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Tryptase and Anaphylaxis

(May 2006)

(Download  Tryptase and Anaphylaxis.pdf)

Clinical Indications

  1. Identify mast cell activation as a cause of clinical anaphylactic/anaphalactoid-like events.
  2. Assess mast cell burden (as in mastocytosis)

Anaphylaxis is a life-threatening clinical problem caused by an allergic (IgE) response to a range of triggers. Approximately 50 to 100 Australians die from anaphylaxis each year. Anaphylaxis, in contrast to milder allergic reactions, is a generalised reaction that involves the respiratory and/or circulatory system, often more than one organ system (respiratory, circulatory and/or skin). These features of anaphylaxis may also occur through non-IgE-mediated direct mast cell degranulation, in which case the phenomenon is called “anaphylactoid”.

Symtom

Other Conditions mimicking anaphylaxis

Wheeze

Upper airways obstruction: fixed / variable / functional

Asthma, pulmonary oedema

Dyspnoea

Asthma, other respiratory or cardiac disorder, reflux, anxiety

Throat Tightness

As per wheeze and dyspnoea above

(Pre-) Syncope

Vasovagal syncope, baroreceptor/neurocardiogenic syncope, autonomic insufficiency, cardiac dysrhythmia, hypoglycaemia, dehydration, anxiety

Flushing

Anaphylactoid, Rosacea, Endocrine causes, Anxiety



Causes of Anaphylactic & Anaphylactoid Reactions

Anaphylactic

Allergic” or “IgE-mediated”

Anaphylactoid

“Direct mast cell secretion”

  • Foods (particularly nuts and seafood)
  • Drugs (particularly beta-lactam antibiotics)
  • Insect stings/bites (bees, wasps and fire ants)
  • Latex
  • Food in context of exercise (+/- food e.g. wheat)
  • “Idiopathic”
  • Drugs (particularly nonsteroidal anti-inflammatory agents (NSAIDs), aspirin, opioids)
  • Radiographic contrast media
  • “Danger” signals (infection, surgery)
  • Physical factors (pressure, heat, cold)
  • Bacterial toxins (scombroid fish)

Diagnosing Anaphylaxis

Accurate diagnosis of anaphylaxis is essential, as prompt administration of adrenaline and presentation to hospital is lifesaving. Careful review of the event and predisposing cause(s) is essential, to enable avoidance of recurrence (if possible); to institute appropriate management (including the “Action Plan”); and to exclude conditions that mimic anaphylaxis. The diagnosis of a life-threatening condition is a significant burden and may reduce quality of life.

Tryptase

The measurement of serum levels of mast-cell specific products can clarify the diagnosis of anaphylaxis in ambiguous circumstances (e.g. defining vasovagal responses versus anaphylaxis, or defining cause for hypotension intraoperatively). Histamine elevation is transient (peak missed if collected beyond one hour) with false-positives occurring through basophil activation in clotted tubes. For this reason tryptase is the preferred marker for demonstrating mast-cell degranulation.

Levels of serum tryptase, a mast–cell specific protease, peak at one hour after an anaphylactic/ anaphalactoid reaction and remain elevated for approximately six hours, making tryptase a useful test for most emergency situations. Ideally, serum tryptase levels should be collected between one and six hours following an anaphylactic episode. Elevated serum tryptase implies either massive mast cell degranulation (as in anaphylaxis) or a condition with too many mast cells (e.g. mastocytosis). It should be remembered that not all cases of true anaphylaxis are accompanied by tryptase elevation. For example, some cases of food-induced anaphylaxis display normal tryptase levels, perhaps through basophil-mediated histamine release. Nevertheless, tryptase elevation has been quoted as possessing 95% sensitivity and 95% specificity for clinically significant mast-cell-mediated anaphylactic/anaphalactoid events, which offers a positive likelihood score of 19 (making anaphylaxis 19-times more likely than before the test was done).

Tryptase Test Summary

Clinical Indications

  • Identify mast cell activation as cause of clinical anaphylactic/ anaphalactoid events
  • Show evidence of increased mast cell burden (as in mastocytosis)

Assay Frequency

Twice weekly

Sample Container

Clotted serum tube (plain tube)

Sample Volume

2 mL

Special Collection Instructions

Collect serum between one and six hours after suspected anaphylaxis

Handling Instructions

Store at 2-8 °C for up to 5 days, otherwise store at –20 °C.

Test Cost

$45 per assay (MBS non-refundable test)

About the Authors

Emeritus Professor Robert Clancy (Director), Dr Glenn Reeves (Staff Specialist), Dr Theo deMalmanche (Registrar), Karla Lemmert (Unit Supervisor) wrote this HAPS Communique. If you have any questions regarding this topic, they can be contacted as follows:

Immunology Contacts

E/Prof Robert Clancy (Director) – 49214018

Dr Glenn Reeves (Staff Specialist) - 49214029

Dr Theo deMalmanche (Registrar) - 49214025

Karla Lemmert (Unit Supervisor) - 49214018

Immunology Laboratory – 49214018