Oral Food Challenge Procedure

Oral Food Challenge Procedure for IgE-mediated (Type I) Reactions


1. Identify candidates for OFC

  • If negative SPT, undetectable food-sIgE level, and no history of convincing immediate food allergy (eg, symptoms limited to behavioral changes or delayed/chronic GI symptoms), then consider gradual home introduction of the food

Indications

  • Diagnosis of food allergy and monitoring resolution of food allergy
  • Expand the diet in persons with multiple dietary restrictions
  • Assess the status of tolerance to cross-reactive foods
  • Assess the effect of heating/processing on food tolerability, e.g., fruits and vegetables that may be tolerated in cooked form in the pollen-food allergy syndrome, or egg or milk that may be tolerated when baked in foods
  • Low likelihood of reacting to the food as predicted by the food reaction history, levels of serum food-sIgE; and/or results of SPT and the patient’s age.
    • Factors that favor a negative OFC:
      • Clinical: recent accidental ingestion without symptoms, no history of severe reaction, food not usually associated with fatal anaphylaxis, no asthma.
      • Testing: smaller wheal on SPT and lower food sIgE generally associated with lower risk for positive OFC (Table 1).

Table 1
~50% Negative OFC
Test
sIgE (ImmunoCap)
----SPT----
----Cow’s milk----
≤2
n/a
Egg
≤2
≤3
Peanut
≤2 with
and ≤5 without history of reaction
≤3
Note: Peanut sIgE <0.35 still associated with 4-28% chance of reactivity

Relative Contraindications

  • Recent convincing anaphylactic reaction to the food
  • Unstable asthma
  • Cardiovascular disease
  • Beta-blockers
  • Pregnancy
  • Medical conditions that may interfere with interpretation (eg, uncontrolled eczema and severe allergic rhinitis)
  • High likelihood of reacting to the food as predicted by the food reaction history, levels of serum food-specific IgE antibody; and/or results of SPT and the patient’s age.
    • Factors that favor a positive OFC:
      • Clinical: recent reaction to food in past 6-12 mo, history of severe reactions in past, food usually associated with fatal anaphylaxis (peanut, tree-nut, seeds, shellfish, finned fish), comorbid asthma, beta-blocker, cardiovascular disease, difficult IV/airway access.
      • Testing: larger wheal on SPT and higher food sIgE generally associated with higher risk for positive OFC (Table 2).
Table 2
~95% Positive OFC
Test
-----sIgE (ImmunoCap)-----
-----SPT-----
-----Cow’s milk-----
≥15 (≥5 if <1 yo)
≥8
Egg
≥7 (≥2 if <2 yo)
≥7
Peanut
≥14
≥8
Fish
≥20
n/a
Walnut
≥18.5

~73-74% Positive OFC
Soy
≥30

Wheat
≥26



Special considerations for cow's milk (DRACMA)

OFCs In Children With Previous Anaphylactic Reaction
  • A recent anaphylactic reaction to cow’s milk contraindicates OFCs except in the following situations:
    • If the severe reaction occurred immediately after simultaneous introduction of many foods at the same time: typical example is the introduction of the first solid meal including CM proteins (and many other putative food allergens) in a breast-fed infant.
    • For the assessment of tolerance to cow’s milk after a reasonable period from previous anaphylactic reaction.
  • In these cases, the hospital setting with ICU availability is mandatory.

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2. Determine type of OFC

  • Open OFC – unblinded challenge with food in natural form, usually done if objective symptoms are expected and there is low potential for bias. If subjective or difficult to verify symptoms result, consider blinded OFC.

  • Single-blind (±placebo) OFC – food is disguised, used if potential for patient bias or history of symptoms that are subjective or difficult to verify.
    • SBFC – patient told that the test food may or may not be served during the challenge, then the disguised food is given.
    • SBPCFC – placebo and test food given, ideally in 2 sessions (one with placebo, one with test food) separated by ≥2 hours. Patients with subjective symptoms may need multiple sessions (eg, 3 sessions with test food, 2-3 with placebo). Patients with delayed symptoms may need longer interval between sessions.

  • DBPCFC – gold standard for diagnosis of food allergy, minimizes patient and observer bias. Test food prepared and coded by third party and the sequence of sessions (placebo or test food) is random.
    • Administrations of active and placebo challenges on separate days is preferred. If the active and placebo test challenges are given on the same day, they should be separated by 3 h. Administration of active and placebo doses in the same challenge is not recommended.



3. Select location for OFC

  • For OFC with a greater likelihood of severe reactions, the decision to perform OFC in the office should consider support staff, distance from the hospital, EMS response time, and office preparation. Otherwise, these OFCs are preferably conducted in a hospital with supervision and immediate availability of emergency treatment.
    • DBPCFC performed prior to oral IT trials (where reactions are expected to occur) are typically performed as an inpatient with IV access, and modified dosing schedules (e.g. lower starting dose, increased interval between doses, extended observation time)
  • When there is a very high risk for a severe reaction but OFC is required, challenges preferably should be done in the ICU.
  • Consider IV access for: previous severe reaction, severe asthma (even without severe reaction history), older children and adults with difficult IV access

4. Obtain/disguise food for OFC

  • Obtain sufficient quantity of food; the total quantity tested should approximate the regular, age-appropriate single-serving size of the food
    • For tree nut challenges, ideally use tree nuts in the shell to prevent risk of contamination by other nuts, but if not available (e.g. cashew, pine nut), can triple wash using drop of dish soap then dry; family may roast and salt after rinsed
  • Disguise food for blinded OFC
    • In infants and young children, infant formulas and applesauce are convenient vehicles.
    • Other vehicles used are fruit juices, oatmeal, puddings, potato pancakes, mashed potato, ground lean meat patties, and fruit smoothies.
    • Flours of wheat, rye, oat, rice, barley, corn, potato, and soy; dried milk; and egg powders can be added to almost any food vehicle.
    • Meats and fish can be masked in another tolerated ground meat. Canned tuna fish, which is tolerated by most patients with fish allergy, can be used to mask the aroma of fish (if tuna allergy has been ruled out).
    • If placing food in capsules, consider that it is difficult to administer larger quantities of food in capsules; using processed food in capsules (eg, dehydrated powder) may destroy relevant allergens; patients may have difficulty swallowing them; early oral symptoms are bypassed; and capsules may be more resistant to digestion, resulting in delayed absorption, and requiring longer dosing intervals (30-60 min) and longer observation (>2 hours).
  • Prepare placebo - may be another food of a similar texture, look, smell, mouth feel, and taste to the challenge food and known to be tolerated by the patient. When capsules are used, dextrose is an excellent placebo. For substances such as chocolate that make the capsule dark, carob is an effective choice.

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5. Determine challenge dosing


  • Initial dose is typically 0.1-1% of regular age appropriate serving (0.1% ≈ 1-5 mg of food protein and 8-10 mg of the whole food). Initial dose should be lower than the amount of food that the patient reacted to in the past (if known).
    • Sicherer: total challenge dose equal to a full age-appropriate serving (8-10 g of the dry food, 16-20 g meat or fish, and 100 mL wet food) administered in gradual increments
    • In high risk patients (history of anaphylaxis, persistent asthma, reactions to trace amounts of food), consider lower initial dosing steps (10 mcg, 100 mcg, 1 mg at 30 min intervals). This may not be possible without special equipment to weigh minute amounts of food.
    • Dose that will elicit a reaction in 1% of any patient with food allergy:
      Eliciting dose 1 percent.png
  • Determine interval between doses; typically 15-30 minutes (30-60 minutes if using capsules).
  • Determine rate of dose increases
    • Working group: 0.1%, then 0.5%, 1%, 4%, 10%, 20%, 20%, 20%, 25% of a regular age-appropriate serving
    • PRACTALL: a general challenge schedule consisting of 3, 10, 30, 100, 300, 1000, and 3000 mg of food protein q20 min; "likely to be appropriate for most foods, patients, clinical situations, and settings"
  • A pitfall of using lower starting doses and longer intervals is the increased likelihood of partial desensitization and false-negative results

practall challenge schedule1.pngpractall challenge schedule 2.png

  • If performing OFC to food additive, consider protocols that have been published previously:

ofc3.png

Special considerations for cow's milk (DRACMA)

Panel recommendations for milk challenges in IgE-mediated CMA:
  1. Use the same type of milk the patient will be consuming everyday in case of negative challenge.
  2. Chose the least allergenic placebo possible, with preference for the type of milk the patient will be administered everyday in case of positive challenge.
  3. Start with a dose clearly under the expected threshold dose, for example, the amount that the patient reacted to previously.
  4. In general, one drop, or a 0.1 mL dose, is suitable for starting, but in high-risk cases one drop of CM:water 1:100 can be used.
  5. Give a dose every 20–30 minutes; this will minimize the risk of severe allergic reaction and allow precise identification of the lowest provoking dose.
  6. Increase the doses using a logarithmical modality, for instance: 0.1, 0.2, 0.5, 1.5, 4.5, 15, 40, and 150 mL (total 212 mL); or 0.1, 0.3, 1.0, 3.0, 10, 30, and 100 mL (total 145 mL); or 0,1; 0,3; 1, 3, 10, 30, and 100 mL (total 144 mL). Total dose should be calculated according to the maximum consumed per serving or based on the total weight of the patient.
  7. To minimize the possibilities of identification, dilute the verum with the placebo 50:50 when administering CM.
  8. Administer a placebo sequence in identical doses on a separate day.
  9. Discontinue the procedure on first onset of objective symptoms or if no symptom develop after challenge.
  10. Consider only reactions occurring within 2–3 hours after stopping the procedure.
  11. Complete a negative procedure with open administration of CM.

For delayed reactions, the same rules apply except:
  • Rule 4: start with a 0.1 mL dose.
  • Rule 5: does not apply.
  • Rule 6: the interval in that case should be calculated according to the clinical history.
  • Rule 11: consider reactions occurring within 24 – 48 hours after stopping the procedure.

Special considerations for baked/cooked/heated egg and milk challenges

Milk
Egg
  • Challenge material used for baked milk challenges (Nowak-Wegrzyn)
    • Muffin containing 1.3 g of milk protein (nonfat dry milk powder; Nestle Carnation) baked at 350 F for 30 min
    • If muffin tolerated, challenged same day (2 hours after muffin) with waffle (<0.625 inches thick to ensure thorough heating), containing 1.3 g of milk protein (nonfat dry milk powder; Nestle Carnation) cooked in a waffle maker at ~500F for 3 min
    • If muffin/waffle tolerated, challenged 6 months later to Amy’s cheese pizza (Amy’s Kitchen, Inc), containing 4.6 g of milk protein, baked at 425F for 13 min or longer
    • Muffin, waffle, and pizza were administered in 4 equal portions over 1 hour. Subjects were monitored throughout and for 2-4 hours after completion of the challenge.

  • Mt. Sinai outpatient OFC baked milk muffin recipe
    • 1 cup cow's milk
    • 2 tbsp canola oil
    • 1 tsp vanilla
    • 1 egg or 1-1/2 tsp egg replacer (e.g. Ener-G brand)
    • 1-1/4 cup flour
    • 1/2 cup sugar
    • 1/4 tsp salt
    • 2 tsp baking powder
    • Preheat oven to 350 F. Combine dry ingredients and mix with wet ingredients. Pour in to muffin cups and bake for 30-35 minutes, or until golden brown and firm to the touch. Yields 6 muffins (1.3 g cow's milk protein per muffin)
    • Alternative: standard cake mix with 1 cup of cow's milk, where the total challenge dose contains ~1.3 g cow's milk protein
    • Muffin dosing: 1/8, 1/8, 1/4, 1/2 q15 min

  • Boston Children's baked milk challenge
    • Parents were instructed to prepare muffins or cupcakes at home. Each muffin or cupcake contained 1.3 g of milk protein from nonfat dry milk powder, baked at 350 F in an oven for 30 minutes.
    • A standard graded open food challenge consisted of increasing increments every 15 minutes of one-fourth (325 mg), half (650 mg), and 1 1/4 (1,625 mg) muffin or cupcake, totaling 2.6 g of milk protein

  • See section 10 below for passed baked milk challenge discharge instructions
  • Challenge material used for baked egg challenges (Nowak-Wegrzyn)
    • Muffin containing 1/3rd of an egg (~2.2 g of egg protein) baked at 350 F for 30 min
    • If muffin tolerated, challenged same day (2 hours after muffin) with waffle (<0.625 inches thick to ensure thorough heating) containing 1/3rd of an egg (~2.2 g of egg protein) cooked in a waffle maker at approximately 500 F for 3 min
    • Muffin and waffle were administered in 4 equal portions over 1 hour. Subjects were monitored throughout and for 2-4 hours after completion of the challenge.

  • Mt. Sinai outpatient OFC baked egg muffin recipe
    • 1 cup flour (or flour substitute)
    • 1/4 tsp salt
    • 2 tablespoons of rice milk (or soy milk, cow's milk, almond milk)
    • 1 tsp baking powder
    • 1/4 tsp cinnamon
    • 2 eggs
    • 1/2 cup sugar
    • 1/4 cup corn oil
    • 1/2 tsp vanilla
    • 1 cup mashed ripe banana or apple sauce
    • Preheat oven to 350 F. Combine dry ingredients and mix with wet ingredients. Pour in to muffin cups and bake for 30-35 minutes, or until golden brown and firm to the touch. Yields 6 muffins (1/3 whole egg per muffin).
    • Alternative: standard cake mix with 3 eggs added, where the total challenge dose contains ~1/3 whole egg
    • Muffin dosing: 1/8, 1/8, 1/4, 1/2 q15 min

  • HealthNuts study of 1 year old infants
    • Bake vanilla cake mix (Green’s Foods Limited, Glendenning, NSW, Australia) as per packet instructions with 2 x 60 g eggs made into 12 small muffins (10 g whole egg/muffin)
    • Increase dose every 15 minutes if no allergic reaction is noted:
      • A ‘‘crumb’’
      • 1/12 muffin
      • 1/6 muffin
      • 1/4 muffin
      • 1/2 muffin


  • Note: a later onset of reaction may be seen with baked egg (toward the end of a 2 hour observation period) compared to lightly heated egg (scrambled egg or French toast)

  • See section 10 below for passed baked egg challenge discharge instructions
Heated egg milk recipes.png

Special considerations for alpha-gal meat/cow's milk challenges

  • Oral food challenge with appropriate duration of observation (usually 3-6 hours)
  • Small amounts of meat (1 strip of bacon) is frequently tolerated but 2 pork sausage patties (~86 g) reliably induces symptoms; larger amounts (e.g. plate of barbeque) associated with increased severity of reactions
  • Fattier cuts of beef (ribs) more likely to elicit reaction than lean (deli ham or tenderloin)
  • Positive food challenge more likely with recent tick bite booster (within 1-4 weeks), as the alpha-gal sIgE level seems to decrease with time


6. Prepare patient

  • Obtain informed consent
  • Eliminate suspect food strictly from diet for 2 weeks prior to OFC.
  • Discontinue medications that may interfere with interpretation: H1 antihistamines (oral/intranasal) up to 10 days, H2 antihistamine 12h, tricyclic antidepressant up to 3 weeks, montelukast 24h, albuterol 8h, ipratropium (inhaled/intransal) up to 12h, systemic steroids up to 2 weeks.
  • Consider discontinuation of drugs that may worsen reactions to foods: antacids (H2 blockers, PPI, etc.), aspirin, NSAIDs.
  • NPO for 4 hours prior to OFC for anticipated immediate reactions, 12 hours for anticipated delayed reactions.

7. Administer OFC

  • Obtain baseline vital signs, PEF or spirometry, and physical exam.
  • Consider IV placement in history of FPIES or anaphylaxis, severe asthma, difficult IV access, anticipated need for IV medications for resuscitation.
  • Nurse or physician to supervise patient throughout OFC.
  • Re-examine prior to each dose.
  • Vital signs with re-examination at first signs of reaction. Repeat PF or spirometry if respiratory symptoms noted.
  • In case of subjective complaints (throat itching, mouth itching, skin itching, or nausea) a period of observation to allow for resolution of symptoms should be undertaken before administering a subsequent dose. A challenge may be considered positive if subjective symptoms follow 3 doses of test food but not placebo.
  • Isolated throat tightness or pruritus, nausea, abdominal pain, or general malaise, may represent a prodromal phase of a more severe reaction. A longer observation period before the next dose or discontinuation of an OFC followed by treatment may be prudent.
  • PRACTALL: In case of subjective symptoms:
    • Continue the challenge, in spite of the subjective symptoms, until the subject exhibits objective symptoms
    • If the patient is unable or unwilling to continue the challenge because of the subjective symptoms, then discontinue the challenge and consider the final administered dose to be right censored (how much more the patient could tolerate and remain symptom free would be unknown)

when_is_ofc_positive.png
(Niggemann, Allergy 2010)

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Steps to minimize OFC risk (Wood)

  • Adjust the starting dose and challenge protocol for individual patients who might be at higher risk of a severe reaction.
  • Utilize experienced observers who have been trained to do food challenges and who are present throughout the challenge, continually interacting with and re-examining the patient at regular intervals.
  • Stop the challenge as soon as the observer(s) is convinced that a reaction is occurring.
  • Prepare all medications that might be needed before the challenge so that they can be administered without delay.
  • Perform challenges only in settings where all measures that might be needed to treat a severe reaction are readily available.

8. Interpret results

  • Most positive challenges demonstrate skin symptoms. GI symptoms are more likely after challenges with hen’s egg and peanut (compared with challenges with cow’s milk, soy, and wheat). Respiratory symptoms are more likely after peanut challenges compared with challenges with cow’s milk, hen’s egg, soy, and wheat.
  • The OFC is negative if the patient tolerates the entire challenge, including the masked and open portions of a blinded OFC and observation period.
  • Longer observation periods may be necessary in patients with later onset of symptoms in previous reactions, such as GI complaints and/or eczema. Depending on the severity of the previous delayed reactions, observation may be warranted under physician supervision, or a patient may be discharged home and instructed to keep a log of symptoms.
  • Later onset of reaction may be seen with baked egg (toward the end of the 2 hour observation period) compared to lightly heated egg (scrambled egg or French toast)

HealthNuts objective positive challenge criteria

    • Used in study of 12 month old Australian infants
    • OFC positive if 1 or more of the following is observed within 2 hours of ingestion of a dose during food challenge:
      • 3 or more concurrent noncontact urticaria persisting >5 min
      • Perioral or periorbital angioedema
      • Vomiting (excluding gag reflex)
      • Evidence of circulatory or respiratory compromise

PRACTALL

Scoring and interpreting challenge outcome.png

9. Determine post-challenge care (in office)

  • In case of negative OFC:
    • Generally may be discharged after an observation period of ≥2 h (unless clinical history of delayed onset reaction)
    • If challenged with a disguised food, consider an open feeding of a normal serving of undisguised food ≥2 hours after the OFC. This recommendation is based on 3% chance of reaction after a negative OFC, possibly due to larger amount of food ingested during an open feeding, effects of the disguising vehicle matrix on allergen absorption, or subclinical reactions caused by gradual administration.
  • In case of a positive OFC, the patient should remain under observation after symptoms have resolved (2-4 h after resolution of symptoms for immediate hypersensitivity reactions is usually recommended).
    • Patients with mild symptoms (few hives that resolved promptly with or without treatment) might be discharged after a 2 h period after resolution of symptoms.
    • Patients with minimal residual symptoms such as a few new hives or swollen lips may be sent home after 4 hours.
    • Patients with a past history of a severe biphasic reaction should be observed for a longer period even in the absence of symptoms. Biphasic anaphylactic reactions to foods are reported in the literature, with symptoms starting as late as 6 hours.

10. Discharge instructions

  • Negative OFC:
    • Patient to refrain from eating the food until the next day because of the small possibility of a delayed reaction to OFC
    • The recommendation for eating a food after a negative OFC should reflect the manner in which the food was prepared during the OFC because tolerance to the cooked versions of many foods does not predict tolerance to the less cooked forms
    • Regular ingestion of the food should be encouraged
      • In one study, patients who outgrew peanut allergy had an ~8% chance of having a recurrence, and the risk of recurrence was higher if peanut was avoided after a negative OFC. Recommended that patients eat concentrated forms of peanut at least monthly to maintain tolerance, and that patients who eat peanut frequently carry epinephrine for ≥1 year after a negative OFC. If they eat peanut infrequently or in limited amounts, then epinephrine should be available indefinitely at all times.
      • Wood: for those who clearly had a peanut allergy and outgrew it, we recommend a full serving of peanut (4-5 grams of peanut protein) at least once a week; we have not identified anyone eating peanut at least once per month who experienced a recurrence
  • Negative baked egg/milk challenge (Mt. Sinai)Mt sinai baked milk at home.png
    • Patient should ingest 1-3 servings/day of the following daily:
      • Store-bought baked products (cookies, breads, bagels) with egg/milk listed as the 3rd ingredient or further down the list of ingredients
      • Home-baked products that have 1 egg (or 1 cup milk) per 1 cup of flour or 1-2 eggs (or 1 cup milk) per batch of a recipe (yield 6 servings). If you offer home baked products, feed 1 serving at a time with at least 2 hours between servings
      • Avoid products that do not qualify as baked egg: french toast, quiche, scrambled eggs, custard, etc.


  • Positive OFC:
    • Allergic food avoidance should be reinforced, and recommendations for follow-up visits and evaluations within 6 to 12 months should be provided.
    • Emergency treatment plans for allergic reactions, a prescription for a self-injectable epinephrine device, education regarding food avoidance, and dietary implications of food avoidance should be provided.
    • For patients with severe reactions during the challenge, providing emergency medications on discharge should be considered.


OFC Procedure for Food Protein-induced Enterocolitis Syndrome (FPIES)



References