by Major M. P. Vora, M.B.B.S., D.V.D.
Ex- Hon. Senior Venereologist, St. George’s Hospital, Bombay.
The Indian Practitioner
A monthly journal of Medicine Surgery & Public Health.
Volume No – XXII, Number. 4 of April 1969.
Page No. 195 to 198.
This article was specially contributed to The Indian Practitioner.
AFTER inoculation of Treponema pallida in the body, they enter local lymphatics, multiply and reach through blood stream all the tissues of the body within about 2 to 3 days. The generalisation of the syphilitic infection occurs long before the appearance of the chancre, the primary lesion. Hence syphilis is generalised first, subsequently localised and dispersed. Some Tr. pallida escape from the circulation and initiate metastatic lesions in and around the vessels and some tissues especially of ectodermal origin. After a variable period of generalisation, Tr. pallida disappear from the blood stream and surface lesions and the process of resolution starts. Thus syphilis is charecterised by repeated episodes of Tr. pallidaemia, metastatic lesions and resolution till the immune forces of the host have reached the maximum immunity. The period during which the immunity reaches its peak varies widely from patient to patient and takes about 2 to 4 years’ duration. The experience shows that the power to prevent dissemination of organisms in the body is disturbed or upset by administration of subcurative or irregular antisyphilitic therapy in the early stages of syphilitic infection. The serious dangers of inadequate or irregular treatment of early syphilis will be apparent. Involvement of the cardiovascular or nervous system is more frequent in inadequately treated syphilis than in syphilis which receives no treatment at all or which receives regular and adequate treatment during its early stages.
The process of resolution of metastatic lesions goes on to completion in a small proportion of cases ending in what is called “biologic cure”; while in a large proportion of cases, on the contrary, one or more foci persist in various locations. If the presence of these foci is hidden beyond diagnostic reach the state of infection is called “latent”. If the patient has an obvious lesion of syphilis such as rash, mucous patch, optic atrophy etc., then the patient cannot be regarded as having latent syphilis. Thus the term latent syphilis is limited to the presence but not the location of syphilitic foci. The presence of syphilitic foci in the central nervous system is generally not beyond the diagnostic reach; it can be detected by the examination of the cerebrospinal fluid. Therefore, unless the C.S.F. has been shown normal, the patient cannot be regarded as having latent of inapparent syphilis. This is one of the basic requirements for the conclusion of latency. If the evidence of syphilis is present in the C.S.F. and there are no clinical signs and symptoms, the stage of the disease is called asymptomatic neurosyphilis. Very often metastatic lesions in the aorta can remain hidden beyond diagnostic reach for a long period. Uncomplicated syphilitic aortitis is often without physical signs and symptoms; it is extremely difficult to diagnose it accurately even with all the means that are available. Though the presence of neurosyphilis cardiovascular syphilis does not become clinically evident for many years, the initial infection or the process of metastatic lesions in these systems begins during the period of early Tr. pallidaemia.
As surface lesions are absent, the individual with latent syphilis should not theoretically transmit the infection to others at this stage. However, as recurrences of generalisation of infection can occur at any time until the forces of resistance have fully developed i.e. 2 to 4 years, such an individual is likely to develop metastatic lesions, which may or may not be infectious, depending on the duration of the infection and whether the surface of the body is involved. Until the possibility of re-dissemination of infection has been remote, the individual is likely to be infectious and the prognosis and the principles of therapy of either latent or early infectious syphilis are identical.
It is customary to subdivide the latent syphilis into early and late at a point of about 2 to 4 years after the onset of infection. This classification is arbitrary and is based on the assumption that there would be no recurrent episodes of Tr. pallidaemia after this period. There is no unanimity of opinion among venereologists as to the exact duration of infection, which can be termed early latent. Some like to restrict it to the infection of two years’ duration, while others prefer it to the infection of four years’ duration for various reasons. The early latent syphilis may return to metastatic and infectious variety at any time. Once the localisation of the process becomes stabilised, the disease enters into the stage of late latent syphilis. Once the stage of late latency has been reached, the infection may pursue any of the three possible courses:
Because penicillin is now given freely for a number of diseases without an adequate inquiry and serologic test for syphilis, in every case, before its administration, the incidence of latent syphilis has gone up lately. In fact, a large number of syphilitics are masked in early stages making early detection of syphilitic infection a difficult problem by a clinical examination. Approximately 70 to 80 per cent of the syphilitics seen by the general practitioner are in this stage of the disease. It is, therefore, important to bear in mind its clinical entity and to adopt routine serology of the patients to an increasing degree. Many patients with late latent syphilis are either misdiagnosed on the basis of negative non-specific regain test and neglected or over-treated because of the persistent seropositivity. Specific serologic tests for syphilis such as R.P.C.F. or F.T.A.-A.B.S. are unfortunately freely available for the purpose. It is worth remembering that the diagnosis of late syphilis is primarily a clinical one and should not be abandoned on the basis of negative standard serologic test for syphilis such as V.D.R.L. or W.R. Once the true latency has been established, the subsequent course of the infection is usually benign in the majority of cases. It is important, therefore, that this frequently encountered benign form of syphilis should be clearly distinguished from potentially serious and patent forms of infection which require vastly different types of therapy.
In late latent syphilis, the patient has unquestionable serologic positivity and historical evidence of syphilis of more than 2 to 4 years’ duration, but in which no clinical evidence of syphilitic foci in the body be detected by:
Unless these criteria are exhausted, one is likely to overlook detectable and potentially serious syphilitic lesions. It is, therefore, necessary that a physician obtains as early as possible, information made available by these procedures. To establish the latency of syphilitic infection presents no big difficulty; however, it is difficult, at times, to prove that the infection is more than four years’ duration. History, dates of exposure, appearance of the primary lesion, serologic test and treatment will be of considerable help. In the absence of such an evidence, a physician should use his own judgement as to whether the latent infection is early or late. It is advisable to regard syphilis of unknown duration in a young person as an early acquired infection.
The early latent syphilis should be treated in the same way as an early active infectious syphilis, for which 6 m.u. of procain penicillin – G in ten days is considered adequate. The response and the prognosis are invariably good.
Once the true late latency is established, theoretically there is no need for the institution of antisyphilitic treatment. Unfortunately, there is no way in which apparently late latent syphilis can be distinguished from the active disease of the aorta or any other viscera, which has not suffered damage to the point of clinical recognition. Thus a physician is left with no other choice than to treat all the individuals with late latent syphilis. A dose of 12-20 m.u. of procain penicillin – G in 20 days is considered adequate. Since these patients show no clinical evidence of the infection, it will be futile to expect clinical changes in the status of the patient as the result of successful therapy. A precise evaluation of the results obtained can only be made by following the patient throughout his or her life. About 2% of the cases of late latent syphilis who are treated will subsequently develop serious manifestations of late syphilis and show evidence of progression, in spite of an adequate treatment. This is particularly true in the older age group. Experience shows that prolongation of treatment does not help to eliminate this small chance of progression in a small per cent of late latent syphilitics.
Serology: In late syphilis, serologic tests for syphilis do not reverse readily to normality after the treatment. About 50% of the cases will show either serologic reversal or pronounced fall in the titre by the end of a year or two after the completion of treatment. In a small proportion of cases, the titre gets stabilised at a lower level and remains so for years after the treatment. This frequent failure of the serologic tests for syphilis to reverse to negativity after treatment of late latent syphilis is called sero-resistance. This phenomenon of sero-resistance, which is observed in late latent syphilitics, must not be confused with the persistently positive serologic tests in the individual with an obvious progressive lesion of the aorta, nervous system or other viscera. The latter is not considered as an example of sero-resistance. Two important facts concerning sero-resistance need to be clearly understood:
Hence it is irrational and futile to continue antisyphilitic therapy in such cases. Once the serologic tests for syphilis have been repeatedly negative in the individual with late latent syphilis, subsequent true serologic relapse seldom occurs. The T.P.I., R.P.C.F. and F.T.A.-ABS tests are of little value as an index of therapeutic response. They remain positive for a number of years. However, their usefulness is clear for the diagnosis of late symptomatic syphilis where V.D.R.L. or W.R. is often negative. They also help to eliminate biologic false positivity.
The cerebrospinal fluid: The C.S.F. examination as a routine before the institution of treatment both in the early and late latent syphilis is necessary; for, the normal C.S.F. is the pre-requisite for the diagnosis of latency. In case the latent infection is more than four years’ duration, and the first C.S.F. examination reveals no changes in the fluid, the subsequent examination of the fluid is not necessary. Where it is not possible to determine the duration of the infection or the possibility of early latent syphilis cannot be excluded, the C.S.F. should be reexamined 18 to 24 months after the antisyphilitic therapy in the same way as it is done after the treatment of early active syphilis or early latent syphilis. If the C.S.F. shows at the first examination changes or abnormalities, suggestive of neurosyphilis, subsequent examination of the C.S.F. one or more times becomes necessary to find out the response to antisyphilitic treatment. The total cell count and the protein estimation of the fluid are the earliest and the most reliable indices of the successful therapy of neurosyphilis.
It is often overlooked in the treatment of syphilis, that an adequate treatment of syphilis does not mean “cure”, unless the result of repeated examinations, serologic responses and the C.S.F. studies, over a period of years, confirms it. This alone confirms and assures permanency of cure.