SYPHILOTHERAPEUTIC CRITERIA

By

M. P. Vora, M.B.B.S., St. George’s Hospital, Bombay

The Medical Bulletin

Vol. IX, No.24 of 20 th December, 1941; Pages: 711-717.

Syphilis is a contagious disease characterised by alternate periods of activity and quiescence. It is capable extensive mimicry and even the expert clinician may be misled at times. The best ways to avoid mistaking the true cause of many of the symptoms is the maintenance of “a high index of suspicion” and the free use of the serologic test i.e. Wassermann reaction. The most critical period in the course of this infection is the first few weeks. It is at this period biologic cure is possible. Early diagnosis and proper treatment begun, while the infection is still in the sero-negative primary stage, will result in complete cure in practically every case. The longer the period that elapses between the appearance of the chancre and the start of the treatment, the less certainty of complete cure and longer and more expensive the treatment. If the patient undertakes adhere to doctor’s advice, syphilis is curable, biologically in the early stages, and symptomatically in the stages. The early period is equally important in the prevention of transmission of the disease to others. From the point of public health, the early recognition and treatment of the disease is essential; for, a vast majority syphilitic infections are transmitted by the patients who have had the disease of less than 2 to 3 years’ duration. Hence major efforts in the control of syphilis - if they are to succeed - ought to be concentrated on early syphilis. Nevertheless, the treatment of late syphilis cannot be neglected.

Syphilis may be acquired or inherited. The earliest manifestation in acquired syphilis is a localised ulcer, popularly known as chancre. This primary lesion does not always present the classical picture, and far less does it do so in the first few weeks when the characteristic hardness or induration is not developed. The clinical examination alone is, therefore, not enough to arrive at a diagnosis. Dark-field examination is of great value, helping to confirm the diagnosis in practically all the early cases. The chief value of this examination lies in its ability to demonstrate Tr. pallida long before blood reaction becomes positive. Suspicious genital lesions should not receive either general treatment or such local treatment as will militate against accurate diagnosis, till Tr. pallida have been detected or several negative examinations are reported. Possibility of a positive dark-field examination result increases if saline dressing is applied to the lesion for a few days, prior to the examination. When the lesion arouses doubt, but Tr. pallida cannot be found in repeated attempts, it is necessary that the blood serologic reaction be determined at intervals of 2 to 3 weeks for at least three months. The usual advice “Every genital lesion to be regarded as syphilitic until proved otherwise” is an excellent one; however, the practice of treating inadequately genital lesions without proper diagnosis is not safe. Haphazard treatment on suspicion is dangerous. It makes the early detection of instilled disease difficult; it leaves the patient unable to mobilize natural defensive forces, and causes vital organs more vulnerable to the infection. Therapeutic test is never justifiable in a suspected case of early syphilis. Proof of infection is obligatory. Therapeutic test may be permissible in the late suspected cases. It is hardly necessary to say that if the therapeutic test is positive, treatment for syphilis must be continued and prolonged in accordance with the usual code of practice in syphiology. It is important to remember that the treatment of the primary lesion is only of secondary interest, while the diagnosis is of first importance.

The syphilitic virus spreads very rapidly after the primary inoculation and by the time chancre has developed, the disease is practically always generalised. No tissue is immune and all organs of the body as a rule is affected. Subsequently, one or more tissues or organs bear the brunt of the infection, resulting in a variety of lesions, and a variety of signs and symptoms. The symptomatology is so diverse, and so wide is the variation in the clinical signs, that it is very difficult to define or to depend on it for guidance; and the disease is often far advanced, before it can be recognised. Therefore, it is of the utmost importance to examine all the organs of the body symptomatically in a patient in whom the disease is suspected. Special attention should be paid to the heart, great vessels, nervous system, and the fundus of the eye, and an attempt should be made to find out the exact damage the disease has done to the patient. On this fact depend the basis of treatment and its appropriate modification.

The diagnosis of secondary syphilis, like that of the primary stage is a matter of clinical suspicion. Syphilitic skin rashes appear 6 to 10 weeks after the infection and vary considerably in different patients. So great is the similarity between the skin eruptions of secondary syphilis and those of non-syphilitic origin, that whenever the slightest doubt is felt about the cause of any skin eruption, one should not hesitate to employ a microscopic or a serologic test. An extensive secondary syphilis of the skin apparently protects the patient against late central nervous system involvement.

Pregnancy tends to suppress signs and symptoms of syphilis and in many cases of syphilis during pregnancy, it is unusual to find active manifestation of the disease in the mother. It is, therefore, necessary to do, as early as possible, one or more serologic tests in every pregnant woman. Stronger advocacy cannot be made for a routine use of blood Wassermann, in the 3 rd and the 5 th month of pregnancy, in all women passing through an antenatal care. Pregnancy is not a contra-indication to the energetic treatment of early syphilis. The fact that a syphilitic woman has received treatment prior to pregnancy should not, however, prevent the administration of further treatment during the pregnancy. Satisfactory are the results if the specific treatment is commenced, in the first three months of pregnancy, and continued to full-term. As a measure of safeguard the question of treatment of the infected mother during subsequent pregnancies should always be considered.

Inherited syphilis and congenital syphilis are preventable if, at every antenatal centre, an active search for cases of syphilis is made and an energetic prenatal treatment of the syphilitic mother is instituted, at an early stage of pregnancy. The average untreated syphilitic mother has but one chance in six, of bearing a living infant. But if syphilis is recognised early in pregnancy and properly treated, the infant will almost always be living and uninfected.

Latent syphilis, according to the definition, is rarely detected by clinical examination. Physical signs are not necessarily absent, but they are neither obvious nor easy to be detected. Routine serological test alone is helpful. The fact that a number of cases of latent syphilis are exposed by routine use of this test argues strongly in favour of the test. The early involvement of the nervous or cardiovascular mechanisms is often incidious and asymptomatic, and is likely to be ascribed to other causes, unless special diligence is shown and extra care is taken in the examination of the patient. In every case, the possibility of the syphilitic infection of these vital organs should always be borne in mind and investigated, long before irreparable and destructive changes have been wrought.

Similarly slow healing lesions, iritis, iridocyclitis, interstitial keratitis, polyarticular arthritis, periosteitis, headaches, breathlessness, hoarse voice, urinary disturbances like incontinence of urine, sensory or motor disturbances, paralysis, miscarriages, sterility, partial or complete deafness, etc. need thorough investigation as regards the cause.

Wassermann reaction is used as an aid to clinical judgment and not to supplant the clinical common sense. It is a laboratory help and not the final court of appeal. It should be employed more liberally. “it is important that even if the blood of a patient shows positive Wassermann reaction, one is not justified in attributing to syphilis, all the infirmities from which the patient suffers. Always suspect syphilis but be slow to diagnose it”. A positive Wassermann reaction does not necessarily indicate syphilis. For, the presence of a reagin like component of the serum or an organic disease other than syphilis (yaws, leprosy, malaria etc.) may give a false positive Wassermann.

In a treated or untreated case of syphilis, a positive Wassermann of the blood serum indicates the presence of syphilitic infection in the body. A negative Wassermann does not prove the absence of syphilis in the first few weeks of the infection; similarly a negative Wassermann after a course of treatment, does not indicate that a patient is cured. Once the diagnosis of syphilis is made, the patient should be treated independently of Wassermann reaction till the average and desirable treatment is completes; because negative reactions occur during the treatment, and relapses may occur long before apparent clinical cure. Unsafe is the frequent tendency to examine blood after a few injections or before the required treatment is finished, and to depend on those results. This is particularly true in early syphilis. A negative Wassermann reaction in early syphilis does nor mean ultimate cure, and to stop or interrupt treatment at this point, exposes the patient to a very grave danger of subsequent disastrous relapse. A reference to blood Wassermann, however, may be useful as a guide to treatment in early syphilis. The response of the blood test to treatment is an accurate measure of the efficiency of treatment in early but not in late syphilis. In late syphilis, on the contrary, blood Wassermann is of little value as an index of treatment; Wassermann fastness is common and this may be true even when the spinal fluid changes completely disappear.

Since blood Wassermann becomes positive in majority of cases after a period varying from 4 to 8 weeks of infection, it is from this time onwards, that the serologic examination of the blood is important. Wassermann reaction may be negative in some cases of late syphilis and even in inherited syphilis. The factors which influence and tend to negative the results are the previous treatment, the interval which has elapsed since the last treatment was administered, (whether such treatment has been by arsenic, bismuth or mercury), serologic latency, alcohol, presence of antiseptics or water in the syringe, faulty procedure or observation, and an error in labelling.

In cases of latent syphilis, the possibility of reactivating Wassermann by a preliminary injection and then testing blood for positivity and increasing titre, should not be omitted. “Provocative Wassermann is often of great value in diagnosis of previously untreated cases. It is, however, of no value as a criterion of cure. The test is significant only when positive; absence of provocative effect does not signify freedom from syphilis. In late syphilis, the test is more often negative than positive.”

Value of speeding up the diagnosis and early and adequate specific therapy, in complete cure and control of syphilis, has been sufficiently stressed, it however, needs to be generally recognised. If this is done in the seronegative primary stage, practically no case should ever show signs of syphilis or become seropositive, and complete cure can be assured generally. In all types of syphilitic infections, the treatment should not be begun until the patient has been submitted to a thorough medical and physical examination. It is important to impress on the patient that the disappearance of signs and symptoms of syphilis does not in any case mean that the disease is cured. The need for strict and systematic supervision of the patient and maintenance of general health throughout the treatment is imperative. With the age of the disease, the need for individual study of the patient and appropriate modification of the treatment becomes all the more essential. The importance of routine examination of the spinal fluid in every patient with syphilis, early or late, will be apparent from the fact, that the spinal fluid abnormalities antedate the appearance of obvious clinical damage in the nervous system by many years. The latent neurosyphilis can only be discovered by means of spinal fluid studies (serologic, cytologic, chemical etc.). Lumbar puncture should be delayed upto 6 to 12 months of treatment in early syphilis; while it should be done, before the start of treatment in late syphilis. In no case of syphilis the examination of the cerebrospinal fluid should be omitted before it is given up as cured and a convenient time, in early s cases, is 1 to 2 years from the cessation of treatment.

It is essential to give combination of drugs. Arsenic, bismuth or mercury, and iodides are the sheet anchors of syphilitic treatment. Mercury, though still used in certain cases, has been superseded by bismuth. Arsenotherapy is, of course, the primary weapon against Tr. pallida and should always be used when rapid treponemicidal action is essential, as in early syphilis. Early infection demands an intensive arsenical therapy. Heavy metals and iodides are usually adjunctive only and should not be ordinarily used alone. Heavy metals assume increasing importance in the treatment of late syphilis, especially where complications are present. In rare cases, in which it is inadvisable to administer arsenic, yet in which prompt therapeutic effect is highly desirable, as in secondary stage, one may use soluble preparation of bismuth (or colloidal mercury sulphide) intramuscularly, every third day, for several weeks and later on shift to an insoluble preparation of bismuth. Surface lesions usually become non-infectious after a few weeks.

Treatment of early syphilis presents little difficulty and can be systematized in most patients, as they are usually younger and able to tolerate the strain of intensive and continuous treatment. The aim of this treatment is not suppression, but complete eradication of the infection and control of infectiousness. The treatment should be maximum in amount consistent with the safety of the patient, and should be continuously carried out, till the point of complete sterilization is reached.

Treatment of late syphilis, on the contrary, is a difficult problem and the patients in these stages require individualized therapy. Treatment is given more for alleviation of symptoms and arrest of progress rather than in the hope of procuring cure. The aim of this treatment is neither serologic nor biologic cure, but symptomatic and clinical cure. Naturally, the therapeutic attack is less intensive and the continuity of the treatment is by no means so essential as in early syphilis. Rest periods or interrupted treatment are probably more helpful. Special diligence in the choice and start of treatment is essential. Treatment with iodide and bismuth should always precede arsenical therapy, at least for a month, to obviate the therapeutic shock. Arsenic must be used very cautiously particularly in nervous and cardiovascular syphilis. Neurosyphilis requires, in addition to arsenic and bismuth, special therapeutic measures like malarial therapy and hospitalization. Treatment of neurosyphilis with arsphenamine or neoarsphenamine and bismuth may improve the patients’ condition but, as a rule, it proves inadequate to arrest the progress of the disease. Pentavalent arsenic like Tryparsamide (M&B) given in conjunction with bismuth or mercury is more effective and in early cases arrests the disease. If there is no favourable response after a couple of courses of tryparsamide therapy, the need for non-specific fever therapy should always be considered.

To control infectiousness and to lay foundation for biologic cure, the therapy should be immediate, continuous and as intensive as the patients’ tolerance for arsenic and bismuth will permit. Treatment must never be discontinued or even temporarily interrupted, merely because the blood Wassermann is or has become negative. If the therapeutic influence of treatment is withdrawn, short of complete sterilization of the patient, a fresh multiplication of the organisms in the tissues and their spread are likely to occur. “The effect of inadequate treatment varies with the duration of infection. In early syphilis, a little treatment maybe worse than none. In late syphilis this is probably not true”. The relapse is more frequent in inadequately treated patients with early syphilis than in patients with early syphilis than in patients who have already developed frank secondary syphilis. Late lesions in central nervous system and cardiovascular system are distinctly more frequent after inadequate treatment of early syphilis.

To attain biologic cure in seronegative primary stage of syphilis, most authorities consider, that the treatment should be continued for a minimum of 2 to 3 unit courses without a break; and for early seropositive cases primary and secondary, the treatment should be continued 12 to 18 months, after the disappearance of all signs and symptoms, and blood and cerebrospinal fluid have remained normal for a year. “A safe rule in early syphilis in general is to administer continuous treatment until blood Wassermann and cerebrospinal fluids have become normal and have remained so for one year. In most cases this will not be difficult”. In late syphilis the prolongation of treatment for 2 to 3 years after all signs and symptoms have disappeared and the Wassermann reaction -, if possible - has reversed, are considered essential. Here, the criterion of Wassermann reversal should not be insisted on; in fact, it is of little value as a measure of length of treatment. The effect of treatment is better gauged by clinical standard and in terms of “arrest”. The response of the abnormal spinal fluid to treatment should be used as a guide to treatment in neurosyphilis.

In early syphilis, serologic reversal of blood serum is expected during the first course; sero-resistance after two full courses or six months’ treatment is dangerous and is a definite indication for the examination of the cerebrospinal fluid. It not uncommonly indicates, - in absence of irregulat treatment - the involvement of the nervous system. In late syphilis, persistently positive Wassermann is much more likely to be due to bone, visceral or cardiovascular involvement than early in the disease.

In early syphilis the study of the spinal fluid should be deferred until completion of the second course. If the initial examination of the fluid is negative, it should be repeated 12 to 18 months after the completion of treatment. If negative, after this period, the patient may be assured with reasonable certainty that he will not develop neurosyphilis.

It must be remembered that with the completion of required treatment and return of clinical and serological normality, the responsibility of the medical attendant is by no means ended. Subsequent relapse may occur and a real protection against this relapse and progression lies in rigid post-treatment “follow-up” in every case, for a period of five years. This fact should be made known to the patient and his co-operation for periodic supervision should be sought.

I am indebted to Lt. Col. Jelal M. Shah, I.M.S., Superintendent, Sir J.J. Group of Hospitals, Drs. S. Noronha, M.B.E., D.T.M. (Lond.), D.T.M.H. ( Eng.) and V.V. Gupte, M.B.B.S., D.O.M.S. for their suggestions. I acknowledge with thanks the use of monograph by J.E. Moore, M.D., in preparation of this article.