sBT Levels Research Articles

Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal

BackgroundA score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking. ObjectiveThis study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment. MethodsWe included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: −1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points). ResultsThese variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %. ConclusionsFurther studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.

Elderly Patients and Insect Venom Allergy: Are the Clinical Pictures and Immunological Parameters of Venom Allergy Age-Dependent?

Insect venom is one of the most common triggers of anaphylaxis in the elderly population. Venom immunotherapy (VIT) remains the only treatment for Hymenoptera venom allergy (HVA). However, little is known about the differences in indication for VIT in the group of patients aged 60 years and older. The objective of this study was to assess the clinical and diagnostic differences of HVA in elderly patients. The study compared data from patients aged ≥ 60 (N = 132) to data from patients aged from 11 to 60 years (N = 750) in terms of HVA severity, comorbidities, and immunological parameters, namely, intradermal testing (IDT), specific IgE (sIgE) levels against extracts and major allergenic molecules, and serum tryptase level (sBT). The severity of systemic HVA (I-IV Müller scale) did not differ between adults and seniors. However, the severity of cardiovascular reactions (IV) increased with age, while the frequency of respiratory reactions (III) decreased. No differences were found in the immunological parameters of sensitization IDT, venom-specific IgE concentrations, or sIgE against Api m 1, 2, 4, 5, and 10 between patients below and above 60 or 65 years of age. Differences were noted for sIgE against Ves v1 and Ves v5; they were higher and lower, respectively, in seniors. In the seniors group, sBT levels were higher. Elevated tryptase levels, along with the aging process, can represent a risk factor within this age category. Nevertheless, advanced age does not influence the immunological parameters of immediate HVA reactions, nor does it impact the diagnosis of HVA.

Basal Tryptase High Levels Associated with a History of Arterial Hypertension and Hypercholesterolemia Represent Risk Factors for Severe Anaphylaxis in Hymenoptera Venom-Allergic Subjects over 50 Years Old

Introduction: Allergy to Hymenoptera venom (HV) may lead to life-threatening anaphylaxis. Some of the factors influencing the symptom’s severity are still undetermined. The aim of this study was to identify the clinical aspects associated with the most severe reactions in a population with HV allergy, by comparing clinical and immunochemical biomarkers between patients with previous local large reactions (LLRs) and systemic reactions (SRs). Methods: We selected adult patients with a history of HV allergy, with positive diagnostic tests and a correlation with one single Hymenoptera species. Age, gender, atopy, serum basal tryptase (sBT) value, total IgE, venom-specific IgE, history of hypertension, cardiovascular diseases, and hypercholesterolemia were compared between patients with previous LLRs and SRs. Results: 460 adult patients (381 SRs, 79 LLRs) were included. Age (p = 0.0097), male gender (p < 0.0001), arterial hypertension (p = 0.046), hypercholesterolemia (p = 0.009), and higher sBT levels (p = 0.0004) were significantly associated with severe reactions as independent variables. Moreover, considering the previous variables as risk factors, there was a significant and progressive increase in the odds of being Mueller III + IV as the number of positive variables increased. Patients with sBT ≥6.4 ng/mL adjusted for any of the positive variables had increased the risk of Mueller grade IV reaction (p < 0.0001). Conclusion: According to our results, older age, male gender, arterial hypertension, hypercholesterolemia, and increased levels of sBT ≥6.4 ng/mL are risk factors for severe anaphylaxis to HV in adults. Atopy and allergic asthma do not increase the risk of HV-induced SRs.

Factors predicting anaphylaxis in children with tree nut allergies.

Background: Tree nut (TN) allergies are the most common cause of fatal anaphylaxis and generally are ongoing food allergies throughout life. Objective: To investigate the predicting factors for TN anaphylaxis in children. Methods: Children with TN allergy were divided into anaphylactic and nonanaphylactic groups, those who had an anaphylactic reaction with at least one type of TN and those with any type of reaction other than anaphylaxis with TNs, respectively. Children with TN allergies were evaluated for the predictors of anaphylaxis by using multivariate logistic regression analysis. Results: A total of 184 children (ages 4.9 years; 3.2-6.9 years) with TN allergy were included in the study. Of these, 90 experienced an anaphylactic type of reaction on exposure to at least one type of TNs. Comparisons of the two groups showed that concomitant asthma, skin-prick test, specific immunoglobulin E, total immunoglobulin E, and serum basal tryptase (sBT) levels were significantly higher in the anaphylactic group compared with the nonanaphylactic group. In multivariate analysis, female gender (odds ratio [OR] 4.905 [95% confidence interval {CI}, 1.266-19.001], p = 0.021), sBT levels (OR 2.287 [95% CI, 1.431-3.654], p < 0.001), concomitant egg white allergy (OR 4.135 [95% CI, 1.016-16.481], p = 0.048), and concomitant asthma (OR 3.874 [95% CI, 1.109-13.526], p = 0.034) were risk factors for anaphylaxis. The optimal cutoff value for sBT was 2.06 ng/mL, with a sensitivity of 85.9% and a specificity of 69%, as well as an area under the curve 0.810 (95% CI, 0.717-0.903, p < 0.001). The sBT levels of 1.94 ng/mL and 5.30 ng/mL predicted clinical reactivity at 50% and 95% probabilities. Conclusion: Different aspects, including gender, higher mast cell load and/or activation, and a stronger atopic background (e.g., coexisting egg allergy, asthma), contributed to the development of anaphylactic reactions to TNs in children.

Serum Baseline Tryptase Level as a Marker for the Severity of Anaphylaxis

Background: Anaphylaxis is a severe and potentially fatal allergic disease or hypersensitivity reaction with variable clinical presentation. Biomarkers in anaphylaxis could be useful to improve diagnosis, to allow endotyping of patients, and to predict risk. Objective: To investigate the role of serum basal tryptase (sBT) levels in the management of patients with anaphylaxis. Methods: Patients with at least 1 episode of anaphylaxis were selected among those who attended the Allergy Clinics of the Clinical Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, upon evaluation by allergy/immunology specialists of our medical staff. Demographic and clinical data were obtained using a structured questionnaire. sBT levels were determined using the ImmunoCAP Tryptase immunoassay. Results: 57 patients (56.1% female) with a median age of 35 years (range 7–87 years) participated in the study. sBT levels ranged from 2.57 to 21.19 ng/mL (mean 5.17 ng/mL), with no significant differences in patients with anaphylaxis due to different triggers. Mean levels were 4.93; 5.2; 5.41, and 5.24 ng/mL for patients who had anaphylaxis due to Hymenoptera venom (n = 17), foods (n = 13), drugs (n = 13), and idiopathic disease (n = 14), respectively. Significantly higher sBT levels were observed in patients with severe anaphylaxis (grade IV) than in patients with mild-moderate disease (grades II/III) (mean levels 6.61 vs. 4.71 ng/mL, respectively). Conclusion: High sBT levels may help to identify patients at increased risk of more severe anaphylaxis, prompting physicians to initiate immediate therapy to avoid further acute episodes.

Factors that predict disease severity in atopic dermatitis: The role of serum basal tryptase

Increased numbers of mast cells that contain tryptase are found in lesional atopic dermatitis (AD) skin. The association of serum basal tryptase (sBT) with anaphylactic reactions and mast cell diseases has recently been shown in children with venom and food allergy. We aimed to identify the risk factors that predict the severity of AD and the association of sBT levels with AD and disease severity. AD diagnosis was made according to Hanifin and Rajka criteria. Disease severity was scored by the objective scoring atopic dermatitis (SCORAD) index. The sBT levels were measured. Skin-prick testing, total immunoglobulin E, eosinophil percentages and counts, and a questionnaire concerning the history of atopic diseases and the risk factors of AD were applied. The children, ages 0.5 to 3.0 years, with AD (n = 85) were analyzed in two groups according to the presence (AD+/atopy+ [n = 55]) or absence (AD+/atopy- [n = 30]) of skin-prick test positivity. The comparisons were made with an age- and sex-matched control group (n = 82). The median (interquartile range) sBT in the AD+/atopy+, AD+/atopy-, and control groups were 5.01 ng/mL (2.75-6.79 ng/mL), 3.02 ng/mL (1.67-4.44 ng/mL), and 2.63 ng/mL (1.31-4.49 ng/mL), respectively (p = 0.003). The median (interquartile range) sBT levels were higher in patients with moderate-severe objective SCORAD index scores compared with the those with mild disease (3.85 ng/mL [2.04-5.91 ng/mL] versus 2.80 ng/mL [1.83-3.48 ng/mL]; p = 0.038). Multivariate logistic regression analysis showed that an sBT level of ≥3.9 ng/mL (odds ratio 8.77 [95% confidence interval, 1.87-41.18]; p = 0.006) was independently associated with an increased risk of moderate-severe AD (objective SCORAD index). To our knowledge, this was the first study that indicated that sBT levels may be important in the AD disease process and associated with the disease severity and atopy.

Diagnostic Value of Serum Baseline Tryptase Levels in Childhood Asthma and Its Correlation With Disease Severity

S Gao, J Fan, Z Wang. Int Arch Allergy Immunol. 2016;171(3–4):194–202 To determine if the measurement of serum baseline tryptase (sBT) levels can accurately diagnose pediatric asthma and predict asthma severity. The study included 114 asthmatic children between the ages of 5 and 12 years. Within the cohort, 36 children had mild intermittent asthma, 38 had mild persistent asthma, and 40 had moderate to severe persistent asthma. In addition, 34 age-matched healthy children were included as controls. Serum baseline tryptase …

Diagnostic Value of Serum Baseline Tryptase Levels in Childhood Asthma and Its Correlation with Disease Severity

Background: The aim of this study was to explore whether serum baseline tryptase (sBT) levels might be a useful marker not only for the accurate diagnosis of childhood asthma, but also for the prediction of disease severity. Methods: A total of 114 asthmatic children were enrolled in this study, 36 of whom had mild intermittent asthma, 38 had mild persistent asthma, and 40 had moderate to severe persistent asthma. Additionally, 34 age-matched healthy children were enrolled as controls. The sBT levels of these populations were measured using a fluoroenzymeimmunoassay kit. The diagnostic performance of sBT levels and their correlation with asthma severity were systematically investigated using receiver operating characteristic (ROC) analysis and correlation analysis. Results: Children with mild and moderate to severe persistent asthma had significantly increased sBT levels as compared to those with mild intermittent asthma and healthy controls. ROC analysis further demonstrated that sBT levels not only appear to be highly sensitive and specific for distinguishing asthmatic children from healthy controls, but also show good accuracy for the differentiation of various asthmatic subgroups. Correlation analysis revealed that in all asthmatic subgroups sBT levels were significantly correlated with a variety of key markers that reflect the disease severity of asthma, including childhood asthma control test scores, serum IgE and interleukin-13 levels, blood eosinophil counts, and pulmonary test parameters. Conclusions: sBT levels may have a potential use in supporting a diagnosis of asthma in children and as a predictor of disease severity.

Basal serum tryptase is not a risk factor for immediate-type drug hypersensitivity during childhood.

High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs. Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) μg/l vs. 2.8 (1.6-4.3) μg/l vs. 2.6 (1.8-3.6) μg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) μg/l, mild anaphylaxis 3.0 (1.9-4.9) μg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) μg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.

Added sensitivity of component-resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis.

Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component-resolved approaches to diagnose this high-risk patient group. To address the component-resolved sIgE sensitization pattern and diagnostic sensitivity in hymenoptera venom-allergic patients with elevated sBT levels and/or mastocytosis, a panel of yellow jacket and honeybee venom allergens was applied on a widely used IgE immunoassay platform. Fifty-three patients with mastocytosis and/or elevated sBT tryptase level and systemic reactions to hymenoptera venoms were analyzed for their IgE reactivity to recombinant yellow jacket and honeybee venom allergens by Immulite3 g. sIgE reactivity to Ves v 1, Ves v 5, Api m 1 to Api m 4 and Api m 10 was found at a similar frequency in hymenoptera venom-allergic patients with and without elevated sBT levels and/or mastocytosis. However, the use of the recombinant allergens and a diagnostic cutoff of 0.1 kUA /L allowed the diagnosis of patients with otherwise undetectable IgE to venom extract. The diagnostic sensitivity of yellow jacket venom allergy using the combination of Ves v 1 and Ves v 5 was 100%. In high-risk patients with elevated sBT levels and/or mastocytosis, the use of molecular components and decreasing the threshold sIgE level to 0.1 kUA /L may be needed to avoid otherwise undetectable IgE to hymenoptera venom extracts in about 8% of such patients.

Increased Osteopontin Levels in Children Undergoing Venom Immunotherapy May Serve as a Marker of Clinical Efficacy

Background: Venom immunotherapy (VIT) has its effect by modulating various mediators resulting in immune tolerance. The aim of this study was to measure changes in plasma osteopontin (OPN) and serum basal tryptase (sBT) levels over the course of 1 year of VIT in children with venom allergy. Methods: Children who suffered from a large local reaction (LLR) or a systemic reaction (SR) after insect stings were included along with control subjects. Measurements were performed before the initiation of VIT and 6 and 12 months after it had been started. Results: A total of 58 children (24 with SR, 18 with LLR and 16 control subjects) with a median age of 9.5 years (range 6.7-12.8) were enrolled. The plasma OPN levels of patients with LLR [median 1,477 ng/ml, interquartile range (IQR) 1,123-1,772] were significantly higher than patients with SR (882 ng/ml, 579-1,086; p < 0.001) and healthy control subjects (1,015 ng/ml, 815-1,203; p = 0.002). A significant increase in plasma OPN levels in children was determined after the 1-year VIT. The sBT levels of children with SR (4.1 ng/ml, 3.6-5.8) were significantly higher than children with LLR (3.1 ng/ml, 2.5-4.0) and control subjects (3.0 ng/ml, 2.9-3.8; p = 0.001). There was no significant change in the sBT levels of the patients after the 1-year VIT. Conclusions: The results of our study showed higher baseline levels of OPN in children with LLR compared to control subjects and children with SR. In children with SR, OPN levels were increased after the 1-year VIT. Our results may suggest a possible association between OPN and successful VIT in children.

Serum basal tryptase levels in healthy children: correlation between age and gender.

Tryptase is used as a marker in many clinical conditions such as mast cell activation and systemic anaphylaxis. Normal levels of the serum basal tryptase (sBT) are determined in adulthood; however, data about nonallergic healthy children is limited. This study was designed to determine the normal sBT levels in healthy children. Total sBT levels were measured in 113 sera from healthy nonallergic children, for routine follow-up or diagnosis of illnesses that are not known to induce changes in serum tryptase levels. One hundred thirteen children aged 0.16-9.91 years (male/female subjects, 68/45 [60%/40%]) with a median (interquartile) age of 3.36 years (1.94-5.68 years) were evaluated. The sBT level was determined to be 3.30 ng/mL (2.38-4.36) median (interquartile) for the whole group. There was a tendency of higher sBT levels for boys than girls (3.49 [2.56-4.64 ng/mL] and 2.91 ng/mL [2.16-4.16 ng/mL], respectively); however, these findings were not significant (p = 0.12). The analysis of the whole group revealed that sBT levels were inversely related with age (r = -0.259; p = 0.006); and the decrease of sBT with age was more prominent in girls (r = -0.282; p = 0.02) than in boys. The highest sBT levels were found in the 0- to 1-year age group (all, 4.67 ng/mL [4.04-6.39 ng/mL]; boys, 5.34 ng/mL [4.04-6.39 ng/mL]; girls, 4.48 ng/mL [3.23-16.26 ng/mL]). The sBT levels in healthy children are similar to those in adults except in infancy. Interestingly, sBT levels tend to decrease slightly with age. Although they did not reach significance, sBT levels were found to be higher in boys compared with the girls.

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

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.

PD41 ‐ Risk factors for side effects during venom immunotherapy in children with hymenoptera venom allergy

Results We enrolled 45 children with a mean ((± standart deviation) age of 10.0 ± 3.4 years. VIT with wasp venom was initiated in 39 patients (87%) and with honeybee venom in 6 patients (13%). Seventeen patients (37.8%) had encountered lokal or systemic side effects during VIT. Side effects were present in 41 out of 1448 injections (2.8%). There was no significant difference at sBT levels of children with (4.3 μg/L [3.7-6.3]) or without (4.2 μg/L [3.1-4.7]) side effects (p=0.303). Multivariate logistic regression analysis revealed presence of asthma (odds ratio; [95% confidence interval] (14.2 [2.0–123.5]; p=0.008) as a significant risk factor for side effects during VIT in children. Conclusion Results of our study determined an association between accompanying asthma and side effects during VIT. Patients with asthma may need a particularly high degree of surveillance during VIT procedure.

Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy

A relationship between serum basal tryptase (sBT) levels, anaphylactic reactions, and clonal mast cell diseases was shown recently in adults with venom allergy, but the relationship between sBT levels and IgE-mediated food allergy and anaphylaxis is not known. In this study, children with food allergy (FA; n=167) were analyzed in two groups according to the presence (FA+/A+; n=79) or absence of anaphylaxis (FA+/A-; n=88) and were compared with a control group (n=113). Median sBT values in FA+/A+, FA+/A-, and control groups were 4.0ng/ml (2.8-5.8), 3.6 (2.3-4.5), and 3.3 (2.4-4.4), respectively (P=0.022). sBT measurements higher than the cutoff values of 5.7 and 14.5 were associated with 50% and 90% predicted probabilities, respectively, of moderate to severe anaphylaxis. Children with tree nuts/peanut allergies had significantly higher levels of sBT than children with milk and egg allergy (P=0.022). Results suggest that sBT levels may predict moderate to severe anaphylaxis in children with food allergy, which may follow a particular pattern according to the food allergy phenotype.

Serum Tryptase Monitoring in Indolent Systemic Mastocytosis: Association with Disease Features and Patient Outcome

BackgroundSerum baseline tryptase (sBT) is a minor diagnostic criterion for systemic mastocytosis (SM) of undetermined prognostic impact. We monitored sBT levels in indolent SM (ISM) patients and investigated its utility for predicting disease behaviour and outcome.MethodsIn total 74 adult ISM patients who were followed for ≥48 months and received no cytoreductive therapy were retrospectively studied. Patients were classified according to the pattern of evolution of sBT observed.ResultsOverall 16/74 (22%) cases had decreasing sBT levels, 48 (65%) patients showed increasing sBT levels and 10 (13%) patients showed a fluctuating pattern. Patients with significantly increasing sBT (sBT slope ≥0.15) after 48 months of follow-up showed a slightly greater rate of development of diffuse bone sclerosis (13% vs. 2%) and hepatomegaly plus splenomegaly (16% vs. 5%), as well as a significantly greater frequency of multilineage vs. mast cells (MC)-restricted KIT mutation (p = 0.01) together with a greater frequency of cases with progression of ISM to smouldering and aggressive SM (p = 0.03), and a shorter progression-free survival (p = 0.03).ConclusionsMonitoring of sBT in ISM patients is closely associated with poor prognosis disease features as well as with disease progression, pointing out the need for a closer follow-up in ISM patients with progressively increasing sBT values.

Importance of serum basal tryptase levels in children with insect venom allergy

The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 μg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 μg/l (2.5-4.0)] and healthy control subjects [2.9 μg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 μg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.

Validation of the REMA Score for Predicting Mast Cell Clonality and Systemic Mastocytosis in Patients with Systemic Mast Cell Activation Symptoms

Background: A variable percentage of patients with systemic mast cell (MC) activation symptoms meet criteria for systemic mastocytosis (SM). We prospectively evaluated the clinical utility of the REMA score versus serum baseline tryptase (sBt) levels for predicting MC clonality and SM in 158 patients with systemic MC activation symptoms in the absence of mastocytosis in the skin (MIS). Methods: World Health Organization criteria for SM were applied in all cases. MC clonality was defined as the presence of KIT-mutated MC or by a clonal HUMARA test. The REMA score consisted of the assignment of positive or negative points as follows: male (+1), female (–1), sBt <15 µg/l (–1) or >25 µg/l (+2), presence (–2) or absence (+1) of pruritus, hives or angioedema and presence (+3) of presyncope or syncope. Efficiency of the REMA score for predicting MC clonality and SM was assessed by receiver operating characteristic (ROC) curve analyses and compared to those obtained by means of sBt levels alone. Results: Molecular studies revealed the presence of clonal MC in 68/80 SM cases and in 11/78 patients who did not meet the criteria for SM. ROC curve analyses confirmed the greater sensitivity and a similar specificity of the REMA score versus sBt levels (84 vs. 59% and 74 vs. 70% for MC clonality and 87 vs. 62% and 73 vs. 71% for SM, respectively). Conclusions: Our results confirm the clinical utility of the REMA score to predict MC clonality and SM in patients suffering from systemic MC activation symptoms without MIS.

Oral ingestion of Streptococcus thermophilus does not affect mucositis severity or tumor progression in the tumor-bearing rat

Preventative or adjunctive agents for the amelioration of small intestinal chemotherapy-induced mucositis are not currently available for clinical use. We have previously demonstrated that oral ingestion of Streptococcus thermophilus (TH-4) partially attenuated chemotherapy-induced mucositis in the rat. Here we assess the effects of TH-4 on small intestinal damage and tumor progression in tumor-bearing rats with experimentally-induced mucositis. Female Dark Agouti tumor-bearing (mammary adenocarcinoma) rats (n = 36; 139 ± 1 g) had small intestinal damage induced via the administration of methotrexate (MTX). Rats were administered MTX; (1.5 mg/kg intramuscular) or saline at 0 and 24 h; with daily gavage administration of TH-4 (109 cfu/mL) or skim milk from -48 to +96 h post-MTX. Rats were allocated to groups (n=9): saline control, TH-4 control, MTX control or TH-4+MTX. The non-invasive 13C-sucrose breath test (SBT) was conducted prior to tumor inoculation, pre-MTX (-24 h) and prior to sacrifice (96 h) to monitor gut function. At sacrifice small intestinal segments were excised and assessed for sucrase and myeloperoxidase activity as well as histological damage. Irrespective of TH-4 treatment, MTX-treated rats had a significant decrease in bodyweight, SBT levels, sucrase and myeloperoxidase activity, and histological damage score (p < 0.05) compared to saline and TH-4 control rats. TH-4 treatment did not result in tumor progression (p > 0.05) but failed to alleviate mucositis indices. Although TH-4, at a dose of 109 cfu/mL, yielded neither protection nor amelioration of chemotherapy-induced mucositis, progression of mammary adenocarcinoma was unaffected.

Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels

Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects. The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens. Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations. Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders. The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.