Negative peripheral blood KIT mutation in anaphylaxis patients: a false reassurance for mast cell disease

Published online: August 1, 2021

Diagnosis of primary mast cell disorders necessitates a bone marrow examination. When typical red/brownish skin lesions are observed, there is often an indication for a bone marrow examination. However, patients frequently experience anaphylaxis without these typical skin lesions, and their baseline tryptase is normal or only slightly elevated (<30 ng/mL). In this scenario the decision to perform a bone marrow biopsy is not straightforward. A new technique detecting the KIT D816V mutation in the blood of patients has been suggested as a screening tool for primary mast cell disorders. However, the reliability of this assay has not been thoroughly evaluated in this specific population.

In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, De Puysseleyr and colleagues investigated the performance of the KIT D816V mutation assay in this specific group of primary mast cell disorder patients with anaphylaxis. The authors selected 74 patients who experienced severe anaphylaxis but without typical mastocytosis skin lesions and a baseline tryptase of < 30 ng/mL. Most of these patients suffered from a venom induced anaphylaxis. All the patients had a bone marrow biopsy. KIT mutational analysis was performed in both blood and bone marrow. The results of the detection of KIT D816V mutation in blood were compared to the results of the bone marrow biopsy.

In about half (40/74) of the patients a diagnosis of a primary mast cell disorder was established.
Comparison of KIT mutational assay between blood and bone marrow examination showed that in 24 out of the 40 patients, the diagnosis of a primary mast cell disorder would have been overlooked when decision for bone marrow examination would have relied on the result of the assay in blood. Based on these results the authors conclude that in patients without typical mastocytosis skin lesions and a baseline serum tryptase < 30 ng/mL who experience anaphylaxis, determination of KIT D816V mutation in blood is of limited value in making a diagnosis of an underlying primary mast cell disorder.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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