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.