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Is a condition such as congenital syphilis within the purview of pediatric emergency medicine? The following case histories would suggest that it is.

In this prospective study, neonates with clinical congenital syphilis were investigated to determine if penicillin therapy caused a deterioration in liver function. The relationship between circulating immune complexes and liver involvement was monitored, and the efficacy of steroid therapy as an adjunct in the treatment of congenital syphilis was investigated. Thirty neonates with clinical congenital syphilis were randomly assigned into two groups: one group received penicillin therapy only, and the other group penicillin and prednisone as an adjunct. Twenty-one infants who did not have clinical or serological syphilis, born to seropositive mothers, served as a "control" group. Liver function tests, full blood counts, and immunological studies were performed at various intervals up to 3 months of age. Although the symptomatic groups differed significantly from the asymptomatic group in most of the parameters measured, there were no significant differences noted between the two symptomatic groups at any time point. No direct relationship between penicillin therapy and either deteriorating liver function or the presence of circulating immune complexes could be demonstrated. Also, prednisone therapy did not modify any of the parameters studied.

Of 23 children with infections of the clavicle, 11 had pyogenic osteomyelitis, four had tuberculosis, and eight (infants) had congenital syphilis. Acute pyogenic infections were treated by drainage. Resection of the clavicle was performed in chronic cases. Curettage and antituberculosis drugs were effective for children with tuberculous infection of the clavicle. Procaine penicillin was used for the treatment of congenital syphilis. Biopsy is generally necessary to differentiate chronic infection from neoplasm.

A retrospective review of 766,742 hospital admissions was performed between 1966 and 1986 at the University of Iowa Hospital for the diagnosis of congenital syphilis. Although 88 individuals were identified with this diagnosis, adequate treatment was documented in only 33 (38%). Thirty-nine of the 88 individuals identified were initially seen for visual complaints by the ophthalmology department. We recommend that all physicians increase their index of suspicion for this disease, and institute appropriate therapy and follow-up if late congenital syphilis is diagnosed.

Hepatitis is a known manifestation of congenital syphilis, however hepatitis developing during penicillin therapy is unknown. Ten patients of congenital syphilis were studied and serial liver enzymes were done before and after starting penicillin therapy. Eight of the ten patients developed hepatitis after initiating penicillin therapy. Whether hepatitis in these cases was secondary to toxic reaction to the products of treponemal lysis or an autoimmune reaction needs to be investigated.

Together with the new rise of recent syphilis in the adult woman, congenital syphilis reappears sporadically in our countries, where prophylactic measures (prenatal serology) are sometimes defeated. It remains much more frequent in developing countries. One should know how to interpret a positive serology in a newborn, as it may only reflect passive transplacental transfer of maternal antibodies. One should on the other hand think of syphilis again when the clinical signs are more or less suggestive, the typical picture not being, by far, the most frequent. In spite of the efficacy of Penicillin G: 50,000 U/kg/day during 10 days, neonatal death rate for congenital syphilis is in the neighbourhood of 10%. Our major effort should therefore be aimed at prevention.

With the introduction of penicillin after World War II, the incidence of syphilis in the United States decreased. Because of penicillin's great success, clinical trials stopped after an initial period of intensive investigation. Syphilis is a difficult disease to study; the natural history may span decades in an individual, and diagnosis and outcome are usually defined serologically, not clinically or bacteriologically. Although the recommended penicillin regimens changed, clinical trials were not repeated. Furthermore, because the early studies occurred before modern clinical-trial methodology was developed, interpretation of the results is difficult. As a result, while current regimens for syphilis therapy are effective, they may or may not be optimal. With the accumulation of reports of treatment failures and the recent appearance of human immunodeficiency virus, current regimens for the treatment of syphilis are being questioned. As background for a meeting at which treatment guidelines were reviewed, the available literature on syphilis therapy is summarized herein.

A 20-year-old woman developed multifocal bone pain. Diagnostic radiology revealed thickened periosteum, and syphilis serology was positive (T. pallidum haemagglutination test 1:5120). She also had discrete signs of congenital syphilis, with retinitis pigmentosa and Hutchinson's incisors. Skeletal scintigraphy demonstrated increased uptake even in radiologically unremarkable bones. The bone pain decreased after four-week administration of 1 M units of penicillin G daily. Scintigraphy one year later showed regression of the increased uptake, skeletal radiology did not reveal significant changes. This case shows that late manifestations of congenital syphilis still occur today. The stigmata of such an infection can be minute and easily missed. Skeletal scintigraphy is better for demonstrating active bone involvement than conventional radiology.

An alarming increase in the incidence of syphilitic labyrinthitis has prompted us to review the pathology of this condition. The temporal bones of two patients with congenital syphilis of the ear were studied histopathologically. They showed diffuse osteitic changes in the otic capsule associated with severe hydrops and degeneration of the membranous labyrinth. The posterosuperior wall of the external auditory canal as well as the auditory ossicles showed numerous connective tissue filled spaces surrounded by thin bony trabeculae. These lesions probably represent healed luetic osteitis. There was severe degeneration of the sensorineural structures in the cochlea. A finding of particular interest was the infiltration and fibrous obliteration of the ductus endolymphaticus in both cases. The significance of these findings in relation to the pathophysiology and treatment of syphilitic labyrinthitis is emphasized.

The diagnosis and management of patients with suspected treponemal infection of the temporal bone pose some challenges. The following points deserve emphasis: 1) the MHA-TP or FTA-Abs is recommended over the reagin serologic tests (VDRL, RPR); 2) one should regard this process as an attempt to define a subgroup of patients with sensorineural hearing loss who will benefit from a combination of antibiotics and steroid therapy rather than explicitly diagnosing infection of the temporal bone. The response rate to therapy is limited; but, otosyphilis, as one of the few treatable causes of sensorineural hearing loss, must be suspected in the differential diagnosis of a wide range of otologic patients.

Pregnant women with untreated syphilis have high rates of adverse pregnancy outcome. Early syphilis in pregnancy, if not treated, results in 40% loss either by spontaneous abortions, stillbirth, or perinatal death. Another 40% of such pregnancies result in an infant born with congenital syphilis. Only 20% of such pregnancies result in a normal infant. Currently recommended treatment of early syphilis in pregnant women uses a dosage of 2.4 million U of benzathine penicillin G. Because of the potentially disastrous effect syphilis has on pregnancy outcome, the occurrence of any treatment failure must be considered seriously. In this brief report we present clinical summaries of four pregnant women treated for syphilis who represent probable treatment failures.

A case is reported in which erythromycin was used successfully to treat maternal syphilis but failed to adequately treat the fetus. This report and similar studies suggest that oral erythromycin is not a reasonable alternative drug for the treatment of lues in the penicillin-allergic gravid female.

The diagnosis of congenital syphilis is difficult since it depends mainly on the results of serological tests. The results of five serological tests (three specific and two non-specific) in nine neonates with congenital syphilis are compared with those obtained in three with passively acquired antibodies. It appeared that the serological diagnosis of congenital syphilis must be based on the finding of specific neonatal antibodies in cord serum, which give positive results to the fluorescent treponemal antibody absorption test for immunoglobulin M, together with high titres of total IgM and negative results to latex tests. The non-specific tests are useful for confirming the efficacy of treatment. The mean number of cases of congenital syphilis in Seville is 0.81/1000 live births.

Three patients with early congenital syphilis are described. A slight degree of prematurity was a common feature. Symptomatology consisted in a combination of various lesions of the skin, bones, respiratory and nervous systems. Despite prompt initiation of therapy with penicillin, one patient died a few hours after birth. Another patient's death was attributed to a secondary Klebsiella overinfection. This demonstrates the severity of the syphilitic injury for the newborn infant when it manifests itself at birth.

Four decades of treatment of syphilis with penicillin confirm the absolute superiority of this drug in all stages of the disease. Various long-acting repository preparations (particularly benzathine penicillin G) are used in treatment of early and late syphilis, and even for prophylactic treatment, with satisfactory results. Treatment schedules and follow-up criteria for examination and indications for retreatment vary little among various authors and countries. Adverse reactions to penicillin, in particular the allergic reactions, make alternative treatment with other antibiotics (tetracyclines, erythromycin, etc) sometimes necessary.

Uninterrupted methods of specific and prophylactic treatment of pregnant women and children, born from syphilitic mothers, were offered. A new preparation--novocainic salt of benzyl penicillin was used in specific and prophylactic treatment of pregnant women.

Acquired and congenital syphilis are both known causes of potentially reversible sensorineural hearing loss. Various therapeutic regimens, including penicillin and/or corticosteroids have been used in the past as treatment for otosyphilis. Response rates have varied from 15% to 80%. In this retrospective study, 13 patients with otosyphilis were treated with a combined course of long-term penicillin and prednisone. A significant response was defined as a 15% improvement in the discrimination score and/or the pure tone average. Initial response rates were 35% with a lasting response rate of 15%. Discrimination scores improved more commonly than pure tone averages. No patient with congenital syphilis or profound deafness had a lasting response. An analysis of possible reasons for failure of therapy is discussed.

Penicillin remains the treatment of choice for syphilis, with sustained low blood levels curing virtually all patients having early syphilis and halting disease progression in most patients with symptomatic syphilis. Tetracycline, erythromycin or cephalothin yields similar cure rates for patients with early syphilis who are allergic to penicillin. The efficacy of non-penicillin regimens for the treatment of late syphilis is uncertain. Results of Venereal Disease Research Laboratory (VDRL) or other reagin tests should become negative or remain at very low titer following adequate therapy, although results of Treponema pallidum immobilization (TPI) and fluorescent treponemal antibody-absorbed (FTA-ABS) tests often remain positive.

For the more than three decades since benzathine penicillin G was discovered it remains unique as the only antibiotic formulation that can provide serum drug concentrations for several weeks following a single intramuscular injection. Benzathine penicillin G has withstood the test of time as the ideal drug to treat early, infectious syphilis and to prevent and treat Group A streptococcal infections. It has proved to be extraordinarily effective for the prevention of rheumatic fever recurrences and is a major reason for the marked reduction in the morbidity and mortality in countries where carefully monitored prophylaxis programs have been established.

A pregnant woman with a history of allergy to penicillin was diagnosed as having primary syphilis. Two successive courses of erythromycin therapy failed to cure the infection. Penicillin desensitization and therapy were initiated and were successful. The newborn was diagnosed as having probable congenital syphilis. This case emphasizes the need for close follow-up of pregnant women after erythromycin treatment for early syphilis.

A patient with congenital syphilis and nephrotic syndrome is reported. The renal biopsy with light microscope showed glomerulopathy with epithelial proliferation. Irregular, nodular, electrodense material was identified with the electron microscope in subepithelial spaces and immunofluorescence showed irregular granular positivity for IgG, IgM and fibrin, which confirmed a disease due to immune complexes. Pencillin and physical rehabilitation were sufficient therapy for the recovery of this patient.

For the congenital syphilitic patient to develop sensorineural deafness is uncommon. For the congenital syphilitic patient to have persistence of treponemes after treatment is rare. To demonstrate viable organisms in the inner ear perilymph of the congenital syphilitic patient, despite treatment with penicillin, has not been recorded to date. This is a case report of such a patient.

A case of congenital syphilis is described in which the diagnosis was not made until the age of 9 and with persistance of metaphyseal changes in spite of prolonged penicillin treatment.

Simultaneous serum and CSF samples were obtained following the intramuscular administration of 50,000 units/kg of aqueous procaine penicillin G in 25 neonates. Penicillin activity was detected in the sera and CSF of all patients. Peak serum levels were noted at four hours (mean +/- SEM, 17.1 +/- 6.3 micrograms/ml). Peak CSF levels were noted at 12 hours (0.70 +/- 0.35 microgram/ml). The serum level at 24 hours was 2.1 +/- 0.98 microgram/ml (range, 0.2 to 5.8 micrograms/ml); the CSF level at 24 hours was 0.12 +/- 0.05 micrograms/ml (range, 0.03 to 0.27 microgram/ml). These results demonstrate that spirocheticidal levels (greater than or equal to 0.03 microgram/ml) are achieved for at least 24 hours in the CSF following the intramuscular administration of aqueous procaine penicillin G in neonates.

Thirty-three cases of congenital syphilis that were seen at The Children's Hospital, Camperdown, over a 34-year period were reviewed. Twenty-nine cases were examples of early congenital syphilis, as the patients developed clinical features in the first two years of life, and the other four cases were examples of late congenital syphilis, with the clinical features developing between two years and nine months of age and 10 years of age. Twenty-five patients were symptomatic at the time of admission to hospital. The most common clinical feature on the patient's presentation to hospital was a maculopapular or vesiculobullous skin eruption which occurred in 13 of the infants. Hepatic and splenic enlargement were present in 12 cases, and nine children had the "snuffles". Five of the children died. Patient follow-up occurred in fewer than 40% of cases and three of the children who were followed-up suffer from developmental delay. Congenital syphilis can occur in all social groups but is most common in infants who are premature or are small for gestational age and are born to young, unmarried mothers of low socioeconomic status. The treatment of congenital syphilis is simple and effective although the patients may need to be linked with community-health facilities to assist in their compliance with follow-up appointments.