Immunologic Treatment

Filed under: 4 - Atopic Dermatitis

In order to make an attempt to understand the rationale of immunologic treatment it is first necessary to consider in some detail the immunophysiologic principles involved. The antibody (atopic reagin) which has to do with atopic dermatitis is fixed in the vascular loops in the papillae of the corium, and can often also be detected in the blood, contained mostly or possibly entirely in the gamma globulin fraction. The com­monly accepted theory has been that when antigen, inhaled or ingested, reaches the sensitized skin tissue, an immunologic reaction results with the production of an irritating end prod­uct, possibly histamine, and conse­quent dilatation and increased per­meability of the small cutaneous ves­sels, with a resulting inflammatory reaction and the histologic changes of eczema.

There are those who have said that scratch or intracutaneous tests are entirely useless in the determination of etiology, and that the immediate urticarial type reaction so obtained has nothing to do with the eczema, for the eczematous reaction is a delayed twenty-four-hour type reaction, and is vesicular or papular and never urti-carial. In order to determine etiology the test reaction should produce the lesion of the disease in the same way that eczema (the lesion of the disease)

is produced by the patch test. There is some evidence in favor of this point of view, and some against it.

1. The skin of a patient who has ragweed hay fever gives an immediate urticarial type scratch or intracutaneous test. So does the skin of a patient who has atopic dermatitis due to rag­weed pollen, and only very rarely a positive patch test. If the urticarial type skin test is of etiological signifi­cance in atopic dermatitis due to rag­weed, why do not all patients with ragweed hay fever who show this test have atopic dermatitis as well?

2. If a person with hay fever but no eczema is given too much ragweed extract by inoculation, he is likely to develop urticaria, practically never eczema. A person with atopic derma­titis from ragweed, with or without hay fever, has exactly the same sort of skin test that the person with hay fever alone has. Yet his tolerance to injected ragweed extract is very low, much lower than that of the patient with hay fever alone, and if he is given any but a very small dose of ragweed extract his existing eczema will probably become worse, and he is likely to develop new eczema in places where he did not have it before. This is a delayed twenty-four-hour type reaction. The amount of anti­gen when injected or ingested which will worsen eczema or produce new eczema in a patient who already has eczema is a great deal less than that which will produce urticaria or respira­tory symptoms in a patient who has respiratory allergy alone. Why is this?

It seems clear that there is some predisposing condition in the skin, immunologic or otherwise, in persons with atopic dermatitis, which is not present in those who have hay fever alone, although they both give identi­cal wheal type scratch tests. It is likely that this condition, whatever it may be, in combination with the urti­carial type sensitivity, is responsible for the production of dermatitis, and that atopic dermatitis is not produced without it. Let us call this the X-factor.

3. If I sensitize a small place on my own skin with an egg white reagin containing serum from an eczematous baby, and then eat an egg, or indeed sometimes only an infinitesimal amount of egg white, in about twenty minutes an urticarial wheal appears on the sensitized site-never eczema. If every day I eat small amounts of egg white below the amount necessary to produce urticaria, no eczema ever develops. It is either immediate urticaria or nothing: there is no cumulative reaction. I cannot produce eczema on myself by eating a food to which my skin is sensitized, no matter in what amount I eat it. I can produce only urticaria, presumably because the X-factor is not there.

4. It is true that many times people with atopic dermatitis can eat the foods which give positive skin tests with impunity, so that these tests are often entirely without etiolog­ical significance. In Louis Tuft’s well-known “dust patient,”¹² there were positive intracutaneous tests to twenty-seven different foods, and yet his eczema was proved to be entirely due to house dust, and had nothing whatever to do with the foods to which he gave positive tests. This is a classical paper, and everyone seriously interested in atopic dermatitis should read it.

In spite of these objections which I have enumerated there can be no doubt that sometimes positive scratch or intracutaneous tests indicate etiology, and are of great value in planning treatment. I think that almost all allergists would agree to this, and possibly an occasional dermatologist.

Is it possible to reconcile these somewhat contradictory observations? I think it may be. The following hypothesis, which seems to me to fol­low logically from the observed facts, is suggested. The wheal test reaction is of no significance in atopic derma­titis by itself; it is significant only if it is accompanied by another factor, the X-factor. I have no idea what­ever what this added factor may be. The wheal reaction is, however, some­times indicative of etiology because it is sometimes accompanied by the X-factor. By itself it is of no moment so far as eczema is concerned.

It was shown a good many years ago by Oscar Schloss,¹³ who was in his day the foremost research pediatrist in America, and who has been rarely equalled and never surpassed, that a new food when introduced into the diet of a young infant is often fol­lowed by the development of a posi­tive skin test. This is a normal phe­nomenon. The degree of sensitivity is never high, and the positive test lasts for only a short time. Later Brunner and Walzer¹⁴ showed that even in older children and adults the passage of unsplit food protein through the gastrointestinal mucosa and thence to the blood is a normal phenomenon.

^J3Schloss, Oscar: The Intestinal Absorption of Antigenic Protein, The Harvey Lectures, p. 156, 1924-1925.

“Brunner, Matthew, and Walzer, Matthew: Absorption of Undigested Protein in Human Beings, Arch. Int. Med. 42: 172, 1928.

In atopic people this circulating protein sensitizes the skin more readily than it does in the normal person, and the positive skin tests which result are of much greater degree and last longer, sometimes for many years (fish, nuts). The same is true of environmental allergens, which reach the blood by inhalation. Many of these positive tests, particularly those to foods, may be looked upon as normal for the atopic person and have nothing to do with his symptoms, whether they be those of eczema, hay fever, or asthma. I think the main reasons for this are two:

A. The X-factor is not present; therefore eczema is not produced.

B. The degree of tissue sensitization is not high enough to react with the amount of antigen absorbed.

The immunologic reaction we are discussing depends upon two vari­ables :

(1) The amount of antibody fixed in the tissue.

(2) The amount of antigen which contacts it.

If there is a small amount of anti­body it takes a large amount of anti­gen to produce a reaction, and vice versa.

Several years ago I did some im­munologic experiments on myself with the help of Miss Margaret Scully, who was in charge of the allergy laboratory of the Children’s Hospital at that time. It is not necessary to go into the details of these investiga­tions.

¹²Tuft, Louis, Tuft, Harold S., and Heck, V. Muriel: Atopic Dermatitis, an Experimental Clinical Study of the Role of Inhalant Aller­gens, J. Allergy 21: 181, 1950.

The gist of them was that if a high degree of passive sensitization was produced on my skin by the intracutaneous injection of a serum containing food reagins from an eczematous infant, the eating of the cor­responding food in only small amount caused a wheal to appear on the sensitized site in about twenty minutes. We studied egg white, chicken, pea­nut, wheat, and potato. If the degree of sensitization was only moderate or slight, as determined by serial titra-tion of the sites, no reaction would take place, either urticarial or eczema-tous, even if the food were eaten in large amounts. This simple principle applies to any tissue as well as to the skin, and seems to me of fundamental importance in clinical allergy.

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