Today again I have got the opportunity of presenting a lecture at the continuous medical education program of the Kenya Medical Association-Meru Branch. I am very happy of the occasion given me to show that Chaaria is a hospital in which there is know-how, expertise and scientific effort of continually updating our medical knowledge.
Here below is the abstract of what I have presented.
Bro Dr Giuseppe Gaido
SYPHILIS
Syphilis is an infectious venereal disease caused by the spirochete Treponema pallidum.
Syphilis is transmissible:
- by sexual contact with infectious lesions,
- from mother to fetus in utero,
- via blood product transfusion,
- through breaks in the skin that come into contact with infectious lesions (occasionally).
If untreated, it progresses through 4 stages: primary, secondary, latent, and tertiary.
Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in advanced stages. That is why it is sometimes very difficult to diagnose it.
Epidemiology
Internationally, the prevalence of syphilis varies by region. Syphilis remains prevalent in many developing countries and in some areas of North America, Asia, and Europe, especially Eastern Europe. The highest rates are in South and Southeast Asia, followed closely by Sub-Saharan Africa.
Syphilis is most common during the years of peak sexual activity. Most new cases occur in men and women aged 15-40 years.
Men are affected more frequently with primary or secondary syphilis than women.
Pathophysiology
Treponema pallidum is a spirochete (a fragile spiral bacterium) 6-15 micrometers long. Its small size makes it invisible on light microscopy; therefore, it must be identified by its distinctive undulating movements on dark-field microscopy.
It can survive only briefly outside of the body; thus, transmission almost always requires direct contact with the infectious lesion (fomite transmission, e.g. from toilet seats, is virtually impossible).
Spirochetes also include other human pathogens such as Leptospira, the causative agent of leptospirosis, and Borrelia which causes Lyme disease and relapsing fever.
Syphilis can be either:
è Acquired, i.e. transmitted by intimate contact with infectious lesions (most common) or via blood transfusion (if blood has been collected during early syphilis)
or
è Congenital, i.e. transmitted transplacentally from an infected mother to her fetus.
Moreover syphilis is usually classified into 4 stages:
- primary
- secondary
- latent
- tertiary
Acquired syphilis
In acquired syphilis, T. pallidum rapidly penetrates intact mucous membranes or microscopic dermal abrasions and, within a few hours, enters the lymphatics and blood to produce systemic infection.
Primary syphilis is characterized by the development of a painless chancre at the site of transmission after an incubation period of 3-6 weeks. The lesion has a punched-out base and rolled edges and is highly infectious. Normally chancre is found on the genitals. A small percentage of syphilitic lesions are found on the anus, fingers, oropharynx, tongue, nipples, or other extragenital sites. Regional nontender lymphadenopathy follows invasion. Whether treated or not, healing occurs within 3-12 weeks, with considerable residual fibrosis.
Secondary syphilis develops about 4-10 weeks after the appearance of the primary lesion. During this stage, the spirochetes multiply and spread throughout the body. The immune reaction is at its peak and antibody titers are high.
Systemic manifestations include malaise, fever, myalgias, arthralgias, lymphadenopathy, and rash.
Widespread mucocutaneous lesions are observed over the entire body and may involve the palms, soles, and oral mucosae. Most often, the lesions are macular, discrete, reddish brown, and 5 mm or smaller in diameter; however, they can be pustular, annular, or scaling. All such lesions contain treponemes. Of these, wet mucous patches are the most contagious. Generalized non-tender lymphadenopathy is usually associated.
Other skin findings of secondary syphilis are condylomata lata and patchy alopecia.
Condylomata lata are painless, highly infectious gray-white lesions that develop in warm, moist sites.
The alopecia is characterized by patchy hair loss of the scalp and facial hair, including the eyebrows. Patients with this finding have been referred to as having a “moth-eaten” appearance.
Latent syphilis is a stage at which the features of secondary syphilis have resolved, though patients remain sero-reactive. Some patients experience recurrence of the infectious skin lesions of secondary syphilis during this period. Lesions are less numerous but are still infectious.
Latent syphilis is divided into early latent and late latent. The distinction is important because treatment for each is different. The early latent period is the 1st year after the resolution of primary or secondary syphilis. Asymptomatic patients who have a newly active serologic test after having a serologically negative test result within 1 year are also considered to be in the early latent period. Late latency syphilis is not infectious; however, women in this stage can spread the disease in utero.
When tertiary syphilis occurs, it mainly affects the cardiovascular system (80-85%) and the CNS (5-10%), developing over months to years and involving slow inflammatory damage to tissues.
The 3 general categories of tertiary syphilis are:
l gummatous syphilis (also called late benign)
l cardiovascular syphilis
l neurosyphilis
Regardless of the stage of disease and location of lesions, histopathologic hallmarks of syphilis include endoarteritis (which in some instances may be obliterative in nature) and a plasmacell–rich infiltrate. Endoarteritis is caused by the binding of spirochetes to endothelial cells. The resultant endoarteritis can heal with scarring in some instances.
In certain individuals with tertiary syphilis, the response by sensitized T lymphocytes and macrophages results in gummatous ulcerations and necrosis.
Gummatous syphilis is characterized by granulomatous lesions, called gummas, which are characterized by a center of necrotic tissue with a rubbery texture. Gummas principally form in the liver, bones, and testes but may affect any organ. Although gummas may be identified on the skin, in the mouth, and in the upper respiratory tract, they appear most commonly on the leg just below the knee. Gummas usually are solitary lesions that range from less than 1 cm to several centimeters in diameter. Multiple lesions are generally asymmetric and grouped together.
Patient complaints usually are secondary to bone pain, which is described as a deep boring pain characteristically worse at night. Trauma may predispose a specific site to gumma involvement.
Gummas may break down and form ulcers, eventually becoming fibrotic. Treponemes are rarely visualized or recovered from these lesions.
Cardiovascular syphilis occurs at least 10 years after primary infection. The most common manifestation is aneurysm formation in the ascending aorta, caused by chronic inflammatory destruction of the vasa vasorum, the penetrating vessels that nourish the walls of large arteries. Aortic valve insufficiency may result.
Neurosyphilis has several forms.
If the spirochete invades the CNS, syphilitic meningitis results. Syphilitic meningitis is an early manifestation, usually occurring within 6 months of the primary infection. Patients present with typical symptoms of meningitis, including headache, nausea and vomiting, and photophobia, but are typically afebrile. CSF shows high protein, low glucose, high lymphocyte count, and positive syphilis serology.
Meningovascular syphilis occurs as a result of damage to the blood vessels of the meninges, brain, and spinal cord, leading to infarctions causing a wide spectrum of neurologic impairments.
Parenchymal neurosyphilis includes tabes dorsalis and general paresis.
Tabes dorsalis develops as the posterior columns and dorsal roots of the spinal cord are damaged. Posterior column impairment results in impaired vibration and proprioceptive sensation, leading to a wide-based gait. Disruption of the dorsal roots leads to loss of pain and temperature sensation and areflexia (deep ulcers of the feet can result from loss of pain sensation).
Damage to the cortical regions of the brain leads to general paresis, which mimics other forms of dementia. Impairment of memory and speech, personality changes, irritability, and psychotic symptoms develop and may advance to progressive dementia.
Congenital syphilis
The treponemes readily cross the placental barrier and infect the foetus, causing a high rate of spontaneous abortion and stillbirth.
Most infants with congenital syphilis are born to mothers with syphilis who either were not treated in pregnancy or were treated too late during pregnancy.
Within the first 2 years of life, symptoms are similar to severe adult secondary syphilis with widespread condylomata lata and rash (the rash has a higher probability of being atypical and can be vesicular or bullous). “Snuffles” describes the typical mucopurulent rhinitis caused by involvement of the nasal mucosae. Additional symptoms of early congenital syphilis include the following:
- Periostitis
- Hydrops
- Glomerulonephritis
- Thrombocytopenia
- Neurologic involvement
- Ocular involvement
Late congenital syphilis mainly manifests as neurologic symptoms. Cardiovascular abnormalities are rare.
Findings include bone and teeth abnormalities such as:
- “saddle nose” (due to destruction of the nasal septum)
- “saber shins” (due to inflammation and bowing of the tibia)
- “Clutton’s joints” (due to inflammation of the knee joints),
- “Hutchinson’s teeth” (in which the upper incisors are widely spaced and notched)
- “mulberry molars” (in which the molars have too many cusps).
Tabes dorsalis and general paresis may develop as in adults, with 8th cranial nerve deafness and optic nerve atrophy as well as a variety of other ophthalmologic involvements leading to blindness .
Genital ulcer diseases (including syphilis) are cofactors for the sexual transmission of HIV.
Untreated patients who are HIV positive have an increased risk for rapid progression to neurosyphilis and to its complications.
Patients with HIV are at greater risk for development or relapse of early symptomatic neurosyphilis for up to 2 years after treatment with intramuscular or intravenous penicillin.
All patients diagnosed with a sexually transmitted disease (including syphilis) should be screened for HIV infection.
Antigens of T. pallidum induce host production of treponemal antibodies and nonspecific reagin antibodies. Immunity to syphilis is incomplete.
For example, host humoral and cellular immune responses may prevent the formation of a primary lesion on subsequent infections with T. pallidum, but they are insufficient to clear the organism.
Approximately 1/3 of patients left untreated will develop late complications, with 10% of the total developing cardiovascular syphilis; 6%, neurosyphilis; and 16% gummatous syphilis.
Late complications appear to occur more commonly in men than in women.
Congenital syphilis is the most serious outcome of syphilis in women. A higher proportion of infants are affected if the mother has untreated secondary syphilis, compared to untreated early latent syphilis. Since T. pallidum does not invade the placental tissue or the fetus until the 5th month of gestation, syphilis causes late abortion, stillbirth, or death soon after delivery in more than 40% of untreated maternal infections. Neonatal mortality usually results from pulmonary haemorrhage, bacterial superinfection, or fulminant hepatitis.
For patients diagnosed with either primary or secondary syphilis (without auditory/neurologic/ocular involvement), the prognosis is good following appropriate treatment. T. pallidum remains highly responsive to the penicillins, and cure is likely.
Overall prognosis for tertiary syphilis depends on the duration and extent of disease activity, along with prior attempts to treat the disease.
For example, prognosis for advanced symptomatic disease in cardiovascular syphilis is poor, unless it is treated with high doses of IV penicillin. In contrast, in patients with neurosyphilis complicated by optic atrophy and blindness, the ability to regain vision remains poor despite attempts with high-dose penicillin.
Some general considerations
The extremely variable manifestations of tertiary syphilis produce an extremely broad differential diagnosis, and care must be taken to consider syphilis in cardiac, dermatologic, and neurologic disorders as it is relevant.
When making a primary diagnosis of a generalized rash or an STD, always include syphilis in the differential diagnoses because of its varying manifestations.
Routinely screen all pregnant women for syphilis. Repeat tests in high-risk mothers and patients who live in high-risk areas for syphilis before delivery. Pregnant women who are positive should be considered infected unless there is evidence of adequate treatment in the medical records and sequential serologic antibody titers have decreased.
Per CDC guidelines, any woman who delivers a stillborn infant after 20 weeks’ gestation should be tested for syphilis.
No infant should leave the hospital without the maternal serologic status having been determined at least once during pregnancy.
The 2010 CDC guidelines recommend congenital syphilis screening with serologic testing of the mother rather than the infant. An infant’s serum may be nonreactive to serologic testing if the mother was infected late in pregnancy or if her serologic results are of low titer.
Most infants are born without any clinical evidence of syphilis. Because infants may develop serious disease up to several weeks after delivery, it is important to monitor babies born from positive mothers with serial serological tests. If the mother has been adequately treated for syphilis during pregnancy and the infant has no symptoms, serial VDRL tests for 2 months are adequate. A rising titer over a 2-month course is evidence of active syphilis, whereas falling titers indicate passive maternal antibody transfer.
T. pallidum cannot be cultivated in vitro and is too small to be seen under the light microscope.
Serologic testing is considered the standard method of detection for all stages of syphilis. (Note, however, that serologic tests cannot be used to identify the different species of the treponeme family). In suspected acquired syphilis, first perform nontreponemal serology screening using the Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR)
Sensitivity (percentage of positive tests in affected patients) of the VDRL and RPR tests is estimated to be 78-86% for detecting primary syphilis, 100% for detecting secondary syphilis, and 95-98% for detecting tertiary syphilis.
Specificity (percentage of negative test in non affected patients) ranges around 85-99% and may be reduced (false positive results) in individuals who have coexisting conditions (ie, collagen vascular disease, pregnancy, IV drug use, advanced malignancy, tuberculosis, malaria, viral or rickettsial diseases).
VDRL test results turn positive 1-2 weeks after chancre formation.
Nontreponemal tests usually become nonreactive with time after treatment. However, in some patients, nontreponemal antibodies can persist, sometimes for the life of the patient.
Because of the possibility of false-positive results, confirmation for any positive or equivocal nontreponemal test result should follow with a treponemal test, such as the fluorescent treponemal antibody-absorption (FTA-ABS), quantitative VDRL/RPR, microhemagglutination assay T pallidum (MHA-TP), T pallidum hemagglutination (TPHA), and T pallidum particle agglutination (TPPA) tests. Treponemal enzyme immunoassay (EIA) for immunoglobulin G (IgG) and immunoglobulin M (IgM) may be performed.
FTA-ABS is commonly used as a confirmatory test following positive VDRL or RPR test findings. FTA-ABS has a sensitivity of 84% for detecting primary syphilis infection and almost 100% sensitivity for detecting syphilis infection in other stages. Its specificity is 96%.
Diagnosis of neurosyphilis can be challenging.
The VDRL test on cerebrospinal fluid (VDRL-CSF) is highly specific but has low sensitivity. Therefore, the diagnosis of neurosyphilis usually depends on a combination of reactive serologic test results, CSF cell count, CSF protein, and clinical manifestations with or without a reactive VDRL-CSF.
Some specialists recommend performing an FTA-ABS test on CSF. The CSF FTA-ABS is less specific for neurosyphilis than the VDRL-CSF, but it is highly sensitive.
Current guidelines in clinical infectious diseases state that physicians should evaluate CSF in individuals with latent syphilis of unknown duration or with late latent syphilis if:
1) treatment fails,
2) neurologic or ocular symptoms are present; or
3) the patient has underlying HIV infection.
LP is only relatively indicated in patients with high titers on serological tests (≥1:320). It is also indicated if there are other changes indicative of active syphilis (eg, gumma, aortitis).
Examination of the CSF should include the VDRL test, cell count, and protein level. Abnormalities of any of these measurements combined with a suggestive history and examination strongly indicate the presence of neurosyphilis.
Imaging studies should be performed depending on the organ system involved.
Obtain chest radiography in patients with tertiary syphilis to screen for aortic dilatation. Linear calcification of the ascending aorta on chest films suggests asymptomatic syphilitic aortitis. Radiologic abnormal findings commonly seen with advanced gummas of bone include periostitis, destructive osteitis, or sclerosing osteitis.
CT scanning of the head and body may be used to document the complications of tertiary syphilis.
If the test results are positive for syphilis, the treatment of choice is parenteral benzathine penicillin G.
Dosage and the length of treatment depend on the stage and clinical manifestations of the disease.
EARLY SYPHILIS (less than 1 year duration):
•Benzathine penicillin 2.4 m.u weekly × 2 weeks.
OR
•Procaine penicillin (PAM) 600,000 U IM OD x 10 days
In penicillin allergy use:
Tetracycline capsules 500 mg QDS × 15 days.
OR Erythromycin 500 mg QDS × 15 days.
OR Doxycycline 100 mg OD × 15 days.
LATE SYPHILIS (more than 1year duration):
•Procaine penicillin (PAM) 600,000 U IM OD × 14 days.
OR
•Benzathine penicillin 2.4 m.u. weekly x 4 to 5 doses.
Pregnancy
Use either one of the penicillin preparations or erythromycin. If erythromycin is used, the neonate should be treated soon after birth.
CONGENITAL SYPHILIS
•Aqueous crystalline penicillin G 25,000 U/kg IM, BD for a minimum of 10 days.
OR
•Aqueous procaine penicillin G 50,000 U/kg/day IM OD for a minimum of 10 days.
Clinical and serologic conversions are the endpoints of medical treatment for syphilis.
Follow-up Venereal Disease Research Laboratory (VDRL) test levels should be obtained to document treatment efficacy.
Patients with syphilis should be counselled to notify their partners of infection and to inform them of the need to be treated.
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