Decreased Leg Movement and Pain in a 2-Month-Old Infant

A 2-month-old girl presents for evaluation after a 2-week history of decreased movement of her left lower extremity and perceived pain.The infant was born at term via cesarean section because of active herpetic lesions to a 23-year-old mother with fragmented prenatal care. No maternal or birth records were available at the time of presentation, but per verbal history, the mother was treated for syphilis during pregnancy and was herpes simplex virus positive. Per her mother’s report, the infant had a nonreactive rapid plasma reagin (RPR) test result after birth. She had an uneventful course in the nursery and was discharged home on day of life 3.The infant subsequently established care with a pediatrician and has had appropriate routine care. She has been developing and growing appropriately. The infant has no history of fever or rashes. No trauma is reported.The infant initially presented to the pediatrician 5 days ago, at which time a hip ultrasound was ordered. However, in the interim, her mother observed increased swelling and redness to the leg. She brought the infant to an outside emergency department, where plain radiographs were performed, revealing a left proximal tibial shaft fracture with a possible lytic lesion and associated periosteal reaction (Figure 1). The infant was then transferred to our tertiary care center for further management.Her vital signs are within reference ranges, and examination shows a well-appearing infant. She is noted to have limited active movement of the left leg with mild localized swelling and erythema over the proximal left tibia. She cries when the leg is passively moved. All other extremities are normal in appearance and have full, painless range of motion. There are no conjunctival hemorrhages, abdominal tenderness, rashes, bruises, or wounds.Laboratory test results are collected, including complete blood count (CBC), basic metabolic panel, magnesium, phosphorous, liver function tests (LFTs), lipase, urinalysis, prothrombin time/international normalized ratio (PT/INR), partial thromboplastin time (PTT), erythrocyte sediment rate (ESR), C-reactive protein (CRP), and vitamin D. Abnormal results include a platelet count of 885 000/μL (reference range 288 000–615 000/μL), aspartate transaminase of 107 U/L (reference range 10–35 U/L), alanine transaminase of 201 U/L (reference range 6–45 U/L), CRP of 3.36 mg/dL (reference range <0.50 mg/dL), and ESR of 77 mm/h (reference range 0–20 mm/h). A skeletal survey is obtained: a proximal tibia fracture with periosteal changes is confirmed and believed to be consistent with an aggressive osteolytic lesion, with no additional fractures identified. Magnetic resonance imaging is obtained, which reveals the additional finding of a small sinus tract within the proximal left tibial metaphysis (Figure 2), and subsequently, a needle aspirate bone biopsy is performed that confirms the diagnosis (Figure 3).The differential diagnosis for this suspected pathologic fracture includes primary and metastatic oncologic processes such as Ewing sarcoma, osteosarcoma, and neuroblastoma; osteomyelitis, including syphilitic; and Langerhans cell histiocytosis. Given the fracture’s aggressive osteolytic appearance, direct biopsy was undertaken: the sample stain was positive for spirochetes, confirming syphilitic osteomyelitis.Syphilis is caused by the spirochete Treponema pallidum. Congenital syphilis occurs most often by transplacental transmission but rarely can occur during childbirth.1 Primary and secondary syphilis infections in pregnant women are associated with the highest incidence of fetal transmission.2 Primary syphilis presents with painless indurated mucocutaneous ulcers occurring 3 weeks after exposure. Secondary syphilis presents with fever, malaise, arthralgia, generalized lymphadenopathy, and maculopapular rash including the palms and soles, occurring 1–2 months after exposure.1 The incidence of syphilis in the United States has been rising annually since 2013, with the Centers for Disease Control and Prevention (CDC) having reported incidence of congenital syphilis in 2020 of 57.3 cases per 100 000 live births, a 254% increase from 2016.3Identification by prenatal testing and adequate treatment at least 30 days prior to birth can prevent up to 98% of cases of congenital syphilis.1 Most commonly, prenatal testing is performed by serologic screening with nontreponemal tests: either RPR or VDRL testing. If serologic screen results are positive, then a confirmatory treponemal test is performed.2 Treatment is a penicillin regimen appropriate for the stage of infection. Primary and secondary syphilis are treated with intramuscular benzathine penicillin G 2.4 million units.1Currently, there is no consensus regarding the frequency and timing of testing: recommendations vary among medical organizations, as well as individual state laws. Testing early in the pregnancy at the first prenatal visit is universally recommended, but guidelines for repeat screening during the third trimester and at the time of birth are less consistent. The American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) have joint guidelines that recommend screening for women at high risk at the beginning of the third trimester and universal screening at delivery.4 The American Academy of Family Physicians (AAFP) and CDC recommend screening only for high-risk patients in the third trimester and at delivery.5 The United States Preventative Task Force (USPSTF) recommends testing at delivery only for women who received no prenatal care and thus did not receive early screening.6 Patients classified as high risk include those with HIV, a history of incarceration or commercial sex work, or a positive serology test result in the first trimester or those living in high-prevalence communities.4,6 However, half of all cases of women diagnosed with syphilis in pregnancy did not report high-risk behaviors.1 As of July 2021, 42 states have legal requirements for syphilis screening for all women at first prenatal visit; 15 states require third-trimester screening for all women, with an additional 5 states requiring it for women at high risk; and 5 states require screening at the time of delivery, with an additional 7 states requiring it for women at high risk.7 Of note, even with nontreponemal testing performed multiple times throughout pregnancy, including at delivery, with negative results, there are reported cases of infants developing congenital syphilis when maternal syphilis is contracted very late in pregnancy.8Presentations of congenital syphilis are classified as either early or late. Early congenital syphilis includes clinical manifestations from birth until age 2 years; late congenital syphilis is defined as the appearance of symptoms beyond 2 years.9,10 Classic presentations of early congenital syphilis include the characteristic nasal discharge (“snuffles”), diffuse maculopapular rash, fever, pneumonia, hepatosplenomegaly, jaundice, edema, hemolytic anemia, and thrombocytopenia.9 Late congenital syphilis clinically manifests with Hutchinson’s triad (blunted upper incisors, interstitial keratitis, and sensorineural hearing loss), saddle nose deformity, anterior tibial bowing (“saber shins”), frontal bossing, hard palate defects, and intellectual disability.8–10Skeletal manifestations can occur in both early and late congenital syphilis because of direct infiltration of the organism into the bone. In early congenital syphilis, this can cause isolated fractures or osteoperiostitis of long bones in both the metaphysis and diaphysis, causing pain and decreased movement, referred to as “Pseudoparalysis of Parrot.”2 Because isolated fractures in infants and toddlers without a history of trauma raises suspicion for nonaccidental trauma, early congenital syphilis may easily be mistaken for this entity. In many such cases, review of skeletal surveys shows periosteal reactions of other long bones, on initial presentation or retrospective review.2 In our patient, given the history of maternal syphilis, special attention was paid to the radiographic inspection of all long bones, without any evidence of periosteal reaction or other osseous abnormality outside of the isolated proximal tibia fracture. This patient’s monostotic osteomyelitis is an atypical presentation of syphilitic osteomyelitis.All neonates born to seropositive mothers should be evaluated thoroughly for congenital syphilis, including RPR (or VDRL) test, CBC, LFTs, cerebrospinal fluid (CSF) studies including quantitative VDRL test, and based on the results, skeletal survey, ophthalmology evaluation, neuroimaging, and auditory brainstem responses.4 A confirmed case includes any neonate with an RPR titer that is 4-fold higher than the mother’s titer at delivery or with clinical manifestations (Table 1).3 The recommended treatment for confirmed congenital syphilis is parenteral aqueous crystalline penicillin G 100 000 to 150 000 U/kg/d, administered as 50 000 U/kg every 8–12 hours (based on age) for a total of 10 days.1 A neonate born to a mother who received inadequate treatment or treatment within 30 days of delivery who has a normal physical examination result and RPR titer equal to or less than 4-fold the maternal RPR titer at delivery warrants concern for possible congenital syphilis and should receive treatment with the same regimen.1 If the mother is appropriately treated at least 30 days before delivery but has high RPR titer (≥1:4), the neonate should be treated with a single dose of intramuscular benzathine penicillin G 50 000 U/kg.1 With adequate treatment, clinical features are expected to resolve within 3 months, and RPR titers should decrease 4-fold by 6 months and become nonreactive by 12 and 24 months after therapy.1 Titers that do not decrease suggest either treatment failure or reinfection.8Maternal records obtained during hospitalization documented treatment with penicillin after delivery. The infant’s RPR test result was positive (titer of 1∶8), and confirmatory treponemal test result was reactive. A lumbar puncture revealed pleocytosis with 29 nucleated cells per microliter, but VDRL test result of the CSF was nonreactive. An ophthalmology evaluation was unremarkable. The infant completed a 10-day course of parenteral penicillin with subsequent normalization of transaminases, thrombocytosis, and inflammatory markers. She was discharged home with multidisciplinary follow-up including general pediatrics, infectious disease, and orthopedics.The incidence of syphilis continues to rise in the United States, and so has the incidence of congenital syphilis.Because congenital syphilis can often be asymptomatic or present with nonspecific symptoms, it can be difficult to diagnose without a detailed review of the birth history and high index of suspicion.Delayed diagnosis and initiation of treatment may lead to manifestations of early and/or late congenital syphilis. The bony manifestations of congenital syphilis may be mistaken for accidental or nonaccidental trauma. It is crucial that pediatricians have competence in interpretation of prenatal screening, maternal syphilis treatment, and the evaluation and treatment of congenital syphilis.Nationwide adoption of universal prenatal screening for maternal syphilis at the first trimester, third trimester, and time of delivery should be considered to increase primary prevention of congenital syphilis.