Cow’s milk protein allergy

Dr . Marleen Engelbrecht

Unitas Hospital

Family history

No family history 12 %

One parent with allergies 20 %

Both parents with allergies

> 40 %

Both parents with the same allergy

70 %

Prevalence of CMPA

• 2 – 7 %

• One of the first complementary foods

• Commonly consumed througout childhood

• In later life part of a balanced diet

Why the increase in allergies?

• Hygiene hypothesis: – Reduced microbial exposure during infancy and childhood – Slower maturation of immune system – Reduction of T regulatory cells – Delay in balance between TH1 and TH2 cells

• Possible overuse of antacids???

– Possibly increased antigen uptake

What does cow milk consist of?

Casein

• 80 %

• Heat stable

• 4 caseins (ie. S1, S2, S3, S4)

• Poorly immunogenic – Flexible

– Non-compact structure

Whey

• 20 %

• Heat sensitive

• Globular proteins (lactalbumin, lactoglobulin, bovine serum albumin)

• Strongly immunogenic – Lactoglobulin is major

allergen

– BUT polysensitization in 75 % of patients

Most frequent symptoms of CMPA

Most frequent symptoms of CMPA

• Gastrointestinal tract:

– Frequent regurgitation

– Vomiting

– Diarrhoea

– Constipation (with or without

perianal rash)

– Blood in stools

– Iron deficiency anaemia

Most frequent symptoms of CMPA

• Skin:

– Atopic dermatitis

– Swelling of lips or eye lids (angio-oedema)

– Urticaria

Most frequent symptoms of CMPA

• Respiratory tract:

– Runny nose

– Otitis media

– Chronic cough unrelated to infection

– Wheezing

Most frequent symptoms of CMPA

• General:

– Persistent distress or colic

• Wailing/irritable for more than 3 hrs per day

• At least 3 days per week

• Over a period of more than 3 weeks

Main adverse reactions to food

Non immune mediated Immune

mediated

Auto immune

TYPE OF REACTION

Disorders of digestion-absorption

Pharmacologic reactions Idiosyncratic reactions

Inborn errors of metabolism

Celiac disease

IgE mediated

Mixed IgE mediated

Non IgE mediated

Oral Gastro intestinal tract Skin

Cardiovascular system Respiratory tract

Immediate hypersentitivity

allergy syndrome Immediate

hypersentitivity

Eosinophilic esophagitis Eosinophilic gastritis

Eosinophilic gastoenteritis Atopic dermatitis

FPIES Enterocolitis Enteropathy Proctocolitis

Chronic constipation

Immune mediated reactions

IgE mediated

Mixed IgE mediated

Non IgE mediated

Oral Gastro intestinal tract Skin

Cardiovascular system Respiratory tract

Immediate hypersentitivity

allergy syndrome Immediate

hypersentitivity

Eosinophilic esophagitis Eosinophilic gastritis

Eosinophilic gastoenteritis Atopic dermatitis

FPIES Enterocolitis Enteropathy Proctocolitis

Chronic constipation

Immune mediated reactions

IgE mediated allergic reactions

• Occur within minutes of ingestion of food

• By definition within 2 hrs

• Several organ systems involved

– Gastrointestinal tract

– Skin

– Respiratory tract

• Anaphylaxis most severe reaction

Anaphylaxis • Skin:

– Urticaria and/or angio-oedema

– Pruritis, erythema and flushing

– Immediate worsening of eczema

– Rashes and erythema after contact with fruit of vegetables

– Acute localised urticaria after contact with food

Anaphylaxis

• Gastrointestinal:

– Swelling, tingling and itching of lips and mouth

– Nausea and/or vomiting

– Abdominal pain, cramps or colic

– Diarrhoea

– Oral allergy syndrome

Anaphylaxis

• Respiratory:

– Rhinitis (sneezing, nasal blockage, itching of nose and throat, conjunctivitis)

– Wheeze or tight cough

– Swelling of larynx with stridor

Anaphylaxis

• Behavioural:

– May be noted as first sign of an allergic reaction

– Feeling of impending doom....

MULTISYSTEM OR SYSTEMIC REACTION = ANAPHYLAXIS

Diagnosis of IgE CMPA

• History of allergic symptoms

• Evidence of sensitisation

– Skin-prick testing

– Specific IgE blood testing

• Oral milk challenge

Prognosis of IgE CMPA

• Generally a childhood allergy:

– 50 % develope tolerance by 8 years

– 80 % develope tolerance by 16 years

• Likely to outgrow allergy if:

– Milder allergic reactions like skin symptoms only

– Tolerance of extensively heated cow’s milk e.g. Baked foods

IgE mediated

Mixed IgE mediated

Non IgE mediated

Oral Gastro intestinal tract Skin

Cardiovascular system Respiratory tract

Immediate hypersentitivity

allergy syndrome Immediate

hypersentitivity

Eosinophilic esophagitis Eosinophilic gastritis

Eosinophilic gastoenteritis Atopic dermatitis

FPIES Enterocolitis Enteropathy Proctocolitis

Chronic constipation

Immune mediated reactions

Mixed IgE mediated allergic reactions

• Allergic eosinophilic gastroenteritis

– Heterogenous group of conditions characterised by eosinophilic inflammation if gastrointestinal tract

– No specific diagnostic test

– Respond to exclusion diet

Allergic eosinophilic gastroenteritis

1. Eosinophilic esophagitis

– Intermittend vomiting not responding to conventional treatment

2. Eosinophilic gastritis – Hematemesis

– Looks like stomach outlet obstruction

3. Eosinophilic gastroenteritis – Protein losing enteropathy

– Severe failure to thrive

Mixed IgE mediated allergic reactions

• Atopic dermatitis

– 30 – 40% of children with atopic eczema have food allergy

– CMPA and egg allergy are most common

– Worsening of symptoms within minutes to days later

– Facial eczema aggravated by contact irritation like tomato

– Gold standard is exclusion and reintroduction

IgE mediated

Mixed IgE mediated

Non IgE mediated

Oral Gastro intestinal tract Skin

Cardiovascular system Respiratory tract

Immediate hypersentitivity

allergy syndrome Immediate

hypersentitivity

Eosinophilic esophagitis Eosinophilic gastritis

Eosinophilic gastoenteritis Atopic dermatitis

FPIES Enterocolitis Enteropathy Proctocolitis

Chronic constipation

Immune mediated reactions

Non IgE mediated allergic reactions

• Food protein induced enterocolitis syndrome

– Acute gastrointestinal food hypersensitivity

– Severe protracted diarrhoea and vomiting, pallor and hypotonia

– Associated with CMPA and soya

– Responds to allergen exclusion

Food protein induced enterocolitis

syndrome 1. Food protein induced enterocolitis

– Severe vomiting 1 – 3 hrs after feeding

– Dehydration

2. Food protein induced proctitis

– Blood streaked stools

– Child looks healthy

3. Food protein induced enteropathy

– Severe gastro often with steatoree

Non IgE mediated allergic reactions

• Allergic dysmotility disorders

– CMPA reflux

• Resistant to standard anti-reflux treatment

• Food refusal and gagging on solids

– CMPA constipation

• Insensitivity of external anal sphincter

• Straining on passing stools which are of normal consistency

Treatment

• Avoidance of all CMP

• Breast-fed:

– Maternal CMP exclusion diet

– Maternal calcium supplementation

– Rarely trial on hypoallergenic formula

Treatment

• Hypoallergenic formula: – Partially hydrolized formula

• OOOOOOOO OOOOOOOO OOOOOOOO

• HA formulas

– Extensively hydrolized formula • OOOOO OO OOO OO OOO OO

• Nan Alfare, Similac Alimentum, Nutricia

Pepticate, Allernova

– Amino acid formula • O O O O O O O O

• Neocate

E X P E N S I V E

T A S T E

B E T T E R

Partially hydrolized formula

• OOOOOOOO OOOOOOOO OOOOOOOO OOOOOOOO

• Peptides with molecular weight 3000 – 10000 Da

• Do not meet clinical criteria for hypoallergenicity

• Not to be used for treatment of infants with CMPA

• Prevention of allergies until one year of age

Extensively hydrolized formula

• OOOOO OO OOO OO OOO OO OOO O OOOO OO

• Peptides with molecular weight of < 3000

• Tolerated by 90 % of CMPA infants

• Should be used as first line in majority of CMPA infants

Amino acid formula

• O O O O O O O O O O O O O O O O O O O O O

• Seperate amino acids

• Expensive

• 2 – 10% of CMPA infants still responds to extensively hydrolized formula

• Benefit from amino acid formula

Soy based formula

• Soya based formula does not prevent allergies

• Used in infants > 6/12 with confirmed CMPA who are not allergic to soya

• Tolerated in IgE mediated CMPA in 90 %

• Avoid in non IgE mediated CMPA as up to 50 % of children will react

Soy based formulae

Other mammalian milk

• Goat, ewe, mare and donkey milk are not a suitable alternative in CMPA

• The allergenic protein are similar in all mammalian milk

• Can get anaphylaxis to goat’s milk in CMPA children

• Concerns about

nutritional value

Development of tolerance

• Natural history is for the development of tolerance during childhood

• Follow up to assess development of tolerance and ensure nutritionally complete diet

• IgE mediated reactions: – SPT and IgE

• Non-IgE mediated reactions: – Uneventful intake of allergenic food

• Controlled food challenge

Lactose intolerance

What is lactose intolerance?

• IT IS NOT THE SAME AS COW’S MILK PROTEIN ALLERGY

• Lactose intolerance is the inability to digest lactose, the SUGAR found in milk

MILK ALLERGY LACTOSE INTOLERANCE

Causes of lactose intolerance

• Primary lactase deficiency – Genetic

– Affects adults

– Absence of a lactase persistence allele

• Secondary lactase deficiency – Injury to the small intestines e.g gastroenteritis

• Congenital lactase deficiency – Very rare genetic disorder

– Prevents lactase expression from birth

Symptoms of lactose intolerance

• Abdominal symptoms only

– Abdominal bloating and cramps

– Flatulence

– Diarrhea

– Nausea

– Rumbling stomach

Treatment

• Lactose free milk:

– Most common cause of lactose intolerance in infants are gastroenteritis

– Lactose free milk for short period

– Lactose free milk still contains the normal milk protein and is not indicated for treatment of cow’s milk protein allergy

Take home message

• CMPA is the most common allergy in children

• CMPA can present with gastrointestinal tract, skin and respiratory tract symptoms

• IgE mediated CMPA can cause anaphylaxis

• Mixed and non IgE mediated CMPA can cause a variety of symptoms and is difficult to diagnose

Take home message

• Partially hydrolized formula is indicated for prevention of CMPA and not for treatment

• Extensively hydrolized formula and Amino acid formula are for treatment of CMPA

• Soy based formula does not prevent allergy

• Other mammalian milk is not a suitable alternative in CMPA

Take home message

• Lactose intolerance is not the same as CMPA

• Lactose intolerance causes only abdominal symptoms

• Lactose free milk can not

be used for the treatment

of CMPA