An allergy diagnosis is made by a very careful history, skin prick tests, blood tests (Immuno-CAP RAST), Patch tests, Atopy Patch test & Oral Challenges. A Double-Blind Placebo-Controlled (DBPC) Oral food Challenge is considered the “gold standard” in the diagnosis of food allergies and some drug allergies.

The importance of taking a careful (thorough) history cannot be stressed enough, because not only can a good history give the diagnosis on its own, but it guides the Allergist towards stream-lined allergy testing. Random (battery) testing is financially wasteful and also time consuming and potentially misleading. The allergy tests should only be used to confirm a diagnosis that has been made based on the history.

The aim of oral food challenge is to study the consequences of food ingestion in an objective way. It is well known that the perceived prevalence of food allergies is much higher than the true prevalence, and this is due to the subjective symptoms that are often associated with food ingestion. This is due to a conditioned (Pavlovian) Response.

Clinical uses of oral challenges

• To confirm a diagnosis of food allergy based on history and equivocal skin prick tests & / or Immuno-CAP RAST-type tests. The new Immuno-CAP tests are so sensitive & specific for diagnosing food allergies to milk, egg, peanut, fish, and wheat that oral challenges to these foods are very rarely done to diagnose allergy.
• To diagnose Food Intolerance, where skin tests & blood tests are expected to be negative (not useful).
• To see if a child has grown out of a food allergy, especially when the Immuno-CAP tests are equivocal.
• To re-assure patients who, would otherwise be unconvinced that their symptoms are not attributable to the foods that they have developed a conditioned response to.
• To confirm drug allergies.

Principles of Oral Challenge

The food challenge should replicate normal food consumption in terms of amount and state of the food. The period of observation after the ingestion should match the time period between ingestion & onset of symptoms based on the history.
If co-factors like exercise or ingestion of drugs like NSAIDs are required for the reaction, this has to be replicated in the challenge. For example in patients with food-related exercise-induced anaphylaxis, the ingestion of the suspected food has to be followed by exercise.

Types of Oral Challenges

• Open Challenges – are the simplest oral challenges. The parents, doctor, and the patient know what food is being given. The freshly prepared food is given and the patient is observed for the required time based on the history. The main drawback to an open challenge is the risk of bias influencing the parents’, patient’s or doctor’s observations. If the parent’s belief in food allergy is expected to be disproportionately high, an open challenge should not be done.
• Single-blind challenges – In this case the observer (doctor or nurse) but not the patient or family know the test material. The drawback to this method is bias influencing the observer.
• Double-blind Placebo challenges – In this case either the challenge substance or an indistinguishable inactive (placebo) substance is administered. Neither the child, the parents or the observer know the identity of the administered material.

Challenge Procedure

• 1. A detailed history is essential to determine:
     • Which food/s are suspected.
     • What symptoms are produced.
     • How long after ingestion do the symptoms occur.
     • What is the smallest quantity of food which will produce symptoms.
     • The frequency of the reactions.
     • How reproducible is the reaction, i.e. does the reaction always occur when the food is ingested.
     • Whether the reaction only occurs in the presence of some additional factor, for example, does the reaction only occur if ingestion of the food is followed by exercise?
  2. Elimination diet prior to the challenge
     • Suspected foods need to be avoided for approximately 2 weeks prior to the challenge, because regular consumption of the food could obscure a reaction to a single dose. It is well known that with food intolerance, regular intake of the foods like salicylates will lead to a state of tolerance to the food.
     • The elimination diet also confirms the relevance of the eliminated foods being a trigger for the symptoms.
  3. Preparation of foods for the challenge
     • Dehydrated or dried powdered foods is administered in opaque gelatin capsules or
     • The food is disguised in a carrier food such as apple or vegetable puree or lentil soup. This method is more commonly used than the capsule method.
  4. Placebos
     • If capsules are used, dextrose or lactose powder is the simplest placebo. The vehicles described above, without the addition of anything else can be used as the placebo.
  5. Avoidance of medications
     • Drugs which should be avoided before the challenge include:
       • Antihistamines (for about 72 hrs)
       • Cromoglycate (for 12 hrs)
     • If the foods cause reaction despite the medication, then the medication does not have top be avoided. Also, it is important to note that withdrawing the medication prior to the challenge may precipitate symptoms, which will interfere with the interpretation of the challenge symptoms.
  6. Food Administration
     • This should start with a small quantity, less than that estimated (from the history) to cause symptoms. The dose is then doubled at 45 – 60 minutes intervals. The longer interval for reactions occurring later after the food ingestion (based on the history). The doubling of the dose is continued until the patient has obvious symptoms, or until about 10g of dried or 100g of untreated food have been given. In some cases of food intolerance (with delayed reactions) larger quantities of foods may be required.

Risk of Anaphylaxis during oral challenges

• With a history of previous anaphylaxis related to the food being tested.
• Foods like peanuts, nuts, milk, egg, and fish carry a greater risk of anaphylactic shock than others.
• Patients with atopic eczema are at increased risk for anaphylaxis after strictly eliminating foods that they are allergic to, even though they never had anaphylaxis to that food previously.

Because of the risk of anaphylaxis oral challenges should be done in an environment that is set up to offer full resuscitation.

Pitfalls of Double-blind Placebo-Controlled (DBPC) oral food challenges

DBPC food challenges are considered the “gold standard” for diagnosis of adverse reactions to foods, but do they mimic real-life exposure?

To stop a DBPC food challenge & declare it positive or negative symptoms should be objective and /or repetitive.

Causes of false negative DBPC oral food challenge include:

• Inadvertent drug use during the challenge.
• a short-term specific oral tolerance induction (SOTI) may be induced as increasing amounts of the offended food are administered during a titrated oral food challenge.

Causes of false positive DBPC food challenge include:

• Difficulty in maintaining a strict diet throughout the oral challenge procedure.
• The elimination diet implemented before the challenge might be responsible for the “new” symptoms seen during the trial.