The presence of mast cell clonality in patients with unexplained anaphylaxis.

[cutaneous mastocytosis]

The mechanisms by which mast cells in patients with unexplained anaphylaxis (UEA ) are triggered remain elusive . Onset of episodes is unpredictable and often recurrent . The substantial overlap between the clinical manifestations of UEA and clonal mast cell disorders (CMD ) suggests an association between these rare disorders . The two forms of CMD characterized to date are systemic mastocytosis (SM ) and monoclonal mast cell activation syndrome (MMAS ).To examine the hypothesis that the pathogenesis of UEA reflects the presence of aberrant subpopulations of mast cells .Thirty (14 men , 16 women ) patients (≥ 18 years ) suffering from UEA and with no signs of cutaneous mastocytosis were recruited . Patients underwent an initial complete allergy work-up to confirm the diagnosis of UEA . Level of baseline serum tryptase (sBT ) and total IgE were determined . In addition , a bone marrow examination was performed on all 30 patients to investigate possible underlying CMD .Fourteen (47 %) of our cases (nine men , five women ) were diagnosed with CMD : 10 with SM and four with MMAS . Four of the 10 patients with SM had mast cell aggregates in their bone marrow . All patients with SM exhibited a sBT level > 11 .4 ng /mL , whereas this level was elevated in only two of those with MMAS and four with UAE but not diagnosed with CMD . Total IgE levels were lower in the group of patients with CMD (P < 0 .03 ).The pathogenic mechanism underlying UEA could be explained by the presence of immunophenotypically aberrant mast cells with clonal markers in 47 % of our subjects , indicating that clonal mast cell disorders are present in a substantial subset of these patients . Thus , the presence of CMD should be considered in patients with UEA if they have an elevated level of sBT (≥ 11 .4 ng /mL ) and cardiovascular symptoms such as syncope .