CHAPTER X
_HAY FEVER AS ANAPHYLAXIS THE GOUTY DIATHESIS REAPPEARS_
Fifty years ago de Mussy pointed to the resemblance between hay fever and gout and claimed hay fever as a manifestation of the gouty diathesis. As related in Chapter VII, he based his theory on the resemblance between the history and symptoms of hay fever patients with those of gouty patients. In his day he found both hay fever and gout confined to the Anglo-Saxon race, both hereditary and familial, both exhibiting urticaria, eczema, and asthma, and he recognized that the lesion in the eyes and nose of the hay fever patient was not a true catarrh but an urticaria.
On the other hand, Wolff-Eisner declared that hay fever is an anaphylaxis and this idea has been developed and confirmed by Koessler and others so fully that we must accept it as proven. Let us examine this matter of anaphylaxis to determine whether after all there is any essential difference between the two views of hay fever.
=Anaphylaxis.= The conception _anaphylaxis_ or _lack of protection_ begins with the discovery that a harmless protein injected into a dog will so sensitize him that, after ten days or so, another injection of the same protein will kill him. The point is that the change has occurred in the animal, not in the protein injected. The protein is the same as before and can be injected once into any number of dogs without harm. In this way we explain the cases in which drugs and foods that are harmless to most people may be virulent poisons to those who happen to have been sensitized by a former overdose. The widespread use of antitoxin in diphtheria gave abundant opportunity to study the phenomena of sensitizing a human being with one dose and killing him with another dose of the same thing.
The symptoms of anaphylaxis first observed were urticaria, arthritis, and dyspnoea. Then Bruck showed that what we used to call _idiosyncrasy_ to drugs and foods that are harmless to most people is really an anaphylaxis, attributable to a former overdose of the same thing. Next, it was learned that anaphylaxis may persist through life and be transmitted to the offspring of rabbits and guinea-pigs, illustrating the cases in human families where sensitiveness to a certain food or drug runs down through several generations. Then the dermatologist brought in a list of skin eruptions, urticaria in the lead, as examples of anaphylaxis to certain foods or to poisons generated within the body, especially in the intestines. Then asthma was included among the anaphylactic reactions and, finally, Wolff-Eisner pointed out that the lesion of hay fever is an anaphylaxis. I may add here that this view of hay fever confirms my observation that the lesion is not a catarrhal inflammation but an urticaria.
So we have a picture of anaphylaxis as a sensitiveness to bacterial poisons or to foods or drugs that are harmless to most people expressing itself as an urticaria, an arthritis, an asthma or hay fever. But this is the very group of symptoms on which de Mussy based his theory of gout. When we add that this sensitiveness or anaphylaxis is hereditary and that it is aggravated by foods, drugs, or pollens that are harmless to most people, I submit that we have a pretty picture of the gouty diathesis; for the gouty diathesis, too, is a susceptibility to arthritis, to urticaria, and to asthma from causes that do not trouble other people, and in gout, too, this weakness is hereditary. One thinks of the gouty patient who cannot take iron or digitalis because it aggravates the gouty pain and of the attack of gout that is brought on by a glass of champagne or a piece of beef or a few strawberries that the majority of mankind can take freely without harm. Now, if urticaria, eczema, arthritis, asthma and hay fever form a picture of anaphylaxis, and if these symptoms also form the picture of the gouty diathesis, is it not probable that one of these pictures can be explained in the terms of the other? If the anaphylaxis to the diphtheria antitoxin, horse serum, can develop arthritis, is it not probable that the most striking feature of gout, the inflammation of the joint, is also an anaphylaxis to poisons yet unknown to us but the same poisons that make the gouty urticaria and asthma?
What if gout should prove to be a sensitization or anaphylaxis to uric acid that does not exist in the non-gouty? This would explain the puzzle of one patient full of gouty pains with very little uric acid in his blood while another patient, like the leukæmic, has a blood full of uric acid that does not trouble him.
=The Mechanism of Anaphylaxis in Hay Fever.= The anaphylaxis theory of hay fever is based on the observation that the epithelial cells of the mucous membranes of the eyes, nose, and throat have not lost their primitive power of digesting foreign protein.
Ages ago, when we were amoebæ or little drops of protoplasm, we had no eyes or nose or separate stomach for digesting food. The one little cell body did everything. One of the most important powers of that cell body was its power of digesting and assimilating food, and its most important food was the nitrogenous food or protein from which it built up its own body substance. Now, foreign or food protein cannot be simply absorbed as such. Foreign protein is a poison and never tolerated in the blood. The foreign protein used as food must first be changed into the special kind of protein that the body can use. The foreign protein is changed by splitting its molecule into its simplest parts and then recombining them in the desired form. The complex protein molecule, containing those sixty atoms of carbon that gave the Schrecklichkeit to the German professor of chemistry as related on page 71, is split up again and again into simpler forms. The end products are harmless, but the early splittings produce both poisonous and non-poisonous products. The end-results of these successive splittings, the splinters, as it were, are then combined by the amoeba to form its own kind of protein or body substance.
As we rose in the animal scale, instead of being an amoeba of a single cell, we became constructed of millions of tiny cells and began to set aside certain groups of cells to do special work, the eyes for seeing, the ears for hearing, the lungs for breathing, the digestive organs to prepare our food and a sheath of harder cells over the outside of the body that we call our skin and mucous membranes. Specialized as those cells have been for many generations, they have never forgotten that a foreign protein is a food or, perhaps, an enemy, to be split up and decomposed at sight. So, the epithelial cells of the mucous membrane of the nose and eyes, though they have no longer anything to do with digesting our food, secrete a ferment or enzyme that can split up any protein that may happen along. This process is called _parenteral digestion_ or digestion outside of the intestines; and this theory of the parenteral digestion of protein is the foundation of the anaphylaxis theory of hay fever.
During the growing months of the year the air is full of pollen that is blown in everybody's eyes and nose. In that pollen is a proteid that is digested by the secretion of those mucous membranes, proceeding exactly as food is digested in the stomach and intestines, splitting up the complex proteid molecule into simpler groups, and forming both poisonous and non-poisonous substances. In the normal eyes and nose this splitting of the protein proceeds slowly, forming only minute amounts of poison. As absorption from the eyes and nose is slight, no unpleasant effects are produced.
The first step in the development of hay fever is supposed to be a disturbance in this digestion of protein in the eyes and nose, by which larger amounts of poison are formed and absorbed by the mucous membrane, producing the first poisoning, which, like the first injection into the dog, sensitizes the mucous membrane to other doses of the same poison. It is supposed that disturbance in the protein digestion may be caused by stoppage of the nasal passages, with excessive accumulation of proteid, inhalation of excessive amounts of pollen, forming excessive amounts of poison, or, perhaps, insufficient secretion, so that the splitting-up process is not hastened to its conclusion of harmless products. The anaphylaxis theory halts a little at this point and is not exactly clear about the mechanism of that first poisoning.
After the first poisoning, the epithelia are permanently injured and remain more permeable to protein. They also develop the power of making large amounts of the digesting enzyme, which is absorbed into the blood and is supplied to all the tissues of the body, so that all tissues, including the skin, can decompose the pollen protein. Advantage is taken of this distribution of the protective enzyme in the skin reaction, in which a small area of skin denuded of its superficial epithelia reacts in the form of a hive-like swelling when the pollen that originally affected the patient is brought in contact with it.
The next time that the pollen reaches the eyes and nose the mucous membrane is ready for it with an abundant secretion of enzymes to destroy it. In this intense digestion of the proteid, quantities of the poisonous substances are formed which irritate the eyes and nose worse than before, explaining why hay fever becomes worse with successive attacks.
The inherited form of hay fever is explained by the well-known transmission of anaphylaxis to the offspring. The first case in the line of descent must start with a severe poisoning that lays the foundation of the anaphylactic inheritance.
I would submit to the enthusiastic immunologist that this first sensitization which he takes for granted but cannot prove is the weak spot in his hypothesis. This is the point where he needs help, and it is at just this point that de Mussy's neglected theory of gout completes the picture. The immunologist has not explained why I, a boy growing up with other boys, inhaling the same amounts of pollen as they, catching no more colds than they, and never having any serious illness, became sensitive to pollen while the others did not. There is no recollection of any "first poisoning" by pollen that might have started the anaphylaxis. But, says the immunologist, it was your parents who were sensitized and you inherited the anaphylaxis. Now, my parents lived to old age and had no sign of hay fever, though my brother had it and my children are beginning to sneeze and rub their eyes suspiciously in June and August. But if you associate hay fever with the gouty diathesis, as the clinical histories seem to justify, you enlarge immensely your opportunity to prove ancestral sensitization to whatever unknown poison originally produced the gouty sensitization. This view does not restrict you to ancestral hay fever, but extends it to gout or to any equivalent of gout.
The best work in English on hay fever as an anaphylaxis is the monograph of Karl K. Koessler in Forchheimer's _Therapeusis of Internal Disease_, 1914, Volume 5, page 671, to which the reader is referred for a full discussion of the subject. The same author gives an abstract of his work in the _Illinois Medical Journal_, 1914, page 120. This article in Forchheimer is the most complete that has been written since Sticker's time and covers the ground from Sticker, who knew not anaphylaxis, to Wolff-Eisner, who is not available in English.
I was gratified to find in Koessler a sympathetic soul. He thinks, as I did, that the monograph of Sticker in Nothnagel is the best review of hay fever that we have. He calls it "a remarkable monograph and the standard work on the subject." But why, oh why, K. K. K., in your own masterly article in Forchheimer, did you follow Sticker all through his historical chapter but leave out all that he says of de Mussy's theory of gout or arthritism as the constitutional basis of hay fever and also leave de Mussy and every reference to his work out of your list of _Literature_? The German books are more liberal. While most of them ignore de Mussy and his theory in their text, they all list his writings in the _Literatur_. Has the microbe of bacteriology and the laboratory bitten you so virulently that you can find no place for the gouty diathesis even in an index?
I know that the gouty diathesis is out of date. In fact, all diatheses are out of fashion. Nobody speaks of them now. They went out with the medical philosophies of the eighteenth century. Cellular pathology with its wonderful revelation of the anatomical seat of disease and bacteriology, with its still more wonderful revelation of the external cause of disease, so dazzled the eye and the mind that we forgot that the sensitive animal body behind the attacking microbe had its changes, too, its changes in body chemistry that could not be stated in terms of cells and bacteria. The pendulum is swinging back now to a consideration of the constitution of the body on which the microbe or poison acts, its _resistance_ or _immunity_, its _anaphylaxis_ or _allergie_. With these holiday and lady terms, are we not trying to describe what our ancestors knew as _diathesis_? For what is the old conception of diathesis but just such a hereditary weakness or lack of defense or tendency to disease that our ancestors recognized clinically but could not demonstrate, elusive, difficult to detect, but nevertheless there; like the dog who has been sensitized to an otherwise harmless proteid, who seems well and is well in everything except his susceptibility to that one special cause of disease?
Bacteriology, which first took away the idea of diathesis, is now giving it back. The discovery of the tubercle bacillus as the cause of tuberculosis banished the _tubercular diathesis_ apparently forever; but, step by step, through bacteria and then toxins and antitoxins and now through anaphylaxis and allergie, bacteriology is bringing back the old conception of an inherited or acquired susceptibility to attack. Call the old tubercular diathesis a _sensitization_ and you have made it the most modern of modern discoveries. So, also, step by step, through bacteriology with its toxins and antitoxins and now with anaphylaxis, from the philosophic ash-heap on which we thought to have thrown it for good and all, like an old family cat that we thought was dead, comes creeping back that old conception of a gouty diathesis or arthritism, not as dead as we thought it, to complete the explanation of the existence of hay fever.
I am far from saying that calling hay fever a form of gout ends the subject. I say only that bringing such a common and puzzling disorder as hay fever in line with such a common and puzzling disorder as gout brings us a long step nearer to solving the puzzle that lies behind both of them; and I say also that, in the records of this work, the name of Gueneau de Mussy, who first recognized this relation clinically, deserves a place.
Gout as an anaphylaxis, hay fever as an external expression of gout, what a vista of therapeutic possibilities is opened up by these simple experiments with pollen extracts and foods. The subject ramifies in every direction, touching the gouty form of Bright's disease, gouty heart disease, endocarditis and pericarditis, the popular "hardening of the arteries," which may prove after all not to be due to meat in all cases or alcohol in all cases but certain foods in certain cases, the increase in deaths from heart disease and kidney disease in the fifth decade of life. The correlation of these gouty problems with this work in the prevention and cure of hay fever anaphylaxis awaits a Lister or a Pasteur or a Koch who will have an eye to see and a patient industry to search and find.
When you have established hay fever as anaphylaxis or lowered resistance to a specific proteid, you may be sure that the immunologist will seize the patient as his own, carry him off to the laboratory, and there attempt to raise his resistance or develop immunity to the attacking proteid by giving minute doses of the poison gradually increased. The success of this procedure will be related in the next chapter.