How to tell a food allergy from other adverse reactions to food

February 2006

NEW YORK — Many parents believe their children have food allergies because they define allergy as any adverse reaction to food. However, food allergy is defined strictly as an immune-mediated adverse reaction to food, Anna Nowak-Wegrzyn, MD, explained here at the 18th Annual Infectious Diseases in Children Symposium.

Toxic reactions are often misdiagnosed as food allergy, she said.

“Some of you might have heard about fish reactions in which spoiled fish [that] has a lot of histidine is metabolized to histamine. Somebody eats histamine and then experiences abdominal pain and flushing. It’s mimicking allergic reaction, but this is intoxication. And this group of nontoxic, nonimmune mediated disorders are classic for being confused with food allergy,” she said.

People who are lactose intolerant are missing an enzyme, which causes a reaction to dairy products. The reaction is not caused by the immune system fighting the lactose in the food.

Nowak-Wegrzyn said to remember allergic reactions are immune mediated reactions, and immunoglobulin E (IgE)-mediated food allergic reactions tend to be immediate. “These are the ones that manifest within minutes to hours and they can be life-threatening,” Nowak-Wegrzyn said.

The prevalence of food allergy in children is between 6% and 8%. Although any food is capable of causing an allergic reaction in a predisposed individual, most (over 90%) allergies are caused by cow’s milk, egg, peanuts and tree nuts, soy bean, wheat, fish and shellfish.

“Those foods contain proteins that are resistant to digestion and to cooking and heating; they’re also ubiquitous or they’re being introduced into the diet very early,” said Nowak-Wegrzyn.

Overall prevalence is lower in adults, (2% to 4%) who tend to be allergic to peanut and tree nuts, fish and shellfish. Those are also the most common allergens for life-threatening anaphylactic reactions.

“The prevalence of food allergy is increasing,” she said. Regarding specific allergens, 2.5% of infants younger than 1 year of age are allergic to cow’s milk, but most of them outgrow it, and 1.3% are allergic to egg. Peanut allergy in children has increased, she said.

“At this time it is estimated that, in the United States, peanut allergy affects 0.8% of children compared to 0.4% approximately five to six years ago. So, this is a visible increase in this prevalence,” Nowak-Wegrzyn said.

There are children in whom food allergy is more likely to occur. “Atopic dermatitis is one condition that is like a red flag and roughly one in three children with eczema have at least one food allergy. It is also estimated that 6% of asthmatic children may have respiratory symptoms induced by foods,” she said.

Nowak-Wegrzyn presented several cases to illustrate the differential diagnoses for food allergy.

Case 1

In the first case, a teenaged boy presented with wheezing and lip swelling. He had a history of peanut allergy from a distant reaction at the age of 5. He also had mild, intermittent asthma. He presented to the emergency room because he was short of breath and developed hives minutes after eating a snack that contained almond, according to the package, but did not mention peanuts as an ingredient. At the emergency department (ED), he was found to be wheezing, hypoxic, had diffuse urticaria and he was treated for anaphylaxis.

“This is truly a food anaphylactic, potentially life-threatening reaction,” she said. “However, he has no history of tree nut allergy. So, we don’t really know whether he was allergic to the almond. He probably reacted to some trace contamination of peanut.”

Nowak-Wegrzyn said that cross contamination of nut products is common. “This is an important point: Peanut is so ubiquitous and so it gets into all kinds of food products.”

The other important point of this case is that timing is critical, and people with food allergies should carry injectable epinephrine (EpiPen, Dey Pharmaceuticals) with them. They might not make it to the ED, she said. “A patient like this should have an EpiPen available with him at all times, and he should have injected himself with the epinephrine rather than waiting to get to the emergency room.

“This is important because delayed administration of epinephrine is identified as a risk factor for fatal food anaphylaxis,” she said.

Anaphylaxis is a systemic food allergic reaction that involves two or more organ systems. The symptoms may affect the mouth, airways, gastrointestinal (GI) tract, as well as the skin. GI symptoms tend to be nausea, vomiting and diarrhea; skin symptoms typically are hives, flushing, itching or angioedema.

“The onset of those reactions typically occurs within minutes, up to two hours, but the vast majority start within a couple of minutes up to an hour. Some patients may have so-called biphasic anaphylaxis in which they will improve initially with or without treatment, but within two to four hours, they will experience a second wave of symptoms that can be potentially more severe,” she warned.

Anaphylaxis can be mild. If somebody has sneezing and hives, it is still anaphylaxis. It’s a systemic reaction, but it’s not life threatening. The most worrisome reactions are those that involve the airways, she said. “Although skin symptoms are classic for allergic reactions — hives, itching or urticaria — there are multiple reports that now indicate that the most deadly severe anaphylaxis may progress without any skin manifestations,” she said.

“It is estimated that 30,000 cases of anaphylaxis due to food are occurring every year and there is probably around 150 deaths per year and the majority of the deaths are due to peanuts and tree nuts,” she said.

One study of fatal food-induced anaphylaxis identified 32 fatalities in patients aged 2 to 33 years, but most occurred in young adults and teenagers.

“So, it’s rather unlikely to happen for a child or infant who is in the care of the parents. But as they get older and become independent, this is becoming a reality. There is no difference in gender, but the vast majority of patients have a history of asthma. So, anyone with asthma and food allergy should be viewed as a higher risk person. And over 50% of deaths in this registry were due to peanut followed by tree nuts and some other food such as milk or seeds,” she said.

Only 10% of those patients with fatal reactions had epinephrine at the time of the reaction, even though 95% had a history of food allergy. “This is an important take home message: The risk factors for fatal food anaphylaxis include peanut and tree nut allergy, asthma, as well as delayed administration of epinephrine,” Nowak-Wegrzyn emphasized.

Case 2

The second case involved a 7-year-old girl with hives that presented eight weeks prior to the doctor visit. She had intermittent hives that appeared to be associated with meals. But she had been previously on an unrestricted diet without any problems. This is not a child who should be evaluated for food allergy, she said. “It’s unlikely that the older child with new onset of chronic urticaria and angioedema will have a food allergy,” she said. “However, having said that, I have to emphasize the younger the child, the more likely there will be food involved,” she added.

Chronic urticaria and angioedema is defined as symptoms lasting more than six weeks. In one study that involved more than 220 children who were referred for evaluation of food allergy, 30% had a positive allergy skin test. However, when those tests were followed with oral food challenges, which are the gold standard for diagnosing a food allergy, only 4% had symptoms confirmed.

Case 3

The third case involved an 11-year-old boy who had an itchy mouth after eating certain fresh fruits and vegetables, including apples, peaches, cherries, carrots and celery. However, he did not have the same reaction when he ate produce that was cooked. He had a history of atopy and hay fever. He was allergic to tree pollen with symptoms of allergic rhinitis in the springtime.

“When I saw him I skin tested him to the commercial extracts of those foods, but he was negative. He doesn’t have any skin rashes. However, when I did prick-prick skin test with raw fruit, he had an itchy welt. So, there’s no question — this is pollen food allergy syndrome. It’s a reaction to fresh fruits or vegetables,” she said.

“Traditionally it was described as oral allergy syndrome, reflecting the fact that this is typically a mild allergy. Unlike anaphylaxis or peanut allergy, this is unlikely to progress to systemic symptoms,” she said. The allergy is due to cross reactivity between the pollen IgE and homologous allergens in the plant foods. They are sensitive to heat; therefore, people will not react to the cooked fruits and vegetables, only the raw ones.

“This is a contact allergy that is confined to the oropharynx, but in large studies, up to 8% of patients may have some systemic reactions, including anaphylaxis, but it is relatively uncommon,” she said.

The urticaria is mediated by IgE mast cell activation. The symptoms are immediate: itching, tingling, swelling of the lips, tongue or palate, occasionally pruritus in the ears or throat tightness.

Case 4

The fourth case involved a 13-month-old girl who has had itchy rashes since early infancy. Her management regimen included frequent bathing, lubrication, daily treatment with medium-to-high potency topical steroids and sedating oral antihistamines to help her sleep. She was on a regular diet, including milk, egg and soy, as well as a variety of meats and fruits and vegetables. Her mother said she thought that tomatoes were associated with worsening of the rash. She was otherwise healthy.

Nowak-Wegrzyn said that this is likely to be a food allergy.

“Children with atopic dermatitis are a particular population who are at highest risk for having food allergy. We don’t know why, but that’s the observation we’ve made. And we have one in three chances that this child has at least one food allergy that is responsible for her skin symptoms. However, the more severe the eczema, which doesn’t remit despite the appropriate management … and the younger the child, the more likely food allergy is.”

One would think the mother would have noticed if milk or eggs were causing a reaction, but Nowak-Wegrzyn said that it is not unusual for a caregiver to miss the cause of an allergy. “It’s impossible to identify the offending food if the child is ingesting the food daily. They will have eczema that waxes and wanes, but there will be no particular pattern. However, if you remove the food for at least two weeks and then reintroduce it under supervision, then you will see hives and you will see acute rashes and other symptoms like vomiting or diarrhea in those children,” she said.

The most common food allergy in these children is to egg, which also serves as a marker for the risk of developing hay fever and asthma. Seventy percent of children with eczema and egg allergy by age 5 will develop hay fever and/or asthma. This type of child should be followed, she added.

Case 5

The fifth case was a 14-year-old boy with asthma and allergic rhinitis. He was on a regular diet and he presented with a 12-month history of difficulty swallowing, heartburn, pain and weight loss. He had not improved with proton pump inhibitors, which were given for gastroesophageal reflux.

Nowak-Wegrzyn said this is allergic eosinophilic esophagitis, a mixed IgE and non-IgE mediated disorder, which may be associated with peripheral blood eosinophilia in 50% of children. Clinical symptoms correlate with the extent of eosinophilic infiltration of the bowel wall.

Eosinophilic esophagitis prevalence is increasing to the point that some allergists are calling it an epidemic, according to Nowak-Wegrzyn.

“Ten years ago it was a rare occurrence, now it’s becoming more frequent and this may affect children in infancy, but more commonly we see patients who are adolescents, typically males, typically those with asthma … and they present with symptoms of reflux, vomiting, food refusal, abdominal pain, difficulty swallowing and, in extreme cases, with the weight loss or failure to thrive.”

The diagnosis is not facilitated by available allergy tests because they tend to be negative and, even if they are positive, they correlate poorly with response to the elimination diet, she said. Endoscopy is the gold standard for diagnosis. On endoscopy, esophagus may have a ringed appearance, similar to the trachea, as well as plaques that are typical of the eosinophilic inflammation.

Although most food allergies are outgrown by age 5, allergy to peanuts, tree nuts and shellfish tends to be lifelong. Diagnosis involves taking a detailed history, prick skin testing and measurement of IgE specific to the allergen in blood, as well as physician-supervised oral food challenges that are the standard of food allergy diagnosis.

“I would advise against fishing expeditions and testing for multiple food allergens that are in the child’s diet. If you want to do it in your office, I would suggest screening for the five most common foods: milk, eggs, wheat, soy and peanut. Allergists can offer more involved testing, such as prick skin testing and oral food challenges,” she said.

Management relies on avoidance, nutritional management, recognition and treatment of acute food allergic reactions, as well as counseling on natural history. Some young children may be placed on amino acid–based formulas, but they can be expensive and don’t always taste good. A new product called Neocate Infant tastes better and may be better accepted by patients, she said.

For more information:

• Nowak-Wegrzyn A. Clinical manifestations of food allergy. Presented at: 18th Annual Infectious Diseases in Children Symposium; Nov. 19-20, 2005; New York.