Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
A growing numbers of patients present to allergists with laboratory findings of food sensitization and low likelihood of reaction. It is imperative that the allergisst be able to give patients and parents a definitive answer. Clinical history, skin prick testing (SPT), and serum immunoglobulin E (sIgE) levels can only provide data to suggest the likelihood of reaction. The ultimate diagnosis is provided by an oral food challenge (OFC). An open OFC is safe, provided it is carried out in the office of a board-certified allergist. 85% of U.S. allergists perform oral food challenges for diagnosis of food allergy, however only 6% perform more than 10 OFCs per month (JACI, 2011). The duration of the procedure is 3 to 4 hours.
What is a food challenge?
Food challenge is consuming increasing amounts of suspected food at fixed intervals under observation. It is done by feeding gradually increasing doses of the suspected food at 10-30 minutes until a reaction occurs or a normal amount of the food is eaten without causing symptoms. All negative blind challenges end with an open challenge. Oral food challenges are essential to the diagnosis of food allergy.
Oral Food Challenges (click to enlarge the diagram).
3 Types of oral food challenges: DOS:
Double-blind placebo-controlled food challenge (DBPCFC)
Open food challenge (OFC)
Single-blind placebo-controlled food challenge (SBPCFC)
Open food challenge (OFC)
Both the physician and the patient are aware that the patient is eating the suspected food. The challenge food is not disguised in any way. For example, a child with a history of egg allergy is given increasing doses of scrambled egg every 30 minutes until a whole egg is ingested. Generally, OFC is used when the skin testing for the suspected food is negative.
In a retrospective medical record review of open food challenges in 109 patients, 27% of challenges were positive. Reactions were mild to moderate in 92% of positive challenges. Cutaneous reactions occurred in 68% of positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement. Food specific IgE values did not correlate with reaction severity. Interventions included observation or antihistamine only in 92% of positive challenges. No patient received epinephrine or required hospitalization. Negative challenges to milk, peanut, and egg, were predicted by pre-challenge food specific IgE.
Open food challenges are a safe procedure in the office setting for patients selected based on history and food specific IgE approaching negative predictive values.
Single-blind placebo-controlled food challenge (SBPCFC)
The physician is aware of what the patient is being fed, but the patient is not. The suspected food is disguised so the patient is unaware of the contents. For example, a child with a history of egg allergy is given egg hidden in other food.
Double-blind placebo-controlled food challenge (DBPCFC)
Neither the physician nor the patient know what the patient is being fed. The suspected food is disguised in another food. DBPCFC is the gold standard for diagnosing food allergy. DBPCFC is the method of choice for scientific protocols.
DBPCFC’s have taught us that:
- most case histories are inaccurate
- there is short list of foods in 90% of cases
- most children are allergic 1-2 foods only
The final dose of all 3 -- OFC, SBPCFC and DBPCFC, is open and the same -- a normal portion of the suspected food is ingested openly. All negative blind challenges end with an open challenge (OFC).
Clinical reactivity is ruled out once 10 grams of dry food is ingested.
Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to diagnose food allergy because it eliminates both patient and physician bias. In clinical settings though, open food challenge is the most practical test. DBPCFC is not often performed in non-academic allergy setting.
Preparation before food challenge
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction.
The patients should avoid the suspected food for at least 2 weeks (elimination diet).
Antihistamines should be discontinued at least 5 days prior to the challenge. Intravenous access should be obtained in patients with history of severe reactions.
The patient should be without symptoms, and fasting on the day of the challenge.
The procedure is cumbresome and labor intensive. The suspected food is hidden in opaque capsules to elminate taste and smell. Challenge with different foods on different days.
What is the dose in OFCs?
Typical total doses administered during a food challenge: 8-10 g of the dry food, 100 mL of wet food, doubling the amounts for meat or fish.
Food challenge dosing scheme: divide the total challenge into 7 incremental doses: 1%, 4%, 10%, 15%, 20%, 25%, 25% of the total dose.
Graded doses of either a challenge food or a placebo food are administered every 10-30 minutes. Wait for 30 minutes after the last dose. Clinical reactivity is ruled out once 10 grams of dry food is ingested. Most OFCs use doubling doses every 15 minutes until an age-appropriate serving size is administered.
What happens after the final dose in OFC?
All patients should be monitored for at least 2 hours postchallenge and instructed to contact the allergy clinic for any delayed reactions.
Precautions
Oral challenges should not be performed in patients with a clear history of reactivity or a severe reaction. If there is a history of a severe anaphylactic reaction, do not perform an oral food challenge.
Severity of allergic response is on a continuum:
Subjective --> Objective --> Anaphylaxis --> Death
In asthma, ensure long wash-out periods, FEV1 ≥ 80%, and follow-up with FEV1 hourly for 6 hours after the challenge.
When performed by a board-certified allergist, oral challenge is a very safe procedure. There have been no deaths related to oral food challenge for food allergy, when performed in physician offices, according to literature indexed since 1976.
What happens when the patient "fails" the food challenge?
In a study of 584 food challenges, 43% resulted in an allergic reaction. Of patients who "failed" the challenge, there were 78% cutaneous, 43% gastrointestinal, 26% oral, 26% lower respiratory, and 25% upper respiratory reactions. No patients had cardiovascular symptoms.
There was no difference between foods in the severity of failed challenges or the type of treatment required to reverse symptoms. All reactions were reversible with short-acting antihistamines ± epinephrine, β-agonists, and/or corticosteroids. No children required hospitalization, and there were no deaths.
Other Important Diagnostic Tests in Food Allergy
Skin Prick Tests
Skin prick test (SPT) is the quickest and cheapest test for diagnosing food allergy. SPT can be performed with non-standardized allergens, for example, fresh apple. Some allergists reportedly use themselves as controls to rule out non-IgE mediated reactions.
Positive predictive accuracy of SPT is less than 50%. Negative predictive accuracy is higher than 95%. Negative skin test results essentially confirm the absence of IgE-mediated reactions.
Positive skin prick test or ImmunoCap indicates presence of IgE antibody NOT clinical reactivity (~50% false positive).
Negative skin prick test or ImmunoCap essentially excludes IgE antibody (higher than 95% accuracy).
Patients who passed the OFC without adverse symptoms had significantly smaller SPT wheal size (median, 3 mm vs. 4 mm) and significantly lower sIgE levels to the challenged foods (median, 0.63 kUA/L vs 1.06 kUA/L) as compared with the group that had a reaction during the OFC (JACI, 2011). The majority of reactions, 57%, were cutaneous, 88% were treated with antihistamine alone. Only 1.7% of the challenges required treatment with epinephrine, a rate that is equivalent to systemic reactions to subcutaneous immunotherapy (SCIT).
ImmunoCap Immunoassay (sIgE)
The ImmunoCAP method was developed by Phadia. It utilizes a “sandwich” ELISA technique:
1. The ImmunoCAP sponge has allergen bound to it and serves as the first piece of bread ("bottom half").
2. Patient serum is added and specifc IgE to that allergen binds to the allergen on the sponge - this is the "meat" of the ELISA sandwich.
3. All of the unbound protein is washed away abd anti-IgE is added - this binds to the sIgE that was captured by the sponge in step two. The anti-IgE conjugate is the "second piece of bread" ("top half").
Allergen-specific IgE levels are not comparable between different laboratory methods - for example, ImmunoCAP vs. DPC Immulite 2000. Predictive values of specific IgE levels published in the literature for management of food allergies are based on studies using the ImmunoCAP assay. These predictive values cannot be applied to specific IgE levels from other assay systems.
ImmunoCAP is a IgE fluoroenzyme immunosorbent assay. The levels vary from 0.1 to 100. The previous threshold was 0.35.
Food specific IgE cut off levels which predict 50% pass rate for challenge tests (Perry et al. JACI 2004):
Food IgE level (KUA/l)
Milk 2
Egg 2
Peanut 2
Wheat 2
ImmunoCAP threshold levels (less than 0.1) are well-established for 4 foods: milk, egg, peanuts and wheat.
The new cut-off threshold is 0.1. Specific IgE level of less than 0.1 predicts a negative food challenge test in most patients. It is important to note that in 10–25% of food allergy reactions, sIgE can be undetectable by blood test (http://buff.ly/1e7HAmY).
Negative ImmunoCAP and negative SPT give a 90% chance of a negative food challenge test. SPT provides a lower threshold than ImmunoCAP.
8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).
Diagnostic algorithm for food allergy: SAD Child:
1. Symptoms: close relation between specific food intake and symptoms, often affect 2 or more organs
2. Allergy testing: skin prick testing or ImmunoCAP.
3. Diagnostic diet: restricted diet leads to symptoms disappearance or significant reduction
4. Challenge - oral food challenge.
Comparison of diagnostic methods for peanut, egg, and milk allergy - skin prick test (SPT) vs. specific IgE (sIgE) (click to see the spreadsheet). Sensitivity of blood allergy testing is 25-30% lower than that of skin testing, based on comparative studies (CCJM 2011).
References: Clinical review: ABC of allergies, Food allergy. BMJ 1998;316:1299, figure.
References
Oral food challenge testing for food allergy. JACI, 2009.
Outcomes of office-based, open food challenges in the management of food allergy. JACI, Volume 128, Issue 5 , Pages 1120-1122, November 2011.
Food Allergies. eMedicine.
Risk of oral food challenges. JACI, Volume 114, Issue 5, Pages 1164-1168 (November 2004).
Safety of open food challenges in the office setting. Ann Allergy Asthma Immunol. 2008 May;100(5):469-74.
What is a food challenge? National Jewish Health.
Manifestations of Food Allergy: Evaluation and Management. AFP, 1999.
Overdiagnosis of Food Allergy: IgE and skin-prick testing should be confined to the realm of experts (allergists). Medscape, 2011.
False-negative oral food challenge is a rare occurrence http://goo.gl/VDKY7
PowerPoint Presentations
Food Allergy. Global Resources in Allergy (GLORIA) Module 6.
Food Allergy. Againdra K. Bewtra, M.B.B.S., M.D.
Food Allergy Update. Suzanne S. Teuber, M.D.
Oral Challenge Studies: Purpose, Design and Evaluation. Stefano Luccioli, MD.
Food Allergies in 2006: From The Clinic to The Classroom. Jeffrey M. Factor, MD.
Food Allergy… the nuts and bolts. Tom Gerstner, MD, FRCPC.
Food Allergen Avoidance. V. Dimov, Oct 2008.
Audio and Video
Food Allergy and Additives. Presented by Sami L. Bahna, MD, DrPH. ACAAI Vodcasts 2007 (video).
Challenging children to see if they have overcome a food allergy: a video Health Tip. Plain Dealer, 2010.
Food challenges. National Jewish Health, 2009.
Food challenges. The Today Show, 2009.
When And How Do You Perform Food Challenges? ABC.com.
Food Challenges For Children With Allergies. ABC.com.
General Questions About Food Allergies. ABC.com.
Patients Handouts and Related Reading
The Food Allergy & Anaphylaxis Network.
Putting a face on food allergies - USA Today readers share their stories about dining out with food allergies, 2010.
Milk allergy resolution calculator from CoFAR http://bit.ly/U6TkNS - Mobile version: http://bit.ly/U6TmFn
Twitter comments
@AllergistMommy: Oral challenge uneventful = success! One more person freed from the shackles of peanut allergy!
The Food Challenge Challenge http://buff.ly/Ql0fCh - Remember: No one "fails" a food challenge. The test is either positive or negative.
Published: 07/07/2007
Updated: 05/15/2013
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