Enzyme potentiated desensitization

2 EPD treatment

Enzyme potentiated desensitization, or EPD, is a treatment for allergies developed in the 1960s by Dr. Len
McEwen in the United Kingdom. EPD uses much lower
doses of antigens than conventional treatment, with the
addition of an enzyme, -glucuronidase. EPD is available in the United Kingdom, Canada for the treatment of
hay fever, food allergy and intolerance and environmental
allergies.

The enzyme beta glucuronidase appears to potentiate the

desensitizing eect of a small dose of allergen. The quantities of both are smaller than those occurring naturally
in the body, but not so small that they can be regarded as
homeopathic. Intradermal injections are used. The treatment takes 34 weeks before any eect is seen. For food
and environmental allergies and intolerances treatments
are typically given at two monthly intervals at rst, but
the interval between treatments is gradually lengthened.
Hay fever is treated with two shots of EPD outside the
pollen season.

EPD was under development for the treatment of

autoimmune disease by a United Kingdom company
called Epidyme also owned by Dr. McEwen which has
been granted a United Kingdom patent. Despite encouraging results[1] in an experimental model of rheumatoid
arthritis the company was placed into liquidation in April
2010.[2]

3 Mechanism for EPD

The treatment uses dilutions of allergen and enzyme to
which T-regulatory lymphocytes are believed to respond
by favouring desensitization, or down-regulation, rather
EPD was available in the United States until 2001, when than sensitization. Once activated these lymphocytes
the Food and Drug Administration revoked approval for travel to lymph nodes and reproduce or stimulate simian investigative study which it had previously sanctioned lar T-lymphocytes.
which had allowed EPD to be imported into the USA
without being licensed. The reason given for revoking
approval was that complex mixtures of allergens used in 4 Evidence for the Eectiveness of
EPD treatments were not allowed under FDA rules. Since
EPD
then the FDA has banned importation of EPD[3] for the
following reasons:.
EPD is considered experimental by some doctors and
allergists. However, there is evidence for the ecacy
of EPD in the treatment of hay fever and other con EPD is not licensed.
ditions as a result of nine placebo-controlled, doubleblind trials involving 271 patients. These trials showed
the labeling of the medicine does not contain ade- a signicant improvement in the symptoms with probquate directions for use. (EPD is only supplied to abilities of 0.001 to 0.01 (a chance of one in a thoudoctors who have been through a one week training sand to one in a hundred that the results of the trial
course, and instructions supplied with the medicine would be seen by chance alone assuming EPD had no
would not be adequate)
eect).[7][8][9][10][11][12][13][14] However, one trial involving 183 patients published in the British Medical Journal
showed no overall eect.[15] Dr Len McEwen, inventor of
A related treatment, Low Dose Allergens (LDA), has EPD, speculated[16] that the reason for the failure might
been developed in the US by Dr. Shrader, which, be- have been that the beta glucuronidase enzyme preparaing a compounding rather than a drug, is not regulated by tion was inadvertently heated or frozen during storage in
the FDA, and uses a dierent allergen mix for the US en- the hospital pharmacy, as it is sensitive to the storage temvironment. However, LDA is considered by many in the perature and enzyme from the same manufactured batch
eld to just be a repackaging of EPD that allows its use had been used to treat a number of patients successfully.
to not be subject to the same FDA guidelines that caused However, there is no evidence available after the event
EPD to be revoked.[4][5][6]
to test this theory as the remaining trial materials were

United States use

destroyed immediately after the trial ended.

Safety of EPD

While the ecacy of EPD is sometimes the subject of

controversy among the medical community, the safety of
EPD is demonstrated in one study under the control of an
Investigational Review Board and reported by the American EPD Society. 5,400 patients received at least 3 doses
of EPD with no severe reactions reported.[17] However,
there is at least one known person who has had very serious health complication due to EPD. He went through
the treatment in the 90s, and his health was devastated
from it. He was relatively healthy before the EPD, with
only minor to moderate allergies that he was dealing with,
but within hours of the rst EPD treatment became seriously ill and was never the same again. Clearly this person
was not included in the above study described above, and
therefore one may question where this study was done in
an unbiased way, since the author was quite aware of this
person whose life was devastated by EPD, but somehow
managed to nd a reason not to include this negative data
into the study.

REFERENCES

American Academy of Allergy, Asthma, and Immunology.

7 Restrictions on EPD
EPD has not been developed for treatment of allergy to
insect stings (for which convenventional immunotherapy
is recommended), nor for contact dermatitis and allergy
to drugs.[20] It is not FDA approved.
EPD protocol includes high doses of folic acid that may
increase blood histamine levels. EPD may be contraindicated for patients diagnosed with high blood histamine
(histadelia). To screen for high blood histamine, look
for an elevated basophil count. If the basophil level is
elevated, high blood histamine can be conrmed with a
blood histamine test.
If blood histamine becomes elevated during the course
of EPD treatments, the patient may develop new or increased sensitivity to any environmental agent, including
food, inhalant and even clothing ber. Increased sensitivity may present as acute, rapid-onset headaches and/or
asthma attacks.
An elevated blood histamine level may also introduce or
increase suicidal tendencies.

Comparison of EPD with conventional escalating-dose im- 8 References

munotherapy (hyposensitization) [1] EPD treatment of rheumatoid arthritis proof of concept

By contrast uncontrolled use of conventional (escalating

dose) immunotherapy (hyposensitization not EPD) for
general allergic conditions was believed to be responsible for at least 29 deaths in the UK, and is now banned
in the United Kingdom except in hospital under close
observation.[18] A working party of the British Society
for Allergy and Clinical Immunology reviewed the role of
conventional high dose specic allergen immunotherapy
(not EPD) in the treatment of allergic disease and recommends high dose specic allergen immunotherapy for
treating summer hay fever uncontrolled by conventional
medication and for wasp and bee venom hypersensitivity.
For the recommended indications the risk:benefit ratio
was found to be acceptable for conventional immunotherapy provided patients are carefully selected; in particular,
patients with asthma should be excluded and injections
should be given only by allergists experienced in this form
of treatment in a clinic where resuscitative facilities are
available and patients remain symptom free for an observation period after injection which is sucient to detect
all serious adverse reactions.[19]

results on Epidyme website use of EPD to treat autoimmune diseases.

[2] Insolvency List
[3] FDA Import Alert
[4] EPD & LDA
[5] LDA Therapy
[6] Low Dose Immunotherapy
[7] Brosto J., Fell P. (1990). A single dose desensitisation
for summer hay fever. Eur. J. Clin Pharmacol. 38 (1):
779. doi:10.1007/BF00314808. PMID 2328752.
[8] Astarita C., Scala G., Spoviero S., Franseze A. (1996).
Eect of enzyme potentiated desensitisation in the treatment of pollenosis : A double-blind placebo-controlled
trial. J Investig Allergol Clin Immunol 6 (4): 248255.
PMID 8844502.
[9] Longo G., PoIi F., Bertoli G. (1992). Clinical ecacy
of a new hyposensitising treatment, EPD (Enzyme Potentiated Desensitisation) in the therapy of pollenosis. Riforma Med. (107): 1716.

Conventional escalating-dose immunotherapy (not EPD)

has been used to treat tens of millions of people in the [10] Angelini G., Curatoli G., DArgento V., Vena G. A. PolliUnited States with appropriate medical supervision with a
nosi (1993). Una nuova metodica di immunoterapia.
death rate of less than one in one million according to the
Med. J. Surg. Med.: 2536.

[11] Di Stanislao C. Di Berardino L., Bianchi I., Bologna G.

(1997). A double-blind, placebo-controlled study of preventive immunotherapy with EPD in the treatment of seasonal allergic disease. Allergie et lmmunologie 30 (2):
3942.
[12] Caramia G., Franceschini F., Cimarelli Z.A., Ciucchi
M.S., Gagliardini R., Rulni E. (1996). The ecacy
of EPD, a new immunotherapy, in the treatment of allergic diseases in children. Allergie et lmmunologie. 28
(9): 308310.
[13] Di Stanislao C., Angelini F. et al. (2002). Beta glucuronidase short-term immunotherapy prevents seasonal
rhinoconjunctivitis in grass pollen allergic patients by
modifying dendritic cell phenotype. Allergy 57 (Suppl
73): 767. doi:10.1034/j.1398-9995.57.s73.81.x.
[14] Boscolo M. A., Brivio G. E.P.D. preventive therapy
(McEwen method) vs. placebo: a double-blind trial.
Poster presentation. European Congress of Allergy & Clinical Immunology. Brussels, July 1999.
[15] Radclie M. J., Lewith G. T., Turner R. G., Prescott
P., Church M. K., Holgate S. T. (August 2003).
Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled
study. British Medical Journal. 327 (7409): 2514.
doi:10.1136/bmj.327.7409.251. PMC 167158. PMID
12896934.
[16] Epidyme website Enzyme Potentiated Desensitisation
(EPD) A promising low-dose method of immunotherapy.
Dr. Len McEwen BM., BCh. unpublished paper.
[17] Shrader, W A; Wilkinson R E (September 2001). The
American EPD Study: 19932000 (PDF). White Paper
for United States Senators and Representatives. Enzyme
Potentiated Desensitization (EPD). p. 14. Retrieved 200609-16.
[18] JA Douglass, FC Thien and RE O'Hehir (1997). Immunotherapy in asthma. Thorax (52): 2229.
[19] AJ Frew (1993).
Injection immunotherapy.
British Society for Allergy and Clinical Immunology Working Party.
BMJ 307 (6909): 91923.
doi:10.1136/bmj.307.6909.919. PMC 1679037. PMID
8241857.
[20] L.M. McEwen Enzyme Potentiated Desensistization
(patient pink handbook) 1993

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