Study underscores link between hymenoptera allergy and mast cell disorders

Up to 30% of people with hymenoptera venom allergy may have a clonal mast cell disease like SM.

Most people will get stung by a bee or wasp at some point in their lives, and the majority walk away with nothing more than a swollen, itchy bump. However, for a small group of people, these stings trigger a life-threatening allergic reaction called anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis., which sometimes can signal a deeper, often undiagnosed condition.

A new research review highlights the growing evidence that underlying clonal mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. diseases, such as systemic mastocytosis (SM) and monoclonal mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis. syndrome (MMAS), are major contributors to severe systemic reactions to certain insect stings.

According to the study, published in Current Opinion in Allergy and Clinical Immunology, up to 30% of people with hymenoptera venom allergy (an allergy to a group of insects including bees, wasps, yellowjackets, hornets and some ants) may have a clonal mast cell diseaseMast cell disease A group of conditions in which mast cells behave abnormally by building up in excess, releasing chemicals too easily or both. Includes mastocytosis, mast cell activation syndrome and hereditary alpha-tryptasemia..

The research emphasizes the need for clinicians to actively screen patients who suffer from venom-induced anaphylaxis, especially when their reaction does not include typical allergic symptoms affecting the skin like hives or itching, but instead involves fainting, low blood pressure and rapid heart rate. These symptoms could indicate an underlying clonal mast cell disease.

Diagnostic tools such as the REMA score and blood tests for KIT gene mutations can help identify which patients should undergo bone marrow studies, the gold standard for detecting abnormal mast cells. Advanced techniques like flow cytometry and digital PCR are also improving the ability to find low levels of mast cell disease that might otherwise be missed.

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An accurate diagnosis is important, as individuals with hymenoptera venom allergy plus clonal mast cell disease face a higher risk of severe or fatal reactions to future insect stings. 

Treatment includes lifelong venom immunotherapy (VIT), which gradually exposes the immune system to increasing amounts of insect venom, leading to the development of tolerance. The study notes that VIT therapy is up to 86% effective at preventing severe reactions from future stings. However, the risk returns quickly if the treatment is stopped.

Because of this, the study authors say a multi-disciplinary approach is essential to identify individuals with both hymenoptera venom allergy and clonal mast cell disease to prevent further complications.

“This should involve allergists familiarized with screening tools for the assessment of mast cell clonality (e.g., REMA score and KIT mutation analysis in blood) as well as hematologists/ pathologists trained on highly sensitive diagnostic techniques able to identify and characterize mast cells when they are present at very low frequencies in the bone marrow (e.g., mast cell sorting and flow cytometry),” they wrote.

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