Congenital syphilis (CS) is a preventable infection, yet the incidence has surged to the highest rates in 20 years. Because 50% of live-born infants with CS are asymptomatic at birth, there is an increasing likelihood that pediatric providers will encounter older infants whose diagnoses were missed at birth, emphasizing the importance of timely prenatal screening and treatment. We present one such case of an infant admitted twice at 3 and 4 months of age with long bone fractures and suspected nonaccidental trauma. On her second presentation, several additional symptoms prompted evaluation for and eventual diagnosis of CS. In this case, it is demonstrated that an isolated long bone fracture can be a first presentation of CS, with other classic findings possibly appearing later. Pediatric providers should be familiar with the varied presentations of CS in older children, including the radiographic findings that we describe. The rising rates of CS reveal deficiencies in our current strategy to prevent CS and, thus, we recommend reconsideration of universal syphilis screening in the third trimester and at delivery, with timely treatment to prevent CS during pregnancy.

After a decline in congenital syphilis (CS) rates during the last 3 decades, a resurgence has occurred, with the highest rate in 20 years reported in 2017 (23 cases per 100 000 live births), a 154% increase from 2013.13  The incidence of CS has mirrored the rising rates of primary and secondary syphilis in women, which are associated with higher rates of perinatal transmission than latent syphilis.24  Among pregnant women with syphilis, the proportion with early syphilis has increased (35% in 2012 to 58% in 2016).5  Identifying and adequately treating maternal syphilis at least 30 days before delivery prevents up to 98% of CS cases,6,7  and thus the rising rate of CS signals shortcomings in current CS prevention.

Historically, up to 40% of pregnancies in women with untreated early syphilis will result in spontaneous abortion, stillbirth, or perinatal death.8  Approximately 50% of live-born infants with CS are asymptomatic, making early diagnosis difficult unless syphilis is identified in the mother.1,9  Early CS, which manifests within the first 2 years of life, can present with jaundice, copious nasal secretions, palmoplantar pemphigus, hepatosplenomegaly, hemolytic anemia, and thrombocytopenia.8,10  Skeletal manifestations, including symmetric osteoperiostitis of long bones, are present in up to 60% to 80% of untreated early CS. These can result in pain, decreased movement of an extremity (“Pseudoparalysis of Parrot”), and isolated fractures.1012  The latter prompts a workup for nonaccidental trauma (NAT), which delays evaluation for CS.13 

In previous case reports, authors have described infants who presented with long bone fractures or immobility of an extremity, underwent a full NAT evaluation, and ultimately had CS.1416  Our case of a young infant who was admitted twice in 2 months for long bone fractures concerning for NAT is a contemporary reminder that the clinical suspicion and diagnostic practices must adapt to changing epidemiology. This case report was structured as per the case report guidelines.17 

A 3-month-old Hispanic girl presented to pediatric urgent care for acute right forearm swelling and decreased right arm movement for 2 weeks. A radiograph was concerning for fracture of the distal humerus, prompting a Child Protective Services (CPS) report and hospital admission for NAT evaluation. She was born at term, weight appropriate for gestational age, to a 19-year-old Hispanic woman. The mother reported no illnesses since birth, including no history of trauma. Her physical examination was significant for swelling and limited movement of the right arm but otherwise was normal. A full NAT evaluation was performed (normal head computed tomography and ophthalmologic examination). Aside from the right distal humerus irregularity, her skeletal survey reported periosteal reactions of the bilateral femoral and tibial diaphysis, likely representing physiologic periostitis. Her serum calcium and phosphorus concentrations were normal. Given this negative workup, in conjunction with CPS, she was discharged with close primary care physician follow-up.

At her 4-month well-child check, the infant presented with poor movement of the left arm for 1 week and focal tenderness for 1 day. A radiograph revealed a mildly displaced left proximal humeral fracture, prompting a second admission for suspected NAT with reinvolvement of CPS. Her family reported no history of trauma. On physical examination, she had an immobile, adducted left upper extremity with tenderness to palpation and swelling of the proximal humerus. Additionally, she had a single 1-cm ulcer on the tip of the tongue, 5 ulcerations on the anterior vulva and perianal region (Fig 1A), an evolving rash of the palms and soles (Fig 1B), and hepatomegaly (∼2 cm below costal margin). The initial evaluation was notable for mildly elevated transaminases (aspartate aminotransferase 54 U/L, alkaline phosphatase 712 U/L, gamma-glutamyl transferase 143 U/L). Skeletal survey, in addition to the humeral fracture, revealed ill-defined lucencies at the left fibular head and distal femoral metaphyses and periosteal reactions of the right radius and bilateral femurs and humeri (Figs 2 and 3).

FIGURE 1

On the second admission, the patient’s physical examination showed perianal ulcerations (A; perivulvar ulcerations were also noted) and a red macular rash with central clearing and vesicles (B) was noted most prominently on the second hospitalization day.

FIGURE 1

On the second admission, the patient’s physical examination showed perianal ulcerations (A; perivulvar ulcerations were also noted) and a red macular rash with central clearing and vesicles (B) was noted most prominently on the second hospitalization day.

Close modal
FIGURE 2

Comparison of radiographs from the first (A and B) and second (C and D) admissions. Symmetric periosteal reactions of the femur and tibia are subtly noted on the first skeletal survey that progressed by the second. Interval development of ill-defined lucencies at the distal femoral metaphyses and the left proximal fibula is shown.

FIGURE 2

Comparison of radiographs from the first (A and B) and second (C and D) admissions. Symmetric periosteal reactions of the femur and tibia are subtly noted on the first skeletal survey that progressed by the second. Interval development of ill-defined lucencies at the distal femoral metaphyses and the left proximal fibula is shown.

Close modal
FIGURE 3

Classic CS osteoperiostitis shown by the periosteal reactions and diaphyseal and metaphyseal lucencies of the radius and ulna on the second skeletal survey (B) that were subtle during the first (A). The left humerus radiograph (C) demonstrates a mildly displaced fracture (arrows) through the metaphysis with adjacent periosteal reaction.

FIGURE 3

Classic CS osteoperiostitis shown by the periosteal reactions and diaphyseal and metaphyseal lucencies of the radius and ulna on the second skeletal survey (B) that were subtle during the first (A). The left humerus radiograph (C) demonstrates a mildly displaced fracture (arrows) through the metaphysis with adjacent periosteal reaction.

Close modal

The differential diagnosis included NAT, genetic disorders (skeletal dysplasia or osteogenesis imperfecta), and metabolic abnormalities (hypophosphatemia or vitamin D, zinc, or copper deficiency). Given the ulcerative lesions, sexual abuse (syphilis, herpes simplex virus, HIV) was considered. The following day, her syphilis enzyme immunoassay resulted positive and rapid plasma reagin (RPR) titer was 1:1024. The Department of Pediatric Infectious Diseases recommended maternal testing for syphilis, which was positive (RPR titer 1:4). The infant’s cerebrospinal fluid results (white blood cell: 0/mL; protein: 12 mg/dL; and negative VDRL test) were negative for neurosyphilis. The remainder of her evaluation was normal, including testing for HIV, herpes simplex virus, gonorrhea, and chlamydia; head ultrasonography; ophthalmologic evaluation; and hearing screen.

The infant’s mother revealed that she had received limited prenatal care (PNC; 7 visits but 9 missed appointments) and had a previously undisclosed new sexual partner during the second trimester. Her first trimester screening was negative, but she was not rescreened before or at delivery. She was treated for early latent syphilis on diagnosis.18 

The infant was treated with aqueous penicillin G (50 000 U/kg q 6h intravenously) for 10 days,18  and her left arm was immobilized.12  By the third day of treatment, her ulcerations and macular rash began to resolve. Three months later, at 7 months of age, she had a fivefold reduction in RPR titer (1:32) but showed significant hypotonia and motor delay (poor head control, unable to sit unassisted). She was referred to early intervention for assessment and therapy. By 10 months of age, her RPR titer was 1:16 and motor development had improved, meeting normal milestones for age.

In infants, long bone fractures should always prompt consideration of child abuse.19  Radiographic findings of CS are symmetric osteoperiostitis in the diaphyseal and metaphyseal regions of long bones, and pathologic fractures through the destructive metaphyseal lesions are common.12  The initial skeletal survey in our patient showed bilateral symmetric periostitis of the femurs, which was reported as physiologic periosteal reaction of the newborn. This symmetric thin periosteal reaction of the long bones (commonly tibia and femur) occurs in infants ≤6 months and is believed to be due to rapid growth and loosely adherent periosteum.20  The periosteal reactions and bony lucencies in the second skeletal survey were reported as nonspecific, but in retrospect, these radiographs were classic for CS. In a large series of 302 infants with CS, 197 had skeletal manifestations on radiography, with bilateral symmetric periosteal reactions, osteitis, and metaphyseal changes being the most common findings.12  Bilateral periostitis is considered a physiologic finding in infants, but the presence of additional metaphyseal abnormalities is a clue for CS.

Long-term outcomes of CS remain unclear because of limited reports. In a 5-year clinical follow-up study of treated CS patients, researchers found a higher risk for growth restriction, developmental delay, and microcephaly, particularly if symptomatic at diagnosis. Developmental delay was noted in 11.6% (14 out of 120) of patients, of whom 36% (5 out of 14) had no cerebrospinal fluid abnormalities at diagnosis.21 

Retrospectively, the diagnosis of syphilis was missed at multiple points, starting with inadequate PNC. The Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics, American College of Obstetricians and Gynecologists, and US Preventive Services Task Force recommend universal first trimester screening for syphilis during pregnancy and additional third trimester and delivery screening for women at high risk on the basis of individual risk factors (illicit drug use, multiple or new sex partners, etc) or residence in high-prevalence areas.18,22,23  In our case, the infant’s mother had several risk factors (a new sexual partner and residence in an area with increasing syphilis prevalence) that could have prompted rescreening. Limited, late, or lack of PNC poses a challenge to risk-based third trimester screening and to timely and adequate treatment of syphilis during pregnancy, and is thus one of the most significant individual risk factors for CS.2,6,2427  The CDC found that 28% of mothers of infants with CS from 1999 to 2013 received no PNC and an additional 32% received less than the recommended 10 PNC visits.1 

Third trimester screening based on regional epidemiological risk can be challenging in part because of imprecision of available data. Syphilis data are collected at the county level, which may not capture localized hot spots of transmission. One example is that of Los Angeles, where the 2017 CS incidence was 38.7 cases per 100 000 live births county wide. Two cities within the county collected data: Long Beach’s 2017 incidence was 67.7 cases per 100 000 live births compared with 0 in Pasadena.28  The granularity of prevalence estimates may be insufficient for assessing community level risks.

Universal third trimester screening has been proposed to address the rising incidence, but cost-effective analyses are mixed.2931  Albright et al30  calculated that a national rate of 17 cases of primary and secondary syphilis per 100 000 women or higher would make it cost-effective. The national prevalence in 2013 was 0.9 cases per 100 000 women, which did not meet this threshold. This has risen to 2.3 cases per 100 000 women in 2017 nationally, with a rate of 4.6 cases per 100 000 in California.2  Conversely, Hersh et al29  in 2018 demonstrated strong evidence that universal third trimester screening would be cost-effective and improve maternal and neonatal outcomes. Further supporting this approach, in a 2019 CDC study, researchers found that approximately half of all pregnant women with syphilis and one-third of pregnant women with early syphilis did not report any high-risk behaviors.5  This highlights a significant proportion of women missed by individual risk-based screening recommendations.

Pediatric health care providers will need to have greater familiarity with and suspicion of undiagnosed CS to adapt to the changing epidemiology of syphilis. Radiologists should be alerted to the suspicion of CS to aid in the interpretation of radiographic findings that may mimic normal physiologic processes. Better access to PNC and adherence to the current syphilis prenatal screening guidelines with treatment 30 days before delivery may improve CS prevention. However, because individual risk factors are absent in a large proportion of women with syphilis and community risk may be difficult for local providers to assess, we argue that risk-based testing is insufficient to address the rise in CS and favor reconsideration of universal third trimester and delivery syphilis screening.

Drs Jacobs and Buzi drafted and revised the manuscript; Drs Vu, Mony, and Sofos provided further critical review and revisions; and all authors cared for this patient, approve the final manuscript as submitted, and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

CDC

Centers for Disease Control and Prevention

CPS

Child Protective Services

CS

congenital syphilis

NAT

nonaccidental trauma

PNC

prenatal care

RPR

rapid plasma regain

1
Su
JR
,
Brooks
LC
,
Davis
DW
, et al
.
Congenital syphilis: trends in mortality and morbidity in the United States, 1999 through 2013
.
Am J Obstet Gynecol
.
2016
;
214
(
3
):
381.e1
-
381.e9
2
Centers for Disease Control and Prevention
.
Sexually Transmitted Disease Surveillance 2017
.
Atlanta, GA
:
US Department of Health and Human Services
;
2018
3
Bowen
V
,
Su
J
,
Torrone
E
,
Kidd
S
,
Weinstock
H
.
Increase in incidence of congenital syphilis - United States, 2012-2014
.
MMWR Morb Mortal Wkly Rep
.
2015
;
64
(
44
):
1241
1245
4
Centers for Disease Control and Prevention
.
Syphilis Surveillance Supplement 2013–2017
.
Atlanta, GA
:
US Department of Health and Human Services
;
2019
5
Trivedi
S
,
Williams
C
,
Torrone
E
,
Kidd
S
.
National trends and reported risk factors among pregnant women with syphilis in the United States, 2012-2016
.
Obstet Gynecol
.
2019
;
133
(
1
):
27
32
6
Slutsker
JS
,
Hennessy
RR
,
Schillinger
JA
.
Factors contributing to congenital syphilis cases - New York City, 2010-2016
.
MMWR Morb Mortal Wkly Rep
.
2018
;
67
(
39
):
1088
1093
7
Alexander
JM
,
Sheffield
JS
,
Sanchez
PJ
,
Mayfield
J
,
Wendel
GD
 Jr
.
Efficacy of treatment for syphilis in pregnancy
.
Obstet Gynecol
.
1999
;
93
(
1
):
5
8
8
American Academy of Pediatrics
. Syphilis. In:
Kimberlin
DW
,
Brady
MT
,
Jackson
MA
,
Long
SS
, eds.
Red Book: 2018 Report of the Committee on Infectious Diseases
.
Grove Village, IL
:
American Academy of Pediatrics
;
2018
:pp
773
788
9
Gust
DA
,
Levine
WC
,
St Louis
ME
,
Braxton
J
,
Berman
SM
.
Mortality associated with congenital syphilis in the United States, 1992-1998
.
Pediatrics
.
2002
;
109
(
5
). Available at: www.pediatrics.org/cgi/content/full/109/5/E79
10
Cooper
JM
,
Sánchez
PJ
.
Congenital syphilis
.
Semin Perinatol
.
2018
;
42
(
3
):
176
184
11
Woods
CR
.
Syphilis in children: congenital and acquired
.
Semin Pediatr Infect Dis
.
2005
;
16
(
4
):
245
257
12
Rasool
MN
,
Govender
S
.
The skeletal manifestations of congenital syphilis. A review of 197 cases
.
J Bone Joint Surg Br
.
1989
;
71
(
5
):
752
755
13
Campbell
KA
,
Olson
LM
,
Keenan
HT
.
Critical elements in the medical evaluation of suspected child physical abuse
.
Pediatrics
.
2015
;
136
(
1
):
35
43
14
Connors
JM
,
Schubert
C
,
Shapiro
R
.
Syphilis or abuse: making the diagnosis and understanding the implications
.
Pediatr Emerg Care
.
1998
;
14
(
2
):
139
142
15
Lim
HK
,
Smith
WL
,
Sato
Y
,
Choi
J
.
Congenital syphilis mimicking child abuse
.
Pediatr Radiol
.
1995
;
25
(
7
):
560
561
16
Lee
G
,
Ball
C
,
Sellars
M
,
Hannam
S
.
Congenital syphilis as a differential diagnosis of non-accidental injury
.
Eur J Pediatr
.
2008
;
167
(
9
):
1071
1072
17
Gagnier
JJ
,
Kienle
G
,
Altman
DG
, et al;
CARE Group
.
The CARE guidelines: consensus-based clinical case report guideline development
.
J Clin Epidemiol
.
2014
;
67
(
1
):
46
51
18
Workowski
KA
,
Bolan
GA
;
Centers for Disease Control and Prevention
.
Sexually transmitted diseases treatment guidelines, 2015
.
MMWR Recomm Rep
.
2015
;
64
(
RR
):
1
137
19
Christian
CW
;
Committee on Child Abuse and Neglect
.
The evaluation of suspected child physical abuse [published correction appears in Pediatrics. 2015;136(3):583]
.
Pediatrics
.
2015
;
135
(
5
).
20
Rana
RS
,
Wu
JS
,
Eisenberg
RL
.
Periosteal reaction
.
AJR Am J Roentgenol
.
2009
;
193
(
4
):
W259
W272
21
Lago
EG
,
Vaccari
A
,
Fiori
RM
.
Clinical features and follow-up of congenital syphilis
.
Sex Transm Dis
.
2013
;
40
(
2
):
85
94
22
American Academy of Pediatrics, American College of Obstetricians and Gynecologists
.
Guidelines for Perinatal Care
, 8th ed.
Elk Grove Village, IL
:
American Academy of Pediatrics
;
2017
23
Curry
SJ
,
Krist
AH
,
Owens
DK
, et al;
US Preventive Services Task Force
.
Screening for syphilis infection in pregnant women: US Preventive Services Task Force reaffirmation recommendation statement
.
JAMA
.
2018
;
320
(
9
):
911
917
24
Kidd
S
,
Bowen
VB
,
Torrone
EA
,
Bolan
G
.
Use of national syphilis surveillance data to develop a congenital syphilis prevention cascade and estimate the number of potential congenital syphilis cases averted
.
Sex Transm Dis
.
2018
;
45
(
9S
suppl 1
):
S23
S28
25
Matthias
JM
,
Rahman
MM
,
Newman
DR
,
Peterman
TA
.
Effectiveness of prenatal screening and treatment to prevent congenital syphilis, Louisiana and Florida, 2013-2014
.
Sex Transm Dis
.
2017
;
44
(
8
):
498
502
26
Saloojee
H
,
Velaphi
S
,
Goga
Y
, et al
.
The prevention and management of congenital syphilis: an overview and recommendations
.
Bull World Health Organ
.
2004
;
82
(
6
):
424
430
27
Biswas
HH
,
Chew Ng
RA
,
Murray
EL
, et al
.
Characteristics associated with delivery of an infant with congenital syphilis and missed opportunities for prevention-California, 2012 to 2014
.
Sex Transm Dis
.
2018
;
45
(
7
):
435
441
28
Center for Health Statistics, California Department of Public Health
.
STD control branch.
2018
. Available at: https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/STD-Data-Syphilis-Congenital-Tables.pdf. Accessed January 16, 2019
29
Hersh
AR
,
Megli
CJ
,
Caughey
AB
.
Repeat screening for syphilis in the third trimester of pregnancy: a cost-effectiveness analysis
.
Obstet Gynecol
.
2018
;
132
(
3
):
699
707
30
Albright
CM
,
Emerson
JB
,
Werner
EF
,
Hughes
BL
.
Third-trimester prenatal syphilis screening: a cost-effectiveness analysis
.
Obstet Gynecol
.
2015
;
126
(
3
):
479
485
31
Shiber
L
,
Todia
WJ
.
Cost and clinical utility of repeated syphilis screening in the third trimester in a high-risk population
.
Am J Obstet Gynecol
.
2014
;
210
(
3
):
267.e1
-
267.e5

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.