**4.3 Oral food challenge**

The gold standard to confirm or disprove food allergy is the OFC, particularly doubleblinded, placebo-controlled OFCs [8]. In the case of NFA, OFCs are safe, whereas in IFA, OFCs are time-consuming and carry the potential for severe reactions. They should be performed by experienced health-care professionals who have access to emergency equipment. Despite the mentioned caveats, OFCs are especially useful because observation for 24 hours or more after food exposure allows the assessment of both early and late reactions to the food and thus can detect both IgE- and non-IgE-mediated processes.

#### **4.3.1 Prerequisites for oral food challenge in atopic dermatitis**

#### **Evaluation of clinical severity scores**

For the diagnosis of food allergy, a clinical severity scoring system is necessary. This scoring differs between IFA and NFA. The diagnosis of IFA is straight forward because of the apparent clinical manifestation following a challenge. There are several scoring systems for IFA described by Clark [28] and Noh [6]. The diagnosis of NFA is difficult due to its clinical characteristics, which are almost the same as those of atopic dermatitis, and the SCORAD index and clinical severity scoring systems for AD can be used for NFA [29]. Clinical severity scoring should be done at the initial evaluation, at every visit, and before and after every procedure.

#### 1. Diet record

A dietary diary should be kept during diagnosis and treatment [2]. In the process of management of food allergies in AD, daily diet diaries should be used to record complete basic recipes for each meal. For the supervision of dietary management, all food should be recorded, including elimination diets, open OFCs, and tolerance induction. This is especially important for breast-feeding infants. In such cases, the diet of the mother should be recorded along with the diet of the infant, including the times of ingestion and the time of the appearance of new AD lesions or aggravation of old AD lesions.

#### 2. Elimination diet

236 Atopic Dermatitis – Disease Etiology and Clinical Management

Blood eosinophils provide information on current disease activity of the non-IgE-mediated type [20]. For the evaluation of disease progress and continuing disease activity and for the effective management of non-IgE-mediated allergy including NFA, blood eosinophil levels

Serum ECP should also be followed to determine changes in the disease activity of non-IgE-mediated allergy and the effectiveness of an elimination diet for food additives in

The interpretation of the results of allergen-specific tests, such as the skin prick test and allergen-specific IgE, is often complicated because the number of positive SPT responses, the spectrum of IgE sensitisation and even the results for the same allergen often change in the same individual over time [26]. This variability may be related to the number of allergens tested and the age at which the measurements are performed. The most common food allergens determined with the SPT are soy, cow's milk, peanuts, carrot, hen's eggs whites,

However, changes in reactivity to allergens must be considered to be a natural phenomenon that is affected by the natural outgrowing of food allergy and the gradual acquisition of allergy to inhaled allergens, including house dust mites and pollen [2]. The change in the number of allergens to which a patient responds over time and the change in response to one allergen over time provides the physician with information on the progress of the disease. If the number of sensitised allergens decreases, the allergy itself may be regarded to be decreasing systemically. In addition, if the strength of SPT or the level of food-specific

The gold standard to confirm or disprove food allergy is the OFC, particularly doubleblinded, placebo-controlled OFCs [8]. In the case of NFA, OFCs are safe, whereas in IFA, OFCs are time-consuming and carry the potential for severe reactions. They should be performed by experienced health-care professionals who have access to emergency equipment. Despite the mentioned caveats, OFCs are especially useful because observation for 24 hours or more after food exposure allows the assessment of both early and late

For the diagnosis of food allergy, a clinical severity scoring system is necessary. This scoring differs between IFA and NFA. The diagnosis of IFA is straight forward because of the apparent clinical manifestation following a challenge. There are several scoring systems for IFA described by Clark [28] and Noh [6]. The diagnosis of NFA is difficult due to its clinical characteristics, which are almost the same as those of atopic dermatitis, and the SCORAD index and clinical severity scoring systems for AD can be used for NFA [29]. Clinical severity scoring should be done at the initial evaluation, at every visit, and before and after

A dietary diary should be kept during diagnosis and treatment [2]. In the process of management of food allergies in AD, daily diet diaries should be used to record complete

reactions to the food and thus can detect both IgE- and non-IgE-mediated processes.

**Laboratory follow-up** 

atopic dermatitis.

wheat, and corn [27].

**4.3 Oral food challenge** 

every procedure. 1. Diet record

**Evaluation of clinical severity scores** 

are tested repeatedly on a regular schedule.

IgE is decreasing, the patient may be outgrowing the allergy.

**4.3.1 Prerequisites for oral food challenge in atopic dermatitis** 

An elimination diet should precede an oral food challenge. Without complete elimination of the causes of the allergy provocation, it is difficult to interpret the results of an oral food challenge [2].

For IFA, the causative foods are typically easily recognised by parents and patients; it is therefore easy to eliminate and challenge with foods. However, it is very difficult to recognise the triggers for the diagnosis to be made in NFA. The accumulated statistics for NFA in atopic dermatitis are absolutely necessary [2]. Moreover, in cases of NFA associated with atopic dermatitis, the causative agents are more complicated and may include HDM [30]; thus, all possible allergens must be eliminated for a proper oral food challenge. Fortunately, the proper control of the causative allergens, including food and inhaled allergens, can be evaluated based on stable improvement during an elimination diet. An initial elimination diet is important as an indicator of the proper control of allergy provocation [2].

Once patients show improvement through an initial elimination diet, oral food challenges are conducted. Foods that were not addressed in the initial elimination diet should also be considered. IFN- therapy can be considered when patients do not improve following the initial elimination diet [2] because IFN- therapy itself does not affect allergy provocation during the next OFC [20].

3. Basic general management

Without basic care and the control of allergens other than foods, the precise diagnosis of food allergies may be confusing. This type of management includes the following: 1) Skin care using non-steroid drugs and emollients including moisturizer and aroma oil, 2) House dust mite and other inhaled allergen care (dander, pollen, fungi and others); patients should be tested for allergy provocation by inhaled or environmental allergens, 3) Other factors (infection control, others), 4) Discontinue all medications that affect allergy provocation (steroids, antihistamines, other immunosuppressants, drugs with unknown effects (herbal medications), etc [2].

#### **4.3.2 Elimination diets as a first step in the diagnosis of food allergies**

1. Elimination diet and elementary diet

Diet control for the elimination of food allergy can be assessed using an elimination diet and an elementary diet. An elimination diet is a restriction of the possibly causative foods, whereas an elementary diet permits several safe foods. Both approaches require clinical data from studies [18, 19, 21]; such data are very important because if the clinical statistics are not proper, dietary restriction does not result in clinical improvement. The proper OFC then cannot be advanced further.

For an effective elementary diet, the absolutely safe foods in atopic dermatitis should be addressed. An effective elimination diet is a higher modality because it requires the accumulation of clinical data for statistics regarding the causative foods for atopic dermatitis. Noh and Lee focused on these points, and an effective elimination diet is now available for atopic dermatitis [12, 13, 18, 19, 21].

Food Allergy in Atopic Dermatitis 239

OFC, the challenge material is provided by a third party, such as a dietitian, and the patient, the patient's family, and the observer are unaware of when the test food is administered. Bias is thus minimised. Placebo-controlled challenges may be administered in either a

Indications for an OFC in AD are listed below [2, 20, 32]; 1) Identify foods causing AD for the initial diagnosis of a food allergy and for monitoring resolution of the food allergy, 2) Discriminate between IFA and NFA, 3) Calibrate the provoking dose and determine the clinical severity of the reaction for therapeutic purposes in IFA and in order to monitor progress in IFA treatment, 4) Expand the diet in persons who have multiple dietary restrictions because of subjective complaints, such as headaches or hyperactive behaviour, 5) Assess the status of tolerance to cross-reactive foods, 6) Assess the effect of food processing on food tolerability, e.g., fruits and vegetables that may be tolerated in cooked form in the

The basic concept of OFC is the same for IFA and NFA. However, due to the different clinical characteristics of the two types of allergy, the OFC protocols for each differ significantly in principle and in dosage protocol [7]. OFC is conducted with relevant protocols for IFA or NFA. An OFC for IFA is relatively easy and simple, with higher risk, whereas an OFC for NFA is intricate and all aspects of this OFC should be carefully

IFN- does not inhibit allergy provocation [19]; however, it does improve the pre-existing symptoms and signs of atopic dermatitis, including eczematous skin lesions and pruritus [19, 21]. The clinical characteristics of AD are of the non-IgE-mediated type, and the onset and duration of symptoms and signs are relatively longer [7]. It is difficult to handle or proceed to the next challenge when the patient shows a severe NFA reaction during the challenge. The use of steroids or antihistamines for symptomatic treatment can inhibit the allergic reaction caused by OFC or hide the symptoms of allergy

Rapid onset and apparent clinical manifestations are typical of IFA [7]. During proceeding with the OFC for food allergy, the onset time following challenge, the duration of symptoms and signs, and the various clinical manifestations should be considered. Although the diagnosis of NFA is made based on the change of clinical severity scores, expertise is necessary in the OFC for NFA because the same food may provoke variable clinical

The characteristics of food allergy are well described by Noh and Lee [7]. The clinical characteristics of food allergy to the same food may differ among patients and may differ in the same patient according to the type of food. Some foods, such as shrimp and mackerel, tend to provoke IgE-mediated food allergy, whereas other foods, such as milk, eggs,

manifestations with an unexpected onset time during the challenge.

single-blind or double-blind fashion.

**4.3.5 Indications for an OFC** 

pollen-food allergy syndrome.

provocation during an OFC.

2. Characteristics of OFC

1. IFA and NFA

**4.3.7 Clinical characteristics of OFC** 

considered. - IFN- in OFC

**4.3.6 OFC procedures for IFA and NFA** 

More than 50% of AD patients have NFA . Without the control of allergy provocation, AD cannot be effectively controlled [21]. As a first step in the diagnosis of food allergy, dietary restrictions should be initiated. If a patient shows improvement on an elimination diet, a food allergy to the restricted foods should be strongly suspected. An optimal elimination diet can be achieved by providing a list of the foods to be restricted, which in turn can be determined by clinical statistics.

2. Breast-fed infants

In the case of breast-fed infants, maternal elimination diets are recommended. Once a maternal elimination diet is implemented, improvements are often observed in the infant [31]. If eczema improves during the elimination diet, the clinical relevance of the eliminated foods should be confirmed with standardised, physician-supervised oral food challenges to the mother.
