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Mastocytosis screening: use methylimidazole acetic acid in older overweight people

Published Online: August 13, 2014

Systemic mastocytosis (SM) is characterized by a clonal proliferation of abnormal mast cells in one or more organ systems, including bone marrow. Indolent systemic mastocytosis (ISM) is the most prevalent form. Flushing, (fatal) anaphylaxis, gastro-intestinal complaints and osteoporosis are the most frequently occurring symptoms. Recent evidence shows that at least 13 per 100,000 adults harbor ISM—more than previously thought.

The gold standard for diagnosing ISM is bone marrow examination. Currently, measurement of serum tryptase is the most commonly used test to determine the need for a bone marrow biopsy. However, tryptase levels are elevated by obesity, older age and a decrease in kidney function, which increases the risk on a negative outcome of bone marrow examination in ISM-suspect subjects. Measurement of the histamine metabolites methylhistamine (MH) and methylimidazole acetic acid (MIMA) in 24-hour urine, or in a urine sample in the fasting state, is another—though less commonly used—screening test. Although not commercially available at the moment, both metabolites can easily be determined in laboratories with gas chromatography and mass spectrometry facilities.

In a study recently published in The Journal of Allergy and Clinical Immunology, B. Vos and colleagues demonstrate that determining MIMA can reduce the risk of a negative bone marrow examination outcome. The authors present the results of a retrospective data analysis of all adults from the University Medical Center of Groningen, The Netherlands, in whom bone marrow investigations were performed because of high suspicion of ISM—comparing the diagnostic accuracy of tryptase, MH, and MIMA. To minimize the disturbing influence of exogenous histamine, MH and MIMA were measured in samples collected after an overnight fast, discarding the first voiding after wakening, and subjects were asked to refrain from histamine-rich foods and drinks during 24 hours before urine collection.

In total, 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). In the group of non-ISM subjects, tryptase was elevated by age and body weight, but these factors did not influence MH or MIMA levels. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA was comparable, but in subjects >50 years with a body mass index >25 kg/m2, the diagnostic accuracy of MIMA was substantially and significantly higher compared with tryptase. Therefore, the authors suggest determining MIMA as an indicator of the need for a bone marrow biopsy in overweight subjects of >50 years of age when ISM is suspected in order to avoid a negative outcome from bone marrow examination.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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