Outstanding Issues Need to Be Clarified

Implications for Interdisciplinary Practice

Letter to the Editor The Clinical Features of Hereditary Alpha-Tryptasemia by Prof. Dr. med. Dagmar von Bubnoff, Cand. med. Daniel Koch, Cand. med. Hannah Stocker, Prof. Dr. med. Ralf J. Ludwig, Friederike Wortmann, and Dr. med. Nikolas von Bubnoff in issue 8/2024

We welcome the fact that the authors presented hereditary alpha-tryptasemia (HAT) to a wider readership (1). We wish to share some critical aspects from our perspective. We think it was not unequivocally worked out that most patients with HAT have no symptoms (2, 3). For this reason we take a critical view of the statements in the article that deal with HAT symptoms. The authors present a range of symptoms that reflect multifunctional health problems and that by no means should always prompt further allergological or mast cell specific investigations. Table 2 of the article is misleading, in our opinion, as a control group is lacking—for example, patients with other allergic disorders (1). Furthermore, an additional control group would have made sense—for example, patients with psychosomatic symptoms with suspected mast cell activation syndrome or suspected histamine intolerance. Furthermore, the table does not include details on the age and sex of the study population nor any information on participants’ reason for presenting. As regards the diagnosis one might gain the impression that the HAT analysis but also the determination of the c-Kit-mutation represent measurement modes that are widely available. This is, however, not the case and may even lead to uncertainties for doctors and patients.

The BST measurement is tendentially slightly raised in patients with HAT, but the literature includes studies that showed that the baseline serum tryptase measurement is just as likely to be normal in spite of the presence of the mutation (4).

At this point in time, HAT is a genetic phenomenon whose clinical importance will have to be studied more thoroughly in the future. We advise against including this genetic trait into routine clinical practice before time: outstanding issues should be scientifically cleared up before making diagnostic recommendations.

DOI: 10.3238/arztebl.m2024.0124

Prof. Dr. med. Margitta Worm
Deutsche Gesellschaft für Allergologie und klinische Immunologie, Berlin
Allergologie und Immunologie, Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin Berlin, [e-mail]

Prof. Dr. med. Knut Brockow
Deutsche Gesellschaft für Allergologie und klinische Immunologie, Berlin
Klinik und Poliklinik für Dermatologie und Allergologie, Klinikum rechts der Isar, Technische Universität München

Prof. Dr. med. Karin Hartmann
Deutsche Gesellschaft für Allergologie und klinische Immunologie, Berlin
Klinik für Dermatologie, Universitätsspital Basel, Basel, Schweiz

Prof. Dr. med. Regina Treudler
Deutsche Gesellschaft für Allergologie und klinische Immunologie, Berlin
Institut für Allergieforschung, Charité-Universitätsmedizin Berlin, Berlin

Prof. Dr. med. Bettina Wedi
Deutsche Gesellschaft für Allergologie und klinische Immunologie, Berlin
Klinik für Dermatologie, Allergologie und Venerologie, Comprehensive Allergy Center, Medizinische Hochschule Hannover

Conflict of interest statement

MW is in receipt of consultancy fees. She received honoraria for lectures and travel expenses from Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Leo Pharma GmbH, AstraZeneca GmbH, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH, Lilly Deutschland GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, GlaxoSmithKline GmbH & Co. KG, and FomF GmbH.

KH received grants for lectures and presentations as well as travel expenses from Blueprint, Cogent, Novartis, and Thermo Fisher. She is a member of the advisory boards of Blueprint, Cogent, Menarini, Novartis, and Thermo Fisher.

RT is the head of the anaphylaxis working group in the German Society for Allergology and Clinical Immunology (Deutsche Gesellschaft für Allergologie und Klinische Immunologie, DGAKI). She is the deputy head of the dermatology section in the DGAKI/the allergology working group in the German Dermatological Society (Deutsche Dermatologische Gesellschaft, DDG). She sits on the board of the Network for Online Registration of Anaphylaxis (NORA).

The remaining authors declare that no conflict of interest exists.

References

1. von Bubnoff D, Koch D, Stocker H, Ludwig RJ, Wortmann F, von Bubnoff N: The clinical features of hereditary alpha-tryptasemia—implications for interdisciplinary practice. Dtsch Arztebl Int 2024; 121: 258–64

2. Greiner G, Sprinzl B, Górska A, et al.: Hereditary a tryptasemia is a valid genetic biomarker for severe mediator related symptoms in mastocytosis. Blood 2021; 137: 238–47

3. Chollet MB, Akin C: Hereditary alpha tryptasemia is not associated with specific clinical phenotypes. J Allergy Clin Immunol 2022; 149: 728–735.e2

4. Valent P, Hoermann G, Bonadonna P, et al.: The normal range of baseline tryptase should be 1 to 15 ng/mL and covers healthy individuals with HαT. J Allergy Clin Immunol Pract 2023; 11: 3010–20