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Non-IgE-mediated food allergy: Evaluation and management

Posted:Apr 27, 2021


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Principal author(s)

Elissa M Abrams, Kyla J Hildebrand, Edmond S Chan; Canadian Paediatric Society,Allergy Section

Paediad儿童健康2021 26(3):173-176

Abstract

The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). FPIES presents with delayed refractory emesis, while FPIAP presents with hematochezia in otherwise healthy infants. Acute management of FPIES includes rehydration or ondansetron, or both. No acute management is required for FPIAP. Long-term management of both disorders includes avoidance of the trigger food. The prognosis for both conditions is a high rate of resolution within a few years’ time.

Keywords:Allergy; Food allergy; Food protein-induced enterocolitis syndrome; Food protein-induced allergic proctocolitis

Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies, including food protein-induced enterocolitis syndrome (FPIES), food protein induced allergic proctocolitis (FPIAP), food protein-induced enteropathy (FPE), and other conditions[1]。This practice point focuses on FPIES and FPIAP as the most common of these conditions. The largest prospective study of infants with non-IgE-mediated food allergy reported a cumulative incidence for FPIES of 0.34%[2], and for FPIAP of 0.16%[3.]。However, the estimated prevalence of FPIES and FPIAP varies among studies[4.], and are probably underestimated overall[1]。The pathophysiologies of FPIES and FPIAP are poorly understood but both conditions are believed to be caused by T-cell-mediated inflammation[1][5.]

Clinical manifestations

食物蛋白诱导的内肠癌综合征:FPIES

FPIES.generally presents in infants between 2 to 7 months of age, often in association with the introduction of formula or solids into the diet (although this disorder can also occur into adulthood)[1][2][5.][6.]。急性FPIES的特点是大量的,重复呕吐,通常伴有Pallor或嗜睡(或两者),并且在摄取触发食物后通常发生1至4小时[1][5.][7.]。在首次暴露于触发器食品或经过一段时间的宽容之后,可能会发生迹象[8.]。相关的腹泻,通常代表更严重的FPIE形式,可能发生在5至10小时后[8.]。In rare severe cases, infants may experience associated hypothermia, hypotension, loss of consciousness, hypotonia, acidemia, or methemoglobinemia[1][5.][9.]

In contrast to IgE-mediated allergy, there are no associated cutaneous or respiratory symptoms with FPIES. It is important to include FPIES in the differential diagnosis for an infant presenting to the emergency room with acute-onset emesis, because presentation can be easily confused with viral gastroenteritis, sepsis, or other conditions.

慢性FPIES描述不佳,罕见,并且需要更多的进一步表征研究。慢性FPIE在持续摄入触发器食物的背景下发生。症状是非特异性的,可能包括茁壮成长,贫血,慢性腹泻或呕吐和吸收不良[1]。Symptoms resolve with elimination of the trigger food from the infant diet.

Food protein-induced allergic proctocolitis: FPIAP

FPIAP presents with intermittent, slow-in-onset hematochezia in an otherwise healthy, growing infant, generally in the first 6 months of life (typical onset is in the first 1 to 4 weeks post-delivery)[9.]。There is no associated emesis, diarrhea, or failure to thrive[1]。症状解决了消除母婴饮食的触发食物。

Acute management

FPIES.

历史应关注婴儿饲养模式,包括在临时与反应相关的公式或固体(或两者)的引入。在急性FPIE中,可能存在脱水迹象。

当血液工作急性地进行时,FPIES的婴儿也可以具有白细胞增多,中性粒细胞,血小伤症,甲蛋白血症或代谢酸中毒。但是,血液测试既不敏感,也不具体对FPIES[10.][11.]。In acute FPIES, dehydration can lead to hemodynamic instability, indicating a medical emergency[5.]。Management in the acute care setting includes intravenous (IV) fluid boluses (10 to 20 mL/kg of normal saline[NS]may be required)[10.]。There is increasing evidence that IV or intramuscular (IM) ondansetron (one dose of 0.15 mg/kg; typically 2 mg for patients weighing 8 to 15 kg; 4 mg for those weighing 15 to 30 kg; and 8 mg for those >30 kg) may resolve ongoing emesis and reduce the risk of dehydration when used for acute FPIES[12.]-[14.]。当FPIES严重时,可能考虑IV皮质类固醇(例如,甲基丙酮醇1mg / kg至最大60至80mg),尽管没有研究表明该策略的功效[10.]

FPIAP

In general, the physical examination and blood work will be normal. No acute intervention, including blood work, is required.

Long-term management

FPIES.

Primary management consists of eliminating the trigger food from the infant’s diet (Table 1[11.][15.]。Identification of the trigger food relies largely on clinical history. There is no validated diagnostic testing for FPIES other than an oral food challenge by an allergist (using observed ingestion in the office (OFC)). An OFC would only be recommended if the infant’s history is unclear, such as in the absence of a clear trigger food, an atypical symptom time course, or lack of symptom resolution with trigger food elimination[5.][16.]。对于历史明确历史的婴儿,主要表明,评估FPIE是否已经超出了。不推荐粪便测试,内窥镜检查和射线照相[5.][10.]

Table 1。Food triggers for FPIES, from most to least common
Food Category
Specific foods
Rates
牛奶
6.7.%
Soy
4.1%
Grains
Rice > Oat > Wheat > Corn > Barley
25.。3.%
Egg
11%
Meats/Fish
Chicken > Turkey > Beef > Pork > Lamb > Salmon > Crab
<10%
Vegetables
Sweet potato > Pea > Potato > Carrot > Squash > Kidney bean > Green bean
<10%
Fruits
Banana > Apple > Pear > Peach > Plum > Strawberry > Watermelon > Avocado
<10%
Peanut/Tree nut
Peanut > Tree nut
<10%
Adapted from reference[15.]

与IgE介导的过敏相比,没有必要避免预防性的食品(例如,“可能含有”)标记,并且在大多数情况下,在母乳喂养时不需要母体消除触发器食物[5.][7.]。Nor is having an epinephrine autoinjector required[7.]

FPIES的婴儿可能对多种食物触发作出反应。多种食品FPIE的患病率因地理位置而异,但估计达到大约30%的婴儿用FPIES[11.][15.]。In the absence of a history of reaction, however, avoiding common FPIES triggers during infancy is not recommended[15.]。Although some guidelines suggest delaying introduction of additional common allergens empirically to prevent FPIES, this approach is not recommended. Because IgE-mediated food allergy is more prevalent and generally more difficult to outgrow, the risk of developing an IgE-mediated allergy to foods such as peanut or egg outweighs the benefit of delayed introduction to manage or prevent FPIES[17.]。Rather, introducing commonly allergenic solids at around 6 months of age (and not before 4 months), especially if the child is at risk for IgE-mediated allergy, is recommended[17.]

When an infant has cow’s milk FPIES, extensively hydrolyzed formula should be considered as a feeding alternative[11.][18.]。Recent data suggest that cross-reactivity between cow’s milk and soy-based formulas is low, such that soy-based formula can be considered as an alternative for feeding infants over 6 months of age[2]。在广泛水解的公式中试验少数婴儿似乎需要基于氨基酸的式。[5.][10.]。When the trigger food is rice or oat, avoiding both these grains is recommended because of the high rate of cross-reactivity between the two. Attempting to introduce other grains into the diet of infants who react to either rice or oat is reasonable[10.]

Especially in the context of multiple food FPIES, growth and nutrition must be closely monitored[5.]

FPIAP

When an infant is breastfed, FPIAP typically resolves with the elimination of cow’s milk (and often soy) from the maternal diet. Other possible triggers are egg and corn, which can be removed from maternal diet when symptoms do not resolve with cow’s milk and soy elimination[7.][19.]。In formula-fed infants, FPIAP typically resolves with transition to an extensively hydrolyzed formula[7.][19.][20.]。只有很少是所需的氨基酸的公式[19.][20.]

Prognosis

FPIES.

The natural history of FPIES is a high spontaneous rate of resolution, often in early childhood. A large review of FPIES in childhood noted rates of resolution of 35% by 2 years of age, 70% by 3 years of age, and 85% by 5 years of age[15.]。Solid food-related FPIES may resolve later than cow’s milk or soy FPIES[5.][11.][15.]。Medically supervised OFCs may be considered as early as 12 to 18 months after the most recent reaction[1]。他们应该在一个医疗设置with ready access to IV fluids, although data suggest that infants who require IV fluids tend to be younger or have severe FPIES[5.][21.]。存在不同的OFC协议,具有蛋白质量和观察期的可变性[5.]

FPIAP

FPIAP typically resolves by one year of age[1]。牛奶and soy can then be introduced into both the mother’s and the infant’s diet, one at a time, in an age-appropriate way[7.]。It is not known whether cow’s milk and soy need to be introduced slowly, but this approach may be considered for practical reasons.

When to refer to an allergist

FPIES.

In general, young children with FPIES should be referred to an allergist who can offer OFCs for evaluation, especially before reintroducing a trigger food into the diet. Only an OFC can safely identify when a child has outgrown FPIES. Early referrals can help to ensure timely access to OFCs. Referral is also warranted when the family is hesitant to introduce new foods that have not been tried before.

Some guidelines recommend that allergists perform skin prick testing to measure food-specific IgE levels for a trigger food, because such tests can have prognostic implications (e.g., prolonged course) and identify children at risk for future IgE-mediated reactions[7.]。However, skin prick tests are highly susceptible to false positive results. Such tests should only be conducted with allergist guidance, and OFCs remain the procedure of first line.

Limited access to appropriate test settings in Canada may prompt health care providers to consider other factors. For example, in rural areas, a local paediatrician with admitting privileges may be comfortable conducting an OFC, after consultation with a paediatric allergist remotely. Specialist allergy involvement is not always necessary for infants whose trigger food has been clearly identified and whose family diet has not been otherwise restricted, provided that both the family and clinician are comfortable with ongoing nutritional management.

FPIAP

Infants with uncomplicated FPIAP may not require allergy referral. However, any infant with FPIAP should be evaluated if the trigger cannot be identified, or if the symptoms do not respond to typical trigger food eliminations.

Practice points

  • Acute management of FPIES includes fluid resuscitation or IV/IM ondansetron (or both). No acute management of FPIAP is necessary.
  • FPIE和FPIAP的长期管理涉及消除婴儿饮食中的触发食物。
  • Avoiding cross-reactive foods and precautionary labelling are generally not required.
  • Using an epinephrine autoinjector is not required for FPIES or FPIAP.
  • Closely monitoring nutrition and growth, especially when there are multiple trigger foods or food avoidances, is essential.
  • Both FPIAP and FPIES have high rates of resolution in early childhood. Reintroducing a trigger food at home can occur with FPIAP. For FPIES, reintroduction should occur under medical supervision.

Acknowledgements

This practice point has been reviewed by the Community Paediatrics, Drug Therapy and Hazardous Substances, and Nutrition and Gastroenterology Committees of the Canadian Paediatric Society.


CANADIAN PAEDIATRIC SOCIETY ALLERGY SECTION

Executive members:Elissa M Abrams Md(主席),埃德蒙德·陈MD(秘书财务主管)

Principal authors:Elissa M Abrams MD, Kyla J Hildebrand MD, Edmond S Chan MD


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Disclaimer:The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated:Apr 28, 2021