Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges.

BACKGROUND: Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. OBJECTIVE: The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. METHODS: Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. RESULTS: Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). CONCLUSIONS: Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions.

Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.

BACKGROUND: Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts. METHODS: We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2-800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7-16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244. FINDINGS: The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45-78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0-9; p<0·001). 84% (95% CI 70-93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45-1400; p<0·001) or 25·5 times (range 1·82-280; p<0·001). After the second phase, 54% (95% CI 35-72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79-98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change -1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant). INTERPRETATION: OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. FUNDING: MRC-NIHR partnership.

Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register.

OBJECTIVE: The British Society for Rheumatology Biologics Register (BSRBR) has collected data on adverse events including pregnancies in patients with rheumatoid arthritis treated with anti-tumour necrosis factor (anti-TNF) therapy. The purpose of this report is to summarise the pregnancy outcomes in women treated with anti-TNF in the BSRBR. METHODS: Patients were categorised according to anti-TNF exposure as follows: (1) exposure to anti-TNF and to methotrexate (MTX) and/or leflunomide (LEF) at conception (n=21 pregnancies); (2) exposure to anti-TNF at conception (n=50); (3) exposure to anti-TNF prior to conception (n=59); (4) no exposure to anti-TNF (control group; n=10). RESULTS: Eighty-eight live births in a total of 130 pregnancies were reported in patients who received anti-TNF before or during pregnancy. The rate of spontaneous abortion was highest among patients exposed to anti-TNF at the time of conception (with MTX/LEF 33% and without MTX/LEF 24%). This compared with 17% spontaneous abortions in those with prior exposure to anti-TNF and 10% spontaneous abortions in the control group. Ten terminations were performed. CONCLUSION: Although the results to date have been promising, no firm conclusions can be drawn about the safety of anti-TNF during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception cannot yet be changed.

Vitamin D status and bone mass in UK South Asian women.

INTRODUCTION: Low vitamin D status is prevalent among South Asians living in the UK. The relationship, however, between serum 25-hydroxyvitamin D level (25OHD), serum parathyroid level (PTH) and bone mass in this group of women is unknown. The aim of this study was to determine the association between serum PTH, 25OHD and bone mass in a population based sample of young UK South Asian women. MATERIALS AND METHODS: Names of South Asian women aged 18 to 36 years of Pakistani origin living in the Greater Manchester area were identified from primary care registers using validated computer software. Subjects were invited to attend for (i) a blood test for assessment of serum calcium (Ca), albumin, PTH and 25OHD and (ii) for bone mineral density (BMD) scanning using the following: areal BMD at the hip (femoral neck, total hip) and lumbar spine using dual X-ray absorptiometry (Hologic QDR 4500), and volumetric BMD at the distal radius using peripheral quantitative computed tomography (Norland Stratec XCT 2000). Linear regression was used to determine the association between serum 25OHD, PTH and BMD at the different sites with adjustments made for age. RESULTS: In all, 78 women (mean age 29.2 years) were included in the analysis. Mean serum Ca level was 2.42 mmol/l, 25OHD, 7.9 ng/ml and PTH, 52.8 pg/ml. The majority of women (94%) had serum 25OHD levels 15 ng/ml, though rose progressively in subjects with levels below 10 ng/ml. Serum 25OHD was positively associated with BMD at the hip and spine while PTH was negatively associated with BMD at the hip and spine. When categorized by serum 25OHD level there was an increase in BMD at the total hip and distal radial site at least up to levels of 15 ng/ml. CONCLUSIONS: Despite widespread recognition, hypovitaminosis D is still prevalent among young UK South Asian women. In these women a decrease in serum 25OHD level

Differences in peak bone mass in women of European and South Asian origin can be explained by differences in body size.

There are few data concerning the occurrence of peak bone mass in women of South Asian origin. The aim of this study was to determine the level of peak bone mass in South Asian women in the UK and to determine whether any observed differences could be explained by differences in body size. Two groups of South Asian women, those of (1) Pakistani Muslim and (2) Gujarati Hindu origin, together with a European group aged 18 to 36 years, were recruited from primary-care population age-sex registers in the Greater Manchester area. They were invited to attend for a detailed interview-assisted lifestyle questionnaire and assessment of height and weight. Bone mass density (BMD) at the hip and lumbar spine was measured by dual energy X-ray absorptiometry (DEXA) scan (Hologic QDR 4500). Volumetric bone density was measured at the distal radius using pQCT (Norland Stratec XCT 2000). Linear regression was used to determine whether any observed differences in the level of bone mass could be explained by differences in body size. A total of 119 European women with a mean age of 30.4 years, 98 Pakistani Muslim women with a mean age of 29.2 years and 20 Gujarati Hindu women with a mean age of 29.2 years had bone density measurements performed. The Europeans were taller and heavier than either South Asian group. Peak BMD was greater among the European than the Pakistani women at all three measuring sites, with the Gujarati women having intermediate values at the hip and lumbar spine. Observed differences disappeared, however, after adjusting for height and weight. There were no differences in volumetric density at the lumbar spine or distal radius between the groups. In summary, there are differences in the level of bone mass between European and South Asian women, though these can be explained by differences in bone size, height or weight.