TREATMENT OF CONGENITAL SYPHILIS

by M. P. Vora, M.B.B.S.

ST. GEOGER’S HOSPITAL, BOMBAY.

The Medical Bulletin

Number 13 of Volume No – XI., 1943, Number – 265 of July 3 rd, 1943.

Page No. 233 to 237.

• There can hardly be any controversy about the urgency of expert pediatric care in the treatment of infants and young children. This holds true even in the treatment of congenital syphilis.

• Prophylaxis - Congenital syphilis is a preventable disease and the method of its complete eradication is well known. It hinges on, firstly, the prevention of infection of mothers, secondly, on the diagnosis os syphilis early in pregnancy, at least by the fifth month, and, thirdly on the energetic prenatal treatment of the syphilitic mother with trivalent arsenic and bismuth. Yet, and, indeed, it is very unfortunate -, a number of syphilitic babies are born every year and still a greater number of pregnancies end in either abortion, miscarriage or still-birth.

Necessity to control the transmission of infection to mothers will be obvious when one remembers the fact that in most cases the father has contracted syphilis and has passed on the infection to the mother, who gives birth to a syphilitic infant. The prevention of infection of mother is possible, first, by instituting prompt, intensive and thorough treatment of all cases who contact syphilis, second, by discouraging marriages until a clean bill of health has been given, third by preventing conception, if already married, until all clinical evidence of disease has disappeared. If conception has already taken place, early diagnosis and treatment of mother, as stated below, is indicated.

The early diagnosis of syphilis in pregnant women can be made easily in majority of cases by taking a careful history and employing serological tests, as a routine, preferably before the third month and if negative, repeated at the fifth and the seventh months to spot out those cases of syphilis following conception. The clinical characters of syphilis are either modifies or completely masked during pregnancy; physical examination alone, therefore, cannot be depended on to disclose the disease. From this point, the importance of a routine serological test of pregnant women at every antenatal centre cannot be overestimated.

The chief aim of the syphilis in the pregnant woman is to prevent infection of the foetus; and experience has amply shown that antisyphilitic treatment given to the pregnant woman can in good many cases either eradicate or modify the disease in the foetus. Unless the syphilitic woman receives sufficient treatment during her pregnancy, the chances of her passing on the disease to her unborn baby are substantially great. Therefore, injections of trivalent arsenic and bismuth are arranged in such a way that delivery of the infant is immediately preceded by at least eight to ten weeks’ administration of arsenic. Authorities go a little further than this and recommend a minimum of twenty injections of trivalent arsenic before delivery. Earlier the diagnosis is made; sufficient time is at one’s disposal to carry out adequate treatment. A later diagnosis leaves fewer weeks for the treatment. Where it is necessary, because of the limited time, to shorten the treatment, the major part of the cutting should be on the bismuth and to arrange so as to complete the administration of 8 to 10 injections of arsenic before delivery. To do so, the intervals between successive injections may have to be reduced from usual seven days to five or even four days, especially, in view of the urgent need to be certain of preventing syphilis in the child. The pregnant syphilitic woman should be treated as intensively as her tolerance will permit. Generally she tolerates antisyphilitic therapy fairly well; but this does not relieve one of one’s duty to watch the patient carefully. She should always be observed and studied for the earliest signs and symptoms of intolerance. Minor signs of tolerance are valuable indications for reduction of the subsequent doses and lengthening of intervals.

• Early detection and early treatment of congenital syphilis . The duty of the physician does not terminate with the adoption of prophylaxis. It is further necessary to keep under close observation the newborn and examine it repeatedly until he is satisfied that it has escaped infection; for, it is frequently difficult to eliminate completely, during the first few weeks, the possibility of its having syphilis. Syphilitic infants born of treated mothers or the offsprings of parents who have long-standing syphilis, rarely show evidence of inherited syphilis at birth or during infancy and childhood but may develop syphilitic disease later in life. Just as in adult syphilis, the longer the infection has existed, the harder it is to eradicate the disease from the body, and greater the likelihood there is of permanent damage. The possibilities of preventing the development of the syphilitic stigmata and late lesions, in high a proportion of cases, by adequate treatment of early congenital syphilis are really great. Because of the desirability of early treatment and prevention of development of late lesions (such as cranial bossing, perforation of the palate, saddle-shaped nose, iritis, interstitial keratitis, nerve deafness and Parrot’s pseudo paralysis,) the diagnosis of congenital syphilis should be attempted as soon after birth as possible. This can only be done by repeated physical examination, quantitative serologic tests and X-ray examinations of the long bones for the signs of infection.

A positive serologic test on the cord-blood does not necessarily mean that the infant has syphilis. Such a test may be positive because of the reagin present in the mother’s blood. Treatment of the infant on this score alone is not justified. Subsequent tests should reveal an increasing amount of reagin in the infant’s blood. If they show progressive decline in the amount of reagin or become negative, it is evident that the infant is free from infection. Positive serological tests after the second month are usually regarded as conclusive evidence of infection. Tests should be repeated at sixth month, first year, second year, at puberty and early adolescence. If all of them are negative, probably there is no infection. It is imperative that the children born of syphilitic parents or suspected of inherited syphilis should be kept under observation till they reach adult age.

Therapeutic test or administration of arsenic, bismuth or mercury, alone or in combination, - though it has been in use for a long time, - is scientifically not sound and should not be practiced ordinarily. It should only be had recourse to as a diagnostic procedure when other and more accurate methods have failed to establish diagnosis. For, there are many cases of skin lesions not due to syphilis and in which arsenic or mercury is of value therapeutically. It merely masks the disease.

• Therapeutic problem - Congenital syphilis and acquired syphilis in adults do not differ very much and consequently the principles governing their treatment are more or less the same. It is therefore, necessary to make clear distinction between early and late stages in congenital syphilis, similar to those in acquired syphilis. During the first two years of infant life, there is tendency to lesions of the skin, mucous membrane and muco-cutaneous junctions. These lesions, when present in a clinical recognizable form, are typical of early congenital syphilis and are profoundly similar to those of secondary type occurring in early acquired syphilis. Early congenital syphilis, in contrast to early acquired syphilis, shows severe toxicity, marked constitutional disturbances, concomittent lesions of the viscera especially liver, spleen, kidneys and bones, and has a very high rate of mortality. This peculiar character of early congenital syphilis may be due to the wide-spread nature of the infection, which is acquired in utero and has existed for some time before the child is born, or due to want of sufficient extra-uterine time for the infant to mobilize body’s defensive system or both.

If the infant, unrecognised as syphilitic and untreated, survives first few months, opportunity is provided to build up body’s defenses. It enters the period of latency of several years’ duration and develops lesions of the eye, bones, the inner ears and the nervous system. All manifestations subsequent to puberty are of the tertiary or gummatous type and the risk of death is comparatively negligible.

Thus in early congenital syphilis, the aim of the treatment is two-fold; the actual preservation of life and symptomatic, clinical and biologic i.e. radical cure of the infection, if possible. Both these ends can be accomplished. In the late congenital syphilis, on the contrary, radical cure is probably no longer attainable. The aim of treatment, therefore, becomes symptomatic relief, healing of the lesions, arrest of progress and maintenance of good health and efficiency i.e. symptomatic and clinical cure.

The principle of treatment of early congenital syphilis is the same as that in the early acquired syphilis, i.e. to replace by means of drugs the patient’s own defensive mechanism. Treatment should be given, as far as possible, continuously and without any rest periods. Of course, when intercurrent disturbances are present or intolerance is noticed, the continuity of the treatment may have to be interrupted. Generally speaking treatment should start with arsenic rather than heavy metal. On account of severity of infection the chances of therapeutic shock are greater in infants than in adults. The first dose therefore, should be small, i.e. half the average initial dose for an infant. It is better to administer smaller doses twice a week rather than to give one large dose once a week. In severe cases of the newborn where the lesions are marked, or where the infant I svery young and poor in health, treatment at first must be very guarded. It will be advisable to start with mercury orally or by inunctions and later on to resort to injections; even then the improvement in the condition of the child is often remarkable. The arsenical preparation of choice is Sulpharshenamine or the allied preparation. Sulfarsenol (A.F.D.) has small graduated doses specially designed for use in children. It can be given intramuscularly in concentrated solution, thus avoiding technical difficulties of intravenous route. Its initial dose for infants should be 1 to 1.5 mgm. per kilo body weight and gradually increased to 6 mgm per kilo body weight, and for children 1.5 to 2 mgm. per kilo body weight increased to 8 mgm. per kilo body weight. Acetylarsen for infants (M. & B.) is another drug of proved value. Each two c.c. ampoule is equivalent to 40 mgm. of arsenic and is given subcutaneously or intramuscularly. It is less painful and less likely to give reactions. Its dose can be determined very esily and most accurately. For an infant weighing 8 lbs. (2.2 lbs: Kg.) one may safely start with a dose of 0.2 c.c. and gradually increase to 0.5 c.c., once or twice a week. Neoarsphenamine or the allied preparation, ‘N.A.B.’ may be used because of the rapidity of action but it requires to be given intravenously; for that purpose a vein at the bend of the elbow or at the ankle may be selected. Its dosage is calculated on the basis of body weight. Initial dose is usually 10 mgm. or one cgm. Per Kg. body weight per week, and gradually increased to 25 mgm. per Kg. body weight. Children and infants tolerate all arsenic drugs well, and the toxic reactions are less frequent.

Once the gross lesions have disappeared, and the condition of the child in improved as the as the result of arsenic, one should supplement the treatment with one of the heavy metals, mercury and bismuth. Institution of dual therapy is essential for satisfactory results. Mercury should be used in very young and malnourished infants and children with small buttocks. It may be given in the form of injections, one gram of 50% mercury ointment (the size of a pea) to be rubbed daily for about 15 minutes, or hydrarg. cum creta gr. ¼ to 2, twice a day, orally. Pulvis cret. Aromatic or pulv ipecac co. in elderly children may be added to the grey powder just to correct tendency towards diarrhoea. Bismuth is preferred in cases where the hips are sufficiently large to receive intramuscular injections. It is given in dosage of 2 mgm. per kilo body weight per week. One may start with 0.01 gm. and increase it to 0.025 to 0.05 gm. for an average infant and to 0.01 to 0.2 gm. for an average child at the age of twelve. Because of the small dosage bismuth preparations of weaker strength are to be selected for use. Bisantol M. B.), Bisoxyl (B. D. H.) and Stabismol (Boots) contain 10% metal i.e. 1 c.c. contains 0.1 gm, ½ c.c. 0.05 gm, ¼ c.c. 0.025 gm of bismuth metal. Iodides are unnecessary in early cases. Tonics like Syrup ferri iodide B. P. may be prescribed in between the courses of treatment, which should proceed on the same lines as laid down for adults.

Intolerance to drugs in infants and young children is very difficult to detect unless one keeps a close observation on the general health of the child and notes the gain or loss in weight from week to week. Tolerance must not be exceeded in the least in zeal for continuation of treatment.

A fact which is forgotten too often in the treatment of syphilis, both acquired and inherited, is that the disappearance of the signs of syphilis does not mean cure of the disease. The minimum period of treatment in syphilis in general is frequently stated to be 1 ½ to 2 years, and it cannot be less in any case of inherited syphilis, no matter how slight the manifestations. The duration of treatment should be measured by serological control. The test should be repeated at the beginning of each course. The spinal fluid should be examined, as a routine, and should not be done until at least 6 months of active treatment are over. Treatment should be continued until blood W.R. and cerebrospinal fluid have become and remained normal for one year. The minimum amount, which authorities recommend, is five courses each of arsenic and bismuth spread over an average period of 18 months. Any modification of the suggested plan of treatment is welcome as long as it adheres to the three main principles of alternating, continuous and prolonged treatment. It is also important to prolong “follow-up” every 6 to 12 months until puberty and early adult life.

The principles of treatment of late congenital syphilis are the same as in the late acquired syphilis. The aim of the treatment is symptomatic relief, maintenance of good health, relatively little emphasis being placed on the serological reversal. There is hardly any need for continuity of treatment; the rest periods in between courses are, preferable. Therapeutic attack need not be very energetic. Individualization of the therapy is essential. With the little modification of drugs and dosage the same outline of treatment as in adults may be worked out. Neoarsphenamine is the arsenical drug of choice; and bismuth is preferred to mercury generally. Injections may be given either alternately or concomitantly. Iodides are of special value in late stages of infection. The affections of the cardiovascular and nervous system are very mush less common or unusual in the late congenital syphilis. The outlook is worse in cases of congenital neurosyphilis which usually occurs incidiously at the time of puberty. Tryparsmide should not be used lightly otherwise blindness due to optic atrophy may result. Prolonged treatment and follow-up should be insisted on.