Gastro-intestinal motility and cow's milk protein allergy

165 Pages·2013·11.11 MB·English

JOURNAL OF FOOD ALLERGY
EDITORIAL BOARD
Official Journal of the Brazilian Society of Food Allergy - SBAA
EDITOR-IN-CHIEF
Prof. Aderbal Sabra
University Unigranrio, Rio de Janeiro, Brazil
CONSULTING EDITORS
Katie Allen John Walker-Smith
University of Melbourne, Melbourne, Australia Emeritus Prof of Paediatric Gastroenterology
University of London, Londo, United Kingdom
Jaime Ramirez Mayans
Marcello Barcinski
Instituto Nacional de Pediatría, S.S, Mexico
FIOCRUZ, Rio de Janeiro, Brazil
Joseph A. Bellanti
Georgetown University Medical Center, USA Mauro Batista Morais
Paulista School of Medicine, Sao Paulo, Brazil
Jorge Amil Dias
Centro Hospitalar S. Joao, Portugal Simon Murch
Warwick Medical School, United Kingdom
Jorge Kalil
School of Medicine USP and Annamaria Staiano
Instituto Butantan, São Paulo, Brazil
University of Naples, Federico II, Italy
Giuseppe Iacono
Maria Del Carmen Toca
Di Cristina Hospital, Italy
University of Buenos Aires, Argentina
Glenn Furuta
Neil Shah
Univ. of Colorado Denver School of Medicine, USA
Great Ormond Street Hospital
Olivier Goulet Institue of Child Health
University of Paris 5 René Descartes, Paris, France University College London, United Kingdom
Harland Winter
Harvard Medical School, USA
Journal of Food Allergy
Address: Visconde de Piraja, 330 / 311, 22410-001, Rio de Janeiro, Brazil
Telephone: + 55 21 2513-2161
E-mail: [email protected]
Website: www.journalfoodallergy.com
J FOOD ALLERGY
JOURNAL OF FOOD ALLERGY
Volume 1, Number 2 April - June, 2012
CONTENTS
Editor’s Comment
Aderbal Sabra.............................................................................................................................................................. 147
Original Articles
Gastro-intestinal motility and cow’s milk protein allergy
Yvan Vandenplas, Elisabeth De Greef, Thierry Devreker, Bruno Hauser, Gigi Veereman-Wauters ..........................149
Is there a link between Cow´s Milk Protein Allergy and Renal Tubular Acidosis?
Cervantes-Bustamante R, Ramirez-Mayans JA, Cadena-León J, Zapata-Castilleja C, Zárate-Mondragón F,
Hernández-Bautista V, Montijo-Barrios E, Cazares-Mendez M ................................................................................156
Clinical Features of Eosinophilic Esophagitis in a Consecutive Series of Pediatric Patients in an Australian
Tertiary Referral Center
Mark Nethercote, Ralf G Heine, Shivani Kansal, Shaun SC Ho, CW Chow, Don Cameron, George Alex, Bircan
Erbas, Nicholas Osborne, Luke Stevens, Dominique Davidson, Katrina J Allen ...................................................... 163
Score for the diagnosis of food allergy
Aderbal Sabra, Isaac Tenório, Selma Sabra
UNIGRANRIO, Service Food Allergy........................................................................................................................ 173
Review Article
Ass’s milk in allergy to Cow’s milk protein: a review
Pasquale Mansueto, Giuseppe Iacono, Aurelio Seidita, Alberto D’Alcamo, Salvatore Iacono, Antonio Carroccio .. 181
Information for Authors ........................................................................................................................................... 194
J FOOD ALLERGY
Editor’s CommEnt

Editor’s Comment
Issue number two of JFA is proud to offer you the best articles in Food Allergy, produced by leading
groups in this field all over the world.
Article number one in this issue is from BELGIUN, “Gastro-intestinal motility and cow’s milk pro-
tein allergy” by Yvan Vandenplas, Elisabeth De Greef, Thierry Devreker, Bruno Hauser, Gigi Veereman-
Wauters UZ Brussel, Vrije Universiteit Brussel, from Brussels, Belgium. This nice paper brings to us extra
light in the basic findings of disruption of the GI motor activity in patients with Food Allergy. The motor
activity in food allergy compromises the GI transit and is related to reflux, dyspepsia, small bowel distention
and constipation.
Article number two in this issue is from MEXICO, “Is there a link between Cow’s Milk Protein
Allergy and Renal Tubular Acidosis?” by Cervantes-Bustamante R, Ramirez-Mayans JA, Cadena-León J,
Zapata-Castilleja C, ZárateMondragón F, Hernández-Bautista V, Montijo-Barrios E, Cazares-Mendez M,
Gastroenterology and Nutrition Department, Immunology Department, Instituto Nacional de Pediatría, S.S.,
from Mexico City, Mexico. This nice paper brings new concepts that must be considered in patients with food
allergy and renal tubular acidosis.
Article number three in this issue is from AUSTRALIA-UK, “Clinical Features of Eosinophilic Es-
ophagitis in a Consecutive Series of Pediatric Patients in an Australian Tertiary Referral Center” by Mark
Nethercote, Ralf G Heine, Shivani Kansal, Shaun SC Ho, CW Chow, Don Cameron, George Alex, Bircan
Erbas, Nicholas Osborne, Luke Stevens, Dominique Davidson, Katrina J Allen from the Murdoch Childrens
Research Institute (MN, RGH, NO, LS, KJA), Department of Gastroenterology & Clinical Nutrition, Royal
Children’s Hospital (RGH, SK, SSCH, DC, GA, KJA), Department of Paediatrics, University of Melbourne
(RGH, NO, KJA), Department of Allergy & Immunology, Royal Children’s Hospital (RGH, KJA), Depart-
ment of Anatomical Pathology, Royal Children’s Hospital (CWC, DD), School of Public Health, LaTrobe
University (BE), Melbourne, Australia and European Centre for Environment and Human Health, Peninsula
College of Medicine and Dentistry, University of Exeter (NO), United Kingdom, UK. The way cases of EE
are rising all over the world and its clinical features present the same perspective in Australia as in UK, as
shown in this article by Katie Ellen and her associates.
Article number four in this issue is from Rio de Janeiro-BRAZIL, and expresses the experiences of
Prof Sabra and his group of associates, which have been dealing with food allergy patients for more than 40
years at the Department of Food Allergy at UNIGRANRIO. His group was the first to describe and publish
in Nom-IgE food allergy. The anecdotal way that food allergy is denoted by several clinicians is now on the
path to soon disappear. This article is a joy in the way to facilitate the diagnosis of food allergy, based in
clinical observation and focused and logical anamnesis, in a disease without good biomarkers in the lab tests
for diagnosis. “Score for the diagnosis of food allergy” is the paper, by Aderbal Sabra, Isaac Tenório, Selma
Sabra, from the Department of Food Allergy, UNIGRANRIO, Rio de Janeiro, Brazil.
Article number five in this issue is from ITALY, a nice revision about the use ass milk in the treat-
147
J FOOD ALLERGY
Editor’s CommEnt -
Continued
ment of food allergy. This paper is from the traditional group of Prof Giuseppe Iacono, a professor with large
experience publishing about food allergy for several years. The article “Ass’s milk in allergy to Cow’s milk
protein: a review” by Pasquale Mansueto, Giuseppe Iacono, Aurelio Seidita, Alberto D’Alcamo, Salvatore
Iacono, Antonio Carroccio, from the Internal Medicine, Policlinico University Hospital of Palermo, (PM, AS,
ADA), Pediatric Gastroen terology, “Di Cristina” Hospital (GI, SI), Palermo and Internal Medicine, Hospital
of Sciacca (AC), ASP Agrigento, Italy.
JFA is proud to announce that in the next issue, number three, in press, we will publish the Consensus
in “Caw’s Milk Allergy” by the Latin American Society of Pediatric Gastroenterology, Hepatology and Nutri-
tion – LASPGHAN. “Call for papers” for JFA issue four are open.
Manuscripts submitted for publication should be sent by e-mail with attached text files and figures to:
[email protected]
Aderbal Sabra, MD, PhD
Editor-in-Chief
Journal of Food Allergy
148
J FOOD ALLERGY
ORIGINAL ARTICLE
Journal of Food Allergy, Vol. 01 (2): 149-155, April-June - 2012
Gastro-intestinal motility and cow’s milk protein allergy
Yvan Vandenplas, Elisabeth De Greef, Thierry Devreker, Bruno Hauser, Gigi Veereman-Wauters
UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
ABSTRACT
Cow’s milk protein allergy (CMPA) causes gastrointestinal (GI) motility anomalies. Diagnostic tests do not reliably
differentiate between CMPA and functional GI manifecations. Symptoms of both conditions overlap. A decrease of
symptoms with an extensive hydrolysate and relapse during challenge is not a proof of immune mediated reactions,
since hydrolysates fasten gastric emptying. And a delayed gastric emptying is a pathophysiologic mechanism of gastro-
oesophageal reflux (GER). Thickened formula reduces regurgitation. If a thickened formula does not reduce regurgita-
tion, CMPA may be the underlying condition. A thickened extensive hydrolysate may induce more rapid improvement,
but does not differentiate between CMPA and GER.
Conclusion: As long as there are no objective diagnostic tools to separate GER from CMPA, the physician has two op-
tions: first treat the most likely diagnosis, and switch to the other option if after 2-4 weeks there is no improvement.
Another option is to treat both conditions with one intervention, what will not result in a diagnosis but induce a more
rapid improvement of the complaints.
Key words: Constipation, Gastroesophageal Reflux, Lactose Intolerance, Milk Hypersensitivity
J Food Allergy. 2012; 1: (2) 149-155
INTRODUCTION
The overlap between frequent (functional) more than one organ system is involved (mainly
gastro-intestinal complaints such as gastro- gastrointestinal (GI) and cutaneous symptoms,
esophageal reflux (disease) (GER(D)) and or GI and more general symptoms or more rare
constipation and gastro-intestinal manifestations GI and respiratory tract symptoms), a systemic or
of cow’s milk protein allergy (CMPA) are a topic (auto-)immune or allergic reaction is very likely
of debate since many years. The debate is the (1).
consequence of the fact that objective diagnostic The debate is focused on cow´s milk since
criteria for each of the entities are lacking. Since this is the major food allergen in young infants.
not one manifestation is specific for CMPA, and While regurgitation decreases strongly between 6
since the same is true for GER(D) and constipation, and 12 months of age (2), tolerance to CMP does
and since all conditions are relatively frequent, only develop after the age of one year (1). There
it is a fact that some of the allergic infants will is a pathophysiologic overlap: an allergic reaction
present with GER(D) and/or constipation and that causes inflammation and secretion of substances
some of the infants with GERD or constipation such as histamine, serotonin. The GI-tract reacts to
will have CMPA. Many infants with CMPA the inflammation by altering motility. As a result,
present symptoms in different organ systems (1). the question raises if there is “coincidence” or if
Since gastrointestinal manifestations are only part “one is the logic consequence of the other”. From
of the spectrum of symptoms caused by CMPA, the point of view of the gastroenterologist looking
this paper does not discuss CMPA in general. If to the GI-tract as an organ responsible for transport
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of food from mouth to anus, regurgitation and are more frequently linked to non-IgE mediated
constipation are mainly regarded as “functional allergy. In daily routine, there is no diagnostic
disorders”, since anatomic malformations are testing for non-IgE mediated allergic reactions.
infrequent. Definitions have been proposed in the But, immunoglobulin free light chains (Ig-fLCs)
Rome III criteria (3). dependent allergic hypersensitivity responses have
The recent changes in formula been demonstrated to occur (in mice) (4). Also, in
composition, such as addition of nucleotides, long children affected with IgE-mediated and non-IgE
chain poly-unsaturated fatty acids (LcPUFAs), mediated CMPA or atopic dermatitis (AD), serum
prebiotic oligosaccharides and/or probiotics, are Ig-fLC concentrations were increased, implying
likely to interfere in this debate. All these novelties the relevance of Ig-fLC measurements in the
claim to induce a better immune response and to diagnosis of human allergic disease (4,5). These
decrease allergy. They also potentially change GI findings suggest that in the future parameters may
tract motility. It is for example claimed that stools become available to contribute to the diagnosis of
are softer with the added pre- and probiotics. CMPA, although the overlap between “allergic”
Most of the epidemiologic data on CMPA/I date and “non-allergic” children is important (4). The
from before these additions. Epidemiologic data relationship between Ig-fLC and gastro-intestinal
collected after the formula changes listed above in symptoms has not been investigated.
unselected populations are missing. If the claimed The old term “intolerance” gives rise to
theoretical benefit results in a clinical benefit, the confusion. In order to avoid this, “intolerance” is
incidence of frequent GI complaints should have proposed to be restricted to the incapacity to fully
decreased. digest carbohydrates, mainly disaccharides, of
CMPA is a reproducible clinically which lactose is the most important one. Primary
abnormal reaction to cow´s milk protein (CMP) lactose intolerance is an almost non-existing
due to the interaction between one or more milk disease at this age. Thus, if lactose intolerance
proteins and one or more immune mechanisms. occurs in infants, it is almost always secondary to
About 90% of the patients develop symptoms another disease and the consequence of atrophy or
before the age of 3 months depending on the damage of the villi. Low lactase activity may also
moment of CMP introduction or within 2 months be the consequence of a transitory slow maturation
after introduction. CMPA rarely develops after the in which case the undigested lactose acts as a
age of 12 months. Improvement or disappearance prebiotic. As a consequence, the term “adverse
of symptoms on a CMP-free diet adds substantial reaction” would be preferable to “intolerance”.
evidence to the diagnosis. A factor which often is The question arises how to make the difference
not considered is the time needed for improvement between an “allergic reaction of which the
of symptoms; the sooner, the more likely that immunologic mechanism involved cannot be
allergy may be involved. If the reintroduction of shown in routine” (non-IgE mediated allergy) and
CMP causes relapse of symptoms, the diagnosis a “functional” symptom? Bearing this in mind,
seems established, since a challenge-test is the term “non-IgE mediated CMPA” will be used
considered as the golden standard diagnostic test. to designate this group of infants with adverse
Although false positive diagnostic testing reactions to CMP and no increase of specific IgE
(specific IgE, skin prick test, patch test) does occur, or no clear positive dermatological contact tests
the diagnosis of CMPA is “likely” if patients present such as skin prick or patch tests.
with suggestive symptoms and (one of) these test GER(D) has always been mentioned as
show(s) positive results. But, CMP can also lead one of the presenting manifestations of CMPA.
to non-IgE dependent reactions. Some symptoms Buisseret mentioned “vomiting” as a typical
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presenting symptom of CMPA in a Lancet paper signs and symptoms, the milk volume that
in 1978 (5). Forget reported in 1985 a small series provokes the symptoms and to give symptomatic
of 15 children presenting with recurrent vomiting, treatment if needed (10). The starting dose during
not responding to GER therapy, that became milk challenge should be lower than a dose that
symptom-free on a CMP-free diet (6). Difficulties can induce a reaction and increase stepwise to 100
to demonstrate the relation between CMPA and mL (1,10). More details on the practical aspects
GER are illustrated in the study by Nielsen et al. (7). of a challenge test are discussed elsewhere (1). To
The authors performed a 48 hour pH monitoring rule out a false positive test result due to lactose
in infants presenting with GERD and cow milk intolerance the challenge procedure should be
hypersensitivity; they could demonstrate that the performed with a lactose-free CMP-containing
pH monitoring was more abnormal in infants with milk (10). Challenges should be carried out in a
“GERD and allergy” than in the other groups, but hospital setting in the following circumstances:
a challenge test did not increase reflux (7). Ravelli a previous history of immediate type allergic
et al. used electrogastrography to show that gastric reactions, unpredictable reaction such as in infants
motility reacted different to a CMP-challenge in with positive IgE sensitivity who has never been
control infants, infants with GERD and infants given cow’s milk or has not been given cow’s
with CMPA (8). This abnormal motility could be milk for a long time; severe atopic eczema (due to
related to a delayed gastric emptying (8). A cow´s difficulty in assessment) (10).
milk challenge increases weakly acidic reflux (pH It is known that a double blind challenge
> 4 and < 7) in children with CMPA and GER reduces the number of infants considered
(9) Impedance-pH monitoring may therefore be “allergic” after a positive open challenge with
useful in identifying a subgroup of infants with about one third (11). Infants that react 24 hours
cow’s milk protein-induced GERD (9). or even later to a challenge or react only to large
Unfortunately, only rough estimates can volumes, may not be picked-up by a double
be made on the prevalence or incidence of GI- blind challenge. Although symptoms during the
manifestations of CMPA. The consequence of challenge are most of the time the same as the
the definition that not every allergic reaction is original presenting symptoms, this is not a dogma.
IgE mediated in combination with the fact that During challenge, presenting symptoms may differ
today only IgE-reactivity can be measured in from the original. As said before, infants with non-
daily routine is that non-IgE mediated allergy IgE mediated CMPA tends to become tolerant to
has become a synonym for intolerance or adverse CMP more rapidly than those with IgE mediated
reaction. Studies using a stringent scientific CMPA. The higher the IgE level, the more likely
approach focus mainly on IgE mediated allergy the allergy is going to persist (12). This means that
and/or a positive challenge test, and report 2 to 5% if a challenge is performed some months after the
as the incidence of CMPA. However, up to 10 % initial suspected diagnosis and turns out negative,
or even 15% of the infants seem to develop “some it cannot be concluded that the original diagnosis
adverse” reactions to cow´s milk. of CMPA was erroneous. A negative challenge
There is a quite broad consensus that in only means that at the moment of the challenge the
infants a challenge test can be performed “open”, food is tolerated. And a positive challenge does
mainly because of the complexity of a double blind not confirm that the immune system is involved.
challenge (1). If no symptoms are elicited within Bearing all the above in mind, it seems
two weeks of regular cow´s milk feeding, CMPA reasonable to estimate that between 5 to 10 %
can be excluded. Challenge tests can be performed of the formula fed infants will develop some
in an in-patient or out-patient setting to document
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Motility and food allergy
adverse reaction to CMP. Unfortunately, there include them in guidelines (10). The NASPGHAN-
are insufficient data on the number of supposed ESPGHAN guidelines on the management of
allergic infants that present “only” with GI regurgitation and reflux, recommend in distressed
manifestations. About 20 % of all 3-4 month and regurgitating infants a therapeutic approach
old infants regurgitate more than 4 times a day, with either thickened formula or either an
and this seems to be a threshold for mothers to extensive hydrolysate (13). If a thickened “regular
seek medical help (13). It is probably reasonable infant formula” results in a significant reduction of
to estimate the (recent) prevalence of infant episodes of regurgitation, allergy seems unlikely
constipation below 5%. Prebiotic-supplemented since protein structure did not change. But what
formula is well tolerated by full-term infants. It if an extensive hydrolysate results in a significant
increases stool colony counts of bifidobacteria and reduction of regurgitation? Since hydrolysates
lactobacilli and results in stools similar to those of have a much faster gastric emptying than native
breastfed neonates without affecting weight gain protein, and since delayed gastric emptying is
(14,15). The administration of L reuteri (DSM a pathophysiologic mechanism causing GER,
17938) in infants with chronic constipation had improvement of regurgitation with a hydrolysate
a positive effect on bowel frequency, even when cannot be considered as a proof of allergy. Partial
there was no improvement in stool consistency hydrolysates are not indicated in the treatment
and episodes of inconsolable crying episodes (16). of CMPA (1,10). Partial hydrolysates may be
In the light of the difficulties to distinguish tolerated in about half of the infants with IgE-
between allergy and adverse reactions and mediated CMPA (17). Partial hydrolysates are
functional disorder, the question arises if “the also considered to be more “easily digested”,
overall prevalence of GI-complaints” could although scientific evidence for this statement
not be considered as an equivalent for “IgE and is missing. Several infant formula companies
non-IgE mediated” allergy? In order to obtain commercialised thickened partial hydrolysates. As
more accurate data on prevalence and incidence, a consequence, a thickened extensive hydrolysate
pro-active data collection via questionnaires in may be considered as a treatment option in infants
representative population samples is mandatory to presenting with troublesome regurgitation and in
minimise the impact of parental coping with these whom “allergy” would be a plausible diagnosis
frequent symptoms. on clinical grounds. This attitude would mean
In daily primary health care, it is not that a number of non-allergic infants are given
easy and possibly even not clinically relevant an extensive hydrolysate for no reason, and that
to separate functional disorders from non-IgE a number of allergic infants are given a thickened
mediated allergy if therapeutic options tackling formula for no reason. But, up to now there is no
both conditions can be offered. Efficacy of certain convincing literature regarding nutritional adverse
therapeutic interventions do not help to separate events of a thickened formula or an extensive
non-IgE mediated allergy from functional GI- hydrolysate, if cost is not considered. In difficult
manifestations. The recommended treatment of cases, amino acid based formula (AAF) may
CMPA is elimination of CMP from the mother´s contribute to separate infants with CMPA from
diet in breastfed infants, amino acid based formula those with reflux. Indeed, about 5% of the CMPA
in formula fed infants with “severe” manifestations infants may still react to an extensive hydrolysate
of CMPA (life threatening symptoms, failure to (1). If that is the case, the infant will improve with
thrive) or extensive hydrolysates for the majority AAF. Mainly because AAF are very expensive,
of infants (1,10). Published evidence with the and because reimbursement systems differ from
new rice hydrolysates is too recent and limited to country to country, there is still debate whether
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Motility and food allergy
AAF should be used “first line” (in all infants) or as a “functional disorder” on soy formula exists,
“second line” (only in infants not improving on probably with the same frequency as functional
eHF). A long-term elimination diet and feeding constipation with regular infant formula. Again,
restrictions may lead to intake problems during whether this is “functional” or “non-IgE mediated
diversification. In “clear-cut” CMPA, the CM-free allergy” can be debated. Is constipation really a
diet is recommended at least during 6-9 months symptom of CMPA? According to data from Italy,
and up to the age of 1 year (1). the incidence of constipation is not different in
The difficulties to diagnose CMPA atopic and non-atopic children (19). Therefore,
strengthen the importance of prevention. Infant constipation as single manifestation of CMPA
formula is derived from cow´s milk for the simple seems to be relatively rare. “Anti-constipation
reason that there are there are many cows and formulas” have been commercialised. Although
because cows provide a lot of milk. There is broad some of these formulas have been evaluated
consensus that almost every constituent of cow´s in small trials (20,21), scientific evidence is
milk needs to be adapted according to better fulfil very limited. Since extensive hydrolysates are
the nutritional needs of infants: the total amount known to cause greenish semi-solid stools, their
and proportion of protein, the amount of minerals, use could be considered, although there are no
the addition of nucleotides, LcPUFAs, etc. So, data on the efficacy of extensive hydrolysate in
why not accept that it would also be preferable to infant constipation. An interaction between GER/
change the structure of the proteins and feed every regurgitation and constipation has been advocated
infant a (partial) hydrolysate? Unfortunately, data as well. Frequent regurgitation will result in an
showing benefit of doing so are limited to at-risk excessive loss of water, and may therefore be
populations. There are very limited data showing considered as a risk factor for constipation.
a reduction of CMPA in the general population. In older children, the relation between
This is merely the consequence of methodological functional GI disorders and CMPA seems better
problems regarding the size of the needed study established. In a case control study; 10/52 subjects
populations. There are in absolute numbers more (19.2%) with a diagnosis of CMPA but with a mean
allergic children in the non-at risk group than in age of 8.1 ± 4.48 years, met the Questionnaire
the at-risk group, for the simple reason that the on Pediatric Gastrointestinal Symptoms Rome
non-at-risk group is much larger. III version criteria for diagnosis of an FGID (7
Regarding constipation, a similar irritable bowel syndrome, 2 functional dyspepsia,
criticism can be hypothesised. Several studies 1 functional abdominal pain), whereas none in the
mentioned constipation as a (frequent) symptom control group did (22).
of CMPA. But milk, especially casein, is known
to constipate. Hydrolysates are known to cause CONCLUSION
soft, greenish stools. One of the studies on CMPA
and reflux used soy formula as treatment, thus It is extremely difficult, virtually still
avoiding the stool-softening effect of hydrolysates impossible today, to separate “non-IgE mediated
(18). However this study can be criticised because allergy” from “functional disorders” in infants
it was reported that soy formula was effective in presenting with GI adverse reactions to cow’s
100% of the CMPA allergic infants, while there is milk based formula.
consensus that at least some (around 10%) CMPA If more than one organ system is involved,
infants develop also allergy to soy. Moreover, the diagnosis of “allergy” is much more likely
paediatric gastroenterologists “know” (although than “functional disorder.
epidemiologic data are missing) that constipation In distressed infants presenting with
153