This study aims to determine the frequency of allergy to beef meat in children with allergy to cow's milk by serum measurement. Also, the study aims to assess the sensitivity and specificity of beef IgE in relation to gold standardized of elimination challenge test and to assess effect of eating of cooked meat on symptoms of allergy in those proven to have either CMA alone +/- beef allergy (by serology).

Milk has been recognized as a leading cause for food allergy in children. It is recognized that there is cross-reactivity of bovine serum albumin and bovine γ-globulin which are present in both milk and beef. Thus, children with cow's milk allergy may be instructed to avoid beef.

The true prevalence of beef allergy has been studied only in few research. This current study will add a tertiary center experience in relation of beef allergy to cow's milk protein allergy to fill the gap of knowledge regarding this subject especially in Egypt.

Study Procedures:

Cases will be managed according to the protocol of gastroenterology unit and Allergy, Rheumatology and Immunology Unit, and will be subjected to:

Informed consent: will be obtained from all patient's parents or legal guardians.

All included cases will be subjected to the following phases of the study:

Phase Ⅰ: Recruitment

I. Full medical history taking:

Personal history: Name, age, sex, order of birth, residence, and consanguinity. Complaint.

Present history:

1. Gastrointestinal symptoms

   1. Vomiting (yes/no):

      If yes: onset, course, duration, frequency, force, color, relation to meal, relation to posture and need for IV fluid.

   2. Hematemesis (yes/no):

      If yes: onset, course, duration, frequency, color, need for resuscitation and associated melena.

   3. Diarrhea (yes/no):

      If yes: onset, course, duration, frequency, consistency, blood in stool and straining.

   4. Constipation: (yes/no):

      If yes: onset, course, duration, frequency, consistency, blood in stool and straining.

   5. Other symptoms: colics, nausea, distension, dysphagia, and failure to gain weight.

2. Associated systemic manifestations (Allergic manifestations) including:

   1. Skin allergy (eczema, urticaria, napkin dermatitis).
   2. Chest allergy (wheezing, croup).
   3. ENT manifestations (allergic rhinitis).
   4. Anaphylactic shock.

3. Dietary and nutritional history:

   1. Breast Feeding: (yes/no) If Yes exclusive for how long?

   2. Artificial feeding:

      Age of start, type of formula and indication

   3. Weaning:

Time of start, type of food given (each food and time of introduction especially cow's milk and CMPs) and any problems during weaning (gastrointestinal, respiratory, or skin allergies).

Past history: mode of delivery, NICU admission. Medication history: Type of medications, antireflux medications, laxatives, probiotic.

Family history: atopy, other siblings with CMPA.

II. Careful Clinical examination:

Anthropometric measurements: (weight, height, Wt/Ht ratio and occipto-frontal circumference) Signs of allergy: (atopic dermatitis- allergic rhinitis). Abdominal examination: (Distension-tenderness-organomegaly) Perianal inflammation, napkin rash. All patients suspected of having cow milk allergy will be subjected to elimination re-challenge test (Dupont, 2014).

All patients included in the study were instructed initially to avoid meat products as per protocol of Ain Shams University for 4 weeks.

Blood samples for IgE for beef will be withdrawn at time of enrollment.

Phase Ⅱ:

Patients with history of anaphylaxis will be excluded from this phase. During the oral food challenge (OFC) procedure, patients will be monitored and regularly re-examined prior to each dose and at first signs of reaction. Total dose will be divided into six incremental portions, where every next dose will be double of the previous dose as follows: 1, 2, 4, 8 and 16 g. In case of suspected severe reaction, a much smaller dose was decided (Gonzales González et al. 2018). In cases of anaphylaxis, patients will be given intramuscular epinephrine in the lateral aspect of the thigh and the dose will be calculated based on patient's weight. Dose will be prepared prior to the procedure to avoid any delay.

In case of milder skin reaction or any type of reaction as bronchospasm it will be managed by oral steroids, antihistaminic + any symptom treatment based on what the patient develops. Smaller doses will be given to those who have mild or moderate reaction and those who develop will not continue the OFS.

Inclusion Criteria:

• Children from seven months to three years old newly diagnosed with cow milk allergy at Gastroenterology Unit and Allergy, Rheumatology and Immunology Unit.

Exclusion Criteria:

• Critically ill children.
• Patients diagnosed as immune deficiency.
• Patients receiving long term steroid therapy or anti-histaminic.
• Patients who had anaphylaxis or severe reactions from milk
• Patients with skin diseases which can mask skin reactions