OBJECTIVES OF THIS LECTURE: 1.what’s food allergy 2.Cow’s milk protein allergy & its management 3.Lactose intolerance & its management 4.Knowing special milk formulas

Food Allergy & hypersensitivity: Defined as ‘an immune response to food proteins. It occurs in 4-8% children commonly with those of +ve family Hx of atopy or allergies. Food allergy may be IgE mediated or non-IgE mediated. If a non-immunological reaction to a specific food occurs this is called non-allergic food hypersensitivity or intolerance. Presentation of food allergy varies with the agent and the child's age: in infants the most common causes are milk, egg and peanut in older children peanut, tree nut and fish. Fruit allergy, although common, is usually mild, causing an itchy mouth but no systemic symptoms, is called {oral allergy syndrome} & usually associated with spring hay fever due to cross-reaction with tree pollens. Kiwi fruit, however, can cause anaphylaxis.

Food hypersensitivity is not related to food aversion, where the person refuses the food for psychological or behavioural reasons. Management: It involves avoidance of the food but, especially for milk & nuts, this is very difficult as they may be present in small quantities in many foods and food labels are often unclear. The advice of a pediatric dietician is essential. In addition, the child & family must be able to manage an allergic attack. Written self-management plans and adequate training are essential. Drug Mx for mild reactions (no cardiorespiratory symptoms) is with antihistamines. If the child had a severe reaction or has asthma, Rx is with epinephrine(adrenaline) given IM by auto-injector (e.g. Epipen), which the child or parent should carry with them at all times. .

Cow’s Milk Protein Allergy(CMPA)

Results from an immunological reaction to one or more of milk proteins,only 0.5% of breast fed infants are affected & 5-15% of infants show suggestive symptoms. It is either IgE- or non-IgE mediated. 27% show symptoms within 45 minutes,58% within 2hrs Its incidence 2-6% of children, Prevalence highest < 1 year Cow’s Milk Intolerance: A transient intolerance to lactose and/ or protein found in cow’s milk following an infective episode of diarrhoea CHO intolerance is due to mucosal damage which results in reduced activity of disaccharide enzymes Protein intolerance is an immunomediated reaction to cow’s milk protein following mucosal damage.

Clinical presentation: Early reactions (within 45 minutes): Urticaria Angio-oedema Vomiting Acute flare up of atopic dermatitis Medium (45 minutes to 20 hours) Pallor GIT symptoms Late reactions (after 20 hours) Atopic dermatitis Respiratory symptoms Diarrhoea

IgE-mediated(within 30 min) Non-IgE mediated(hrs-ds) Symptoms of CMPA IgE-mediated(within 30 min) Non-IgE mediated(hrs-ds) Anaphylaxis Skin (50-60%): Angio-oedema Urticaria Pruritis GI (50-60%): Nausea/Vomiting Colicky abdo pain Resp (20-30%): Wheezing Rhinitis Laryngeal oedema Asthma Skin: Dermatitis GIT: Chronic diarrhoea( intestinal protein loss produces edema and a protein-losing enteropathy) Iron deficiency anaemia Colic Food refusal and poor growth GORD Blood in stool Constipation Enterocolitis Eosinophilic oesophagogastroenteropathy Respiratory:asthma

Examples of food allergy and hypersensitivity to milk Examples of food allergy and hypersensitivity to milk. (b and c) Widespread urticaria and lip swelling during milk challenge

Evaluation of a child with suspected CMPA: A comprehensive history:atopic one parent( risk 20-40%) or both(risk 40-50%) or sibling. Symptoms:either GIT, skin or respiratory CMPA in Breast fed Infants: Symptoms include skin or GIT Most of symptoms are mild to severe. Infants with atopic dermatitis: Risk of CMPA x 4 Risk of egg allergy x 8

Diagnosis: Comprehensive allergy focused clinical Hx with careful & complete PE IgE specific antibody (RAST) Skin Prick Testing Elimination Diet & Food Challenge the Dx can be confirmed safely & easily by rectal mucosal biopsy; this shows eosinophilic inflammation of the mucosa. Visual findings at proctoscopy usually include mucosal friability & lymphoid hyperplasia, giving a lumpy, "mosquito-bitten" appearance to the rectal mucosa. Treatment: Breast fed infants: Maternal exclusion diet avoiding food containing ( dairy products) Bottle fed infants: Cows Milk Free formula: Extensively hydrolysed Formulae (e.g., Nutramigen, Pregestamil, or Alimentum). Amino Acid based Formulae Prognosis: 50% resolve in first year of life 60-70% resolve by second year of life 80-90% resolve by fifth year of life Parental reported rate 4x higher

Skin prick testing. A drop of the allergen is placed on the skin, the site is marked and pricked with a needle, and any weal measured. Multiple +ve results are present

Lactose intolerance

Also called lactase deficiency and hypolactasia, is the inability to digest lactose, a sugar found in milk and to a lesser extent milk-derived dairy products. It is not a disorder as such, but a genetically-determined characteristic. Lactose intolerant individuals have insufficient levels of lactase, an enzyme that catalyzes hydrolysis of lactose into glucose and galactose, in their digestive system.  Lactase deficiency has a number of causes and is classified as one of three types: 1.Primary lactase deficiency(Primary adult type-hypolactasia) is genetic, only affects adults and is caused by the absence of a lactase persistence allele.  It is the most common cause of lactose intolerance as a majority of the world's population lacks these alleles. The brush border lactase is expressed at low levels during fetal life; activity increases in late fetal life and peaks from term to 3 yr, after which levels gradually decrease with age.

2.Secondary, acquired, or transient lactase deficiency is caused by an injury to the small intestine, usually during infancy, from acute gastroenteritis(rotavirus infection),celiac disease, chemotherapy, intestinal parasites or other environmental causes. 3.Congenital lactase deficiency(CLD) is a very rare, autosomal recessive genetic disorder that prevents lactase expression from birth.  It is particularly common in Finland. People with congenital lactase deficiency cannot digest lactose from birth, and therefore cannot digest breast milk.

Clinical presentation: The principal symptom is an adverse reaction to products containing lactose (primarily milk), including: abdominal bloating & cramps, flatulence, diarrhea, nausea, borborygmi (rumbling stomach) and vomiting (particularly in adolescents). These appear 30 min- 2 hrs after consumption.  The severity of symptoms typically ↑ with the amount of lactose consumed; most lactose-intolerant people can tolerate a certain level of lactose in their diet without ill-effect.

Pathophysiology: A deficiency of intestinal lactase prevents hydrolysis of ingested lactose. The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached. Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit, which increases the degree of maldigestion. Within the large intestine, free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas. The combined increase in fecal water, intestinal transit, and generated H2 accounts for the wide range of GIT symptoms.

Laboratory Studies: not mandatory, & often simple dietary changes that reduce or eliminate lactose from the diet relieve symptoms. Stool exam: acidic stool PH(A stool pH ˂ 5.3 is suggestive of CHO malabsorption, whereas a stool pH ˃ 5.6 is evidence against this Dx). +ve for reducing substances(non specific) Lactose tolerance test This test is rarely done in clinical practice. Measure serial bd glucose levels after an oral lactose load. A fasting serum glucose level is obtained, after which 50 g of lactose is administered. Measure the serum glucose level at 0, 60, and 120 min. False-negative results occur in presence of DM & small bowel bacterial overgrowth. The Dx is confirmed if the serum glucose level fails to ↑ by 20 g/dL above baseline

Breath hydrogen test(H2-breath test) This is the diagnostic test of choice. Subjects are administered lactose after an overnight fast, after which expired air samples are collected before and at 30-minute intervals for 3 hours to assess hydrogen gas concentrations. A rise in breath hydrogen concentration greater than 20 parts per million over the baseline after lactose ingestion suggests lactase deficiency. Small bowel biopsy This is the criterion standard; however, it is invasive and rarely performed usually necessary. A major advantage is that it provides definitive information. Biopsy samples from the small bowel are assayed for lactase activity. The biopsy results may be normal if deficiency is focal or patchy

DDx Giardiasis Inflammatory Bowel Disease Irritable Bowel Syndrome

Treatment: Dietary adjustment is the primary form of therapy.  Advise patients to reduce or restrict products containing lactose. Lactose-free formulas(LF based on either soy or cow's milk) are very effective. Yogurt and fermented products, such as cheeses, are better tolerated than regular milk. Commercially available lactase enzyme preparations (eg, LACTAID, Lactrase) are effective in reducing symptoms; however, they may not be effective in some pts, partially due to insufficient dosing. Supplemental calcium should also be recommended. In 2ry lactase def., Rx is directed at underlying cause.

Avoid or reduce intake of lactose-containing foods. Diet Avoid or reduce intake of lactose-containing foods. Most patients who are lactose intolerant can ingest as much as 240 mL of milk without an exacerbation of their symptoms. Certain medications and foods contain hidden lactose, such as breads, margarine, salad dressings, and candies. Complications of lactose intolerance: may include osteopenia.