Comparison of nasal valve dysfunction treatment outcomes for temperature-controlled radiofrequency and functional rhinoplasty surgery: a systematic review and meta-analyses.

BACKGROUND: Nasal valve dysfunction (NVD) is a substantial contributor to nasal airway obstruction. Minimally-invasive temp-erature-controlled radiofrequency (TCRF) treatment of the nasal valve is available and comparison with surgical techniques is warranted. METHODOLOGY: Databases: Medline (PubMed), Embase, Cochrane Library. POPULATION: adults with preprocedural nasal obstruction symptom evaluation (NOSE) score >=45. Treatment effects were derived from a random effects model and reported as weighted mean difference in NOSE score between baseline; 3, 6, and 12 months postprocedure. RESULTS: Of 2529 initial articles, 5 studies describing TCRF treatment and 63 studies describing functional rhinoplasty were included. Pooled effect sizes for TCRF treatment and functional rhinoplasty were comparable in all analyses. CONCLUSIONS: TCRF treatment of the internal nasal valve for NVD was associated with sustained effects comparable to functional rhinoplasty addressing the nasal valve only, rhinoplasty without concomitant turbinate treatment, and all rhinoplasty.

An innovative strategy for personalised medicine in a CFSPID case that evolved with time.

We present a challenging case that illustrates how the clinical manifestations in children with CFTR mutations of uncertain significance may change over time. This case highlights the evolution of confirming a diagnosis of CF and emphasises the importance of regular review and monitoring of this patient cohort.

Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity. OBJECTIVES: To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA. METHODS: Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction. RESULTS: The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002). CONCLUSIONS: Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.

Ex vivo investigation of the effect of the transverse arytenoid ligament on abduction of the arytenoid cartilage when performing equine laryngoplasty.

Aims: To investigate the effect of the transverse arytenoid ligament (TAL) on abduction of the arytenoid cartilage when performing laryngoplasty. Methods: Modified prosthetic laryngoplasty was performed on right and left sides of 13 cadaver larynges. Increasing force was sequentially applied to the left arytenoid cartilage at 3 N intervals from 0-24 N, when the force on the right arytenoid cartilage was either 0 or 24 N, before and after TAL transection. Digital photographs of the rostral aspect of the larynx were used to determine the left arytenoid abduction angles for these given force combinations and results compared before and after TAL transection. Longitudinal and transverse sections of the TAL from seven other equine larynges were also examined histologically. Results: Increasing force on the left arytenoid cartilage from 0-24 N produced a progressive increase in the angle of the left arytenoid cartilage (p < 0.001) and increasing force on the right arytenoid cartilage from 0-24 N reduced the angle of the left arytenoid cartilage (p < 0.001). Following transection of the TAL the mean angle of the left arytenoid increased from 36.7 (95% CI = 30.5-42.8)° to 38.4 (95% CI = 32.3-44.5)°. Histological examination showed that the TAL was not a discrete ligament between the arytenoid cartilages but was formed by the convergence of the ligament and the left and right arytenoideus transversus muscles. Conclusions: Transection of the TAL in ex vivo equine larynges enabled greater abduction of the left arytenoid cartilage for a given force. These results indicate that TAL transection in conjunction with prosthetic laryngoplasty may have value, but the efficacy and safety of TAL transection under load in vivo, and in horses clinically affected with recurrent laryngeal neuropathy must be evaluated. Abbreviations: Fmax: Force needed to maximally abduct the left or right arytenoid; TAL: Transverse arytenoid ligament.

Are we underestimating the quality of aviremic hepatitis C-positive kidneys? Time to reconsider.

Kidney Donor Risk Index (KDRI) introduced in 2009 included hepatitis C serologic but not viremic status of the donors. With nucleic acid amplification testing (NAT) now being mandatory, further evaluation of these donors is possible. We conducted a retrospective matched case-control analysis of adult deceased donor kidney transplants performed between December 5, 2014 to December 31, 2016 with the KDRI score and hepatitis C virus antibody (HCV Ab) and NAT testing status obtained from the United Network for Organ Sharing database. The 205 aviremic HCV Ab+ NAT - kidney transplants were compared to KDRI matched control kidneys that were HCV Ab-NAT-. The aviremic HCV kidneys were recovered from donors who were significantly younger, more likely to be white, and less likely to have hypertension and diabetes. The majority of the recipients of the aviremic HCV kidneys when compared to matched controls were HCV positive: 90.2% vs 4.3%. The recipients were significantly older, were on dialysis for a shorter time, and were transplanted sooner. The graft survival of aviremic HCV kidneys was similar (P < .08). If the HCV status of the aviremic kidneys was assumed to be negative, 122 more kidneys could have been allocated to patients with estimated posttransplant survival <20. Seven kidneys would no longer have Kidney Donor Profile Index >85%. Further policies might consider these findings to appropriately allocate these kidneys.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.

A data-driven patient blood management strategy in liver transplantation.

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change.

Previous studies have grouped all donors positive for hepatitis C virus (HCV) antibody (Ab). Only recently has donor HCV nucleic acid testing (NAT) become routine, and the impact of Ab and NAT status on organ utilization is unknown. Using the United Network for Organ Sharing database, we identified 9290 donors from 2015 to 2016 for whom both HCV Ab and NAT data were available and compared organ utilization by HCV status. Overall, 93.8% of donors were Ab negative and NAT negative (Ab-NAT-), 0.15% were Ab negative and NAT positive, 1.8% were Ab positive and NAT negative (Ab+NAT-), and 4.2% were both Ab and NAT positive (Ab+NAT+). Ab-NAT- donors donated at the highest rate for all organs except livers, of which Ab+NAT- donors donated at a higher rate (81.2% vs 73.2%, p = 0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+NAT+ donors, whereas kidneys from Ab- or NAT-positive donors were discarded for reasons related to HCV status. Using a propensity score-matched model, we estimated that using Ab+NAT- donors at the same rate as Ab-NAT- donors could result in 48 more kidney donors, 37 more heart donors, and 15 more lung donors annually. We urge the use of HCV Ab+NAT- donors for appropriately selected and consenting recipients.

A longitudinal analysis of the impact of childhood stress on weight status among Chinese youth.

Limited research has explored longitudinal impact of stress on negative health outcomes, including overweight and obesity in Asian societies. Using data from a longitudinal school-based health promotion study conducted in Wuhan, China from 1999 to 2004, this study investigated the longitudinal effects of childhood stress exposure, including stressors related to school, family, peers, violence and health on overweight, and obesity risk during the transition to adolescence among 2179 Chinese adolescents. Results showed that health stressors were consistently related to higher BMI Z score for both boys and girls baseline, it also predicted higher likelihood of overweight status over time for girls. This finding highlights a particularly challenging time period for girls, suggesting a particular challenging time they face at the intersection of puberty and demanding school environment.

Natural evolution in patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity with NSAIDs-induced urticaria/angioedema (NIUA) the most common phenotype. Loss of hypersensitivity has been reported for IgE-mediated reactions; however, it has not been assessed in nonimmunological reactions such as NIUA. We evaluated NSAID-hypersensitivity over time in NIUA patients. METHODS: Patients confirmed as NIUA by positive drug provocation test (DPT) with acetylsalicylic acid (ASA) during 2005-2012 (V1) were included (n=38). Subjects were prospectively re-evaluated by DPT with ASA/other NSAIDs at two time points between 2013 and 2015 (V2 and V3). Atopy was assessed by skin prick test (SPT) using inhalant and food allergens. RESULTS: Patients were evaluated at V1 and re-evaluated after 60 months (V2; IR:48-81) and a further 18 months (V3; IR:14-24). At V2, the majority (24; 63.15%) tolerated ASA and other NSAIDs (Group A) while 14 (36.84%) still reacted (Group B). At V3, all Group A patients remained tolerant; all Group B patients remained hypersensitive. The number of previous episodes reported at V1 and the percentage of reactions induced by ASA/ibuprofen were significantly lower in Group A (P=.005 and P=.006, respectively). Group A patients developed tolerance 72 months (IR:45-87) after their last evaluated reaction (V1); this interval was shorter in nonatopics (P=.003), patients who experienced reactions over 1 hour after NSAIDs administration (P=.001), and those who experienced isolated urticaria after NSAID intake (P=.024). CONCLUSIONS: NIUA patients may develop tolerance to NSAIDs over time, a process that seems to be influenced by atopy and type of clinical reaction.

Duration of general anaesthetic exposure in early childhood and long-term language and cognitive ability.

BACKGROUND: The anaesthetic dose causing neurotoxicity in animals has been evaluated, but the relationship between duration of volatile anaesthetic (VA) exposure and neurodevelopment in children remains unclear. METHODS: Data were obtained from the Western Australian Pregnancy Cohort (Raine) Study, with language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E] and Total [CELF-T]) and cognition (Coloured Progressive Matrices [CPM]) assessed at age 10 yr. Medical records were reviewed, and children divided into quartiles based on total VA exposure duration before age three yr. The association between test score and exposure duration quartile was evaluated using linear regression, adjusting for patient characteristics and comorbidity. RESULTS: Of 1622 children with available test scores, 148 had documented VA exposure and were split into the following quartiles: ≤25, >25 to ≤35, >35 to ≤60 and >60 min. Compared with unexposed children, CELF-T scores for children in the first and second quartiles did not differ, but those in the third and fourth quartiles had significantly lower scores ([3 rd quartile - Unexposed] -5.3; 95% confidence interval [CI], (-10.2 - -0.4), [4 th quartile - Unexposed] -6.2; 95% CI, (-11.6 - -0.9). CELF-E showed similar findings, but significant differences were not found in CELF-R or CPM for any quartile. CONCLUSIONS: Children with VA exposures ≤35 min did not differ from unexposed children, but those with exposures >35 min had lower total and expressive language scores. It remains unclear if this is a dose-response relationship, or if children requiring longer exposures for longer surgeries have other clinical reasons for lower scores.

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

Update on the Genetic Basis of Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) are unpredictable, complex responses to medicines in predisposed individuals. They represent a major health problem owing to the number of patients affected and the severity of the clinical conditions they can induce. In addition to environmental factors, the underlying mechanisms of DHRs are also influenced by genetic factors, although considerable gaps remain in our knowledge. Therefore, further study of the genetics of DHRs is necessary to shed light on their underlying mechanisms. In this manuscript, we provide an update on the genetic basis of the most frequent types of DHRs, including those mediated by immunological and nonimmunological mechanisms. For the first group, we will focus on immediate reactions to ß-lactam antibiotics, which are associated mainly with the IgE pathway (IL13, IL4R, LGALS3, and NOD2) and antigen presentation (HLA-DRA), and nonimmediate reactions to allopurinol, anticonvulsants, antibiotics, and antiretrovirals, which are often associated with polymorphisms in the HLA system. For the second group, we will focus on nonsteroidal anti-inflammatory drugs, which are mostly associated with genetic variants in enzymes and receptors from the arachidonic acid pathway (eg, ALOX5, ALOX5AP, PTGDR, and CYSLTR1). The information provided here will be of interest for medical practitioners from a range of disciplines who come across these reactions in their clinical practice, as well as for allergologists.

The Genetics of Drug Hypersensitivity Reactions.

DHRs are induced by various mechanisms and encompass a heterogeneous set of potentially life-threatening clinical entities. In addition to environmental effects, individual factors play a key role in this intricate puzzle. However, despite commendable efforts in recent years to identify individual predisposing factors, our knowledge of the genetic basis of these reactions remains incomplete. In this manuscript, we summarize current research on the genetics of DHRs, focusing on specific immune-mediated reactions (immediate and nonimmediate) and on pharmacologically mediated reactions (cross-intolerance to nonsteroidal anti-inflammatory drugs). We also provide some thoughts on potential technological approaches that would help us to decipher the molecular mechanisms underlying DHRs. We believe this manuscript will be of interest not only for allergists and basic researchers in the field, but also for clinicians from various areas of expertise who manage these reactions in their clinical practice.

Differential rates of ischemic cholangiopathy and graft survival associated with induction therapy in DCD liver transplantation.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

Initial immunological changes as predictors for house dust mite immunotherapy response.

BACKGROUND: Although specific immunotherapy is the only aetiological treatment for allergic disorders, the underlying mechanisms are not fully understood. Specific immunotherapy induces changes in lymphocyte Th subsets from Th2 to Th1/Treg. Whether differences in immunological patterns underlie patient response to immunotherapy has not yet been established. OBJECTIVES: We studied the immunological changes occurring during a 1-year period of Dermatophagoides pteronyssinus (DP) immunotherapy and their relation with clinical outcome. METHODS: We included 34 patients with DP allergy who received subcutaneous specific immunotherapy (SCIT) for 1 year. Following treatment, patients were classified as responders or non-responders. Fourteen allergic subjects who did not receive SCIT were included as controls. Peripheral blood was obtained at 0, 1, 3, 6 and 12 months and cultured with nDer p 1. Phenotypic changes, cytokine production and basophil response were analysed by flow cytometry; transcription factors were measured by mRNA quantification. Serum immunoglobulin levels were also measured. RESULTS: After 1 year of SCIT, 82% of cases showed improved symptoms (responders). Although increases in sIgG4 were observed, BAT reactivity was not modified in these patients. Increases in T-BET/FOXP3 as well as nDer p 1-specific Th1/Treg frequencies were also observed, along with a decrease in Th2, Th9 and Th17. These changes corresponded to changes in cytokine levels. CONCLUSION: Patients who respond well to DP-SCIT show immunological differences compared to non-responders. In responders, basal differences include a lower frequency of Th1 and higher frequencies of Th2, Th9 and Th17 cells. After 1 year of treatment, an increased production of sIgG4 was observed in responders, along with a change in Th2 response towards Th1/Treg.

Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis.

BACKGROUND: An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established. OBJECTIVE: To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX. METHODS: Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure. RESULTS: Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX. DISCUSSION: The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely.

Influence of age on IgE response in peanut-allergic children and adolescents from the Mediterranean area.

BACKGROUND: Peanut allergens are common triggers of food allergy. Analyses of sensitization patterns, relationships with other allergens, clinical symptoms, and variation with age are needed. We studied sensitization to Ara h 2, Ara h 9, and Pru p 3 in a peanut allergic children/adolescents and the relationship with peach and pollen. METHODS: Peanut allergic patients aged between 1 and 20 years old were classified into two groups: A) allergic to peanut only and B) allergic to peach and peanut. The IgE response was measured to Ara h 2, Ara h 9, and Pru p 3. RESULTS: Of 964 subjects evaluated, 28% were allergic to peanut. From this group, 68% were also sensitized to pollen. Urticaria was the most frequent entity followed by anaphylaxis and OAS. Fifty-eight percent had Ara h 2- and/or Ara h 9-specific IgE. More than half reported symptoms with peanut alone (Group A) and 35% to peanut and peach (Group B). We observed significant differences in sex, age, onset of symptoms, and sensitization to Artemisia between groups. IgE response to Ara h 2 was more frequent in Group A, and Ara h 9 and Pru p 3 in Group B. We observed a decrease in sensitization to Ara h 2 and an increase to Ara h 9 and Pru p 3 with increasing age. CONCLUSION: Peanut allergy is frequent in subjects with allergy to plant foods, with Ara h 2 and Ara h 9 being two important allergens. In younger patients, Ara h 2 predominates over Ara h 9. The reverse was observed in older patients.

Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future.

Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures.