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.