history of any premarital and extramarital contacts. She did not give any history of genital ulcer and skin rash. Obstetric history revealed that first baby was delivered prematurely at 30 weeks of gestational age (birth weight 1.40 kg) and died after 3 days. Her second pregnancy ended with spontaneous abortion at 7 months of gestational age. Then, she delivered two healthy children who were screened and found to be normal. Her general and local examination revealed no evidence of primary, secondary, and tertiary syphilis. Serum VDRL was found to be reactive in 1:1 dilution. Serum TPHA showed positive.

Enzyme-linked immunosorbent assay for human immunodeficiency virus, hepatitis B surface antigen and anti-hepatitis C virus were negative. Chest radiograph, ECG, and echocardiography were normal. CSF examination was done. It showed 3 white blood cells/mm³, protein 25 mg%, and sugar 56 mg%. CSF-VDRL and TPHA were negative. No significant abnormalities were detected in MRI brain, spinal cord, and MR angiography. She was treated with injection procaine penicillin 12 lakhs units deep intramuscularly after test dose daily for 21 days for treatment of late latent syphilis. Two living healthy children were examined and screened for any evidence of congenital syphilis. Both children were found to be VDRL nonreactive and TPHA negative.

Patients with late latent syphilis are usually asymptomatic. Diagnosis is primarily made using treponemal serology which includes positive nonspecific tests, (VDRL) usually in low titers of 1:8 or less, and universally reactive specific treponemal tests.[6] In our case, the patient was diagnosed by routine screening tests as late latent syphilis. During the primary stage of syphilis, he was treated with oral medications even in the postpenicillin era. During the period of infectious early syphilis, the patient infected his spouse. Her untreated pregnancy was proceeded with series of spontaneous labor, preterm labor and healthy children (Kassowitz law).

As per the World Health Organization (WHO), about 2.1 million pregnant women are diagnosed to have active syphilis each year. Most of them are young females without adequate antenatal care, having 95% chance of transferring the infection to their fetus transplacentally. The WHO estimates that every year, maternal syphilis is responsible for 460,000 abortions or stillbirth and 270,000 congenital syphilis.[7] Despite comprehensive antenatal screening recommendations and inexpensive treatment, adverse pregnancy outcomes with syphilis has long been and continues to be a public health concern. Interventions to improve the outcomes of antenatal syphilis screening has shown that it could reduce the syphilis-attributable incidence of stillbirth and perinatal death by 50%.[8] We are presenting this case for rarity and stressing the importance of implementing the Centres for Disease Control and Prevention recommendation that all the pregnant women should be screened for syphilis in the first antenatal visit in the first trimester and again in late pregnancy[8] for syphilis and treatment with penicillin is an effective measure to prevent the pregnancy adverse outcomes.[9] We are also stressing the importance of routine and partner screening to identify the missing out cases and to give the appropriate treatment.[10]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.