_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.