Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract
TL;DR: Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts, even during maintenance injections, which result in repeated systemic reactions in most patients.
Abstract: Background: Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults Currently, preventive treatment consists of avoidance, which is difficult because of the widespread and often disguised use of peanuts in the food industry Methos: Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited Half were treated with injections of peanut extract: a maintenance level of tolerance was first achieved by a rush protocol, then maintained with weekly injections for at least 1 year The other six were untreated control subjects All patients underwent double-blind, placebo-controlled, oral peanut challenges initially, after approximately 6 weeks, and after 1 year Results: All treated patients achieved the maintenance dose of 05 ml of 1:100 wt/vol peanut extract by the rush injection protocol All experienced increased tolerance to double-blind, placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract, whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections Only three patients remained tolerant of the full maintenance dose The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses, but there was partial ( n =2) or complete ( n =1) loss of protection in the patients who required dose reduction because of systemic reactions Conclusions: Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts Injections result in repeated systemic reactions in most patients, even during maintenance injections For clinical application of this method of treatment, a modified peanut extract is needed
Citations
More filters
Harvard University1, Cincinnati Children's Hospital Medical Center2, Duke University3, University of Arkansas for Medical Sciences4, Icahn School of Medicine at Mount Sinai5, Johns Hopkins University School of Medicine6, National Institutes of Health7, University of Southampton8, St Mary's Hospital9, LSU Health Sciences Center Shreveport10, University of Rochester Medical Center11, Rutgers University12, Boston Children's Hospital13, University of California, San Diego14, University of Colorado Denver15, Oregon Health & Science University16, University of Tennessee Health Science Center17, Food and Drug Administration18, University of California, Irvine19, Scripps Health20, University of Manitoba21, Children's National Medical Center22, University of Rochester23, University of Minnesota24
TL;DR: The National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy, which include a consensus definition for food allergy.
Abstract: Food allergy is an important public health problem that affects children and adults and may be increasing in prevalence. Despite the risk of severe allergic reactions and even death, there is no current treatment for food allergy: the disease can only be managed by allergen avoidance or treatment of symptoms. The diagnosis and management of food allergy also may vary from one clinical practice setting to another. Finally, because patients frequently confuse nonallergic food reactions, such as food intolerance, with food allergies, there is an unfounded belief among the public that food allergy prevalence is higher than it truly is. In response to these concerns, the National Institute of Allergy and Infectious Diseases, working with 34 professional organizations, federal agencies, and patient advocacy groups, led the development of clinical guidelines for the diagnosis and management of food allergy. These Guidelines are intended for use by a wide variety of health care professionals, including family practice physicians, clinical specialists, and nurse practitioners. The Guidelines include a consensus definition for food allergy, discuss comorbid conditions often associated with food allergy, and focus on both IgE-mediated and non-IgE-mediated reactions to food. Topics addressed include the epidemiology, natural history, diagnosis, and management of food allergy, as well as the management of severe symptoms and anaphylaxis. These Guidelines provide 43 concise clinical recommendations and additional guidance on points of current controversy in patient management. They also identify gaps in the current scientific knowledge to be addressed through future research.
2,014 citations
TL;DR: It is demonstrated that oral allergen-gene immunization with chitosan–DNA nanoparticles is effective in modulating murine anaphylactic responses, and its prophylactic utility in treating food allergy is indicated.
Abstract: Food allergy is a common and often fatal disease with no effective treatment We describe here a new immunoprophylactic strategy using oral allergen-gene immunization to modulate peanut antigen-induced murine anaphylactic responses Oral administration of DNA nanoparticles synthesized by complexing plasmid DNA with chitosan, a natural biocompatible polysaccharide, resulted in transduced gene expression in the intestinal epithelium Mice receiving nanoparticles containing a dominant peanut allergen gene (pCMVArah2) produced secretory IgA and serum IgG2a Compared with non-immunized mice or mice treated with 'naked' DNA, mice immunized with nanoparticles showed a substantial reduction in allergen-induced anaphylaxis associated with reduced levels of IgE, plasma histamine and vascular leakage These results demonstrate that oral allergen-gene immunization with chitosan-DNA nanoparticles is effective in modulating murine anaphylactic responses, and indicate its prophylactic utility in treating food allergy
1,119 citations
Nova Southeastern University1, University of Colorado Denver2, University of South Florida3, Yale University4, University of Texas Southwestern Medical Center5, Pennsylvania State University6, University of California, Los Angeles7, University of Washington8, Johns Hopkins University9, Duke University10, Northwestern University11
TL;DR: These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American Col- lege of Allergen,Asthma & immunology (ACAAI); and the Joint Council of All allergy, asthma, and Immunology.
Abstract: These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American Col- lege of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology have jointly accepted responsibility for establishing ''Allergen immunotherapy: A practice parameter third update.'' This is a complete and com- prehensive document at the current time. The medical environ- ment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individ- ual, including those who served on the Joint Task Force, is authorizedtoprovideanofficial AAAAIorACAAIinterpretation ofthesepracticeparameters.Anyrequestforinformationaboutor an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. A current list of published practice parameters of the Joint Task Force on Practice ParametersforAllergyandImmunologycanbefoundinTableE1 in this article's Online Repository at www.jacionline.org. Disclosure ofpotentialconflictofinterest:L.Coxisaconsultant forGenentech/Novartis, Hollister-Stier, and Stallergenes; is a speaker for Novartis; has received research support from Stallergenes; is on the Board of Directors for the American Board of Allergy and Immunology; and is on the US Food and Drug Administration (FDA)'s Allergenic Product Advisory Committee. H. Nelson is a consultant for Merck and Planet Biopharmaceuticals, is a Data and Safety Monitoring Board member of DBV Technologies, and has received research support from ALK-AbellM. Nelson has re- ceivedresearchsupportfromtheDepartmentofDefense,isaspeakerfortheAmerican College of Allergy, Asthma & Immunology (ACAAI), and is a member of the FDA's AdvisoryCommitteeonAllergicProducts.R.Weberisonthespeakers'bureauforAs- traZeneca and Genentech, has received research support from Novartis and Glaxo- SmithKline, and is Committee Chair of the ACAAI. D. I. Bernstein is a consultant and on the advisory board for ALK America, is on the advisory board for Merck, and has received research support from Merck and Schering-Plough. J. Blessing- Moore is a speaker for Merck-Schering/AstraZeneca, Novartis, TEVA, and Meda Alcon and has received research support from Meda. D. A. Khan is a speaker for As- traZeneca and Merck, has received research support from the Vanberg Family Foun- dation and the Sellars Family Foundation, is Conjoint Board Review Chair for the ACAAI,andisapastpresidentoftheTexasAllergy,AsthmaandImmunologySociety. D. M. Lang is a speaker and consultant for GlaxoSmithKline; is a speaker for Astra- Zeneca, Merck, TEVA, Sanofi-Aventis, and Genentech/Novartis; and has received re- search support from Genentech/Novartis. R. A. Nicklas is a fellow for the ACAAI. J. Oppenheimer is a consultant and has provided lectures for AstraZeneca, Merck, and GlaxoSmithKline; and has received research support from AstraZeneca, Merck, Glax- oSmithKline, and Genentech. J. M. Portnoy is a speaker for Phadia, Merck, and CSL Behring; hasreceived researchsupportfromtheUSDepartment ofHousingandUrban Development;andisa board memberof theACAAI board of regents.S.L. Spector has received research support from Genentech, GlaxoSmithKline, Schering-Plough, Aventis, Novartis, Pharmaxis, Boehringer Ingelheim, AstraZeneca, Johnson & John- son, Xyzal, Alcon, Centocor, Sepracor, UCB, Amgen, Capnia, and IVAX. S. Tilles isaspeakerforAlcon; isontheadvisoryboard forALK,Ista,Merck,andStallergenes; has received research support from Alcon, Amgen, Amphastar, Astellas, Boehringer Ingelheim,Ception,Genentech,Icagen, MAP Pharma, MEDA, Merck, Novartis, Rox- ane, and Sepracor; is Associate Editor of Allergy Watchand Annals of Allergy; and is a task force member for the Joint Task Force for Practice Parameters. D. Wallace is a speaker and advisor for Alcon, is a speaker for Merck and Sanofi-Aventis, and is President-Elect of the ACAAI. The rest of the authors have declared that they have no conflict of interest.
1,055 citations
Cites background from "Treatment of anaphylactic sensitivi..."
...There are studies demonstrating efficacy in food hypersensitivity, the first using aqueous subcutaneous injections of peanut.(170,171) Studies with SLITwith hazelnut(172) and milk(173) and oral immunotherapy with peanut,(174) egg,(175,176) and milk(176-178) have demonstrated increased tolerance to these foods (see Summary Statement 103 for further discussion)....
[...]
...In the subcutaneous peanut immunotherapy study there was increased tolerance to oral peanut challenge in all of the treated patients, but there were repeated systemic reactions in most patients, even during maintenance injections, and the authors concluded that a modified peanut extract is needed for clinical application of this method of treatment.(170) There are no FDAapproved formulations for oral immunotherapy or SLIT, and this route of allergen immunotherapy is considered investigational at this time....
[...]
TL;DR: Data from the Avon Longitudinal Study of Parents and Children is used to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge, which could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.
Abstract: Background The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors. Methods We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life). Results Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of p...
811 citations
TL;DR: Microarray data suggest a novel role for apoptosis in OIT, which induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes.
Abstract: Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG 4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.
643 citations
Cites background from "Treatment of anaphylactic sensitivi..."
...Traditional subcutaneous immunotherapy is useful in treating forms of inhalant allergen sensitivity such as allergic rhinoconjunctivitis and asthma(11) but is unsafe in food allergy.(12,13) Oral immunotherapy (OIT) and sublingual immunotherapy have been reported by our group and others to result in induction of clinical tolerance to a variety of food proteins....
[...]
References
More filters
TL;DR: Six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation were identified and the failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome.
Abstract: 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 minute...
1,503 citations
TL;DR: Food-sensitive individuals must self-administer epinephrine promptly at the first sign of systemic reaction, and emergency care providers should be aware of cricothyrotomy as a life-saving procedure.
Abstract: Fatal food-induced anaphylaxis is rarely reported. In 16 months, we identified seven such cases involving five males and two females, aged 11 to 43 years. All victims were atopic with multiple prior anaphylactic episodes after ingestion of the incriminated food (peanut, four; pecan, one; crab, one; fish, one). In six cases the allergenic food was ingested away from home. Factors contributing to the severity of individual reactions included denial of symptoms, concomitant intake of alcohol, reliance on oral antihistamines alone to treat symptoms, and adrenal suppression by chronic glucocorticoid therapy for coexisting asthma. In no case was epinephrine administered immediately after onset of symptoms. Premortem or postmortem serum samples were available from six victims; in each case elevated levels of IgE antibodies to the incriminated food were demonstrated. Food-sensitive individuals must self-administer epinephrine promptly at the first sign of systemic reaction. Emergency care providers should be aware of cricothyrotomy as a life-saving procedure. ( JAMA 1988;260:1450-1452)
520 citations
TL;DR: Preliminary data demonstrating the efficacy of injection therapy with peanut extract is provided and provides a future line of clinical investigation for the treatment of this potentially lethal disease.
Abstract: Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%. Thus, at the present time, this therapy should only be considered investigational and done only in research settings with intensive care unit support immediately available.
460 citations
TL;DR: It appears uncommon for peanut-sensitive patients to lose their clinical reactivity, even after many years have elapsed, according to a longitudinal evaluation of double-blind, placebo-controlled, food challenge to peanut.
Abstract: Between 1973 and 1985, 114 children, aged 2 to 14 years, underwent double-blind, placebo-controlled, food challenge (DBPCFC) to peanut. Thirty-two of 46 children with symptoms produced by DBPCFC to peanut were included in this longitudinal evaluation. Contact was made with the 32 subjects 2 to 14 years after their positive DBPCFC to peanut. All 32 subjects had exhibited a positive puncture skin test to peanut at the time of the original evaluation. Sixteen subjects had experienced symptoms caused by accidental peanut ingestion in the year before contact. Eight subjects had reacted to accidental ingestion in more than 1 year but less than 5 years before contact. Eight subjects had completely avoided peanut since the original evaluation and positive DBPCFC. No subjects could be demonstrated to have "outgrown" their peanut reactivity. All subjects tested continued to have skin reactivity to a puncture skin test with peanut extract. It appears uncommon for peanut-sensitive patients to lose their clinical reactivity, even after many years have elapsed. In addition, data were collected concerning reactions to other legumes and other (nonlegume) nuts. Only two patients with DBPCFC to peanut reacted on DBPCFC to soy or pea (one each). None of the subjects with a positive DBPCFC to peanut reacted to nonlegume nuts.
367 citations
TL;DR: Atopy is common in subjects who experience anaphylaxis, regardless of its origin, and subjects with idiopathic anAPHylaxis are more likely to carry epinephrine for self-administration than those with identifiable causes.
Abstract: Background: A presentation of findings from a large population of anaphylaxis cases. Methods: Retrospective chart review and follow-up questionnaire provided data on 266 subjects (113 males and 153 females) aged 12 to 75 years (mean age, 38 years) who were referred to a university-affiliated private allergy-immunology practice in Memphis, Tenn, for evaluation and management of anaphylaxis from January 1978 through March 1992. Results: Of 266 subjects, 162 (61%) had three or more anaphylactic episodes, 41 (15%) had two episodes, and 63 (24%) had one episode. Atopy was present in 98 individuals (37%). Physicians thought foods, spices, and food additives caused anaphylaxis in 89 individuals (34%); crustaceans and peanut accounted for about half of these cases. Medications were thought to have caused the anaphylactic episodes in 52 individuals (20%); nonsteroidal anti-inflammatory drugs in about half of these cases. Other probable causes included exercise (n=19), latex (n=2), hormonal changes (n=2), and insect bites (n=4). A suspected cause could not be determined in 98 individuals (37%). These subjects were diagnosed as having idiopathic anaphylaxis. Of the 266 subjects, 102 responded to a follow-up survey; 68 (67%) of the 102 were thought to have identifiable causes of anaphylaxis (32 of whom [47%] failed to carry epinephrine syringes for self-administration despite instructions to do so). In contrast, of 34 subjects with idiopathic anaphylaxis who responded to the survey, only three (9%) did not carry epinephrine. Conclusions: (1) Atopy is common in subjects who experience anaphylaxis, regardless of its origin; (2) crustaceans and nonsteroidal anti-inflammatory drugs are the most common food and medication groups, respectively, thought to cause anaphylaxis; (3) causative agents can be identified for two thirds of the subjects, and recurrent attacks are the rule; and (4) subjects with idiopathic anaphylaxis are more likely to carry epinephrine for self-administration than those with identifiable causes. (Arch Intern Med. 1995;155:1749-1754)
248 citations