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Year 3 - Clinical Science and Professionalism > Allergy 1 > Flashcards

Allergy 1 Flashcards

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1
Q

What is the three definitions of hypersensitivity

A
  1. an immune response against a foreign antigen which merits the response but damage occurs to the host due to its vigour e.g. TB
  2. autoimmunity - immune response against autoantigens
  3. allergy - immune response against foreign antigens which do not merit the response and the immune response damages the host
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2
Q

allergy is a subdivision of

A

hypersensitivity

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3
Q

Define allergy

A

immune response against foreign antigens which does not merit the response and the immune response damages the host - mediated by type 1 hypersensitivity

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4
Q

Why is it difficult to maintain type 1 hypersensitivity

A
  • 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
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5
Q

what is an intolerance

A
  • if a substance elicits an adverse reaction without the immune system being involved it is called an intolerance and not allergy
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6
Q

What is an intolerance often due to

A

It is often due to enzyme deficiencies, eg lactose intolerance in people who lack lactase

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7
Q

describe the 5 types of hypersensitivity reactions

A
  • 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
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8
Q

What causes mast cell stimulation

A
  • Surface IgE binding antigen.
  • Complement activation: C5a, C3a.
  • Nerves: axon reflex sensory nerves, Substance P.
  • Direct stimulation.
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9
Q

what are the signs and symptoms of anaphylaxis

A
  • 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.
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10
Q

what type of hypersenstivity is anaphylaxis

A

Type 1 hypersensitivity reaction, with degranulation and activation of mast cells and basophils.

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11
Q

What markers are released in anaphylaxis

A

Histamine and leukotrienes released.

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12
Q

What is the diagnostic test for anaphylaxis

A
  • mast cell tryptase is raised - not raised in milder allergies
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13
Q

What can cause anaphylaxis

A
  • 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
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14
Q

What is the treatment for anaphylaxis

A
  • 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
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15
Q

What is the long term treatment for anaphylaxis

A
  • 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
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16
Q

What is an anaphylactoid reaction

A

Direct or indirect activation of mast cells without IgE

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17
Q

What can cause anaphylactoid

A
  • 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.
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18
Q

what diagnostic tool can be used for anaphylactoid

A

-mast cell tryptase positive

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19
Q

How do you treat anaphylactoid

A

same as anaphylaxis

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20
Q

what is scromboid

A

massive ingestion of histamine from decayed mackerel & other oily fish. Mast cells not involved: tryptase neg.

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21
Q

what are differential diagnosis to anaphylaxis

A
  • MI
  • PE
  • hyperventilation,
  • hypoglycaemia
  • vasovagal
  • phaeochromocytoma,
  • carcinoid
  • systemic mastocytosis
  • Also hereditary or idiopathic angioedema
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22
Q

What is mast cell tryptase raised in

A
  • anaphylaxis
  • anaphylactoid reactions
  • mastocytosis
23
Q

What markers are raised or lowered in anaphylaxis

A
  • mast cell tryptase is raised
  • complement is low due to consumption in hereditary or idiopathic angioedema
  • D dimers is high
24
Q

What is urticaria

A

Raised itchy erythematous rash: wheals (“hives”), with inflammation within the dermis

25
Q

What are the types of urticaria

A
  • Acute

- chronic - longer than a month

26
Q

What are the causes of urticaria

A
  • 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
27
Q

What cells are often involved in urticaria

A
  • mast cells
  • histamine
  • leukotrienes
28
Q

What infections can cause urticaria

A
  • 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.
29
Q

describe how autoimmune illness can cause urticaria

A
  • 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.
30
Q

Describe how cold urticaria is caused

A
  • 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.
31
Q

what gene causes inherited cold urticaria

A

There is an inherited form of cold urticaria due to C1AS1 gene mutation

32
Q

describe how the autonomic system can lead to urticaria

A
  • Cholinergic urticaria, associated with heat and sweating.
  • Smaller wheals.
  • Adrenergic urticaria due to stress.
33
Q

What physical stimuli can cause urticaria

A
  • sunlight
  • heat
  • pressure (including dermographism)
  • vibration
  • probably direct stimulation of mast cells and or nerves
34
Q

describe how exercise urticaria is caused

A

may be associated with IgE to omega gliadin: typical history of exercise within hours of a meal containing gluten causing urticaria, even anaphylaxis

35
Q

describe how hormonal urticaria is caused

A

some women describe attacks of urticaria associated with luteal phase of menstrual cycle: progesterone. Other steroids can cause urticaria.

36
Q

name a mast cell disorder that can cause urticaria

A

urticaria pigmentosa

37
Q

How do you treat urticaria

A
  • 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

38
Q

What is angioedema

A

Swelling of subcutaneous tissues due to fluid collection, because of the release of inflammatory mediators, particularly histamine and bradykinin

39
Q

What molecules are released in angioedema

A

histamine and bradykinin

40
Q

if the angioedema is caused by histamine what does this mean it is caused by

A
  • means its caused by an allergy

- may be idiopathic angioedema

41
Q

If the angioedema is caused by bradykinin what does this mean it is caused by

A
  • Hereditary angioedema
  • Acquired C1 esterase inhibitor deficiency
  • Maybe idiopathic angioedema
42
Q

what happens in allergic angioedema

A

Histamine based

- accompanied by urticaria

43
Q

What happens if angioedema occurs in the airway

A
  • can be lethal
44
Q

What markers are raised in allergic angioedema

A
  • specific IgE allergen may be detected

- mast cell tryptase may be raised, especially in anaphylaxis

45
Q

How many types of hereditary angioedema is there

A

Type 1
Type 2
Type 3

46
Q

describe type 1, 2 and 3 types of hereditary angioedema

A

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.

47
Q

What does C1 esterase inhibitor do

A

made in the liver by hepatocytes and acts to restrain the bradykinin pathway and complement pathway

48
Q

What are the symptoms of hereditary angioedema

A
  • 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.
49
Q

What can cause acquired C1 esterase inhibitor deficiency

A
  • 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
50
Q

What markers are low in acquired C1 esterase inhibitor deficiency

A
  • C4 low
  • C1q may be low,
  • anti-C1q antibodies may be present
51
Q

What is the treatment for angioedema

A
  • 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

52
Q

What should you give in emergency treatment of angioedema caused by bradykinin

A

Icatibant s/c inhibits bradykinin pathway: emergency Rx

53
Q

In idiopathic angioedema what usually works as a treatment

A

tranexamic acid

54
Q

What should all people with angioedema avoid

A

ACE inhibitors

Year 3 - Clinical Science and Professionalism (32 decks)

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