Title: Immunology

Q: Define anaphylaxis
A: Serious allergic reaction of rapid onset that may cause death

Q: Define anaphylactoid
A: Non-IgE mediated reactions that DO NOT require a sensitising event

Q: Clinical criteria for anaphylaxis/anaphylactoid
A: Acute onset with skin and/or mucosal involvement + one of:
 - Respiratory
 - Hypotension
 - Associated symptoms of organ dysfunction e.g. hypotonia, syncope
2 or more of the following after exposure to likely antigen:
 - Skin and/or mucosal
 - Respiratory
 - Hypotension or symptoms thereof
 - Persistent GI symptoms
Consider in all hypotensive patients with exposure to a suspected allergen

Q: What is the prevalence of anaphylaxis to beta-lactams?
A: 1/10 000

Q: Lifetime risk of anaphylaxis
A: 1-3%

Q: Mortality rate of anaphylaxis
A: 1%

Q: What proportion of anaphylaxis fatalities occur in first hour?
A: 50%. The more rapid the onset, the more severe

Q: What proportion of anaphylaxis has biphasic response?
A: 3-20%

Q: When does biphasic anaphylaxis reaction peak?
A: 4-8 hours

Q: When does biphasic reaction of anaphylaxis usually become apparent?
A: Within 4 hours

Q: DDx of anaphylaxis
A: Hyperacute asthma
Angioedema
Gastroenteritis
MI
Arrhythmias
Seizures
Epiglottitis
Hereditary angioedema
Foreign body airway obstruction
Carcinoid syndrome
Vocal cord dysfunction syndrome
Syncope

Q: When do mast cell tryptase levels peak?
A: 15-120 minutes

Q: When should mast cell tryptase levels be taken?
A: 1, 6 and 24 hours

Q: Indications of intubation in anaphylaxis
A: Obvious obstruction
T1 or T2RF
Angioedema
Uvula oedema
Audible stridor
Respiratory distress

Q: Dose of adrenaline in anaphylaxis
A: 0.5mg IM q5-10min
Infusion 10-50mcg/min if refractory

Q: Treatment of anaphylaxis
A: 100% O2
Intubate early if indicated
Adrenaline 0.5mg IM q5-10min +- infusion 10-50mcg/min
20mL/kg N/saline
Hydrocortisone 300mcg IV
IV diphenhydramine 50mg + Ranitidine 50mg
Salbutamol/ipratropium nebs
Glucagon 1mg IV q5min if refractory and on beta-blockers

Q: How long should anaphylaxis be observed for?
A: 4 hours minimum

Q: Discharge plan for anaphylaxis
A: Avoid potential allergen
Discharge script for 3-5 days oral prednisolone + loratidine 10mg daily
EpiPen provision + extra
Education on use
Warning signs of delayed biphasic reaction
Anaphylaxis action plan
Referral to immunologist
MedicAlert bracelet

Q: What proportion of ACEi users suffer angioedema?
A: 0.5%

Q: Management of ACEi angioedema?
A: Adrenaline is used but evidence is lacking.
Steroids and antihistamines fail as not IgE mediated (bradykinin)

Q: What is hereditary angioedema?
A: Autosomal dominant C1 esterase inhibitor deficiency

Q: How does hereditary angioedema present?
A: Angioedema lasting 1-2 days often following minor trauma with family history of same

Q: How common is hereditary angioedema?
A: 1/50 000

Q: Management of hereditary angioedema
A: FFP 10mL/kg IV
C1 esterase inhibitor concentrate 1000IU IV if available
Attenuated androgens are preventative

Q: What proportion of acute drug reactions are due to penicillin?
A: 90%

Q: What proportion of fatal anaphylaxis is due to penicillin?
A: 75%

Q: Cross-reactivity of penicillin allergy to cephalosporins?
A: 7%

Q: Which antibiotics can lead to serum sickness?
A: Cefaclor
Bactrim

Q: Most common symptoms of anaphylaxis?
A: Urticaria/angioedema 60-90%
SOB/wheeze 50%
Laryngeal oedema 50%

Q: Which drugs commonly cause anaphylactoid histamine release?
A: Morphine - In skin. Hypotensive but not bronchospastic
Atracurium, vecuronium, propofol - Widespread. Bronchospastic.
Vancomycin - Widespread.

Q: Does ACEi angioedema have a biphasic response?
A: No. Lasts 12-24 hours and does not recur unless re-exposed to ACEi

Q: What proportion of hereditary angioedema is due to new mutations?
A: 25%

Q: Consequences of antibody deficiency?
A: Encapsulated bacterial infections
Recurrent respiratory infections + sinusitis

Q: Primary antibody deficiency DDx
A: X-linked agammaglobulinaemia
HyperIgM immunodeficiency
Common variable immunodeficiency
IgA deficiency

Q: Secondary antibody deficiency DDx
A: B-cell laeukaemia/lymphoma
Myeloma
Thymoma
Phenytoin - IgA deficiency
Intensive plasmapheresis

Q: Consequences of cellular immunodeficiency
A: Intracellular pathogen and reactivation of latent infections
PCP, Candida, Aspergillus, Toxoplasmosis, Cryptococcus, Cryptosporidium, HSV, CMV, EBV, VZV, JV virus

Q: Primary cellular immunodeficiency
A: DiGeorge syndrome

Q: Secondary cellular immunodeficiency
A: HIV
Hodgkin's lymphoma
T-cell lymphoma
Sarcoidosis
Thymoma
Therapeutic immunosuppression

Q: Complement deficiency consequences
A: Failed lysis of cell walls
Neisseria
Moraxella
Acinetobacter

Q: Acquired complement deficiency
A: SLE
Persistent activation of classical pathway e.g. Neisseria
Myeloma

Q: Consequences of phagocyte deficiency e.g. neutropaenia
A: Bacterial and fungal infection
S. aureus, Gram-negative enteric, Candida and Aspergillus

Q: Primary phagocyte deficiency
A: Chronic granulomatous disease

Q: Secondary phagocyte deficiency
A: Autoimmune neutropaenia
Chemotherapy
Cyclic neutropaenia
Myelodysplastic syndromes
Aplastic anaemia

Q: Combined immunodeficiency syndrome DDx
A: X-SCID
Haematopoietic stem cell transplant (initial 3-4 months + therapeutic immunosuppression)
Critical illness
Asplenia