Christopher S was referred to a London Children’s Hospital by his GP when he was 2 years old because of a worsening eczema. In the weeks before his mother took him to see his GP Christopher had developed hives and a wheeze after eating peanut butter and he now had skin lesions which oozed a clear fluid, pruritis, erythema, swellings of the skin and scratched and infected lesions on his trunk, face, arms and legs with thick scales in his scalp and was clearly uncomfortable and continuously scratching his skin. A clinical history revealed that Christopher had suffered from eczema since he was a few months old, when he developed a scaly red rash over his knees and elbows. He was breast fed for a month, after which he was given a cow’s milk-based formula. After the third feed of the formula milk he started to vomit and to scratch his skin. On the suggestion of a family friend his mother substituted the formula milk with Soya milk and James tolerated this well.
However as his mother introduced new foods to his diet, his eczema worsened, at 11 months he was slightly under weight for his age and he had developed a wheeze and was treated with bronchodilators and on one occasion, following an upper respiratory tract infection, treated with prednisone because of severe breathing difficulties. At the Children’s Hospital a skin culture for Staphylococcus aureus was positive and Christopher was treated with antibiotics, antihistamines and topical steroids and the skin infection resolved and his skin healed.
Laboratory studies revealed 25% eosinophils (normal 0 – 5 %) and a raised serum IgE at >1000 KU/L (normal 8 – 29 KU/L). He was later seen at the allergy clinic, where he was tested for sensitivity to a range of allergens. He was tested in type 1 allergen skin prick tests (wheal and flare) for responses to milk, cod, wheat, egg white, peanut, tree nuts (cashew, almond, pecan, Brazil nut, hazelnut, walnut), herb mix, rice, soya, mould spore, animal dander, various pollen’s and dust mites. He tested positive to milk, egg white, peanut and tree nuts but no reactions to other food or inhaled allergens. He was also tested for allergen specific IgE (see Table) and eosinophil cationic protein (ECP) was also determined and found to be elevated (>15 μg/ml).
Allergen sIgE KU/L Allergen sIgE KU/L
Dust mites 20.6 Milk >100
Dermatophagoides pteronissinus 61.3 Cod 0.2
Cat epithelia 4.2 Wheat 0.6
Moulds (Aspergillus mix) 0.2 Egg white 90.2
Birch 0.0 Peanut >100
Hazel 0.0 Tree nuts mix 51.0
Grass pollen (Lolium mix) 0.0 Soya 0.0
To determine whether any of these foods could be causing his atopic dermatitis, double-blind placebo-controlled food challenges were carried out. He developed hives and wheezing after eating 1 g of egg white, and hives and eczema after drinking 2 g of powdered milk. Christopher was placed on a diet that excluded milk, eggs, peanuts and tree nuts. His parents were advised to cover his mattress and pillows with a plastic covering, to Hoover Christopher’s bedroom regularly and to let the room get plenty of fresh air to decrease exposure to mite allergen. The family had no pets.
PLEASE ANSWER THE FOLLOWING QUESTIONS BELOW
1. Which allergens was Christopher diagnostically shown to be sensitive too? (5 Marks)
2. Give an explanation to why Christopher has positive allergen specific IgE to house-dust mites but does not respond to these allergens in the skin prick test (SPT). (10Marks).
3. What are the major allergens of milk, eggs and peanut and why should there also be responses to other tree nuts if positive to peanut? (10 Marks) .
4. Th-2 like cells can be identified in the peripheral blood and lesions of atopic-dermatitis patients producing IL-4, 5, 13 and also IL-17 from Th17 cells. Explain the role(s) of these cytokines in allergy (10 Marks).
5. Explain the significance of undertaking allergen-induced Basophil histamine, Mast cell PGD2 and Eosinophil Cationic Protein (ECP) release assays in allergy/asthma (15 Marks).
6. Outline the “Hygiene Hypothesis” in relation to allergic disease prevalence (15 Marks).
7. Topical steroids were effective in reducing the eczema associated with Christopher’s atopic dermatitis. Why? (10 marks)
8. What are the immunological changes associated with monoclonal anti-IgE antibody (Omalizumab) treatment of allergic patients? (10 Marks) .
9. Would Christopher be a good candidate for Allergen Specific Immunotherapy (SIT), explain your answer and the changes you might expect in terms of cytokines and immunoglobulin’s (15 Marks).