SIAIP position paper: provocation challenge to antibiotics and non-steroidal anti-inflammatory drugs in children

Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents

What did the doctor say? Patients' comprehension of allergy consultations in a French university hospital

International audienceBackground – While health care specialists have a foundational allergy related knowledge, patients only have some socially and culturally derived notions of health and illness. Hence, sometimes, during the medical consultation, it may be difficult to find a common level of discourse between patients and health care providers. (1) A misunderstanding may be an obstacle to make informed decisions regarding care and adhering to treatment, and potentially breakdown the physician-patient relation. (2) The aim of the present monocentric study was to examine the comprehension of the physician’s discourse by patients, after an allergy consultation. Methods – We conducted a voluntary survey among all consecutive French speaking patients consulting in an Allergy Department of a French university hospital from December 2018 to April 2019. Collected data included patients’ age, gender, education, type of allergy they were suffering from and consulting for (i.e., food, respiratory, drug, hymenoptera, skin, other), and possible sources of information regarding their allergic condition. After the medical consultation, each participant rated the degree of comprehension of different aspects of their visit and physicians’ attitude towards patients. We included open questions to receive comments and suggestions concerning the physician-patient relation. A multivariate logistic regression and content analysis were used to analyze provided information. Results – A total of 200 questionnaires were collected. 31% of patients had a low comprehension of the allergists’ discourse while 69% had a good understanding. Variables influencing it included patients’ level of education, duration of allergic symptoms and of following-up, number of associated allergies, type of allergies from which patients suffer, as well as ways to inform yourself about allergies. Variables that don’t influence the global comprehension were the patient’s age, gender and the physician’s attitude toward the patient. Conclusion – The present pilot study shows that allergists-patients communication should still be optimized. Further investigations are ongoing to verify differences in knowledge representation of allergy related concepts between physicians and allergic patient

What did the doctor say? Patients' comprehension of allergy consultations in a French university hospital

International audienceBackground – While health care specialists have a foundational allergy related knowledge, patients only have some socially and culturally derived notions of health and illness. Hence, sometimes, during the medical consultation, it may be difficult to find a common level of discourse between patients and health care providers. (1) A misunderstanding may be an obstacle to make informed decisions regarding care and adhering to treatment, and potentially breakdown the physician-patient relation. (2) The aim of the present monocentric study was to examine the comprehension of the physician’s discourse by patients, after an allergy consultation. Methods – We conducted a voluntary survey among all consecutive French speaking patients consulting in an Allergy Department of a French university hospital from December 2018 to April 2019. Collected data included patients’ age, gender, education, type of allergy they were suffering from and consulting for (i.e., food, respiratory, drug, hymenoptera, skin, other), and possible sources of information regarding their allergic condition. After the medical consultation, each participant rated the degree of comprehension of different aspects of their visit and physicians’ attitude towards patients. We included open questions to receive comments and suggestions concerning the physician-patient relation. A multivariate logistic regression and content analysis were used to analyze provided information. Results – A total of 200 questionnaires were collected. 31% of patients had a low comprehension of the allergists’ discourse while 69% had a good understanding. Variables influencing it included patients’ level of education, duration of allergic symptoms and of following-up, number of associated allergies, type of allergies from which patients suffer, as well as ways to inform yourself about allergies. Variables that don’t influence the global comprehension were the patient’s age, gender and the physician’s attitude toward the patient. Conclusion – The present pilot study shows that allergists-patients communication should still be optimized. Further investigations are ongoing to verify differences in knowledge representation of allergy related concepts between physicians and allergic patient

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy

International audienceLike in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians’ practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT

Response to commentary by Drs. Poncet and Sénéchal

International audienceWe thank Drs. Poncet and Sénéchal for their interest and critical reading of our paper. We are well aware of their pioneering work on molecular aspects of cypress pollinosis. However, the focus of our paper was rather on epidemiological, clinical and diagnostic features of peach allergy and not towards molecular pollen determinants. We hereby provide answers to direct questions and notions made by Drs. Poncet and Sénéchal. 1. In regard to literature references, we cited those we found relevant for the scope and purpose of the paper and none of the three reviewers suggested citation of additional publications. To our knowledge, the paper by Hugues et al (2006) was indeed the first to report an association between cypress and peach allergy, and it is cited as reference 39 in our paper 1. However, contrary to the assertion by Poncet and Sénéchal, the authors of that paper did not identify a pollen homologue of Pru p 7, which was first reported as an allergen by Tuppo et al in 2013 2 but instead made the notion "Because both allergenic extracts include a 45 kDa-allergen, it should be the shared allergen." Cup a 1, a major allergen in cypress pollen, has a molecular weight of 43 kDa. Experimental data from the Poncet team are currently available for BP14 and snakin-1, neither of which have been officially recognized and named as allergens by the WHO/IUIS Allergen Nomenclature SubCommittee (www.aller gen.org, accessed May 4 2019). Other papers cited by Poncet et al are either replies or reviews. We prefer citation of original, peer-reviewed research. However, the review on cypress pollinosis is also cited in our paper as ref 41. 3 2. This case report of one patient with discordant FABER IgE and BAT results would have brought little if any further information to the reader. In our hands, the FABER test displays highly sensitive detection of IgE to Pru p 7. 3. As noted above, BP14 has not been officially recognized as an allergen. 4. Snakin-1 is out of the scope of our publication. 5. Recombinant Pru p 7 was biochemically and immunologically characterized as described in section 2.6 4 and additionally by circular dichroism spectroscopy, but, given the focus of the paper, we did not consider it relevant to show and elaborate on such data, nor was there space available. It was also not suggested by any of the three reviewers. However, the BAT results shown in Table S3 demonstrate a similar functional potency of natural and recombinant Pru p 7 which suggests an authentic folding of the recombinant protein. o We do not agree that assessment of anti-microbial activity of recombinant Pru p 7 and several of the other specifics mentioned would be necessary to validate the association between cypress pollen allergy and peach allergy as suggested (but not yet done in their publications) by Drs Poncet and Sénéchal. o The cypress species used was Cupressus sempervirens. o The pollen was extracted and clarified by standard methods. We did not consider total protein concentration to be informative in relation to the purpose of the experiment but chose instead to determine the potency of the extract by titrated inhibition of IgE binding to Pru p 7, as described in section 3.5. That potency determination guided the choice of inhibitor concentration in the single-point inhibitions shown in figure 5A. 15% (w/v) means a concentration corresponding to 15 g of pollen (dry weight) per 100 mL of liquid, a manner of expressing concentrations also used by Poncet et al in their papers. o The specificity of inhibition with the pollen extract was ensured by a complete lack of inhibition of binding of dog dander specific IgE to dog dander ImmunoCAP (e5) and is further indicated by the lack of significant inhibition in some samples as shown in figure 5A. Had the inhibitory effect of the cypress pollen extract been due to unspecific blockade of IgE, no such results would have been obtained. We hope that our response will provide sufficient clarity and explanation to the questions raised by Drs. Poncet and Sénéchal

Filaggrin mutations and Molluscum contagiosum skin infection in patients with atopic dermatitis

Background: Although mutations in the filaggrin (FLG) gene have been reported to predispose patients with atopic dermatitis (AD) skin infection susceptibility, to date, the data reported in the literature are still controversial.& para;& para;Objective: To evaluate the role of FLG polymorphisms expression and risk of developing a concomitant Molluscum contagiosum sustained skin infection in the pediatric population with AD.& para;& para;Methods: A total of 100 children with AD and 97 healthy children were enrolled. AD was diagnosed and assessed according to the validated European Task Force on Atopic Dermatitis. DNA samples of patients were analyzed for allelic variants in the promoter and coding exon of FLG. Genotyping was performed with polymerase chain reaction amplification and direct sequencing.& para;& para;Results: Sixteen FLG variants have been detected in 29% of patients with AD: 2 synonymous (rs79808464 and rs116222149), 12 missense (rs11584340, rs113136594, rs145828067, rs374910442, rs747005144, rs145627745, rs144209313, rs74129443, rs192455877, rs150957860, rs138055273, rs147472105), 1 stop gained (rs183942200), and 1 frameshift (rs 558269137). In contrast, only 13% of the control group reported FLG mutations (22 heterozygous variants). In addition, the age at disease onset correlated significantly with FLG variants (P < .001). In addition, the AD with FLG gene variants (rs145627745, rs79808464, rs150957860, rs145828067, rs747005144, rs374910442, rs138055273, rs183942200, rs11584340, and rs113136594) reported moderate to severe Scoring Atopic Dermatitis scores. Finally, the AD group and the AD plus M contagiosum skin infection group had a significant association with FLG mutations when compared with the control group (P < .01).& para;& para;Conclusion: FLG mutations are associated with early onset of AD, more severe clinical course of disease, and a significantly increased risk of M contagiosum sustained skin infection

Mitral valve repair or replacement for ischemic mitral regurgitation? the Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR)

Objective: It is uncertain whether mitral valve replacement is really inferior to mitral valve repair for the treatment of chronic ischemic mitral regurgitation. This multicenter study aimed at providing a contribution to this issue. Methods: Of 1006 patients with chronic ischemic mitral regurgitation and impaired left ventricular function (ejection fraction < 40%) operated on at 13 Italian institutions between 1996 and 2011, 298 (29.6%) underwent mitral valve replacement whereas 708 (70.4%) received mitral valve repair. Propensity scores were calculated by a nonparsimonious multivariable logistic regression, and 244 pairs of patients were matched successfully using calipers of width 0.2 standard deviation of the logit of the propensity scores. The postmatching median standardized difference was 0.024 (range, 0-0.037) and in none of the covariates did it exceed 10%. Results: Early deaths were 3.3% (n = 8) in mitral valve repair versus 5.3% (n = 13) in mitral valve replacement (P = .32). Eight-year survival was 81.6% \ub1 2.8% and 79.6% \ub1 4.8% (P = .42), respectively. Actual freedom from all-cause reoperation and valve-related reoperation were 64.3% \ub1 4.3% versus 80% \ub1 4.1%, and 71.3% \ub1 3.5% versus 85.5% \ub1 3.9 in mitral valve repair and mitral valve replacement, respectively (P < .001). Actual freedom from all valve-related complications was 68.3% \ub1 3.1% versus 69.9% \ub1 3.3% in mitral valve repair and mitral valve replacement, respectively (P = .78). Left ventricular function did not improved significantly, and it was comparable in the 2 groups postoperatively (36.9% vs 38.5%, P = .66). At competing regression analysis, mitral valve repair was a strong predictor of reoperation (hazard ratio, 2.84; P < .001). Conclusions: Mitral valve replacement is a suitable option for patients with chronic ischemic mitral regurgitation and impaired left ventricular function. It provides better results in terms of freedom from reoperation with comparable valve-related complication rates. Copyright \ua9 2013 by The American Association for Thoracic Surgery

Pru p 7 sensitization is a predominant cause of severe, cypress pollen‐associated peach allergy

International audienceBACKGROUND:Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure.OBJECTIVE:We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France.METHODS:Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform.RESULTS:Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests.CONCLUSION AND CLINICAL RELEVANCE:A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy