Hello naylorj,
I'm terribly sorry your baby daughter is afflicted with this disorder,
and glad to hear she loves to eat, as failure to thrive is common in
small children with EE. Do you live near Cincinnati, Ohio? If you have
not had your daughter evaluated at Cincinnati Children's Hospital, you
may be interested to know they are the leading referral center for
disorders of your daugter's kind.They will soon open the nation's
first center for eosinophillic disorders.
http://allergies.about.com/gi/dynamic/offsite.htm?site=http://www.cincinnatichildrens.org/about/news/release/2004/gastrointestinal%2Dstudy.htm
Cincinnati Children's Hospital Medical Center
3333 Burnet Avenue, Cincinnati, Ohio 45229-3039
513-636-4200 | 1-800-344-2462 | TTY: 513-636-4900
http://www.cincinnatichildrens.org/default.htm
"A new Children's Hospital Medical Center of Cincinnati discovery may
have significant implications for children with a eosinophilic
esophagitis, a fast-growing new disease whose symptoms mimic
gastroesophageal reflux, and for adults with reflux who are not being
helped by currently available medications.
In a study published in the January issue of The Journal of Clinical
Investigation, Marc E. Rothenberg, M.D., Ph.D., has established a link
between reflux and allergy -- not only food allergies but also
environmental allergens such as pollens and molds. Dr. Rothenberg, the
study's senior author, and his colleague Anil Mishra, Ph.D., have
developed the first experimental system, a mouse model, for
eosinophilic esophagitis -- a disease whose numbers have exploded in
recent years.
"We're saying that what a person breathes in can actually affect the
gastrointestinal system," says Dr. Rothenberg, who directs the section
of allergy and clinical immunology in Cincinnati Children's Division
of Pulmonary Medicine, Allergy and Clinical Immunology. "There is a
direct link between exposure to allergens that go to the lung --
aeroallergens -- and development of esophageal inflammation."
http://www.cincinnatichildrens.org/about/news/release/2000/12-allergy-reflux.htm?view=content
80 eosinophils/HPF is quite high- one of the Klein's criteria for
diagnosis of EE is the presence of eosinophils "greater than 15-20
per HPF". The numbers of eos per hpf correlates well with the severity
of the disease. Under healthy conditions, eosinophils make up a very
small percent of circulating white blood cells, and are found
primarily in the digestive tract and bone marrow. It is such a shame
that one of the most interesting looking cells seen under the
microscope can cause such problems!
Because EE has only been researched for a short time, a definitive
answer is not posible.Food allergies are thought to be a part of this
disorder, which may be genetic, with airborne allergies recently being
implicated as well. Each patient is different, and as such, the
offending allergens may vary, person to person. Esophagitis is usually
caused by acid reflus. In EE, there is the double whammy of the acid
reflus stimulating eosinophil migration into the esophagus.
http://www.emedicine.com/MED/topic735.htm
Eosinophilic Esophagitis, also known as eosinophilic enteropathy, is
one of several disorders called eosinophilic gastrointestinal
disorders (EGID). This disorder seems to be on the rise, although it
is not clear whether more cases are being diagnosed, or there are more
actual cases.
"To date IEE has been thought to be a rare disorder. Emerging evidence
suggests its prevalence has been underestimated. It may also be the
most frequent form of eosinophilic gastroenteropathy. The flat, only
endoscopically visible form may be more common than the proliferative
type. With knowledge of the typical history and of the distinct
endoscopic pattern, and with adequate diagnostic workup, the disease
will be found more often in the future. Prompt diagnosis also avoids
further diagnostic procedures and permits rapid remission through
treatment with steroids and antihistamines."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7939509&dopt=Abstract
"Furthermore, following mucosal allergen challenge, eosinophils under
the regulation of IL-5 accumulate in the esophagus, an organ normally
devoid of eosinophils at baseline. Notably, eosinophil accumulation in
the esophagus, a common occurrence in a variety of diseases including
gastroesophageal reflux disease (GERD) and primary eosinophilic
esophagitis (EE), can be experimentally induced by aeroallergen or Th2
cytokine (IL-13) delivery to the lung, establishing a primary link
between pulmonary and esophageal eosinophilic inflammation.
Preliminary epidemiology studies have found that these diseases are
not uncommon; for example, in the region of our medical center, we
have calculated that the incidence of pediatric EE is ~1/10,000
individuals."
http://www.ddw.org/user-assets/documents/PDF/session_handouts/2004/books/Monday/Mon1415Rothenberg.pdf
From a study published in The New England Journal of Medicine,
"...shows that rates of a recently identified and debilitating
disorder called eosinophilic esophagitis have risen so dramatically in
recent years that they may be at higher levels than that of other
inflammatory gastrointestinal disorders, such as Crohn's disease or
ulcerative colitis.
"Despite this explosion in incidence rates, there is so little
information available about the disease that patients often suffer for
a number of years before a diagnosis is made," says Marc E.
Rothenberg, M.D., Ph.D., director of allergy and immunology at
Cincinnati Children's Hospital Medical Center and the study's senior
author."
and
"The researchers also discovered a familial pattern to the disease,
which suggests either a genetic predisposition or a relationship to an
unknown environmental exposure, either of which warrant further study,
according to Dr. Rothenberg."
Sensitized individuals may develop esophageal eosinophilic
inflammation in response to exposure to food allergens. However, the
role of allergens in the induction of eosinophilia in the esophagus
has been debated, since there is no direct causal evidence proving
this linkage. In disorders such as gastroesophageal reflux, which
inflicts nearly 50% of the population, eosinophil accumulation is
observed in the esophagus, suggesting the possibility that allergic
hypersensitivity may be contributing to the disease process "
"The pathophysiologic basis of the disorder has remained elusive, and
the role of allergens is debated. At least a subset of those with the
disorder are food responsive and reactive to the usual causative
agents (eg, milk, egg, wheat, soy) but with an increased degree of
multiple food allergies. In patients with food-responsive eosinophilic
gastroenteropathies, the pathophysiological mechanisms seem to include
both cell-mediated and IgE antibody-mediated forms.
Perhaps the most common type of eosinophilic gastroenteropathy and
most difficult to diagnose and manage is allergic eosinophilic
esophagitis. This disorder is particularly challenging to diagnose
because the symptoms overlap those of GER. Patients with allergic
eosinophilic esophagitis have a predominance of dysphagia"
http://pediatrics.aappublications.org/cgi/content/full/111/6/S2/1609
One study showed that inhaling allergens caused large numbers of
eosinophils to migrate to the lung from the bone marrow.Eosinophil
"trafficking" to the esophagus as well. (You can read all the
scientific jargon on the web page page below)
"Eosinophil recruitment into inflammatory tissue is a complex process
regulated by a number of inflammatory cytokines including IL-3, IL-4,
IL-5, GM-CSF, and chemokines like RANTES and eotaxin. Among the
cytokines implicated in modulating eosinophilic inflammation in
allergic diseases, only IL-5 and eotaxin selectively regulate
eosinophil trafficking. IL-5 regulates growth, differentiation,
survival, and activation of eosinophils. Following allergen
inhalation, IL-5 has been clearly demonstrated to provide an essential
signal for the expansion and mobilization of eosinophils from the bone
marrow into the lung (15). In contrast, eotaxin has been shown to have
an integral role in regulating the base-line homing of eosinophils
into the lamina propria of the gastrointestinal tract at sites distal
to the esophagus (e.g., stomach and intestines), but a less
significant role in regulating eosinophils in the lung. In vivo, these
two cytokines are likely to cooperate with each other to modulate
eosinophil trafficking between the peripheral blood and tissue (20);
however, the role of these processes in regulating esophageal
eosinophils has not been examined.
Our results establish that exposure to an inhaled respiratory allergen
promotes eosinophilic esophagitis and that common mechanisms regulate
eosinophilic inflammation in the respiratory tract and esophagus."
http://www.jci.org/cgi/content/full/107/1/83
Because the sudden increase in cases of EE, the American Partnership
for Eosinophilic Disorders (APFED) and the American Partnership for
Eosinophilic Disorders (APFED) has been formed to research and support
EE.
http://allergies.about.com/b/a/110097.htm
http://allergies.about.com/cs/other/a/aa062702a.htm
"The exact pathophysiology of eosinophilic esophagitis is unknown, but
contact of the allergen with the esophageal mucosa is thought to be
the initiating event. This results in moderate-to-severe inflammation
of the esophageal mucosa with more than 15 eosinophils per high-power
field (hpf). A search for food allergens by skin testing,
radioallergosorbent assay testing (RAST) in blood, or patch (skin)
testing is often unrewarding. Whether environmental agents can be
causative is unknown."
http://www.emedicine.com/PED/topic714.htm
"Food allergens are typically water-soluble glycoproteins with
molecular weights of 10-70 kd. These characteristics facilitate the
absorption of these allergens across mucosal surfaces. Moreover, food
allergens are generally resistant to proteolysis and are heat-stable.
Several food allergens are purified and well-characterized, such as
peanut Ara h1, Ara h2, and Ara h3; chicken egg white Gal d1, Gal d2,
and Gal d3; soybean-Gly m1; fish-Gad c1; and shrimp-Pen a1. Closely
related foods frequently contain allergens that cross-react
immunologically (ie, specific IgE antibodies determined by skin prick
or in vitro testing) and only rarely cross-react clinically. Finally,
cross-reactive allergens have been identified among certain foods and
airborne pollens (see Oral allergy syndrome). Conserved homologous
proteins likely account for this cross-reactivity."
http://www.emedicine.com/med/topic806.htm
"There are several possibilities for initial sensitization and
subsequent challenge in EE. The possible routes of antigen exposure
are summarized in Table 2. First, both initial sensitization and
subsequent challenge may occur
in the esophagus as antigens pass through in the form of foods,
swallowed aeroallergens and pathogens, and secretions from upper and
lower airways. Beneficial effects of an elemental diet in pediatric EE
suggest food
proteins as major responsible antigens. Second, an experimental model
of EE shows that initial sensitization with aeroallergens in the
bronchus is essential, with secondary challenge in the esophagus by
passive ingestion of
aeroallergens deposited in the naso-oral cavity."
Page 5
http://usagiedu.com/articles/ee/ee.pdf
Zantac and GERD
Researcher have long noted the link between asthma patients and acid
reflux. When asthma patients were treated for GERD (acid reflux)
asthme flares decreased dramtically. Researchers have applied this to
EE research, and are finding a great correlation between acid reflus
and esophagela eosinophils.
Ranitidine (Zantac) is the drug of choice for most forms of
esophagitis. Keeping stomach acid out of the esophagus is important to
prevent mucosal burns and acid reflux. ........
"However, the entity of eosinophilic esophagitis has emerged since
1997 and has been defined well enough to allow it to be distinguished
from reflux esophagitis, with which it was probably previously
confused. Refinements (though not simplification!) in the definition
of Barrett esophagus are still in evolution. This review will
summarize these newer concepts and briefly review the standards of
diagnosis of reflux esophagitis."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15255030
" Some debate exists as to how frequently this occurs, since
irritability in an infant with GER could be the presenting symptom. It
may be hard to differentiate from colic. Therapy for excessive gas
and/or changing formulas often are employed, especially since parents
may note pain and crying, pulling up of legs, and abdominal
distention.
Although most cases of colic self-resolve and only require
conservative measures, a minority of infants may benefit from reflux
therapy, specifically antacids or H2 antagonists. This is true
especially if a history of frequent regurgitation or other
characteristic posturing is noted by the parent or physician.
Before beginning motility agents (eg, Reglan), be certain to document
that upper GI anatomy is normal."
http://www.emedicine.com/PED/topic714.htm
See the bottom of Page 4 for a reference to using Zantac to prevent
esophageal reflux.
http://www.apfed.org/pdf/Treatment%20of%20EGID%2010-04.pdf
This web site, Patients up to date, has some excellent information.
The site requests that information not be copied elsewhere. To
summarize, the site explains how the esophagus has only recently been
considered an immunologically active organ, capable of attracting
eossinophils in response to allergens. The article goes on to explain
that even heartburn (acid reflux) can be stimulated by the
accumulation of eosinophils.
http://patients.uptodate.com/topic.asp?file=esophdis/11927
" In a study published in the January 2000 issue of The Journal of
Clinical Investigation, Marc E. Rothenberg, M.D., Ph.D., established a
link between reflux and allergy - not only food allergies but also
environmental allergens such as pollens and molds. Dr. Rothenberg, the
study's senior author, and his colleague Anil Mishra, Ph.D., have
developed the first experimental system, a mouse model, for
eosinophilic esophagitis - a disease whose numbers have exploded in
recent years.
"We're saying that what a person breathes in can actually affect the
gastrointestinal system," says Dr. Rothenberg, who directs the section
of allergy and clinical immunology in Cincinnati Children's division
of Pulmonary Medicine, Allergy and Clinical Immunology. "There is a
direct link between exposure to allergens that go to the lung --
aeroallergens -- and development of esophageal inflammation."
http://allergies.about.com/library/blcinchildrenshosp122700.htm
Diet and Medication
"It is believed that whole food proteins are the most common
precipitators of an EG "attack." Most with this condition are forced
to eat a restricted diet and/or drink elemental formulas containing no
whole food proteins, such as Neocate, Elecare, etc. (see formula
list). Some people with EE/EG/EC are even fed elemental formulas via
gastrostomy tube, or are limited to TPN (blood-vessel feeding) due to
the severity and complications of the disease. The condition itself is
not fatal, but complications can be quite serious. EG is known to
occur sometimes during the second stage in a 3-stage eosinophilic
disease called Churg-Strauss Syndrome."
"Once the diagnosis has been made, it is useful to look for specific
food allergies, as an elimination diet may be successful if a limited
number of food allergies are identified. One of our patients with
mucosal disease had improvement after elimination of seafood. Katz et
al reported that an elimination diet might fail to prevent recurrence,
but our patient has
remained well for more than 3 years. In general, patients responded
quickly and well to steroids, as was true in our series. The
appropriate duration of steroid treatment has been unknown, but short
courses followed by a repeat course for a
relapse have been described. Patients with refractory relapsing
disease are usually placed on long-term low-dose steroids or
immunosuppressive therapy."
Page 3
http://www.wjgnet.com/1007-9327/9/2813.pdf
Because there is no known cure for EE, EG or EC, medications are used
for maintenance of symptoms and prevention of full-blown attacks (or
"flare-ups"). The only known medication to successfully stop the
eosinophilic inflammation in EE, EC and EG is prednisone.
Fluticasone Propionate (Flonase, Flovent) has been helpful in most
cases of EE, if the medicine is swallowed so that it comes directly in
contact with the esophageal tissues that are infiltrated with the
eosinophils. Elemental formulas are also very effective for EE.
Cromolyn Sodium (Gastrocrom) has been used with some success for EG,
but does not work in all cases. Azathioprine and other
immunomodulators have also been used with some success, but often the
side-effects lead to discontinuance of the medication. An experimental
steroid called Budesonide may be helpful but no clinical trials have
been done with EG, EC or EE to my knowledge. Some people have found
they can reduce the severity of an "attack" if they take long-acting,
nondrowsy antihistamines (like Claritin, Allegra or Zyrtec) but no
clinical trials to my knowledge have been done on EG/EE/EC with such
medications. Finally, a new class of asthma medications called
leukotriene inhibitors, is showing some mixed results in clinical
trials for asthma patients, and has been used experimentally in cases
of EG/EE, but again with mixed results.
http://c4isr.com/NEED/NEED%20Docs/what%20is%20ee.htm
"With regard to eosinophilic esophagitis, the diagnosis is made based
on the number of eosinophils and the degree of epithelial hyperplasia
(all markedly higher than in just Gastroesophageal Reflux alone). The
presence of positive skin tests indicates that he has the allergic
variant. We find that a strict dietary avoidance is very helpful. It
has to be strict and comprehensive - all foods that are positive on an
extended food prick testing panel. We also recommend strict
environmental control since aeroallergens have also been implicated in
the disease pathogenesis. We generally re-scope after three months of
this intervention. Refractory patients are then treated with "inhaled"
fluticasone - don't use the spacer and have them swallow the drug.
Some patients require elemental diets, if they don't respond to the
other treatments."
http://www.aaaai.org/aadmc/ate/esophagitis.html
"Foods responsible for the majority of significant food allergy in
infants, children, and adults are as follows:
Infants: Cow?s milk; soy
Children: Cow?s milk; egg; peanut; soy; wheat; tree nuts (walnut,
hazel, etc); fish; shellfish
Adults: Peanut; tree nuts; fish; shellfish
Elimination of the causal protein should result in resolution of
symptoms, although the time to resolution may be prolonged in some
disorders (weeks in eosinophilic esophagitis). In some cases,
adjunctive tests such as endoscopy/biopsy may be helpful to show
resolution of pathology.
A general approach to the diagnosis of food allergy incorporating
history, diagnostic tests, elimination diets, and challenge (see Table
7 of the original guideline document) is outlined in Figure 1 of the
original guideline document, but a variety of adjustments in approach
may be warranted for particular disorders/symptom complexes as
described in the accompanying technical review and as mentioned above
for infants. Specific information concerning procedures for performing
oral food challenges is given in the accompanying technical review."
http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=3059&nbr=2285
Elemental Diet: This means eliminating protein from the diet.Special
liquid amino acid formulas are given, as amino acids don't cause
allergic reactions as do whole or partial proteins.Elemental diets
supply all needed nutrients and put no stress on the digestive system.
Page 2
Food trials can begin after a favorable response to elimination and
elemental diets.
http://www.apfed.org/pdf/Treatment%20of%20EGID%2010-04.pdf
"Use of an elemental diet (Vivonex) as the sole source of nutrition
for an average of four weeks successfully induced remission in 96
(85%) of the patients. Treatment failure was not related to site of
disease, disease activity, or the sex or age of the patient. Long-term
follow-up showed that 22% of the patients relapsed within six months.
Later, the annual relapse rate was 8-10%. Patients with disease
complicated by fistula or perianal involvement relapsed earlier than
those with uncomplicated disease."
http://www.findarticles.com/p/articles/mi_m0887/is_n11_v9/ai_9170682
Walgreens Online sells an elemental formula
http://www.walgreens.com/store/product.jhtml?PRODID=374079&CATID=100672
"RESULTS: Of 346 patients with chronic gastroesophageal reflux disease
symptoms and eosinophils on esophageal biopsy, 51 (14.7%) were
ultimately diagnosed with EoE. There was significant improvement in
vomiting, abdominal pain, and dysphagia after the elemental diet. The
median number of esophageal eosinophils per high-powered field (HPF)
decreased from 33.7 before the diet to 1.0 after the diet (p <0.01).
The average time to clinical improvement was 8.5 days. CONCLUSIONS:
Elemental diet resulted in striking improvement in both symptoms and
histologic evidence of disease in children and adolescents with EoE,
as identified by strict diagnostic criteria."
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12738455&dopt=Abstract
Steroids, both inhaled and oral, and leukotriene inhibitors are
commonly used to treat EE. "Treatment includes an elimination diet
and/or inhaled corticosteroids, which children swallow so the
medication reaches the esophagus rather than going to the lungs"
http://www.findarticles.com/p/articles/mi_m0BJI/is_13_30/ai_63972281
http://www.apfed.org/pdf/Treatment%20of%20EGID%2010-04.pdf
"Montelukast is a selective inhibitor of the leukotriene D4 receptor,
used successfully to treat asthma.60 They studied 8 patients with EE,
beginning montelukast 10 mg/day, and adjusted the dosage according to
tolerance and symptoms up to 100 mg/day. Once symptom relief had been
achieved, the dosage was reduced to a maintenance level between 20 to
40 mg/day. Seven patients (88%) showed complete improvement in
dysphagia, although montelukast did not eradicate eosinophils
themselves in the esophagus. The majority of patients were able to
discontinue acid-suppression therapy. The only adverse effects
included nausea and myalgia during the 14-month treatment."
Page 6
http://usagiedu.com/articles/ee/ee.pdf
" "Two major pharmaceutical companies have an antibody in human trials
that blocks IL-5," adds Dr. Rothenberg. "These drugs are being tried
for asthma, but based on our findings I'd like to see IL-5 blockers
tried in patients with eosinophilic esophagitis."
Children with eosinophilic esophagitis often have abdominal pain,
difficulty swallowing, vomiting, failure to thrive and weight loss.
Just a few years ago, incidents of the disease were rare. Now, Dr.
Rothenberg and his colleagues at Cincinnati Children's food allergy
clinic treat about 60 cases each year. Physicians throughout the
United States also report an explosion in the number of cases."
http://allergies.about.com/library/blcinchildrenshosp122700.htm
Outcome
I can not, of course, predict the outcome for your daughter, but it
sounds as if she is getting great care, and doing well. I believe many
of the "scary" things you have read are referring to children who do
not respond to GERD therapy, who already have esophageal stenosis
and/or damage, asthma, delayed gastric emptying or other complications
requiring surgery.
http://www.paaap.org/pdf/teleconf/032603/khan.pdf
"In the absence of associated eczema, IgE levels and peripheral
eosinophils are normal. Strict elimination of the offending protein
will produce
dramatic recovery in 10 to 21 days and, with the exception of gluten,
the patient can resume the offending protein by 4 to 6 years of age."
Page 3
http://www.shsweb.co.uk/neocate/prof/docs/focus%201%20magazine.pdf
"Prolonged avoidance of the identified foods resulted in persistent
improvement of symptoms in these ten children. Eight of ten patients
were able to discontinue all of their anti-reflux medications. All
were able to eat a wide variety of foods. None became dependent on the
formula." Page 7-8
http://www.shsweb.co.uk/neocate/prof/docs/focus%201%20magazine.pdf
"By using high-resolution endoscopic ultrasound in 11 children with
EE, Fox et al. showed that the total thickness of the esophageal wall
is increased significantly in EE (2.8 vs. 2.1 mm), mainly by the
increase in the thickness
of the mucosa and submucosa. Although the muscularis propria was
slightly thickened, the circular muscle was not. One atypical elderly
male patient, with an esophageal stricture, underwent an endoscopic
ultrasound that showed asymmetric thickening of the muscularis propria
of the distal esophagus.37 These studies suggest that EE may involve
more than just the epithelium of the esophagus."
http://usagiedu.com/articles/ee/ee.pdf
"Despite recent advances in EE research, a number of questions remain
to be answered. Is the incidence of EE truly increasing in a similar
fashion with other atopic diseases? Why is EE more prevalent in men?
What are
the responsible antigens and how important are aeroallergens? What is
the actual route(s) of antigen exposure? Do pediatric patients outgrow
EE as they become older? If so, is it host-dependent or
antigen-dependent? Should extrinsic and intrinsic EE be treated
similarly? Can eosinophil granule proteins directly affect neural
transmission in the esophagus?"
Page 7
http://usagiedu.com/articles/ee/ee.pdf
You can read about GERD and fundoplication, in an answer I completed
in March, 2004
http://answers.google.com/answers/threadview?id=318187
Additional Information:
You may want to watch out for latex and sulfite allergy in your
daughter as these too are IgE mediated allergic responses.
http://www.aaaai.org/aadmc/ate/foodallergy.html
Clinical Trials
http://www.clinicaltrials.gov/ct/screen/BrowseAny?path=%2Fbrowse%2Fby-condition%2Faz%2FE%2FD004802%2BEosinophilia&recruiting=true
I hope this has adequately answered your questions. If not, or if I
have duplicated information you already had, please request an Answer
Clarification, before rating, and I will be happy to assist you
further. I wish you and your daughter the best!
Regards,
crabcakes
Search Terms
eosinophilic esophagitis research
eosinophils esophagus
eosinophilic esophagitis outcome
elemental diet
EE treatment |
