Allergies - condensed lecture notes Lecturer: Paul Franklin PDF

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Summary

ALLERGIESAn allergy is a ‘damaging immune response by the body to a substance, especially a particular food, polled, fur, or dust, to which it has become hypersensitive.Antigens = allergensIt is unknown why people get allergies; there is a strong genetic predisposition.Hallmark is an inappropriate p...

Description

ALLERGIES

An allergy is a ‘damaging immune response by the body to a substance, especially a particular food, polled, fur, or dust, to which it has become hypersensitive. Antigens = allergens It is unknown why people get allergies; there is a strong genetic predisposition. Hallmark is an inappropriate production of IgE against allergens that cause masr cell degranulation; normally IgE/mast cell activity should be directed against parasitic infections. Hypersensitivity Reactions (Gell and Coombs classification): -

Type

Type I  IgE mediated (allergy) Type II  Antibody-mediated cytotoxic Immediate Type III  Immune complex mediated Type IV  Delayed-type hypersensitivity (DTH)

Reaction

Mediators

Clinical Manifestations Systemic Early Effects First exposure to I Anaphylaxis: Histamine and heparin: pollen: (IgE mediated) Allergen gets into Increase vascular IL-4 drives B cells to blood stream, permeability, smooth Common allergens: produce IgE in muscle contraction, mucus dyspnoea, decrease Vaccines, penicillin, response to pollen BP, bronchiole secretion. nuts, seafood, eggs, antigens, Chemotactic factors: constriction, GI and Pollen specific IgE milk, bee/wasp/ant bladder SM Attract eosinophils and binds to mast cell. venom, dust mites, contraction, shock. neutrophils mold spores, animal Proteases: Death within minutes Second exposure to hair, latex if untreated. Mucus secretion, pollen: Treat with complement activation, Acute release of mast epinephrine degradation of blood cell contents (degranulation) causes vessels basement Asthma: membrane allergic rhinitis Leukotrienes and Extrinsic; due to (hayfever) e.g. prostaglandins: inhaled airborne bronchoconstriction, allergens (pollen, inflammation, intestinal Secreted after tissue disruption caused by mast dust, fumes, etc). remodelling cell degranulation, similar Food Allergies: effects to histamine Urticaria Anaphylaxis Later Effects Arrival of pro-inflammatory Insect stings eosinophils and neutrophils

Histamine’s Effect on Smooth Muscle Bronchial Smooth Muscle Vascular Smooth Muscle H1 receptors located on the bronchial H1 receptors located on endothelial cells of blood vessels SM cells Activation of receptor increases Ca2+ leading to SM contraction i.e. Activation causes BRONCHOCONSTRICTION

Activation causes an increase in Ca2+ which causes the release of mediators such as NO which causes SM relaxation via c GMP i.e. Activation causes VASODILATION H2 receptors are also found on vascular SM cells; activation causes an increase in c AMP, leading to SM relaxation.

Release of Histamine can occur by two processes: 1. Energy and Ca2+ dependent degranulation reaction: The release of histamine from mast cells is induced by – -

IgE fixation to mast cells (sensitisation) and subsequent exposure to a specific antigen Complement activation, mediated by immunoglobin G or M, may also induce degranulation

2. Energy and Ca2+ independent release (displacement): Displacement is induced by – -

Drugs e.g. morphine, tubocurarine, guanethidine and amine antibiotics Mast cells damage, which is caused by either noxious agents, e.g. venom, or mechanical trauma, can release histamine

Treatment of Anaphylaxis Adrenaline (epinephrine): -

Intramuscular (IM) injection into middle of thigh is the first choice ROA of adrenaline for the management of anaphylaxis IV dosing

Allergic Rhinitis (Hay Fever) -

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Inhaled allergen triggers reaction in nasal mucosa Watery exudate from nose, eyes, upper respiratory tract, sneezing and coughing Can be seasonal or perennial Seasonal antigens:  Pollens from grasses, flowers, weeds or trees  Grass pollen is responsible for hay fever and is the most common type of seasonal allergic rhinitis Perennial allergic rhinitis (vasomotor rhinitis) may be due to antigens from house dust, fungal spores or animal dander but symptoms can be caused by pungent odours or fumes such as perfumes

Treatment -

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Antihistamines e.g. azelastine nasal spray, sodium cromoglicate nasal spray, corticosteroids e.g. beclometasone or budesonide nasal spray Patients failing to respond may obtain relief from IM injection of a long acting steroid (reserved for patients with severe symptoms) Vasomotor rhinitis may respond to ipratropium bromide nasal spray

Hives (Urticaria) -

Raised, red patches of skin that are usually very itchy Many causes, both allergic and non-allergic Usually come and go within a few hours/days

Clinical Usefulness of Antihistamines -

Allergic rhinitis (common cold) Allergic conjunctivitis (pink eye) Allergic dermatological conditions Urticaria (hives) Angioedema (swelling of the skin) Pruritus (insect bites) Anaphylactic reactions (severe allergies) Nausea and vomiting (first generation H1-antihistamines) Sedation (first generation H1-antihistamines)

Penicillin Allergy -

Penicillin can cause any of the types of G&C immunologic hypersensitivity reactions although type I and type IV are most commonly encountered All penicillin contains both a beta-lactam ring and a thiazolidine ring; individual penicillin is distinguished by the nature of the side-chain group (R). These structures can act as antigens

Eczema/Dermatitis -

Eczema and dermatitis are interchangeable Atopic (allergic) eczema is the most common form (increased IgE) Often occurs in young children Red skin rash Strong hereditary predisposition

Skin Structure -

2 main layers: 1. Dermis – 3 to 5 mm thick, contain blood vessels, hair follicles and sweat glands. 2. Epidermis – surface layer varies in thickness, composed of four layers of keratinocytes (skin cells), formed in basal layer to stratum corneum; change from plump nucleated cells to flattened dead cells that are shed (takes about 28 days).

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Compaction of epidermal cells due to protein called filaggrin:  Filaggrin can be broken down in amino acids to make natural moisturising factor Cells are held together by protein bridges – desmosomes  Dead skin cells are shed when these bridges are cleaved by skin proteases Dendritic cells are antigen-presenting cells (APCs) which play a critical role in the regulation adaptive immune response

Pathophysiology of Eczema -

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Acute stage:  Fluid escapes from dilated dermal blood vessels to produce oedema  Collect into tiny blisters where the skin is thick e.g. palms and soles  Skin is red, hot, swollen and itchy  Papules and tiny blisters  Exudation and crusting  Scaling Chronic stage:  Less oedema and vesiculation  More thickening of epidermis  Skin is drier and scalier  Lichenification – dry, thickened, leathery skin  Painful fissures Both stages accompanied by inflammatory cell infiltration of the dermis and epidermis

Treatment of Type I Hypersensitivity -

Avoid allergen if possible Antihistamines Anti-prostaglandins Hypo sensitisation: injections of low doses of allergen may cause a shift from IgE to IgG as the dominant antibody formed

Emollients -

Use continuously, even when skin is clear Should be suited to child’s needs and preference Unperfumed Use every day Prescribe in large quantities Easily available at nursery, school, etc.

Topical Corticosteroids -

II Antib cytoto

Potency tailored to severity Mild potency for neck and face; moderate potency for severe flares (3-5 days) Moderate or potent preparations for short periods; only for flares in vulnerable sites (7-14 days) Do not use potent preparations in children without specialist dermatological advice

d

endogenous (although exogenous chemicals, i.e. haptens, can also lead to type II HS), Antigen/antibody complex may lead to: - Complement activation  lysis - ADCC - Opsonisation  phagocytosis

III Immune complex disease

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groups To other RBC blood groups

Haemolytic disease of the new born (HDN) Drug-induced haemolytic anaemia (penicillin)

These are normal reaction but when unwarranted tissue damage occurs, it is considered a HS

Reaction time is minutes to hours

Antibody (IgG)/attaching to soluble antigen leads to complex formation, Immune complexes may deposit in: - Blood vessel walls - Synovial joints - Glomerular basement membrane - Choroid plexus - Skin (SLE) - General (serum sickness)

Reaction may take 310 hours after exposure to the antigen

Damage occurs due to: - Anaphylatoxin release due to complement activation which attracts neutrophils and causes mast cell degranulation - Neutrophils unable to phagocytose immune complexes so they release their granule content leading to more inflammation - Platelet aggregation also results from complement activation

Effects known as Arthus reaction Localised reactions: - oedema and redness - tissue necrosis Can occur in the skin following insect bites Can occur in the lungs e.g. ‘farmer’s lungs’ from inhaling mouldy hay particles Generalised reactions: Serum sickness (following treatment with antiserum to a toxin) Autoimmune dieases e.g. SLE, rheumatoid arthritis

Infectious diseases e.g. meningitis, hepatitis, malaria IV Delayed type HS

TH cells that have been sensitised by an antigen develop TH1, leading to macrophage recruitment and activation.

Reactions are delayed for 1-2 days due to migration of macrophages and Tcells.

Hallmark is the large number of macrophages at the reaction site and that it takes an average of 24 hours to manifest after repeat exposure

Reactions are frequently displayed on the skin: itching, redness, welling, pain.

First contact sensitises a person, Subsequent contact elicits a reaction

Anaphylactic shock may occur Examples: TB skin test Poison ivy Metals Latex...