lniernational lournal of STD & AIDS 1992; 3: 161-167
EDITORIAL REVIEW
Congenital syphilis Jacqueline M Boot-, Arnold P Oranje-, Ronald de Groot2, Gerrie Tan" and Ernst Stolz! 11?ep~rtment~ of "Dermato-venereoiogq and 2pediatrics, Erasmus University Hospital DIJkzlgt-Sophla Children's Hospital, Rotterdam, The Netherlands, and 3Department of Sengerema Hospital, Sengerema, Tanzania
INTRODUCTION
Congenital syphilis (CS) is a disease that occurs wor~d-,:"ide. The.disease CS is referred to as early CS if diagnosed In the first 2 years after birth and as late CS if diagnosed later. The disease can be prevented if the mother is treated effectively during pregnancy. In Europe, USA and Austraha, pregnant women are routinely screened for infe~tions at prenatal check-ups, only at the end of the first 3 months. CS, however, is still ~ncou~tered in countries in which such screening IS carried on. In these cases, infection could have occurred after screening or when screening could have. been totally omitted. Large epidemiological StUdI~S ~ate b~ck to the beginning of this century. Studies In .which advanced techniques were used frequ~ntly Involved only a small number of patients. A review of current knowledge on CS is presented. EPIDEMIOLOGY
The first reported data on the prevalence of congenital syphilis dates back to the beginning of this century. From 1891 to 1910, almost 2000 different untrea~ed syphilis patients were Investigated". Extensive follow-up investigations in these patients were conducted from 1949 to 19512 • The results showed t~at 26% of the infants born to syphilitic moth~rs did not develop syphilis (remained seron~g~tIve), were seropositive but were without chru~al manife~~ationof.syphilis and 49% displayed ~anifest syphilis. The nsk of prenatal transmission ~s dependent on the duration of pre-existing ~nfec~on '. The longer was the period of existing InfeCtIo.n ~n the mother, the lesser was the risk of transmission of the infectionvs. Additional studies showed that the incidence of stillbirths due to congenital syphilis reached a peak between the 6th ?nd t~e 8th month of pregnancy3. In 1917, Har~an investigated 150 syphilitic mothers and 150 healthy mothers for obstetrical complications. In the former group, 39% of the mothers delivered a healthy baby whereas in the latter group 79% of the mother~ delivered a healthy baby'.
2?%
Correspondence to: Arnold P Oranje, Department of Dermatovenereology, PO Box 70029, 3000 LL Rotterdam, The Netherlands
Transmission of syphilis from the pregnant ",,:omen .to the infant depends on the stage of the disease ~ ~he mother s.6 • Fiumara et al. s investigated 59 syphilitic mothers. All mothers with primary or secondary syphilis delivered either a stillborn or a premature or a syphilitic infant. This is in contrast to deliveries in mothers with late latent syphilis in 20% of whom premature or stillbirths were observed and in 10% of whom the infants displayed manifest syphilis. Even though a healthy infant was born after an earlier pregnancy, a subsequent pregnancy may still result in the birth of an infant with CS. Fiumara et al. 7 illustrated such a course of CS in a family in which 5 out of the 8 children were infected. Five pregnancies resulted respectively in a stillbirth after 7 months, in a boy with CS, in triplets, two of whom had CS, in twins, one of whom had CS and a healthy daughter. Infection ~ay occur at any stage of the pregnancy. It was previously assumed that infection did not occur before the 18th week when Langhans' cell layer had vanished, but Hager" reported that spirochetes were already present in the first trimester. Clinical manifestations occur only after the 18th week, probably because the immune system of the fetus has matured by then". The incidence of CS is not only determined by the num?~r of women with primary and secondary syphilis, but also by the quality of prenatal care. The prev~ence of primary and secondary syphilis varies considerably. In the United States and in Northern Europe, the prevalence of pregnant seropositives was estimated at 0.1-0.6%10, whereas a prevalence of 7.6% was observed in a South African study in 198211 •
In the United States, the number of notified cases of CS declined until 1978 (total 108 cases), increasing slightly to a total of 268 notified cases in 1985u . The effect of prenatal care is reflected by the following set of data. From 1982 to 1985, only 52% of the mothers who delivered a syphilitic baby had received prenatal care, whereas 95% of the all pre~ant women had received such care. In the Uruted States, the figures for 1985 to 1988 showed an increase of 25% in the number of notified cases ?f primary and secondary syphilis in 198713 • This Increase seemed to be linked with an increase in drug abuse ('crack')l4.1S. The increase in all groups of women was higher than that in men. The number
162
International Journal of SID & AIDS Volume 3 May/June 1992
of cases of CS increased by 21% to 10.5 cases per 100,000 live births. From 1986 to 1988, there was an increase of more than 500% in New York City". The number of new notifications partly depends on the definition that is used. Cohen'? showed that the actual incidence was probably five times higher than the official reported incidence. Boot18,19 also reported similar data in The Netherlands. In the period 1982-1985, 17 infants were diagnosed as having CS18,19. This represents 2.5 cases per 100,000 live births.
lesions, particularly blisters on the extremities which may partially progress into desquamation". The skin may also show a 'blueberry muffin' appearance as a result of dermal haematopoiesis in rare cases 28. Pre- and dysmaturity have been reported in patients with CS30,32,33, but an aetiological link is not clear. Even a coincidental link was not observed by Srinivasan's who investigated 78 neonates with a positive serology with or without clinical manifestations. No differences were also observed in the birth weights or duration of pregnancy between different groups.
CLINICAL MANIFESTATIONS The clinical manifestations of congenital syphilis (CS) can be divided into manifestations present prior to birth, at birth and after birth. Prenatal symptoms These number only a few. A reduced level of matemal l.Z-d-oestradiol and oestriol was observed in the third trimester of pregnancy in mothers with syphilis-". In a case report, Savage-! described a pregnancy in which an abnormal ECG was observed a few days before full term. CS was diagnosed in the infant after caesarean section.
Postnatal manifestations
Cutaneous abnormalities Nasal discharge, a classic symptom is initially watery becoming progressively thicker and purulent (purulent rhinitis). The varied array of cutaneous lesions in CS resembles that of acquired secondary syphilis. The lesions may be macular, papular or maculopapular. A petechial rash may also be observed. The intertriginous sites may be eczematoid, sometimes with tmpetiginization-". The palmoplantar desquamation which may also be present at birth may progress to a presentation with multiple palmoplantar milia 36 • Condylomata lata are considered as a symptom of CS typically towards the end of first year after birth":
Perinatal manifestations
Haematological abnormalities
Certain abnormalities may be observed in the placenta and the umbilical cord at birth. Recently, attention has been drawn to the presentation of necrotizing funisitis that may be related to CS22. The macroscopic presentation of the cord may provide a characteristic clue for CS. Segmentally, oedematous red and pale-blue spiral-form zones with alternate white streaks are present. The vascular walls are highly thickened, white and surrounded by a white opaline region. In necrotic funisitis, a deep inflammatory infiltrate in the matrix of the umbilical cord sometimes accompanied by signs of phlebitis and thrombosis is observed. Morphological abnormalities in the placenta have been reported by various investigators-v
EDITORIAL REVIEW
Congenital syphilis Jacqueline M Boot-, Arnold P Oranje-, Ronald de Groot2, Gerrie Tan" and Ernst Stolz! 11?ep~rtment~ of "Dermato-venereoiogq and 2pediatrics, Erasmus University Hospital DIJkzlgt-Sophla Children's Hospital, Rotterdam, The Netherlands, and 3Department of Sengerema Hospital, Sengerema, Tanzania
INTRODUCTION
Congenital syphilis (CS) is a disease that occurs wor~d-,:"ide. The.disease CS is referred to as early CS if diagnosed In the first 2 years after birth and as late CS if diagnosed later. The disease can be prevented if the mother is treated effectively during pregnancy. In Europe, USA and Austraha, pregnant women are routinely screened for infe~tions at prenatal check-ups, only at the end of the first 3 months. CS, however, is still ~ncou~tered in countries in which such screening IS carried on. In these cases, infection could have occurred after screening or when screening could have. been totally omitted. Large epidemiological StUdI~S ~ate b~ck to the beginning of this century. Studies In .which advanced techniques were used frequ~ntly Involved only a small number of patients. A review of current knowledge on CS is presented. EPIDEMIOLOGY
The first reported data on the prevalence of congenital syphilis dates back to the beginning of this century. From 1891 to 1910, almost 2000 different untrea~ed syphilis patients were Investigated". Extensive follow-up investigations in these patients were conducted from 1949 to 19512 • The results showed t~at 26% of the infants born to syphilitic moth~rs did not develop syphilis (remained seron~g~tIve), were seropositive but were without chru~al manife~~ationof.syphilis and 49% displayed ~anifest syphilis. The nsk of prenatal transmission ~s dependent on the duration of pre-existing ~nfec~on '. The longer was the period of existing InfeCtIo.n ~n the mother, the lesser was the risk of transmission of the infectionvs. Additional studies showed that the incidence of stillbirths due to congenital syphilis reached a peak between the 6th ?nd t~e 8th month of pregnancy3. In 1917, Har~an investigated 150 syphilitic mothers and 150 healthy mothers for obstetrical complications. In the former group, 39% of the mothers delivered a healthy baby whereas in the latter group 79% of the mother~ delivered a healthy baby'.
2?%
Correspondence to: Arnold P Oranje, Department of Dermatovenereology, PO Box 70029, 3000 LL Rotterdam, The Netherlands
Transmission of syphilis from the pregnant ",,:omen .to the infant depends on the stage of the disease ~ ~he mother s.6 • Fiumara et al. s investigated 59 syphilitic mothers. All mothers with primary or secondary syphilis delivered either a stillborn or a premature or a syphilitic infant. This is in contrast to deliveries in mothers with late latent syphilis in 20% of whom premature or stillbirths were observed and in 10% of whom the infants displayed manifest syphilis. Even though a healthy infant was born after an earlier pregnancy, a subsequent pregnancy may still result in the birth of an infant with CS. Fiumara et al. 7 illustrated such a course of CS in a family in which 5 out of the 8 children were infected. Five pregnancies resulted respectively in a stillbirth after 7 months, in a boy with CS, in triplets, two of whom had CS, in twins, one of whom had CS and a healthy daughter. Infection ~ay occur at any stage of the pregnancy. It was previously assumed that infection did not occur before the 18th week when Langhans' cell layer had vanished, but Hager" reported that spirochetes were already present in the first trimester. Clinical manifestations occur only after the 18th week, probably because the immune system of the fetus has matured by then". The incidence of CS is not only determined by the num?~r of women with primary and secondary syphilis, but also by the quality of prenatal care. The prev~ence of primary and secondary syphilis varies considerably. In the United States and in Northern Europe, the prevalence of pregnant seropositives was estimated at 0.1-0.6%10, whereas a prevalence of 7.6% was observed in a South African study in 198211 •
In the United States, the number of notified cases of CS declined until 1978 (total 108 cases), increasing slightly to a total of 268 notified cases in 1985u . The effect of prenatal care is reflected by the following set of data. From 1982 to 1985, only 52% of the mothers who delivered a syphilitic baby had received prenatal care, whereas 95% of the all pre~ant women had received such care. In the Uruted States, the figures for 1985 to 1988 showed an increase of 25% in the number of notified cases ?f primary and secondary syphilis in 198713 • This Increase seemed to be linked with an increase in drug abuse ('crack')l4.1S. The increase in all groups of women was higher than that in men. The number
162
International Journal of SID & AIDS Volume 3 May/June 1992
of cases of CS increased by 21% to 10.5 cases per 100,000 live births. From 1986 to 1988, there was an increase of more than 500% in New York City". The number of new notifications partly depends on the definition that is used. Cohen'? showed that the actual incidence was probably five times higher than the official reported incidence. Boot18,19 also reported similar data in The Netherlands. In the period 1982-1985, 17 infants were diagnosed as having CS18,19. This represents 2.5 cases per 100,000 live births.
lesions, particularly blisters on the extremities which may partially progress into desquamation". The skin may also show a 'blueberry muffin' appearance as a result of dermal haematopoiesis in rare cases 28. Pre- and dysmaturity have been reported in patients with CS30,32,33, but an aetiological link is not clear. Even a coincidental link was not observed by Srinivasan's who investigated 78 neonates with a positive serology with or without clinical manifestations. No differences were also observed in the birth weights or duration of pregnancy between different groups.
CLINICAL MANIFESTATIONS The clinical manifestations of congenital syphilis (CS) can be divided into manifestations present prior to birth, at birth and after birth. Prenatal symptoms These number only a few. A reduced level of matemal l.Z-d-oestradiol and oestriol was observed in the third trimester of pregnancy in mothers with syphilis-". In a case report, Savage-! described a pregnancy in which an abnormal ECG was observed a few days before full term. CS was diagnosed in the infant after caesarean section.
Postnatal manifestations
Cutaneous abnormalities Nasal discharge, a classic symptom is initially watery becoming progressively thicker and purulent (purulent rhinitis). The varied array of cutaneous lesions in CS resembles that of acquired secondary syphilis. The lesions may be macular, papular or maculopapular. A petechial rash may also be observed. The intertriginous sites may be eczematoid, sometimes with tmpetiginization-". The palmoplantar desquamation which may also be present at birth may progress to a presentation with multiple palmoplantar milia 36 • Condylomata lata are considered as a symptom of CS typically towards the end of first year after birth":
Perinatal manifestations
Haematological abnormalities
Certain abnormalities may be observed in the placenta and the umbilical cord at birth. Recently, attention has been drawn to the presentation of necrotizing funisitis that may be related to CS22. The macroscopic presentation of the cord may provide a characteristic clue for CS. Segmentally, oedematous red and pale-blue spiral-form zones with alternate white streaks are present. The vascular walls are highly thickened, white and surrounded by a white opaline region. In necrotic funisitis, a deep inflammatory infiltrate in the matrix of the umbilical cord sometimes accompanied by signs of phlebitis and thrombosis is observed. Morphological abnormalities in the placenta have been reported by various investigators-v
