Primary syphilis is characterized by syphilitic chancre and regional lymphadenitis. A painless papule appears at the site of inoculation 2–6 wk after inoculation with T. pallidum. The papule soon develops into a clean, painless ulcer with raised borders called a chancre. The chancre, usually on the genitals, contains viable T. pallidum and is highly contagious. Extragenital chancres can be seen also, depending on the site of primary inoculation. Adjacent lymph nodes are generally enlarged. The chancre heals spontaneously within 4–6 wk, leaving a thin scar.
Untreated patients develop manifestations of secondary syphilis 2–10 wk after the chancre heals. Manifestations of secondary syphilis are related to spirochetemia and include a nonpruritic maculopapular rash, which can cover the entire body, and notably involving the palms and soles ( Fig. 215-2 ). Pustular lesions may also develop. Condylomata lata, which are gray-white to erythematous wartlike plaques, can occur in moist areas around the anus and vagina, and white plaques called 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, as may be meningitis, which occurs in 30% of patients with secondary syphilis, manifested by cerebrospinal fluid (CSF) pleocytosis and elevated protein level, although the patient may not show neurologic symptoms. Secondary infection becomes latent within 1–2 mo after the onset of the rash. Relapses with secondary manifestations can occur during the 1st year of latency, a period referred to as the early latent period. No relapses occur after the 1st year. What follows is late syphilis, which may be either asymptomatic (late latent) or symptomatic (tertiary). At this stage, patients may begin showing the manifestations of tertiary disease, which include neurologic, cardiovascular, and gummatous lesions. The lesions are granulomas of the skin and musculoskeletal system resulting from the host's delayed hypersensitivity reaction
Congenital Infection.
Untreated syphilis during pregnancy has a transmission rate approaching 100%. Fetal or perinatal death occurs in 40% of affected infants. Among survivors, manifestations have traditionally been divided into early and late stages. The early signs appear during the 1st 2 yr of life, and late signs appear gradually during the 1st 2 decades. Early manifestations result from transplacental spirochetemia and are analogous to the secondary stage of acquired syphilis. Approximately 66% of infected infants are asymptomatic at the time of birth and are identified only by routine prenatal screening; if they are untreated, symptoms develop within weeks or months.
The early manifestations of congenital infection are varied and involve multiple organ systems ( Table 215-1 ). Hepatosplenomegaly, jaundice, and elevated liver enzymes are common. Histologically, liver involvement includes bile stasis, fibrosis, and extramedullary hematopoiesis. Lymphadenopathy tends to be diffuse and to resolve spontaneously, although shotty nodes may persist. Coombs negative hemolytic anemia is characteristic. Thrombocytopenia is often associated with platelet trapping in an enlarged spleen. Characteristic osteochondritis and periostitis ( Fig. 215-3 ) and mucocutaneous rash ( Fig. 215-4 ), pre senting with erythematous maculopapular or bullous lesions, followed by desquamation involving hands and feet, are common. Mucous patches, rhinitis (snuffles), and condylomatous lesions ( Fig. 215-5 ) are highly characteristic features of mucous membrane involvement in congenital syphilis. Bone involvement occurs frequently. Roentgenographic abnormalities include 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 and often results 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. Clinical manifestations of renal involvement include hypertension, hematuria, proteinuria, hypoproteinemia, hypercholesterolemia, and hypocomplementemia. They appear to be 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.
TABLE 215-1 -- Clues That Suggest a Diagnosis of Congenital Syphilis[*]
| EPIDEMIOLOGIC BACKGROUND | CLINICAL FINDINGS |
| Untreated early syphilis in the mother | Osteochondritis, periostitis |
| Untreated latent syphilis in the mother | Snuffles, hemorrhagic rhinitis |
| An untreated mother who has contact with a known syphilitic during pregnancy | Condylomata lata |
| Bullous lesions, palmar/plantar rash | |
| Mother treated for syphilis during pregnancy with a drug other than penicillin | Mucous patches |
| Hepatomegaly, splenomegaly | |
| Mother treated for syphilis during pregnancy without follow-up to delivery | Jaundice |
| Nonimmune hydrops fetalis | |
| Generalized lymphadenopathy | |
| Central nervous system signs; elevated cell count or protein in cerebrospinal fluid | |
| Hemolytic anemia, diffuse intravascular coagulation, thrombocytopenia | |
| Pneumonitis | |
| Nephrotic syndrome | |
| Placental villitis or vasculitis (unexplained enlarged placenta) | |
| Intrauterine growth restriction |
The late manifestations result primarily from chronic inflammation of bone, teeth, and the CNS. Skeletal changes due to persistent or recurrent periostitis and associated thickening of bone include frontal bossing, a bony prominence of the forehead(olympian brow), unilateral or bilateral thickening of the sternoclavicular third of the clavicle (clavicular or Higouménaki sign), an anterior bowing of the midportion of the tibia (saber shins), and convexity along the medial border of the scapula (scaphoid scapula). Dental abnormalities are common and include Hutchinson teeth ( Fig. 215-6 ), which are the peg or barrel-shaped upper central incisors that erupt during the 6th yr of life; abnormal enamel, which results in a notch along the biting surface; and mulberry molars, the abnormal 1st lower (6 yr) molars characterized by a small biting surface and an excessive number of cusps. Defects in enamel formation lead to repeated caries and eventual tooth destruction.
A saddle nose ( Fig. 215-7 ), a depression of the nasal root, is a result of syphilitic rhinitis that destroys the adjacent bone and cartilage. A perforated nasal septum may be an associated abnormality. Rhagades are linear scars that extend in a spokelike pattern from previous mucocutaneous fissures of the mouth, anus, and genitalia. Juvenile paresis, an uncommon latent meningovascular infection, typically presents during adolescence with behavioral changes, focal seizures, or loss of intellectual function. Juvenile tabes with spinal cord involvement and cardiovascular involvement with aortitis are extremely rare.
Other late manifestations of congenital syphilis may represent a hypersensitivity phenomenon. These include unilateral or bilateral interstitial keratitis with symptoms such as intense photo phobia and lacrimation, followed within weeks or months by corneal opacification and complete blindness. Less common ocular manifestations include choroiditis, retinitis, vascular occlusion, and optic atrophy. Eighth nerve deafness may be unilateral or bilateral, appears at any age, presents initially as vertigo and high-tone hearing loss, and progresses to permanent deafness. The Clutton joint represents a unilateral or bilateral synovitis involving the lower extremities (usually the knee), which presents as painless joint swelling with sterile synovial fluid; spontaneous remission usually occurs after a period of several weeks. Soft tissue gummas (identical to those of acquired disease) and paroxysmal cold hemoglobinuria are rare hypersensitivity phenomena.
Diagnosis of primary syphilis is confirmed when T. pallidum is demonstrated by dark-field microscopy or direct fluorescent antibody–T. pallidum testing on specimens from skin lesions, placenta, or umbilicus. Nontreponemal tests, which are the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests, detect antibodies against phospholipid antigens on the surface of treponeme that cross react with mammalian cardiolipin antigens. The nontreponemal tests usually become nonreactive within 1 yr of adequate therapy for primary syphilis and within 2 yr of adequate treatment for secondary disease. With congenital infection, these tests become nonreactive within a few months after adequate treatment. Treponemal tests, which measure antibody specific for T. pallidum, include the T. pallidum hemagglutination assay (TPHA), the fluorescent treponemal antibody absorption (FTA-ABS) test, and the T. pallidum particle agglutination (TPPA) test. Treponemal tests are used for confirmatory testing of positive results of the nontreponemal antibody tests. Treponemal antibody titers become positive soon after initial infection and usually remain positive for life, even with adequate therapy. These antibody titers do not correlate with disease activity and are not quantified. They are useful for diagnosis of a 1st episode of syphilis and for distinguishing false-positive results of nontreponemal antibody tests but are of limited usefulness in the evaluation of response to therapy and possible reinfections. The nontreponemal tests (VDRL, RPR) are uniformly nonreactive in Lyme disease. Passively acquired antibody is suggested by neonatal titer at least 4-fold (i.e., a 2-tube dilution) less than the maternal titer. The diagnosis of neurosyphilis is established by demonstrating pleocytosis and increased protein in the CSF, and a positive CSF VDRL test along with neurologic symptoms. The CSF VDRL test is very specific but relatively insensitive (22–69%) for neurosyphilis.
Symptomatic infants should be thoroughly evaluated (see Table 215-1 ) and treated. Asymptomatic infants considered at risk for congenital syphilis because the maternal nontreponemal and treponemal serology is positive should be evaluated if (1) maternal treatment was inadequate, unknown, or undocumented; (2) maternal treatment was ≤30 days before delivery; (3) the mother was treated with erythromycin or another nonpenicillin regimen; or (4) the maternal nontreponemal titers did not decrease sufficiently to demonstrate a cure (4-fold or greater). If the maternal treatment was adequate and ≥1 mo before delivery, the infant's positive nontreponemal test result represents passively acquired antibody and the infant does not need treatment at delivery, but follow-up serology should be obtained. If the maternal evaluation is incomplete, these infants are assumed infected and treated.
TABLE 215-2 -- Recommended Treatment of Neonates (≤4 wk of age) With Proven or Possible Congenital Syphilis
| CLINICAL STATUS | EVALUATION | ANTIMICROBIAL THERAPY[*] |
| |||
| Proven or highly probable disease[†] | CSF analysis for VDRL, cell count, and protein | Aqueous crystalline penicillin G, 100,000–150,000 U/kg/day, administered as 50,000 U/kg/dose IV every 12 hr during the 1st 7 days of life and every 8 hr thereafter for a total of 10 days |
| |||
| CBC and platelet count |
| |||||
| Other tests as clinically indicated (e.g., long bone radiography, liver function tests, ophthalmologic examination) | ||||||
| OR |
| |||||
| Penicillin G procaine,[‡] 50,000 U/kg/day IM in a single dose for 10 days |
| |||||
| Normal physical examination and serum quantitative nontreponemal titer the same or <4-fold> | | |
| |||
| CSF analysis for VDRL, cell count, and protein | Aqueous crystalline penicillin G IV for 10 days[‡] |
| |||
| CBC and platelet count | OR |
| ||||
| Long bone radiography | Penicillin G procaine,[‡] 50,000 U/kg/day IM in a single dose for 10 days[§] |
| ||||
| OR |
| |||||
| Penicillin G benzathine, 50,000 U/kg IM in a single dose[§] |
| |||||
| None | Clinical, serologic follow-up, and penicillin G benzathine, 50,000 U/kg IM in a single dose[∥] |
| |||
| None | None[¶] |
|
The diagnosis of neurosyphilis in the newborn with syphilitic infection is difficult owing to the poor sensitivity of the CSF VDRL test in this age group and the lack of CSF abnormalities. A positive CSF VDRL test result in a newborn warrants treatment for neurosyphilis, even though it might reflect passive transfer of antibodies from serum to CSF. More importantly, it is now accepted that all infants with a presumptive diagnosis of congenital syphilis should be treated with regimens effective for neurosyphilis because this cannot be reliably excluded.
TABLE 215-3 -- Recommended Treatment for Syphilis in People >4 Weeks of Age
| | CHILDREN | ADULTS |
| Congenital syphilis | Aqueous crystalline penicillin G, 200,000–300,000 U/kg/day IV administered as 50,000 U/kg every 4–6 hr for 10 days[*] | |
| Primary, secondary, and early latent syphilis[†] | Penicillin G benzathine,[‡] 50,000 U/kg IM up to the adult dose of 2.4 million U in a single dose | Penicillin G benzathine, 2.4 million U IM in a single dose |
| OR | ||
| If allergic to penicillin and not pregnant, Doxycycline, 100 mg orally twice a day for 14 days | ||
| OR | ||
| Tetracycline, 500 mg orally 4 times/day for 14 days | ||
| Late latent syphilis[§] or latent syphilis of unknown duration | Penicillin G benzathine, 50,000 U/kg IM up to the adult dose of 2.4 million U, administered as 3 single doses at 1 wk intervals (total 150,000 U/kg, up to the adult dose of 7.2 million U) | Penicillin G benzathine, 7.2 million U total, administered as 3 doses of 2.4 million U IM each at 1 wk intervals |
| OR | ||
| If allergic to penicillin and not pregnant, Doxycycline, 100 mg orally twice a day for 4 wk | ||
| OR | ||
| Tetracycline, 500 mg orally 4 times/day for 4 wk | ||
| Tertiary | — | Penicillin G benzathine, 7.2 million U total, administered as 3 doses of 2.4 million U IM at 1 wk intervals |
| If allergic to penicillin and not pregnant, same as for late latent syphilis | ||
| Neurosyphilis[∥] | Aqueous crystalline penicillin G, 200,000 to 300,000 U/kg/day, given every 4–6 hr for 10–14 days in doses not to exceed the adult dose | Aqueous crystalline penicillin G, 18–24 million U/day, administered as 3–4 million U IV every 4 hr for 10–14 days[¶] |
| OR | ||
| Penicillin G procaine,[†] 2.4 million U IM once daily PLUS probenecid, 500 mg orally 4 times/day, both for 10–14 days[¶] |
Prevention
In pregnant women without optimal prenatal care, serologic screening for syphilis should be performed at the time pregnancy is diagnosed. Any woman who is delivered of a stillborn infant ≥20 wk of gestation should be tested for syphilis. In communities and populations with a high prevalence of syphilis, or for patients at high risk, testing should be performed at least 2 additional times: at the beginning of the 3rd trimester (28 wk) and at delivery
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