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History of Enzyme Potentiated Desensitization (EPD - now LDA in this country) Immunotherapy

W.A. Shrader, Jr., M.D.

Please note: neither EPD nor LDA are approved by the Food and Drug Administration.


            Enzyme Potentiated Desensitization (EPD) is a unique method of immunotherapy, developed in the 1960s, which involves treating all types of allergy with combinations of a large variety of extremely low dose allergens.  EPD is a cell-mediated type of immunotherapy.  It has been employed to treat multiple conditions and is a long lasting treatment option for allergy and autoimmune illnesses.  It has also been employed for many conditions not generally thought to be due to any type of allergy or autoimmune disease.  EPD is no longer available in the USA and has been replaced by Ultra Low Dose Enzyme Activated Immunotherapy (LDA).

            This site summarizes the results of treatment with EPD of 10,372 patients for various conditions from 1993 through 2000 by members of the American EPD Society (AEPDS).  The AEPDS was a group of over 70 physicians specifically trained to administer EPD immunotherapy.  From 1993 through 2000, the study was formally supervised by the Institutional Review Board (IRB) of the Great Lakes College of Clinical Medicine (GLCCM).


            Enzyme Potentiated Desensitization (EPD) is a method of immunotherapy developed by the clinical and academic allergist, Leonard M. McEwen, M.D., in England in the mid 60's.  The method involves desensitization with combinations of a wide variety of extremely low dose allergens (10-14 to approximately 10-7, or 1 part in 100 million to as low as 1 part in 1 quadrillion).  These allergens are given with the enzyme, beta-glucuronidase.  The beta-glucuronidase likely acts as a lymphokine, a substance that potentiates the immunizing ability of the allergens.  EPD appears to specifically induce the production of "activated" T-suppressor cells.  These cells actively turn off the T-helper cells that are acting inappropriately and producing the symptoms of allergy

Comparison of EPD to conventional immunotherapy

Conventional "escalating dose" (where the dose is started "low" - usually 1 to 10,000, and increased over time to as high as 1 to 10, 1 to 20 or 1 to 100) immunotherapy is employed in this country primarily to treat hay fever and cat and dust mite allergy, which are primarily IgE mediated.  This type of therapy works by causing the patient to produce "blocking antibody" (specific IgG), 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 is the treatment.  In order to produce adequate levels of blocking antibody, studies have shown that it requires administration of very high doses of allergen.  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 anaphylaxis, massive swelling, collapse and death.

            In England, "conventional" (escalating dose) immunotherapy has now been banned by the Medicines Commission (26 deaths had been reported) except when given in a hospital setting where emergency resuscitation equipment is immediately available. On the other hand, EPD is allowed to be administered in physicians' offices in England.  Hence there has been a virtual demise of conventional high dose immunotherapy in England.  In the United States, at least 60 deaths have been recorded since treatment began in the 1930s as a result of conventional immunotherapy, but the actual number is likely closer to 100.

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.  EPD immunotherapy, however, is cell-mediated and extremely low dose.  The highest ending dose ("maintenance" dose) of EPD is at least 10 million times less than the standard maintenance dose for conventional immunotherapy.  EPD immunotherapy is now the only allergy immunotherapy permitted to be used in a physician's office outside a hospital setting in the United Kingdom.

            The danger of fatal or life-threatening systemic reactions to EPD treatment is negligible.  Well over 350,000 doses of EPD have been given worldwide, and again - unlike other types of immunotherapy - life-threatening reactions to EPD have not been reported since use was begun over 40 years ago.

Conventional escalating dose immunotherapy generally does not generally offer long lasting benefit, and it cannot easily be stopped without the return of significant symptoms in 3 to 12 months.  It has been suggested by several previous studies of EPD immunotherapy that this method of treatment can produce much longer lasting desensitization than does conventional immunotherapy, with treatments lasting as long as 1-5 years.  Historically, approximately half of patients who have responded to EPD were able to stop permanently after between 10 and 20 treatments.

Conventional immunotherapy must usually be 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, but rarely less often.

EPD immunotherapy, on the other hand, is only administered every two months or less often, according to previous published studies and our 7-year study.  Treatment is required only every two months initially for a period of 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 intervals of three months or longer, at which time treatment may be discontinued or significantly reduced (intervals of a year or less often are common) for the majority of patients.

            EPD includes mixtures of antigens developed by Dr. McEwen over the past 30 years that may act quite "universally."  This means patients allergic or intolerant to most substances have responded to treatment.  Available EPD mixtures include inhaled pollens, danders, dust and mites, a wide range of bacteria, fungi, yeast (including candida species), molds, all foods (except EPD will not desensitize to raw carrot and raw apple), many food additives, most common chemicals (except pesticides and herbicides), formaldehyde, detergents (for contact skin sensitivity), wood terpenes, and mosquito (which likely cross reacts with other non-venomous insects).  EPD treatment for bee venom anaphylaxis is currently under investigation in England.

            EPD has the distinct advantage that it effectively treats a very wide variety of immune and autoimmune disorders (and others not generally perceived to be immune-related), including illnesses that respond poorly -- or not at all -- to other methods of treatment of any kind. Some of the conditions being treated successfully with EPD include hay fever [8,11, 14,15,25], dust mite allergy [16,20] perennial rhinitis [6], asthma [6,14,16,20], urticaria ("hives") [14], eczema (dermatitis) of most all varieties [14], angioedema (swelling of the face, lips, etc.) [6,14], anaphylactic reactions (life-threatening swelling, usually involving the airways) to most known substances [14], food (or food additive/preservative) allergy or intolerance [7,12], adverse responses to chemicals ("multiple chemical sensitivity" or "MCS") [14], ADHD (Attention Deficit Hyperactivity Disorder) [13,14], autism, Tourette's syndrome, irritable bowel disorders, Crohn's Disease, ulcerative colitis [7] migraine and other headaches [14,16,17,21] rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosis [27], to name just a few.

EPD Study Results

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Last modified: December 12, 2019