Low Dose Allergen Immunotherapy (LDA):

The Allergy Treatment of the Future – Here Now

by W.A. Shrader, Jr., MD, FAAEM

What is LDA?

Low dose allergen immunotherapy (LDA) is a unique method of immunotherapy, far different from other allergy treatments for ently generalle currentas been employed to treat multiple conditions and appears to be a long- lasting reatment option for allergy and many autoimmune illnesses. It has also been employed for many conditions not generally assumed to be due to any type of allergy or autoimmune disease.

History of LDA

LDA is patterned after enzyme potentiated desensitization (EPD), developed by the brilliant clinical and academic allergist Leonard M. McEwen, MD, in England in the mid-1960s.^1–9 The method involves desensitization with combinations of a wide variety of extremely low-dose allergens (10⁻¹⁴ to approximately 10⁻⁶, or 1 part in 10 million to as low as 1 part in 1 quadrillion). These allergens are given with the enzyme beta-glucuronidase. The beta-glucuronidase acts as a lymphokine, a substance that potentiates the immunizing ability of the allergens. EPD appears to specifically induce the production of activated T-regulator (T_reg) cells, once known as T-suppressor cells, which can live in the circulation for many years.

I published my own EPD study in 1993 after 2 years of administration of EPD to 134 patients in my office.¹⁴ As a result of the impressive improvement of most of those patients, I became enthusiastic about EPD and approached Dr. McEwen with the idea of doing a much larger study. He was enthusiastic.

I founded the American EPD Society, a group of physicians to study Dr. McEwen’s EPD treatment, and we conducted the largest study of EPD ever done, from 1993 through 2001. Over 100 physicians participated in the study in the US and Canada from 1993 to 2002 and gathered data from approximately 10,500 patients. We studied the effects of EPD on 65 different conditions (my website, www.drshrader.com, includes the study results and more detailed information about LDA). I thought that most of the results from the study were extremely impressive.

Conditions treated successfully with EPD include hay fever , dust mite allergy, perennial rhinitis, asthma, urticaria (“hives”), eczema (dermatitis) of most all varieties, angioedema (swelling of the face, lips, etc.), food (or food additive/preservative) allergy or intolerance, adverse responses to chemicals (multiple chemical sensitivity, or MCS), ADHD (attention deficit/hyperactivity disorder), autism, Tourette’s syndrome, irritable bowel disorders, Crohn’s disease, ulcerative colitis, migraine and other headaches, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosis. ^{6–8,11–14–17,20,21,25,27}

Unfortunately, in April 2002, the supply of EPD was no longer available in the US. In response to patients who depended on this mode of therapy for continued quality of health, and by working with a compounding pharmacy to fill the US supply need, I created a therapy similar to EPD. I call this treatment LDA, short for low dose allergen therapy, and it has been used in the US and Canada since 2002.

My formulation uses the same active components as EPD, but it has many more pollens, foods, chemicals, and other allergens. The use of LDA is limited by necessity in the US because it is available only by prescription for specific physicians’ patients, and not as a retail product. Many physicians now using LDA had used EPD in this country many years ago. Although no formal data about LDA have been published as yet, 10 years of experience with it by over 50 physicians (now nearer 90) indicates that the same conditions that responded to EPD respond similarly to LDA.

The Difference between LDA and Conventional Allergy Immunotherapy

Conventional “escalating dose” immunotherapy (where the dose is started “low” – generally 1 to 10,000, and increased over time to as high as 1 to 10, 1 to 20, or 1 to 100) is employed in this country by many allergists, primarily to treat hay fever and cat and dust mite allergy, which are primarily IgE mediated. This type of immunotherapy works by causing the patient to produce “blocking antibody” (specific IgG antibody), which inhibits the histamine-releasing ability (which produces the allergy symptoms) of the mast cell.

The higher the level of blocking antibody that can be produced, the more successful the treatment. To produce adequate levels of blocking antibody, studies have shown that administration of very high doses of allergen is required. Therefore, treatment using this method often causes intolerable swelling and other side effects before clinical efficacy can be attained, and can be dangerous due to the risk of severe reactions such as massive swelling, anaphylaxis, collapse, and even death. Furthermore, only inhalants – not foods or chemicals – are used.

Deaths from conventional escalating dose immunotherapy are generally a result of anaphylaxis. This is due to the extremely high dose of antigen required to produce a significant clinical effect and high level of antibody. LDA immunotherapy, however, is cell-mediated (probably T_Reg) and extremely low dose. The very highest possible dose of LDA (some LDA antigens are lower) is at least a million times less than the standard dose for conventional immunotherapy.

The danger of fatal or life-threatening systemic reactions to LDA treatment is negligible. Well over 400,000 doses of EPD and an estimated 300,000 of LDA have been given worldwide, and – unlike many other types of immunotherapy – life-threatening reactions to EPD or LDA have never been reported.

Conventional escalating dose immunotherapy is generally administered twice weekly for the first four to six months of treatment. Once the very high-maintenance dose is reached, the treatment interval may be extended to once every two weeks or even monthly, but rarely less often without return of symptoms. Conventional escalating dose immunotherapy cannot usually be stopped without the return of some or significant symptoms within 3 to 12 months of cessation.

As I stated previously, LDA immunotherapy is extremely low dose and administered infrequently, only every two months at first, and later less often. Treatment is required only every two months initially for approximately 12 months. After that time, the treatment interval may generally be extended to three months or longer. Most adults with significant problems require 16 of 18 treatments at these intervals of two months or less often, at which time treatment often may be discontinued. Of the approximately 50% of patients who cannot discontinue LDA after 16 to 18 treatments without return of some symptoms, the majority will continue treatment longer at intervals of 6 months to a year. Children (under 12) may often stretch their treatments out earlier, and stop sooner without return of symptoms. Children as young as 1 month of age have been treated safely.

LDA Treatment

LDA is administered using intradermal injections of 0.05 (1/20) cc in the skin of the forearm or sometimes in the leg. The method of intradermal injection is quite simple, and the LDA antigens are administered exactly as you would an intradermal skin test. The average patient receives 1 to 2 injections (usually one on each forearm) per treatment.

The response to LDA does not take long to appear, and certainly over 60% of patients note a significant positive response with their first treatment. Almost all patients respond positively by the third treatment, and if no response is noted by then, we generally reevaluate the situation. About 1 in 25 patients does not respond with strongly positive results until having had 6 treatments. The overall response rate for all conditions treated with LDA is approximately 65% to 95%, depending on the condition being treated. The overall failure rate (no improvement) is about 9%.

LDA includes mixtures of antigens originally developed (for EPD) by McEwen that act quite “universally,” as the antigens in LDA are cross-reactive. This means patients allergic or intolerant to most substances have responded to treatment. I added several more antigens to LDA when it was formulated for use here, although I am not certain that the antigens which I added improved the treatment in general except for that of chemical sensitivity. Available LDA mixtures include (1) inhalants (inhaled pollens, animal dander, dust and mites, insects, fungi, yeast including Candida species and molds); (2) foods and food additives; (3) chemicals (containing most common chemicals and scents, formaldehyde, and detergents, except for pesticides and herbicides); and (4) woods, (a mixture of many common and exotic woods), used for the treatment of contact skin sensitivity in woodworkers.

Other specific LDA mixtures, which I do not have space to discuss here, but work by way of a mechanism called molecular mimicry, are available to treat several specific autoimmune diseases, such as rheumatoid arthritis, ulcerative colitis, ankylosing spondylitis, scleroderma, and others.

LDA has a few disadvantages compared with other types of immunotherapy. For example, most patients must adhere to a very restricted diet the day before, the day of, and the day after LDA treatment. There are also a number of medications (such as antihistamines and aspirin) that may significantly reduce or destroy the effect LDA if taken in the three weeks after treatment.

On the other hand, LDA has tremendous advantages, and has a distinct advantage in that it appears to effectively treat a very wide variety of disorders not generally perceived to be immune-related or caused by allergy, including illnesses that respond poorly – or not at all – to other methods of treatment of any kind. This would include migraine headaches, ADD/ADHD, Tourette’s and Raynaud’s syndromes, and many others.

It is very important to note that LDA is dramatically effective for the treatment of eczema of all kinds. When you compare this with the usual dermatological treatment with topical steroids that is not really curative and goes on essentially forever, there is no comparison.

LDA immunotherapy has worked well for angioedema, which consists of facial swelling, swelling of the lips or eyes or swelling of other parts of the body, primarily as a result of acute and chronic food allergy, but potentially caused by many substances. There is no safe and effective traditional immunotherapy for this condition. The best that conventional treatment can do with these conditions is by advising avoidance (when the substance is known) and using drug therapy and epinephrine to treat the problem.

Likewise, immediate food allergy, which can cause anaphylaxis (a condition that is generally life-threatening), has no effective treatment except for emergency drug treatment and avoidance of the offending food agent. This includes such potentially fatal problems as peanut and shrimp or shellfish allergy. After 10 years of use, LDA appears to work well for this condition and can prevent death from accidental exposure to anaphylaxis-inducing foods.

Overall, LDA immunotherapy is considered a miraculous treatment by thousands of patients across the US and Canada who rely on it for treatment of a myriad of problems. LDA is available in the US, Canada, and the UK. A list of treating physicians who employ LDA immunotherapy (now about 90) can be found at www.drshrader.com. This now includes naturopaths in states where they are permitted to administer injection therapy.

Note

: LDA is not approved by the Food and Drug Administration.

Notes

1. McEwen LM. Ganderton MA. Wilson CW. Black JH. Hyaluronidase in the treatment of allergy. Br Med J. 1967;ii:507–508.

2. McEwen LM, Starr MS. Enzyme potentiated hyposensitization I: The effect of pre-treatment with beta-glucuronidase, hyaluronidase and antigen on anaphylactic sensitivity of guinea pigs, rats and mice. Int Arch Allergy. 1972;42:152–158.

3. McEwen LM. Enzyme potentiated hyposensitization II: Effect of glucose, glucosamine, N-acetylamino-sugars and gelatin on the ability of beta- glucuronidase to block the anamnestic response to antigen in mice. Ann Allergy. 1973;31:79–83.

4. McEwen LM. Effects of sugars and diols on enzyme potentiated desensitization. J Physiol. 1973 Apr.;230(1): 65–66.

5. McEwen LM, Nicholson M, Kitchen I, White S. Enzyme potentiated hyposensitization III: Control by sugars and diols of the immunological effect of beta-glucuronidase in mice and patients with hay fever. Ann Allergy. 1973;31(11):543–550.

6. McEwen LM, Nicholson M, Kitchen I, O’Gorman J, White S. Enzyme potentiated hyposensitization IV: Effect of protamine on the immunological behavior of beta-glucuronidase in mice and patients with hay fever. Ann Allergy. 1975;34:290–295.

7. McEwen LM. Enzyme potentiated hyposensitization V: Five case reports of patients with acute food allergy. Ann Allergy. 1975;35:98–103.

8. McEwen LM. A double-blind controlled trial of enzyme potentiated hyposensitization for the treatment of ulcerative colitis. Clin Ecol. 1987;5(2):47–51.

9. McEwen LM. Hyposensitization. In: Brostoff J, Challacombe SJ, eds. Food Allergy and Intolerance. London: Bailliere Tindall; 1987:985–994.

10. Fell P. Brostoff JA. Single dose desensitization for summer hay fever. Eur J Clin Pharmacol. 1990;38:77–79.

11. Eaton KK. Preliminary studies with enzyme potentiated desensitization in canine atopic dermatitis. Environ Med. 1991;8:140–141.

12. Longo G, Poli F, Bertoli G. Efficacia clinica di UN novo trattemento iposensibilizzante, EPD (enzyme potentiated desensitization) nella terapia Della pollinosi. Reforma Med. 1992;107:171–176.

13. Eggar J, Stolla A, McEwen LM. Controlled trial of hyposensitization in children with food-induced hyperkinetic syndrome. Lancet. 1992 May 9;339:1150–1153.

14. Shrader Jr WA, McEwen LM. Enzyme potentiated desensitization: A sixteen month trial of therapy with 134 patients. Environ Med. 1993;9(3–4):128–138.

15. Angelini G, Curatoli G, D’Argento V, Vena GA. Pollinosi: una nuova metodica di immunoterapia. Medit J Surg Med. 1993;253–256.

16. Eggar J, Stolla A, McEwen LM. Hyposensibilisierung bei nahrungsmittelinduzierter migrane. Aktuelle Neuropadiatrie. 1992. Lishka A, Bernett G, eds. 1992. Ciba-Geigy Verlag, Wehr. 1993;287–291.

17. Eggar J, Stolla A, McEwen LM. Controlled trial of hyposensitization in children with food induced migraine. Cephalgia. 1993;13: Suppl. 216.

18. Di Stanislao C. Mazzocchetti E. Bologna G Chimenti S. EPD secondo McEwen. Studio cliniico, istologia e immunoistochimico. Bollentino de dermatologia allergologia e professionale. 1994;2.

19. Astarita C et al. Effects of enzyme potentiated desensitization in the treatment of pollinosis: A double-blind placebo-controlled trial. J Investig Allergol Clin Immunol. 1996 July–Aug 6(4): 248–255.

20. Cantani A, Vanda Ragno V, Monteleone A, Lucenti P. Businco L. Enzyme-potentiated desensitization in children with asthma and mite allergy: A double-blind study. J Investig Allergol Clin Immunol. 1996 Jul.–Aug;6(4):270–276.

21. Galland L, McEwen LM. A role for food intolerance in childhood migraine. World Ped Child Care. 1996;6:2–8.

22. Pulec JL. Enzyme-potentiated desensitization: a major breakthrough [editorial]. Ear Nose Throat J. 1996 Oct;75(10):640.

23. Caramia G, Franceschini F, Cimarelli ZA, Ciucchi MS. Gagliardini R. Ruffini E. The efficacy of E.P.D., a new immunotherapy, in the treatment of allergic diseases in children. Allerg Immunol. 1996 Nov;28(9):308–310.

24. Ippoliti F, Rivi R, Businco L. Effect of preseasonal enzyme potentiated desensitization (EPD) on plasma IL-6 and IL-10 in grass pollen-sensitive asthmatic children. Allerg Immunol. 1997;29(5):120,123–125.

25. Di Stanislao C, Mazzocchetti E, Bologna G Chimenti S. A double-blind, placebo-controlled study of preventative immunotherapy with EPD in the treatment of seasonal allergic disease. Allerg Immunol. 1997;29(2):39–42.

26. Ward WA. Enzyme potentiated desensitization (EPD): a potential revolution in allergy care. Curr Opin Otolaryngol Head Neck Surg. 2000;8:273–276.

27. Shrader Jr WA. The use of bacterial antigen EPD and LDA immunotherapy for the treatment of rheumatoid arthritis and reactive arthritis: the role of molecular mimicry. Unpublished. 1996; revised 1998, 2000. See www.drshrader.com.

W.A. Shrader, Jr., MD, FAAEM

Board Certified in Environmental Medicine