SOME LITTLE-UNDERSTOOD EFFECTS OF SERUM THERAPY.
By M. BEDDOW BAYLY, M.R.C.S., L.R.C.P.
(From the Medical World, April 6th, 1934).
OUR excellent contemporary, the Medical World, published the following article, the importance of which can scarcely be overstated. The original paper of Dr. Bayly is fortified by numerous references and by valuable illustrations which regretfully were left out through lack of space. Those who are interested in the subject should obtain a copy of the original from the office of the Medical World, 56 Russell Square, W.C.I. – EDITOR, “HEAL THYSELF”.
ALTHOUGH other therapeutic agents may be dangerous to the health and life of the patient if administered without due regard to technique and dosage, it must be conceded that to none of them have there been ascribed such terrible and tragic consequences to health and life as have all too frequently followed the use of animal sera, even when accompanied by the utmost skill in manufacture and application.
That they occur far more often than is generally realized is frankly admitted by those authorities who from time to time report cases which have come under their observation. But so great is the almost mystical veneration in which antitoxic sera are held by medical science, and so powerful the commercial interests which benefit by their extended use, that it has come to be regarded as almost a breach of medical etiquette to criticize adversely this form of treatment, or even report untoward results when they occur.
There must be few of my readers who cannot recall instances of cases which have been, consciously or unconsciously, “hushed up”, especially in Coroners Courts, for fear that discredit might be cast upon the practice either of serum-therapy or vaccination.
Truth has no greater enemy than fear. Let us, therefore, for the sake of the dignity of our profession, frankly face some of the facts which experience has brought to light, and then have the courage to think the problem out afresh for ourselves, without reference to outside influences or ulterior considerations.
The fact that many who have already done this have come to the conclusion that, so far as serum therapy is concerned, the game is not worth the candle, should prove at least the practice of serum-therapy is by no means so beyond question as its more fervent advocates would like us to believe.
There is a classical story related of the great John Hunter that when he was approached by Edward Jenner, and was falteringly informed by him that he thought he had a remedy against small- pox, he replied abruptly: “Dont think! TRY!” This story is supposed to indicate the genius of Dr. Hunter, but it appears to the writer that this advice represents precisely the line we have too often taken, to the detriment alike of our patients and of our art, namely, to experiment with unknown remedies first and refuse to think about them even when their harmful effects have become apparent to everyone else.
At the present day those three words might well form the slogan of the manufacturing chemists who, as Lord Horder remarked recently, have become the doctors mental masters instead of his servants; how often do they not say in effect, if not literally, when urging us by means of their specious advertisements to purchase a supply of some new products of the laboratory: “Dont think TRY!”.
Let us now consider what are the peculiar dangers associated with serum-therapy, apart from any question of faulty technique either in manufacture or in administration. (I have purposely omitted any reference to the series of tragic fatalities which, during the past fifteen years, have been, on investigation, attributed to such errors.).
THE INHERENT DANGERS.
They fall under three main headings:.
(I) Immediate. This may take the form of sudden collapse and may sometimes be followed rapidly by death.
(2) Delayed. This may take the form of (a) rashes, joint pains, etc., which may occur after a few days; (b) a state of hypersensitiveness known as “anaphylaxis” which may lead to severe illness, prostration and death.
(3) Remote. This may take the form of numerous chronic and intractable types of disease which, as often as not, are never traced to their true cause.
Let us examine these in greater detail.
(I) Many cases of sudden collapse and death in previously healthy individuals, following injection with serum as “contacts”, have been recorded in the medical press ever since the classical tragedy of the death of Dr. Robert Langerhans own son a few minutes after a prophylactic dose of anti-diphtheritic serum in 1896.
In 1924 Lamson collected data of forty-one similar deaths due to the administration of sera. Numerous instances occurred during the Great War, both in horses and troops, but in the general carnage little interest was aroused.
In the Medical Press and Circular of January 19th, 1932, the statement is made that “It is almost always with antitetanic or antidiphtheritic serum that fatal accidents or paralysis occurs.”.
Any inoculation of a foreign proteid through the skin may have this result. The peculiar chemical idiosyncrasy of the blood to which it is ascribed has been termed “allergy ” to distinguish it from the acquired sensitive (Anaphylaxis) presently to be described. The distinction, however, has never been very clearly or satisfactorily defined.
(2) (a) Serum Disease, which occurs in about 40 per cent of the inoculated, has been investigated by many workers since it was first studied by Von Pirquet and Schick in 1903-4. The widespread use of antitoxic sera in diphtheria, and later for tetanus, erysipelas, meningitis, scarlet fever, etc., has requested in a large increase in the actual incidence of this condition according to Dr. Mitchell, who declared a few years ago that it was “evident that some factor is operating to cause an increase in the incidence of serum-disease, and that refinement of serum alone will not solve the problem” (my italics).
In the Medical Press and Circular (January 19th, 1927) it is estimated that serum reactions occur in 12-15 per cent. of cases of children after the first injection, rising to 50 per cent. for subsequent ones, and in 75 per cent of adults.
Even higher figures are mentioned in the Epitome of the British Medical Journal (December 31st, 1932). Statistics from a Chicago hospital, collected over a period of 19 years, show that reaction occur in 28.1 per cent of cases with diphtheria antitoxin, 22.7 per cent of cases with diphtheria antitoxin, 22.7 per cent. with scarlet fever antitoxin, and 81 per cent with meningococcic serum.
The symptom usually arise some three to fourteen days after the injection of the serum. They formed the subject of an interesting monograph n 1918 by Dr. E. W. Goodall, who collected and published observations on 3,500 cases of serum sickness following injections of diphtheria antitoxin.
They consists of rashes, generally urticarial in character, severe joint pains, glandular enlargement, abscesses at the sit of the injection (even when strict asepsis has been observed), pyrexia, cardiac paralysis, vomiting and diarrhoea. These sequelae of antitoxic sera have been so well described that it is unnecessary to deal with them here in greater detail. Those interested are referred to the standard text-books on the subject.
In point of fact, it seems to be eminently desirable that the serum-therapist should familiarize himself with them to a far fuller extent than is usually the case, if one may judge by the extremely casual manner in which advice is given to the practitioner to inject serum on the assumption that it may do some good and wont do any harm, even if the diagnosis should turn out to be quite other than that anticipated.
One would imagine that had the importance of these not inconsiderable discomforts and dangers to the patient been more fully appreciated, it would have been realized how wrong is the practice of administering a serum before some diagnosis has been reached which would at least indicate the logical appropriateness of that particular serum.
Dr. Estcourt-Oswald is by no means the only practitioner who has issued a warning against this unjustifiable procedure which should, in view of grave risks to the patient, be regarded as malpractice.
Dr. L. J. Witts, Assistant Physician at Guys Hospital, in the course of a clinical lecture delivered not long ago on “Fallacies and Dangers in Treatment”, referred to it in the strongest terms. He was dealing more particularly with the use of anti- streptococcal serum “when there is no evidence that it is effective.” “You expose your patient”, he said, “to the risk of an immediate serum accident; you may inflict on him the painful disease of serum-sickness, in which the tortures of the cutaneous irritation, and the swollen joints may be almost unbearable, and finally you sensitize him to serum so that his life may be imperiled in the hour of need, when it may be essential to inject a potent serum.”.
I am not concerned here with discussing whether or not serums are ever effective or necessary. My view coincides in this matter with that of Sir Almroth Wright, who declared that the whole body of beliefs in serum therapy rested, in his opinion, “on a foundation of sand.” I believe there are far better ways of dealing with disease than by the use of sera which, in addition to the dangers now being discussed, turn our attention from the investigation and treatment of the real causes of the various complaints from which mankind suffers. I hope I may have the privilege and opportunity of laying my views on these matters before the reader at a later date.
In this article I am calling attention to what appears to me to be unappreciated ill-effects of animal sera.
Dr. L. J. Witts warning regarding the danger of anaphylaxis brings me to the next sub-division.
THE DANGER OF ANAPHYLAXIS.
(2) (b) This is a possibility with which medical practitioners seem peculiarly unfamiliar; otherwise one would have been tempted to believe that the importance and universality of this phenomenon had been deliberately and wantonly ignored in the interest of, and under the powerful though subtle influence of, the profit making manufacturers. (I have shown elsewhere that one horse purchased for, say, ten pounds, will in nine years produce serum of which the retail value is in the neighborhood of L48,000.).
In using the word “universality” I mean to indicate that every single person injected becomes sensitized in more or less degree, no matter what serum has been employed; and that this condition may be manifested at any time thereafter in that persons life if a serum of any type derived from the same species of animal injected for a subsequent illness. Moreover, no one can foretell the likelihood of a severe reaction occurring in any particular individual.
When one realizes the horrible and sometimes fatal nature of these reactions (presently to be described) the warning against the indiscriminate use of sera in inappropriate cases will be seen to have especial force. Let me again remind the reader of the advice, constantly offered to the practitioner by Medical Officers of Health and others, of which the following is a typical example. Writing in the British Medical Journal (July 22nd, 1933), Dr. L. Cobbett exhorts: “Let the doctor never wait for the saw [throat], but give antitoxin with the least possible delay . . .”.