This is the slide version of Dr Joshua Milner's video Trypped up by Tryptase

1. Trypped up by tryptase
Joshua Milner, MD
Genetics and Pathogenesis of Allergy Section
Laboratory of Allergic Diseases

2. Ehlers-Danlos Hypermobility
type
Somatic clonal mast cell
disorders
Itching
Flushing
Rapid GI pain
Headache
Loss of blood pressure
Venom Anaphylaxis
Idiopathic
Anaphylaxis
Joint hypermobility
Retained 1o dentition
Scoliosis
Pectus
Dysautonomia/POTS
Abdominal
pain/IBS/dysmotility
Chronic Pain
“Brain fog”
Easy bruising/bleeding
Anxiety/Depression

3. Hornyetal.Dtsch.Arztebl.Int.2008Carter,etal.AnesthAnalg.2008

4. What is tryptase?
• Made mostly by mast cells
• Almost everyone has some tryptase
floating around
• Goes up when you have certain kinds of
allergic reactions
• Is higher at baseline
– in people who have bad allergic reactions,
especially to bee stings
– In mastocytosis: rare clonal proliferative
disease
– In certain forms of the mast cell activation

5. Prevalence of elevated tryptase in the
general population
n = 420
4.3% (n = 18): >11.4ug/L
Gonzalez-Quintela. Clin Chem Lab Med. 2010But, who cares?

6. Fellinger et al. Allergol Immunopathol. 20
Elevated basal serum tryptase is associated
with ‘MCAS symptoms’ and others

7. ii. iii.i. v.iv.
vii.vi. viii. ix.
Familial hypertryptasemia:
A dominant inheritance pattern
Lyons et al. J. Allergy Clin. Immunol. 2014
x.
xiii.
xii.
xi.
?
xvi.
xv.
xiv.

8. There are lots of ways to get
flushing, tachycardia, loss of blood
pressure, belly pain, and even hives
Hormonal
-Thyroid
-Menopause
Autonomic
(nerves and
blood vessels)
-Idiopathic
dysautonomia
-Carcinoid
Stress
-physical– e.g.
exercise
-psychological
stress
Mast cells

9. Tryptase itself can act on nerves and blood vessels to cause very similar responses to what our
patients have. It is thought to occur through a receptor called PAR2
Abdullah Kutlar Blood 2013;122:1846-1847
©2013 by American Society of Hematology

10. Mast cells mixing with
stress/illness

11. Prior to speech,
pretreatment with mast
cell stabilizer (cromolyn)
stops the leaky gut!
Getting up here and speaking is
worse than electric shock
Vanuytsel et al, Gut 2014
Gut gets leaky
Both cause “stress” but only one leads to
the production of certain hormones

12. A few points to clarify
• These symptoms may or may not be due
to mast cells being abnormally activated.
Some folks had increased production of
other products of mast cells, others did
not.
• Normal appearing, but increased in
number mast cells can be found in the
skin, gut or bone marrow biopsies of
symptomatic patients, but in plenty of
folks, there were normal numbers
• Blocking mast cells and what they make

13. And let me be crystal clear
• This isn’t all in anyone’s head.
• There are real physiologic issues
emanating-- probably from the mast cells--
that make things worse when other stimuli
come into play– like stress, anxiety,
infection, eating, running, etc.
• So part of it is in our nervous system, part
of it is not. Part of it may well be tryptase
acting on blood vessels, nerves, and
connective tissue.
• So, again, that does NOT mean it’s all in

14. So what’s next?
• How many symptoms are direct effects of
mast cells releasing what’s inside them vs.
direct effects of tryptase itself vs. our
responses to long term exposure to these
mast cell contents
– Changes to cells and connective tissue
– Changes to behavioral responses
• Treat symptoms in the meantime.
– Manage mast cells and their mediators
– Manage stress of all forms
• Perhaps block stress hormones?

15. Acknowledgements & Thanks