Milk Induced Entero

8/11/2019 Milk Induced Entero

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Introduction

Many food proteins can act as antigens in humans. Cow's milk proteins are most frequently implicated

as a cause of food intolerance during infancy. Soybean protein ranks second as an antigen in the first

months of life, particularly in infants with primary cow's milk intolerance who are placed on a soy

formula. From school age on, egg protein intolerance becomes more prevalent.

Several clinical reactions to food proteins have been reported in children and adults. Only a few of these

have a clear allergic immunoglobulin E (IgE)mediated pathogenesis. For this reason, the term "food

protein intolerance" is usually preferred to "food protein allergy," in order to include all offending

specific reactions to food proteins, no matter the pathogenesis.[1] In children, GI symptoms are

generally most common, with a frequency ranging from 50-80%, followed by cutaneous symptoms (20-

40%), and respiratory symptoms (4-25%).

Epidemiology

Frequency

United States

In a national survey of pediatric allergists, the prevalence rate of cow's milk allergy was reported to be

3.4%, whereas the prevalence rate of soy protein allergy was 1.1%. During the 10-year period of 1997-

2006, food allergy rates significantly increased among both preschool-aged and older children.[6] In

2007, the reported food allergy rate among all children younger than 18 years was 18% higher than in

1997.

International

Incidence of food allergy in children has been variously estimated at 0.3-8%, and the incidence

decreases with age. Food allergies affect 6-8% of infants younger than 2 years. In a cohort of 1,749

newborns from the municipality of Odense in Denmark who were prospectively monitored for the

development of cow's milk protein intolerance during the first year of life, a 1-year incidence of 2.2%

was reported.Varying incidences of specific intolerances have been reported in different countries.

Whether these differences are due to genetic or cultural factors is unclear.To evaluate the prevalence of

food allergy among different countries in Europe, the EuroPrevall project was launched in June 2005.

Subsequently, the EuroPrevall-INCO project has been developed to evaluate the prevalence of food

allergies in China, India, and Russia.


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Mortality/Morbidity

Most of the cases of food protein intolerance can be resolved with dietary management. A few cases of

severe anaphylactic reactions to food proteins have been reported. A report from the United Kingdom

suggests an incidence of 0.22 severe cases per 100.000 children per year (15% of cases were fatal or

near fatal).

Food allergy is mainly a problem in infancy and early childhood. Cow's milk allergy or intolerance usually

develops in early infancy. In most of the cases, the onset of symptoms is closely related to the time of

introduction of formula based on cow's milk.

In a prospective study from Norway, the prevalence of atopic dermatitis in the first 2 years was 18.6%

with no significant difference between preterm and term children. Adverse reactions to food were

found in 15.8% (a similar prevalence in premature and term children).Typical atopic dermatitis on the

face of an infantTypical atopic dermatitis on the face of an infant.

An unselected prospective study indicated that 42% of infants who developed cow's milk protein

intolerance were symptomatic within 7 days (70% within 4 wk) following the introduction of cow's

milk.[6] Cow's milk protein intolerance has been diagnosed in 1.9-2.8% of general populations of infants

aged 2 years or younger in different countries of northern Europe, but incidence fell to approximately

0.3% in children older than 3 years.

Symptoms

Usually, the GI manifestations are isolated, without any sign of atopic dermatitis, urticaria, rhinitis,

conjunctivitis, or wheezing.

In proctocolitis syndrome, the child (usually a young infant) appears healthy, without any weight

loss or other physical problems.

In food-induced GI anaphylaxis, these symptoms (eg, atopic dermatitis, urticaria, rhinitis,

conjunctivitis, wheezing) can occur, and, therefore, the child must be checked for the presence

of systemic signs of allergic reaction.

The infant with enterocolitis syndrome can be dehydrated as a consequence of diarrhea,

vomiting, or both. Signs of dehydration include blunted eyes, dry mucous membranes, andhypoelastic skin.

In the unusual instances of nonceliac food-induced enteropathy, infants present with signs and

symptoms of malabsorption syndrome. Dystrophy, growth failure, edema (hypoalbuminemia),

rickets (vitamin D malabsorption), and hemorrhages (vitamin K malabsorption) can all be

present.


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Pathomechanism

The major food allergens are water-soluble glycoproteins (molecular weight [MW], 10,000-60,000) that

are resistant to heat, acid, and enzymes. Cow's milk contains more than 20 protein fractions. In the curd,

4 caseins (ie, S1, S2, S3, S4) can be identified that account for about 80% of the milk proteins. The

remaining 20% of the proteins, essentially globular proteins (eg, lactalbumin, lactoglobulin, bovine

serum albumin), are contained in the whey. Casein is often considered poorly immunogenic because of

its flexible, noncompact structure. Historically, lactoglobulin has been accepted as the major allergen in

cow's milk protein intolerance. However, polysensitization to several proteins is observed in about 75%

of patients with allergy to cow's milk protein.

The proteins most frequently and most intensively recognized by specific IgE are the lactoglobulin and

the casein fraction. However, all milk proteins appear to be potential allergens, even those that are

present in milk in trace amounts (eg, serum bovine albumin, immunoglobulins, lactoferrin). In each

allergen, numerous epitopes can be recognized by specific IgE presence. Cow's milk proteins introduced

with maternal diet can be transferred to the human milk. Many studies have focused on the presence ofbovine lactoglobulin throughout human lactation. The GI tract is permeable to intact antigens. The

antigen uptake is an endocytotic process that involves intracellular lysosomes. Cow's milk proteins

introduced with maternal diet can be transferred to the human milk. Many studies have focused on the

presence of bovine lactoglobulin throughout human lactation. Antigen uptake has been found to be

increased in children with gastroenteritis and with cow's milk allergy.

Studies have demonstrated that food allergens are transported in large quantities across the epithelium

by binding to cell surface IgE/CD23, which opens a gate for intact dietary allergens to transcytose across

the epithelial cells that protect the antigenic protein from lysosomal degradation in enterocytes.Some

antigens can move through intercellular gaps[3] ; however, the penetration of antigens through the

mucosal barrier is not usually associated with clinical symptoms. Under normal circumstances, food

antigen exposure via the GI tract results in a local immunoglobulin A (IgA) response and in an activation

of suppressor CD8+ lymphocytes that reside in the gut-associated lymphoid tissue (oral tolerance).

In some children who are genetically susceptible, or for other as-of-yet-unknown reasons, oral tolerance

does not develop, and different immunologic and inflammatory mechanisms can be elicited.[4] Whether

nonimmunologic mechanisms can have a role in the development of specific intolerances to foodproteins is still disputed. Some evidence suggests that reduced microbial exposure during infancy and

early childhood result in a slower postnatal maturation of the immune system through a reduction of

the number of T regulatory (Treg) cells and a possible delay in the progression to an optimal balance

between TH1 and TH2 immunity, which is crucial to the clinical expression of allergy and asthma

(hygiene hypothesis).[5] Genetic variations in receptors for bacterial products are likely to be related to

allergic sensitizations. On the other hand, intestinal infections may increase paracellular permeability,


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allowing the absorption of food proteins without epithelial processing. As a consequence, infectious

exposures can be an important contributory factor in the pathogenesis of food protein allergies.

Food protein intolerance can be IgE-mediated or non-IgE-mediated. Local production and systemic

distribution of specific reaginic IgE plays a significant role in IgE-mediated reactions to food proteins.

Morphologic studies have demonstrated the role of GI T lymphocytes (ie, intraepithelial lymphocytes) in

the pathogenesis of GI food allergy. The pathogenetic role of the eosinophils in food-induced

eosinophilic GI diseases has not been defined. Vast evidence describes the occurrence of

immunoglobulin G (IgG) food protein antibodies.The major food allergens are water-soluble

glycoproteins that are resistant to heat, acid, and enzymes.

Cow's milk contains more than 20 protein fractions. In the curd, 4 caseins can be identified that account

for about 80% of the milk proteins. The remaining 20% of the proteins, essentially globular proteins (eg,lactalbumin, lactoglobulin, bovine serum albumin), are contained in the whey. Casein is often

considered poorly immunogenic because of its flexible, noncompact structure. Historically, lactoglobulin

has been accepted as the major allergen in cow's milk protein intolerance. However, polysensitization to

several proteins is observed in about 75% of patients with allergy to cow's milk protein.

The proteins most frequently and most intensively recognized by specific IgE are the lactoglobulin and

the casein fraction. However, all milk proteins appear to be potential allergens, even those that are

present in milk in trace amounts (eg, serum bovine albumin, immunoglobulins, lactoferrin). In each

allergen, numerous epitopes can be recognized by specific IgE presence. Cow's milk proteins introduced

with maternal diet can be transferred to the human milk. Many studies have focused on the presence of

bovine lactoglobulin throughout human lactation. The GI tract is permeable to intact antigens. The

antigen uptake is an endocytotic process that involves intracellular lysosomes.

Cow's milk proteins introduced with maternal diet can be transferred to the human milk. Many studies

have focused on the presence of bovine lactoglobulin throughout human lactation. Antigen uptake has

been found to be increased in children with gastroenteritis and with cow's milk allergy. Studies have

demonstrated that food allergens are transported in large quantities across the epithelium by binding tocell surface IgE/CD23, which opens a gate for intact dietary allergens to transcytose across the epithelial

cells that protect the antigenic protein from lysosomal degradation in enterocytes.

Some antigens can move through intercellular gaps; however, the penetration of antigens through the

mucosal barrier is not usually associated with clinical symptoms. Under normal circumstances, food


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antigen exposure via the GI tract results in a local immunoglobulin A (IgA) response and in an activation

of suppressor CD8+ lymphocytes that reside in the gut-associated lymphoid tissue (oral tolerance).

Diagnosis

Skin test responses to cow's milk or other food proteins and detection of food-specific immunoglobulin

E (IgE) antibodies are usually positive in children with IgE-mediated food allergy. However, most of the

food protein intolerances are not IgE-mediated. A double-blind, placebo-controlled, oral food challenge

is the ideal method for confirming histories of adverse reactions to food proteins. However, this

approach is rarely used in clinical practice.

In addition, even double-blind, placebo-controlled challenges can have pitfalls. Encapsulated food

extracts minimize the potential to elicit oral, esophageal, or airway reactions and could also result in

increased risk because absorption of food might be delayed.

The following tests are indicated in assessing food protein intolerance:

Skin testing with food extracts

This is often used to screen patients with suspected IgE-mediated food allergies.

Skin testing is usually completed by the prick technique, which is a reliable means of detecting

IgE antibodies to food in children.

A positive skin test result merely implies the presence of food-specific IgE antibodies. A negative

skin test result has a high predictive accuracy (estimated to be >95%). Unfortunately, a positive


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prick test result is a poor predictor of clinical symptoms during food challenges. The positive

predictive accuracy widely varies but has been estimated to be lower than 50%. In children

younger than 2 years, the negative predictive accuracy of the skin test result is not as good as in

older children; however, a positive test result is more likely to be significant.

Composition and quality of the extracts are also a significant consideration. Sometimes, testing a

drop of the milk that is used to feed the child (eg, formula milk, soy milk, others) is preferable.

Serum immunoassays: Serum immunoassays to determine food-specific IgE antibodies are often used to

screen for antigen-specific IgE in the patient's serum. Enzyme-linked immunosorbent assays (ELISAs)

have been replacing methods that use radiation (eg, radioallergosorbent test [RAST]). Unfortunately,

determination of specific IgE involves the same problems as the skin test. A negative test result has a

high predictive accuracy with a low sensitivity, whereas a positive test result has a low predictive value.

Fecal leukocyte testing: Fecal eosinophils are a significant clue to the diagnosis of allergic colitis.

However, although eosinophils predominate after a single acute challenge, the findings on fecal smears

at diagnosis are more likely of the inflammatory type, with a predominant population of lymphocytes

and neutrophils and a small number of eosinophils.

Atopy patch testing: Several studies are evaluating the use of the atopy patch test for delayed

intolerances to food proteins. However, no standardized reagents or methods of interpretations are

currently available, and the additional diagnostic information in some studies appears marginal.

Treatment

The definitive treatment of food protein intolerance is strict elimination of the offending food from the

diet.

Breastfeeding is the first choice in infants without lactose intolerance. The mother should

eliminate cow's milk (and eventually eggs and fish or other implicated foods) from her diet.

As many as 50% of children affected by cow's milk protein intolerance develop soy protein

intolerance if they are fed with soy-based formulas. Therefore, soy-based formulas should not

be used for the treatment of cow's milk protein intolerance. Use complete milk protein

hydrolysates in infants who cannot be breastfed. Partially hydrolyzed formulas are absolutely

not indicated in children with cow's milk protein intolerance. Occasionally, children may develop

intolerance toward complete hydrolysated formulas. In these cases, use amino acidbased

formulas, which are now widely available and are balanced in trace elements and vitamins.

Administration of food allergens as immunotherapy carries a greater risk of adverse and

potentially severe allergic reactions compared with the administration of inhalant allergens.

Based largely on the clinical experience published in European trials, the general impression is


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that food allergen exposure through the oral or sublingual routes is less risky than through the

subcutaneous route, but this perception has yet to be definitively demonstrated.

Recombinant monoclonal humanized anti-immunoglobulin E (IgE) therapy has been approved

for the treatment of asthma with associated environmental allergies, but the response can vary

with food allergies.

A 9-herb formula based on traditional Chinese medicine is currently under investigation as a

treatment for food allergy.

Milk Induced Entero

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