Syphilis is a systemic disease prevalent all over the world and is due to treponema pallidum, a spirochaete which is usually transmitted by sexual contact. Syphilis may be congenital or acquired which is further divided into three stages. Primary, secondary and tertiary.
Primary form is characterized by a primary lesion which generally appears after an incubation period of three weeks. In the secondary stage there are generally mucocutaneous lesions widely distributed and abundant with generalized lymphadenopathy. This stage may remain latent for a number of years when it manifests with neurovascular and distinctive lesions in many tissues.
Syphilis disease is caused by a thin delicate aerobic organism called Treponema pallidum which survives only for a few hours under natural conditions but survives in stored blood for 72 hours. It is destroyed by heat, antiseptics and the process of drying.
Humans are the only natural host. Though many mammals can be infected by this organism yet only humans and apes show syphilitic lesions. Infection spreads generally by sexual contact. It may also be conveyed by contamination of skin abrasions with secretions from infected lesion, the most dangerous being primary sore and moist secondary lesions.
It is not necessary for a person transmitting the infection to be suffering from external genital lesions. The period during which a person suffering from syphilis may convey infection varies. After second year infectivity declines and is reduced to minimum after five years. In case of congenital syphilis infection occurs in the second half of pregnancy.
After gaining entry into the body, treponema rapidly develops and within a few hours reaches the lymphatics and blood stream to produce infection. It nearly effects all organs or tissues in the body making a pattern of tissue injury.
The syphilitic lesions at every stage are in the form of granuloma consisting of epitheloid cells, plasma cells, numerous small lymphocytes and some giant cells. There is vasculitis leading to obliterative arteritis. This results in necrosis and ulceration of the tissues leading to scar formation. The immune responses and immunologically mediated protection do have a role to play in initial response.
Late stage of tissue injury is seen many years after the primary infection and is in the form of gumma seen any where in the body and consists of a centre of coagulative necrosis surrounded by macrophages, inflammatory reaction and obliterative endarteritis. Erosion of gumma leaves behind a shaggy ulcer.
Acquired syphilis consists of three distinctive stages, primary, secondary and tertiary. Of these the first two stages are most infective.
This stage is characterized by the appearance of a small papule, which is painless and single called chancre. It appears at the site of inoculation usually on the penis, vulva or cervix after an incubation period ranging from ten days to three months after sexual contact.
In homosexuals the lesion may be found in the anal canal or rectum. The papule quickly enlarges, surface becomes eroded and ulcerates forming a punched out ulcer with a dull red areola and in duration round about. The sore does not bleed easily and oozes out serum which is teaming with spirochetes.
The course of primary sore varies. In some it is just a fleeting lesion and may not be noticed. Ordinarily a sore which remains untreated lasts for eight to ten weeks leaving behind a button of in-durated tissue and a thin scar.
Soon after the appearance of primary lesion the nearest lymph glands become enlarged. The glands are firm, rubbery and discrete. Shortly generalized lymphadenopathy particularly in cervical axillary and epitrochlear areas appears. Even after healing of the lesion the lymph node enlargement persists.
One to three months after the appearance of the chancre, secondary stage of syphilis develops. It is characterized by wide spread diffuse or patchy mucocutaneous rash accompanied by symptoms of malaise, sore throat, weight loss, headache, anorexia, arthralgia, low grade fever and generalized lymphadenopathy.
The rash is wide spread, distributed symmetrically and abundantly. Earliest lesion is macule which is rose colored round or oval with ill defined margins. It is present on chest, flanks, back, abdomen, palms and soles. Papules which are round, brownish red or coppery firm to feel also appear at this time.
The character of rash is polymorphic (macules papules or pustules) with little variation in size. Mostly rash is maculopapular, non-itching but in some cases pustular, follicular, annular or scaly lesions are seen.
A more severe form is Icthymatous type in which papule breaks down quickly and the underlying tissue becomes ulcerated. In addition to skin lesions, papules may become large flashy looking masses due to constant moisture and rubbing. These are called moist papules or condylomata lata. They are rounded in outline with broad base and flat top. These are the most infective lesions of syphilis, and exude serum packed with treponema.
Condylomata are seen at the mucocutaneous junctions e.g. round the anus, on the labia, between the buttocks, on the lateral aspects of scrotum and other warm moist areas of the body. Mucous surfaces of the oral cavity especially lips and pillars of faucës show snail track ulcers.
On the tongue the mucous lesions appear as pink, bald spots after the papillae have been shed in the necrotic process. Mucous patches are also found in the nose, septum, and floor of the mouth and extend downwards to larynx causing hoarseness of voice.
In addition to eruptions patients in secondary stage shows involvement of other organs in the body. There is generalized lymphadenopathy with glands being non-tender, discrete rubbery; joints and bursae involvement with limitation of movements.
Aching pains in the long bones are due to mild periostitis. These pains are very severe and are worse at night time. Eyes show acute iridocyclitis, pupillary abnormalities, optic neuritis and retinitis pigmentosa picture. Syphilitic hepatitis is characterized by jaundice and high levels of alkaline phosphatase. Renal movement may take place in the form of nephrotic syndrome or immune complex glomerulonephritis.
After a variable period ranging from three to twelve months after the primary and secondary stages the patient enters into a latent period. It may be early or late latent phases. Early latent stage is the first year after infection while in the late latent stage patient may have latent form of the disease persisting for years. In both these phases the organisms are present iii the tissues and may intermittently be shed in the blood stream. This stage is diagnosed by terponemal antibody tests.
The pathogenesis of this stage began in early stage of the disease. Sometimes secondary and tertiary stage may merge into each other. The classical lesion is a typical distinctive lesion called ‘gummata’ which tends to be localized and asymmetrical in distribution. The gummata may be in the form of small pea shaped nodules joining together to form a continuous ridge present on areas exposed to friction or injury.
But the commonest lesion is a painless rounded swelling, rubbery in consistency which to start with is a small nodule and progressively increases in size and involves deeper tissues such as muscle or bone. The central portion of gummata undergoes necrosis forming a gummatous ulcer. On healing a tissue paper scar is formed.
The mucous membranes of mouth and throat are often involved and the process may commence either in the hard palate or musculature of the tongue. In the tongue gummata may reach the surface and cause diffuse gummatous infiltration and even punched out ulcers.
Chronic superficial glossitis and leukoplakic patches appear on the margins of tongue, mucous surfaces of cheek and at angle of the mouth. Patient generally complains of pain in the tongue and is unable to tolerate spicy and acidic foods.
Tertiary stage also involves bones and often the diagnosis is difficult. Bones most commonly involved are tibia, skull, clavicle, stemum and femur but any bone in the body can be involved. Patient complains of a gnawing boring pain which is very severe at night. It may be in the form of periostitis.
Radiologically some bones show sclerotic lesions while in some bones especially of skull there are osteoporotic areas surrounded by sclerosis (moth eaten appearance). Gummata may produce destruction and there may be perforation of palate, or bridge of nose destroyed.
Central nervous system involvement in tertiary stage probably began in the early phase of disease though it may not be clinically apparent for number of years. The major involvement is in the parenchymatous or meningovascular forms.
Meningovascular syphilis is associated with diffuse involvement of meninges along with local or wide spread involvement of small medium or large vessels. It may produce acute syphilitic meningitis, basal meningitis, retrobulbar neuritis and hemiplegia. In parenchymatous form the lesions generally are tabes dorsalis, general paralysis of insane (GPI) and optic atrophy. In the spinal forth of meningovascular syphilis there is meningomyelitis, acute transverse myelitis, syphilitic pachymeningitis, erb’s paraplegia and amyotrophy.
Cardiac involvement is mainly limited to large vessels. Common lesions are syphilitic aortitis, aortic regurgitation, saccular aneruysm of the ascending and arch of aorta and coronary ostial stenosis. Cardiac symptoms generally occur at periods varying from ten to thirty years after the primary infection. Asymptomatic aortitis may be suspected if there are linear calcification in the ascending aorta on X-ray abdomen.
Treponema pallidrum are passed from an infected mother to the foetus, transmission occurring at any time during gestation. But the lesions of congenital syphilis develop only in foetus affected after the fourth month.
This suggests that the pathogenesis of congenital syphilis depends on the immune response of the host. Depending upon the degree of the infection the foetus may die in utero or soon after birth or it may survive. Adequate treatment of mother before the sixteenth week of pregnancy can prevent foetal damage.
Surviving infants usually show a wide spread, fulminant picture of disease. The manifestations may be early appearing within the first two years of life and late which appear after two years and leave late stigmata.
The early manifestations are in the form of running or blocked nose (snuffles) fever, wasting. The infant is undersized marasmic with a hoarse cry, and maculopapular eruptions which are wide spread and involve almost the whole body. Sometimes bullae appear and contain serum or pus which is highly infective.
Condylamata appear on the mucoscutaneous junctions. Baby has a wrinkled skin and a wizened look. Alopecia is there. Occasionally growth of black hair on head occurs (syphilitic wig). Radiating fissures form along the angle of the mouth. Liver usually is enlarged. Kidneys may show albuminuria. Bony lesions in the form of osteochondritis develop within six months of birth.
These occur at the end of long bones and are very painful. The infant may not move the limbs because of pain (pseudoparalysis). Knee joints may show painless effusions,
In the late stage which develops after two years, lesions may appear at any time. There is generally interstitial keratitis in the eyes with choroiditis and retinitis. Neurological symptoms resemble juvenile general paralysis of insane. Meningovascular syphilis or optic atrophy is rare. Eighth nerve deafness is common. Gummatous lesions of palate and periostitis resemble that of adult syphilis.
Stigmata of congenital syphilis include Hutchinson’s teeth (upper central incisors are notched, widely spaced, broader at the base than at the cutting edge with central notches—peg-shaped) and mulberry molars, the sixth year molars which have poorly multiple developed cusps numbering more than usual four.
Skull shows frontal bossing. There is saddle shaped nose and maxilla which is poorly developed. Palate is high arched. Other stigmata include nerve deafness, optic atrophy, chorioretinitis and intrstitial keratitis.
Sero diagnosis of syphilis. It may be made by:
1. Non-specific tests like Wasserman’s test, Kahn’s test and venereal disease research laboratory (VDRL) test. These tests use cardiolipin antigen and are useful for screening purposes. They become positive within three to four weeks after primary infection and the titre progressively increases in secondary stage. These generally become negative by six months after treatment. False positive results may occur in patients of infectious mononucleosis, malaria, leprosy, hepatitis, tuberculosis, mycoplasma infection and connective tissue disorders.
2. Specific tests include treponema pallidum immobilization test (TPI) and T pallidum haemagglutination assay (TPHA) and fluorescent treponema antibodies absorbed test (FTA-ABS). These are highly specific tests. FTA-ABS becomes positive in early part of infection while iTT is positive in late stages. Also FTA-ABS is positive in patients with latent and late syphilis and remains positive for life even after treatment.
TPI test is the most specific treponemal test but is more laborious. Out of all the tests both specific and non-specific all the tests are positive almost 100 per cent in secondary stage while FTA-ABS gives almost hundred per cent (96-100%) positivity in primary secondary and tertiary stages of syphilis.
3. Treponemas in chancres, condylomata, mucous patches and infected secretions may be visualised by dark-field microscopy. In cases of neurosyphilis, CSF is examined for increased protein concentration and pleocytosis. VDRL test may be specific if it is not contaminated with blood. Higher sensitivity is seen in meningovascular syphilis and low in asymptomatic neurosyphilis and tabes dorsalis, Lange’s colloidal gold curve may show a paretic or luetic curve. FTA-ABS test is more specific.
Treatment of syphilis
The aim should be to achieve cure as well as make the patient non- infective at the earliest. In all patients with primary or secondary forms of syphilis a daily injection of 600,000 units of procaine penicillin intra-muscularly for ten days is the treatment of choice. For patients sensitive to penicillin, Cap. Tetracycline 500 mg four times a day or Erythromycin 500 mg four times a day for two weeks is the alternative treatment.
For latent and tertiary syphilis treatment is as above but for longer periods (2-3 weeks).
Classification of syphilis
(c) Latent—Early latent (within 2 years of infection)
Late latent (after two years 0f infection)
(a) Early manifestations (within 2 years of life)
(b) Late manifestations (after 2 years of birth)
(c) Residual stigmata of syphilis.
For cardiovascular and neurosyphilis procaine penicillin 600,000 units I/M a day for 14-21 days. The course may have to be repeated after an interval of 2 to 3 months. In cases of neurosyphilis dose of procaine penicillin is 2-4 mega units given intramuscularly daily with probenecid 500 mg four times a day for 10-14 days.
Patients of syphilis who are receiving penicillin may develop Jarisch-Herxheimer reaction due to destruction of large number of organisms. It may develop in 50 per cent of patients with primary disease and follows a few hours after first injection. It is characterized by general malaise, headache, rigors and fever lasting for few hours.
Cases of secondary syphilis are liable to get in 90 per cent of the cases while in neurosyphilis the disease may be exacerbated. In a number of cases the reaction is transient and subsides within a few hours. This reaction can be prevented by giving prednisolone 20 mg 24 hours before giving penicillin and continued for two days. Penicillin should not be withheld for fear of this reaction.
In infants with congenital syphilis Injection procaine penicillin 25,000 units/kg/dose intra-muscularly twice daily for 10 days or crystalline penicillin G. 25,000 units/kg/dose intravenously twice daily for ten days.
Follow up. All patients should be followed up for two years. CSF be examined after one year. After successful treatment VDRL progressively declines and becomes negative in 12 months time. If a patient is negative in all counts (clinically and serologically) at the end of two years he is declared cured.
Tests for syphilis
1. Dark field examination of treponema
2. Serological tests: (a) Non-specific Kahn’s test, W.R. and VDRL tests, (b) Specific – Treponema pallidum immobilization test JH & T. pallidum haemagglutination assay (TPHA)
3. Fluorescent treponema antibodies absorbed test FTA-ABS.