PEDIATRICS (ISSN 0031 4005). Copyright © 1990 by the American Academy of Pediatrics.
Allergy
Pathophysiology
EFFECTS OF COMBINED MATERNAL AND INFANT FOOD-ALLERGEN AVOIDANCE ON DEVELOPMENT OF ATOPY IN EARLY INFANCY: A RANDOMIZED STUDY
Zeiger RS, Heller S Mellon MH, et al. J Allergy Clin Immunol. 1989;84:72-89.
Study Population
Study infants were born between November 12, 1981 and July 25, 1984. They were selected from a group who had parents with a history of atopy.
Methods
Participants were divided into two groups.
I. Prophylaxis Group (N = 103). During the third
trimester and while they were breast-feeding, women were instructed to avoid totally all milk, egg, and peanut products, to avoid concentrated soy (tofu), to limit wheat to no more than two servings daily, and to use other grains to fulfill their cereal and starch needs. They were also given prenatal vitamins and calcium supplements of 1500 mg daily. When breast-feeding was stopped, Nutra-migen was to be fed to the baby until 12 months of age. They were to avoid solid foods until 6 months of age, starting with nonlegume vegetables followed by rice at 7 months, meat at 8 months, noncitrus juices at 9 months, cow’s milk at 12 months, and wheat, soy, corn, and citrus thereafter at monthly intervals.
II. Control Group (N = 185). Women in the control
group were encouraged to follow standard diets for preg-nancy and lactation, and they were given Enfamil when discontinuing breast-feeding. They were instructed to introduce solid foods as per the American Academy of Pediatrics recommendation.
III. Common to both study groups were the encourage-ment of breast-feeding for at least 4 to 6 months and the use of Tri-Vi-Flor. Parents were given intensive educa-tion on reducing environmental allergens and tobacco smoke in the house.
Findings
The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated group (16.2%) com-pared to the control group (27.1%), resulting from re-duced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% vs 16.4%), caused primarily by fewer positive mild skin tests (1% vs
12.4%). The prevalence of allergic rhinitis, asthma, and inhalant skin test was unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower at 4 months only, and comparable at 24 months.
Reviewer’s Comments
This rigorous food avoidance schedule makes it diffi-cult to suggest this routinely to all parents. It also sup-ports the clinical observation that food allergy appears to be important in skin-associated problems, but less so with manifestation of atopy in the respiratory tract.
RUSSELL J. Hopp, DO
Omaha, NE
EFFECT OF MATERNAL AVOIDANCE OF EGGS, COW’S MILK, AND FISH DURING LACTATION UPON ALLERGIC MANIFESTATIONS IN INFANTS
Hattevig G, Kjellman B, Sigurs N, Bj#{246}rkst#{233}nB, Kjellman NIM. Clin Exp Allergy. 1989;19:27-32. Purpose of Study
This study was conducted to determine if a 3-month avoidance of eggs, cow’s milk, and fish by mothers breast-feeding their infants would reduce allergic disease of these infants.
Methods
All pregnant women receiving prenatal care at two Swedish hospitals were invited to take part in the study if atopy was likely to be present. The likelihood of atopy was determined by the presence of allergic disease in both parents, or one parent plus one sibling, or two siblings. If only one parent or one sibling had allergic disease, the infant’s cord blood had to be at least 0.9 kU/m. One hospital used the diet restriction, the other did not. Examinations were performed at 3, 6, 9, 12, and 18 months. Skin-prick test to egg white, cow’s milk, and fish were done at 9 months.
Findings
Atopic dermatitis incidence was less for the infants of mothers who restricted their diet. However, this was significant only at 3 and 6 months. There were no differ-ences for bronchial obstruction, urticaria, anaphylaxis, rhinitis, or conjunctivitis at any age. There were no significant differences between the infant groups by skin tests performed at age 9 months.
Conclusion
mci-dence and severity of atopic dermatitis for the first 6 months of life of atopic infants. However, other allergic manifestations and skin test sensitivity at 9 months were unaffected.
Reviewer’s Comments
The same study using a longer duration of dietary control would be indicated. A control group of formula-fed infants would also be interesting. Another treatment group, using an elemental formula, would be very helpful in determining if other food allergens via breast milk would account for the overall poor results from maternal dietary control. We still need data from such studies to best advise “breast or bottle,” and what to put in the breast (via mother’s diet) or in the bottle.
CLIFTON T. FURUKAWA, MD Seattle, WA
THE NATURAL HISTORY OF PEANUT ALLERGY
Bock SA, Brian MD, Atkins FM. J Allergy Clin Immunol. 1989;83:900-904.
Purpose of Study
This study was designed to investigate the persistence of peanut allergy years after the diagnosis had been confirmed.
Methods
Between 1974 and 1985, 114 children, aged 1 to 14 years, were examined by a double-blind peanut challenge because of a history of adverse reactions to peanuts. Out of this group, 56 children had a positive double-blind peanut challenge manifested by gastrointestinal, cuta-neous, and/or respiratory symptoms. Of the 46 children with positive challenges, 32 were included in a longitu-dinal study. Contact was made with these subjects in 1987 and 1988, 2 to 13 years after their initial double-blind peanut challenge. Telephone interviews were con-ducted and the following information was obtained: (1) precautions taken to avoid peanut ingestion, (2) the most recent ingestion of peanuts (accidental or intentional), (3) symptoms that occurred, (4) treatment required, (5) any other symptomatic ingestion since the original chal-lenge, and (6) any further evaluation including skin test-ing or subsequent deliberate challenge with peanut under medical supervision. (There was none; all declined further oral challenges.)
Findings
Of the 32 patients, 8 had avoided peanuts completely since the original positive challenge. Sixteen patients had experienced symptoms caused by accidental peanut ingestion in the year before contact. Eight patients had reacted to accidental ingestion in more than 1 year but less than 5 years before contact. All subjects still exhib-ited a positive peanut puncture skin test. The loss of
their peanut reactivity could not be demonstrated in the patients.
Conclusion
This study suggests that it is uncommon for peanut-sensitive patients to lose their clinical reactivity.
Reviewer’s Comments
Although 32 subjects were instructed on peanut avoid-ance and made an effort to avoid peanut ingestion, 24 subjects still experienced accidental peanut ingestion. This indicates the need for more effective methods of educating food-allergic individuals in both avoidance and treatment. Hopefully, similar studies will be undertaken in an attempt to determine which food allergies persist and which food reactions are likely to resolve with time in order to counsel our patients better.
DONNA L. SCHUSTER, MD
Herndon, VA
PASSIVE EXPOSURE TO CIGARETTE SMOKE DOES NOT INCREASE ALLERGIC SENSITIZATION IN CHILDREN
Ownby DR, McCullough J. J Allergy Clin Immunol. 1 988;82:634-638.
Purpose of Study
This study was conducted to determine if children exposed to passive parental cigarette smoke would be sensitized more frequently to common allergens or would have elevated levels of allergen-specific IgE.
Study Population
Children in two groups were 2 to 17 years of age. The first group consisted of 100 children from a general pe-diatric practice selected solely because of need for venous blood draw. The second group of 91 patients was from the same pediatric practice, referred because of respira-tory tract symptoms and need for allergy evaluation.
Methods
Both pediatric cohorts were required to answer a ques-tionnaire regarding family smoking habits, and a sample of blood was drawn to measure levels of IgE and IgD. IgE levels specific for cat, dog, mite, ragweed, grass, cockroach were done by enzyme-linked immunosorbent assay.
Findings
Reviewers’ Comments
Passive smoke exposure has been related to exacerba-tion of respiratory complaints. Apparently this mecha-nism is not related to sensitization of children to common allergens by passive smoking. As exposure to smoke tends to exacerbate asthmatic symptoms, however, passive ex-posure to smoke should still be avoided.
RUSSELL J. Hopp, DO
Omaha, NE
ALMA M. HERRERA, MD
Washington, DC
Diagnosis
RELATIONSHIP BETWEEN SKIN-PRICK TESTS, THE MULTIPLE ALLERGOSORBENT TEST, AND
SYMPTOMS
OF ALLERGIC
DISEASE
Finnerty JP, Summerell 5, Holgate ST. C/in Exp Allergy. 1 989;1 9:51-56.
Purpose of Study
This study was conducted to investigate how well a new in vitro method for specific IgE measurement (the MAST-CLA) correlates with scratch testing and clinical history.
Study Population
Forty-seven atopic patients (predominantly adults) who volunteered to undergo immediate skin-prick testing and donate a blood sample for MAST-CLA.
Methods
Immediate skin-prick testing was carried out using 10 common aeroallergens including dust mite, mold, cat, grass, and certain other pollens. A positive skin test was defined as one having a wheal diameter greater than or equal to 5 mm. The MAST-CLA test was done using the same antigens. The technique consisted of the patient’s serum reacting with multiple cellulose threads, each one precoated with a specific antigen. The degree of specific IgE binding to antigen on the string was determined by incubating the string with a goat anti-human IgE labeled with horseradish peroxidase. To quantify this binding a photoreagent mixture (which has luminescence in the presence of horseradish peroxidase) was then reacted with the string, and the chemiluminescence was recorded on Polaroid film. The individual brightness of each “white band” was measured by a densitometer and correlated directly with the amount of specific IgE present in the patient’s serum. Subjects also completed questionnaires, and from this it was clinically determined if a patient was grass and/or cat allergic.
Findings
Overall total agreement (agreed positive and agreed negative results) between the two types of testing was 78.5%. Correlation between MAST-CLA and skin testing
was statistically significant for all allergens except Alter-naria where the agreement was quite poor. MAST-CLA results agreed with the patient’s clinical history of sen-sitivity to grass and/or cat in 75% to 85% of cases; skin testing resulted in an agreement of 75% to 83%.
Conclusions
1. There is strong agreement between conventionally positive wheal skin-prick tests (wheal greater than 5 mm) and MAST-CLA results in 9 of 10 different aeroallergens studied (agreement 78.5% of time).
2. Poor agreement was found between these two tests when Alternaria was the allergen.
3. MAST-CLA was as good as skin-prick testing in predicting a true clinical allergy (based on history) to grass and cat.
4. These agreement findings are similar to previously reported results for the radioallergosorbent test.
MICHAEL J. WELCH, MD
San Diego, CA
SKIN TESTING AT THE CESSATION OF
IMMUNOTHERAPY
Schuller D. Pediatr Asthma Allergy Immunol. 1 988;2:1 29. Purpose of Study
This study was conducted to evaluate the need to repeat allergy skin testing at the termination of immu-notherapy.
Study Population
Children aged 3 to 14 years were enrolled in the study if they were observed by the investigator for 2 years following completion of a course of immunotherapy.
Methods
All children received a course of immunotherapy. In selected children (nonrandom) skin tests were repeated following the completion of a course of immunotherapy. In children with positive skin tests after immunotherapy appropriate environmental controls were undertaken. During the observation period a scoring system was de-vised to assess symptoms and medication use. Children were observed for a minimum of 2 years.
Findings
Reviewer’s Comments
The findings in this study agree with previous litera-ture which indicates that repeat skin testing following a course of immunotherapy is of little value in most pa-tients. This study, however, is plagued by its retrospective design. In addition, the author does not provide us with the antigens used for skin testing. There also is no specific information regarding allergen avoidance techniques used in selected patients. Finally, children selected for skin testing were not selected on a random basis.
JOHN A. ZORA, MD
Atlanta, GA
CROSSALLERGENICITY IN THE LEGUME BOTANICAL FAMILY IN CHILDREN WITH FOOD HYPERSENSITIVITY
Immunol. 1 989;83:435-440.
Purpose of Study
J. Sampson HA. J Allergy Clin
Peanut and soybean are two of the most common food antigens causing allergic reactions in food-allergic chil-dren. Many allergists feel that a person allergic to peanut also is most likely allergic to other legumes because of common cross-reactivity substances. The purpose of this study was to investigate if multiple legume food allergies are common or uncommon despite extensive cross-reac-tivity observed with skin-prick tests and radioallergosor-bent test results.
Methods
The study group consisted of 69 children with one or more prick tests positive to legume (peanut, soybean, green bean, pea, and lima bean). All patients were off antihistamines for 7 to 10 days, cromolyn sodium for 1 month, and all suspect foods were eliminated from the patients’ diets for 7 days before challenge. Each patient was admitted to the hospital and was challenged to five legume antigens (peanut, soybean, pea, green bean, and lima bean) by double-blind, placebo-controlled oral food challenge unless there was a recent history of a life-threatening anaphylactic reaction to one of the foods suspected. Two double-blind challenges were performed each day, one containing placebo and the other contain-ing the challenge food substance. Up to 8 to 10 g of powdered food or placebo substitute was administered in opaque capsules or given during a 1-hour period in in-creasing doses. The type, severity, time of onset, and duration of symptoms were recorded for each challenge.
Findings
Among the 69 patients challenged, 43 positive reac-tions occurred in 41 patients (59%). Only 2 of 41 patients with challenge-proven legume sensitivity (5%) had clini-cally relevant food hypersensitivity to more than one legume. Both of these individuals had a history of
ana-phylaxis after peanut ingestion and a positive double-blind, placebo-controlled oral food challenge to soybean. These two patients consumed the other legume antigens without difficulty. Peanut hypersensitivity accounted for 31 of the positive reactions (72%), soybean accounted for 10 (25%), and pea accounted for two (5%) of the positive challenges. There were no positive challenges with green bean or lima bean. 87 of 130 positive skin-prick tests (66%) were clinically false positive.
Among patients with a positive prick test to peanut (N
= 60) the mean wheal size was larger in patients with a
positive vs a negative oral food challenge to peanut (P <
.001).
Conclusion
The results of these oral food challenges demonstrated that clinically important cross-reactivity to legumes in children is very rare.
Reviewers’ Comments
This study contradicts claims that clinically relevant intrabotanical cross-reactivity is common in the legume family which is one of the most frequent botanical fami-lies incriminated as being responsible for multiple aller-gies. The authors feel that the practice of individually challenging each suspect antigen should be generalized to all food groups. They feel that following the suggestion will improve patient compliance, life-style, and ease in following a nutritionally complete diet which is less lim-ited.
DONNA L. SCHUSTER, MD
Herndon, VA
DAVID F. GRAFT, MD
Minneapolis, MN
ALMA M. HERRERA, MD
Washington, DC
RUSSELL J. Hopps, DO
Omaha, NE
COTTONSEED HYPERSENSITIVITY: NEW CONCERNS ABOUT AN OLD PROBLEM
Atkins FM, Wilson M, Bock SA. J Allergy C/in lmmunol.
1988;82:242-.250.
Purpose of Study
This study was conducted to report the findings of cottonseed hypersensitivity in patients with severe a!-lergic reactions to foods.
Study Population and Methods
Findings
Skin testing with extracts prepared from ingredients in the food supplements revealed marked sensitization of all the subjects to cottonseed protein. Double-blind food challenge performed in two subjects revealed significant systemic reactions. The remaining subjects were not chal-lenged due to the significant nature of their reactions. Placebo challenges were not positive. Cottonseed protein was thought to be the cause of the systemic reactions in these patients.
Reviewer’s Comments
Cottonseed has a tremendous exposure in daily life: mattresses, pillows, breads, crackers, cookies, etc. Cotton-seed protein is likely to be a relatively important antigen responsible for systemic allergic reactions to ingested products as its exposure increases. It is important to point out that cottonseed oil does not seem to have the same antigen effect as cottonseed protein and appears to be safe in cottonseed protein-sensitive individuals.
ALMA M. HERRERA, MD
Washington, DC
IMPORTED
FIRE
ANT
ALLERGY
IN YOUNG
CHILDREN: SKIN REACTIVITY AND SERUM IgE ANTIBODIES TO VENOM AND WHOLE BODY EXTRACT
Bahna SL, Strimas JH, Reed MA, Butcher BT. J Allergy Clln Immunol. 1 988;82:41 8-424.
Purpose of Study
This study was conducted to compare the levels of serum-specific antibodies to imported fire ant whole body extract to imported fire ant venom to each other in the study group and with those in atopic control subjects.
Study Population
Nineteen children (aged 15 to 39 months) with a his-tory of an imported fire ant sting which was followed by a systemic reaction were studied. Each patient had a history of the characteristic pustule formation.
Methods
All subjects were skin-tested with whole body extract to S invicta and S richteri. Of 19 patients 18 had a skin test 2+ or larger. Serum was tested for total IgE level and for specific IgE antibodies by radioallergosorbent test with whole body extract and venom of S invicta. In vitro studies were compared with those of age- and sex-matched atopic controls.
Findings
The range of total IgE level in serum was not signifi-cantly different than in the control subjects, although it was higher in the study group. The imported fire ant
whole body extract and venom radioallergosorbent test was also higher in the imported fire ant-allergic group, although the imported fire ant whole body extract ra-dioallergosorbent test fell within the same range as 26% of that found in the atopic control group. The imported fire ant venom radboallergosorbent test, in contrast, clearly separated all the imported fire ant-allergic pa-tients from the atopic controls.
Reviewers’ Comments
The present study indicates that the imported fire ant venom appears to be superior to the currently available whole body extract. Although some studies are currently available which also report venom to be superior to whole body extract, further studies addressing the clinical re-sponse to desensitization with venom vs whole body extract need to be performed.
ALMA M. HERRERA, MD
Washington, DC
RUSSELL J. Hopp, DO
Omaha, NE
SAFE ADMINISTRATION OF MUMPS-MEASLES-RUBELLA VACCINE IN EGG-ALLERGIC CHILDREN
Greenberg MA, Birx, DL. J Pediatr. 1 988;1 13:504-506.
Purpose of Study
In the past, egg allergy was a contraindication to administration of vaccines grown on avian embryos. More recently, protocols have been devised to test for sensitivity to the vaccines themselves. This article reports results of a simplified procedure for testing with mumps-measles-rubella vaccine.
Study Population
Fifteen children, 15 to 36 months old, with history of urticaria, gastrointestinal symptoms, respiratory symp-toms, or hypotension, within 2 hours of egg ingestion, and a positive skin-prick test to whole egg extract (greater than 3 mm induration) were examined.
Methods
Intradermal tests were done with 1:100 dilution of mumps-measles-rubella vaccine, saline, and histamine. A positive test was defined as induration and erythema at least 5 mm or greater than saline control.
Findings
All 15 patients had negative intradermal tests to mumps-measles-rubella vaccine. They were each immu-nized with a full dose without incident.
Reviewers’ Comments
testing with 1:100 then 1:10 dilution. The present study reports quite a small group of patients with very modestly positive skin test to egg extract. Until there is more experience with mumps-measles-rubella testing in egg-allergic patients, probably the more conservative “Red Book” protocol should be followed.
MARY ELLEN FRIEDMAN, MD
Downey, CA
Treatment
THE EFFECT OF CAT REMOVAL ON ALLERGEN CONTENT IN HOUSEHOLD-DUST SAMPLES
Wood RA, Chapman MD, Atkinson NF, Eggleston PA. J Allergy C/in Immunol. 1 989;83:730-734.
Methods
In 15 homes, samples of house dust were collected from a one square meter of carpeted area using a hand-held vacuum cleaner at baseline and at 4- to 5-week intervals during a 9- to 43-week period after removal of a cat. Samples were sieved to produce fine dust and extracted in borate-buffered saline. They were then analyzed for the major cat allergen Fel d I with a two-site radio-immunoassay using monoclonal antibodies. As a control, all samples were also analyzed for Der p I and Der
f
I, the major allergens of dust-mites.Findings
Preliminary studies demonstrated that the extraction and assay techniques were highly reproducible. The var-iability in weekly dust samples from homes with or with-out cats was found not to be statistically significant. In contrast, with regular vacuuming, the levels of Fel d I in
sequential dust samples from the 15 homes from which cats were removed gradually declined. By the 20th week after cat removal, levels in 8 homes were within or very close to the upper 95% confidence limit of about 1 FDA unit/g dust of the 10 control homes without cats. Median
Fel d I content was 61.2 U/g initially and fell to 44.7 at 4 weeks, to 4.2 at 10 weeks, to 1.8 at 15 weeks, and to 0.7 at 32 weeks.
Three homes were steam cleaned; no added benefit was seen. In two homes, aggressive environmental control measures (removal of all carpets and furniture) resulted in rapid declines in Fel d I content (26.6 U/g to unde-tectable and 472 U/g to 4.4 U/g in 1 and 4 weeks, respectively). Three homes demonstrated persistent ele-vations of cat allergen for 20 or more weeks. Median Der p I and Der
f
I levels remained stable. The authors conclude that it generally takes longer than previously suspected to reduce cat allergen levels to those found in homes without cats.Reviewer’s Comments
Fel d I, the major cat allergen, is produced in cat’s salivary glands and sebaceous glands of cat’s skin. It is a major cause of perennial allergic rhinitis and allergic
asthma. This study demonstrates that a trial of tempo-rary removal of a cat from a home to evaluate allergic symptoms is likely to be of little value. As an aside, I think that it would have been interesting to see the effect on the mean data calculations of excluding the two homes in which aggressive measures resulted in rapid declines of cat allergen.
DAVID E. GRAFT, MD
Minneapolis, MN
Upper
Airway
Disorders
Pathophysiology
INFLAMMATORY MEDIATORS IN CHRONIC OTITIS MEDIA WITH EFFUSION
Skoner DP, Stillwagon PK, Casselbrandt ML, et al. Arch Otolaryngol Head Neck Surg. 1 988;1 14:1131-1133.
Purpose of Study
This study was conducted to define the role of inflam-matory mediators in chronic middle ear disease.
Methods
One hundred and two patients, aged 1 to 23 years (mean age 4.9 years), with persistent otitis media with effusion unresponsive to antimicrobial therapy, were studied. Fluid was obtained during insertion of tympan-otomy tubes and cultured and assayed for histamine, neutrophil chemotactic factor of anaphylaxis, and/or 13,14-dihydro-15-keto-prostaglandin F2a(a prostaglandin metabolite). Twenty-two patients also had their plasma evaluated.
Findings
All the mediators were higher in the middle ear effu-sions than in the plasma. The mean histamine content of the mucoid secretions was significantly higher than that of purulent and serous effusions. Twenty-two per-cent of the effusions yielded pathogenic organisms. The highest histamine levels were found in the effusions positive for Haemophilus influenzae.
Conclusion
