Aspirin-induced Urticaria Research Articles

Aspirin-Induced Delayed Urticaria in Children with Kawasaki Disease: A Retrospective Case-Control Study.

BackgroundAspirin remains a key component of the standard therapy for Kawasaki disease (KD) in children. Although it is well known that aspirin can cause hypersensitivity such as aspirin-induced urticaria (AIU), AIU in children with KD has not been described.MethodsA retrospective case-control study was conducted to investigate AIU clinical features, biochemical parameters, treatment and outcomes in children with KD. Furthermore, biomarkers for predicting AIU were explored using the receiver operating characteristic (ROC) curve analysis.ResultsWe identified 46 AIU cases with 22 boys and 24 girls during April 2015–May 2019. Eighty-nine age-matched KD patients without AIU were randomly chosen as controls. The proportions of children with allergy history and aspirin doses administered in the 2 groups were found not to be significantly different. AIU group had substantially higher baseline C-reactive protein and NT-proBNP levels, and increased neutrophil percent. AIU appeared 6.0 (4.0, 8.0) days after aspirin treatment. Aspirin withdrawal and anti-allergic treatment were applied for AIU, and AIU disappeared in 1–3 days. Baseline NT-proBNP predicted AIU with an AUC of 0.70 (95% CI [0.60 to 0.79]) for sensitivity and specificity of 72.1% and 62.5%, respectively, for a cut-off value of 612.9 mg/L. The length of hospital stay for AIU patients was significantly greater compared with controls.ConclusionAIU in KD children is not related to gender or aspirin dose, and those with AIU have more severe inflammation at admission. Aspirin should be withdrawn for AIU management. Baseline NT-proBNP may serve as a valuable biomarker to predict AIU.

Pathogenetic aspects of chronic urticaria. Retrospective and prospective analysis of the patients of the Department of Dermatology, Poznan University of Medical Sciences.

IntroductionUrticaria is a disease with a complex pathomechanism. Confirmation of the cause in chronic urticaria seems to be a great challenge for specialists.AimTo assess the frequency of different types of urticaria and their coexistence in 1 patient, diseases associated with chronic urticaria and the frequency of accompanying oedema.Material and methodsThe study was divided into two parts. Retrospective analysis included 441 chronic urticaria patients at the age of 15 or older hospitalized in 10 years. Information from history of the disease has been placed in a specially designed form. For the prospective analysis 78 patients have been chosen out of 441 subjects previously qualified for retrospective analysis.ResultsThe most common type of urticaria was autoimmune (27.9% R; 30.8% P), spontaneous (19.3% R; 39.7% P) and aspirin-induced urticaria (17.5% R; 25.6% P). The most common coexisting types of urticaria were autoimmune with aspirin-induced (7.5% R; 10.3% P) and autoimmune with dermographic urticaria (3.2% R; 5.1% P). In more than half of the patients (66.7%) one type occurs only. Angioedema coexisted in over half of the patients (58% R; 69.2% P) Among the coexisting comorbidities in people with accompanying angioedema, statistically significant differences appeared in patients with thyroid diseases (19.9% with oedema and 4.9% without oedema). Among drug users, there was a greater difference between the percentage of patients with or without angioedema than among non-drug users.ConclusionsIt was found that among the inducing factors – pressure and stress and among drugs taken for diseases other than urticaria – NSAIDs had an influence on the persistence of symptoms in P patients.

Gene Polymorphism of Aspirin-Induced Urticaria in Children With Kawasaki Disease.

Objective: To investigate the distribution of the single nucleotide polymorphism (SNP) of LTC4S A-444C in children with Kawasaki disease in northern China and determine whether LTC4S A-444C SNP is associated with aspirin-induced urticaria (AIU).Methods: The clinical data of children with Kawasaki disease hospitalized in our center from April 2015 to November 2017 were collected, and fluorescence in situ hybridization was used to detect the LTC4S A-444C. According to the genotype, the subjects were divided into three groups: AA genotypes, AC genotypes, and CC genotypes. The incidence of AIU in the three groups was calculated and the relationship between LTC4S A-444C SNP and AIU was analyzed.Results: (1) A total of 574 children with Kawasaki disease were enrolled in the study. The allele frequencies for A, C were 980 (85.4%), 168 (14.6%). (2) Twenty-five cases of AIU in AA genotypes, with a positive rate of 6%, 11 cases of AIU in AC genotypes, with a positive rate of 7.5%, 2 cases of AIU in CC genotypes, with a positive rate of 18.2%. CC genotypes had higher incidence of AIU than that of AA and AC genotypes. However, there was no significant difference among the three groups (P > 0.05).Conclusion: The proportion of CC genotypes of LTC4S A-444C in children with Kawasaki disease in northern China is lower than that of AA genotypes and AC genotypes, and the incidence of AIU of CC genotypes is higher than that of AC genotypes and AA genotypes.

Aspirin Intolerance: Experimental Models for Bed-to-Bench.

Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-to-bench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.

A functional promoter polymorphism of the human IL18 gene is associated with aspirin-induced urticaria

Urticaria is the commonest cutaneous reaction caused by aspirin or other nonsteroidal anti-inflammatory drugs. The pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, but appears to involve mast cell activation and neutrophil infiltration. To investigate the genetic contribution of interleukin (IL)-18, which can amplify acute inflammation by promoting mast cell activation, neutrophil migration and cytokine production, to the pathogenesis of AIU. A case-control association study was performed using 275 patients with AIU and 196 normal healthy controls in a Korean population. Two promoter polymorphisms of the IL18 gene (-607A/C and -137G/C) were genotyped using the primer extension method. The functional effect of the IL18 gene promoter polymorphism was investigated through in vitro studies including a luciferase reporter assay and electrophoretic mobility shift assays (EMSAs) and ex vivo studies involving neutrophil chemotaxis assays. A significant association was detected between both AIU in general and the aspirin-intolerant acute urticaria (AIAU) phenotype and the IL18 promoter polymorphism -607A/C. Patients with AIAU showed higher frequencies of the C(-607) G(-137) haplotype, ht1 [CG], compared with controls (P=0·02). Moreover, ht1 [CG] showed a high transcript haplotype by the luciferase activity assay, and EMSAs identified a -607C allele-specific DNA-binding protein as CREB2. Neutrophil chemotactic activity was highest in subjects with AIU exhibiting the high transcript haplotype, ht1 [CG] (P=0·019). The high transcript haplotype ht1 [CG] of the IL18 gene may contribute to the development of acute cutaneous inflammation sensitive to aspirin, leading to the clinical presentation of AIAU.

Association of interleukin 10 promoter polymorphism at -819 T>C with aspirin-induced urticaria in a Korean population

Association of interleukin 10 promoter polymorphism at -819 T>C with aspirin-induced urticaria in a Korean population

Functional variability of the adenosine A3 receptor (ADORA3) gene polymorphism in aspirin-induced urticaria

To improve understanding of aspirin hypersensitivity, this study focused on adenosine as a noncyclooxygenase target molecule of aspirin. Adenosine may affect the release of histamine from cutaneous mast cells through a mechanism mediated by the adenosine A3 receptor. To investigate the genetic contribution of adenosine A3 receptor gene (ADORA3) polymorphisms in the pathogenesis of aspirin-induced urticaria (AIU) in a case-control association study in a Korean population. A case-control association study was performed in 385 patients with AIU and 213 normal controls from a Korean population. The functional variability of genetic polymorphisms in the ADORA3 gene was analysed in in vitro studies that included a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA), and ex vivo studies that included real-time polymerase chain reaction for mRNA expression in peripheral blood mononuclear cells and a histamine release assay. A significant association of ADORA3 promoter polymorphism at -1050G/T was found with the phenotype of AIU. Patients with AIU showed higher frequency of the haplotype, ht1 (T(-1050) C(-564) ), compared with normal healthy controls. Moreover, ht1 (TC) was found to be a high-transcript haplotype by the luciferase activity assay, and a -564C allele-specific DNA binding protein was found by EMSA. Increased basophil histamine release was noted in subjects who had the high-transcript haplotype, ht1 (TC). These results suggest that the high-transcript haplotype, ht1 (TC), of the ADORA3 gene may contribute to the development of cutaneous hyper-reactivity to aspirin, leading to the clinical presentation of AIU.

A Great Variety of Aspirin-Induced Urticaria

A Great Variety of Aspirin-Induced Urticaria

Réintroduction de l’aspirine à dose antiagrégante après urticaire ou angio-œdème induits par des doses anti-inflammatoires

Aspirin is one of the most widely prescribed drugs in the world on account of its analgesic, antipyretic, and anti-inflammatory properties. Its effect on platelet aggregation makes it the first choice for prophylaxis in cardiovascular, neurological and obstetric diseases. However, a history of aspirin-induced urticaria and/or angioedema is usually a contraindication for further prescription of the drug. The aim of this article was to demonstrate that patients presenting aspirin-induced cutaneous reactions at anti-inflammatory doses can safely benefit from aspirin reintroduction at platelet-inhibitory doses. Patients with a history of aspirin-induced urticaria and/or angioedema referred to our department between January 2000 and June 2008 for double-blind placebo-controlled reintroduction at platelet-inhibitory doses for a medical indication were enrolled in this study. Seventy patients with aspirin hypersensitivity as well as a medical indication for this therapy were referred to our department. Of these, 38 (54.3%) had a history of aspirin-induced urticaria and/or angioedema, including three laryngeal oedemas (7.9%). All subjects received platelet-inhibitory doses of aspirin (maximal total dose: 400mg/day) in double-blind placebo-controlled fashion during a one-day hospitalization period. None of the patients presented an immediate hypersensitivity reaction. Only one patient, who had received a cumulative dose of 200mg/day, reported diffuse urticaria and facial angioedema of no clinical significance the following day. He had a history of chronic urticaria. This article demonstrates the safety of reintroducing platelet-inhibitory doses of aspirin in patients in whom it is indicated and reporting aspirin-induced urticaria and/or angioedema with anti-inflammatory doses. However, patients with a history of chronic urticaria should undergo a challenge with the lowest platelet-inhibitory dose (75mg/day) in order to minimize the risk of aggravating their condition.

Association of TNF-α promoter polymorphisms with aspirin-induced urticaria

Although the pathogenesis of aspirin-induced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-alpha, a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-alpha promoter polymorphisms in the development of AIU, we performed an association study of TNF-alpha promoter polymorphisms with AIU phenotype. Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-alpha gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a single-base extension method. Haplotype analyses were done. The genotype frequencies of TNF-1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controls in both co-dominant (P = 0.014, P = 0.007) and dominant (P = 0.007, P = 0.004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P = 0.004, Pc = 0.02) and dominant models (P = 0.002, Pc = 0.01). These findings suggest that the two promoter polymorphisms of TNF-alpha at -1031T>C and -863C>A may contribute to the development of AIU.

Clinical course and urinary eicosanoids in patients with aspirin-induced urticaria followed up for 4 years

Little is known about the course of aspirin-induced urticaria. A special regulatory role of cysteinyl leukotrienes and prostaglandin D(2) (PGD(2)) has been postulated. We performed a long-term observation on clinical course, aspirin sensitivity, and urinary eicosanoids in patients with aspirin-induced urticaria. For 4 years, we followed up 22 patients with chronic idiopathic urticaria and aspirin hypersensitivity who restrained from the use of aspirin and other COX-1 inhibitors. Aspirin challenges were performed in 2002 (all results were positive) and repeated in 2006. Levels of urinary leukotriene E(4) (LTE(4)) and the main PGD(2) metabolite, 9 alpha 11 beta PGF(2), were measured at the same time points. During the follow-up period, the severity of urticaria has decreased. In 14 of 22 patients, the results of aspirin challenge remained positive. In 2002, these 14 patients responded to aspirin with a significant increase in urinary LTE(4) and 9 alpha 11 beta PGF(2) levels. When studied 4 years later, they showed a similar response of 9 alpha 11 beta PGF(2) (P = .047) and a tendency toward an increase in LTE(4) level (P = .057). There was a correlation between the urinary LTE(4) concentration after aspirin challenge and the intensity of skin eruptions. The dose of aspirin had no effect on the magnitude of response of both LTE(4) and the PGD(2) metabolite. In the remaining 8 patients, negative aspirin challenge results were not associated with changes in the urinary eicosanoids studied. Aspirin hypersensitivity manifesting as urticaria/angioedema remains present after 4 years in about two thirds of patients. Aspirin-precipitated skin reactions associate with increased excretion of LTE(4) and PGD(2).

Association of TNF-?? promoter polymorphisms with aspirin-induced urticaria

Association of TNF-?? promoter polymorphisms with aspirin-induced urticaria

Aspririn and nonsteroidal anti-inflammatory drug hypersensitivity

Acetylsalicylic acid (ASA) or aspirin and nonsteroidal anti-inflammatory drug (NSAID) sensitivities encompass a diverse group of both pharmacological and hypersensitivity reactions. Conventionally, hypersensitivities include aspirin-exacerbated respiratory disease (AERD), ASA-induced urticaria, and anaphylaxis. With an increasing prevalence of coronary artery disease in an aging population, aspirin continues to play a significant role in cardiac prophylaxis in a large patient population. Invariably, the clinician will encounter patients with clear indications for aspirin therapy but a history of aspirin sensitivity. Although protocols have been established for aspirin challenge and desensitization, it is not always an efficacious or safe procedure. This article reviews the different classifications of ASA/NSAIDs hypersensitivities to better guide the clinician in dealing with this patient population. History of crossrelativities between multiple NSAIDs implies a non-IgE-mediated process. Similarly, a history of monosensitivity to one NSAID implies an IgE-mediated process, although specific antibodies are often elusive. Despite the name, AERD can potentially be exacerbated by all cyclooxygenase (COX) inhibitors based on dose-dependent inhibition of COX-1. Aspirin desensitization can be achieved to improve both upper and lower respiratory symptoms for most patient with AERD. Aspirin desensitization can usually be achieved for those in need of the antiplatelet effects of aspirin, with the exception of those with aspirin-induced urticaria and baseline chronic urticaria. However, desensitization should only be attempted in those with stable coronary artery disease because the process of desensitization carries the inherent risk of anaphylaxis/anaphylactoid reaction, which may further increase cardiac demand and bring about ischemic injury. Therefore, desensitization is reserved until coronary artery disease is stabilized.

Use of ketoprofen oral challenges to detect cross-reactors among patients with a history of aspirin-induced urticaria

In patients with a history of urticaria induced by a single nonsteroidal anti-inflammatory drug (NSAID), advising elimination of all drugs that inhibit cyclooxygenase 1 (COX-1) can lead to unnecessary avoidance of useful NSAIDs. To classify patients with a history of aspirin-induced urticaria as cross-reactors or single-drug reactors by oral challenges with another strong COX-1 inhibitor, namely, ketoprofen. Forty otherwise healthy patients with a history of acute urticaria after the ingestion of aspirin underwent single-blind, placebo-controlled oral challenges with ketoprofen. In patients who did not tolerate ketoprofen, tolerance tests with drugs exerting either COX-1 inhibition at high doses (acetaminophen and nimesulide) or no COX-1 inhibition at therapeutic doses (rofecoxib and tramadol) were performed. In 24 patients (60%), ketoprofen induced urticaria that was controlled by an intravenous antihistamine; 18 (75%) of the 24 patients reacted after the first provocative dose. On subsequent challenges, 3 (38%) of 8 ketoprofen reactors did not tolerate nimesulide, whereas acetaminophen tramadol and rofecoxib were tolerated by 18 of 18, 14 of 14, and 16 of 16 ketoprofen reactors, respectively. Three ketoprofen reactors reported the onset of spontaneous recurrent urticaria 1 to 3 years after the challenge tests. In patients with a history of urticaria induced by a single NSAID, oral challenges with alternative COX-1 inhibitors are helpful in detecting whether they are true single-NSAID reactors; weak COX-1 inhibitors should be challenged subsequently only in those who show multiple-NSAID intolerance.

Genetic markers for differentiating aspirin-hypersensitivity.

Aspirin-induced asthma (AIA) and aspirin-induced urticaria/angioedema (AIU) are two major aspirin-related allergies. We summarize recent findings related to their molecular genetic mechanisms in order to identify genetic susceptibility markers for differentiating AIU and AIA. The overproduction of cysteinyl leukotriene has been suggested as a mechanism in both AIU and AIA. Increased expression of CYSLTR1 with CYLSTR1 and CYSLTR2 polymorphisms are new findings in AIA, while the ALOX5 promoter polymorphism has been noted in AIU. An HLA study suggested that DPB1*0301 is a strong genetic marker for AIA, and that HLA DRB1*1302 and DQB1*0609 are markers for AIU susceptibility. Several single nucleotide polymorphisms (SNPs) in the promoters of EP2, TBX21, COX-2, FcεRIβ, and TBXA2R were associated with AIA, while an FcεRIα promoter polymorphism was associated with AIU. The functional studies of the key genes involved in AIA and AIU are summarized. The identification and functional study of genetic markers for AIA and AIU susceptibility would further elucidate the pathogenic mechanisms and facilitate the development of early diagnostic markers to establish therapeutic targets.

Familial aggregation of aspirin-induced urticaria and leukotriene C4 synthase allelic variant

We have reported that in patients with chronic idiopathic urticaria (CIU) who reacted adversely to aspirin, the frequency of the (-444)C allele of the leukotriene C(4) synthase gene (LTC4S) was higher than in patients who tolerated aspirin well. To study the pattern of aspirin-induced urticaria (AIU) in two families, with special interest on the polymorphisms of LTC4S (AA, AC, CC) and the glutathione S-transferase M1 and P1 genes (GSTM1 and GSTP1). Of 74 patients with CIU and a history of aspirin hypersensitivity studied by us, two patients (probands) gave a family history of aspirin intolerance. Oral challenge tests with aspirin were carried out in members of these families. Genomic DNA samples were obtained from peripheral blood to study the polymorphisms of LTC4S, GSTM1 and GSTP1. In family 1 the aspirin challenge test confirmed AIU in three of five (60%) individuals, but in family 2 only in two of seven (29%). In both families, the variant genotypes of LTC4S (AC or CC) were present in the parents, but only one of them had CIU. In family 1, with both parents healthy, the three children had AIU; in two it was associated with variant LTC4S genotype. In family 2, urticaria following aspirin ingestion was present only with variant LTC4S genotype. In patients of both families with positive aspirin challenge test, deletion of the GSTM1 gene was present. AIU aggregates in families inheriting the LTC4S(-444)C allele. Segregation of aspirin sensitivity in these families does not follow a clear Mendelian pattern. A common deletion of GSTM1, one of several enzymes involved in conjugation of a wide range of electrophilic substances with glutathione, was present in all individuals ascertained to have AIU.

Mechanism of chronic urticaria exacerbation by aspirin

In some patients with chronic idiopathic urticaria (CIU), aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase 1 (COX-1) precipitate wheals and swelling. There is no in vitro diagnostic, and diagnosis can be established only by provocation challenges with aspirin or other NSAIDs. Skin reactions triggered by aspirin are associated with the inhibition of cyclooxygenase, specifically COX-1, but not COX-2, and are characterized by overproduction of cysteinyl leukotrienes (cys-LTs). Aspirin and other NSAIDs should be avoided, but highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can probably be safely used. Evidence has been accumulated that these reactions are due to the interference of aspirin-like drugs with arachidonic-acid metabolism. In this article, we discuss the mechanism of these reactions, and the characteristic course of aspirin-induced urticaria and its management.

The human leucocyte antigen‐DRB1*1302‐DQB1*0609‐DPB1*0201 haplotype may be a strong genetic marker for aspirin‐induced urticaria

Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood. In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirin-intolerant asthma and normal control in a Korean population. Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine-aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis. The allele frequencies of HLA-DRB1(*)1302 (18.1%) and HLA-DQB1(*)0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P=0.0004; 2.0%, P=0.0024) and in normal controls (8.1%, P=0.0005; 3.2%, P=0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P>0.05, respectively). In haplotype analysis, the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P=0.0014) and normal controls (2.0%, P=0.0006). These findings suggest that the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.

Aspirin Sensitivity

Although acetylsalicylic acid (aspirin) is commonly used for patients with chronic cardiovascular disease, a minority of patients have a sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs. To provide a diagnostic strategy for evaluating and treating patients with aspirin sensitivity, with additional consideration for issues specific to patients with coronary artery disease (CAD). Published articles were identified through a search of MEDLINE and the Cochrane databases using the dates 1966 to June 2004 and the search terms aspirin allergy, coronary artery disease, aspirin desensitization, and aspirin sensitivity. References of retrieved articles were also reviewed for pertinent studies. Articles were included in this review if they were controlled studies, published in the English language, and appeared in a peer-reviewed journal. The prevalence of aspirin-exacerbated respiratory tract disease is approximately 10% and for aspirin-induced urticaria the prevalence varies from 0.07% to 0.2% of the general population. Aspirin sensitivity is most often manifested as rhinitis and asthma or urticaria/angioedema induced by cross-reacting nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase 1. The primary mechanism of sensitivity is less often related to drug-specific IgE antibody production leading to urticaria/angioedema and rarely to anaphylaxis. Most patients with acetylsalicylic acid sensitivity are able to undergo desensitization therapy safely and successfully except in cases of chronic idiopathic urticaria. However, there have not been any randomized trials that specifically focus on the efficacy of aspirin desensitization. Furthermore, experience with acetylsalicylic acid desensitization in patients with CAD is very limited. After successful desensitization, acetylsalicylic acid therapy must be indefinitely continued to prevent resensitization. Acetylsalicylic acid sensitivity is common and desensitization can be performed safely in many patients. Large-scale trials are warranted to determine the safety and efficacy of acetylsalicylic acid desensitization therapy in patients with concomitant CAD because data are currently limited to small case series.

Intolerance to nonsteroidal anti-inflammatory drugs might precede by years the onset of chronic urticaria

Background: Recent studies have found that most otherwise normal subjects with a history of acute urticaria induced by several nonsteroidal anti-inflammatory drugs (NSAIDs) show a wheal-and-flare reaction on intradermal injection of autologous serum. This phenomenon has been previously observed in patients with chronic urticaria (CU) and suggests a possible common background in CU and NSAID-induced urticaria. A relationship between these 2 conditions is further suggested by the fact that up to 30% of patients with CU have a worsening of their skin disorders after the ingestion of chemically unrelated NSAIDs. Objective: I sought to assess whether otherwise normal subjects with multiple or single NSAID intolerance show a propensity to have CU. Methods: Two hundred eighty otherwise normal patients with an unequivocal history of acute urticaria induced by NSAIDs seen during the last 10 years were studied. On the basis of both clinical history and oral challenge tests with at least 2 alternative NSAIDs, the patients were classified as having single or multiple NSAID intolerance. All the patients were re-evaluated within the end of 2002, 1 to 10 years after the first visit, to assess the onset of CU. One hundred allergic adults without a history of CU and of drug allergy followed up for 1 to 10 years were used as control subjects. Results: One hundred fifty-nine and 121 patients were finally considered as having single or multiple NSAID intolerance, respectively. At the follow-up visit, 93 (33%) of 280 patients had CU. The prevalence of CU was very similar in subjects with single or multiple NSAID intolerance (48/159 [30%] vs 45/121 [37%], respectively; P = not significant). Only 1 (1%) of 100 atopic control subjects had CU during the follow-up period (P < .001). Among single NSAID reactors, patients who had CU had a significantly higher prevalence of intolerance to aspirin than those who did not have CU (36/48 [75%] vs 41/111 [37%], P < .001), whereas the latter had a markedly higher prevalence of intolerance to pyrazolone drugs (52/111 [47%] vs 10/48 [21%], P < .01). Altogether, only 12 (15%) of 82 patients intolerant to drugs other than aspirin versus 36 (47%) of 77 aspirin reactors had CU (P < .001). Conclusion: NSAID intolerance might precede the onset of CU by years. Both multiple and single NSAID reactors with a history of aspirin-induced urticaria seem at higher risk for CU than patients with a history of single intolerance to NSAIDs other than aspirin. (J Allergy Clin Immunol 2003;111:1095-8.)