Hypersensitivity - allergy and the skin Flashcards
Define what hypersensitivity reactions are
They are a group of pathological processes that arise from an exaggerated but normal immune response. These excessive immune reactions cause tissue damage in response to different antigens such as:
- Infectious pathogens
- Environmental antigens
- Self-antigens (host molecules)
This is the pathophysiological basis for many chronic diseases, including allergy and autoimmunity
Appreciate this pic of an overview of Type I - IV hypersensitivities
Give a brief overview of type II hypersensitivity and the type of reactions it involves
- It is IgG or IgM mediated
- These Ab’s react with cell surface antigens stimulating inflammatory responses & tissue damage which is mediated by complement system proteins, phagocytes or natural killer cells
List the main examples of type II hypersensitivity reactions
- Autoimmune haemolytic anaemia
- ITP
- Goodpasture’s syndrome
- Pernicious anaemia
- Acute haemolytic transfusion reactions
- Rheumatic fever
- Pemphigus vulgaris / bullous pemphigoid
Give a brief overview of type III hypersensitivity
- These are immune complex-mediated
- These complexes consist of an aggregate of interacting antigens & IgG antibodies. They can be depositied in various tissues (often affecting the lungs, kidneys & nlood vessels)
- They cause tissue damage via activation of the complement system, & recruitment & activation of neutrophils
List the main examples of type III hypersensitivity reactions
These reactions are commonly systemic disorders:
- SLE
- Rheumatoid arthritis
- Serum sickness
- Post-streptococcal glomerulonephritis
- Extrinsic allergic alveolitis (especially acute phase)
- Necrotizing vasculitis
- Arthus reaction (reaction that occurs several hours to days following the intradermal injection of a vaccine)
What is the general management of type II hypersensitivity reactions ?
- (Avoidance)
- Decrease inflammation = Corticosteroids
- Decrease production of antibody = Immunosuppression
Refamilarise with the complement pathways
Go back and have a look at principle lecture on this to refamiliarise
What is an allergy ?
It is a hypersenstivitity disorder in which the body reacts to a nomrally harmless substance in the environment. The substance which causes this reaction is called an allergen
What is the hypothesis of why allergy prevalence in westernised countries is increasing ?
The ‘hygeine hyopthesis’ = improved sanitation and decreased incidence of infectious disease
Describe Type I hypersensitivity reactions giving what they are mediated by and some examples of type I reactions
These are immediated allerigc type reactions which are mediated by IgE antibody (so think is this an allergic response)
Exposure to allergen cause binding of IgE to mast cells. When then exposed later again to the allergen it causes rapid crosslinking of the receptors, signal transduction and degranulation of mast cells. Vasoactive & inflammatory substances are then released into surrounding tissues.
What is the normal function of mast cells & what do they produce?
They are resident in tissues, especially at interface with external environment which are important in defence against parasites (e.g. worms)
They produce vasoactive inflammatory substances:
- Histamine, Tryptase, Heparin
- Leukotrienes, prostaglandins,
- Pro-inflammatory cytokines
These inflammatory substances:
- Increase blood flow
- Contraction of smooth muscle
- Increase vascular permeability
- Increase secretions at mucosal surfaces
List the main examples of type I hypersensitivity reactions
- Atopy (Asthma, Hayfever, Eczema)
- Urticaria
- Angioedema
- Food allergy
- Drug allergy and anaphylaxis
- Allergic rhinitis
List the different types of allergens causing type I hypersensitivity
- House dust mite
- Pollen and animal dander
- Foods
- Drugs
- Latex
- Bee & wasp venom
What is the most common type of hypersensitivity reaction ?
Type I
What are the clinical features of type I hypersensitivity reactions ?
Occurs quickly after exposure to allergen (minutes – 1-2 hours). Presentation is influenced by site of contact:
- Asthma
- Urticaria
- Angioedema
- Allergic rhinitis (hayfever)
- Allergic conjunctivitis
- Diarrhoea and vomiting
- Anaphylaxis
Name the reaction shown and specifically what type of reaction is it ?
Urticaria - type I hypersensitivity reaction
What is the clinical presentation of urticaria ?
- Very itchy
- Lesions appear within 1 hour
- Lasts 2-6 hours, sometimes 24 hours
- “hives”, “wheals”, “nettle rash”
What condition is shown here and what specifically what type of reaction is it ?
Angioedema - type I hypersensitivity reaction
- Localised swelling of subcutaneous tissue or mucous membranes
- Non pitting oedema
What type of reaction is wheezing/asthma ?
Type I hypersensitivity reaction (histamine is released from mast cells causing type I reaction resulting in bronchoconstriction ==> asthma)
Anaphylaxis is also a type I hypersensitivity what are the common signs and symptoms of anaphylaxis ?
- feeling lightheaded or faint
- breathing difficulties – such as fast, shallow breathing
- wheezing
- a fast heartbeat
- clammy skin
- confusion and anxiety
- collapsing or losing consciousness
What investigations are done to test for IgE allergies ?
- History – most important!
- Specific IgE (RAST) – specificity & sensitivity 70-75% (2nd most common test)
- Skin prick or prick-prick testing (SPT) - 90% Specificity & sensitivity 90+% (gold standard)
- Challenge test - only done if SPT is negative
- Serum mast cell tryptase level (during anaphylaxis)
What is the managment for people with type I hypersensitivities?
Drugs:
- Anti-histamines - to prevent effects of mast cell activation
- Corticosteroids - anti-inflam agent
- Adrenaline autoinjector (for anaphylaxis)
- Block mast cell activation (mast cell stabilisers – sodium cromoglycate)
- Immunotherapy
Education/awarness:
- Allergen avoidance
- Medic Alert bracelet
- Information & Education
Describe type IV hypersensitivity reaction and what mediates it
It is T-cell mediated (not antibody mediated)
CD4+ helper T cells recognize antigen (it is antigen specific) in a complex with MHC II major histocompatibility complex on the surface of antigen-presenting cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ Th1 cells. CD4+ T cells secrete IL-2 and interferon gamma, inducing the further release of other Th1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.
List the main examples of type IV hypersensitivity reactions
- Tuberculosis / tuberculin skin reaction
- Graft versus host disease
- Allergic contact dermatitis
- Scabies
- Extrinsic allergic alveolitis (especially chronic phase)
- Multiple sclerosis
- Guillain-Barre syndrome
How long does the onset of a type IV hypersensitivity usually take to occur?
24-48 hours
Give some examples of causes of Type IV hypersensitivity reactions
What is wrong with the patinet here ?
Type IV hypersensitivity to Nickle in the belt buckle
What is a possible cause of the axillary dermatitis shown in the pic ?
Deodorant
What is the gold standard diagnostic test for patients with suspected allergic contact dermatitis ?
Skin patch testing.
The allergens or groups of allergens that we choose to test depends on the history, pattern of dermatitis, occupation, hobbies, etc
What is irritant contact dermaitis and is it immunologically mediated ?
It is dermatitis which forms due to contact with agents that abrade, irritate and traumatize skin directly it does not require prior sensitization and the pattern depends on exposure.
It is not immunologically mediated (to do with trauma/abrasion)
Can allergic contact dermatitis and irritant contact dermaitis co-exist ?
Yes - everyone occupation has its fair share of both allergens and irritants.
e.g. Metal workers
- Irritant - Cutting oils /fluids; solvents; metal shavings/dusts.
- Sensitiser (allergen) - Additives/preservatives in cutting fluids; chromium; nickel.
Give a couple examples of endogenous (having an internal cause or origin.) types of skin disease
- Actopic dermatitis - associated with asthma and hayfever.
- Psoriasis - scaly, plaques on extensor surfaces
What is the best way to treat contact dermaitis (be it irritant or allergic)?
Avoidance - if complete avoidance is not possible then it can eb treated with combination of emollients, topical steroids or phototherapy. Occassionally, we may have to use immunosuppressants
Appreciate the conclusions/summary from this lecture
- Allergy is a hypersensitivity disorder causing an exaggerated immune response to normally harmless substances in the environment
- Prevalence of allergy is increasing
- Allergen avoidance is a key component of allergy management but can be difficult
- Not all “reactions” are caused by allergy
