Biomedical subjects
H A Sampson
Publications and source records attributed to H A Sampson.
Fatal and near-fatal anaphylactic reactions to food in children and adolescents.
BACKGROUND AND METHODS: Reports of fatal or near-fatal anaphylactic reactions to foods in children and adolescents are rare. We identified six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation. All the cases but one occurred in one of three metropolitan areas over a period of 14 months. Our investigations included a review of emergency medical care reports, medical records, and depositions by witnesses to the events, as well as interviews with parents (and some patients). RESULTS: Of the 13 children and adolescents (age range, 2 to 17 years), 12 had asthma that was well controlled. All had known food allergies, but had unknowingly ingested the foods responsible for the reactions. The reactions were to peanuts (four patients), nuts (six patients), eggs (one patient), and milk (two patients), all of which were contained in foods such as candy, cookies, and pastry. The six patients who died had symptoms within 3 to 30 minutes of the ingestion of the allergen, but only two received epinephrine in the first hour. All the patients who survived had symptoms within 5 minutes of allergen ingestion, and all but one received epinephrine within 30 minutes. The course of anaphylaxis was rapidly progressive and uniphasic in seven patients; biphasic, with a relatively symptom-free interval in three; and protracted in three, requiring intubation for 3 to 21 days. CONCLUSIONS: Dangerous anaphylactic reactions to food occur in children and adolescents. The failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome.
Food allergy and the role of immunotherapy.
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Fish hypersensitivity. II: Clinical relevance of altered fish allergenicity caused by various preparation methods.
In double-blind, placebo-controlled, oral food challenges with fish, a 12-fold higher false-negative rate was found compared with other food antigens. In an effort to elucidate this discrepancy, cooked lyophilized fish extracts (used in double-blind, placebo-controlled, oral food challenges) were compared with cooked, nonlyophilized fish extracts (used in open challenges) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot, and ELISA-inhibition assays. Altered fish allergenicity as a result of food processing was examined with canned tuna and salmon. Forty-five children and young adults with food allergies, including 18 patients with IgE-mediated hypersensitivity to fish, were challenged with canned tuna. All 45 challenges with canned tuna were negative. Two of these patients are allergic to salmon and also have negative reactions to challenges with canned salmon. In vitro investigation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of tuna and salmon extracts revealed a striking loss of definable protein fractions in the canned fish extract when compared with raw and cooked fish extracts, and immunoblot analyses demonstrated minimal IgE-specific binding to the canned fish extracts. In addition, decreased allergenicity of the canned tuna and salmon was demonstrated by ELISA-inhibition assay and by negative oral challenges with canned salmon in two patients allergic to salmon. Collectively, these findings suggest that some of the major allergens responsible for IgE-mediated food allergy to fish are more labile than previously recognized.
Fish hypersensitivity. I. In vitro and oral challenge results in fish-allergic patients.
The purpose of this study was to determine whether patients allergic to one fish species can safely eat other fish species. Eleven atopic, food-allergic children and young adults with histories consistent with IgE-mediated fish hypersensitivity were skin prick tested to 10 fish species. Skin prick tests (SPTs) were positive to all 10 fish in eight of the 11 patients, and the remaining three patients had at least two positive fish SPTs. Positive oral challenges occurred to only one fish in seven of the patients, to two fish species in one patient, and to three fish species in two patients. One patient did not react to any of the fish tested. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses were performed on raw and cooked protein extracts from nine of the 10 fish species used in SPTs. Several protein bands in the raw-fish extracts appeared to denature with cooking and form high molecular weight conglomerates. Immunoblot analyses with sera from documented fish-allergic patients demonstrated specific IgE binding to protein bands from fish to which patients were not clinically allergic, as determined by oral challenge. In ELISA-inhibition assays, the concentration of fish antigen required to achieve 50% inhibition was similar for fish to which the patients were clinically allergic as compared to fish to which they were clinically tolerant. SPT and in vitro evidence of IgE-specific cross-reactivity does not necessarily correlate with symptomatic fish allergy. In addition, these fish-hypersensitive patients were able to consume one or more other fish species without adverse allergic reactions.
Diagnostic approaches to the patient with suspected food allergies.
Adverse food reactions may be secondary to food allergy (hypersensitivity) or food intolerance. The clinical manifestations of food allergies depend on the target organ affected. Gastrointestinal, respiratory, and cutaneous symptoms are the most common of the clinical responses. The medical history, physical examination, and various in vivo or in vitro tests are useful in the diagnostic evaluation. Double-blind, placebo-controlled food challenges are the standard for diagnosis of food allergies. Presumptive diagnosis of food allergy based on patient history and on results of skin test or radioallergosorbent test is no longer acceptable, except in cases of severe anaphylaxis after an isolated ingestion of a specific food. Unless the physician provides an unequivocal diagnosis of food allergy, people will continue to alter their eating habits on the basis of misconceptions of food allergy.
Immunologic changes associated with the development of tolerance in children with cow milk allergy.
The purpose of this study was to determine whether cow milk-specific antibody responses correlated with the development of clinical tolerance in cow milk-allergic children. Double-blind, placebo-controlled food challenges were performed annually in 29 patients with cow milk allergy. Clinical reactivity was lost in 11 (38%) of 29 patients. The median age for all patients at the time of diagnosis by these food challenges was 3 years; more than 80% of patients in each group had atopic dermatitis as part of their presenting symptoms. Casein-specific and beta-lactoglobulin-specific IgE, IgG, IgG1, and IgG4 antibody concentrations were analyzed in all patients at regular intervals. In the patients becoming clinically tolerant to cow milk, the IgE-specific antibody concentrations and IgE/IgG-specific ratios for both milk proteins were lower initially and decreased significantly with time, in comparison with those in the group who retained clinical sensitivity. The concentrations of IgG1- and IgG4-specific antibody to casein and the IgE/IgG1 and IgE/IgG4 ratios for both casein and beta-lactoglobulin were significantly less in the patients losing clinical reactivity. No differences in the IgG-specific concentrations were observed in either group at any of the evaluation times noted above. Monitoring similar casein-specific and beta-lactoglobulin-specific IgE concentrations and IgE/IgG ratios may help predict which patients will ultimately lose their clinical reactivity to cow milk.
Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine.
We evaluated the safety of the measles-mumps-rubella (MMR) combination vaccine in 140 children with egg hypersensitivity. All children, regardless of vaccine skin test results or severity of egg hypersensitivity, were safely immunized with the MMR vaccine. Systemic reactions to MMR vaccine in two nonallergic children were documented, indicating that reactions unrelated to egg protein can occur. With the use of a competitive enzyme-linked immunosorbent assay, the standard MMR injection was found to contain approximately 37 pg of ovalbumin-like material. This study provides 95% confidence that at least 97.5% of egg-allergic children will tolerate MMR vaccine without significant difficulty. Skin testing was not found to be helpful in predicting an adverse reaction. We recommend that the American Academy of Pediatrics consider revising its current policy regarding skin test response to MMR vaccine and administration of MMR vaccine to egg-allergic children.
The antigenicity and allergenicity of microparticulated proteins: Simplesse.
New technologies are allowing the food industry to develop products from standard foods which may not be recognized in its modified form by food allergic patients. One such product, Simplesse, has been formulated by microparticulation of egg white and/or cows' milk proteins and is used as a fat substitute in many fat-laden foods. The purpose of this study was to determine whether the process of microparticulation altered the allergenicity/antigenicity of egg white and cows' milk proteins compared to the starting materials. Soluble protein fractions of Simplesse and its respective starting materials were compared to egg white, cows' milk protein, an ultra-filtered egg white/condensed milk mixture, and/or a whey concentrate by SDS-polyacrylamide gel electrophoresis. In addition, sera from 16 patients with documented egg and/or cows' milk hypersensitivity and two controls who were not allergic to egg or milk were used to assess potential allergenicity/antigenicity of these products by immunoblot (Western blot) analysis. There were heterogeneous IgE and IgG binding patterns to the food fractions among these food allergic patients suggesting differing sensitivity patterns among the individuals tested. However, utilizing both SDS-PAGE and immunoblot analyses, the major allergens in the microparticulated products were the same as those found in the starting materials, egg and cows' milk. In addition, there was no evidence of 'novel' protein fractions in the Simplesse test materials compared to the starting materials.
Food hypersensitivity and dietary management in atopic dermatitis.
Although immune dysfunction is known to play an integral role in the development of atopic dermatitis, no clear delineation of the underlying pathogenic mechanism(s) responsible for this disorder has been proposed. Several factors are known to trigger flares of atopic dermatitis. In the extrinsic form of this disorder, food and airborne allergens may provoke flares of eczema. Research implicating food hypersensitivity in the pathogenesis of atopic dermatitis includes studies of food allergen avoidance in newborn infants at high risk for atopic disease, investigations of children with blinded food challenges, and therapeutic trials of allergen-elimination diets. Taken together, these studies demonstrate a significant pathogenic role for food hypersensitivity in about one-third of children with atopic dermatitis.
Endothelins and the nervous system.
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The immunopathogenic role of food hypersensitivity in atopic dermatitis.
Food hypersensitivity is reported to play an immunopathogenic role in atopic dermatitis in approximately one-third of children. In 320 selected children with moderate to severe atopic dermatitis, 63% of children were found to have food hypersensitivity by double-blind placebo-controlled food challenges. Both IgE-mediated mast cell and mononuclear cell activation appear responsible for the eczematous lesions resulting from ingestion of food allergens.
Adverse food reactions.
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Safety of an amino acid-derived infant formula in children allergic to cow milk.
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Allergic reactions to milk-contaminated "nondairy" products.
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Identification of soy protein allergens in patients with atopic dermatitis and positive soy challenges; determination of change in allergenicity after heating or enzyme digestion.
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Anaphylactic reactions to a psyllium-containing cereal.
Historical data were obtained by questionnaire and telephone survey on 20 of 24 women with reported allergic reactions to a psyllium-containing cereal, Heartwise. Protein fractions from this new cereal, as well as from psyllium mucilloid and a psyllium-containing laxative, Metamucil, were extracted, quantitated, and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Patients' sera were collected, and specific IgE and IgG antibodies to these psyllium antigens were detected by immunoblotting techniques. Of the 20 women evaluated, all but six were nurses. Eighteen (90%) of the women had historical and/or laboratory evidence of atopy. Exposures included ingestion or dispensing of psyllium-containing products. Only three women denied prior exposure to psyllium. Symptoms developed shortly after small amounts of the cereal were ingested and most commonly included moderate to severe wheezing, throat and chest tightness, and urticaria. All the women required medical therapy, 11 (55%) in an emergency room. Specific IgE and IgG antibodies to various psyllium protein fractions were documented in all the subjects. It was concluded that individuals sensitized by occupational exposure to psyllium dust are at high risk for allergic reactions to ingested psyllium-containing products.