I. General content
1. Applicable age range: 0-1 year old infants. Ning Peng, Department of Pediatrics, Songyuan City Hospital of Traditional Chinese Medicine
2. Definition.
(1) Allergen: It is an antigen that can cause an allergic reaction. Most of the allergens that react with IgE and IgG antibodies are proteins.
(2) Allergic: also known as atopic, is an individual or family can produce specific IgE (sIgE) antibodies to small doses of allergens (usually proteins). “Allergy” should be carefully defined and requires confirmation of the presence of sIgE antibodies in the child.
(3) Allergy: It is a hypersensitivity reaction induced by immune mechanisms. Allergy can be mediated by humoral (antibodies) or cellular immunity. In most cases, the antibodies that cause allergic reactions belong to the IgE class and can be classified as IgE-mediated allergic reactions.
(4) Genetic allergies: Also known as atopic diseases, typical “allergic” individuals with allergic symptoms have atopic reactions [e.g., atopic asthma, etc.]. The presence of positive skin tests and serum specific IgE antibodies, although important, are not the only indicators to determine whether an individual has atopic reactivity.
Classification of allergic diseases in infancy and main immunological mechanisms
Classification IgE T cells Eosinophilic IgG
Mediated Mediated Cell-mediated Mediated
Classification of affected organs Skin allergy-mediated
Atopic dermatitis ++ ++ +
Angioedema ++
Urticaria ++ +
Gastrointestinal allergies
Eosinophilic gastroenteritis + + ++
Respiratory allergies
Allergic rhinitis ++ + + +
Allergic asthma ++ + ++
Ocular allergies ++
Systemic allergic reactions
Anaphylaxis ++
Classification of allergen types Food allergy ++ + + + +
Inhalation allergen allergy ++
Drug allergy ++ + +
III. Prevention
1. Educational work: to educate parents about infant allergic diseases in general.
2. Medical history taking: focus on understanding the family history of allergic diseases. 3.
3. primary prevention: the main target is infants who have not yet been sensitized (have not yet produced allergen-specific IgE), and measures include both for the mother and the infant.
(1) Maternal life and diet: The effectiveness of prenatal control of the mother’s diet in preventing infant allergy is unclear and should be approached with caution. Maternal smoking increases the risk of infant allergy and active and passive smoking should be avoided as much as possible.
(2) Lactating mother’s diet: Food allergens can be passed to the infant through breast milk, but at low levels. Lactating mothers of infants at high allergy risk (parents or siblings with genetic allergies, etc.) should reduce intake of commonly allergenic foods, including: milk, eggs, peanuts, shelled seafood, etc.
(3) Infant diet: The most important route of exposure to exogenous allergens in infancy is the digestive tract, with food as the main allergen. Early infant diet should be based on dairy products.
(1) Main methods: Exclusive breastfeeding can effectively reduce the occurrence of allergies in infancy. Breastfeeding is recommended for the first 6 months after birth. If an allergic disease has occurred in an exclusively breastfed infant, it is recommended that the mother should attempt to avoid suspected allergenic foods such as milk and make adjustments to the local diet. Infants generally delay the addition of solid foods until after 6 months of age, and for foods that are likely to cause allergies (e.g., milk, eggs, etc.) it is recommended that they be added after 12 months of age.
②Secondary approach: moderately hydrolyzed protein formula can be used for mixed or manual feeding of infants at high allergy risk. It is recommended to use it as early as possible after initiation, as early exposure to whole milk formula may lead to sensitization of the organism. Feeding should continue through infancy, and solid foods should be added gradually after the immune and digestive systems are moderately well developed (after 6 months of age).
③Other methods: soy milk formula: not recommended abroad for the prevention of allergic diseases in children, and there is a lack of clinical research evidence in China.
④Probiotics (yuan): The appropriate use of probiotic strains (prebiotics) with clear functions has a role in the prevention of allergies in infancy.
4. Secondary and tertiary prevention: The main target is infants who have developed allergic symptoms, and the measures are similar to treatment.
5. Environmental control: The effect of early exposure to inhaled allergens on the later occurrence of allergy is currently controversial and no consensus can be reached yet. For infants who have already developed food allergy, it is recommended to reduce the amount of dust mites in the environment, including reducing indoor dust accumulation, controlling the temperature and humidity of the indoor environment, and using anti-mite bedding if possible for children with proven dust mite allergy. when recurrent respiratory infections or chronic cough symptoms occur around 12 months of age, inhalation allergen allergy evaluation should be performed to avoid blind antibiotic treatment.
IV. Diagnosis
(I) Target selection
For infants in the sensitization stage but without clinical symptoms, there is no consensus opinion on the evaluation of sensitization status. The diagnosis is mainly for infants with clinical symptoms. The clinical manifestations of allergic diseases in infancy are complex, and the diagnostic procedures for allergic diseases should be carried out in conjunction with a detailed medical history and the characteristics of clinical symptoms.
(II) Procedures and methods
1. History taking: A complete and detailed history taking (including family history of allergy) is the basis for the diagnosis of infantile allergic diseases. Allergic diseases have a strong tendency to run in families, but the occurrence of allergic diseases is also more common in those without a family history.
Most of the allergic symptoms that appear early in infants are caused by food allergies. The possibility of food allergy should be highly suspected at a young age and when allergic symptoms are severe. Symptoms of food allergy in infants often involve more than two organs and systems, for example, the presence of skin symptoms along with gastrointestinal symptoms (which can vary in severity). Since the main foods of artificially fed infants are milk and eggs, milk and eggs should be excluded separately for a short period of time to assist in the diagnosis; breastfed infants should be questioned in detail about the mother’s diet.
Children with severe allergic reactions should be asked in detail whether hoarseness, laryngeal edema, respiratory distress or anaphylaxis has occurred after feeding.
The history of food allergy should include: the suspected food that triggered the reaction; the amount of food intake; the time of symptoms after food intake; and the presence of other triggering factors. Detailed questioning of the above history can help determine the choice of further adjunctive food allergen testing types. Avoid unnecessary wastage of allergen testing by blindly performing allergen testing. Diagnosis is dependent on dietary history. 20% of the population has had symptoms due to food, while only about 1% of the population has a true food allergy. The number of foods that cause symptoms is limited. Eggs, milk and peanuts are common in infants.
2. Physical examination: The clinical presentation of allergic children varies depending on whether the allergic symptoms are acute or chronic, and the organs and systems involved.
Acute severe food allergy may present with dyspnea due to laryngeal edema, airway obstruction, pallor, low breath sounds in the lungs or wheezing sounds (in severe cases, increased heart rate and decreased blood pressure). Other positive signs that may be found are cyanosis of the lower eyelids (“allergic eye shadow”), pale edema of the nasal mucosa, and wheezing sounds in the lungs. Dry skin, rash and post-rash scratching.
For infants in growth spurts, weight gain and growth status are important components of the physical examination. In addition to congenital malformations, metabolic abnormalities and other diseases, the presence of allergic diseases should be noted if the growth of the child is slowed.
3. Clinical manifestations: The clinical manifestations of allergy in infancy mainly occur in the skin, digestive and respiratory systems (Table 2). When the symptoms and signs described in Table 2 appear, attention should be paid to exclude allergy and further relevant auxiliary examinations should be performed.
Table 2 Common signs and symptoms of allergy in infants
Involved tissues and organs Signs and symptoms
Gastrointestinal tract Vomiting, diarrhea, gastroesophageal reflux, constipation (with or without perianal rash), bloody stools, iron deficiency anemia; in severe cases: growth retardation, iron deficiency anemia, hypoproteinemia, enteropathy or severe colitis
Skin Atopic dermatitis, edema of the face, lips, eyelids (angioedema), urticaria after eating, pruritus; in severe cases: hypoproteinemia, growth retardation or iron deficiency anemia
Respiratory tract (non-infectious) Itchy nose, runny nose, otitis media, chronic cough, wheezing; in severe cases: acute laryngeal edema or airway obstruction
Eye Itchy, watery eyes, transient eyes, bulbar conjunctival congestion
Systemic Persistent restlessness and abdominal pain ≥3d/week (crying/irritation, ≥3h/d) for more than 3 weeks, growth retardation; in severe cases: anaphylaxis
4. Ancillary tests.
(1) Non-specific tests: have suggestive and reference value for diagnosis.
①IgE: elevated serum total IgE level.
(2) Peripheral blood eosinophil ratio: total leukocyte count may be normal. When eosinophils account for 5%-15% of total leukocytes, it suggests allergic reaction; when it accounts for 16%-40%, it suggests the presence of allergic reaction or other conditions (e.g.: drug hypersensitivity reaction, tumor, autoimmune disease, parasitic infection); when it accounts for 50%-90%, it is mostly seen in eosinophilia syndrome or visceral larval migratory disease.
(3) Eosinophil examination of secretions: eosinophils are present in the secretions of conjunctiva or nasal mucosa (nasal swab examination) and sputum.
(2) Specific test: mainly refers to determine the type of allergen. It should be noted that positive results of simple allergen testing (skin test, serum sIgE) must be combined with clinical manifestations to determine the type of allergen causing the allergy.
① Skin test: standardized concentration of antigen skin test is used. The skin test has a high positive predictive value for the diagnosis of inhalant allergies, such as allergic rhinitis and conjunctivitis; it has a high negative predictive value for food allergies. There are 2 skin test methods, the skin prick or intradermal test. The prick test can detect most allergens. The intradermal test is more sensitive but less specific and can be used to assess the sensitivity to allergens in children with negative or suspected positive prick tests; it is not indicated for infants.
Each skin test should have a negative control (separate dilutions) and a positive control (histamine, 10 mg/ml for the prick test and 1:1000 dilution for the intradermal test). False positives are seen in those with a positive skin scratch sign, where the wind mass and erythema are caused by rubbing or scratching the skin. False negatives are seen in cases of improper storage of allergen extracts, expiration or use of drugs (e.g. antihistamines).
Skin prick testing with an allergen should be contraindicated in persons who have had a severe allergic reaction to that allergen (systemic allergic reaction, severe asthma attack). Skin testing should also be avoided during the acute phase of an allergic reaction.
There is no age limit for skin prick testing. In infancy, due to the thin and tender skin, the skin prick technique is more demanding and the skin prick test results should be judged with caution. Allergen spot-prick (prick to prick) tests are mainly used for children with allergy to fresh vegetables or fruits (e.g., mouth allergy) and rare substances. It is difficult to prepare these reagents for commercial use. For milk, egg and other food and inhalation allergens, it is difficult to control the allergen concentration directly with the substance in question, and the test results are difficult to standardize and carry certain risks.
②Serum allergen-specific IgE assay: It can be applied to infants of all ages. However, the positive results obtained from the test must be combined with clinical manifestations and avoidance tests to determine the type of allergen. quantitative measurement of serum sIgE concentration by the UniCAP system is considered the gold standard for in vitro detection of sIgE. The concentration of allergen sIgE is useful in helping to determine the relationship between allergen type and clinical manifestations, and the likelihood of clinical signs and symptoms is increased when allergen sIgE concentrations are high. Since food allergy may be a T-cell, eosinophil-mediated immune response, a negative food allergen sIgE test does not exclude the possibility of allergy, especially in gastrointestinal-related food allergies. In this case, further patch test or avoidance test is required for diagnostic differentiation.
(3) Patch test: For infants with delayed allergic reactions, skin tests and serum sIgE tests can be used if the allergen cannot be identified.
(5) Avoidance test: It can be used in infants with food allergy whether the allergen sIgE is detected or not. It is mainly used to help clarify the type of allergen by short-term avoidance of the suspected food consumed daily and observing changes in clinical symptoms and signs. Generally, a food is strictly avoided for 2 weeks at a time, and if a non-IgE-mediated allergic reaction is considered for at least 4 weeks (including compounded foods containing the food component in question), the improvement of clinical signs and symptoms is observed. If clinical signs improve significantly, it is suggested that the infant’s allergy may be related to this food. Further addition of such food, if the clinical manifestations worsen, confirms the allergenic nature of the above food (the latter is a provocation test). This procedure allows screening of suspected foods on a case-by-case basis.
6. Food diary: A food diary should be kept when a food allergy is suspected or when an avoidance test is performed. A food diary is a supplement to the medical history. Parents keep a detailed record of the food the child eats each day (including what is only put in the mouth) for a specific period of time. Lactating mothers should also keep track of their own food and drink, and record in detail the symptoms and timing of the child’s symptoms. Sometimes a causal relationship between food and symptoms is found in the diary, and some hidden food allergens are discovered.
7. Double-blind, controlled-placebo food provocation test: It is mainly used for food allergy diagnosis in infancy. Because most food allergies can be diagnosed by the above method, although it is the gold standard for food allergy diagnosis, it is recommended to be used only in a few well-equipped allergy diagnosis centers due to the risk of serious allergic reactions and the complexity and strict requirements of the procedure.
V. Treatment
Treatment is aimed at infants with allergic diseases. It mainly includes environmental control, dietary control and drug treatment.
(I) Environmental control
Environmental control is the first step in the treatment of any allergic disease. The main activity space during infancy is indoors, so the main content of environmental control involves indoor allergen control.
Families with infants and children with a family history of atopic disease need to limit indoor pet ownership. Although it is not yet possible to completely remove dust mites from living rooms, existing methods and measures can significantly reduce the amount of dust mites and mitigate the severity of dust mite allergy onset, the number of episodes, and the dosage of preventive medications. Keeping the indoor environment ventilated and dry can help reduce dust mites and avoid mold growth.
(ii) Dietary control
The treatment of food allergy relies mainly on avoiding allergic foods. The common foods to be avoided are milk and eggs.
1. Main methods.
(1) Milk allergy and infants with persistent and/or severe allergy symptoms: completely avoid formulas and foods containing milk proteins. The main formulas available: amino acid formula, deeply hydrolyzed protein formula. Duration of treatment is at least 3-6 months. Results are usually seen after at least 1-2 weeks. Those who have experienced severe systemic allergic reactions (e.g. anaphylaxis), angioedema and other life-threatening clinical manifestations should continuously avoid any food containing milk proteins.
②Mild milk allergy (mainly refers to mild eczema) infants: long-term use of amino acid formula and deeply hydrolyzed protein formula is generally not recommended. You can try to add moderately hydrolyzed protein formula after 1-3 months of using amino acid formula and deeply hydrolyzed protein formula, and continue to use it if you can adapt to it; if you cannot adapt, you should try to add moderately hydrolyzed protein formula after 1-2 years. You can also try moderately hydrolyzed protein formula directly.
(③) Egg and other food allergies: in principle, they should also be avoided. Whether to add them again after clinical symptoms have improved should also be decided based on the situation of those with similar milk allergies.
④Breast-fed infants with allergy: breastfeeding is generally not stopped and the mother may engage in dietary avoidance. The mother should avoid allergenic foods for at least 2 weeks. Some mothers of children with atopic dermatitis and enteritis may avoid allergenic foods for up to 4 weeks. If the infant’s allergy symptoms improve significantly and disappear after the mother avoids the allergenic food, the mother may add the avoided food to the diet and resume it if the symptoms do not reappear. If symptoms reappear after the addition of a food, the mother should avoid that food completely during breastfeeding. If the mother’s diet does not improve the child’s symptoms, the mother should return to her normal diet.
Severe atopic dermatitis causing growth loss in infants due to breastfeeding is rare and can be discontinued. Feeding with amino acid formula, deeply hydrolyzed protein formula or moderately hydrolyzed protein formula can be tried.
⑤ Infants with transitional foods: ensure that they do not contain allergy-inducing food components.
2. Alternative methods: ①Soy milk feeding: There is a lack of clinical research evidence in China, so it can be tried according to the specific situation of the child as appropriate. ② Other animal milk products: should be used with caution because in addition to the possibility of cross-reactivity, their nutritional content may not meet the needs of infants.
(iii) Drug therapy and others
1) Antihistamines: The choice of antihistamines in infancy is based on the first generation of antihistamines, represented by chlorpheniramine maleate and promethazine. Second-generation antihistamines still lack extensive clinical and pharmacokinetic study data, the representative drugs are loratadine and cetirizine, if used in infants > 6 months of age should be cautious and short-term.
2. Mast cell stabilizers: Representative drugs are sodium cromoglycate and nedolomide, which can block the release of mast cell mediators and are mainly used for other drugs (e.g. antihistamines, topical corticosteroids) that are ineffective or intolerant. They are mainly used for topical use in respiratory and ocular allergies.
3. leukotriene receptor antagonists: mainly used in children over 1 year of age and adults, with less research on the use in infancy. They are also used in a few countries and regions for infants >6 months of age. For infants >6 months of age who develop respiratory allergies, short-term use may be appropriate depending on clinical manifestations.
4. Hormonal drugs: Systemic glucocorticoids can be used for a short time in children with severe eczema, severe wheezing episodes, angioneurotic edema and systemic allergic reactions. Non-IgE-mediated allergic diseases in infants are mainly treated with glucocorticoids for symptomatic relief.
5. Topical treatment: Most children need topical glucocorticoid cream or ointment, which can be changed for 3-4 weeks to prevent tolerance. Also, add emollients 1-2 times a day and avoid too frequent bathing. Prevent excessive dryness of the skin after bathing.
Other treatments: UV and microwave therapy may reduce symptoms in some severe cases where topical hormone use is ineffective. Vitamins, trace elements and herbal medicine can be used as adjunctive treatment.
6. 1:1000 epinephrine application: Any child with IgE-mediated acute allergy can be applied at 0.01mg/kg subcutaneously at a time.
7. Addition of probiotics or prebiotics: may help to improve the clinical symptoms of infantile eczema. Probiotics or prebiotics may be added as appropriate for infants with recurrent gastrointestinal allergies or diarrhea.
Chinese Journal of Pediatrics, Vol. 47, No. 11, November 2009