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DIETARY PROTEIN INTOLERANCE

DEFINITION:

An inflammatory disorder involving the intestines due to exposure to specific dietary antigens resulting in 3 clinical entities.

EPIDEMIOLOGY:

incidence: O.5 - 7.5% of infants
age of onset:
- usually in first 3 months of life
- when exposed to dietary antigens
risk factors:

1. Specific Dietary Proteins

1. Cow's Milk Proteins

beta-lactoglobulin (#1 cause), alpha-lactoglobulin, casein, bovine serum albumin, gamma-lactoglobulin - marked similarity antigenically between cow's and goat's milk proteins
much higher protein content than human breast milk

2. Soy Proteins

8-50% of children with cow's milk protein intolerance will also have soy protein intolerance

3. Human Breast Milk Proteins

rare and likely due to maternal cow's milk ingestion

4. Formulas

beef and lamb-based formulas

2. Familial

family history of cow's milk protein intolerance +/- atopy
atopy: severe atopic diseases (eczema, asthma) in an infant under 12 months of age

3. Post Infectious Diarrhea

diarrhea allows passage of large dietary antigens and may produce a secondary dietary protein intolerance

PATHOGENESIS:

dietary protein intolerance is an immunologically-mediated response to a dietary antigen and four mechanisms of inflammation are involved:

1. Allergic Reaction

1. Immediate Hypersensitivity

IgE mediated
elevated IgE anticow's-milk antibody levels
can cause:
- immediate anaphylactic hypersensitivity (< 1 mg)
- exacerbations of eczema +/- urticaria within 45 minutes of ingestion of a small volume

2. Non-allergic Reactions

2. Cytotoxic Hypersensitivity

IgG and/or IgM mediated
when these complement-fixing antibodies bind comple-ment via the classical pathway -> lysis of target cells (cytotoxic)

3. Immune Complex Hypersensitivity

IgG, IgA, and/or IgM mediated
characterized by immune-complex formation

4. Delayed Hypersensitivity

T-cell mediated
eczema, bronchitis, and/or diarrhea occur 24-72 hours after the ingestion of normal volumes (> 300 mls/day) of cow's milk

the binding of proteins in the immature gut followed by an in-creased uptake and subsequent sensitization may play a role in producing a high incidence of protein sensitivity in the small infant

PATHOLOGY:

1. Small Intestinal Biopsy

milder changes than seen in Celiac Disease
patchy mucosal lesions of varying severity with shortened villi and elongated crypts
increased intraepithelial lymphocytes and eosinophils
lamina propria cellularity
plasma cells with antibodies to milk proteins in mucosa

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

1. Small Intestine - 3 Clinical Entities

1. Acute Diarrhea

diarrhea - immediately after antigen ingestion
- watery, non-bloody
others - vomiting & abdominal cramps (irritability)

2. Chronic Diarrhea

diarrhea - chronic, non-bloody
others - FTT, anorexia, mild malabsorption

3. Excessive Enteric Protein and Blood Loss

diarrhea - bloody diarrhea (occult vs gross)
- iron-deficiency anemia
others - protein-loosing enteropathy +/- pulmonary inflitrates (Heiner's Syndrome)
generalized edema

2. Mouth

recurrent, shallow, mucosal ulcerations, perioral dermatitis

3. Stomach

immediate hypersensitivity occurs in the stomach resulting in a syndrome of:
- acute vomiting
- watery or bloody diarrhea
- glottic swelling, fatal anaphylactic shock

4. Colon

pancolitis causing profuse bloody diarrhea

2. Manifestations of Atopy

1. General

irritability, lethargy, fever, cyanosis after eating a small quantity of antigen
colic

2. Skin

perioral erythema, urticaria, angioedema, atopic eczema

3. Respiratory

wheeze, stridor, rhinitis

INVESTIGATIONS:

1. Diagnosis

1. Gold Standard

double-blind placebo-controlled food challenge with dietary protein antigen to be tested presented in a liquid vehicle (infants) or capsule (children) form

2. Clinical Trial

remove offending antigen from diet
- acute symptoms subside within 2 days
- chronic " 1 week
rechallenge initially with small amounts of antigen (1-5 cc) increasing progressively over a few days
- failure if resumption of symptoms within 48 hours of rechallenge (may recur anywhere from 30 min -> 21 days)

3. Allergy Testing

generally not useful in infants

1. In Vivo

skin testing, pin prick

2. In Vitro

RAST, ELISA, MAST

2. Endoscopy/Sigmoidoscopy

biopsy - see Pathology
sigmoidoscopy for diagnosis of milk or soy protein colitis - friability after mucosal wiping

3. Serum

elevated circulating eosinophils
elevated serum levels of IgA and/or IgG to specific antigen
Malabsorption (check CBC, ferritin, albumin, folic acid)
iron-deficiency anemia, metabolic acidosis

4. Stools

blood, eosinophils

MANAGEMENT:

1. Supportive

remove offending antigen
rehydration if dehydrated
iron and nutritional supplements

2. Diets

1. Non-milk Containing Dietary (therapeutic) Formulas

protein (casein) hydrolysate (elemental) formulas
- Alimentum, Nutramigen, Progestamil
processed (evaporated, powdered) milk
- Carnation Good Start
rechallenge after 1 year, if fails use therapeutic formula for another 3-6 months then rechallenge

3. Medications

? sodium cromoglycate (Intal)

4. Prevention

prolonged breast-feeding

5. Natural History (see J. Peds. 116:862, 1990):

1. Cow's Milk Allergy (CMA) is not transitory

28% clinical tolerance by 2 years
56% clinical tolerance by 4 years
78% clinical tolerance by 6 years

2. Common for patients with CMA to acquire other atopic disorders

43% allergic rhinitis
40% asthma
21% atopic eczema
although many of these children become milk tolerant, they subsequently develop other atopic disorders even though they have been on milk-free diets

3. High incidence (75%) of adverse reactions to non-cow's milk foods

58% - eggs
47% - soy milk
35% - oranges
35% - peanuts
22% - casein hydrolysate
18% - bananas
16% - wheat

Pediatric Database - DIETARY PROTEIN INTOLERANCE

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