THE DANGER OF MODERN TREATMENTS


Owing to the peculiar constitution of protein the appearance of the signs and symptoms of shock may be delayed months and even years, and the longer the delay the more difficulty grows the problem of combating them. may be seriously interfered with by the production of man-made milder infections.”


SOME LITTLE UNDERSTOOD EFFECTS OF SERUM THERAPY.

(From the Medical World, April 6th, 1934)

THE ARTHUS PHENOMENON.

Anaphylaxis may take the form of sudden collapse resembling that seen in primary “allergic” sensitiveness; this is serious enough, but the particular form which I wish to bring to the notice of the reader consists in the appearance of massive gangrene at the site of injection, resulting, in severe cases, in the subsequent death of the patient. It has been known as then Arthus phenomenon ever since the French research worker of that name reported its occurrence in animals in 1903.

These experiments, however, in spite of the intense suffering they must have caused to the animals employed, appear to have been devoid of any benefit to mankind, for, apart from a few isolated examples, little attention was paid to the phenomenon in man until quite recent times.

Dr.I.Harrison Tumpeer, an American authority on the subject, mentions that Lucas and Gay called attention in 1909 to similar effects in children who had been inoculated with several doses of diphtheria antitoxin as a prophylactic, and suggests that the infrequency of such reports was due “to the fact that repeated administration of antitoxin was not a common practice”. He then makes the somewhat contradictory statement that “Undoubtedly subsequent reactions in the nature of the Arthus phenomenon occurred following additional use of horse-serum for other reasons, but they were disregarded or not sufficiently appreciated until 1927….”.

As I have pointed out before, it is not difficult to supply reasons for such omissions. It is quite customary to ignore the ill-effects of current practices until their obviousness makes further disguise well-nigh impossible. Dr.Tumpeer goes on to add, “With the advent of the toxin-antitoxin era, a new situation developed in which sensitization to horse-serum was produced by three injections at weekly intervals of the minute quantities of horse serum present in the ordinary toxin-antitoxin mixtures.

In 1927 Gatewood and Baldridge described six cases. the severest of which occurred in a nurse of twenty-five. The particulars they gave are briefly as follows:-.

(1) The nurse was Schick negative in January, 1925, but, “in spite of this she was given toxin-antitoxin mixture in three doses, February 6th, 13th and 20th.” She developed diphtheria in November, 1925, and was given antitoxic serum in one arm and the corresponding hip. This was followed by acute general enlargement of the superficial lymph nodes. On the ninth day a further injection of serum in the other arm and corresponding thigh resulted in the arm becoming red, swollen and tender, and by the second day both arm and leg were twice the normal size. By the ninth day after the second injection the skin of the thigh lesion had become a black eschar; free incision yielded no pus although the tissue was necrotic.

On the twenty-sixth day the discharge from the wound became purulent. On incision, “the abscess cavity was found to extend from the knee to the hip and around the thigh to the inner aspect. In the previous wound there presented a mass of neurotic tissue which was removed. It involved subcutaneous fat, fascia late and muscle, and was a mass the size of a fist.” The left arm, which has undergone all the changes of the thigh, was later incised, yielding a thick yellow necrotic material. The nurse eventually recovered.

The authors predicted that the Arthus Phenomenon might logically be expected to be reported more frequently with the increased use of horse-serum. And they were right, for in 1931, for instance, Dr. I. Harrison Tumpeer described the following case:-.

(2) A girl of five years had received the usual three injections of toxin-antitoxin in 1926 when one year old. In 1927 she was pronounced Schick negative. She developed diphtheria in 1930, and an injection of serum was given in the left gluteal region, followed three days later by a second dose on the opposite side. In three hours the buttock began to swell and became extremely tender, until eventually the whole region became black and gangrenous. By the ninth day a deep area of ulceration appeared at the margin, separating the necrotic tissue from the normal.

On the twelfth day the child began to complain of extreme pain over the right lower quadrant of this area, and an incision yielded thick yellow pus. From now onwards the condition spread over the abdominal wall and thigh until the sixteenth day, when a large necrotic mass, 6 inches by 8 inches, was cut away under anaesthesia. The author writes, “This large piece of gangrenous skin with subcutaneous fat and fascia was lifted off much as a lid from a stove . . . the underlying muscles lay exposed almost entirely independent of fascia which sloughed, and a large amount of which had come away in the discharge.

After apposition, the muscles lay exposed much as in an anatomic dissection. The skin was undermined upward as far a the umbilicus, medially beyond the midline, and as low as the lowest portion of the popliteal space. subcutaneous fat and fascia of the right buttock, hip and thigh, as far as the knee joint.” In spite of assiduous irrigation of the wound she became rapidly worse, suffering considerable pain. Following a blood transfusion on the twenty-seventh day of illness, she became cyanotic, vomited, become unconscious, and died a few hours afterwards.

(3) The third case was reported by Dr. H.E. Irish and Dr. E.C. Reynolds in 1933, and occurred in a boy aged two years and four months. He developed symptoms suggesting meningitis and was given three injections of anti-meningococcic serum on three successive days, and a further dose four days later. The three usual toxin- antitoxin inoculations had been performed at the age of eleven months, and he had been normal in weight and mentality. The serum was injected into the buttocks and was followed by an urticarial eruption over the entire body, the edematous swelling of the face being sufficient to close the eyes.

Delirium with a temperature of 103 persisted for three days, when he became rigid. He was then given a further injection of serum in the left buttock; within an hour the site became purple, and on the following day a similar injection into the right buttock resulted in a similar reaction. During the next few days the areas of purple swelling extended from the buttocks over the front of the abdomen and right thigh, and large blebs about one and a half inches in diameter appeared. Six days later these gave rise to a bloody watery discharge.

At this time the child was admitted into hospital, and presented gangrenous areas on both buttocks, both sides of the abdomen, and the thighs. There was a patch of pneumonia in the right lung and a left otitis media. There was no evidence of meningitis present, and, seeing that no diagnostic test of the cerebro-spinal fluid had been made, this case supplies a further instance of the “inappropriate” use of serum. Despite the removal of large masses of necrotic tissues, surgical drainage and three blood transfusions, the child died in twenty-one days from admission to hospital.

For further details of these carefully recorded cases the reader is referred to the original articles from which the foregoing accounts are derived. They will be well repaid for such study.

It is necessary to emphasize once more that this phenomenon of mass gangrene is one which may occur without previous warning in any child who has been at any time subjected to the so-called immunizing inoculations of toxin-antitoxin, should a further injection of horse serum be given. It is not a particularly comforting thought for any parent to feel that the possibility of such a tragedy hangs over his child for an indefinite period, no matter how carefully the injection has been carried out and despite all precautions in manufacture. The danger is inherent in serum-therapy.

As Dr. Harrison Tumpeer remarks:-.

“It is reasonable to suppose that many individuals inoculated with toxin-antitoxin derived from horse serum might subsequently require horse serum for such conditions as scarlet fever, pneumonia, tetanus, haemorrhage, or even diphtheria itself. In such individuals there would be present, to some degree at least, the laboratory conditions of Arthus.”.

Longcope and Rakemann have stated that “the injection of horse serum in small or large amounts in human beings is always followed sooner or later by the development of (specific) hypersensitiveness of the skin”.

Nor is the problem affected by the smallness of the dose; for in an article on this very point in the Journal of Immunology Dr. S. B. Hooker of Boston writes:- “That such a tiny amount of horse serum (about 0.01 mil. in the total individual dose of toxin- antitoxin, and 0.005 mil. in the test dose) should suffice to develop allergic conditions in previously non-sensitive human beings was regarded as a phenomenon of considerable biological interest”.

Gatewood and Baldridge, after referring to the definite demonstration by Hooker of the production of skin hypersensitiveness in otherwise normal and insensitive individuals by the injection of toxin-antitoxin, go on to declare that: The statement from most commercial biological laboratories as well as many workers in the field in immunity, that the amount of horse serum in toxin-antitoxin mixtures is too small to be sensitizing, seems to us to be untenable.”.

M. Beddow Bayly