Etiology

Syphilis is caused by Treponema pallidum, a long, motile spirochete with finely tapered ends belonging to the family Spirochaetaceae. The pathogenic members of this genus include T. pallidum subspecies pallidum (venereal syphilis), T. pallidum subspecies pertenue (yaws), T. pallidum subspecies endemicum (bejel or endemic syphilis), and T. pallidum subspecies carateum (pinta). Because these microorganisms stain poorly and are below the detection limits of conventional light microscopy, detection in clinical specimens requires dark-field or phase contrast microscopy or direct immunofluorescent staining. T. pallidum cannot be cultured in vitro.

Epidemiology

In addition to presentation at sexually transmitted disease clinics, patients with syphilis are increasingly seen by primary care providers in private practice settings. Two forms of syphilis occur in children. Acquired syphilis is transmitted almost exclusively by sexual contact, including oral sexual exposure. Less common modes of transmission include transfusion of contaminated blood or direct contact with infected tissues. After an epidemic resurgence of primary and secondary syphilis in the USA that peaked in 1989, the annual rate declined 90% by 2000. The total number of cases of primary and secondary syphilis has subsequently increased since 2000, particularly among men who have sex with men. Despite a decrease among women for almost a decade, their rates have also increased every year since 2004. By 2007, U.S. reported cases of syphilis had risen for the 7th straight year, a 15% increase from 2006 among men and women. Cases of congenital syphilis rose by 13% in the same time period (Fig. 210-1). Rates in the southern USA and among non-Hispanic blacks are disproportionately high.

Figure 210-1 Congenital syphilis (CS) rate among infants aged <1 yr and rate of primary and secondary syphilis (P&S) among girls and women aged ≥10 yr: National Electronic Telecommunication System for Surveillance, USA, 1995-2008. CS rates from 1995 to 2006 were calculated using yearly live birth data as denominators. Rates for 2007 and 2008 were calculated using live birth data for 2006.

(From Centers for Disease Control and Prevention: National vital statistics system: birth data [website]. http://www.cdc.gov/nchs/births.htm. Accessed August 25, 2010.) P&S syphilis rates were calculated using bridged race population estimates for 2000-2007 based on 2000 U.S. Census counts. (From CDC Wonder: Bridged-race resident population estimates, United States, state and county, for the years 1990-2008 (website). http://wonder.cdc.gov/wonder/help/bridged-race.html. Accessed August 25, 2010.) (From Centers for Disease Control and Prevention: Congenital syphilis—United States, 2003-2008, MMWR Morb Mortal Wkly Rep 59:413–417, 2010.)

Congenital syphilis results from transplacental transmission of spirochetes. Women with primary and secondary syphilis and spirochetemia are more likely to transmit infection to the fetus than are women with latent infection. Transmission can occur at any stage of pregnancy. The incidence of congenital infection in offspring of untreated or poorly treated infected women remains highest during the first 4 yr after acquisition of primary infection, secondary infection, and early latent disease. Risk factors most commonly associated with congenital syphilis are lack of prenatal care and cocaine drug abuse, unprotected sexual contact, trading of sex for drugs, and poor treatment of syphilis during pregnancy (Fig. 210-2). Confirmed cases of acquired or congenital syphilis should be reported to the local health department.

Figure 210-2 Diagnoses of congenital syphilis (CS) in the USA, 2002.

(From Centers for Disease Control and Prevention: Primary and secondary syphilis—United States, 2002, MMWR Morb Mortal Wkly Rep 52:1117–1120, 2003.)

Clinical Manifestations and Laboratory Findings

Many persons infected with syphilis are asymptomatic for years or do not recognize the early signs of disease. Primary syphilis is characterized by a chancre and regional lymphadenitis. A painless papule appears at the site of entry (usually the genitals) 2-6 wk after inoculation that develops into a clean, painless, but highly contagious ulcer with raised borders (chancre) containing abundant T. pallidum. Extragenital chancres can occur at other sites of primary entry. Oral lesions can be mistaken for aphthous ulcers or herpes. Adjacent lymph nodes are generally enlarged and nontender. The chancre heals spontaneously within 4-6 wk, leaving a thin scar.

Untreated patients develop manifestations of secondary syphilis related to spirochetemia 2-10 wk after the chancre heals. Manifestations of secondary syphilis include a generalized nonpruritic maculopapular rash, notably involving the palms and soles (Fig. 210-3). Pustular lesions can also develop. Condylomata lata, gray-white to erythematous wartlike plaques, can occur in moist areas around the anus and vagina, and white plaques (mucous patches) may be found in mucous membranes. A flulike illness with low-grade fever, headache, malaise, anorexia, weight loss, sore throat, myalgias, arthralgias, and generalized lymphadenopathy is often present. Renal, hepatic, and ophthalmologic manifestations may be present. Meningitis occurs in 30% of patients with secondary syphilis and is characterized by cerebrospinal fluid (CSF) pleocytosis and elevated protein level. Patients with meningitis might not show neurologic symptoms. Secondary infection becomes latent within 1-2 mo after onset of rash. Relapses with secondary manifestations can occur during the first year of latency (the early latent period). Late syphilis follows and may be either asymptomatic (late latent) or symptomatic (tertiary). Tertiary disease is marked by neurologic, cardiovascular, and gummatous lesions (nonsuppurative granulomas of the skin and musculoskeletal system resulting from the host’s hypersensitivity reaction).

Figure 210-3 Secondary syphilis. Ham-colored palmar macules on an adolescent with secondary syphilis.

(From Weston WL, Lane AT, Morelli JG: Color textbook of pediatric dermatology, ed 3, St Louis, Mosby, 2002.)

Congenital Infection

Untreated syphilis during pregnancy has a vertical transmission rate approaching 100%, with profound effects on pregnancy outcome. Fetal or perinatal death occurs in 40% of affected infants. Premature delivery can also occur. Neonates can also be infected at delivery by contact with an active genital lesion.

Most infected infants are asymptomatic at birth and are identified only by routine prenatal screening. In the absence of treatment, symptoms develop within weeks or months. Among infants symptomatic at birth or in the first months of life, manifestations have traditionally been divided into early and late stages. All stages of congenital syphilis are characterized by a vasculitis, with progression to necrosis and fibrosis. The early signs appear during the first 2 yr of life, and the late signs appear gradually during the first 2 decades. Early manifestations vary and involve multiple organ systems, resulting from transplacental spirochetemia and are analogous to the secondary stage of acquired syphilis (Table 210-1). Hepatosplenomegaly, jaundice, and elevated liver enzymes are common. Histologically, liver involvement includes bile stasis, fibrosis, and extramedullary hematopoiesis. Lymphadenopathy tends to be diffuse and resolve spontaneously, although shotty nodes can persist.

Table 210-1 LATE MANIFESTATIONS OF CONGENITAL SYPHILIS

SYMPTOM/SIGN	DESCRIPTION/COMMENTS
Olympian brow	Bony prominence of the forehead due to persistent or recurrent periostitis
Clavicular or Higouménaki sign	Unilateral or bilateral thickening of the sternoclavicular third of the clavicle
Saber shins	Anterior bowing of the midportion of the tibia
Scaphoid scapula	Convexity along the medial border of the scapula
Hutchinson teeth	Peg-shaped upper central incisors; they erupt during 6th yr of life with abnormal enamel, resulting in a notch along the biting surface
Mulberry molars	Abnormal 1st lower (6 yr) molars characterized by small biting surface and excessive number of cusps
Saddle nose*	Depression of the nasal root, a result of syphilitic rhinitis destroying adjacent bone and cartilage
Rhagades	Linear scars that extend in a spoke-like pattern from previous mucocutaneous fissures of the mouth, anus, and genitalia
Juvenile paresis	Latent meningovascular infection; it is rare and typically occurs during adolescence with behavioral changes, focal seizures, or loss of intellectual function
Juvenile tabes	Rare spinal cord involvement and cardiovascular involvement with aortitis
Hutchinson triad	Hutchinson teeth, interstitial keratitis, and 8th nerve deafness
Clutton joint	Unilateral or bilateral painless joint swelling (usually involving knees) due to synovitis with sterile synovial fluid; spontaneous remission usually occurs after several wk
Interstitial keratitis	Manifests with intense photophobia and lacrimation, followed within weeks or months by corneal opacification and complete blindness.
Eighth nerve deafness	May be unilateral or bilateral, appears at any age, manifests initially as vertigo and high-tone hearing loss, and progresses to permanent deafness

* A perforated nasal septum may be an associated abnormality.

Coombs-negative hemolytic anemia is characteristic. Thrombocytopenia is often associated with platelet trapping in an enlarged spleen. Characteristic osteochondritis and periostitis (Fig. 210-4) and a mucocutaneous rash (Fig. 210-5A, B) manifesting with erythematous maculopapular or vesiculobullous lesions followed by desquamation involving hands and feet (see Fig. 210-5C) are common. Mucous patches, persistent rhinitis (snuffles), and condylomatous lesions (Fig. 210-6) are highly characteristic features of mucous membrane involvement and contain abundant spirochetes. Blood and moist open lesions from infants with congenital syphilis and children with acquired primary or secondary syphilis are infectious until 24 hours of appropriate treatment.

Figure 210-4 Osteochondritis and periostitis in a newborn with congenital syphilis.

Figure 210-5 A and B, Papulosquamous plaques in 2 infants with syphilis. C, Desquamation on the palm of a newborn’s hand.

(A and B, From Eichenfeld LF, Frieden IJ, Esterly NB, editors: Textbook of neonatal dermatology, Philadelphia, 2001, WB Saunders, p 196. C, Courtesy of Dr. Patricia Treadwell.)

Figure 210-6 Perianal condylomata lata.

(From Karthikeyan K, Thappa DM: Early congenital syphilis in the new millennium, Pediatr Dermatol 19:275–276, 2002.)

Bone involvement is common. Roentgenographic abnormalities include Wimberger’s lines (metaphyseal demineralization of the medial aspect of the proximal tibia), multiple sites of osteochondritis at the wrists, elbows, ankles, and knees, and periostitis of the long bones and rarely the skull. The osteochondritis is painful, often resulting in irritability and refusal to move the involved extremity (pseudoparalysis of Parrot).

Central nervous system (CNS) abnormalities, failure to thrive, chorioretinitis, nephritis, and nephrotic syndrome may also be seen. Manifestations of renal involvement include hypertension, hematuria, proteinuria, hypoproteinemia, hypercholesterolemia, and hypocomplementemia, probably related to glomerular deposition of circulating immune complexes. Less common clinical manifestations of early congenital syphilis include gastroenteritis, peritonitis, pancreatitis, pneumonia, eye involvement (glaucoma and chorioretinitis), nonimmune hydrops, and testicular masses.

Late manifestations (children >2 years of age) are rarely seen in developed countries. These result primarily from chronic granulomatous inflammation of bone, teeth, and CNS and are summarized in Table 210-1. Skeletal changes are due to persistent or recurrent periostitis and associated thickening of the involved bone. Dental abnormalities such as Hutchinson teeth (Fig. 210-7) are common. Defects in enamel formation lead to repeated caries and eventual tooth destruction. Saddle nose (Fig. 210-8) is a depression of the nasal root and may be associated with a perforated nasal septum.