[Show abstract][Hide abstract] ABSTRACT: This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.
Full-text · Article · Aug 2015 · Acta Dermato-Venereologica
[Show abstract][Hide abstract] ABSTRACT: IgE antibodies specific for the major birch pollen allergen frequently cross-react with Bet v 1 homologous food proteins, for example Cor a 1 in hazelnut and Mal d 1 in apple. Specific immunotherapy with birch pollen (BP-SIT) induces IgG4 antibodies that inhibit IgE binding to Bet v 1. However, information on cross-reactivity of BP-SIT-induced Bet v 1-specific IgG4 antibodies with food allergens is limited. In this study, we investigated the kinetics of production, cross-reactivity, and IgE-blocking activity of Bet v 1-specific IgG4 antibodies emerging during conventional BP-SIT and whether IgG4-epitopes overlapped with IgE epitopes.
IgE and IgG4 levels specific for Bet v 1, Mal d 1, and Cor a 1 were determined in 42 birch pollen-allergic patients before and during BP-SIT. Inhibition of IgE binding was studied by IgE-facilitated antigen-binding assays and basophil activation tests. Furthermore, inhibition of IgE-mediated activation of food allergen-reactive Bet v 1-specific T-cell lines was assessed. Competitive immunoscreening of phage-displayed peptides was applied to select mimotopes recognized by IgE and IgG4 antibodies, respectively. The resulting mimotopes were mapped on the surface of the 3D structure of the allergens using a computer-based algorithm.
BP-SIT significantly increased Bet v 1- and food allergen-reactive IgG4 antibodies. In parallel, allergen-specific IgE levels decreased significantly. Sera containing food allergen-reactive IgG4 antibodies inhibited IgE binding, basophil activation, and IgE-mediated food allergen-induced T-cell proliferation. Predicted IgE and IgG4 epitopes on all allergens showed high overlap.
Our results indicate that BP-SIT may induce Bet v 1-specific IgG4 antibodies that cross-react with related food allergens and inhibit IgE binding by epitope competition.
[Show abstract][Hide abstract] ABSTRACT: Background: A 29-year-old female presented with a first-time anaphylactic reaction.
History revealed the intake of “Schwarzbeernocken”, a Tyrolean speciality containing
blueberries, 1 hour prior to the onset of symptoms. We aimed to identify the culprit
allergen. Methods: Serum from a blueberry allergic donor was studied for IgE reactivity
to blueberry, mugwort (Artemisia vulgaris) and birch (Betula verrucosa) pollen extract
in IgE immunoblot experiments. IgE inhibition experiments and N-terminal sequencing
were performed to further identify the putative blueberry allergen. In addition, blueberry
extract was evaluated for cross-reactive allergens with sera from a Bet v 1- and a monosensitized
mugwort pollen-allergic patient.
Results: Blueberries contain a 9 kDa allergen which cross-reacts with Pru p 3, the nonspecific lipid transfer protein from peach, and shows sequence homology with cabbage lipid transfer protein. No allergen homologous to Bet v 1 could be identified in blueberries.
Conclusion: Blueberry lipid transfer protein represents a relevant food allergen which can cause severe anaphylactic reactions. However, blueberries apparently do not contain any Bet v 1-homologue. This protein family is found in many other foods and known as the most common cause of oral allergy syndrome in the Northern hemisphere.
[Show abstract][Hide abstract] ABSTRACT: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.
Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase.
In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models.
22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate.
It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.
[Show abstract][Hide abstract] ABSTRACT: Nowadays, clinical and evidence based guidelines are considered one of the major efforts to improve patient care in medical practices as well as hospital settings. In the literature, clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances", which promote both clinically effective standards and cost-effective care [1–4]. Despite controversial discussion about the clinical impact of guidelines [5, 6], they may provide workable recommendations that may thus be important for improving the individual patient's care [1, 4]. Adverse drug reactions (drug allergies, drug hypersensitivities) often represent a major hazard for the affected patient, and a definite diagnosis is important for further drug therapies in most cases. In this context, any diagnostic procedure must be preceded by an individual risk-benefit assessment. Drug provocation testing is regarded as the gold standard, but this kind of testing should be performed in accordance with established criteria and, in the vast majority of cases, in a hospital setting. In this paper we present a clinical guideline for drug provocation testing in Austria.
Full-text · Article · Oct 2011 · Wiener klinische Wochenschrift
[Show abstract][Hide abstract] ABSTRACT: Nowadays, clinical and evidence based guidelines are considered one of the major efforts to improve patient care in medical practices as well as hospital settings. In the literature, clinical guidelines have been defined as "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances", which promote both clinically effective standards and cost-effective care. Despite controversial discussion about the clinical impact of guidelines, they may provide workable recommendations that may thus be important for improving the individual patient's care. Adverse drug reactions (drug allergies, drug hypersensitivities) often represent a major hazard for the affected patient, and a definite diagnosis is important for further drug therapies in most cases. In this context, any diagnostic procedure must be preceded by an individual risk-benefit assessment. Drug provocation testing is regarded as the gold standard, but this kind of testing should be performed in accordance with established criteria and, in the vast majority of cases, in a hospital setting. In this paper we present a clinical guideline for drug provocation testing in Austria.
Full-text · Article · Sep 2011 · Wiener klinische Wochenschrift
[Show abstract][Hide abstract] ABSTRACT: Food allergens are frequent causes of anaphylaxis. In particular in children and adults they are frequent elicitors of severe allergic reactions, whereas in adults food allergens range among venom and drugs. Since 2006 severe allergic reactions from Germany, Austria and Switzerland are collected in the anaphylaxis registry. Currently 78 hospitals and private practises are connected. From July 2006 until February 2009 1,156 severe allergic reactions were registered. Among children and adolescents (n = 187, age range from 3 months to 17 years) food allergens were with 58% the most frequent elicitors. In the adult group (n = 968, 18 - 85 years) food allergens were on the third position (16.3%) following venom and drugs. In children legumes (31%) and in particular peanuts were frequently responsible food allergens, followed by tree nuts (25%) where hazelnut was the most frequent elicitor. In adults fruits (13.4%) induced most often severe food dependent anaphylaxis, but also animal products (12.2%); among these most frequently crustaceans and mussels. Cofactors were often suspected in food dependent anaphylaxis, namely in 39% of the adult group and in 14% of the children and adolescence group. In adults drugs (22%) and physical activity (10%) were reported as the most frequent cofactors, in children physical activity was suspected in 8.7% and drugs in 2.6%. Concomitant diseases like atopic dermatitis, allergic asthma or allergic rhinoconjunctivitis were reported in 78% of children and adolescents and in 67% of the adults. In conclusion foodinduced anaphylaxis, their cofactors and concomitant diseases in affected patients are age-dependent. The data offers to identify risk factors of anaphylaxis.
[Show abstract][Hide abstract] ABSTRACT: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms.
Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured.
Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).
Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.
No preview · Article · Jan 2011 · Wiener klinische Wochenschrift
[Show abstract][Hide abstract] ABSTRACT: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors.
Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT.
In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models.
Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy.
Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.
Full-text · Article · Jul 2010 · The Journal of allergy and clinical immunology
[Show abstract][Hide abstract] ABSTRACT: To investigate the efficacy of the endothelin receptor antagonist, bosentan, in patients with RP secondary to SSc without pre-existing digital ulcers.
Single-centre, randomized, prospective, double-blinded comparison of bosentan and placebo. Patients received either 62.5 mg bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 12 weeks or matching doses of placebo.
Of the 17 patients enrolled, 16 completed the study and 1 withdrew from the study due to the reversible development of peripheral oedema. Compared with placebo, bosentan did not improve the frequency, duration, pain or severity of RP attacks. However, in contrast to placebo, bosentan significantly improved the functional scores. With respect to baseline, the scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12 (P = 0.03) and 20 (P = 0.01), and the United Kingdom functional score changes at Weeks 8 (P = 0.038) and 16 (P = 0.039).
Bosentan is not effective in SSc-related RP without pre-existing digital ulcers, but it might benefit functional impairment in those patients.
European Union Drug Regulating Authorities Clinical Trials, https://eudract.emea.europa.eu, EudraCT-Nr 2004-002686-21.
Full-text · Article · Mar 2010 · Rheumatology (Oxford, England)
[Show abstract][Hide abstract] ABSTRACT: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined.
Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting.
In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models.
Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction.
In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.
Full-text · Article · Nov 2009 · The Journal of allergy and clinical immunology
[Show abstract][Hide abstract] ABSTRACT: Allergen-specific subcutaneous immunotherapy (SCIT) is an antigen-specific therapy of IgE-mediated allergies. In the present study, we analyze the epitope specificities of antibody responses induced by SCIT with allergen extracts from pollen of trees belonging to the order Fagales (birch, alder, hazel) adsorbed onto aluminum hydroxide.
The IgE, IgG1-4 and IgA responses to defined recombinant allergens (birch pollen: Bet v 1; alder pollen: Aln g 1; hazel pollen: Cor a 1; apple: Mal d 1) as well as to Bet v 1-derived recombinant fragments and synthetic peptides were analyzed in sera from patients who had undergone SCIT for different periods of time.
Long-term SCIT (>1 year; cumulative dose >1,000,000 SQ units) induced more pronounced IgG1, IgG2 and IgG4 responses to Bet v 1 and Bet v 1-related allergens according to the degree of sequence homology (Bet v 1>Aln g 1>Cor a 1>Mal d 1) than short-term SCIT (<1 year; cumulative dose <1,000,000 SQ units). In contrast to patients treated for <1 year, patients treated for >1 year mounted distinct IgG1, IgG2 and IgG4 responses against sequential Bet v 1 epitopes. No relevant allergen-specific IgA or IgG3 responses were induced by short- or long-term SCIT. Using a competitive ELISA assay, it could be shown that serum IgG from patients undergoing long-term SCIT inhibited IgE reactivity to Bet v 1 better than IgG from patients undergoing short-term SCIT.
SCIT with allergen extracts adsorbed onto aluminum hydroxide induces IgG responses against new epitopes that block IgE binding and cross-react with structurally related allergens depending, among other factors, on duration of treatment and cumulative injected dose.
No preview · Article · Sep 2009 · International Archives of Allergy and Immunology
[Show abstract][Hide abstract] ABSTRACT: Although exact numbers on the prevalence of histamine intolerance are lacking, it seems to be on a rise during the last years. The estimated prevalence in the population is 3%. This is particularly true for middle-aged female patients. A deficiency of 1 of the histamine metabolizing enzymes, diamine oxidase (DAO) has been postulated as the main causal factor. Recently, a commercial radioimmunoassay for determination of DAO activity has been launched. To evaluate the clinical impact of this assay for the diagnosis of hista- mine intolerance, we performed a prospective, multicentre study in 207 adult patients. In 77 patients, a diagnosis of histamine intolerance was made based on clinical criteria, in 67 a diagnosis "in question", and 61 healthy patients without anamnestic evidence for histamine intolerance served as a control. Interestingly, no correlation between diamine oxidase serum levels and clinical status could be found in any of the 3 groups. We, therefore, recommend further investigations, before determination of DAO serum activity should be used as a screening tool for the diagnosis of histamine intolerance.
[Show abstract][Hide abstract] ABSTRACT: The anaphylaxis register enables for the first time the registration of anaphylactic reactions in German- speaking countries. The reactions are reported by clinics and practices with allergological specification in Germany, Austria, and Switzerland. Data of a one-year pilot phase demonstrates that the most common triggers of anaphylaxis are foods in children and insect stings in adults. In case of emergency for only 11% of the reported reactions epinephrine was used. This data shows the necessity of registration and analysis of anaphylactic reactions to achieve an improved management of patients in the future.
[Show abstract][Hide abstract] ABSTRACT: Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.
Full-text · Article · Nov 2007 · The Journal of Immunology
[Show abstract][Hide abstract] ABSTRACT: Various studies have shown the clinical efficacy of sublingual immunotherapy in grass pollen-induced rhinoconjunctivitis. However, even short-term treatment with grass extracts might cause sensitizations to formerly unrecognized antigens.
To determine whether the antibody profiles are changing in patients receiving a defined grass pollen extract prior to and during the grass pollen season.
A randomized, double blind, placebo-controlled, multicenter phase I/I111 trial was started prior to the commencement of the grass pollen season. Patients with grass pollen allergy were randomly allocated to four groups, and received daily a standardized tablet at different doses. Treatment was started 8 weeks prior to the beginning of the pollen season and stopped at the end of the season. Blood samples were taken at the beginning of the study, at the beginning and the end of the pollen season, and one year after commencement of the study.
At the beginning of the study, all patients tested positive for the major grass pollen allergens, but negative to the minor antigens. In all patients, the degree of antibody reactivity rose considerably after starting active treatment and fell back to the initial values within one year. Immunoglobulin (Ig) E antibodies to the minor antigens remained negative, independent of treatment and seasonal exposure. In contrast to IgE, specific IgG antibodies to all allergens tested revealed no specific trend.
Immunotherapy with grass allergen tablets was accompanied by an increase in grass-specific IgE antibodies, which further increased during pollen exposure, followed by a post-treatment drop in patient- and disease-specific antibodies. During this short course of treatment, no patient developed any additional sensitizations.
Full-text · Article · Feb 2007 · Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología
[Show abstract][Hide abstract] ABSTRACT: The high prevalence of latex sensitization in patients with spina bifida (SB) has been attributed to repeated and early exposure to latex products. Other diseases such as gastroschisis/omphalocoele and post-haemorrhagic/congenital hydrocephalus are also associated with repeated and early latex exposure.
The aim of the study was to evaluate whether the high prevalence of latex sensitization in patients with SB is rather related to the underlying disease itself than to disease-associated known risk factors.
We compared children with SB (n=35), children with gastroschisis/omphalocoele (G/O, n=20) and children with post-haemorrhagic/congenital hydrocephalus (PH, n=45). All children with SB and PH had a ventriculo-peritoneal shunt since a very young age. Patients who underwent three or less surgical procedures matched in terms of age, number of operations, atopy and gender distribution, and were analysed for IgE sensitization rates to latex.
In the SB group, 16 of 35 patients (46%) showed elevated latex-specific IgE antibodies in contrast to one of 20 patients (5%) in the G/O group and four of 45 patients (8.9%) in the PH group (P<0.0005 and P<0.005, Fisher's exact test). Comparing matched control groups (<or=3 operations), the effects remained significant (P<0.05 and P<0.01).
This study suggests that the SB population bears a disease-associated propensity for latex sensitization. This effect cannot be explained exclusively by a higher number of operations and differences related to atopy, age or gender.