PURPOSE OF THE STUDY.
There is substantial overlap between the clinical manifestations of unexplained anaphylaxis (UEA) and clonal mast cell disorders (CMDs). The objective of the study was to examine the hypothesis that the pathogenesis of UEA reflects the presence of aberrant subpopulations of mast cells.
Thirty (14 men, 16 women) patients (aged ≥18 years) referred to the Mastocytosis Centre at the Karolinska University Hospital for suspicion of a clonal mast cell disorder, with history of ≥1 episodes of UEA and without signs of cutaneous mastocytosis, were recruited for study.
Initial retrospective data were collected through review of electronic records. UEA was diagnosed after exclusion of potential anaphylaxis triggers including foods, medications, exercise, insect bites, menstruation, or other precipitating factors. Baseline serum tryptase (sBT) and serum total immunoglobulin (Ig)E were measured for all patients. Morphology, histology, and immunochemistry of bone marrow mast cells were evaluated in all patients to investigate possible underlying CMD. Bone marrow flow cytometry and analysis of the D816V mutation were performed in 26 patients. Patients with no bone marrow pathology were considered to have idiopathic anaphylaxis (IA). After study enrollment, disease activity was evaluated prospectively through follow-up visits. Data on age, gender, atopic sensitization, atopic disease(s), clinical course, therapies, and duration of follow-up were collected for each patient.
Fourteen (47%) of the 30 studied patients were diagnosed with CMD: 10 with systemic mastocytosis (SM) and 4 with monoclonal mast cell activation syndrome (MMAS). Four of the 10 patients with SM had mast cell aggregates in their bone marrow. All patients with SM exhibited an elevated (>11.4 ng/mL) sBT level. Baseline serum tryptase was elevated in 2 patients with MMAS and 4 patients with UAE not diagnosed with CMD. Total IgE levels were significantly higher in patients with IA than in those with CMD, resulting in an inverse correlation between IgE levels and sBT levels. Syncope was the most common clinical manifestation in patients with both IA and CMD. Urticaria/angioedema occurred more often in patients with IA, whereas flushing was more prevalent in patients with CMD. There were no significant differences in respiratory or gastrointestinal symptoms between groups.
In 47% of studied subjects, episodes of UEA can be explained by the presence of an aberrant mast cell population expressing clonal markers that may contribute to a hyperreactive mast cell phenotype. The presence of CMD should be considered in patients with UEA with an elevated sBT (≥11.4 ng/mL), recurrent episodes of UEA, and particularly in men who experience cardiovascular symptoms.
The comprehensive data presented in the current study support the hypothesis that CMDs are present in a substantial subset of patients with UEA. Until the presence of CMD is established or refuted, UAE is therefore a more appropriate term than IA. Clinicians should consider bone marrow examination in patients with UAE. Although thought to be less common in children than adults, UAE has certainly been reported in the pediatric literature. Additional studies are needed to evaluate whether and how frequently episodes of UEA in the pediatric population can be attributed to CMD.
- Copyright © 2015 by the American Academy of Pediatrics