Allergy 1 Flashcards
What is the three definitions of hypersensitivity
- an immune response against a foreign antigen which merits the response but damage occurs to the host due to its vigour e.g. TB
- autoimmunity - immune response against autoantigens
- allergy - immune response against foreign antigens which do not merit the response and the immune response damages the host
allergy is a subdivision of
hypersensitivity
Define allergy
immune response against foreign antigens which does not merit the response and the immune response damages the host - mediated by type 1 hypersensitivity
Why is it difficult to maintain type 1 hypersensitivity
- some type 2, type 3 and type 4 reactions are traditionally called allergic
- the differential diagnosis lists of causes of urticaria, angioedema etc and have allergic and non allergic items intermingled
what is an intolerance
- if a substance elicits an adverse reaction without the immune system being involved it is called an intolerance and not allergy
What is an intolerance often due to
It is often due to enzyme deficiencies, eg lactose intolerance in people who lack lactase
describe the 5 types of hypersensitivity reactions
- Type I hypersensitivity: IgE mast cells, anaphylaxis etc
- Type II hypersensitivity: autoantibodies against self structures
- Type III immune complex mediated
- Type IV T-cells + macrophages, with or without granulomas.
- Type V Stimulatory autoantibodies: Graves’ disease
What causes mast cell stimulation
- Surface IgE binding antigen.
- Complement activation: C5a, C3a.
- Nerves: axon reflex sensory nerves, Substance P.
- Direct stimulation.
what are the signs and symptoms of anaphylaxis
- Drop in blood pressure – syncope,
- Bronchospasm – wheeze.
- Urticaria – red itchy raised rash.
- Angioedema – swelling with fluid in subcutaneous tissues – if in mouth, pharynx & respiratory tract gives stridor, death.
- Gastrointestinal – abdominal pain, vomiting, diarrhoea.
what type of hypersenstivity is anaphylaxis
Type 1 hypersensitivity reaction, with degranulation and activation of mast cells and basophils.
What markers are released in anaphylaxis
Histamine and leukotrienes released.
What is the diagnostic test for anaphylaxis
- mast cell tryptase is raised - not raised in milder allergies
What can cause anaphylaxis
- Arthropod venoms (bee, wasp stings etc)
- drugs IV and oral - antibiotics (beta lactams and others), neuromuscular blocking agents (suxamethonium), peptide hormones (ACTH, insulin), monoclonal, polyclonal antibodies, antisera, plasma
- foods = peanuts and other legumes, true nuts - walnuts, cashew, almond, hazelnut, shellfish and fish, egg, milk, latex, banana, avocado, kiwi, chestnut, potato, tomato, omega gliadin
What is the treatment for anaphylaxis
- Adrenaline IM - self administered
- oxygen 100%
- IV fluids - may need vasopressor agents
- IV glucocorticosteroids and antihistamines; no cochrane evidence that these will work
- admit and observe because of late phase; 8 hours
- may need tracheostomy
What is the long term treatment for anaphylaxis
- identify antigen responsible: history, skin prick tests, specific IgE tests
- can use prophylactic antihistamine if going into likely situation
- carry adrenaline injection device
- desensitisation is available for some antigens
What is an anaphylactoid reaction
Direct or indirect activation of mast cells without IgE
What can cause anaphylactoid
- Some drugs: opiates, vancomycin, anaesthetic agents, NSAIDs. Radiocontrast agents.
- Foods: strawberries.
- Physical stimuli: exercise (but this may involve IgE to omega- gliadin), cold, trauma.
- Immune complex reactions (type III hypersensitivity) to blood products, IVIG, antisera, antibodies.
what diagnostic tool can be used for anaphylactoid
-mast cell tryptase positive
How do you treat anaphylactoid
same as anaphylaxis
what is scromboid
massive ingestion of histamine from decayed mackerel & other oily fish. Mast cells not involved: tryptase neg.
what are differential diagnosis to anaphylaxis
- MI
- PE
- hyperventilation,
- hypoglycaemia
- vasovagal
- phaeochromocytoma,
- carcinoid
- systemic mastocytosis
- Also hereditary or idiopathic angioedema
What is mast cell tryptase raised in
- anaphylaxis
- anaphylactoid reactions
- mastocytosis
What markers are raised or lowered in anaphylaxis
- mast cell tryptase is raised
- complement is low due to consumption in hereditary or idiopathic angioedema
- D dimers is high
What is urticaria
Raised itchy erythematous rash: wheals (“hives”), with inflammation within the dermis
What are the types of urticaria
- Acute
- chronic - longer than a month
What are the causes of urticaria
- Type 1 hypersensitivity - usually acute
- type III hypersensitivity
- autoimmune causes
- infections
- cold urticaria
- autonomic system
- physical stimuli
- exercise urticaria
- hormonal
- mast cell disorders
- Iron, B12 and folate deficiency
What cells are often involved in urticaria
- mast cells
- histamine
- leukotrienes
What infections can cause urticaria
- acute viral infections, Helicobacter pylori, prodromal Hepatis B, Lyme disease, cat-scratch fever, acute or chronic bacterial infections, parasitic infections. These may be acute or chronic. Probably immune complexes.
describe how autoimmune illness can cause urticaria
- Autoantibodies to Fc-epsilon receptors on mast cells/basophils may be responsible for much chronic urticaria.
- SLE may cause chronic urticaria, either through autoantibodies to mast cells or immune complexes, or cryoglobulins.
- Vasculitis is a cause of chronic urticaria: painful rather than itchy, leave bruise & iron pigmentation when lesions resolve due to extravasation. Serum/blood products injected which cause urticaria may cause vasculitis, via immune complexes & type III hypersensitivity.
Describe how cold urticaria is caused
- caused by cryoglobulinaemia (SLE and other autoimmune diseases, leukaemias and lymphomas, infections, idiopathic.
- Also mycoplasma infections, which cause haemolytic anaemia.
- All these can cause Raynaud’s phenomenon.
- There is an inherited form of cold urticaria due to C1AS1 gene mutation.
what gene causes inherited cold urticaria
There is an inherited form of cold urticaria due to C1AS1 gene mutation
describe how the autonomic system can lead to urticaria
- Cholinergic urticaria, associated with heat and sweating.
- Smaller wheals.
- Adrenergic urticaria due to stress.
What physical stimuli can cause urticaria
- sunlight
- heat
- pressure (including dermographism)
- vibration
- probably direct stimulation of mast cells and or nerves
describe how exercise urticaria is caused
may be associated with IgE to omega gliadin: typical history of exercise within hours of a meal containing gluten causing urticaria, even anaphylaxis
describe how hormonal urticaria is caused
some women describe attacks of urticaria associated with luteal phase of menstrual cycle: progesterone. Other steroids can cause urticaria.
name a mast cell disorder that can cause urticaria
urticaria pigmentosa
How do you treat urticaria
- Antihistamines are the main treatment
- take up to 4x BNF recommended dose
if this does work
- Ranitidine - H2 antagonists
- Montelukast - inhibits leukotriene synthesis - not totally effective
if this fails
- omalizumab - monoclonal that binds to IgE
What is angioedema
Swelling of subcutaneous tissues due to fluid collection, because of the release of inflammatory mediators, particularly histamine and bradykinin
What molecules are released in angioedema
histamine and bradykinin
if the angioedema is caused by histamine what does this mean it is caused by
- means its caused by an allergy
- may be idiopathic angioedema
If the angioedema is caused by bradykinin what does this mean it is caused by
- Hereditary angioedema
- Acquired C1 esterase inhibitor deficiency
- Maybe idiopathic angioedema
what happens in allergic angioedema
Histamine based
- accompanied by urticaria
What happens if angioedema occurs in the airway
- can be lethal
What markers are raised in allergic angioedema
- specific IgE allergen may be detected
- mast cell tryptase may be raised, especially in anaphylaxis
How many types of hereditary angioedema is there
Type 1
Type 2
Type 3
describe type 1, 2 and 3 types of hereditary angioedema
Type 1 deficiency of C1 esterase inhibitor, which exercises restraint on the classical complement pathway and on the bradykinin pathway.
Type 2: mutation of the C1 esterase inhibitor - C1 inhibitor test level may be normal but will not function normal
Type 3. Mutation of Factor XII gene, which initiates bradykinin pathway as well as intrinsic clotting pathway.
What does C1 esterase inhibitor do
made in the liver by hepatocytes and acts to restrain the bradykinin pathway and complement pathway
What are the symptoms of hereditary angioedema
- Episodes of angioedema of limbs trunk, perineum, face, within mouth and airway: life-threatening.
- Also intra-abdominal, when causes pain and swelling, when may present as acute abdomen.
- C4 depleted and low.
What can cause acquired C1 esterase inhibitor deficiency
- Autoimmune disease
- haematological malignancy especially if paraproteins, cryoglobulins
- Infections - Hep B, Hep C, Helicobacter
- ACE inhibitors can also inhibit C1 esterase inhibitors and thus cause angioedema
What markers are low in acquired C1 esterase inhibitor deficiency
- C4 low
- C1q may be low,
- anti-C1q antibodies may be present
What is the treatment for angioedema
- antihistamines
C1 inhibitor esterase deficiency
- anabolic steroids - increase production of C1 esterase inhibitor
tranexamic acid - antifibrinolytic - effective treatment for angioedema
C1 inhibitor iv or rarely s/c (human blood product), also genetically engineered form.
Icatibant s/c inhibits bradykinin pathway: emergency Rx
Lanadelumab monoclonal inhibits bradykinin pathway
What should you give in emergency treatment of angioedema caused by bradykinin
Icatibant s/c inhibits bradykinin pathway: emergency Rx
In idiopathic angioedema what usually works as a treatment
tranexamic acid
What should all people with angioedema avoid
ACE inhibitors
