Markedly Increased Diamine Oxidase During Acute Anaphylaxis Is Associated With an Underlying Clonal Mast Cell...

Diamine oxidase (DAO) degrades histamine, the key mediator in anaphylaxis, yet its relationship with clonal mast cell disorder (CMD) in the context of anaphylaxis is unclear. We evaluated whether DAO during anaphylaxis differs by CMD status.

We enrolled 35 emergency-department patients with acute anaphylaxis to drugs (7 patients), food (2 patients), or Hymenoptera venom (26 patients). Tryptase, DAO, and histamine degradation were measured during anaphylaxis and convalescence. CMD was defined by detecting KIT p.D816V in peripheral blood leukocytes using highly sensitive qPCR. Post-mortem DAO and tryptase were also compared in two fatal Hymenoptera venom-triggered anaphylaxis (HVA) cases with CMD versus 13 non-anaphylaxis controls.

KIT p.D816V was detected in 6 (17%); all had severe HVA and normal basal tryptase. During anaphylaxis, DAO increased markedly in CMD (median 1142%), but only modestly in KIT p.D816V-negative patients (median 20%; p < 0.0001), independent of trigger or severity. Acute DAO was ~5-fold higher in CMD (median 101 vs. 18 U/mL), while convalescent DAO was similar (both 14 U/mL). Despite markedly elevated DAO, we observed impaired histamine degradation in acute anaphylaxis plasma. Receiver-operating-characteristic analyses showed strong discrimination for CMD using acute DAO (AUC 0.92; cut-off 53 U/mL; sensitivity 83%; specificity 97%) and percentage increase from convalescence (AUC 0.97; cut-off 223%; sensitivity 83%; specificity 100%). Post-mortem DAO lacked specificity, whereas post-mortem tryptase supported the diagnosis of fatal anaphylaxis and CMD.

DAO concentrations rise markedly during anaphylaxis in CMD and may help identify individuals at the highest risk. Further studies should refine the diagnostic utility and elucidate the mechanisms by which DAO may amplify anaphylaxis in CMD.