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Indolent Systemic Mastocytosis

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What Drives Hypersensitivity Reactions in Mastocytosis?

—An analysis of registry data concluded that hypersensitivity reactions in patients with mastocytosis are caused by exposure to certain triggers, including low tryptase levels and stings from certain insects. Here’s what else the team learned.

By Deborah L. Ungerleider, MD, FAAP

Mastocytosis is a disease in which mast cells (MCs) accumulate in 1 or more organs, leading to variable symptoms, including pain, nausea, flushing, and diarrhea. There are also different types of mastocytosis, one of which is systemic mastocytosis (SM). A major concern for patients with SM (and some of the other types of mastocytosis) is hypersensitivity, particularly severe reactions, such as anaphylaxis, which can be caused by triggers that cause the release of MC mediators and can lead to decreased quality of life.1

To investigate this further, an international team of researchers looked at the prevalence of hypersensitivity reactions (HRs) in patients with mastocytosis to determine the triggers that were most likely to lead to anaphylaxis. Additionally, they examined whether there were other risk factors for severe anaphylactic reactions. Their findings were recently published online in the journal Allergy.1

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Several different types of mastocytosis are analyzed

The authors used data from the European Competence Network on Mastocytosis (ECNM) registry collected between 2012 and 2019 on 2485 adults with mastocytosis from Europe and the U.S.1 These patients, who were a median age of 48.2 years, had different types of mastocytosis, as follows:

  • Indolent SM (ISM), 58.9%
  • Mastocytosis in the skin (MIS), 14.9%
  • SM with associated hematological neoplasm (SM-AHN), 9.6%
  • Cutaneous mastocytosis (CM), 9.1%
  • Aggressive SM (ASM), 3.5%
  • Smoldering SM (SSM), 2.1%
  • MC leukemia (MCL), 1.5%
  • MC sarcoma (MCS), 0.05%

What are the triggers?

Overall, 38.1% of patients in the ECNM registry had at least 1 HR, including the initial and follow-up visits. Hymenoptera venom anaphylactic reactions from insect stings were more common in men and in older people, whereas food, drug, and inhalant reactions occurred more often in women. The patients with inhalant allergies were generally younger.

Altogether, Hymenoptera venom anaphylactic reactions were the most prevalent, occurring in 21.1% of patients, versus 0.3% to 8.9% in the general population. Most commonly, these were reactions to wasps, with 52% of patients with Hymenoptera venom HR having had venom immunotherapy.

Drug reactions occurred in 8.7% of patients (most commonly to nonsteroidal anti-inflammatory drugs and antibiotics); inhalant triggers were found in 5.6% (most commonly from pollens and house dust mites); food allergies were present in 5.5% (mostly from nuts, alcohol, strawberries, peanuts, and fish); and other triggers were reported in 3%. As might be expected, some patients had reactions to more than 1 trigger.

In terms of mastocytosis subtypes, the investigators found that HR caused by Hymenoptera venoms occurred more commonly in patients with less-advanced SM: 79% in patients with bone marrow (BM) mastocytosis, 47% in patients with ISM, 32% in MIS, 31% in SSM, and 30% in maculopapular cutaneous mastocytosis. Conversely, drug allergy occurred more often in advanced SM, namely MCL (16.2%), ASM (12.5%), and SM-AHN (3.8%).

Tryptase and mast cell burden

A major risk factor for all types of HRs was the level of tryptase at the initial visit. When the tryptase level was ≥ 90 ng/mL, the risk of hypersensitivity was higher (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.68 to 2.66; P < .00001). The highest risk, however, was found to be for Hymenoptera venom (OR 3.08, 95% CI 2.20 to 4.28; P < .00001) and inhalant allergies (OR 3.50, 95% CI 1.76 to 6.59; P < .00002). Patients with ISM had an increased risk (OR 2.67, 95% CI 2.24 to 3.19; P < .00001), especially for Hymenoptera venom (OR 5.59, 95% CI 4.13 to 7.26; P < .00001) but not as much for other allergic reactions (OR 1.68, 95% CI 1.001 to 2.820; P < .041). 

When looking at the effect of MC infiltrates in BM, the authors found that when the MC percentage was < 15% by BM immunohistochemistry, there was more HR overall (OR 2.40, 95% CI 1.77 to 3.24; P < .00001) and for Hymenoptera venom (OR 4.46, 95% CI 2.88 to 6.89; P < .0001); conversely, HR to drugs was more common when patients had a higher MC burden.

Patients were then divided into 2 groups by risk of HR: high risk for patients with ISM and/or tryptase level < 90 ng/mL and low risk for everyone else, levels of which were confirmed by univariate and multivariate analyses.

Did new hypersensitivities occur?

During the 4-year follow-up, the investigators found that 4.8% of patients had ≥ 1 new HR. Of those patients, 87% had no HRs at their initial visit. The types of HRs that were reported at follow-up visits were Hymenoptera venom in 32% of patients, drugs in 25%, inhalants in 20%, food in 13%, and other factors in 17%. In patients with new HRs, 71% had ISM, 11% had CM, 10% had MIS, and 4% had SM-AHN. A single case only was reported for each of the following: SSM, ASM, and MCL.

Additionally, most of these patients with HRs met the high-risk criteria, with both factors—diagnosis of ISM and tryptase level < 90 ng/mL—occurring in 64%, versus 41% in those without HRs. Both factors were also present in 65% of patients who had HRs at the initial visit and in 59% of patients who developed their HR during follow-up.

Limitations and conclusions

The authors mentioned some limitations to their study, including the fact that the data were based on observations of physicians and on retrospective analyses, and that they weren’t confirmed by an oversight committee or monitoring system. The study also excluded hereditary alpha tryptasemia, an emerging genetic risk factor for severe symptoms, as it wasn’t included in the registry for most patients. Lastly, methods of diagnosis varied between the 27 ECNM centers from which the data were gathered.

Despite these limitations, the authors believe that their findings provide value for clinicians across the world who diagnose and treat various forms of mastocytosis.

“Our data confirm the importance of insect venom allergy as the predominant trigger of HR in mastocytosis,” the authors concluded. “From the patients’ perspective, a vital question at diagnosis of mastocytosis is the potential risk of insect venom-related HR over time, even when no history of a venom-related HR or venom-induced allergy is found.”1

Published:

Deborah Ungerleider is a New Jersey-based pediatrician and freelance medical writer and editor who covers numerous aspects of medical practice.

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