A peanut allergy warning
|Classification and external resources|
Peanut allergy is a type of food allergy distinct from nut allergies. It is a type one hypersensitivity reaction to dietary substances from peanuts that causes an overreaction of the immune system. It is recognized "as one of the most severe food allergies due to its prevalence, persistency and potential severity of allergic reaction." Physical symptoms of allergic reaction can include mild pruritus, urticaria, angiodema, eczema, facial swelling, sneezing, rhinitis, asthma, abdominal pain, drop in blood pressure, cardiac arrest and anaphylaxis. Peanut allergy is the most common cause of fatal food-related anaphylaxis.
Peanut allergy is present in 0.6% of Americans.
Symptoms of peanut allergy are related to the action of Immunoglobulin E (IgE) and other anaphylatoxins, which act to release histamine and other mediator substances from mast cells (degranulation). In addition to other effects, histamine induces vasodilation of arterioles and constriction of bronchioles in the lungs, also known as bronchospasm. At least 11 peanut allergens have been described.
Symptoms can include mild pruritus, urticaria, angiodema, facial swelling, rhinitis, vomiting, diarrhea, acute abdominal pain, exacerbation of atopic eczema, asthma, cardiac arrest and anaphylaxis.
The exact cause of someone developing a peanut allergy is unknown. A 2003 study found no link to maternal exposure to peanuts during pregnancy or during breast-feeding. The study did find a positive correlation between the amount of time a child is breastfed and odds that the child would develop peanut allergy. The study also indicated that exposure to soy milk or soy products was positively correlated with peanut allergies. However, an analysis of a larger group in Australia found no linkage to consumption of soy milk, and said that the appearance of any linkage is likely due to preference to using soy milk among families with known milk allergies. Studies have shown that the application of lotions containing peanut oil to inflamed skin may cause peanut sensitization and allergy in children.
Food allergies seem far less common in underdeveloped countries. The hygiene hypothesis is an attempt to understand why this is the case. Proponents of the hypothesis say that the relatively low incidence of childhood infections in developed countries contribute to an increased incidence of allergic diseases. The hypothesis may also explain why first-born children are more likely to have an allergic disease. More recent research (2014) published in the Journal of Allergy and Clinical Immunology has shown that the method used in cooking peanuts may result in the different incidence of allergies in developed nations in the west and undeveloped areas, as peanuts are much more frequently roasted in the west, whereas in other parts of the world peanuts are most frequently boiled, fried, or eaten raw
A British study has found that consuming peanuts in infancy lowers the risk that a child will develop peanut allergies, and the American Academy of Pediatrics, in response to ongoing studies that showed no reduction in risk of atopic disease, rescinded their recommendation to delay exposure to peanuts along with other foods. The academy also found no reason to avoid peanuts during pregnancy or while breastfeeding. A study conducted jointly in Israel and United Kingdom noted a nearly tenfold increase in incidence of peanut allergy among British children compared to Israeli children. The study also found that Israeli children consumed peanuts at a much younger age than their British counterparts, whose parents delayed peanut consumption upon the recommendation of British pediatricians. Pediatric associations in Britain and Australia recommend delaying introduction until age 3 and have not changed their recommendations as of 2009.
A February 2014 study published in JAMA Pediatrics found that peanut consumption by pregnant women without peanut allergies led to a decreased likelihood that their children would develop peanut allergies. Researchers found that children whose mothers ate nuts at least five times a month were 69 percent less likely to have nut allergies than those whose mothers rarely ate nuts.
||The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. (August 2014)|
According to the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health, the prevalence rate of the allergy is 0.6% in the United States. In a 2008 study, self-reported incidence of peanut allergy was estimated to affect 1.4% of the population of the United States, triple the 0.4-0.6% rate found in a 1997 study. In England, an estimated 4,000 people are newly diagnosed with peanut allergy per year (11 per day); 25,700 having been diagnosed with peanut allergy by a clinician at some point in their lives. Nicholas Christakis of Harvard Medical School asserts that recent increases in peanut allergies, and the measures taken in response, show elements of mass psychogenic illness: hysterical reactions grossly out of proportion to the level of danger. According to Scott Sicherer of the Jaffe Food Institute at the Icahn School of Medicine at Mount Sinai, peanut allergy is one of the most dangerous food allergies, and one of the least likely to be outgrown.
The Asthma and Allergy Foundation of America estimates that peanut allergy is one of the most common causes of food-related death. However, there is an increasing body of medical opinion that the measures taken in response to the threat may be an over-reaction out of proportion to the level of danger: "About 3.3 million Americans are allergic to nuts, and even more—6.9 million—are allergic to seafood. However, all told, serious allergic reactions to foods cause just 2,000 hospitalisations a year (out of more than 30 million hospitalisations nationwide). And only 150 people (children and adults) die each year from all food allergies combined." Media sensationalism has also been blamed.
Prevalence among adults and children is similar—around 1%—but at least one study shows self-reports of peanut allergy are on the rise in children in the United States. The number of young children self-reporting the allergy doubled between 1997 and 2002.
In 2013 Miranda Waggoner, a postdoctoral researcher at the Office of Population Research in the Woodrow Wilson School of Public and International Affairs reported that the increase in self-reported incidence of the allergy, previously thought to be rare, could not be correlated with medical data confirming the self-reported incidence. Peter Conrad, a medical sociologist at Brandeis University specializing in the medicalization of society, said of the study: This paper helps us understand how a relatively rare disorder, peanut allergies, has become seen as a public risk and even as a childhood epidemic. While the individual risk is high, the risk on a population level is small. Sometimes the public's response to a disorder may significantly outpace the actual public health risk potential.
Routes of exposure
While the most obvious and dangerous route for an allergic individual is unintentional ingestion, some reactions are possible through external exposure. Airborne particles in a farm- or factory-scale shelling or crushing environment, or from cooking, can produce respiratory effects in exposed allergic individuals. Empirical testing has discredited some reports of this type and shown some to be exaggerated. Residue on surfaces has been known to cause minor skin rashes, though not anaphylaxis. In The Peanut Allergy Answer Book, Harvard pediatrician Michael Young characterizes this secondary contact risk to allergic individuals as rare and limited to minor symptoms. Some reactions have been noted to be psychogenic in nature, the result of conditioning and belief rather than a true chemical reaction. Blinded, placebo-controlled studies by Sicherer et al. were unable to produce any reactions using the odor of peanut butter or its mere proximity.
Diagnosis and treatment
Diagnosis of food allergies, including peanut allergy, begins with a medical history and physical examination. National Institute of Allergy and Infectious Diseases guidelines recommend that parent and patient reports of food allergy be confirmed by a doctor because "multiple studies demonstrate 50% to 90% of presumed food allergies are not allergies."
Skin prick tests can be used to confirm specific food allergies. Skin prick tests are designed to identify specific IgE bound to cutaneous mast cells. During the test, a glycerninated allergen extract drop is placed on the patient's skin. The patient's skin is then pricked through the drop. This procedure is repeated with two controls: a histamine drop designed to elicit an allergic response, and a saline drop designed to elicit no allergic response. The wheal that develops from the glycerinated extract drop is compared against the saline control. A positive allergic test is one in which the extract wheal is 3mm larger than the saline wheal. A positive skin prick test is about 50% accurate, so a positive skin prick test alone is not diagnostic of food allergies.
The "gold standard" of diagnostic tests is a double-blind placebo-controlled oral food challenge. At least two weeks prior to an oral food challenge, the patient is placed on an elimination diet where the suspected allergen is completely avoided. During the oral food challenge, the patient is administered a full age-appropriate serving of a suspected allergen in escalating size increments. The patient is continuously monitored for allergic reaction during the test, and the challenge is stopped and treatment administered immediately at the first objective sign of allergic reaction.
Oral food challenges do pose "inherent and significant risks." In a study of 584 oral food challenges administered to 382 patients, 48% (253) of challenges resulted in allergic reactions. 28% (72) of these challenges resulted in "severe" reactions, which were defined by the study as a patient having: lower respiratory symptoms; cardiovascular symptoms; or any four other, more minor, symptoms. Double-blind placebo-controlled oral food challenges are also time consuming and require close medical supervision. Because of these drawbacks to the double-blind placebo-controlled oral food challenge, open food challenges are the most commonly used form of food challenge. Open food challenges are those in which a patient is fed an age-appropriate serving of a suspected food allergen in its natural form. The observation of objective symptoms resulting from ingestion of the food, such as vomiting or wheezing, is considered diagnostic of food allergy if the symptoms correlate with findings from the patient’s medical history and laboratory testing such as the skin prick test.
Currently there is no confirmed treatment to prevent or cure allergic reactions to peanuts and strict avoidance of peanuts is the only way to avoid an allergic reaction. The principle treatment for acute allergic reaction is epinephrine, which is generally administered by an epinephrine injector. Antihistamines can be administered in addition to epinephrine. Patients should undergo medical observation following an acute reaction.
An early trial of injecting escalating doses of peanut allergen was conducted in 1996. However, one participant died seconds after injection from laryngospasm due to a pharmacy error in calculating the dose. The death abruptly ended one of the only studies on injected allergen desensitization to peanut allergies.
A desensitization study at Duke University was done with escalating doses of peanut protein. Eight children with known peanut allergy were given escalating doses of peanut protein in the form of a ground flour mixed into apple sauce or other food. Children in the study had peanut IgE level > 7 kU/L and a positive skin prick test. The first day, they were given 0.1 mg of peanut protein, with the amount increased gradually to 50 mg, if tolerated, over that first day. About ½ of the children tolerated 50 mg dose by the end of the day, while the others were able to reach 12.5 mg or 25 mg. The children then took daily doses of peanut at home, returning to the hospital every two weeks for dose increases until they reached 300 mg peanut protein a day, or the equivalent of a single peanut. The maintenance phase lasted up to 18 months, depending on how much peanut protein the child tolerated. Seven children completed the study. These children were given a "food challenge" to peanut flour, exposing them to up to nearly 8 grams, or the equivalent of more than 13 peanuts. Five of the seven children tolerated the equivalent of 13 peanuts at the food challenge at the end of the study. The children’s immunologic findings were similar to those seen with other types of immunotherapy—an initial rise followed by a decline in peanut-specific IgE and IgG. They also had a rise in peanut-specific IgG4 throughout the study, which is thought to be a marker of protection in other forms of immunotherapy.
In February 2009 a successful desensitization study was announced by Addenbrooke's Hospital in Cambridge, England. An example of the oral rush immunotherapy protocol is the administration of diluted peanut at a dose of 0.1 mg (1 mL of a 1 gram/10L solution), and escalating by 10 fold every 30 minutes. Once a maximum dose of 50 mg is reached (1 mL of a 5 gram/100 mL solution), or when systemic or local reaction occurs, the escalation is stopped. The patient is maintained on this maximum day one dose daily and the dose is escalated by a less rapid twofold increase each week, or each month, depending on tolerance. Reactions are treated with antihistamines, and if needed anaphylactic drugs. In 2014 the same group announced new trial results, where more than half the children involved in a second stage of the trial were able to tolerate doses equivalent to around 10 peanuts per day. One fifth of the children who received the therapy reported mild adverse events, most commonly an itchy mouth. However, one child had to withdraw from the trial after two doses.
Standard protocols are being developed by several clinical trials being conducted in the United States. Pre- and post-study serum anti-peanut IgE levels are measured, and varying doses and escalation schedules are being compared to placebo in blinded study protocols. Actual desensitization treatments are being carried out in the community using modified protocols. Success has been reported in both rapid (short duration of weeks) and slower protocols (spread over months) with minimal systemic reactions. The first day of the protocol often required inpatient hospital admission, or observation in a physician's office equipped with resuscitative drugs and with IV access). Frequent follow up is required during the desensitization trials to treat reactions and modify the protocol if needed. Because of the relative safety of oral rush immunotherapy, some in the medical community have questioned if desensitization is better than living with peanut allergy.
However, there are unknown risks of oral desensitization, such as the development of eosinophilic esophagitis, recurrence of allergy after completing desensitization protocols, and the frequent reactions that occur during these protocols.
Sublingual immunotherapy desensitization
Sublingual immunotherapy desensitization is the process of allergen desensitization by putting gradually increasing doses of an allergy extract under a patient's tongue. The extract is then either spat or swallowed. Using the sublingual spit technique, the allergen extract is held under the tongue for a short period before the patient spits out the vaccine. The sublingual spit technique was used in some early studies of sublingual immunotherapy. The majority of studies use the sublingual swallow technique, wherein the allergen extract is held under the tongue for 1–2 minutes before the patient swallows the vaccine. A 2014 review of sublingual immunotherapy desensitization found that "the applicability of [sublingual immunotherapy] in the general population of patients with food allergy remains unclear."
Epicutaneous immunotherapy desensitization
Epicutaneous immunotherapy desensitization is the introduction peanut protein extract to intact skin in order to desensitize those with peanut allergies.
In a study published in October 2010, a group peanut-sensitized mice was treated with DBV Technology's Viaskin patch and exposed to peanut allergens. Another group was treated with subcutaneous immunotherapy prior to exposure to peanut allergens. The study found that epicutaneous immunotherapy was as "efficient" in treatment as subcuntaneous immunotherapy. An additional study found that epicutaneous immunotherapy was efficacious in treating gastro-intestinal lesions induced by sustained oral exposure to peanut allergens in peanut-sensitized mice. Further study has shown that application of epicutaneous immunotherapy patches on broken or stripped skin reinforces allergic reactions in peanut-sensitive mice.
Later in 2010, a clinical Phase Ib study was conducted in the US to assess the safety of epicutaneous immunotherapy in humans with peanut allergy utilizing Viaskin patches. 100 subjects were included in this study. 90% of subjects in the study experienced mild to moderate adverse events locally around the treatment site, but no serious adverse events or epinephrine use by the subjects were reported. In 2013, DBV Technologies began stage two of the study, which examined the safety and effectiveness in humans of its Viaskin epicutaneous immunotherapy system, which utilizes a patch applied on the skin to deliver PPE to users. Safety data from this study was taken after 12 and 18 months and was consistent with the findings of the previous study.
In June 2014, DBV Technologies presented preclinical data at the 2014 European Academy of Allergy and Clinical Immunology Meeting. The data and findings of the Viaskin patch presented at the meeting showed further potential of Viaskin gaining footing in immunotherapy. The conclusion after 5 presentations at the meeting was that the patch has lasting effects on patients, even after the EPIT treatment had been stopped.
North Carolina Agricultural and Technical State University received a patent in 2012 for a process to reduce allergens in peanuts 98 percent or more. The process was developed by Dr. Jianmei Yu, a food and nutrition researcher, and two former A&T faculty members, Dr. Mohamed Ahmedna and Dr. Ipek Goktepe, both of whom are now at Qatar University.
The process treats roasted peanuts, removed from the shell and skin, with food-grade enzymes commonly used in food processing. The treatment consists of soaking the peanuts in an enzymatic solution. The treatment reduces two key allergens, Ara h 1 to undetectable levels and Ara h 2 by up to 98%. The resulting peanuts look and taste like roasted peanuts. The peanuts are not genetically modified.
The effectiveness of the process was demonstrated in human clinical trials at the University of North Carolina at Chapel Hill, using skin-prick tests.
N.C. A&T has signed an exclusive license for the process with Alrgn Bio. The company announced in October 2014 that batches of peanuts were available to food processing companies for evaluation. It said it would work with food processors and manufacturers to establish the process as “the industry standard for peanuts and peanut-derived ingredients.”
In collaboration with Xemerge, Dr. Yu is continuing to refine the process by testing the effectiveness of additional food-grade enzymes.
Research funding was provided by the Agriculture and Food Research Initiative of the U.S. Department of Agriculture.
Some commentators, including Dr. Nicholas Christakis of Harvard Medical School, have said that measures taken (especially in schools) to ensure allergic children are not exposed to peanut allergens are disproportional to the actual risk of such exposure. Dr. Christakis has also said that popular responses to the danger of peanut allergies "bear many of the hallmarks of mass psychogenic illness." Studies have shown that self-reported incidence of food allergies is higher than clinically-observed incidence of food allergies.
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