T2-L1: Allergic Disease

Question 1

What are the two broad categories of rhinitis?

Answer 1

Rhinitis can be allergic or non-allegoric.

Allergic rhinitis can be seasonal or perennial. Seasonal is mainly mediated by pollen (summer) or moulds (autumn/winter).
Symptoms include blocked/runny/itchy nose

Non-allergic rhinitis can be due to vasomotor stimulation, infective, structural, drugs, hormonal or polyps.

Treatment is antihistamines and intranasal steroids.

Question 2

What is Asthma?

Answer 2

Disease of inflammation & hyper-reactivity of small airways. In childhood, aero-allergic stimuli are common, house dust mites are of key significance. The symptoms are immediate and IgE mediated. Damage to the airways is due to a late phase response. Damaged airways are hyper-reactive to non-allergic stimuli such as fumes.

Question 3

What is the pathogenesis of Asthma?

Answer 3

Allergen is presented, inducing T cell proliferation and differentiation into the TH2 cells - secretes cytokines (IL4, IL30 and IL5). They have their own role e.g. IL5 induces eosinophils maturation and IL4 and IL30 have a role in stimulating B cells towards the IgE phenotype. They B cells class switch and differentiate into plasma cells secreting IgE antibodies.

Question 4

How is Dermatitis classified?

Answer 4

Classified into eczema, contact dermatitis and other. Eczema can be either Atopic dermatitis (also asthma and rhinitis) or non-atopic and so is not seen with the other conditions.

• Causes an intense itching, blistering, cracking of skin etc.
• Often we see a family association
• House dust mite is the major allergic trigger
• Treatments include steroids, moistures etc.

Question 5

What is the main protein involved in the maintenance of the skin barrier?

Answer 5

Filaggrin (lack of it distrupts the barrier) acts as the main protein that leads to disruption of the barrier so the infection can happen quicker.

Question 6

Give a summary of sensitisation and acute phase response.

Answer 6

Sensitization - the allergen is presented by a APC, causing a T cell to differentiate into a Th2 cell. It secretes the cytokines which makes the Beta cells to turn to plasma cells. This leads to immunological memory.

In the acute phase response there is release of vasoactive amines, lipid mediators, chemokine and other cytokines.

Question 7

Give a summary of late phase inflammation.

Answer 7

Following migration to sites of allergen exposure under the influence of chemokines and other cytokines, allergen-specific T cells are reactivated and clonally expand. Local IgE-facilitated antigen presentation by dendritic cells (DCs) increases T-cell activation. Local IgE production is seen in allergic rhinitis and asthma but not in allergic skin inflammation (the main example of which is atopic dermatitis).
There is:
- Smooth muscle cell activation and hyper-reactivity for contraction, release of chemokine and pro-inflammatory cytokines.
- Increased endothelial-well adhesion and inflammatory cell transmigration
- Eosinophil activation and release of mediators chemokines and pro-inflammatory cytokines
- Basophil entry to tissues, mast cell and basophil degranulation leading to the release of monoamines, lipid mediators, chemokine and cytokines.
- T cell activation and proliferation of IgE facilitated and non-IgE facilitated presentation of allergens by inflammatory dendritic cells.
- In allergic rhinitis and asthma Th2 cytokine mediated induction of increased mucus production and induction of bronchial epithelial cell apoptosis
- In atopic dermatitis Th1 cell mediated induction of keratinocyte apoptosis and epithelial cell activation, and release of chemokine and pro-inflammatory cytokines.

Question 8

How is specific IgE testing used?

Answer 8

Using the patients blood, their antibodies will bind to the antigen. You will need to determine whether it is IgE. There is a mechanism for detection. This is usually enzyme based.

These are arbitrary units but a value of >0.5 tends to equate to an allergy.

You initially extract allergens from the environment of create them.

Question 9

How can we test for allergies?

Answer 9

• Skin Prick Test - You have a positive (normally histamine) and a negative control (usually saline). You put a single drop of allergen on the skin.

We look for a palpable lump. We usually get a floral (red) response around the lump. We then measure the response in millimetres. To be positive the lump must be greater the 2mm. This is 2mm more than the negative control. This is usually 0. Some patients do generate responses without being exposed to an allergen (dermatographicurticaria).

• Specific IgE Testing
• Intradermal testing - More invasive. You use more allergen. You inject a tiny amount into the dermis. You create a blank and inject diluted versions of preparations and mark the size of the spot. You do not use a positive control as histamine is quite irritant and produces a large response. You use a negative control. The spot needs to increase by 3mm by the time of injection. The results take a bit longer. This is primarily done for drug allergies.
• Basophil activation test - Measure the antibodies that are bound to basophils in the blood

Question 10

What are advantages and disadvantages of specific IgE testing?

Answer 10

Advantages:
Safe

Disadvantages - high number of false positives and false negatives you are measuring the free IgE in circulation not bound to cells

Question 11

What are advantages and disadvantages of skin prick tests?

Answer 11

Advantages:
- Quick and good patient satisfaction

Disadvantages:
- False negatives and positives

Question 12

What are treatments for allergies?

Answer 12

Treatment for allergies:

• Avoidance
• Antihistamines, steroids, adrenaline
• Specific immunotherapy (subcutaneous or sublingual)

Indications:

• Life threatening reactions to Wasp & Bee sting
• Severe Hay fever
• Animal dander allergy

Contraindications:

• Multiple allergies
• Food allergy
• Eczema
• Spontaneous Urticaria – idiopathic conditions where you get spontaneous reactions without any trigge

Question 13

What is the difference between a food allergy and a food intolerance?

Answer 13

Food allergy are immune mediated whereas an intolerance is non-immune mediated.

Question 14

How can adverse reactions to food manifest clinically?

Answer 14

• Gastrointestinal - vomiting, diarrhoea, oral symptoms
• Respiratory (upper & lower) - rhinitis, bronchospasm
• Cutaneous
○ urticaria, angioedema
• Anaphylaxis

Question 15

Give major food allergens.

Answer 15

Major Food Allergens 
	• Water soluble glycoproteins 10 - 60 kd
		○ Cow’s milk
		○ Egg
		○ Legumes - peanut; soybean; tree nuts
		○ Fish
		○ Crustaceans / molluscs
		○Cereal grains

Question 16

What aspects of a drug allergy are important when taking a history?

Answer 16

History
• Indication for the drug
• Detailed description of the reaction
• Time between drug intake and onset of symptoms
• Number of doses taken before onset
• Aware of pharmacological effects and non-immunological ADR

Question 17

Give examples of cytokines released by Th2 cells?

Answer 17

IL4, IL30 and IL5 - They have their own role e.g. IL5 induces eosinophils maturation and IL4 and IL30 have a role in stimulating B cells towards the IgE phenotype. They B cells class switch and differentiate into plasma cells secreting IgE antibodies.

Question 18

How can we use information about cytokines in treatment?

Answer 18

New treatments involve IL4 and IL13 inhibitors to treat asthma and eczema. Anti-IL5 is used in patients with a high eosinophil count. There are therapies targeting the cytokines involved in the pathway. Il4 and IL13 have common receptors and inhibitors are used in both asthma and eczema.

Question 19

What is the gold standard for allergy testing?

Answer 19

The gold standard for allergy testing is the Graded Challenge Test. This is exposing the patient to the allergen in a graded fashion It is done in a clinical setting. The idea is if you give the whole amount you can induce anaphylaxis but you start with a small amount and gradually increase the dose. You then test for any signs of allergy.