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Definitions and Epidemiology
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Syphilis is one of the “great pretenders” because the disease may manifest with a broad range of signs and symptoms that mimic many other diseases. It has been a serious public health concern for centuries. The infection causes disease in both adults and children and, when acquired during pregnancy, poses a serious threat to the fetus.
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Syphilis is caused by T. pallidum, a motile spirochete and one of four treponomemal pathogens that cause human disease. A significant peak in the incidence of acquired and congenital syphilis occurred in the late 1980s and early 1990s, with a dramatic decrease in the rates of both types of disease in the last decade (Figure 50–4). The incidence of disease varies by race and region with the highest rates of infection found in African Americans and Latinos living in urban areas of the southern and northeast United States.2,32–34
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Outside the newborn period, syphilis is primarily transmitted through sexual contact with an infected individual. Involvement with multiple sexual partners, poverty, illicit drug use, and coinfection with HIV are the risk factors most consistently associated with disease acquisition.34,35
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In congenital syphilis, the disease is transmitted from mother to infant via transplacental passage or through contact with infectious lesions at the time of delivery. The infection can be transmitted at any stage although risk of transmission varies with the stage of disease in the mother. Pregnant women with untreated primary or secondary syphilis have a 60–90% transmission rate compared to a 10–30% transmission rate in latent disease.2,32 Lack of, or inadequate, prenatal care is a major contributor to vertical transmission rates of infection from mother to infant and the disease is almost completely preventable when detected and treated during pregnancy.34,35
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Clinical Presentation
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Thirty to forty percent of women with untreated syphilis in early pregnancy suffer complications such as spontaneous abortion, stillbirth, or preterm delivery. Other complications include placentomegaly, hydrops fetalis, and perinatal death.2,34 Up to one-third of surviving infants with congenital syphilis are symptomatic at birth. Manifestations of congenital syphilis are divided into early and late findings.34 Early signs and symptoms occur in the first 2 years of life, mainly presenting in the first 3–8 weeks. Early symptoms, attributable to active infection and inflammation, include low birth weight, failure to thrive, lymphadenopathy, hydrocephalus, edema, fever, or a maculopapular rash that later desquamates. Respiratory and gastrointestinal manifestations include respiratory distress, bloody rhinitis called “snuffles,” hepatosplenomegaly, hepatitis, and jaundice. Hematologic findings include Coombs-negative hemolytic anemia and thrombocytopenia. Bony lesions, frequently seen in untreated infants, are often symmetric and occur at multiple sites. They include osteochondritis of joints, periostitis, and cortical demineralization of long bones. Painful lesions give rise to “pseudoparalysis of Parrot,” a condition where an infant refuses to move an affected extremity.2,32–34
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Late manifestations, those appearing after the age of 2 years, occur in ∼40% of untreated infants. These findings are typically the result of tissue scarring due to initial infection. These findings include frontal bossing, destruction of the nasal cartilage (saddle nose deformity), anterior bowing of shins (or saber shins), multicuspid first molars (mulberry molars), peg-shaped upper incisors (Hutchinson teeth), linear scars from the corners of the mouth (rhaghades), seizures, interstitial keratitis, and eighth nerve deafness.2,32,34
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Neurosyphilis may be either an early or late manifestation of congenital infection. It is often asymptomatic and may present in an acute or chronic manner. Acutely, the disease may manifest as meningitis with signs of increased intracranial pressure and abnormal CSF findings.32,34 Neurosyphilis may also present in a chronic manner with evidence of progressive and evolving disease, characterized by cranial nerve abnormalities, loss of developmental milestones, seizures, hydrocephalus, and strokes.34
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A variety of tests are available for the diagnosis of syphilis. A direct diagnosis can be made if spirochetes are visualized with special stains, by DFA, or by dark-field microscopy in specimens of placenta, cord, amniotic fluid, or infectious lesions. While direct visualization of the organism provides a clear and definitive diagnosis, it is not always practical or possible. Serologic diagnosis is possible using available treponemal-specific and nontreponemal-specific testing.32–34
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Nontreponemal tests are screening tests that include the Venereal Disease Research Laboratory (VDRL) slide test, the rapid plasma reagin (RPR) test, the automated reagin test (ART). They provide quantitative results that can be used to follow treatment efficacy and disease status. Adequate treatment is indicated by a fourfold decrease in antibody titer, usually seen by 6 months, while reinfection or failure of antibiotic therapy is detected by a fourfold increase. Negative serologic status is expected after adequate treatment within 1–2 years. Nontreponemal tests have a high rate of false-positive results attributable to other infections or medical conditions such as varicella, Epstein–Barr virus, systemic lupus erythematosus, and other collagen vascular disease, or tuberculosis. A reactive nontreponemal test must be confirmed by a treponemal-specific test.32,34
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Occasionally, a surplus of antibody in blood samples inhibits antibody–antigen complexes, resulting in false-negative reactions. This reaction, termed the prozone phenomenon, is a rare occurrence that can be overcome by dilution of the serum sample. Dilution should be performed when suspicion of infection is high, the infant or fetus has signs suggestive of congenital infection yet maternal serology is negative.32,33
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Confirmatory treponemal-specific tests, which detect antibodies to surface proteins, include the fluorescent treponemal antibody absorption test (FTA-ABS) and the microhemagglutination for T. pallidum (MHA-TP). Once these tests become positive, they remain so for life and cannot be used to evaluate treatment or disease status. False positives occur in the face of infections caused by other spirochetes such as Yaws (caused by Treponema pertenue, a subspecies of T. pallidum), Pinta (caused by Treponema carateum), and Lyme disease (caused by Borrelia burgdorferi).32,33
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Prenatal diagnosis and treatment of syphilis significantly reduces the risk of vertical transmission. With the recent resurgence of syphilis, particularly in communities with limited resources, careful and tenacious follow-up of pregnant women with the disease and efficient identification of infected newborns is critical in combating this preventable childhood infection.36 Accordingly, the Centers for Disease Control (CDC) and American Association of Pediatrics (AAP) recommend comprehensive screening for the infection in pregnant women. Nontreponemal testing should be routinely obtained during early prenatal care at the beginning of pregnancy. For women in high-risk categories, testing should be repeated at the beginning of the third trimester as well as at the time of delivery. Maternal serology should be known prior to the discharge of all infants. A reactive VDRL or RPR should be confirmed with a treponemal-specific test. If syphilis is diagnosed in pregnancy, repeat serologies are required at the end of treatment to document response to therapy and to evaluate for possible reinfection.32,33
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The diagnosis of congenital syphilis is classified as confirmed, presumptive, or possible based on both maternal and infant factors. The classification aids clinicians in evaluation and treatment decisions. Box 50–1 represents clinical and surveillance definitions adapted from the recommendations of the Committee on Infectious Disease, American Academy of Pediatrics.32–34
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Any newborn whose mother has a positive serology should have a thorough physical examination and blood sent for the same serologic test as its mother to facilitate comparison of titers. Table 50–5 serves as a guide for the interpretation of serologic tests obtained in women with suspected disease and their infants. The combination of nontreponemal- and treponemal-specific tests and the comparison between maternal and infant results allows for risk assessment of disease. Infants merit a complete investigation if their titers are fourfold greater than their mothers, if they manifest disease, or if their mothers’ titers have risen fourfold.32 Due to the potentially devastating effects of untreated syphilis, evaluation of newborns is also warranted when maternal serologies are reactive and questions exist regarding the adequacy of maternal treatment.32 Infants with suspected disease by any of the above criteria should be evaluated for stigmata of disease by physical examination, radiologic evaluation, and laboratory testing.2,32
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Infants with congenital disease require treatment to avoid the long-term and serious sequelae of untreated congenital syphilis such as deafness, blindness, mental retardation, and facial deformities. Congenital syphilis is treated with aqueous crystalline penicillin (PCN) G 50,000 units/kg every 12 hours for first week of life and then every 8 hours for a total of 10 days or Procaine PCN G 50,000 units/kg/d administered intramuscularly for 10 days. If more than 1 day of therapy is missed, the entire treatment course must be repeated.2,32–34
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Adequate follow-up for infants initially evaluated and treated is essential in the assessment of late manifestations of disease. After completion of treatment, current recommendations suggest follow-up clinical examination at 1, 2, 4, 6, and 12 months of age. Serologic testing is recommended at 2, 4, 6, and 12 months after completion of therapy or until the results are nonreactive or the titers have fallen fourfold. Titers should be undetectable by 6 months. Persistent or rising titers between 6 and 12 months of age are an indication for further evaluation including CSF sampling and retreatment with PCN G for 10–14 days.2,32
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Infants with clinical or laboratory findings consistent with neurosyphilis require repeat CSF evaluations every 6 months until the CSF examination is normal. Patients whose 6-month CSF samples demonstrate positive VDRL reactivity or persistent leukocytosis at 2 years require retreatment.2,32