The Maximum Intradermally Tolerated Dose (MITD) Method of Food Allergy Testing and Immunotherapy: New Concepts

by Joseph B. Miller, M.D.

("The Environmental Physician", Fall 1994)

Abstract:

I have long noted that the symptom-relieving dose in intradermal relief-dose ("neutralizing") testing was almost always 0.05 ml of the strongest concentration that produced a negative wheal. Any concentration stronger than this almost always produced a positive wheal, equivalent to a mild local reaction, sometimes accompanied by symptoms, equivalent to a mild systemic reaction. The strongest negative wheal concentration (SNWC) usually did neither; it was almost always totally tolerated, both locally and systemically.

In a 4-year analysis of 50,421 consecutive tests, I found that the strongest negative wheal concentration was the symptom-relieving concentration in 98.8% of tests in which symptoms were elicited. So in these tests, the strongest negative wheal concentration could be termed the "maximum intradermally tolerated concentration". In the remaining 1.2% of symptom-associated tests, relief occurred on the second (or in one patient, the third) negative wheal concentration. In this 1.2%, the SNWC failed to relieve, i.e., the induced symptoms continued on. Therefore, the SNWC was not totally tolerated, although it produced a negative wheal. The second negative wheal concentration, which did provide relief in these tests was, therefore, the maximum intradermally tolerated concentration in these instances. Summing up, in essentially 100% of all tests in which symptoms were induced and relieved, the maximum intradermally tolerated dose was the effective immunotherapeutic dose. This was true of both inhalants and foods. I feel justified, therefore, in defining this allergy testing procedure as the Maximum Intradermally Tolerated Dose (MITD) Method. This contrasts it with the Maximum Subcutaneously Tolerated Dose Method of build-up treatment for inhalants long employed in allergy immunotherapy.

I then utilized the strongest negative wheal concentration to treat clinically food-sensitive and inhalant-sensitive patients who produced positive wheals but no symptoms on testing; by wheal-based testing alone, these patients almost invariably obtained the same remarkable immunotherapeutic relief on the strongest negative wheal concentration, despite displaying no symptoms on testing. Finally, I found that the subset of patients with clinically food-induced or inhalant-induced syndromes, who did not display test symptoms and who also did not produce positive wheals even on 0.05 ml of Concentration #2, almost invariably obtained the same remarkable relief on immunotherapy with Concentration #2.

This suggested that testing could be made more efficient by first finding the strongest negative wheal concentration in all tests, and secondly utilizing the second negative wheal concentration when needed in the 1.2% of symptom-associated tests in which symptoms might remain. The same principle turned out to be true with other extracts, e.g. Influenza Virus Vaccine, Candida extract, oak-ivy extract, and others. This has standardized and streamlined the procedure and made it more objective, more efficient, more error-free, and more free of test symptoms. It has also freed us from the concept that provocation and neutralization of symptoms were necessary for successful diagnosis and treatment.

Introduction:

In 1964, I was practicing by conventional allergy concepts--and suffering from severe daily migraine. At that time, I did not know that migraine was largely a food-allergy syndrome. I was unable to determine the cause or obtain relief from my own background, and received no help from multiple physicians of several pertinent specialties.

Then I heard a lecture by Dr. Carleton Lee on an intradermal food test procedure which he called provocation-neutralization. Migraine was at the top of his list of responding syndromes. I immediately tested myself, and reproduced ("provoked") headache with specific concentrations of extracts of milk, wheat, corn, and chocolate--my favorite foods. Much to my astonishment, I found, with each of these extracts, that a concentration different from the provoking concentration relieved ("neutralized") the headache within ten minutes.

I then used subcutaneous injections containing the relieving doses of these foods twice a week. After three weeks, my migraine headaches were virtually gone--and still are.

For the past 30 years, I have been studying this remarkable system of allergy immunotherapy in carefully selected patients, and have added to the long list of responding syndromes and useful extracts other than foods. In addition, I have been interested in systematizing and teaching methods of obtaining greater efficiency, precision, and objectivity, and have published some of my experiences.(1-10) This report contains descriptions of more recent observations and concepts.

The Unique Rapid Relief Response:

Intradermal testing utilizes 1:5 serial concentrations (dilutions) of food extracts (some now term this a sequential-incremental system). One such concentration, specific for each food extract in each patient, provides rapid relief of symptoms that may have been induced by just-prior intradermal injections of other concentrations of that extract. When later administered subcutaneously as a regularly-scheduled immunotherapeutic injection, 0.05 ml of this concentration usually will then provide a major degree of protection from the symptoms caused by ongoing exposures to this food.

The individualized treatment doses for all the foods are combined into a single immunotherapeutic solution. This solution can be injected subcutaneously in judiciously selected patients with remarkable effectiveness and safety, and with virtually complete freedom from significant local or systemic side effects.

No build up of doses is needed, and none is desirable. Nothing can be gained by build-up, and much can be lost by building from relieving doses to overdoses. The optimal, effective, safe maintenance doses of all the allergens in the solution have already been determined by intradermal testing. They cannot get any better. Therefore, the very first subcutaneous treatment injection contains the full maximally effective, maximally safe maintenance doses of all the foods.

Favorable response usually occurs very rapidly. Relief of chronic food (or inhalant, etc.) symptoms begins by the time testing is completed in 55% of my patients. Injection by injection, this percentage increases. Within 3 weeks, 93% of my patients have achieved marked relief.

It is characteristic for relief to occur shortly after each immunotherapeutic injection. If symptoms are present at the time of an injection, relief occurs within 30 minutes in 40% of the patients, within one hour in 60%, within two hours in 77%, and on the same day in 88%. Some who take their injections at bedtime note their improvement on arising.

The Maximum Intradermally Tolerated Concentration Has Provided Relief in Virtually 100% of Tests:

I recently analyzed 50,421 consecutive tests perfumed on 1,525 patients over four years in my office. In this series, 98.8% (6,748 tests) of relief-providing (neutralizing) doses in the 6,829 tests which had produced symptoms in 834 patients occurred on the strongest negative wheal concentration (SNWC). In the remaining 81 symptom-associated tests (1.2%), in which test symptoms did not clear on the SNWC, the symptoms cleared on the second (77 tests, or 1.12%), or the third (4 tests, or 0.06%) negative wheal concentration. No weaker concentrations than these were required in this series.

Seven patients accounted for two-thirds of the second negative wheal doses (55 of the 81 tests). After retesting, their doses reverted to the strongest negative wheal dose. One of these patients (E.L.), in 1989, accounted for 38 of the 77 second negative wheal doses and all four of the third negative wheal doses. After she improved as was later retested, all her doses reverted to the strongest negative wheal dose. I have had no tests in which the third negative wheal dose was required since then, and even the need for the second negative wheal dose has become progressively less frequent.

This reversion to the SNWC is the usual situation. Thus, for homeostasis, the human immune protective system displays an almost universal need for the strongest negative wheal concentration. This may be looked upon as the anti-inflammatory non-wheal-producing concentration on step weaker than the pro-inflammator wheal-producing concentration. Even in the 1.2% of tests in which the body is unable to tolerate the SNWC on initial testing, a brief course of immunotherapy usually quickly produces tolerance and need, then, for the strongest negative wheal concentration.

In the 1.2% of tests in which the strongest negative wheal concentration is not the symptom-relieving concentration, the strongest negative wheal concentration cannot be called a tolerated dose at that time because it is accompanied by a continuation of test symptoms. Therefore, in these few instances, the second (or third) negative wheal concentration is the maximum intradermally tolerated concentration. So in this four-year study, the term "maximum intradermally tolerated concentration" has defined 100% of tests in which symptoms were induced and relieved. Therefore, this method can be accurately described as the Maximum Intradermally Tolerated Dose Method. (It could also be termed the Relief Dose Method or the Optimal Dose Method, since both these terms describe it also.)

Even so, there is a rare instance in which a test is not completed, either because of an inability to find a relieving dose that day, or because of the discomfort or possible danger to continuing the test. Many such patients can be retested successfully later with milder or no symptomatology.

Selection of patients for initial testing must consider many factors. Some patients are not selected for testing at all, and some are discontinued from testing if they experience uncomfortable symptoms or poor neutralizing capacity.

The remarkable consistency of physiologic need of the body for the strongest negative wheal concentration has an additional beneficial aspect. When the history indicates allergenicity of a food, inhalant, or other incitant, but no symptoms can be induced during intradermal testing, 0.05 ml of the strongest negative wheal concentration will almost invariably provide relief in therapy--without ever having produced symptoms during testing. In other words, patients who do not display symptoms on testing, but do display positive wheals, can be tested successfully and relieved of life-long suffering by whealling alone. Therefore, we can provide the same striking benefits to non-symptom-reacting patients who are allergically sensitive and who display positive wheals but do not display symptoms on testing.

Thirdly, there is also a subset of patients who display neither symptoms nor positive wheals on testing. In these patients, 0.05 ml of Concentration #2 is negative for all or many active allergens. Innumerable clinical trials have revealed that in these instances, 0.05 ml of Concentration #2 is not only tolerated, producing neither symptoms nor positive wheals, but is also almost invariably protective in immunotherapy. It provides relief to patients who have failed to find help even in multiple major medical centers. It is a near-universal protective dose in such patients, providing rapid relief (usually in one-half to two hours) after each injection, as well as ongoing protection by means of regularly scheduled immunotherapeutic injections.

The Wheal is an Almost Infallible Guide to the Perfect Treatment Dose Whether or Not Symptoms are Induced:

This primarily wheal-based system provides an objective, precise, reliable, repeatable method of testing. Unlike primarily symptom-based test systems, dependent on provocation of symptoms by the intradermal, sublingual, or subcutaneous route, it puts this method onto firm objective footing and provides relief for patients who do not display symptoms by any route of test administration of antigens.

Wheals are measurable, visible, palpable, and photographable for objective evidence of accuracy in testing and for correlating symptom-initiation or subsidence with wheal positivity or negativity. This wheal-based test system also provides precision in determining the perfect treatment dose. The ultimate evidence of effectiveness of wheal-based testing is the ongoing relief of symptoms during regularly scheduled immunotherapy, the return of symptoms when the regularly scheduled injection is delayed, and the rapid relief (usually within 30 minutes to 2 hours) when the delayed injection is finally administered. The willingness, or rather eagerness, of the patients to continue these injections for years speaks further to effectiveness, as does the success of MITD therapy in infants as young as three months of age.

The near-infallibility of the wheal in indicating the optimal therapeutic dose has been consistently overlooked. Investigators have simply not adequately studied intradermal serial concentration (sequential-incremental) testing. Many conventional allergists do not employ intradermal testing, particularly for foods. Most of those who do, utilize only a single concentration (usually 1:1000) of an antigenic extract. This cannot provide the quantitative bioassay-type information obtained by testing with a series of concentrations of different strengths. Furthermore, they usually intradermally test several antigens simultaneously, so if symptoms arise, they do not usually know which antigen caused them. In addition, they consider all test symptoms as adverse systemic reactions, and miss the opportunity to seek the perfect treatment dose by determining the strongest negative wheal concentration of the causative antigen.

Test and Treatment Dose Volumes:

The treatment dose of each allergen is invariably 0.05 ml, but in testing, two volumes are used. These are the 0.01 ml volume, which usually produces about a 4 mm wheal, and the 0.05 ml volume which usually produces about a 7 mm wheal. The 0.01 ml volume is not readily measurable on the syringe so is defined as the volume that produces approximately a 4 mm wheal.

The 0.05 ml volume produces a greater symptom response than the 0.01 ml volume, and a highly reliable relief response in both testing and immunotherapy. In addition, it is virtually 100% reliable in producing wheal responses that correlate with symptom responses. The 0.01 ml volume usually produces fewer, milder, or no symptoms in testing, but is slightly less reliable in correlating wheals with symptom responses.

Therefore, in order to minimize test symptoms, I test all patients to all antigens with 0.01 ml volumes until I have determined the SNWC with the 0.01 ml volume. I then "verify" negativity by administering 0.05 ml of that concentration. In 89% of such tests, the 0.05 ml volume has produced a negative wheal as did the 0.01 ml volume, and this dose has been the effective treatment dose. However, in 11% of such instances, the 0.05 ml volume has produced a positive wheal when the 0.01 ml volume had produced a negative wheal. In these 11%, 0.05 ml of the next weaker concentration has been negative and has been the effective treatment dose.

For example, suppose 0.01 ml/#2 produces a positive wheal and no symptoms. The next dose will be 0.01 ml/#3. If this produces a negative wheal, the next dose will be 0.05 ml/#3. If this produces a negative wheal, it is the treatment dose, and the test has been completed. However, in 11% of tests, the 0.05 ml/#3 will produce a positive wheal, in which case 0.05 ml/#4 will produce a negative wheal, will relieve any symptoms that may have been induced, and will be the effective treatment dose.

Deletion of Concentration #1 From Testing:

Stable extracts are critical for accurate testing and retesting. Non-glycerinated extracts arrive at the office in various stages of decreasing potency, and the decrease continues after dilution, requiring much retesting. Glycerinated extracts are remarkably stable and are little subject to loss of potency even when later diluted and even at room temperature. Almost all of my patients have tolerated glycerinated extracts, and I use them almost exclusively. The chief disadvantage is that glycerin produces a non-specific positive wheal in 80% of tests with the #1 concentration, which contains 10% glycerin. This does not occur with #2 or weaker concentrations.

When a positive wheal has occurred on Concentration #1, I have been unable to distinguish whether it was a non-specific positivity due to glycerin or a specific positivity due to allergen, despite measuring schemes by which the non-specific and specific responses have been said to be distinguishable.

In my experience, the #1 concentration is rarely useful as a relief-dose concentration. When it has been utilized in immunotherapy, it has usually soon started producing symptoms, and the #2 concentration has been needed for relief. Furthermore, delayed overdose reactions are more likely to occur from the #1 concentration than from any other. On the other hand, 0.05 ml of #2 has been a near-universal beneficial immunotherapeutic and protective dose in patients who display a negative wheal and no symptoms on 0.05 ml of #2. Therefore, I now rarely use Concentration #1 in testing. This has markedly decreased the incidence of delayed overdose reactions, has made test procedures more accurate and less time consuming, and has greatly reduced the need for retesting.

Wrap-up Injections:

If testing is completed in one day, ten combined treatment doses are made up, and one is administered to the patient before leaving the office. If testing requires more than one day, a "wrap up" injection of all doses determined the first day is administered subcutaneously at the end of the day. All doses determined over a two-day period will be injected subcutaneously at the end of the second day; and so on each day. When testing is completed, the first complete immunotherapeutic injection is administered in the office. In all instances, the patient is observed for thirty minutes for both local and systemic reactions. Characteristically, there is no local or systemic reaction, and the patient often volunteers that he is already feeling better, often after the first or second wrap-up injection. In the event of a local reaction or the induction of symptoms from a wrap-up injection, the antigens tested that day must be omitted from the treatment injections until they can be retested. In this manner, the accuracy of doses and the safety and effectiveness of the injections are verified, and the possibility of adverse reactions from subsequent injections is minimized.

Some Fundamental Concepts in Testing:

Some physicians with minimal or no personal experience with the relief-dose or MITD method of testing seem to think that it is a "mathematical" symptom-based system in which symptoms are produced in every test by a concentration either stronger or weaker than the relieving concentration, and that no symptoms occur on relieving concentrations. This is far from the truth, and has led to major investigative errors. So let us correct these errors by taking a close look at overdose, relief-dose, and underdose wheals and their accompanying symptoms as they actually occur.

1. Overdoses Produce Positive Wheals but may or may not Produce Symptoms:

Overdoses (concentrations stronger than the relieving concentration) do not always produce symptoms, but virtually always (98.8%) produce a characteristic positive wheal. This wheal is blanched, hard, raised, and disk-shaped i.e., with sharply demarcated cliff-like borders, like a disk). It is as though the underlying mediator-activated dermal capillaries with their attached mast cells have extruded fluid into the site of the intradermal injection, ballooning up the wheal to the point that the skin over the wheal has become stretched and blanched. Although there is a relatively large amount of allergenic material in the positive wheal, symptoms are not always expressed, or at least not in the ensuing 10 minutes. They may finally be expressed 10 to 30 minutes later, or even hours later after the patient has left the office.

2. Relief Doses and Underdoses Produce Negative Wheals but may or may not Produce Symptoms:

When a positive (overdose) wheal is produced, consecutively weaker concentrations in the 1:5 series are then injected intradermally at 10-minute intervals. A concentration is soon reached which produces a negative wheal. This is the first (strongest) negative wheal concentration. All concentrations weaker than this (underdose concentrations) will also produce negative wheals.

The negative wheal is not blanched, hard, raised, or disk-like. Rather, it is relatively soft and flat, and may be either neutral-colored or erythematous, but not blanched. The borders are sloping and irregular in shape as though the injected material has been draining out of the wheel, absorbing into the underlying tissues, leaving the wheal somewhat shrunken and deflated, with frayed out, slightly wrinkled, uneven borders.

In addition, the positive overdose wheal will have usually (not always) grown 2 mm or more in average diameter in 20 minutes. By contrast, the negative wheal usually grows less than 2 mm in average diameter. The blanching, hardness, and discoid characteristics are the most reliable indicators of positivity, even more than the 2 mm growth of the wheal, and constitute the strongest indication of overdosage and the need to inject the next weaker concentration.

Common Errors in Symptom-Based Testing:

1. The Erroneous Rejection of Relieving Doses if Accompanied by Symptoms:

As described, a positive overdose wheal does not always produce symptoms, and not always in the ensuing 10 minutes. When the strongest concentration which produces a negative wheal is then injected, the overdose symptoms often emerge within minutes after this negative-wheal injection. Therefore, the symptoms arise after the administration of the negative wheal relieving dose, and may not have cleared by the end of the ten minute observation period. Then the relieving dose may be rejected by the physician because of the emergence and persistence of symptoms, and a weaker dose (an underdose) prematurely chosen for that antigen. This leads to poor therapeutic response and a need for retesting, due to the erroneous conclusion by the physician and patient that the poor therapeutic response indicates a defect in the system.

2. The Erroneous Acceptance of Underdoses as Treatment Doses:

The same error is made when symptoms arise after the injection of the strongest negative wheal dose, even when no positive wheal dose has been previously injected. The error consists in then injecting the next weaker concentration (an underdose), after which the symptoms often subside, possibly because of the increasing benefit of the previously injected strongest negative wheal dose. This results in erroneous acceptance of the underdose as the treatment dose, and also results in treatment with the underdose. This, too, leads to a poor response and a need for retesting.

One of the most common errors in this system of testing is the use of underdoses as treatment doses. This error can usually be avoided by simply repeating the strongest negative wheal dose one or more times to allow it to finally clear out the induced symptoms rather than prematurely going to weaker doses.

In 761 tests (1.5% of the 50,421 consecutive tests being reported on), test symptoms failed to clear on a single test injection of 0.05 ml of the strongest negative wheal concentration. A second injection of the identical concentration produced clearing in 576 (76% of the 761 tests). A third such identical injection was required in 138 (18%), a fourth in 40 (5%), and a fifth in 7 (1%). More than five identical doses were not required in this series.

If using repeated neutralizing doses does not clear the symptoms, or symptoms worsen while repeating the strongest negative wheal concentration, 0.01 ml of the second negative wheal concentration is then indicated. Usually symptoms will begin to improve on this test dose. If symptoms do begin to improve or at least do not worsen on 0.01 ml of the second negative wheal concentration, then 0.05 ml is utilized and will almost always provide final clearing of the symptoms. If symptoms worsen on the second negative wheal dose, a return to the first negative wheal dose will often provide relief, although it had not done so previously. NOTE: Regardless of how many repetitions of the symptom-relieving dose are required during testing, the immunotherapeutic dose need only be 0.05 ml.

3. The Erroneous Acceptance of Overdoses as Treatment Doses:

Symptoms sometimes occur on a positive overdose wheal and then clear before the 10 minutes are up. A useful clinical concept is that the antigen or the wheal has become gradually more tightly "bound" so that no more antigen escapes from it, at least for the time, so the symptoms clear. Because of symptom clearance, overdoses may be used erroneously as relief doses when testing is based entirely on symptom-clearing.

Accepting overdoses as treatment doses often results in delayed absorption of the antigen from the un-neutralized bound wheal after the patient has finished that test or even after he has left the office (delayed overdose symptoms). Furthermore, overdoses do not stand up to the final test of accuracy in immunotherapy in that they fail to optimally protect the patient from exposures to that antigen, or even cause mild local reactions or symptoms after therapeutic injections. An adverse local or systemic reaction to a therapeutic injection virtually never occurs when the doses are correct, so their occurrence is almost always a signal that retesting is indicated.

This third error can be avoided, and the need for retesting reduced, by never accepting a positive wheal concentration as a relieving concentration, even if symptoms subside on that concentration.

So, during symptom-based testing, errors may arise because of three seemingly paradoxical responses:

(1) An overdose can be accompanied by no test symptoms or even by relief of test symptoms, yet will not be a suitable dose for immunotherapy;

(2) An under dose can be accompanied by relief of test symptoms, yet will not be a suitable dose for immunotherapy;

(3) A relieving dose can be accompanied for ten minutes or longer by newly-arisen test symptoms rather than by relief, yet will be the safe, effective dose for immunotherapy.

Under dose Symptoms Require Constant Vigilance but are Infrequent and are Usually not Reliably Repeatable:

An under dose concentration is defined as any concentration weaker than the relieving concentration. Surprisingly, an under dose concentration can at times cause "under dose symptoms" on intradermal administration, rarely if at all on subcutaneous administration. These under dose test symptoms sometimes occur more rapidly and more dramatically than the symptoms produced by overdose concentrations, and can be severe.

In under dose reactions, it is a useful clinical concept that the antigen has been absorbed into the circulation rapidly to impact target organs abruptly rather than being bound in the skin over a longer period of time and released slowly as in a positive overdose wheal. It is interesting that under dose symptoms occur predominantly on intradermal test injections rather than subcutaneous treatment injections. This suggests a role for intradermal Langerhans Cell activation, since these potent cells are present in the epidermis but not in subcutaneous tissues.

Overdose vs. Underdose Symptoms:

Opposing mechanisms of homeostatis (exemplified by sympathetic vs. parasympathetic actions, norepinephrine vs. acetylcholine, etc.) are suggested by some test reactions. Overdose symptoms are often different and opposite to under dose symptoms. Overdose symptoms are often slower in onset and may be accompanied by tenseness, irritability, flushing, warm skin, and "hot sweats", resembling over-stimulation of neuromuscular as well as hemodynamic homeostatic mechanisms. On the other hand, under dose symptoms are often more rapid in onset and are more often accompanied by limpness, weakness, faintness, pallor, cool skin, and "cold sweats", resembling inhibition or depression of these homeostatic mechanisms. The important clinical point is that, when under dose symptoms occur rapidly, the immediate intradermal injection of the strongest negative wheal dose usually relieves the under dose symptoms quickly.

Because of the rapid and dramatic onset of symptoms which have sometimes occurred from under doses, it is important for physicians to be constantly vigilant in awareness of this possibility. The purpose of this vigilance is to be ready to immediately administer stronger (rather than weaker) concentrations for quick relief whenever negative-wheal under dose symptoms should occur. Repeated reminders of this over the years were to counter the common error of always going weaker when symptoms occur. It is important to head for the positive wheal landmark, which guides us to the next weaker concentration, the strongest negative wheal concentration, which almost invariably provides relief.

To summarize, symptoms can arise of subside on overdoses, relief doses, and under doses. Symptom changes alone are simply not reliable guides to the selection of treatment doses, much less to double-blind studies.

Errors in Double-Blind Studies Using Symptom-Based Testing:

Somehow the message concerning constant underdose vigilance became interpreted erroneously by some non-users, and possibly even by some users of this system. Jewett(11) developed the notion, possibly from his own test experiences, that every underdose must produce such symptoms reliably and repeatedly. This is far from the truth.

It was this false assumption that led Jewett, a professor of orthopedics with no background in either allergy management or the relief-dose allergy system, to devise a flawed protocol and perform a predictably "negative" double-blind study. His simplistic theory was that the whole test system was based on the assumption that every under dose produces symptoms, and that the failure of under doses to always produce symptoms reliably and repeatedly was proof that the entire testing and treatment system was invalid.

The fact is that under dose symptoms are uncommon; they only occurred in 2.88% of all tests in which symptoms occurred in the 50,421 consecutive tests analyzed in my office. And when it does occur, retesting the same extract in the same patient usually results in failure of under dose symptoms to recur on the second test. It is not reliably repeatable, so it cannot be a valid basis for a double-blind study. The scientific world does not know this because it has no hands-on experience with the system, and hailed Jewett's persuasively written paper of a fallacious study as definitive proof of the ineffectiveness of the entire system.

Retesting:

When the body's dosage needs change during the course of therapy, retesting determines the new dosage needs and restores response immediately. This is particularly true if the initial relief doses are weak. The need for retesting may occur early if some of the doses were erroneous initially due to symptom-based testing. So retesting when indicated is an important part of maintaining optimum response. However, testing by current concepts described in this paper has markedly reduced the need for retesting.

Convincing the Patient During Testing vs. During Treatment:

Some physicians will undoubtedly still prefer to test by trying to produce and relieve test symptoms rather than utilizing the primarily wheal-based system described. When it occurs, the production and rapid relief of symptoms is very convincing to the patient and to the physician. However, dependence on symptom production for diagnosis of food (or inhalant) allergy misses the majority of real clinically important allergens, since many will produce symptoms on ingestion (or inhalation) but not on skin testing. I prefer to provide more appropriate coverage and to eliminate or minimize test symptoms, and let patients be impressed by the rapid, marked relief they obtain within days or weeks after starting immunotherapy.

Test Symptoms Must be Relieved:

It must be emphasized that whealing is not the only factor involved. When symptoms occur, they must be relieved, even if the relieving concentration is the second negative wheal concentration, or even the third.

If a symptom-relieving concentration cannot be found, symptoms can be relieved by one or more small doses of Sus-Phrine, e.g. 0.03 to 0.05 ml. Sus-Phrine is a preservative-free quick-acting long-lasting aqueous solution and suspension of epinephrine. This can be supplemented if needed by other medications such as a steroid, e.g. prednisone 30 mg. in the office and possibly again in the evening if indicated. (Neither epinephrine nor steroids interfere with testing or wheal responses.) They physician's judgement and the nature of the symptoms must determine such procedures.

Summary:

Relief dose testing can be made much more accurate and efficient, and the need for retesting much diminished, by first seeking the strongest negative wheal concentration (SNWC). By testing only with 0.01 ml volumes until the SNWC is determined, and then verifying with 0.05 ml, much test symptomatology can be eliminated. Use of 0.05 ml of the SNWC will relieve induced test symptoms in 98.8% of tests in which symptoms are induced. Essentially, all of the remaining symptom-associated tests (1.2%) will produce relief on the second negative wheal concentration. When a single dose of the SNWC fails to relieve, one or more repetitions of this dose (as long as symptoms are not worsening), will often provide relief and prevent the error of prematurely changing to underdose concentrations. This can markedly diminish the incidence of underdose symptoms. Overdose reactions also can be markedly reduced by avoiding the use of Concentration #1.

When relief occurs on the strongest negative wheal dose, any dose stronger than this will produce a positive wheal, a symptom, or both--so it is the strongest intradermally tolerated dose. When symptoms persist on this dose, it is not a tolerated dose; then the next weaker dose will almost invariably provide relief, thus becoming the maximum intradermally tolerated dose (the strongest dose that does not produce a positive wheal or a symptom). Summing up, in essentially 100% of tests, this procedure can thus be described and defined as the Maximum Intradermally Tolerated Dose Method.

References:

1. Miller JB: Food Allergy: Provocative Testing and Injection Therapy. Springfield: Charles C Thomas, Publisher, 1972.
2. Miller JB: Relief At Last! Neutralization for Food Allergy and Other Illnesses. Springfield: Charles C Thomas, Publisher, 1987.
3. Miller JB: Intradermal provocative-neutralizing food testing and subcutaneous food extract injection therapy, in Food Allergy and Intolerance, Brostoff J and Challacombe SJ (Ed.). London: Bailliere Tindal, 1987, pp 932-946.
4. Miller JB: A double-blind study of food extract injection therapy: A preliminary report. Annals of Allergy, Vol. 38, No. 3, March 1977, pp 185-191.
5. Miller JB: Hidden food ingredients, chemical food additives, and incomplete food labels. Annals of Allergy, Vol. 41, No. 2, August, 1978, pp 93-98.
6. Miller JB, Lee C, Binkley EL, and Hardt S: Relief of Influenza symptoms by the provocative-neutralizing method--A preliminary report. Journal of the Medical Association of the State of Alabama, Vol. 41, No. 7, January, 1972, pp 493-502.
7. Miller JB: Influenza: Rapid relief without drugs. Clinical Medicine, Vol. 81, No. 9, September, 1974, pp 16-19.
8. Miller JB: Treatment of active herpes virus infections with influenza virus vaccine. Annals of Allergy, Vol. 42, No. 5, May, 1979, pp 295-305.
9. Miller JB: Rapid relief of varicella and infectious mononucleosis through immunotherapy. Annals of Allergy, Vol. 47, No. 5, 1981, pp 135-136.
10. Miller JB: Relief of premenstrual symptoms, dysmenorrhea, and contraceptive tablet intolerance. The Journal of the Medical Association of the State of Alabama, Vol. 44, No. 2, August, 1974, pp 57-60.
11. Jewett DL, Fein G, Greenberg M: A double blind study of symptom provocation to determine food sensitivity. NEJM, Vol. 323, NO. 7, August 16, 1990, pp 429-33.