Hypersensitivity Flashcards
SLE is which type of hypersensitivty?
Type 1
Type 2
Type 3
Type 4
SLE is which type of hypersensitivty?
Type 1
Type 2
Type 3
Type 4
ANA antibodies
Describe the different types of hypersensitivity reactions with regards to the immunological mediators [4] and onset [4]
Type 1:
- Allergies
- IgE mediated
- rapid onset (within one hour)
Type 2:
- Antibody
- IgG or IgM
- Hours to days
Type 3:
- Immune complex mediated
- 1-3 weeks
Type 4:
- T cell mediated
- Days to weeks
ABCDE
Allergy; antiBody, immune Complex, Delayed
What type of pathogens are Th1,2 & 17 good at fighting? [3]
Th1 - intracellular
Th2 - helminthic
Th17 - extracellular
What is atopy? [1]
Predisposition to develop allergic hypersensitivity reactions (usually to common environmental stimulus)
Type 1 hypersensitivity reactions are mediated by:
IgA
IgM
IgG
IgE
IgD
Type 1 hypersensitivity reactions are mediated by:
IgA
IgM
IgG
IgE
IgD
Describe the sensitisation and activation phases of allergy [2] (early phase)
Sensitisation:
- After entry of an allergen into the body, it is taken up by antigen-presenting cells that interact with T-helper type 2 (Th2) cells that signal for stimulation of B-cells within lymphoid tissue.
- This leads to allergen-specific IgE production by B cells
- The released IgE then binds to mast cells and some basophils located around the body, particularly in the skin, gut and lungs.
Activation:
- patient is re-exposed to the same allergen and it diffuses in the proximity of these mast cells it can lead to binding on the IgE antibodies.
- Binding leads to cross-linking and aggregation that initiates intra-cellular signalling.
- If this signal is strong enough, it leads to activation and degranulation causing release of massive amounts of chemical mediators including histamine, tryptase, cytokines, prostaglandin and leukotrienes.
Describe the late phase response of type 1 immediate hypersensitivity
Mediated by eoisinophils, basophils and lymphocytes - 4/6 hours later and causes chronic allergic disease
They cause local inflammation, vessel dilatation, loss of vascular integrity and fluid extravasation leading to oedema.
Describe what is meant by oral allergy syndrome
Allergic reaction to certain foods (especially fruit and veg) in the mouth; due to cross-reactivity because of previous allergic rhinitis / atopy
How do you diagnose Typ1 immediate hypersensitivity? [5]
Total IgE vs specific IgE
Serum tryptase (released from mast cells)
FBC - eisinophils
Histamines (but v short lived)
OR
Allergen expoxure - skin prick test - measure the size of the reaction to a control
What is important to note about skin prick test? [1]
Can’t have taken anti-histamines prior to test
How do you treat:
- Mild allergic reactions [2]
- Severe allergic reactions [2]
Mild allergic reactions:
- Antihistamines
- Corticosteroids
Severe allergic reactions:
- IM adrenaline 0.5-1mg
- IV hydrocortisone
Describe when and how many samples of mast cell tryptase you should take [+]
Mast cell tryptase is one of the major proteins released during activation and degranulation
Immediate sample: taken as soon as possible after onset. Should NOT delay treatment
Second sample: taken at 1-2 hours after onset. Should be no later than 4 hours. Minimum required sample
Third sample:taken at least 24 hours after onset. Often taken at follow-up allergy clinic. Acts as the baseline level
Describe the treatment protocol in emergency anaphylaxis
ABCDE
- IM adrenaline 1mg/ml (1:1000) in anterolateral aspect middle of thigh
- Establish airway & give high flow O2
- If no response - repeat IM adrenaline after 5 minutes & IV fluid bolus
4. If no improvement after 2 doses of adrenaline - follow refractory algorithm
What are the doses for IM adrenaline for:
Adults and children > 12
6-12 year olds
6 months - 6 years
< 6 months
Adult and child >12 years old:
- 500 micrograms IM (0.5 mL of 1mg/mL adrenaline)
6-12 years old:
- 300 micrograms IM (0.3 mL of 1mg/mL adrenaline)
6 months - 6 years:
- 150 micrograms IM (0.15 mL of 1mg/mL adrenaline)
< 6 months:
- 100-150 micrograms IM (0.1-0.15 mL of 1mg/mL adrenaline)
How does adrenaline work to treat anaphylaxis? [2]
Alpha-adrenergic receptors:
- causes vasoconstriction that reverses peripheral vasodilation and reduces tissue oedema
Beta-adrenergic receptors:
- causes bronchodilation, increases myocardial contractility and suppresses histamine/leukotriene release. Also inhibits mast cell activation
How do you treat refractory anaphylaxis? [1]
The principal treatment is initiation of an adrenaline infusion.
Repeated doses of intramuscular adrenaline should be given at 5 minute intervals whilst the intravenous infusion is being prepared and ongoing fluid resuscitation should be administered.
Describe what is meant by a biphasic anaphylaxis reaction
This refers to the recurrence of symptoms several hours later in the absence of exposure to the allergen.
The biphasic reaction is estimated to occur in around 5% of patients with anaphylaxis
Due to the risk of a biphasic reaction patients are traditionally observed for a period of 6-12 hours
Name 5 examples of pathologies that cause type 2 HS reaction [5]
Autoimmune anaemia and thrombocytopenia
Acute rheumatic fever
Goodpastures
MG
Hyper acute graft rejection
Describe the pathophysiology of Goodpastures syndrome [1]
How do you diagnose? [2]
GBM antibodies directed agaisnt a3-chain of collagen IV (forms the basement membrane)
Diagnosis: Biopsy with
- IgG immune complexes
- C3
This is Goodpastures. What cellular infiltration is present? [1]
Leukocytes
What is serum sickness? [1]
What type of hypersen. reaction? [1]
Drug contains protein from another animal - produce immune complex agaisnt it
Type 3
Polyarteritis nodosa occurs after HBV infection.
What o
FYI
Complexes bind via Fc region and activate other cells (e.g. via neutrophils)
Nearly 100% of SLE patients have which auto-antibodies? [1]
ANA
How do you treat type 3 HS? [3]
Which drug is particularly used for SLE? [1]
Hydroxycholoroquine
Type 4 hypersensitivity is mediated by which cell types? [1]
Name 4 examples
T cell mediated - take longer !
- Contact dermatitis
- Chronic graft rejection
- Drug hypersensitivity
- Granuloma
How do you treat nickel hypersensitivity? [2]
Avoid nickel
Topical steroids and calamine lotion
300
What is a Type V reaction? [1]
Give an example [1]
Antibody binding to receptor (c.f. blocking) on non-immune cells
E.g Graves
150
How do you treat urticaria? [2]
What can you use to treat chronic urticaria? [1]
Antihistamines or steroids
Chronic: Omalizumab
Serum tryptase
A 5-year-old boy is brought to the emergency department with sudden onset wheezing and swelling of his tongue, face and hands. On assessment there is evidence of airway compromise.
What is the correct dose of 1 in 1,000 intramuscular adrenaline to treat this patient?
150 micrograms
150 milligrams
500 micrograms
500 milligrams
1000 micrograms
150 micrograms
You are called to the treatment room of a GP surgery as a 12-month-old boy has developed a rash and breathing difficulties following a routine vaccination. On examination he is developing swelling around the mouth and neck. What is the most appropriate initial action?
Phone 999 and reassure mother
IM adrenaline 150 mcg (0.15ml of 1 in 1,000)
IM adrenaline 300 mcg (0.3ml of 1 in 1,000)
IM adrenaline 50 mcg (0.05ml of 1 in 1,000)
Salbutamol nebuliser stat
IM adrenaline 150 mcg (0.15ml of 1 in 1,000)
6 months - 6 years adrenaline dose for anaphylaxis 150 mcg (0.15ml 1 in 1,000)
In the treatment of anaphylaxis, you can repeat adrenaline every [] minutes
5 minutes
A 25-year-old lady presents to the GP with itchy eyes. She describes a gritty feeling in both her eyes and has noticed that they stick together in the morning. The grittiness is also worst first thing when she wakes up. She complains of no other symptoms.
Given her presentation what is the most likely diagnosis?
Dry eye syndrome
Blepharitis
Cellulitis
Basal cell carcinoma (BCC) of the eyelid
Allergic Rhinitis
Blepharitis
An 11-year-old girl is brought to the Emergency Department by her parents after the sudden appearance of widespread blistering, sore mouth and skin tenderness. She also has a three-day history of high fevers and malaise. She has no past medical history except amoxicillin for an ear infection two weeks ago.
She appears systemically unwell with a temperature 39.2ºC, heart rate 187 bpm, blood pressure 100/54 mmHg, respiratory rate 22 /min and SpO2 98%.
On examination, there are widespread erythematous bullae and vesicles covering almost half the body surface. Lesions are also present on the oral mucosa and beginning to affect the eyes. Nikolsky’s sign is positive.
What is the most likely diagnosis?
Toxic epidermal necrolysis is a rare but important side effect of which to be aware of penicillins