Anaphylaxis

Question 1

List some anaphylaxis DDx?

Answer 1

• Shock (life threatening)
o Distributive- septic, non-septic (e.g. inflammatory, asthma, CNS injury, anaphylactic) (e.g. status asthmatics)
o Hypovolaemic- haemorrhagic (e.g. trauma), non-haemorrhagic (dehydration, burns)
o Cardiogenic- cardiomyopathic (e.g. MI, HF), arrhythmogenic (e.g. VE), mechanical (e.g. valvular insufficiency)
o Obstructive- pulmonary vascular (e.g. PE), mechanical (e.g. tension pneumothorax, cardiac tamponade)
• Allergy
o Allergic asthma exacerbation
o Anaphylaxis (allergic), anaphylactoid (non-allergic)
• Respiratory- foreign body obstruction
• Psychology- panic attack (possibly precipitated by allergy)

Question 2

What Ix would you order?

Answer 2

Vitals (priority)- HR, BP, temp, RR, SpO2

Blood tests
o FBC- WBC (eosinophilia/atopy), RBC (anaemia, bleeding), platelets (coagulation)
o ESR-CRP- inflammatory process
o Coag prolife- coagulation disorder (e.g. Haemophilia A, B, C or Vit K deficiency), platelet disorder (e.g. immune thrombocytopenia), mixed (e.g. von Willebrand, DIC)
o DIC (increased APTT/PT)
o UEC- renal function
o LFTs- liver function
o Troponins- cardiac cause
o Mast cell tryptase (elevated in anaphylactic and anaphylactoid)- elevated 3hrs post-reaction, remaining for >6hrs
o Histamine- peaks 5-15mins, remaining for 1hr
o ABG- hypoxia, hypercapnia (type 2 respiratory failure), lactate
o Blood culture- sepsis
o Serology- IgE (allergic reaction)

Imaging
o CXR- ARDS (“ground glass”)

Question 3

What Ix can later be done to confirm the allergy?

Answer 3

o In vitro IgE testing (allergen-specific IgE in human serum)
o Skin test: scratch test w allergen
o Challenge test: increasing amounts of offending allergen (best test, contraindicated in anaphylaxis Hx)

Question 4

Differentiate between type 1 and type 2 respiratory failure?

Answer 4

Type 1: Hypoxaemic
• Hypoxia without hypercapnia 
• PO2 < 60mmHg (on RA)
• Path: disease involves lung itself
• Causes: ARDS

Type 2: Hypercapnic/ventilatory 
• Hypoxia WITH hypercapnia 
• PCO2 > 50mmHg 
• Path: failure of alveolar ventilation
• Causes: COPD, drug OD

Question 5

Describe the pathophysiology behind the clinical manifestations of anaphylaxis?

Answer 5

• Swollen face/lips/tongue: histamine release -> act on H1-H3 receptors -> increase vascular permeability -> extravasation of fluid -> angioedema
• Urticaria: histamine release -> vasodilation -> flare hyperaemia
• Pruritus: histamine release -> excitation of unmyelinated C fibers
• Stridor: histamine release -> increase vascular permeability -> fluid extravasation -> angioedema of larynx and pharynx -> URT obstruction
• Wheeze (bilateral): histamine release -> stimulate leukotriene release -> lower airway constriction
• Tachypnoea: attempt to compensated increase in CO2 by hyperventilation (similarly trying to raise pH to compensate lactic acidosis)
• Pale: systemic hypoperfusion -> shock
• Drowsy: histamine -> systemic vasodilation -> poor cerebral perfusion

Question 6

Describe the pathogenesis of an anaphylactic reaction?

Answer 6

Initial allergen exposure:
⇒ antigens detected by dendritic APCs -> taken to local LNs
⇒ presented to CD4 T-cells
⇒ IgM B-cells class switch into IgE B-cells (mediated by IL-4 and IL-5)
⇒ IgE B-cells produced IgE antibodies -> diffuse through tissue and bind to mast cell surfaces
-> Immune system sensitization takes approx. 1 week

Subsequent allergen exposure:
⇒ allergen directly binds to surface-bound IgE
⇒ IgE cross-linking -> induce widespread mast cell degranulation
-> acute phase mediator release (15mins): histamine, adenosine, chemotactic factors
-> late phase release (6hrs, persists 72hrs): phospholipase A2, platelet aggregating factor, mast cell cytokines

Question 7

Describe the indication and MAO of adrenaline?

Answer 7

Indication: haemodynamic instability (prevention of shock), anaphylaxis

MA: non-selective agonist of all adrenergic receptors (including a1, a2, B1, B2, B3) -> stimulate the sympathetic nervous system -> reverse haemodynamic compromise
o Alpha 1 and 2 – vascular smooth muscle contraction -> peripheral vasoconstriction (skin, mesentery) to counteract central vasodilation
o B1 -> positive chronotropic effects (increase rhythm/HR) and positive ionotropic effect (contractility) -> increase BP
o B2 -> bronchodilation and prevention of further histamine release

Note: adrenaline given over noradrenaline in anaphylactic shock (more affinity for B adrenergic receptors -> more bronchodilation).
Noradrenaline used in septic shock (more affinity for alpha adrenergic receptors -> vasoconstriction)

Question 8

How is adrenaline administered during an anaphylactic reaction?

Answer 8

Route: IM (controlled release and reduced toxic SE)

Question 9

List some SE of adrenaline?

Answer 9

SE: anxiety, palpitations, arrhythmia, peripheral necrosis (due to SNS overexcitation)
OR MI, HTN, intracranial haemorrhage (rare)

Question 10

Describe the initial management of anaphylaxis?

Answer 10

• Remove allergen
• Call assistance
• Primary survey:
A) Intubate if obstruction, airway trauma, inability to protect airway, head injury
B) High flow O2 >10L/min
C) Raise legs above heart, 2 large bore IV
• IM adrenaline immediately (mid thigh)- 0.5mL, repeat every 5mins as needed
• Supportive: IV saline 20mL/kg (if hypotensive), vitals
• Monitor for prolonged or biphasic reactions (>4hrs post adrenaline)
• Observe overnight (if severe, concomitant illness, poor access)

Question 11

Describe follow-up management of anaphylaxis?

Answer 11

• Antihistamines- oral, non-sedating antihistamines to relieve symptoms (itch, urticaria)
• Corticosteroids (prednisolone 1mg/kg, max 50mg/day, x2 days)
- reduce risk of symptom recurrence, relief of persistent wheeze
- MA: immunosuppressive effects (inhibits cytopkine production, promote T-cell apoptosis, decrease B cell antibody synthesis, decrease neutrophil proliferation)
• Adrenaline autoinjector (prescribed for future relief during reactions)
• Allergy specialist referral