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W J Pichler

Publications and source records attributed to W J Pichler.

At least 19 recordsLinked to original sources
PubMed2006

T cell-mediated hypersensitivity to quinolones: mechanisms and cross-reactivity.

BACKGROUND: Quinolones are widely used, broad spectrum antibiotics that can induce immediate- and delayed-type hypersensitivity reactions, presumably either IgE or T cell mediated, in about 2-3% of treated patients. OBJECTIVE: To better understand how T cells interact with quinolones, we analysed six patients with delayed hypersensitivity reactions to ciprofloxacin (CPFX), norfloxacin (NRFX) or moxifloxacin (MXFX). METHODS: We confirmed the involvement of T cells in vivo by patch test and in vitro by means of the lymphocyte proliferation test (LTT). The nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones were investigated through the generation and analysis (flow cytometry and proliferation assays) of quinolone-specific T cell clones (TCC). RESULTS: The LTT confirmed the involvement of T cells because peripheral blood mononuclear cells (PBMC) mounted an enhanced in vitro proliferative response to CPFX and/or NRFX or MXFX in all patients. Patch tests were positive after 24 and 48 h in three out of the six patients. From two patients, CPFX- and MXFX-specific CD4(+)/CD8(+) T cell receptor (TCR) alphabeta(+) TCC were generated to investigate the nature of the drug-T cell interaction as well as the cross-reactivity with other quinolones. The use of eight different quinolones as antigens (Ag) revealed three patterns of cross-reactivity: clones exclusively reacting with the eliciting drug, clones with a limited cross-reactivity and clones showing a broad cross-reactivity. The TCC recognized quinolones directly without need of processing and without covalent association with the major histocompatability complex (MHC)-peptide complex, as glutaraldehyde-fixed Ag-presenting cells (APC) could present the drug and washing quinolone-pulsed APC removed the drug, abrogating the reactivity of quinolone-specific TCC. CONCLUSION: Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent.

Adult↗
PubMed2006

Adverse side-effects to biological agents.

Biological agents-like cytokines, monoclonal antibodies and fusion proteins are widely used in anti-inflammatory and tumour therapy. They are highly efficient in certain diseases, but can cause a great variety of adverse side-effects. Based on the peculiar features of biological agents a new classification of these adverse side-effects of biological agents is proposed - related but clearly distinct from the classification of side-effects observed with chemicals and drugs. This classification differentiates five distinct types, namely clinical reactions because of high cytokine levels (type alpha), hypersensitivity because of an immune reaction against the biological agent (beta), immune or cytokine imbalance syndromes (gamma), symptoms because of cross-reactivity (delta) and symptoms not directly affecting the immune system (epsilon). This classification could help to better deal with the clinical features of these side-effects, to identify possible individual and general risk factors and to direct research in this novel area of medicine.

Biological Products↗
PubMed2006

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

Administration, Oral↗
PubMed2006

The butterbur extract petasin has no effect on skin test reactivity induced by different stimuli: a randomized, double-blind crossover study using histamine, codeine, methacholine, and aeroallergen solutions.

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

Administration, Inhalation↗
PubMed2005

Reducing the risk of anaphylaxis during anaesthesia: guidelines for clinical practice.

These guidelines represent a consensus of experts in the field of immediate hypersensitivity reactions occurring during anaesthesia. They were based on international science, and implemented in France under the auspices of the French Society for Anaesthesia and Intensive Care (SFAR: Société Française d'Anesthésie et de Reanimation). Their aim was to provide the most valid, widely accepted, effective and easily teachable guidelines that current knowledge, research and experience can provide. This paper presents the main extracts of these recommendations with the most relevant clinical implications.

Anaphylaxis↗
PubMed2005

Multiple drug hypersensitivity--proof of multiple drug hypersensitivity by patch and lymphocyte transformation tests.

BACKGROUND: Multiple drug hypersensitivity (MDH) was first described in 1989 by Sullivan et al. as drug allergies to two or more chemically different drugs. So far, the diagnosis of MDH was associated almost exclusively with antibiotics and was defined based on history alone. AIMS OF THE STUDY: The objective of this study was to prove MDH by two independent tests, namely patch (PT) and lymphocyte transformation (LTT) tests. METHODS: Here we present 7 patients matching the definition of a MDH which were documented by positive LTT as well as PT to different drugs. RESULTS: Three of the 7 patients developed sensitization to the different compounds during the same treatment period and had one longer-lasting allergic reaction. For another 4 patients sensitization to the different drugs occurred at distinct time points. CONCLUSIONS: Our data support the concept of a MDH syndrome. The multiple sensitizations can be proven by skin and in vitro tests. We propose two subtypes of MDH: MDH, which develops against different drugs given simultaneously, and a second subtype, where the sensitizations develop sequentially. Antibiotics are often involved, but we also found sensitization to antiepileptics, hypnotics, antidepressants, local anesthetics, corticosteroids and other drug classes.

Adult↗
PubMed2004

[Allergy to house dust mites: allergy independent symptoms dominate].

A sensitisation to allergens has not always a clinical relevance. Therefore, the history has an uppermost importance for defining the relevance of a sensitisation. In contrast to the history in seasonal rhino-conjunctivitis, which causes typical complains in a restricted time period patients with house dust mite allergy seem to have less defined complaints. To define the most relevant symptoms of this frequent allergy, we evaluated 35 patients with clearly defined house dust mite allergy by a questionnaire and evaluated the same questionnaire also in a control group of 18 patients without sensitisation or asthma. The symptoms described in the patient group confirm that symptoms of house dust mite allergy are frequently not related to a direct allergen exposure. Some patients complained about itchy red eyes in the morning, but the majority of symptoms occurred independent from allergen exposure. These are blocked nose as well as exercise induced asthma. These symptoms are present all year around and are not only restricted to mite exposed areas. They are probably related to the underling eosinophilic inflammation. Thus exercise induced asthma and blocked nose are symptoms, which may indicate a mite allergy, particular in younger patients.

Adolescent↗
PubMed2004

Incidence of anaphylaxis with circulatory symptoms: a study over a 3-year period comprising 940,000 inhabitants of the Swiss Canton Bern.

BACKGROUND: Diagnosis of anaphylaxis is clinically based and usually straightforward. However, data on the epidemiology of anaphylaxis, particularly the most profound and life-threatening form such as anaphylactic shock are limited and thought to be under-reported. OBJECTIVE: The primary aim of this study was to investigate the incidence and the causes of severe anaphylaxis with circulatory signs in the Canton Bern, which comprises about 940 000 inhabitants or approximately one-seventh of the population of Switzerland. METHODS: During a 3-year period, 1 January 1996 to 31 December 1998, all medical records (7739 documents) from the two allergy clinics of the Canton Bern have been reviewed. In addition, all seven board-certified specialists of the Foederatio Medicorum Helveticorum (FMH) in Allergology and Clinical Immunology of this Canton as well as all 17 hospitals with emergency units of this area have been contacted for cases with an anaphylactic event not referred to the allergy clinics. RESULTS: Overall, 226 individuals, 106 females (47%) with a mean age of 41 years (range, 5-74 years) and 120 males (53%) with a mean age of 38 years (8 months-83 years) were diagnosed as having presented generalized, life-threatening anaphylaxis with circulatory symptoms. Altogether, these patients experienced 246 episodes of severe systemic reactions. In addition, death due to anaphylaxis occurred in three subjects. The annual incidence of anaphylaxis per 100 000 inhabitants per year ranged between 7.9 and 9.6 cases. Hymenoptera stings (58.8%), drugs (18.1%), and foods (10.1%) were the most commonly identified culprits for anaphylaxis. In 5.3% of all anaphylactic events, the cause could not be identified. CONCLUSION: The incidence rate of severe life-threatening anaphylaxis with circulatory signs in the Canton Bern, Switzerland, with 7.9-9.6 per 100 000 inhabitants per year is comparable to the findings of other epidemiological investigations. In most events, a causal agent or allergen could be identified by a careful allergological examination.

Adolescent↗
PubMed2004

Cytotoxic mechanisms in different forms of T-cell-mediated drug allergies.

BACKGROUND: Cytotoxic mechanisms are involved in different forms of drug induced exanthems. METHODS: Here we compare the killing pathways of CD4+, CD8+ and CD4/CD8+ T-cell lines (TCL) and clones derived from patients suffering from maculopapular, bullous and pustular drug eruptions. In vitro, perforin and Fas-mediated killing was analysed in cytotoxicity assays against autologous Epstein-Barr virus (EBV)-transformed B-cell lines, Fas-transfected mouse lymphoblasts and natural killer (NK)-target cells. In addition, affected skin lesions and the TCL and clones were stained for perforin and FasL-expression. RESULTS: We detected perforin and some FasL-mediated killing in all three types of exanthems. Some of the drug-specific T-cell clones analysed exerted mainly perforin-, other more FasL-mediated killing showing no strict relationship between their perforin- and Fas-mediated cytotoxic capacity. Using a cell culture method focusing on the generation of cytotoxic T cells, we detected drug-specific CD8+, TCRalphabeta+ T cells, which failed to proliferate to drug presentation by antigen presenting cells but killed in a drug dependent way. Interestingly, these cells had substantial natural killer-like T cell(s) like features as they were CD56+ and CD94+ and had the ability to kill the NK-sensitive cell line K562. CONCLUSION: Our data underline the important role of cytotoxic mechanisms in different forms of drug induced exanthems and suggest that even some T cells with NK-like characteristics may be involved in drug hypersensitivity.

Cell Line↗
PubMed2004

The lymphocyte transformation test in the diagnosis of drug hypersensitivity.

Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.

Drug Hypersensitivity↗
PubMed2004

Effect of tree pollen specific, subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut.

BACKGROUND: The efficacy of specific immunotherapy (SIT) in pollen allergy is well established. However, its effect on pollen associated food allergy particularly the oral allergy syndrome (OAS) is not definitely ascertained. OBJECTIVE: The purpose of this controlled prospective study was to investigate whether SIT with tree pollen, mainly birch, has an effect on OAS induced by apple or hazelnut in birch pollen-allergic individuals. METHODS: Twenty-seven birch pollen-allergic subjects with OAS induced by apple or hazelnut underwent open oral provocation tests (OPT) with increasing doses (1 to 128 g) of fresh apple or ground hazelnut 1 year apart. Fifteen of 27 subjects were treated with SIT and 12 were not. Skin-prick test with birch pollen, apple and hazelnut, and specific serum IgE, IgG and IgG4 to rBet v 1, apple and hazelnut were determined. RESULTS: Thirteen of 15 (87%) SIT-treated subjects could eat significantly (P <0.001) more of apple or hazelnut without any symptoms/signs. The average tolerated quantity increased from 12.6 to 32.6 g apple after 1 year in this group. In contrast, only one of 12 (8%) individuals without SIT was able to consume a higher amount without symptoms. On evaluating laboratory parameters, only IgG4 antibodies to rBet v 1 were found to be significantly (P <0.01) increased in the SIT-treated group after 1 year. CONCLUSIONS: The study shows that SIT with extracts containing birch pollen has a positive impact on OAS to apple or hazelnut in birch pollen-allergic individuals. In spite of this outcome, the amount of apple/hazelnut tolerated is still small. Thus, the effect of SIT on the patients' management of OAS remains limited.

Administration, Cutaneous↗
PubMed2004

Diagnosis of nonimmediate reactions to beta-lactam antibiotics.

Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common during beta-lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug-specific T-cell clones obtained from the circulating blood and the skin, suggest that a type-IV (cell-mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work-up, the patient's history is fundamental; patch testing is useful, together with delayed-reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard to in vitro tests, the lymphocyte transformation test may contribute to the identification of the responsible drug. Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions to beta-lactams.

Adult↗
PubMed2003

Hypersensitivity reactions to carbamazepine: characterization of the specificity, phenotype, and cytokine profile of drug-specific T cell clones.

Administration of carbamazepine (CBZ) causes hypersensitivity reactions clinically characterized by skin involvement, eosinophilia, and systemic symptoms. These reactions have an immune etiology; however, the role of T cells is not well defined. The aim of this study was to characterize the specificity, phenotype, and cytokine profile of CBZ-specific T cells derived from hypersensitive individuals. Proliferation of blood lymphocytes was measured using the lymphocyte transformation test. CBZ-specific T cell clones were generated by serial dilution and characterized in terms of their cluster of differentiation and T cell receptor V beta phenotype. Proliferation, cytotoxicity, and cytokine secretion were measured by [(3)H]thymidine incorporation, (51)Cr release, and enzyme-linked immunosorbent assay, respectively. HLA blocking antibodies were used to study the involvement of antigen-presenting cells. The specificity of the drug T cell receptor interaction was studied using CBZ metabolites and other structurally related compounds. Lymphocytes from hypersensitive patients (stimulation index: 32.1 +/- 24.2 [10 microg ml(-1)]) but not control patients (stimulation index: 1.2 +/- 0.4 [10 microg ml(-1)]) proliferated upon stimulation with CBZ. Of 44 CBZ-specific T cell clones generated, 10 were selected for further analysis. All 10 clones were either CD4+ or CD4+/CD8+, expressed the alpha beta T cell receptor, secreted IFN-gamma, and were cytotoxic. T-cell recognition of CBZ was dependent on the presence of HLA class II (DR/DQ)-matched antigen-presenting cells. The T cell receptor of certain clones could accommodate some CBZ metabolites, but no cross-reactivity was seen with other anticonvulsants or structural analogs. These studies characterize drug-specific T cells in CBZ-hypersensitive patients that are phenotypically different from T cells involved in other serious cutaneous adverse drug reactions.

Adult↗
PubMed2003

Scratch-patch and patch testing in drug allergy--an assessment of specificity.

BACKGROUND: Adverse drug reactions occur frequently in daily practice, but the identification of the eliciting drugs is difficult due to a lack of standardized procedures. The aim of this study was to evaluate and compare scratch-patch and patch tests prospectively with frequently used drugs in persons exposed or not exposed to the drug in order to define a nonirritating concentration. MATERIALS AND METHODS: Altogether, 23 different drugs, mainly antibiotics and analgesics, were evaluated. Any contraindications for patch tests were excluded by a questionnaire. Sixty-one healthy individuals were tested. They were divided into two groups: Group 1 consisted of individuals who hadn't been exposed to the drug; Group 2 was comprised of individuals who had been exposed to the drug, without side effects. Each individual was tested with 10-20 scratch-patch and patch tests. The tests were performed on the upper back. Freshly prepared drug solutions were applied, on one side after scarification of the epidermis, on the other side without. Scratch-patch tests were read at 24 and 48 h, patch tests after 48 and 72 h. In addition, we included 73 individuals with a drug allergy to illustrate that the chosen drug concentrations are able to elicit a positive reaction in truly sensitized individuals. RESULTS: A positive reaction in the non-exposed and nonallergic individuals was considered to be an irritant reaction (IR). In Group 1 (non-exposed individuals), 341 scratch-patch tests were performed, with 22 showing a reaction at the first reading, 3 at the second. Of the 341 patch tests performed in this group, 21 reactions were observed at the first reading, and 7 at the second. In Group 2 (exposed individuals), 141 scratch-patch tests were performed, with 5 IR at the first reading and 1 at the second. Of the 138 patch tests performed in this group, 6 individuals showed an IR at the first, 2 at the second reading. The majority of IR were four drugs, namely cefuroxim, acetylsalicylic acid, propyphenazone/drofenin-HCl, and celecoxib. Lowering the concentration did not reduce the unspecified irritant skin reaction, while a change of the solvent (petrolatum instead of PBS) did reduce the IR. CONCLUSIONS: Our data show concentrations of 23 drugs suitable for scratch-patch or patch tests, as they do not elicit IR. Fourteen of these test preparations elicited a positive reaction in truly sensitized individuals, demonstrating that the test preparation is suitable to identify sensitized persons. Scratch-patch tests are an interesting alternative to patch tests, as they do not elicit more IR than patch tests but can be evaluated earlier. Certain drugs solved in PBS are irritant over a wide dosage range and need to be applied in petrolatum.

Adult↗
PubMed2002

[Chronic idiopathic urticaria: effectiveness of fexofenadine. A double-blind, placebo controlled study with 21 patients].

Chronic urticaria defined as repeated or daily eruptions of wheals within a week over a period of at least 1 1/2 months is a frustrating problem not only for the patient but also for the physician. Since a cause will seldom be identified, therapy is symptomatic. In this study the effect of fexofenadine the active metabolite of terfenadine on pruritus, wheal formation and subjective feedbacks has been investigated in 21 patients with chronic urticaria. The study was double-blind, placebo-controlled designed. Following a 1-week washout period all study subjects received fexofenadine 180 mg OD for 3 weeks; thereafter the subjects were randomized for another 3 weeks in a placebo and fexofenadine arm. This study showed that fexofenadine had a beneficial effect on urticaria, particularly pruritus, and the patient-reported symptoms. Reports on side effects were non characteristic and not different between fexofenadine and placebo. Prolongation of QTc intervals or other cardiac side effects have not been observed. Fexofenadine 180 mg is a new antihistamine that is effective in the treatment of chronic urticaria and that has a profile of side effects similar to placebo.

Adult↗