Elevated Tryptase in EoE Is an Independent Phenomenon Associated with Extra-Esophageal Symptoms.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease characterized histologically by > 15 eosinophils per high-power field (eos/hpf). Esophageal mucosal mast cells have been implicated in EoE pathogenesis. The association of atopy with EoE has been established but has not been correlated with levels of serum tryptase. The lack of concurrent atopy in some patients suggests the possibility that atopy may either be the related subtype of EoE or may be a sign of comorbidities. No study has looked at whether patients present with different phenotypes/comorbid disease when they have evidence of elevated serum tryptase. We hypothesized that these patients differ with respect to presentation and comorbidities with more refractory GI disease. AIMS: To examine whether elevations of serum tryptase associate with different, more severe clinical presentations in EoE patients which may be explained via mast cell activation. MATERIALS AND METHODS: Retrospective chart review identified 72 patients with EoE with results for serum tryptase between 2015 and 2016. Patients were classified as TryptaseHI (tryptase > 10.9 µg/l) and TryptaseLO (< 10.9 µg/l). Clinical characteristics and treatment response were compared using univariate analysis and multivariate regression between the groups. RESULTS: Out of 72 patients, 12 were tested as TryptaseHI (16.7%, 95% CI 8.1-25.3%). TryptaseHI was associated frequently with asthma (P = 0.0003), urticaria (P = 0.002), arthralgia (P = 0.005), sinusitis (P = 0.03), nausea/vomiting (P = 0.046), and eosinophilic gastrointestinal disease (P = 0.001). Asthma and arthralgia were found to be significantly associated with TryptaseHI (P = 0.0013, P = 0.0098, respectively). Mucosal eosinophil counts and tryptase levels were not correlated (R2 0.095, P = 0.77). Tryptase did not resolve with resolution of esophageal eosinophilia. CONCLUSIONS: We found that EoE patients with elevated tryptase levels more commonly presented with asthma, urticaria, arthralgia, nausea/vomiting, sinusitis, and more distal eosinophilia. This indicates that atopy in EoE patients warrants further exploration. The lack of correlation between histologic remission and reduction of serum tryptase levels post-treatment suggests that mast cell activation may be an independent, yet associated disease. More study into this unique association is warranted.

Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women.