A 16-year-old boy with asthma, chronic rhinitis, and multiple food allergies presented to the Pediatric Allergy & Immunology Clinic for evaluation of food allergies after a hospitalization requiring PICU admission for a hypocalcemia-induced seizure. In November 2018, the patient first developed aches and pains while playing volleyball and experienced intermittent tingling in the hands and lips. He experienced chest pressure and was evaluated at an Urgent Care Center, in which he was found to have a prolonged QT (measurement of ventricular polarization [consisting of QRS complex, ST segment, and T wave] on electrocardiogram [ECG]) interval. He was referred to Pediatric Cardiology, and the QTc interval (508 milliseconds) was confirmed in December 2018. Electrolytes obtained were found to be significant for hypocalcemia, with a serum calcium level of 7.3 mg/dL (normal between 8.4 and 10.2 mg/dL), and normal sodium, potassium, and magnesium levels. He had a normal stress test and exercise capacity for his age. It was thought that his symptoms were related to significant electrolyte imbalance, which could explain the significant QTc prolongation as well as muscle cramps, but overall, these symptoms were improved. He was not restricted from activity and was encouraged to take electrolyte tablets during and after sports practices to see if the long QT interval would improve.
In March 2019, he had a generalized tonic-clonic seizure in his home after a day of school and volleyball practice. He was given 2 doses of epinephrine separated by 60 seconds because of parental concern for anaphylaxis. The seizure lasted for ∼3 minutes, and he was somnolent until EMS arrived. He was admitted to the PICU for correction of severe hypocalcemia (calcium level of 4.8 mg/dL, normal 8.4–10.2 mg/dL), and was found to have an elevated parathyroid hormone, concerning for vitamin D deficiency.
Potential causes of vitamin D deficiency were ruled out, including vitamin D resistance, autoimmune or genetic hypoparathyroidism, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, end-stage renal or liver disease, metastatic parathyroid disease, post-radiation injury, exposure to heavy metals, phosphate, citrated blood transfusion or drugs that could lead to low vitamin D, hyper/hypo-magnesemia, Fanconi and “Hungry Bone” syndromes, limited sun exposure, low animal fat intake, fat malabsorption. He was followed closely by Pediatric Endocrinology, and vitamin D supplementation started after calcium levels improved to levels >7 mg/dL. The vitamin D deficiency was ultimately attributed to his severely limited diet in the setting of multiple food allergies that were diagnosed in early childhood. In summary, a teenager with a severely limited diet due to food allergies presented with a hypocalcemia-induced tonic-clonic seizure.
Because of multiple food allergies diagnosed in early childhood, the patient had eliminated wheat, milk, eggs, peanuts, tree nuts, fish, shellfish, blueberries, and beef. He was solely breastfed until 9 months of age when he was transitioned to soy formula. Around that time, he developed diffuse hives after touching (not ingesting) spaghetti and subsequently underwent comprehensive food allergy skin prick testing (SPT) with an allergist. Positive SPT results led to the removal of wheat, milk, egg, peanut, tree nuts, fish, and shellfish from his diet, although many of these foods had not yet been ingested. As a toddler, his diet was further restricted after he developed difficulty breathing with blueberry bar ingestion and abdominal pain/diarrhea with beef ingestion. He continued for many years without these foods until evaluation at our hospital during this admission for hypocalcemic seizures.
Since his initial presentation to our Pediatric Allergy & Immunology Clinic, he has been tested for each of these foods and has reintroduced numerous foods on the basis of favorable repeat testing via oral challenges. Thus far, he has passed challenges to wheat, baked/unbaked milk, baked egg, blueberries, beef, and shrimp and, subsequently, introduced finned fish at home. He continues to avoid peanuts, tree nuts, and unbaked eggs, with a plan to proceed with challenges to select tree nuts and unbaked eggs.
This case illustrates the importance of clinical discretion in the workup of food allergies and avoidance recommendations when the history is not suggestive of an IgE (Immunoglobulin type E)-mediated reaction. The following discussion examines the evidence behind the management of this patient and provides an analysis of consequences associated with long-term, early childhood food avoidance.
Skin Prick and Serum IgE Testing: When Is Broad Food Allergy Panel Recommended?
The proper diagnosis of a food allergy requires patients to have both an appropriate clinical history and valid allergy testing via SPT or serum-specific IgE levels.1 Importantly, patient-reported clinical history should guide clinicians to offer focused food allergy testing; there is no indication for food panels, which tests for multiple foods. As recommended in national guidelines after the Learning Early about Peanut Allergy trial,2 infants with severe eczema, egg allergy, or both should introduce peanuts as early as 4 to 6 months of age. Although these guidelines recommended strong consideration for peanut testing in high-risk patients, newer consensus statements propose that testing and/or in-office introduction is not required and home introduction or supervised oral challenge are options for any positive test result. Other potentially allergenic complementary foods should not be deliberately delayed after food introduction has commenced at ∼6 months of age.3
In this case, the patient received broad food allergy testing after experiencing diffuse hives in response to just physical contact with spaghetti. Important clinical history to consider includes the timing of symptoms after contact with spaghetti (≤2 hours is expected for food allergy), other associated symptoms (shortness of breath, cough, wheeze, vomiting, diarrhea, swelling), and whether there was an alternative explanation for symptoms, such as irritant skin reaction, in this case. Food allergy IgE panels have no role in the workup of food allergies; specific foods to which it was thought to cause a reaction should be selectively tested because false positive tests are possible.4 Suspected foods should then be challenged on the basis of testing and history.1 Not only does the diagnostic value of IgE testing decrease when the history is not suggestive of an IgE-mediated reaction, inappropriate testing can lead to improper use of health care resources and cause serious, long-term, adverse outcomes for children and their families because of resulting unnecessary food avoidances.1
Psychosocial Harms of Early Childhood Food Avoidance
Although inappropriate treatments can lead to inadequate growth and restricted nutrient intake, as reported in this case,5 indiscriminate food allergy testing can also have serious psychological consequences on patients and their families. Food allergies and avoidance can impact a child’s lifestyle, mental health, food cost, and health care cost.5,6 Some children with IgE-mediated allergic reactions to food have reported fear responses so severe that they developed posttraumatic stress symptoms.7 Emotional distress can arise because of separation from an adult caregiver, fear of unpredictable allergic responses in unfamiliar environments, and even bullying by peers about their medical restrictions.5 Childhood food allergies have also been reported to correlate with parental decreases in quality of life and increases in rates of anxiety and depression.8 This case serves as an important reminder of the medical outcomes and social impacts of early-childhood food avoidance.
Finding Balance for Safe Food Avoidance Practices
The primary strategy for the prevention of hypersensitivity reactions is complete avoidance of all potential allergens.9 The Food and Drug Administration, therefore, requires the clear identification of all major food allergens on packed foods and beverages. The Food Allergen Labeling and Consumer Protection Act of 2004 identified 8 foods as major food allergens (milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soybeans), with the recent addition of sesame. Advisory statements such as “may contain [allergen]” or “produced in a facility that also uses [allergen]” are not required by law, but can be used to warn consumers about unavoidable cross-contact.10 The concern for accidental ingestion motivates many providers and parents to strictly avoid foods with the potential of exposing a patient to even diminutive amounts of an allergen, as was the case in this case presentation.11 The patient’s strict avoidance of any potentially related foods was for his safety but also resulted in severe medical complications. Precautionary allergy labeling intends to ensure safe food exposures, but patients with food allergies have also reported confusion about labeling, paying more for foods, and diminished quality of life.12 This highlights the need for a more effective method of determining which foods meet the threshold to require warning labels so patients and their parents can make better-informed decisions on food avoidance.
Cost-Effectiveness
The fundamental role of value-based care is to ensure patients receive the best clinical outcomes at the lowest expense.13 Recent estimates reveal that the incidence of pediatric food allergies has also increased to 8% to 12%, making it even more imperative for clinicians to pursue appropriate workups.14 There are many aspects of food allergy care that are noted to be cost-inefficient, including screening without proper indications, delayed oral tolerance testing, and accessing emergency medical services without indications when exposed to an allergen.15 Food reintroductions in an oral challenge clinical setting are costly and time-consuming, causing missed work/school days in addition to the cost of the procedure itself. Patient and parental education centered on personal preferences can help minimize low-value care without compromising individuals’ comfort.11 In-patient admissions offer a touchpoint for families and may offer an opportunity to discuss medication and food allergies listed. Children, as opposed to adults, often outgrow food and medication allergies, and thus, evaluation with an allergist is recommended.
Lessons Learned
This report highlights the overall importance of clinicians utilizing discretion when offering patients expensive and potentially harmful diagnostic testing, as well as insight into the harms of strict food avoidance across multiple food groups. Based on this patient’s most recent skin prick and serum IgE results, several of the restricted foods would be safe for consumption at home or for an oral challenge in the office. By spending the time to initially educate patients and caregivers about the implications and management of food allergies, clinicians can potentially minimize the long-term negative nutritional, medical, and psychosocial consequences of severe food restriction. For the hospitalized pediatric patient, when food allergies are noted, even if tangential to the reason for admission, inquiring further about dietary, social, and family impact, as well as confirming allergist involvement, would add immensely to preventative and value-based care.
Dr Bogale drafted the initial case presentation and reviewed the final manuscript; Dr Hershberger reviewed and revised the manuscript; Dr Stern reviewed and revised the manuscript and managed his outpatient allergy care; Dr Jhaveri critically reviewed and revised the manuscript and managed his inpatient allergy consultation and outpatient Allergy care; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: No external funding.
CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.
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