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Atopic Dermatitis: Role of Food House Dust Mite Allergens: Methods
Atopic Dermatitis: Role of Food House Dust Mite Allergens: Methods
Atopic Dermatitis: Role of Food House Dust Mite Allergens: Methods
G.J.A. Casimir, MD, Ph1Y; J. Duchateau, MD, PhD; B. Gossart; Ph. Cuvelier, MIY;
F. Vandaele, MD*; and H.L. Vis, MD, PhD*
ABSTRACT. Objective. The aim of this study was to The prevalence of atopic disease in the general
evaluate the humoral immune response to cow milk population has increased in the developed countries
(CM) protein, soya protein, and house dust mites in a
during the past 25 years and is usually estimated to
group of 64 CM-fed infants, who had atopic dermatitis as
the sole atopic manifestation, by measuring not only IgE affect 10% to 20% of individuals.12 So the prevalence
but also specific IgG antibodies (Ab) against bovine of atopic dermatitis (AD) has increased from 3% to
IJ-lactoglobulin, soya float aqueous extracts, and Der P1 4% of the population during the 1960s to 10% in the
antigens. 198Os.
Methods. A CM-free diet (Nan HA, Nestle) was given
In 60% of cases, the disease begins before the age of
to these 64 CM-fed infants and the sensitivity to CM
I years and usually in the second or third month.
proteins was established by a positive challenge test with
the offending food in improved infants. The serum was However, it can occur earlier, and several cases have
obtained just before the start of the CM-free diet, at the been described
in which the disease appeared during
first consultation. The patients were dassified into two the second or third week after birth.
groups according to their clinical response to the hy- The role of food allergy has been clearly estab-
poallergenic formula.
lished as a trigger of AD in infants. In particular, cow
Results. Thirty-one infants (group 1) improved dra-
matically (positive challenge test), and 33 (group 2) did milk (CM) proteins are known to provoke clinical
not improve with the exclusion diet but did improve af- symptoms in the skin, in the form of itching, AD, and
ter eviction of dust-producing items in the environment. urticaria.6 Atopic dermatitis in CM protein allergy is
The two groups were different in terms of their total IgE observed in about 30% of cases.7 It can be favored by
immunoglobulin concentration (higher in group 1, P <
regional dietary habits such as precocious weaning
.05) and concentration of specific IgE Ab against CM
protein (more frequent in group 1, P < .01). The IgG Ab
or reduced by prophylactic use of casein hydrolysate
concentrations against -lactoglobulin, the major CM formulas.8
antigen (P < 10-4), and against soya protein (P < .01) The role of inhalants such as house dust mites
were significantly more elevated in the group improved (HDM) in the pathogenesis of AD has been suspected
by the diet, with a threshold above which the response on the basis of several observations, including the
to the exclusion diet could be predicted as positive. On
positivity of direct skin tests, the presence of specific
the contrary the level of specific IgG Ab against house
dust mites was four times higher in group 2 than in IgE antibodies,9 the improvement of the disease after
group 1. Twenty-nine of the 33 infants of group 2 im- reduction of the quantity of antigens,1#{176} and, finally,
proved after eviction of dust-producing items in the the fact that children suffering from AD, born during
environment. the months of maximal exposure to mite, show a
Conclusions. It is proposed that specific IgG Ab con-
higher prick-test reactivity.
centrations against I3-lactoglobulin, soya protein, and
Der P1 antigen be determined in infants and children Cow milk, like HDM, can induce a specific anti-
suffering from atopic dermatitis as a means of predicting body response in symptomatic and healthy per-
the response to an exclusion diet, and a possible role of sons1112 of all Ig classes (C, M, A, D, and E). The
house dust mites in the pathogenicity of the disease is diagnosis of CM protein allergy is usually estab-
suggested. Pediatrics 199392:252-256; atopic dermatitis,
lished by the presence of specific reagins, demon-
allergens, house dust mites.
strated by their quantification in the serum or by
positive skin-prick tests. However, the correlation be-
ABBREVIATIONS. AD, atopic dermatitis; CM, cow milk; HDM,
tween specific IgE in the serum or positive skin-prick
house dust mite; SP, soya protein; Ab, antibody; BLG, bovine
-lactoglobulin; Der P1 antigen, major allergenic protein of HDM tests and the challenge test is poor (60% and 53%,
extract. respectively); comparative sensitivities are, respec-
tively, 56% and 44% and specificity 67% (for IgE and
skin-prick test).13
From the *H#{244}pital Universitaire des Enfants Rome Fabiola; Department of The aim of this study was to evaluate the humoral
Immunology, H#{244}pital Universitaire Saint-Pierre; and Free University of
immune response against CM protein, soya proteins
Brussels, Belgium.
Received for publication Nov 20, 1992; accepted Mar 1, 1993. (SP), and HDM in infants with AD, by measuring not
Reprint requests to (G.J.A.C.) Head of Ailergy-Pulmonology Unit, H#{244}pital only IgE but also specific IgG antibodies (Ab) against
Universitaire des Enfants Reine Fabiola, Universit#{233} Libre de Bruxeiles
bovine 13-lactoglobulin (BLG), soya flour aqueous
(ULB), Avenue II Crocq 15, 1020 Brussels, Belgium.
PEDIATRIcS (ISSN 0031 4005). Copyright C 1993 by the American Acad- extracts, and the major allergenic protein of HDM
emy of Pediatrics. extract (Der P1 antigens).
Measurements
consent
acariddes
was obtained
(eg, Timasil).
from the parents for each child.
Statistical
The
analysis.
Analysis
Mann-Whitney and x tests were used for statistical
In all cases, total IgE and specific IgE and IgG Ab concentrations RESULTS
were measured against two food allergens (CM and SP) and
against HDM. The measurements of total IgE and of specific IgE
Tables I and 2 and Figs 1 through 4 summarize the
Ab were performed using the Pharmacia CAP system (Brussels, results.
Belgium) (F2 allergen for CM, f14 for SP, and Dl for HDM). Of 64 infants, 31 (group 1, 48%) were dramatically
The serum was obtained just before the start of the CM-free improved by the CM-free diet. Thirty-three infants
diet, at the first consultation.
(group 2, 52%) did not improve with the diet. The age
For the detection of specific IgG against milk proteins, the major
CM allergen was chosen: purified bovine BLG (Sigma). Soya flour at time of diagnosis and the sex ratio were not sta-
aqueous extracts and Der P1 (Bencard) antigens were the other tistically different for the two groups.
two allergens tested. Anti-BLG, anti-SP, and anti-Der P1 IgG Ab The Hanifin score was not statistically different in
levels were determined in a solid-phase enzyme-linked immuno- the two groups of patients when they were enrolled
sorbent assay test as follows: 96-well polystyrene microplates
(NUNC) were passively coated with the antigens to be tested (50
in the study, before the start of the CM-free diet.
pg/mL of carbonate buffer, pH 9.2) and the adsorption capacities The median total IgE Ab concentration was higher
were then saturated with gelatin (Hemacel, 3% vol/vol); after a in the improved infants than in the others (71 and 22
Group I Group 2 P
Enrollment n = 31 n = 33
Age at inclusion, mo
Median 4 4.5 NS
Range 0.5-36 0.5-51
Boys 20 16
Girls 11 17
Total IgE, IU/mL
Median 71 22 <.05
Range 4-1540 2-700
Antibodies
RAST CM + (N < 0.35 PRU/mL) 12 2 <.01
RAST soya + (N < 0.35 PRU/mL) 3 2 NS
RAST HDM + (N < 0.35 PRU/mL) 8 8 NS
Anti-BLG IgG (AU) 4
Median 436 91 <10
Range 309-6205 19-291
SD 1140 63
Anti-SP IgG (AU)
Median 45 24
Range 11-3141 9-436 <.01
SD 584 74
Anti-Der P1 IgG (AU) 4
Median 31 126 <10
Range 8-590 5-1000
* Abbreviations: RAST, radioallergosorbent test; CM, cow milk; PRU, peripheral resistance unit; HDM,
house dust mite; BLG, 13-lactoglobulin; AU, arbitrary unit; SP, soya protein; Der P1, Der P1 antigen,
major allergenic protein of HDM extract; NS, not significant.
Group 1 Group 2
Erythema 2.8 0.7 0.8 0.2 1.7 0.6 2.7 0.6 2.6 0.7 2.0 0.2
induration 1.7 0.2 0.4 0.1 1.4 0.8 1.8 0.3 1.9 0.3 0.8 0.2
Pruritus 2.7 0.6 0.3 0.2 2.1 0.7 2.5 0.7 2.3 0.6 1.1 0.3
* Values represent mean SD. CM-free D, cow-milk-free diet; HDM, house dust mite.
DISCUSSION
This prospective clinical study documents the es-
sential role of CM proteins in the development of AD
in infants, as already documented by several au-
thors,7 but it also shows that pneumallergens such as
HDM could play a major role in the illness, even in
infants. We used two criteria to assess the role of CM
*IIL..IIJt
in the illness: the beneficial response to a CM-free
beforeafter CM freeD,after challenge diet and a positive challenge test with CM proteins,
erythema #{149} induration #{149} pruHt using the
clinical score of Hanifin as an integrated
Fig 1. Hanifin scores for group 1. CM-free D, cow-milk-free diet. parameter of clinical improvement.
The observed prevalence of 48% (31 /64 cases) of
improved patients under a CM-free diet confirms the
results of other studies.17
Nan HA is primarily recommended, as are other
hypoallergenic formulas, for prophylactic use18 in in-
fants considered to be at risk on the basis of a family
history of allergy and/or positive IgE screening at
birth.
However, since this study was conducted, a few
cases of clinical reaction to hypoallergenic formulas
(casein and whey protein hydrolysates), prescribed
for therapeutic use, have been reportecP920; in
most cases these clinical manifestations disappeared
with the introduction to the diet of a semielemental
beforeafter CM freeD,HDM eviction formula.
erythema induration prurit
These observations clearly indicate that no protein
Fig 2. Hanifin scores for group 2. CM-free D, cow-milk-free diet; hydrolysate formula can offer absolute protection
HDM, house dust mite.
against allergic reactions when used therapeutically
with food-allergic patients. Of course, our aim in this
study was not to determine whether or not Nan HA
IU/mL, respectively). Some infants had low IgE 1ev- was safe, but to analyze the immunological response
els, but they were no different from the others in of patients, by recording their clinical response both
terms of their clinical symptoms or anamnestic data. to the diet and to challenge with CM proteins.
Specific IgE Ab were found in 39% (12/31) of the All of the infants were classified as high IgE re-
CM-free diet-improved infants and in only 6% (2/33) sponders, as their total IgE serum concentration ex-
of the unimproved group; this difference was signif- ceeded normal values for an age-matched control
icant (P < .01), although there was no difference group.21 The median IgE value of group I was higher
between the two groups for specific IgE against SP than that of group 2, reflecting the stimulated pro-
(10% and 6%) and against HDM (26% and 24%, duction of reagins in response to food antigens,
respectively). which might be related to the importance of expo-
IgG Ab concentrations against BLG and against SP sure to these allergens in this case.
were significantly more elevated in group I (im- Detection of specific IgE Ab to CM was very poorly
proved by the diet) than in group 2. All patients in indicative of sensitization status, being found in only
group I had IgG Ab against BLG above a threshold of 39% (12/31) of group 1 infants, although the level of
300 arbitrary units. The median anti-BLG IgG Ab specific reagins was higher in good CM-free diet re-
concentration was four times greater in group I than sponders. These results are in agreement with those
in group 2 (two times greater for SP); in contrast, the reported elsewhere despite using the recently mod-
level of specific IgG Ab against HDM was four times ified radioallergosorbent test from Pharmacia (CAP
higher in group 2 than in group I. system). Indeed, the CAP system is reported to be
6000 2
,- 5000
200
, 4000
0
3000
. 2000
1000
C
Fig 3. Immunogiobulin G antibodies OH vaSuss ovs 300 A.U. oil voluss imdv 300 A.U.
against bovine 13-iactogiobulin (BLG)
and soya protein in groups I and 2.
AU, arbitrary unit.
GroLp 1.IgG soya GL9 2J soya
3500 454
400
30
350
: 300
200
1500
. 1
100
100
500
Sc
39% (12/31) of group I infants, although the level of with symptoms of CM protein allergy. But it was not
specific reagins was higher in good CM-free diet re- possible to discriminate clearly between these pa-
sponders. These results are in agreement with those tients on the basis of their Ab concentrations because
reported elsewhere despite using the recently mod- of the lack of a clear-cut limit between asymptomatic
ified radioallergosorbent test from Pharmacia (CAP and symptomatic patients.
system). Indeed, the CAP system is reported to be Applying a clinical criterion (the response of
more sensitive than its former equivalent, owing to symptomatic CM-fed infants to a CM-free diet), we
the increased availability of bound antigen in vitro. observed a threshold of anti-BLG Ab concentration
A similar lack of sensitivity also has been reported above which all patients are good responders to the
for skin tests17 showing that circulating or tissue- exclusion diet: All these patients showed a level of
fixed IgE Ab could not be detected at all in about one anti-BLG Ab titer above the threshold of 300 arbi-
third to one half of young atopic patients applying trary units in our test system. This concentration
the investigation criteria. When compared with the could be used as a prospective criterion of the ex-
patients of group 2, those of group I were more pected clinical response to a CM-free diet of CM-fed
frequently CM IgE Ab positive, whereas the preva- patients with AD. This confirms our experience for
lence of SP and HDM antigens was similar (in the other clinical manifestations, eg, asthma or allergic
two groups), indicating the relative specificity of CM rhimtis.- Firer et a124 also found that in AD patients
protein IgE detection. Ig Ab concentrations against CM allergens can be
Surprisingly, 25% (8/31) of subjects had detectable elevated.
levels of IgE Ab against HDM, whatever their re- The serum level of anti-Si IgG Ab was also higher
sponse to the CM-free diet, a result emphasizing the in infants of group 1, which could reflect the already
extent of early sensitization of the atopic infants to described association between SP and CM protein
this antigen (see below). We known that immune- hypersensitivity observed in about 30% of cases.6
globulins (A, M, G) against CM proteins can be The patients of group 2 had significantly higher
found in all subjects receiving CM in their daily diet, serum concentrations of anti-Der P1 IgG Ab than
but show more elevated concentrations in patients those of group 1, suggesting the possible role of
MIAMI, July 9-In a decision that could signfficantly broaden childrens rights if
upheld, a juvenile court judge in Orlando ruled today that an 11-year-old boy has
the legal right to sue for separation from his parents.
Judge Thomas S. Kirk held that the boy . . . has standing to request that all legal
ties to his parents, whom he accuses of abandonment and neglect, be severed.
Though a minor, the boy has the same constitutional right to protect his funda-
mental interests as an adult ...
Rohter L Boy wins right to sue parents for separation. The New York Times. July 10, 1992.
Noted by J.F.L., MD
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been published continuously since . Pediatrics is owned, published, and trademarked by the American
Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright
1993 by the American Academy of Pediatrics. All rights reserved. Print ISSN: .
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://pediatrics.aappublications.org/content/92/2/252
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has
been published continuously since . Pediatrics is owned, published, and trademarked by the American
Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright
1993 by the American Academy of Pediatrics. All rights reserved. Print ISSN: .