Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

The global burden of chronic urticaria for the patient and society.

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.

The utility of monitoring trimellitic anhydride (TMA)-specific IgG to predict IgE-mediated sensitization in an immunosurveillance program.

BACKGROUND: Workplace exposure to trimellitic anhydride (TMA) can elicit TMA-specific IgE (sIgE), which may lead to occupational asthma (OA). An occupational immunosurveillance program (OISP) has been implemented to monitor TMA exposure and immunologic outcomes. The purpose of this study was to determine whether TMA-specific IgG (sIgG) responses can discriminate between TMA-exposed workers with and without sIgE responses. METHODS: Serum TMA-specific antibody (IgG, IgG4, and IgE) levels were estimated longitudinally (years 2006 to 2014) in TMA-exposed workers recruited in low, medium, and high exposure areas. sIgG and sIgE titers plotted against exposure duration were compared between workers with (a) sIgG only and (b) with sIgG who developed sIgE. RESULTS: Among 92 TMA-exposed workers continuously monitored for sIgG and sIgE, 38 developed sIgG; 11 developed a sIgE response 342.38 ± 186.03 days posthire and were removed from exposure. The average detection time of sIgG in removed workers (159 ± 92 days) was significantly shorter than for actively exposed workers with only sIgG (346 ± 187 days). Workers with earlier sIgG responses of higher titer (mean value 42.25 µg/mL) compared to delayed responders with lower sIgG titers (mean value 14.79 µg/mL) more frequently developed sIgE responses. Hierarchical clustering showed the initial magnitude and exposure time required for detectable sIgG production discriminated between workers with only sIgG from workers who subsequently produced sIgE. CONCLUSIONS: This study demonstrates the utility of longitudinally monitoring TMA-specific antibodies in an OISP as exposed workers with early sIgG responses and of higher magnitude are more likely to develop TMA sIgE sensitization.

Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.

Positive impact of omalizumab on angioedema and quality of life in patients with refractory chronic idiopathic/spontaneous urticaria: analyses according to the presence or absence of angioedema.

BACKGROUND: Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. OBJECTIVE: Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. METHODS: Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. RESULTS: Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. CONCLUSION: Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL.

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.

Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report.

Rhinitis is an umbrella term that encompasses many different subtypes, several of which still elude complete characterization. The concept of phenotyping, being the definition of disease subtypes on the basis of clinical presentation, has been well established in the last decade. Classification of rhinitis entities on the basis of phenotypes has facilitated their characterization and has helped practicing clinicians to efficiently approach rhinitis patients. Recently, the concept of endotypes, that is, the definition of disease subtypes on the basis of underlying pathophysiology, has emerged. Phenotypes/endotypes are dynamic, overlapping, and may evolve into one another, thus rendering clear-cut definitions difficult. Nevertheless, a phenotype-/endotype-based classification approach could lead toward the application of stratified and personalized medicine in the rhinitis field. In this PRACTALL document, rhinitis phenotypes and endotypes are described, and rhinitis diagnosis and management approaches focusing on those phenotypes/endotypes are presented and discussed. We emphasize the concept of control-based management, which transcends all rhinitis subtypes.

Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate.

BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived C1-inhibitor (pdC1-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1-INH has not been studied in patients with HAE. METHODS: This open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1-INH functional activity, C1-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough C1-INH functional activity. RESULTS: After SC CSL830 administration, a dose-dependent increase in trough functional C1-INH activity was observed. C1-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event. CONCLUSIONS: Subcutaneous volume-reduced CSL830 was well tolerated and led to a dose-dependent increase in physiologically relevant functional C1-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.

Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial.

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group.

Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.

Assessment of rebound and relapse following ecallantide treatment for acute attacks of hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable and recurring attacks of angioedema. This study assessed potential attack rebound and relapse following treatment with ecallantide, a plasma kallikrein inhibitor approved for HAE attack treatment. METHODS: Results were integrated from 2 double-blind, placebo-controlled studies of ecallantide treatment for HAE: EDEMA3-DB and EDEMA4. Symptoms were assessed by treatment outcome score (TOS), mean symptom complex severity (MSCS) score, and global response. Patients with improvement at 4 h post-dosing in all three measures followed by any sign of worsening at 24 h were considered to show potential rebound if worsening was beyond baseline or potential relapse if not beyond baseline. Likeliness of rebound or relapse was determined by the number of measures showing worsening and the magnitude of worsening. Patients receiving placebo who met the criteria for rebound/relapse were evaluated for descriptive comparison only. RESULTS: Significantly more ecallantide-treated patients (42 of 70) compared to placebo (26 of 71) showed improvement in three measures at 4 h and were thus eligible for rebound/relapse (P = 0.006). Of the nine ecallantide-treated patients with signs of worsening at 24 h, none were likely rebound, one was assessed as possible rebound, one as likely relapse, and two as possible relapse. No patient with potential rebound/relapse experienced new symptoms after dosing. Medical intervention was required in one ecallantide-treated patient. CONCLUSION: Ecallantide was efficacious for treating acute HAE attacks. Relapse was observed in a small proportion of patients, and there was little evidence of rebound.

Template requirements for in vivo replication of adenovirus DNA.

The adenovirus (Ad) DNA origin of replication was defined through an analysis of the DNA sequences necessary for the replication of plasmid DNAs with purified viral and cellular proteins. Results from several laboratories have shown that the origin consists of two functionally distinct domains: a 10-base-pair sequence present in the inverted terminal repetition (ITR) of all human serotypes and an adjacent sequence constituting the binding site for a cellular protein, nuclear factor I. To determine whether the same nucleotide sequences are necessary for origin function in vivo, we developed an assay for the replication of plasmid DNAs transfected into Ad5-infected cells. The assay is similar to that described by Hay et al. (J. Mol. Biol. 175:493-510, 1984). With this assay, plasmid DNA replication is dependent upon prior infection of cells with virus and only occurs with linear DNA molecules containing viral terminal sequences at each end. Replicated DNA is resistant to digestion with lambda-exonuclease, suggesting that a protein is covalently bound at both termini. A plasmid containing only the first 67 base pairs of the Ad2 ITR replicates as well as plasmids containing the entire ITR. Deletions or point mutations which reduce the binding of nuclear factor I to DNA in vitro reduce the efficiency of plasmid replication in vivo. A point mutation within the 10-base-pair conserved sequence has a similar effect upon replication. These results suggest that the two sequence domains of the Ad origin identified by in vitro studies are in fact important for viral DNA replication in infected cells. In addition, we found that two separate point mutations which lie outside these two sequence domains, and which have little or no effect upon DNA replication in vitro, also reduce the apparent efficiency of plasmid replication in vivo. Thus, there may be elements of the Ad DNA origin of replication which have not yet been identified by in vitro studies.

Polymorphisms in the human CC chemokine receptor-3 gene.

CC chemokine receptor (CCR)-3 is a seven-transmembrane-spanning G-protein-coupled receptor (GPCR) that is involved in the recruitment of inflammatory cells in allergic responses and acts as a co-receptor for entry of HIV into cells. Selected polymorphisms in GPCRs have been shown to have dramatic effects on the manifestation and/or susceptibility to a variety of diseases. In this report, we tested whether the human CCR-3 gene locus is genetically polymorphic. Using single-stranded conformational polymorphism analysis of genomic DNA, the CCR-3 gene is shown to contain four nucleotide polymorphisms with allele frequencies ranging from 0.005 to 0.13. Two polymorphisms encode for an amino acid change. One of these polymorphisms encodes for a non-conservative change of arginine to glutamine at position 275 of the third extracellular loop. Stratification of the DNA samples into a population with asthma suggested no change in this allele's frequency. Another polymorphism encodes for a leucine to proline substitution in the intracellular cytoplasmic tail of CCR-3. The most frequent polymorphism, T51C, occurs in 26% of individuals and encodes for a silent substitution. Thus, CCR-3 contains several genetic variations which may have consequences in disease processes that involve this receptor.

Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma.

Histamine is involved in the pathophysiology of asthma, and histamine N-methyltransferase (HNMT) plays the dominant role in histamine metabolism in human bronchial epithelium. Levels of HNMT activity in human tissues are controlled, in part, by inheritance. A common C314T polymorphism within the HNMT gene results in a Thr105Ile change in encoded amino acid, and the T314 allele is associated with decreased levels of both HNMT enzymatic activity and immunoreactive protein. Therefore, presence of the T314 allele would be expected to result in reduced histamine metabolism and increased bronchoconstriction. We characterized this common, functionally significant polymorphism in DNA samples from 237 randomly selected Caucasian control subjects and 192 samples from Caucasian asthmatic patients. Allele frequencies for the T314 HNMT allele were 0.08 in the control samples and 0.14 in samples from Caucasian asthmatic patients (odds ratio = 1.9, P < 0.01), indicating a significant increase in the frequency of subjects with low HNMT activity among asthmatics. The association between a common, functionally significant genetic polymorphism for HNMT and asthma suggests that individual variation in histamine metabolism might contribute to the pathophysiology and/or response to therapy of this disease.

Immune responses in farm workers after exposure to Bacillus thuringiensis pesticides.

Although health risks to pesticides containing Bacillus thuringiensis (Bt) have been minimal, the potential allergenicity of these organisms has not been evaluated. Therefore, a health survey was conducted in farm workers before and after exposure to Bt pesticides. Farm workers who picked vegetables that required Bt pesticide spraying were evaluated before the initial spraying operation (n = 48) and 1 and 4 months after (n = 32 and 20, respectively). Two groups of low- (n = 44) and medium- (n = 34) exposure workers not directly exposed to Bt spraying were also assessed. The investigation included questionnaires, nasal/mouth lavages, ventilatory function assessment, and skin tests to indigenous aeroallergens and to a variety of Bt spore and vegetative preparations. To authenticate exposure to the organism present in the commercial preparation, isolates from lavage specimens were tested for Bt genes by DNA-DNA hybridization. Humoral immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody responses to spore and vegetative Bt extracts were assayed. There was no evidence of occupationally related respiratory symptoms. Positive skin-prick tests to several spore extracts were seen chiefly in exposed workers. In particular, there was a significant (p < 0.05) increase in the number of positive skin tests to spore extracts 1 and 4 months after exposure to Bt spray. The number of positive skin test responses was also significantly higher in high (p < 0.05) than in low- or medium-exposure workers. The majority of nasal lavage cultures from exposed workers was positive for the commercial Bt organism, as demonstrated by specific molecular genetic probes. Specific IgE antibodies were present in more high-exposure workers (p < 0.05) than in the low and medium groups. Specific IgG antibodies occurred more in the high (p < 0.05) than in the low-exposure group. Specific IgG and IgE antibodies to vegetative organisms were present in all groups of workers. Exposure to Bt sprays may lead to allergic skin sensitization and induction of IgE and IgG antibodies, or both.

Potentially fatal asthma and syncope. A new variant of Munchausen's syndrome in sports medicine.

We report a case of Munchausen's syndrome in a 19-year-old female college athlete who presented with potentially fatal asthma and recurrent syncopal episodes. Failure to control her asthma with the appropriate medications and the lack of objective findings on both physical examination and diagnostic testing raised the possibility of factitious disease. Munchausen's syndrome, although not described with any frequency in asthmatic patients, should be considered in the differential diagnosis of those patients refractory to aggressive medical management.