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Pascal Demoly

Publications and source records attributed to Pascal Demoly.

At least 19 recordsLinked to original sources
PubMed2006

IFN-gamma-mediated inhibition of human IgE synthesis by IL-21 is associated with a polymorphism in the IL-21R gene.

IL-21 is a cytokine produced by CD4+ T cells that has been reported to regulate human, as well as, mouse T and NK cell function and to inhibit Ag-induced IgE production by mouse B cells. In the present study, we show that human rIL-21 strongly enhances IgE production by both CD19+ CD27- naive, and CD19+ CD27+ memory B cells, stimulated with anti-CD40 mAb and rIL-4 and that it promotes the proliferative responses of these cells. However, rIL-21 does not significantly affect anti-CD40 mAb and rIL-4-induced Cepsilon promoter activation in a gene reporter assay, nor germline Cepsilon mRNA expression in purified human spleen or peripheral blood B cells. In contrast, rIL-21 inhibits rIL-4-induced IgE production in cultures of PBMC or total splenocytes by an IFN-gamma-dependent mechanism. The presence of a polymorphism (T-83C), in donors heterozygous for this mutation was found to be associated not only with lower rIL-21-induced IFN-gamma production levels, but also with a lower sensitivity to the inhibitory effects of IL-21 on the production of IgE, compared with those in donors expressing the wild-type IL-21R. Taken together, these results show that IL-21 differentially regulates IL-4-induced human IgE production, via its growth- and differentiation-promoting capacities on isotype-, including IgE-, committed B cells, as well as via its ability to induce IFN-gamma production, most likely by T and NK cells, whereas the outcome of these IL-21-mediated effects is dependent on the presence of a polymorphism in the IL-21R.

B-Lymphocytes↗
PubMed2006

Treating allergic rhinitis in pregnancy.

Numerous pregnant women suffer from allergic rhinitis, and particular attention is required when prescribing drugs to these patients. In addition, physiologic changes associated with pregnancy could affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have been published. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one "safe" drug from each major class used to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (eg, beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few H1-antihistamines can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intranasal decongestants. Finally, pregnancy is not considered to be a contraindication for the continuation of immunotherapy.

Animals↗
PubMed2005

Comparison of pharmacovigilance algorithms in drug hypersensitivity reactions.

BACKGROUND: A firm diagnosis of drug hypersensitivity, because it may re-induce the reaction, is seldom confirmed. Causality assessment algorithms are therefore of interest. AIMS: The objective of this work was to compare three algorithms in the diagnosis of drug hypersensitivity. METHODS: Evaluation of 120 clinical histories of drug hypersensitivity was carried out: 60 involving beta-lactams (50%) and 60 involving non-steroidal anti-inflammatory drugs (50%). Each of these groups of patients underwent a standardised allergy diagnosis, which included a detailed anamnesis, skin tests and, often, provocation tests under strict hospital surveillance. Unaware of the final allergy diagnosis, scores were established for all of the cases and compared using algorithms suggested by Begaud and coworkers [2, 20], Jones [13] and Naranjo et al. [21]. RESULTS: Although the methods of Jones [13] and Naranjo et al. [21] were perfectly concordant (k=1), no concordance was noted using the Begaud and coworkers [2, 20] method. CONCLUSIONS: All three algorithms are dissimilar regarding the diagnosis of drug hypersensitivity.

Adult↗
PubMed2005

Accuracy of a pharmacovigilance algorithm in diagnosing drug hypersensitivity reactions.

BACKGROUND: This study was performed to evaluate the diagnostic accuracy of a pharmacovigilance algorithm in patients with 1 or more histories suggestive of drug hypersensitivity. METHODS: We performed a retrospective analysis of a clinic case series. We analyzed patients with suspected clinical reactions of drug hypersensitivity. Patients with severe skin reactions were excluded. Patients with history of drug allergy were subjected to additional testing to validate this history. Following a detailed clinical history, skin tests were performed. If skin tests were not available or validated, drug provocation tests were conducted. Assessment of causality was established by an investigator unaware of drug testing results using a pharmacovigilance algorithm that was then compared with the final diagnosis. RESULTS: A total of 677 consecutive patients with 1001 reactions were analyzed. No score could be given because of the absence of 1 of the criteria required for 204 reactions (20.4%). For 720 reactions (71.9%), a dubious causality assessment score was given. Drug hypersensitivity was confirmed by drug testing in 175 reactions (17.5%) and eliminated in 826 reactions (82.5%). Sensitivity of the algorithm was 10.3% and specificity was 76.9%. Although there were 1.7% false-positive scores, there were no false-negative scores. The logistic regression that was performed to look for independent clinical risk factors linked to the drug hypersensitivity diagnosis found 3 parameters: likely causality assessment score, drug reintroduction in clinical history, and delay between reaction and last drug intake of less than 1 hour. CONCLUSION: A pharmacovigilance algorithm is not accurate for the diagnosis of drug hypersensitivity reactions and cannot replace drug allergy testing.

Adolescent↗
PubMed2005

Anaphylactic reactions--value of skin and provocation tests.

Drug hypersensitivity reactions are a daily worry for the clinicians, in particular anaphylactic reactions. The tools allowing a definite diagnosis are few and poorly validated. They include a thorough clinical history, standardized skin tests, reliable biological tests, and sometimes drug provocation tests. These tools are currently being evaluated by the European Network of Drug Allergy, under the aegis of the EAACI drug hypersensitivity group of interest.

Anaphylaxis↗
PubMed2005

Update on beta-lactam allergy diagnosis.

Allergic reactions to penicillin and cephalosporin antibiotics are common. The mechanisms involved are heterogeneous and not yet completely understood. However, clinical and immunologic studies suggest that type I (IgE-mediated) and type IV (cell-mediated) pathogenic mechanisms are involved in most immediate and non-immediate reactions, respectively. The diagnostic procedure has recently been standardized under the aegis of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interest group on drug hypersensitivity. In this review, we describe the general guidelines for evaluating subjects in whom there is suspicion of allergic reactions to beta-lactams.

Anti-Bacterial Agents↗
PubMed2005

Epidemiology of hypersensitivity drug reactions.

PURPOSE OF REVIEW: Hypersensitivity drug reactions are but one of the many different types of adverse drug reactions. They may be potentially life-threatening, prolong hospitalization, affect drug prescribing patterns of physicians and result in socioeconomic costs. This review summarizes current knowledge on the incidence, prevalence, mortality and risk factors for these reactions in different populations. RECENT FINDINGS: Hypersensitivity reactions represent about one third of all adverse drug reactions. Adverse drug reactions affect 10-20% of hospitalized patients and more than 7% of the general population. Severe reactions including anaphylaxis, drug hypersensitivity syndromes, Stevens Johnson syndrome and toxic epidermal necrolysis are also associated with significant morbidity and mortality. Although several risk factors have been identified, their clinical importance has not been fully understood. Future progress in immunogenetics and pharmacogenetics may help identify populations at risk for specific types of reactions. SUMMARY: Well designed epidemiological studies on hypersensitivity drug reactions are lacking as most studies have been on adverse drug reactions. Such studies will be helpful in identifying patients at risk of developing such reactions, in particular severe reactions, and implementing early preventive measures.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

[Nasal allergy and asthma: one or two diseases?].

Epidemiological studies have shown that rhinitis and asthma are associated. At least four out of five asthmatics suffer from rhinitis and one out of four rhinitic subjects develop asthma. Recent progress in cellular and molecular biology confirms that the same inflammatory cells and similar mechanisms participate in the pathophysiology of the two diseases. Histological findings show that although nasal inflammation resembles bronchial inflammation, specific remodelling features that are present in asthma are lacking in rhinitis. This may be due to the different embryologic origin of the two organs. These similarities explain certain clinical interactions and are the basis of the ARIA (Allergic Rhinitis and its Impact on Asthma)--WHO guidelines recommending that symptoms of rhinitis be sought in asthmatic subjects and symptoms of asthma in rhinitic subjects.

Anti-Allergic Agents↗
PubMed2004

Confirmation of the diagnosis of natural rubber latex allergy by the Basotest method.

BACKGROUND: The flow cytometry CD63-based basophil activation test (Basotest has already been validated for the diagnosis of immediate-type allergy such as venom, house dust mite or cypress pollen allergies. The aim of this study was to evaluate the performance (specificity and sensitivity) of Basotest in the diagnosis of natural rubber latex allergy. METHODS: We included 46 latex allergic patients (clinical symptoms of latex allergy, positive latex skin prick tests and/or latex specific IgE) and 33 control subjects and performed Basotest on all subjects. RESULTS: The sensitivity and specificity of Basotest were 84.8 and 87.9%, respectively, when we considered the theoretic cut-off at 15% of CD63-positive cells. Using ROC curves, the optimal cut-off was evaluated at 22%, for which sensitivity and specificity were 79.3 and 96.7%, respectively. CONCLUSION: The Basotest is a reliable test in addition to clinical history and tests already validated (such as skin prick tests and specific IgE) to confirm the diagnosis of natural rubber latex allergy.

Adult↗
PubMed2004

Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction.

BACKGROUND: Drug hypersensitivity reactions are common and can be life-threatening. Confirmation of the diagnosis should be rigorous and based on clinical history and a physical examination, possibly followed by skin tests and drug provocation tests. OBJECTIVE: To describe the outcome of drug provocation tests in evaluating patients with histories suggesting drug allergy. DESIGN: Retrospective analysis of clinic case series. SETTING: The department for drug allergy at a university hospital. PATIENTS: 898 consecutive patients with suspected immediate drug allergy referred to the clinic between September 1996 and August 2001. Patients with severe skin reactions and those with positive results on skin tests for beta-lactams were excluded. INTERVENTION: Single-blinded administration of increasing doses of the suspected drug, up to the usual daily dose, under strict hospital surveillance. RESULTS: 1372 drug provocation tests were performed using various drugs, including beta-lactams (30.3%), aspirin (14.5%), other nonsteroidal anti-inflammatory drugs (11.7%), paracetamol (8.9%), macrolides (7.4%), and quinolones (2.4%). There were 241 (17.6%) positive drug provocation test results. Drug provocation reproduced the same symptoms, albeit milder and of a shorter duration, in the following patients: 13 (5.4%) with a history of anaphylactic shock, 17 (7.0%) with a history of anaphylaxis without shock, 10 (4.1%) with a history of laryngeal edema, 19 (7.9%) with a history of bronchospasm, 160 (66.4%) with a history of urticaria, and 22 (9.1%) with a history of maculopapular eruption. All adverse reactions were completely reversed by prednisolone, H(1)-antihistamines, and epinephrine as needed. LIMITATIONS: Falsely negative results on drug provocation tests may have occurred because of loss of sensitization, rare cofactors not included in the diagnostic procedure, and tolerance induction during provocation. CONCLUSIONS: Drug provocation tests in individuals with suspected drug allergy performed in carefully controlled settings can confirm drug hypersensitivity.

Adolescent↗
PubMed2004

[Hypersensitivity to insulin].

GREAT PROGRESS: The use of purified insulins obtained by genetics has dramatically lowered the frequency of insulin hypersensitivity. This frequency has decreased from 1 to 55% with non purified insulins and to 0.1 to 2% with newly generated insulins. DIAGNOSTIC MEASURES: The anamnesis should clarify the allergic background of the patient, previous treatments with insulin, their duration of use and any eventual reactions. Examination of the lesions must assess the type (papule, eczema, purpura), the localization and extent. The second step skin tests, when negative, eliminate the responsibility of the insulin tested. They also participate in the search for cross-reactions between the various insulines. Their positivity is not always synonymous of hypersensitivity. STRATEGY TO BE APPLIED: In the case of localised cutaneous reactions, spontaneous regression is generally observed, the association of an oral antihistamine and/or the fractioning of the dose and its injection on several different sites often leads to the disappearance of these reactions. If the reactions persist, topical or oral corticosteroids of short duration can be useful. Finally, the switch to another insulin or even a tolerance induction with the least skin test reactive insulin as a last resource. The most severe systemic reactions are an indication for tolerance induction.

Animals↗
PubMed2004

Classification and epidemiology of hypersensitivity drug reactions.

Nonimmune hypersensitivity reactions are unpredictable adverse drug reactions that are clinically similar to allergic reactions for which no drug-specific antibodies or T lymphocytes are identified. Few tools allow a definite diagnosis, and most of the available ones need to be validated. True epidemiologic data are limited, and most of the available information on the incidence, mortality, and socioeconomic impact should be discussed with caution.

Drug Hypersensitivity↗
PubMed2003

[ERAP, a pharmaco-epidemiologic survey on perennial allergic rhinitis in every day medical practice in France].

OBJECTIVE: In order to gain knowledge on the management of perennial allergic rhinitis by the practitioners in France, a survey (Enquête épidémiologique sur la rhinite allergique per-annuelle en pratique quotidienne--ERAP) was developed. METHODS: In the year 2000, 1 346 doctors (including 689 general practitioners) enrolled 3 507 patients consulting for a fall/winter exacerbation of allergic rhinitis. Both doctors and patients filled out a specific questionnaire on the care networks, clinical characteristics, diagnostic modalities and treatment of allergic rhinitis, together with the patients'personal feelings. RESULTS: The patients were bothered on average 6 days a week (5.8 +/- 1.8 days) and 3 months a year (9.2 +/- 7.7 consecutive weeks) by symptoms largely exceeding the ENT area, with frequent ocular symptoms (36.7%), cough (31.9%), sleep disturbances (35.2%) or dyspnea (9.4%). In 70.3% of the patients rhinitis affected their professional life and 90.9% their daily life. The nose was examined in 63.3% of patients and a search for asthma was conducted in 39.3%. In 45.3% subsequent skin prick tests were scheduled and in 53.5% specific IgE measurements and in 33.5% subsequent specialized consultation. Prescribed drugs were mainly oral antihistamines (75.3%) and local glucocorticosteroids (48.5%). Prescriptions were written for a mean duration of 8 weeks. 78.6% considered that the information that they had received was adequate and easy to understand, but 61.1% of patients would have liked to have received more advice. Furthermore, only 48.7% followed their doctor's prescription scrupulously, and 34.3% adapted the prescription. CONCLUSION: Perennial allergic rhinitis indeed impairs quality of life and its management in France is now better understood.

Administration, Topical↗