💥 Approach to Elevated Tryptase 💥
A patient without a history suspicious for anaphylaxis or angioedema presents with an elevated serum tryptase.
How do we interpret this uncommonly sent lab test?
A patient without a history suspicious for anaphylaxis or angioedema presents with an elevated serum tryptase.
How do we interpret this uncommonly sent lab test?
🐉 Tryptase (along with histamine) is the most abundant & best characterized preformed granule released by mast cells.
🐉 Mast cells release tryptase (among other molecules) upon stimulation by:
- Allergens
- Drugs
- Toxins
- Physical stimuli
- Infections
🐉 Mast cells release tryptase (among other molecules) upon stimulation by:
- Allergens
- Drugs
- Toxins
- Physical stimuli
- Infections
🐉 Symptoms related to mast cell degranulation include:
- Cardiovascular (hypotension, dizziness, tachycardia)
- Respiratory (throat swelling, dyspnea, wheeze)
- Cutaneous (flushing, pruritis, urticaria)
- GI (cramping, N/V)
- Naso-ocular (itchy eyes/nose)
- Cardiovascular (hypotension, dizziness, tachycardia)
- Respiratory (throat swelling, dyspnea, wheeze)
- Cutaneous (flushing, pruritis, urticaria)
- GI (cramping, N/V)
- Naso-ocular (itchy eyes/nose)
While the degree of tryptase elevation correlates with anaphylaxis severity, the level peaks 1-2 hours after degranulation. Therefore:
⛳️ ~1/3 of patients have normal tryptase during an anaphylactic event
⛳️ ~1/3 of patients have normal tryptase during an anaphylactic event
Additionally, serum total tryptase measures both protryptase (constitutively secreted) & mature tryptase (released by trigger).
⚪️ A clinically significant increase is considered greater than [baseline] + 20% + 2 ("20+2 rule")
⚪️ Normal baseline levels = 1 to 11.4 ng/mL
⚪️ A clinically significant increase is considered greater than [baseline] + 20% + 2 ("20+2 rule")
⚪️ Normal baseline levels = 1 to 11.4 ng/mL
The DDx of elevated tryptase can be broken down into a 4-pass system:
💥 1st pass = *dangerous* secondary causes
💥 2nd pass = *chronic & Rx-related* secondary causes
💥 3rd pass = primary causes
💥 4th pass = genetic causes
💥 1st pass = *dangerous* secondary causes
💥 2nd pass = *chronic & Rx-related* secondary causes
💥 3rd pass = primary causes
💥 4th pass = genetic causes
If clinical picture isn't compatible with dangerous anaphylaxis/angioedema, consider Rx-related & chronic secondary causes first:
💊 Opioids, NSAIDs/Aspirin, & IV contrast
♥️ CKD/ESRD & CAD (2/2 chronic organ inflammation)
🟠 Parasitic infections
💢 Chronic urticaria
💊 Opioids, NSAIDs/Aspirin, & IV contrast
♥️ CKD/ESRD & CAD (2/2 chronic organ inflammation)
🟠 Parasitic infections
💢 Chronic urticaria
3rd, can consider rarer, primary causes:
- Mast cell activation syndrome
- Mastocytosis
- Other hematologic malignancies
📚 NOTE: in mastocytosis, the total/mature tryptase ratio is > 20
- Mast cell activation syndrome
- Mastocytosis
- Other hematologic malignancies
📚 NOTE: in mastocytosis, the total/mature tryptase ratio is > 20
Finally, can consider genetic syndromes such as familial hypertryptasemia:
🧬 Arthralgias, GERD, flushing, vibratory urticaria, dysautonomia (POTS, IBS)
🧬 Baseline tryptase is usually > 8 ng/mL
🧬 Arthralgias, GERD, flushing, vibratory urticaria, dysautonomia (POTS, IBS)
🧬 Baseline tryptase is usually > 8 ng/mL
To wrap up, conditions that mimic anaphylaxis are listed below.
Tests & findings supportive of these etiologies listed in green!
Tests & findings supportive of these etiologies listed in green!
Major thanks to @YaleIM_Chiefs' @Luke_Legakis for reviewing this framework!
Other pearls welcome 😄
References:
1) #H969243563" target="_blank" rel="noopener" onclick="event.stopPropagation()">uptodate.com
2) rcpjournals.org
3) pubmed.ncbi.nlm.nih.gov
4) karger.com
Other pearls welcome 😄
References:
1) #H969243563" target="_blank" rel="noopener" onclick="event.stopPropagation()">uptodate.com
2) rcpjournals.org
3) pubmed.ncbi.nlm.nih.gov
4) karger.com
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