Report
of
a Probable
Case
By PHYLLIS
M.
WRIGHT,M.D.,
AND TETSUJI INOUE,M.D.
Torrance, Ca/if.I
MPROVED
methods
of
prevention,
diagnosis
and
treatment
of maternal
syphilis
have
greatly
reduced
the
opportunities
to study
the
transmission
of
congenitally
acquired
syphilis to the third generation.
Although there are reports in the literature concerning third-generation cases, many
of them fail to stand up under careful scrutiny. It has been emphasized by Moore1 and
Stokes,
Beerman
and
Ingraham2
that
in
the
earlier
literature
the
diagnosis
was
made
either on clinical signs alone or on the basis of a positive serologic test obtained soon after
birth
without
clinical
or
roentgenologic
confirmation
of
the
disease.
Some
of
these
cases
must be excluded as it is now well accepted that babies born of seropositive mothers may
show positive serologic tests up to 70 days after birth without actually being infected.1
In Japan congenital syphilis still occurs frequently and, because of economic factors,
these cases often remain untreated, thus affording a greater possibility for the occurrence of
third-generation syphilis.
A probable
case
which
fulfills
the
criteria
of Fournier
and
Finger3
is presented
here.
CASE REPORT
M. W. was first seen in the Nagasaki clinic of the Atomic Bomb Casualty Commission at 13 wk.
of age because his mother’s postpartum serologic tests for syphilis were strongly positive. Since the baby had typical syphilitic stigmata and strongly positive serologic tests a diagnosis of congenital
syphilis was made. It was noted at that time that the mother had facies of congenital syphilis with severe corneal scarring. A family study (chart 1) was then made to determine whether her infant was a case of third-generation syphilis.
First Generation
A. Baby’s maternal grandfather, A. S., a 62 yr. old Japanese farmer, had gonorrhea at age of 20
yr.followed by development of swelling in R inguinal region which was subsequently removed without sequelae. Fifteen years ago he developed weakness of R leg with backache which was
diag-nosed as neuralgia and for which he remained in bed for 3 yr. He had complained of some weakness of R leg ever since. He had never received specific antisyphilitic or penicillin therapy for any reason.
He had had no previous serologic tests.
Positive findings on physical examination were hypertension of 174/84 mm.Hg, arteriosclerosis of retinal vessels, several areas of vitiligo on trunk and a “punched-out” depigmented penile scar (Fig. 1), the surface of which was covered with thin skin. Neurologic examination was normal, and there appeared to be no appreciable weakness of R leg.
On 2 occasions the Kolmer-Wassermann test was 3+ with no titre and the
cardiolipin-microfloccu-lation and Kline tests were doubtful. Examination of spinal fluid was refused.
A diagnosis of probable latent syphilis was made on basis of serologic tests, history, and penile scar.
From the Atomic Bomb Casualty Commission.
Sponsored by the Atomic Bomb Casualty Commission with funds supplied by the Atomic Energy
Commission.
(Received for publication July 10, 1952.)
I
11
Ac
Ac62 A3 Ae). A.L2 A,vL3466
PHYLLIS M. WRIGHT AND TETSUJI INOUF(,)
-CHART 1. Family study of Nf. XT.
B. Baby’s maternal grandmother, S. S.. a 60 yr. old Japanese peasant woman, gave no history of syphilitic symptoms or knowledge of infection. She had never had serologic tests, had received no
specific antisyphilitic treatment (including penicillin), and had never been examined by a physician.
Her 1st pregnancy occurred at age of 18 yr. and terminated at 5 mo. in a spontaneous abortion of unknown cause. Second pregnancy was a stillborn breech delivery at term after a 3 day labor. Infant was large and well-developed with no obvious abnormalities and cause of death was unknown. Third, 4th and 9th pregnancies resulted in normal, full term infants who are flOW alive and well, but who were not available for serologic testing. Fifth pregnancy was a normal full term baby, now alive and well, who is seronegative. Sixth pregnancy was I. W.. a congenital syphilitic infant and
mother of the 3rd generation case in this study. Seventh and 8th pregnancies resulted in normal
babies who are now alive and well and are seronegative.
For past 10 yr. she had had a chronic cough productive of yellow sputum with no fever, night sweats or weight loss. She had slight palpitation on climbing hills which had increased during past 3 yr. Otherwise, she had been well and was able to do usual hard work in the fields.
Physical findings revealed a small, poorly nourished peasant woman. Tonsils and adenoids were markedly hypertrophied. Chest was normal except for limited motion of both diaphragms. Moist rales were heard throughout both lung fields.
Chest RG revealed soft and nodular, occasionally confluent, densities throughout both lungs which
were interpreted as either atypical tuberculosis or metastatic lesions from a primary undetermined source. Remote possibility of some unusual type of syphilitic invoIv’iii of lungs was also con-sidered. No definite diagnosis could be made from films. Sputum smear and culture were negative for acid fast bacilli. On 2 occasions her blood cardiolipin-microflocculation test was 4+ with a 1:2
titre, Kline was 4+ and the Kolmer-Wassermann was doubtful. Examination of spinal fluid was refused. A diagnosis of probable latent syphilis was made.
Second Generation
I. W, was the 31 yr. old daughter of S. S. She was a normal, full term baby said to be of normal
birth weight who developed severe conjunctivitis immediately after birth which cleared after 3 days
without treatment. No corneal changes were noticed after this and vision was good. At age of 1 yr. she had a generalized skin eruption of unknown etiology which lasted for several months.
1
FIG. 1. A. S., first-generation syphilis patient, showing penile scar.
She had no other serious illnesses and at age of 22 yr. married a man who died 3 mo. later from acute appendicitis. No information could be obtained concerning possibility that this man might have had syphilis. There were no pregnancies from this marriage and patient denied any history of primary
Oi secondary syphilitic lesions following that marriage.
She remained in good health until age of 26 yr. when she married her present husband. He had no history of syphilis and had repeatedly negative serologic tests for syphilis, last 2 of which were done at this clinic in course of this study.
- First pregnancy was in 1949 and resulted in a normal, full term, spontaneous delivery. This baby
was examined in this clinic at age of 2#{189}yr. at which time no signs of congenital syphilis were noted and serologic tests for syphilis were negative.
Second pregnancy was M. \XT, who had congenital syphilis (see below). Mother’s first serologic
tests were done during this pregnancy and were reported as “strongly positive.”
468 PHYLLIS M. WRIGHT AND TETSUJI INOUF
#{149}‘,/
____
liG. 2. 1. W., second-generation syphilis patient. showing saddle nose.
FiG. 3. I. \X., orneal
FIG. 4. M. W., third-generation syphilis patient, showing desquamation.
of the incisor borders. There were no sabre shins. The rest of physical examination was normal
including the gait and the neurologic examination. Chest RG was normal.
Cardiolipin-microflocculation test was 4+, titre 1 :64; Kline was 4+ ; and Kolmer-Wassermann was 4+, titre I : 128, Spinal fluid was clear and colorless with 26 WBC (24 lymphocytes) and 13 RBC/cmm. Spinal fluid protein was 60.0 mg./100 cc. and spinal fluid Kolmer-Wassermann was 4+ with a titre of 1:16. Colloidal gold curve was 5 5 5 4 3 2 1 000.
A diagnosis of congenital syphilis with neurosyphilis and inactive interstitial keratitis was made.
Third Generation
M. W. was second baby of this congenitally syphilitic mother who had had one previous normal pregnancy 2#{189}yr. before.
He was delivered spontaneously after 40 wk.’ gestation and weighed 3350 gm. at birth. He was
breast fed and did well until 35 days of age. At that time he became irritable and cried excessively,
especially when handled. Pallor and persistent rhinitis appeared at 2 mo. of age. At 2#{189}mo. of age
he had a febrile episode of undetermined cause which subsided spontaneously. Weight gain had been good and mother felt he was doing well. He was brought to clinic at 3 mo. of age for routine
exami-nation because of his mother’s positive postpartum serologic tests for syphilis.
S
FIG. 5. M. W., third-generation syphilis patient, RG of tibia and fibula taken before treatment.
FIG. 6. M. W., third-generation syphilis, RG of elbows taken before treatment.
470 PHYLLIS M. WRIGHT AND TETSUJI INOUE
severe desquamation. There were shiny red desquamating areas around finger and toe nails. Remaining skin area was normal. There was purulent nasal discharge without rhagades or excoriation. Mucous membranes were normal. Heart and lungs were normal. Abdomen was markedly distended by a
large firm liver which was palpable 5 cm. below costal margin and a hard spleen which extended
7
cm. below costal margin. There were bilateral fluctuant transilluminating testicular masses thought to be hydroceles. Baby was reluctant to move extremities and screamed whenever light pressure was applied. There were several 1 cm. cervical nodes bilaterally but no enlargement of axillary, inguinal or epitrochlear nodes. Deep tendon and superficial reflexes were normal and Moro reflex was still present.There was a moderately severe anemia, RBC count 2.8 million cmm., Hgb. 6.4 gm./100 cc., and
a leukocytosis of 23.2 thousand/cmm. Cardiolipin-microflocculation test was 3+, titre I :256, Kolmer-Wassermann was 3+, titre 1 :512. Spinal fluid was clear, colorless and contained 5 lymphocytes/cmm.; protein was 68 mg./100 cc. and Kolmer-Wassermann was 4+, no titre.
Chest RG was normal. RG of long bones showed moderately severe osteitis at proximal ends of ulnae and distal ends of humeri and medial borders of proximal ends of tibiae (Figs. 5 and 6) . There
was slight generalized periosteal elevation of most of the long bones. There were bands of increased density at distal ends of radii and ulnae with bands of decreased density just proximal to them. The changes were considered pathognomonic of congenital syphilis.
A diagnosis of congenital syphilis was made and the baby was treated with 96 hr. penicillin,
2.400,000 u., over a 2 wk. period, and made an uneventful recovery. Six months later the only
re-inaining clinical sign was a spleen palpable 2 cm. below costal margin. RG of bones showed good
healing. RBC count was 4.3 million/cmm. and Hgb. was 11.2/100 cc.
Cardiolipin-microfloccula-tion was 4+ and the Kolmer-Wassermann was negative.
DIScuSSION
According to the concepts of Fournier and Finger, as quoted from Stokes,2 the
following criteria must be met in making the diagnosis of third-generation syphilis.
“Acquired syphilis must be demonstrated in the grandmother and preferably also in the grandfather.” The grandparents reported in this study both had positive serologic tests and
the grandfather had a penile scar and history of venereal disease.
“Prenatal, as distinguished from acquired syphilis, must be demonstrated in the mother
of the third-generation case. Acquired syphilis must be excluded in her case and the
with a history of eye disease in early childhood. While many other conditions such as
riboflavin deficiency and tuberculosis, which are common in Japan, can give rise to corneal
opacities, slit-lamp examination is a valuable aid in the differential diagnosis and in this
case corroborated the diagnosis of congenital syphilis. The mother also presented the
typical facies of depressed nasal bridge and abnormal teeth. Her serologic tests were
strongly positive.
There is, however, a possibility that she was reinfected by her first husband on whom
information is not available. Reinfection of congenital syphilitic patients
has
been re-ported but most of the early cases of congenital syphilis were diagnosed from clinicalobservation alone and were not substantiated by modern serologic testing so that well-documented cases are exceedingly rare.4’5
Syphilis has been excluded in the father of the third generation case on the basis of
negative history and repeatedly negative serologic tests and thus he cannot be considered as a source of reinfection. Extramarital relations by the mother cannot be positively ruled
out although they were specifically denied. This remains the factor which can never be
satisfactorily excluded and is thus common to all cases of presumed third-generation
syphilis reported so far.
“There must be incontestable evidence of prenatal syphilis in the third generation.”
The baby reported here had classical physical signs including rhinitis, hepatosplenomegaly,
bone pain, roentgenographic evidence of osteitis and periostitis and strongly positive
serologic tests at the age of 1 3 weeks, so that there can be no question of the diagnosis.
,
‘Manifestations must appear soon after birth in both the second and third generation.”This is
difficult
to
prove in the second-generation case reported here as the early history of the mother is vague. Her history of early skin lesions is common to many Japanesechildren and is probably not significant. Symptoms of interstitial keratitis appeared
some-what earlier than usual in her case. The diagnosis was easily made in her infant at the age
of 13 weeks.
SUMMARY
A family study tracing a syphilitic infection from grandparents to mother to infant is
presented. Data are presented which fulfill the rigid criteria necessary for diagnosis of a
case of third-generation syphilis.
REFERENCES
I. Moore, J. E., Treatment of Modern Syphilis, ed. 2. Springfield. III., Charles C Thomas, Publisher, 1943, pp. 486 and 516.
2. Stokes, J. H., Beerman, H., and Ingraham, N. R., Modern Clinical Syphilology, ed. 3, Philadelphia
and London, W. B. Saunders Company, 1944, p. 1080. 3. Fournier and Finger, quoted from Stokes and others.
4. Hahn, R. D., Reinfection in congenital syphilis, Am. J. Syph. 25:200, 1941. 5. Allison. S. D.. Reinfection in congenital syphilis, Am. J. Syph. 26:2 12, 1942.
SPANISH ABSTRACT
Un
Caso
Probable
de
SIfilis
Cong#{233}nita a Traves
de
Tres
Generaciones
Los autores presentan el caso de un niflo de 13 semanas con sifilis cong#{233}nita en cuya madre y .ibuelos maternos fu#{233}posible diagnosticar su origen.
Al abuelo materno, de 62 a#{241}osde edad se le hizo diagnostico de sIfilis por presentar historia de infecci#{243}n ven#{233}rea, cicatriz excavada en pene y Ia reacci#{243}n de Kotmen Wassermann con 3+.
472 PHYLLIS M. WRIGHT AND TETSUJI INOUE
siguiente naci#{243}un niiio a t#{233}rmino pero muerto despu#{233}s de tres dIas de trabajo de parto. El tercero, cuarto, quinto y noveno embarazo dieron ni#{241}ossanos, a t#{233}rmino, viven pero se desconoce su
sero-logla, con excepci#{243}ndel quinto ni#{241}oque es negativa. Del sexto embarazo naci#{243}un ni#{241}ocon sIfllis
cong#{233}nitay es Ia madre del enfermo, que es el motivo de este relato. El s#{233}ptimo y el octavo embarazo
dieron niflos sanos, a t#{233}rmino y con reacciones serol#{243}gicas negativas a la sIflhis. Las reacciones
sero-l#{243}gicaspara lues fueron tambi#{233}npositivas en la abuela.
La madre del enfermo padeci#{243}de lesiones oculares tempranamente en su infancia que dejaron cicatrices corneanas intensas que al examen oftalmol#{243}gico se diagnosticaron como de origen lu#{233}tico. Adenias, tenia Ia facies, tipica con el puente nasal deprimido y dientes anormales, sus reacciones
serol#{243}gicasy en liquido cefalorraquideo fueron intensamente positivas, haci#{233}ndose el diagn#{243}stico de
sifilis cong#{233}nitacon neurosifilis. Tuvo dos ni#{241}osen su segundo casamiento, el primero fu#{233}sano y
con reacciones negativas y ci segundo, que es el ni#{241}oque se estudia tenia sifilis cong#{233}nita.
El enfermo en cuesti#{243}nnaci#{243}bien pero a los 35 dias se puso muy irritable y Iloraba mucho,
especialmente al moverlo. A los tres meses se Ic examin#{243}encontr#{225}ndosele rinitis, hepato y espleno-megalia, dolores #{243}seosy roentgenologicamente habia osteoperiostitis. Sus reacciones serol#{243}gicas fueron
intensamente positivas a las 13 semanas de vida.
Dc acuerdo con los conceptos de Fournier y Finger, se deben llenarlos siguientes requisitos para
hacer el diagn#{246}stico de sifihis cong#{233}nitaen tercera generaci#{243}n:1*._Debe demostrarse la presencia de
sifilis adquirida en Ia abuela y de preferencia en el abuelo tambi#{233}n. 2-Se debe demostrar Ia pre-sencia de sifihis en la madre pero #{233}stadebe ser cong#{233}nita y no adquirida. Esta Ciltima debe excluirse y
probarse que ci padre es sano. 3#{176}.-Deben encontrarse pruebas incontrovertibles de siflhis prenatal en Ia tercera generaci#{243}n. 4#{176}-Las manifestaciones sifllIticas deben aparecer poco despu#{233}s del naci-miento tanto en la segunda como en Ia tercera generaci#{243}n.
-En el caso relatado el 1#{176}punto parece estar plenamente demostrado, el2#{176}no lo es
satisfactoria-mente, pues Ia madre cas#{243}dos veces y aunque el esposo del segundo casamiento y padre del enfermo
no tuvo antecedentes ni reacciones lu#{233}ticas positivas, del primer esposo no se supo nada sobre ci
particular. Tampoco se puede excluir Ia posibilidad de sifilis por contacto sexual extramarital aunque
estos fueron negados especificamente. El 3#{176}punto se comprob#{243} a satisfacci#{243}n pero ci 4#{176}es vago en lo referente a Ia segunda generaci#{243}n o sea Ia madre y plenamente seguro en su hijo.
