Secondary syphilis is characterized by a skin rash that appears 1-6 months (commonly 6 to 8 weeks) after the primary infection. This is a symmetrical reddish-pink non-itchy rash on the trunk and extremities, which unlike most other kinds of rash involves the palms of the hands and the soles of the feet; in moist areas of the body the rash becomes flat broad whitish lesions called condylomata lata. Mucous patches may also appear on the genitals or in the mouth. A patient with syphilis is most contagious when he or she has secondary syphilis.
Other symptoms common at this stage include fever, sore throat, malaise, weight loss, headache, meningismus, and enlarged lymph nodes. Rare manifestations include an acute meningitis that occurs in about 2% of patients, hepatitis, renal disease, hypertrophic gastritis, patchy proctitis, ulcerative colitis, rectosigmoid mass, arthritis, periostitis, optic neuritis, iritis, and uveitis.
Tertiary syphilis
Tertiary syphilis occurs from as early as one year after the initial infection but can take up to ten years to manifest - though cases have been reported where this stage has occurred fifty years after initial infection. This stage is characterised by gummas, soft, tumor-like growths, readily seen in the skin and mucous membranes, but which can occur almost anywhere in the body, often in the skeleton. Other characteristics of untreated syphilis include Charcot's joints (a degeneration of joint surfaces resulting from loss of proprioception), and Clutton's joints (bilateral knee effusions). The more severe manifestations include neurosyphilis and cardiovascular syphilis.
Neurological complications at this stage include generalized paresis of the insane which results in personality changes, changes in emotional affect, hyperactive reflexes, and Argyll-Robertson pupils, a diagnostic sign in which the small and irregular pupils constrict in response to focusing the eyes, but not to light; Tabes dorsalis, also known as locomotor ataxia, a disorder of the spinal cord, often results in a characteristic shuffling gait.
Cardiovascular complications include aortic aortitis, aortic aneurysm, aneurysm of sinus of Valsalva, and aortic regurgitation, and are a frequent cause of death. Syphilitic aortitis can cause de Musset's sign (a bobbing of the head that de Musset first noted in Parisian prostitutes).
Latent syphilis
Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease. Latent syphilis is further described as either early or late. Early latent syphilis is defined as having syphilis for one year or less from time of initial infection without signs or symptoms of disease. Late latent syphilis, then, is infection for greater than one year but having no clinical evidence of disease. The distinction is important for two reasons, therapy and risk for transmission.
In practice, the time of initial infection is often not known and in this case should then be presumed to be late for the purpose of therapy. Early latent syphilis may be treated with a single IM injection of a long-acting penicillin. Late latent syphilis, however, requires three such injections, each a week apart. For infectiousness, however, late latent syphilis is not considered contagious while early latent is. Thus, if the duration of infection is not known, one should presume the patient is early and contagious.
Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary or tertiary syphilis. Fetus in the utero is most liable to be infected with syphilis after the fifth month. According to the CDC, 40% of births to syphilitic mothers are stillborn, 40-70% of the survivors will be infected, and 12% of these will subsequently die prematurely. Manifestations of congenital syphilis include abnormal x-rays; Hutchinson's teeth (centrally notched, widely-spaced peg-shaped upper central incisors); mulberry molars (sixth year molars with multiple poorly developed cusps); frontal bossing; saddle nose; poorly developed maxillae; enlarged liver; enlarged spleen; petechiae; other skin rash; anemia; lymph node enlargement; jaundice; pseudoparalysis; and snuffles, the name given to rhinitis in this situation. Rhagades, linear scars at the angles of the mouth and nose result from bacterial infection of skin lesions. Death from congenital syphilis is usually through pulmonary hemorrhage. Affected children are highly infectious until about 2 years of age.
Neurosyphilis
Neurosyphilis refers to a site of infection involving the neurologic system. As such, neurosyphilis may occur at any stage of syphilis. Neurosyphilis in patients with HIV infection is well described. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV epidemic. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, remain incompletely characterized. Furthermore, the alteration of host immunosuppression by ART in recent years has further complicated such characterization.
Approximately 35% to 40% of persons with secondary syphilis have asymptomatic CNS involvement, as demonstrated by any of the following on CSF examination: an abnormal cell count, protein level, or glucose level; or demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test. Acute syphilitic meningitis usually occurs within the first 2 years of infection; 10% of cases are diagnosed at the time of the secondary rash. Patients present with headache, meningeal irritation, and cranial nerve abnormalities, typically involving cranial nerves at the base of the brain. Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary infection. Unlike the sudden onset of thrombotic or embolic stroke syndromes, meningovascular syphilis is associated with prodromal symptoms lasting weeks to months before focal deficits of a vascular syndrome are identifiable. Prodromal symptoms include unilateral numbness, paresthesias, extremity weakness, headache, vertigo, insomnia, and psychiatric abnormalities such as personality changes. The focal deficits initially are intermittent or progress slowly over a few days.
Testing
It was only in the 20th century that effective tests and treatments for syphilis were developed.
In 1906, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the prevention of syphilis. By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of transmission of syphilis to others, even though it did not provide a cure for those infected. In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positive reactions than the Wasserman test. Both of these early tests have been superseded.
Present-day syphilis tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests, while useful, are still not completely specific, as many other conditions can cause a positive result. Tests based on monoclonal antibodies and immunofluorescence, including Treponema pallidum haemagglutination assay (TPHA) and Fluorescent Treponemal Antibody Absorption (FTA-ABS), are more specific, but are still unable to rule out related treponomal infections such as yaws and pinta. However, a simple microscopy of chancre fluid using dark ground illumination provide a quick and effective test.
In one of the best-documented episodes of unethical human medical experimentation in the twentieth century, the Tuskegee syphilis study continued to study the lifetime course of syphilis in a group of African Americans long after effective treatments for syphilis were available. In the July 17, 1998 issue of the journal Science, a group of biologists reported complete sequencing of the genome of T. pallidum.
Treatment
History
There were originally no effective treatments for syphilis. The most common in use were guaiacum and mercury: the use of mercury gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury". Though no proper studies were done to prove it, mercury may have been an effective means to treat syphilis. It was administered multiple ways including by mouth and by rubbing it on the skin. One of the more fascinating methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed in the box and a fire was started under the box which caused the mercury to vaporize. It was a gruelling process for the patient and the least effective for delivering mercury to the body.
As the disease became better understood, more effective treatments were found, beginning with the use of the arsenic-containing drug Salvarsan from 1910, and later, Neosalvarsan.
Unfortunately, these drugs were not 100% effective, especially in late disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time malaria was used as treatment because it produces prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with quinine which was available at that time. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvunct therapy.
These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively cured for the first time.
Current treatment
The first choice treatment for Primary, secondary, and early latent infection remains penicillin, in the form of Benzathine penicillin G, 2.4 MU IM in a single dose. Individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracyclines (100 mg orally twice a day for 14 days). Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined and close clinical and serologic follow-up is essential. If ceftriaxone is used for the treatment of early syphilis, some experts recommend 1 g daily, given intramuscularly or intravenously, for 8 to 10 days. (47,159,160)
For late latent and infections of unknown duration- If the CSF examination yields no evidence of neurosyphilis, then a total of 7.2 million units of benzathine penicillin G is recommended (administered as 3 doses of 2.4 million units by intramuscular injection weekly for 3 successive weeks). If allergic, then tetracyclines may be used for this stage also, but for 28 days instead of the normal 14.
For patients diagnosed with neurosyphilis (including ocular or auditory syphilis with or without positive LP results), aqueous crystalline penicillin G is the treatment of choice (administered as 18-24 million units intravenously per day; ie, 3-4 million units every 4 hours or continuous infusion for 10-14 days). If intravenous administration is impossible, then aqueous procaine penicillin G is an alternative (administered as 2.4 million units intramuscularly daily plus probenecid 500 mg by mouth 4 times daily for 14 days). Procaine injections are painful, however, and patient compliance may be difficult to ensure. To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G (total 7.2 million units intramuscularly) after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis. No oral antibiotic alternatives are recommended for the treatment of neurosyphilis, but in special circumstances the only alternative that has been studied is ceftriaxone 2 g intramuscularly for 14 days.
Alternative regimens (eg, tetracyclines) are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy. Skin testing or desensitization to facilitate therapy with penicillin is recommended in pregnant patients and for treatment of latent syphilis and neurosyphilis in other patients with HIV infection. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.
Oral Azithromycin given as a single dose of 2 g has been used successfully to treat syphilis in a pilot study of 328 patients in Tanzania (Riedner 2005), but resistance to azithromycin (eg, as high as 56% in San Francisco in 2004)[2] has made it an unacceptable alternative.
HIV-infected patients with early syphilis may have a higher risk of neurologic complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small.
Before administering any treatment, clinicians should warn all patients about the possibility of a Jarisch-Herxheimer reaction, which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients.[3] This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with acetaminophen and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.
Syphilis in art and literature
There are references to syphilis in William Shakespeare's play Measure for Measure, particularly in a number of early passages spoken by the character Lucio. For example, Lucio says "[...] thy bones are hollow"; this is a reference to the brittleness of bones engendered by the use of mercury which was then widely used to treat syphilis.
Jonathan Swift's poetry mentions syphilis as a condition of prostitution which reaches the highest ranks of society. See, for example, "A Beautiful Young Nymph Going To Bed" and "The Progress of Beauty".
Some critics have argued that the character of Edward Rochester's first wife, Bertha, in Charlotte Brontë's novel Jane Eyre, suffers from the advanced stages of syphilitic infection, general paresis of the insane, and point to corroborative evidence within the text to substantiate this view.
Henrik Ibsen's controversial (at the time) play Ghosts has a young man who is suffering from a mysterious unnamed disease. Though it is never named, the events of the play make it plain that this is syphilis, an inheritance from his dissolute father. Dr Rank in Ibsen's play A Doll's House also has inherited syphilis.
The novel Candide by Voltaire describes Candide's mentor and teacher, Pangloss, as having contracted syphilis from a maidservant he slept with; the syphilis has ravaged and deformed his body. Pangloss explains to Candide that syphilis is 'necessary in the best of worlds' because the line of infection - which he explains - leads back to Christopher Columbus. If Columbus had not sailed to America and brought back syphilis, Pangloss states, the Europeans would not have been able to enjoy 'New World wonders' such as chocolate. (One of the purposes of the novel was to satirize Leibniz's philosophy as Pangloss's disingenuous rose-tinted viewpoint.) Pangloss eventually loses an eye and an ear to the syphilis before he is cured.
The artist Kees van Dongen produced a series of illustrations for the anarchist publication L'Assiette au Beurre showing the descent of a young prostitute from poverty to her death from syphilis as a criticism of the social order at the end of the 19th century.
Also, in Charles Dickens' novel Tale of Two Cities, references are made that allude to the main character, Sydney Carton, having syphilis.
Mention must be made of the anonymous American medical students' description of syphilis in a series of early 20th-century American limericks, using medical terminology to ghastly comic effect. It was first published in Journal of the American Medical Association January 1942: [4]
Thomas Disch in his novel Camp Concentration describe a fictional strain of syphilis that enhances intelligence but is lethal.
In Thomas Mann's novel Doktor Faustus, the Faust character, Adrian Leverkühn, acquires his genius for musical composition from the neurological effects of syphilis.
In Dick Francis' novel, Bonecrack the character Enso Rivera is suffering from megalomania caused by syphilis.
See also
- Other treponematous diseases:-
- Yaws is a tropical disease characterized by an infection of the skin, bones and joints; it is caused by a spirochete bacterium, Treponema pallidum, sp. pertenue, also called Treponema pertenue
- Pinta - caused by Treponema carateum
- Bejel - caused by Treponema endemicum
External links