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The nuts and bolts of peanut allergy

The principles for successful management of peanut allergy include patient education,
treatment of the acute reaction, and appropriate follow-up care.

Alex T. Vu, MD; Minh-Tri Duong, PharmD

Alex T. Vu is a board-certified allergist/immunologist at Partners in Allergy and Asthma Care, Valrico, Florida. Minh-Tri Duong is a clinical pharmacist at Tampa General Hospital and Director of the Pharmacy Practice Residency Program, Tampa, Florida. The authors have indicated no relationships to disclose relating to the content of this article.

CASE

A 24-year-old Asian male presents to the clinic with complaints of oral pruritus, facial flushing, and nausea intermittently after meals. He has a history of childhood eczema and had a severe anaphylactic reaction to peanut butter at age 4 years. His mother reported that he experienced shortness of breath, facial swelling, and flushing several minutes after eating the peanut butter. After a complete history and physical examination and a laboratory investigation, peanut allergy was diagnosed. The patient now avoids all peanut products but still reports episodes of worsening symptoms when eating certain foods. How should this patient be managed?

DISCUSSION

An allergy is a state of hypersensitivity that is induced by exposure to an antigen or allergen and that results in harmful immunologic reactions on subsequent exposures. Allergic reactions to food account for 30,000 anaphylactic episodes, 2,000 hospitalizations, and 200 deaths each year in the United States.¹ The majority of these fatal and near-fatal reactions are due to exposure either to peanuts or to tree nuts.² A national, random telephone survey found that 1.1% of Americans, or 3.3 million people, are allergic to peanuts, tree nuts, or both.³ The prevalence of peanut allergy continues to rise in the United States and in other westernized countries.⁴ This article reviews the epidemiology, diagnosis, and management of peanut allergy.

Peanut allergens The peanut consists of the kernel and the outer skin, called the testa. The kernel is made up of 50% oil, 30% protein, 10% carbohydrate, and a mix of ash, moisture, and fiber.⁵ The testa is 50% carbohydrate and 20% fiber.⁵ Peanut proteins are the primary allergens, and three have been identified: vicillin (Ara h 1), conglutin (Ara h 2), and glycinin (Ara h 3).⁵ Because peanut oil does not usually contain peanut protein, it is unlikely to cause symptoms. Nonetheless, patients who have had severe reactions (anaphylaxis, angioedema) to peanuts should avoid cooking with, eating, or using peanut oil.

Milk, eggs, peanuts, and tree nuts are responsible for 90% of food allergies that occur in children. In comparison, shellfish, peanuts, tree nuts, and fish cause most of the symptomatic food allergies that ocur in adults⁶ (see Table 1).

The prevalence of peanut allergy is rising in the United States.⁴ In the past several decades, growing demand for “quick-energy” foods has made the peanut a staple of the American diet. During pregnancy and lactation, consumption of peanuts by the mother exposes the fetus or infant to peanut proteins in-utero or via breast milk;⁷ and the immaturity of the child’s immune system may predispose toward the development of allergy.⁸ This might explain why young children can have an allergic response after the first ingestion of peanut proteins.⁹ Cooking methods using higher temperatures—such as roasting instead of broiling or frying—alter the peanut proteins, making them more allergenic. Peanut allergy is more prevalent in the United States than in China, and this may be partly attributable to preferred cooking methods in each country—roasting in the United States and boiling or frying in China.¹⁰

People with peanut allergy are also at risk for reactions to other legumes and nuts. About 15% of persons allergic to peanuts experience symptoms with ingestion of soybeans, and 25% to 35% will also react to tree nuts—usually walnuts, followed by cashews, almonds, pecans, pistachios, Brazils, and macadamia nuts.⁸

Pathophysiology The main function of the GI tract is to process ingested food into a form that can be used for energy and cell growth. This requires that the mucosal cells lining the GI tract be able to distinguish between harmful and harmless foreign proteins. The nonpathogenic immunologic response that permits the processing of ingested antigens without any sequelae is called oral tolerance.¹¹ The loss of oral tolerance leads to an allergic response.

Although the underlying immunologic mechanisms that are involved in oral tolerance have not been fully elucidated, a failure to develop or a breakdown in oral tolerance is known to result in excessive production of food-specific IgE antibodies.¹² These antibodies predominantly bind to receptors on mast cells and basophils. When food penetrates the mucosal barriers and reaches IgE antibodies bound to mast cells and basophils, mediators (histamine, leukotrienes, and others) are released, resulting in arteriole vasodilation, smooth muscle contraction, bronchoconstriction, increased vascular permeability, and mucus secretion. This sequence of events results in symptoms of immediate hypersensitivity or anaphylaxis.

The activated mast cells may release cytokines that incite the late-phase reaction. In the 24 to 48 hours after exposure to the allergen, inflammatory cells (lymphocytes and monocytes) infiltrate the area. With repeated food exposure, the inflammatory cells release histamine-releasing factor, a cytokine that binds to mast cells and basophils and increases their releasibility.¹³ Cytokines released during this period elicit the symptomatology of the late-phase of the biphasic reaction (see Figure 1).

Clinical manifestations Exposure to peanuts may cause mild to severe symptoms of anaphylaxis in an allergic patient. Food-induced anaphylaxis usually includes one or more of the manifestations listed in Table 2. Progressive respiratory symptoms, hypotension, and dysrhythmias occur with near fatal or fatal reactions. The symptoms are often mistaken for severe status asthmaticus or an acute cardiovascular event. It is not known why peanuts provoke different constellations of symptoms in different people. Patients with a history of asthma and/or atopy may experience more severe reactions. A history of symptoms and signs during a systemic food reaction may be useful, as the symptom pattern tends to reflect prior reactions.

Symptoms generally develop within minutes to a few hours of ingestion. Biphasic reactions are noted in up to one third of patients.² The biphasic response involves initial symptoms (primary phase), followed by a quiescent period, then by the return of symptoms (secondary phase) several hours later. The secondary reaction may be similar, less severe, or more severe than the initial reaction.² The secondary reaction is unpredictable but is generally more likely with severe initial reactions.

Diagnosis The diagnosis of peanut allergy is based on the history, physical examination, and pertinent laboratory and other diagnostic tests. Anaphylaxis is a syndrome, and there is no single element of the complete assessment that excludes or establishes the diagnosis. Rather, the constellation of findings in the appropriate circumstance and a response to treatment support the diagnosis of anaphylaxis. The medical history is the most important diagnostic tool. The diagnosis is largely dependent on the patient’s recollection of symptoms and the examiner’s ability to differentiate between disorders provoked by food hypersensitivity and other etiologies. Questions that should be asked during the history are listed in Table 3¹⁴.

A small number of foods are responsible for the vast majority of cases of food-related anaphylaxis. Behavioral symptoms and “adverse reactions” to dyes and additives are rare or nonexistent.⁵ Food allergy and atopic dermatitis commonly occur together.¹⁵ Despite the importance of the history in making the diagnosis, the circumstances of anaphylaxis often make the accuracy of the history suspect. Confirmatory or refuting information should be sought from others who observed the reaction, particularly when the diagnosis is unclear.

Special attention during the physical examination should be placed on the vital signs and on the cutaneous, respiratory, and GI systems. Tachycardia and hypotension suggest anaphylaxis. Urticaria, angioedema, or a morbilliform rash is probably the most common physical finding. Wheezing in both lung fields or over the trachea (stridor) is essential to document and indicates bronchial and bronchiolar narrowing. If stridor is present, this suggests tracheal or laryngeal narrowing and potential airway obstruction, but wheezing without stridor can eventually lead to airway compromise due to impaired gas exchange, particularly in a patient with asthma. Abdominal guarding, rebound, abnormal bowel sounds, and bloody stools are important elements of the abdominal examination. Bloody stools suggest an infectious or nonallergic cause of symptoms.

After a careful history and physical examination, one or two foods should stand out as the potential cause of the patient’s symptoms. Initial testing includes a diet diary and an elimination diet. The patient is first asked to document everything consumed and any associated symptoms during a specified period of time, ranging from days to months. The diary should include gum, candies, spices, condiments, and beverages. This method collects information on a prospective basis and is not dependent on the patient’s memory. The diet diary is useful but not perfect since patients may omit some ingested items or be unaware of the variety of ingredients in some foods.

If an offending food is identified through the diary, the food is then eliminated from the diet to see if symptoms resolve. The success of this step depends on the identification of the correct allergen(s), the ability of the patient to completely avoid the offending agent, and the assumption that other factors do not provoke similar symptoms. When the diet diary and elimination diet suggest a certain food as the culprit, the patient should be referred to an allergist for confirmatory tests.

These may include prick skin testing (PST) and/or radioallergosorbent testing. PST is specific and easy to perform and is preferred to detect food allergy. A positive test result means only that the patient has a possible symptomatic reaction to the food, but a negative result excludes IgE-mediated food allergy. However, a positive PST result along with a clinical history consistent with food allergy effectively confirm the diagnosis.

The gold standard for diagnosing a food allergy is the double-blind, placebo-controlled food challenge.¹⁴ In this test, the patient is given the suspected food or a placebo and monitored for reactions. All negative challenges must be confirmed by an open feeding under observation. The risks associated with this method limit its use in clinical practice; single-blind or open food challenges are more commonly utilized. Such challenges are more readily performed in an outpatient setting.

Management The three principles for successfully managing peanut allergy include patient education, treatment of the acute reaction, and providing appropriate follow-up. The cornerstone of management is education.

Patients should be instructed to avoid all peanut products and all foods that potentially contain peanut protein. They should be taught to check the labels of suspect foods, including baked products, cereals, Asian dishes, crackers, ice cream, and health bars. Avoiding high-risk situations such as buffets, ice-cream parlors, and unlabeled candies and desserts may reduce the incidence of reactions. Patients are advised to call their airlines when traveling to find out if peanuts or foods containing peanut byproducts are being served and to request alternative meal options. Several airlines have eliminated peanut snacks because of one reported anaphylactic reaction during flight caused by peanut dust when packages were opened.^2,16 Highly processed oils (eg, acid-extracted, heat-distilled oils such as olive, canola, palm, and corn oil [and lard]) do not contain peanut proteins and thus are safe. Cold-pressed or extruded peanut oils should be avoided as these may contain proteins that are allergenic.¹⁵

Patients should also understand that certain medications must also be avoided. Severe, life-threatening anaphylactic reactions have been reported in peanut-allergic patients who have used ipratropium (Atrovent) or ipratropium/albuterol (Combivent) metered-dose inhalers (MDIs).^17,18 Both products utilize a suspension agent, soy lecithin, which contains trace amounts of soy protein.^17-19 While the MDIs should be avoided, patients may safely be prescribed ipratropium nasal spray and nebulizer solutions, as these formulations do not contain soy lecithin.

Another drug, a formulation of micronized progesterone marketed under the trade name Prometrium, should also be avoided because the capsules contain peanut oil.²⁰ Clinicians and patients should be aware of the trace amounts of peanut proteins or soy lecithin in various pharmaceutical products.

Despite using caution, however, patients will probably be inadvertently exposed to peanut allergens. When anaphylaxis occurs, they should be brought to the emergency department. Treatment entails placing the patient in a recumbent position and elevating the legs to maximize blood flow to the brain, heart, lungs, and other vital organs. Supplemental oxygen and airway assessment should be performed. Normal saline should be administered if the patient is hypotensive.

Epinephrine 0.3 mg, 1:1,000 weight-to-volume, injected IM in the anterior lateral thigh, permits the fastest systemic absorption in adults.²¹ For children, the recommended epinephrine dose is 0.01 mg/kg. The dose can be repeated every 5 to 10 minutes if there is no clinical improvement. Histamine-receptor inhibitors such as diphenhydramine and ranitidine in standard doses may be used as adjunctive therapy. Diphenhydramine is preferred because it can be administered IV. Although oral prednisone or IV methylprednisolone have been used, systemic corticosteroids have not been shown to mitigate the acute reaction; they may, however, reduce the severity of the secondary phase. Nebulized albuterol is a consideration if bronchospasm occurs. Beta-blockers increase the severity of anaphylaxis by blunting the effects of epinephrine, and IV glucagon may be useful to reverse the blunting in patients taking beta-blockers.

After the anaphylaxis resolves, patients should be observed for several hours to determine whether a secondary response develops. Instructions should be provided to return immediately or seek emergent care if symptoms recur within 24 hours of the initial episode. Sometimes, overnight observation is warranted. Patients should carry self-injectable epinephrine (eg, EpiPen) in case anaphylaxis occurs. Once the patient is discharged, follow-up should be scheduled with the primary care provider within a couple days, and the primary care clinician should refer the patient to an allergist for further evaluation.

New treatments While the cornerstone of management for peanut allergy relies on patient education, avoidance, and treatment of acute reactions, new therapies are constantly being investigated. The use of activated charcoal for the acute management of peanut allergy has been studied in a nonrandomized investigation.²² Activated charcoal forms non-IgE-binding complexes with peanut proteins, preventing their absorption and thus preventing the allergic response. Since accidental exposures to peanuts usually involve small amounts, theoretically, low doses of activated charcoal may be used to prevent an allergic response.

A new drug, omalizumab (Xolair), is the first recombinant human anti-IgE monoclonal antibody approved by the FDA for the treatment of allergic asthma.²³ Omalizumab forms a complex with IgE and reduces the release of mediators from mast cells and basophils.²⁴ Anaphylaxis from peanut allergy is also IgE-mediated, so omalizumab has potential for treating this condition. In a randomized control trial, the drug allowed study patients to increase their tolerance of peanuts from one half a peanut (before treatment) to nine peanuts (after treatment) before developing symptoms of anaphylaxis.²⁵ Increased tolerance means less likelihood that anaphylaxis will develop with accidental exposure. Although omalizumab is approved only for allergic asthma, the FDA has given it fast-track status for peanut allergy and a multicenter trial is currently underway.

Outcome The peanut-allergic patient in this case was instructed to continue avoiding all peanut products and asked to carefully read all food labels. Instruction on how to use injectable epinephrine was provided. The patient was told that when injectable epinephrine is required, he should seek immediate emergency care.

REFERENCES

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