A new study published in Frontiers in Allergy found that individuals with early or nonadvanced forms of systemic mastocytosis (SM) without skin involvement face a significantly heightened risk of experiencing anaphylaxis.
Researchers from Italy analyzed data on 162 adults diagnosed with SM between 2009 and 2025, including some whose disease was only recognized after an anaphylactic episode. These are known as “prediagnostic” cases. The results showed that 29 of the individuals studied (approximately 18%) experienced at least one anaphylactic episode.
The researchers found that the absence of cutaneous (skin) involvement was one of the strongest predictors of severe allergic reactions. Among patients with skin lesions, only 8.8% experienced anaphylaxis, while the rate rose to nearly 40% in those without skin lesions. This pattern held true both in prediagnostic SM and in people diagnosed with the indolent form of the disease.
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Additionally, the analysis showed that hymenoptera venom was the leading trigger for anaphylaxis in these less-advanced cases without skin involvement, while drug-induced reactions were more frequent in advanced SM.
The study’s authors note that individuals in the prediagnostic phase (who may present to allergists rather than hematologists) represent a particularly vulnerable group. Without the classic cutaneous symptoms, SM can remain undiagnosed until a life-threatening allergic reaction occurs. For this reason, they recommend heightened awareness among clinicians managing venom or drug hypersensitivity, as well as consideration of baseline tryptase testing and KIT mutation analysis in unexplained anaphylaxis cases.
“The findings support the need for personalized allergological workup, as anaphylaxis risk varies significantly based on disease subtype and cutaneous involvement,” they wrote.
The study has several limitations, including that it was done at a single center with a limited sample size. Relying on medical records may have also led to incomplete data, and without genetic testing the researchers could not search for hereditary alpha-tryptasemia (HαT), a genetic trait that increases the risk of severe anaphylaxis in people with SM. The authors call for more research, including more studies to investigate the prevalence of HαT in different SM subtypes to better understand which patients are most at risk for severe allergic reactions.
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