Analysis of plasma histamine levels in patients with mast cell disorders

Abstract

The use of plasma histamine determinations as a screening tool to distinguish patients with recurrent unexplained anaphylaxis, flushing, or both from those with mastocytosis has never been evaluated. This retrospective study was designed to determine if plasma histamine levels can be used as a screening test. Values of plasma histamine levels, measured using a sensitive radioenzymatic assay, from 41 patients with mastocytosis, 26 patients with recurrent unexplained anaphylaxis, and 76 normal subjects were statistically analyzed to determine diagnostic usefulness and accuracy. Patients with mastocytosis were subdivided into four smaller groups on the basis of clinical and histopathologic findings: (1) isolated urticaria pigmentosa, (2) indolent systemic mastocytosis, (3) mastocytosis with dysmyelopoiesis, and (4) lymphadenopathic mastocytosis with eosinophilia. The distribution of plasma histamine values among patients with unexplained anaphylaxis strongly resembled that among the normal subjects (p greater than 0.50, Smirnov test), whereas patients with mastocytosis tended to show moderate to marked elevations above the upper limit of normal (617 pg/mL). The geometric mean plasma histamine levels in mastocytosis subgroups 2, 3, and 4 were found to be quite similar (1,085, 1,976, and 1,433 pg/mL; p greater than 0.50, F-test); moreover, each mean level was significantly greater than those of the normal subjects and of patients with unexplained anaphylaxis (p less than 0.01, Scheffé multiple comparison test). Analysis of the 27 sets of plasma histamine values collected on patients with indolent systemic mastocytosis revealed that the earliest value observed fell below 617 pg/mL in eight patients (30%). A similar analysis applied to the two earlier values indicated that both values would fall below 617 pg/mL in 9% of the patients. Data in four patients with mastocytosis demonstrated a diurnal variation in plasma histamine, with the highest values observed in the early morning (approximately 2:00 A.M.) and the lowest values in the afternoon (approximately 2:00 P.M.). We conclude that, on average, patients with mastocytosis have elevated plasma histamine levels, whereas patients with unexplained anaphylaxis have plasma histamine levels within the normal range during asymptomatic periods; that plasma histamine levels in patients with mastocytosis exhibit a diurnal variation; and that plasma histamine determinations alone are not useful to screen patients for mastocytosis.