Case Description:
A 51 year old female was diagnosed with indolent systemic mastocytosis
(SM) in 2013. She had vague ongoing symptoms including flushing,
itching, telangiectasias, hives, and bloating for over ten years. Other
issues, such as nasal congestion, rhinorrhea, cough, and wheezing, had
been going on since childhood. The triggers, such as heat, friction, and
diet, were often variable as well. These symptoms were occasionally
relieved with Cetirizine. On 4/2013, a skin biopsy revealed
telangiectasia macularis eruptive perstans, and results were positive
for c-kit and tryptase. Bone marrow biopsy from 7/10/2013 revealed
atypical mast cells with spindle morphology, as well as CD117, CD25, CD2
positivity. KIT D816V mutation was negative on the bone marrow biopsy.
As she continued to have symptoms of diarrhea, itchiness, hives, and
headaches, Cromolyn, Hydroxyzine, and injectable Omalizumab were
started. Injectable epinephrine for possible anaphylaxis was also
provided, but the patient never had an anaphylactic episode. Although
some of the symptoms were controlled, other gastrointestinal symptoms
including the bloating and diarrhea persisted. Given that her symptoms
were still not optimally controlled, the patient was started on Imatinib
in 2015, which improved the symptoms of SM. However, this caused
significant transaminitis so Imatinib was discontinued. Midostaurin was
then prescribed but the medication caused rashes, hepatotoxicity, and
nausea so it was discontinued on 12/2018. In 2019, the patient’s serum
KIT mutation was found to be positive. She was then enrolled in an
expanded access clinical trial. At the time, Avapritinib 200mg daily was
used to treat aggressive SM, but the dosage was not yet established for
indolent SM. Because there was hepatotoxicity to other tyrosine kinase
inhibitors, the patient was started on a decreased dose of Avapritinib
at 100mg daily on 4/2020. Over time there were three subsequent dose
reductions of Avapritinib as the patient had gastrointestinal adverse
events and because the indolent SM trials were done at 25mg daily. In
8/2020, Avapritinib was decreased from 100mg daily to 100mg every other
day when she was having nausea, mental fog, and burning tongue ulcers.
The mental fog resolved at this lowered dose and the gastrointestinal
distress was improved but ongoing. There was also occasional skin
flushing and nausea which was improved with the medication. In 3/2021,
the dosage was adjusted to 75mg daily since the patient was able to
tolerate it well for a few months. In 7/2021, she developed Covid-19
infection as well as neck, shoulder, and chest pain so she stopped the
medication completely for several weeks. The medication was resumed at
25mg daily after her recovery from the infection and musculoskeletal
pain. Avapritinib 25 mg daily has since been controlling the patient’s
serum tryptase levels, itchiness, and gastrointestinal symptoms very
well with no toxicities to the medication. Currently the patient still
takes Famotidine, Cromolyn and Hydroxyzine. She only occasionally takes
Ondansetron prophylactically, and she has stopped taking Pantoprazole
completely.