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Index

B. More information:
As discussed in the previous newsletter, cow's milk can induce various types of adverse reactions. This newsletter will continue the discussion of adverse reactions that have been recorded in the literature, and will continue to focus on allergic reactions (IgE as well as non-IgE-mediated reactions).

Adverse reactions to cow's milk categorised by organ/bodily system involved:

Gastrointestinal:

  • Abdominal bloating, abdominal pain, diarrhoea, nausea and vomiting1,2,3,4,5

  • Constipation6,7,8,9,10,11,12,13,14,15,16

  • Esophagitis and eosinophilic esophagitis9,17,18,19

  • Food Protein-Induced Enterocolitis Syndrome, which generally presents in the 1st year of life with diarrhea, emesis, and irritability. When there is a delay in diagnosis, persistent exposure to cow's milk leads to increasing enteric inflammation manifesting as bloody diarrhea, vomiting, anemia, dehydration, and failure to thrive. The area in the gastrointestinal tract that is affected generally determines the types of symptoms that are experienced (because different regions of the intestinal mucosa would show varying degrees of inflammation and villous atrophy). The extent of enteric inflammation may be limited to mild proctitis, pancolitis, or true enterocolitis with esophagitis, gastritis, enteropathy, and colitis.20,21 Several studies have recorded an association between cow's milk and colitis,22,23,24,25,26 proctocolitis,9,27,28,29,30,31,32 enterocolitis,9,33,34,35,36 necrotizing enterocolitis,37 cow's milk protein sensitive enteropathy,5,38 and intestinal inflammation and malabsorption.5,39,40,41

  • Occult blood loss associated with cow's milk allergy can be a cause of iron deficiency anemia in children.5,29,42,43,44,45

  • Regurgitation and vomiting are common manifestations of cow's milk protein allergy in infants. This is usually ascribed to gastroesophageal reflux (GER). In sensitized infants, cow's milk induces severe gastric dysrhythmia and delayed gastric emptying, which may exacerbate GER and induce reflex vomiting.46 In up to half of the cases of GER8 in infants younger than 1 year, there may be an association with cow's milk allergy. In a high proportion of cases, GER is not only associated with milk but also milk allergy-induced.9,47,48

  • Although colic associated with vomiting has mostly been attributed to GER (itself often associated with milk ingestion: see immediately above), a secondary form resulting from food hypersensitivity has been described.9,50,107,108,109,110
  • Dermatological:

    • Urticaria, eczema, atopic dermatitis, angioedema and erythematous rashes2,3,9,49,50,51,52,53,54,55,56,57,58
    • Cutaneous vasculitis

    Respiratory:

  • Rhinoconjunctivitis60

  • Otitis media61,62

  • Wheezing, bronchospasm or asthma49,60,63,64,65,66

  • Rhinitis, rhinorrhea, sinusitis and bronchitis54,67,68

  • Cough54

  • Pulmonary hemosiderosis/Heiner syndrome (a very rare syndrome characterised by recurrent episodes of pneumonia associated with pulmonary infiltrates, hemosiderosis, gastrointestinal blood loss, iron deficiency anemia, and failure to thrive in infants and young children)69,70,71,72,73,74
  • Nervous system:
    A fairly common manifestation of cow's milk allergy:

  • Inability to fall asleep, restless and disturbed sleep75,76,77


  • Less common manifestations:
  • Milk has been found to induce migraine as well as non-migrainous headache.78,79

  • In some studies, it was shown that shaking of the head from side to side has been triggered by milk (amongst other foods). It has been suggested that, in susceptible individuals, foods can trigger movement disorders through acting on dopamine and other neurotransmitter pathways in the brain.80

  • It has been suggested that there is a relationship between cow's milk and mental disorders such as infantile autism, schizophrenia and hyperactivity.39,81,82,83
  • It has been postulated that cow's milk has a role in the onset of convulsive crises, even if limited to certain types of epilepsy such as the cryptogenetic partial form.84
  • Systemic:

  • Anaphylaxis.49,85,86,87 Two groups of infants and young children with severe life-threatening reactions can be identified: those with anaphylaxis within minutes of ingestion of small volumes of milk, and those in whom 30-60ml of milk elicit an anaphylactic response with bile-stained vomiting, hypotonia and acidosis within 1-2 hours of milk ingestion.88 Food-dependant exercise-induced anaphylaxis has also been recorded.89,90

  • Acute recurrent pancreatitis.91,92

  • Hypersensitivity to milk can induce glomerulopathy93 as well as immune complex glomerulonephritis, which can result in a nephrotic syndrome.93,94,95 Another report has indicated milk to be the cause of steroid-resistant nephrotic syndrome with mesangial proliferation.96

  • Neonatal thrombocytopenia97 with or without TAR syndrome (a rare genetic congenital disorder that is characterized by thrombocytopenia and other physical abnormalities)98
  • Other manifestations:

  • Symptomatic exacerbations of general inflammatory arthritis, rheumatoid arthritis and seronegative monoarticular juvenile chronic arthritis in susceptible individuals. Septic arthritis of the hip joint, secondary to the ingestion of raw milk, has also been reported.99,100,101 Milk products have also been found to cause episodic rheumatic pain, synovitis and changes in immune complexes and IgE antibodies,102,103,104 whether or not there was underlying arthritis.105

  • Behcet's disease/syndrome (a multisystem, inflammatory, relapsing chronic disorder that may include mucocutaneous, ocular, genital, articular, vascular, central nervous system or gastrointestinal involvement).106

  • Melkersson-Rosenthal syndrome (cheilitis granulomatosum, fissured tongue, facial nerve paralysis).111

  • Nocturnal enuresis.112
  • compiled by Karen du Plessis B.Sc. Diet.
    karen@allergyadvisor.com
    Food & Allergy Consulting & Testing Services (FACTS)
    PO Box 565
    Milnerton 7435
    South Africa


    C. Comments by our editors

    Prof Janice M. Joneja Ph. D., RDN
    This case study and discussion strongly emphasise the fact that although we believe we know quite a lot about IgE-mediated allergic reactions, our knowledge of the non-IgE-mediated responses to food components is very limited, and in some cases virtually non-existent. We can cite the four types of hypersensitivity reactions (Type I (immediate IgE-mediated); Type II (IgG-mediated with involvement of body cells); Type III (IgG-immune complex mediated), and Type IV (delayed T-cell-mediated), and postulate one or more of these mechanisms to explain some of the symptoms and phenomena discussed in the section on symptoms. However, many of the conditions mentioned are currently poorly defined in terms of the precise reaction mechanisms responsible for the clinical signs, and it is clear that a great deal of research will be needed before we can understand them. Once the mechanisms are defined, it may be possible to develop laboratory tests to identify each specific condition. In the meantime, the message is loud and clear. The food components responsible for the clinical conditions must be identified and avoided. At the present time, our only method of achieving this is elimination of the suspect food, and challenge of each food component by reintroducing it and observing the patient's reactions, to determine it's effect on body systems. A method for carrying out this process was briefly outlined in the December Newsletter.
    Sabine Spiesser B.Sc. Dip. Ther. Diet.
    When evaluating a child with failure to thrive, it is vital to determine whether a child is not taking in, not being offered, or not retaining adequate calories. The causes could be organic indicating malnutrition due to a medical condition or non-organic due to social or behavioural issues leading to insufficient dietary intake. Normally, one would have expected weight gain acceleration on change from breast milk to formula. The decreased weight gain should have been a concern at this stage.

    A detailed nutritional evaluation and social history should be obtained early and patients with a failure to gain weight monitored closely. Post diagnosis the family should be counselled with regards to adequate energy intake to allow for catch-up growth. The toddler should be monitored during the weaning period to allow early detection and management of possible future food sensitivities.

    Dr. Harris Steinman M.B.Ch.B.
    This case report clearly demonstrates that one should listen closely to a patient and strive to make a diagnosis using laboratory tests as an adjunct to, and not in place of, one's clinical judgment. Detection or non-detection of IgE does not equate with a diagnosis or non-diagnosis of allergy.

    For more information on this subject and other allergy and intolerance related topics, visit:
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    E. CPD Questions (for South African dietitians only)

    This CPD session is now closed. Please contact karen@allergyadvisor.com for more information.

    PLEASE ANSWER ALL THE QUESTIONS
    1. True or false: Cow's milk ingestion can cause constipation.
    (a.) True
    (b.) False

    2. Which is true regarding Milk Protein-Induced Enterocolitis Syndrome?
    (a.) It generally presents in the 1st year of life with diarrhea, emesis, and irritability.
    (b.) It can present with more severe symptoms, such as bloody diarrhea, vomiting, anemia, dehydration, and failure to thrive.
    (c.) The area in the gastrointestinal tract that is affected generally determines the types of symptoms that are experienced.
    (d.) All of the above.

    3. Which of the following is not true regarding milk-induced gastroesophageal reflux:
    (a.) It is characterised by regurgitation and vomiting.
    (b.) Cow's milk induces severe gastric dysrhythmia and delayed gastric emptying, which may exacerbate gastroesophageal reflux.
    (c.) In almost all cases of gastroesophageal reflux in infants younger than 1 year there may be an association with cow's milk allergy.
    (d.) It may be associated with colic.

    4. Can milk exacerbate eczema?
    (a.) Yes
    (b.) No

    5. Which of the following is a more common nervous system manifestation of cow's milk allergy?
    (a.) Autism.
    (b.) Inability to fall asleep, restless and disturbed sleep.
    (c.) Schizophrenia.
    (d.) Shaking the head from side to side.

    6. Which of the following has not been associated with cow's milk-induced anaphylaxis?
    (a.) Anaphylaxis within minutes of ingestion of small volumes of milk
    (b.) Anaphylaxis with bile-stained vomiting, hypotonia and acidosis within 1-2 hours of ingestion of 30-60ml of milk
    (c.) Lactose intolerance
    (d.) Food-dependant exercise-induced anaphylaxis

    7. Which of the following has been associated with hypersensitivity to milk?
    (a.) Glomerulopathy
    (b.) Nephrotic syndrome
    (c.) Steroid-resistant nephrotic syndrome
    (d.) All of the above

    8. Can milk allergy present as colic?
    (a.) Yes
    (b.) No


    Answers

    1. a [X] b [ ]   2. a [ ] b [ ] c [ ] d [X]   3. a [ ] b [ ] c [X] d [ ]
    4. a [X] b [ ]   5. a [ ] b [X] c [ ] d [ ]   6. a [ ] b [ ] c [X] d [ ]
    7. a [ ] b [ ] c [ ] d [X]   8. a [X] b [ ]    


    1. a. True
    2. d. All of the above
    3. c. In almost all cases of gastroesophageal reflux in infants younger than 1 year there may be an association with cow's milk allergy
    4. a. Yes
    5. b. Inability to fall asleep, restless and disturbed sleep.
    6. c. Lactose intolerance
    7. d. All of the above
    8. a. Yes

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