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Background: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative., Objective: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity., Methods: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic., Results: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib., Conclusions: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses., (© 2021 S. Karger AG, Basel.)

Mesalazine is a key drug used for remission induction and maintenance therapy in inflammatory bowel disease (IBD). We sometimes encounter patients who develop allergic reactions to the drug and inevitably discontinue treatment. Of 692 patients who received mesalazine for IBD between 2014 and March 2020, 33 diagnosed with mesalazine allergy (43 episodes) were included, and their clinical manifestations were evaluated. For ten patients undergoing desensitization therapy, therapeutic outcomes were evaluated. The incidence of mesalazine allergy was 4.8%. The time from the start of oral medication to allergy onset was 10 ± 5 days for the first allergic attack and 2 ± 1 days for the second and subsequent allergic attacks. The observed clinical symptoms included fever (93%), diarrhea (26%), abdominal pain (23%), and bloody stool (12%). Drug-induced lymphocyte stimulation test was performed in 85% of the patients (28/33), and the sensitivity was 51%. Desensitization therapy with a time-dependent mesalazine granule formulation was successful in nine of the ten patients (90%), allowing them to receive 2000 mg or more of the drug. Fever was a common allergic symptom, and its presence appeared to be useful for distinguishing mesalazine allergy from exacerbation of the primary disease. Desensitization therapy was useful in patients with mesalazine allergy.

Background: After antibiotics, nonsteroidal anti-inflammatory drugs (NSAID) are one of the leading drug classes responsible for hypersensitivity reactions in children. The drug provocation test (DPT) is the criterion standard for diagnosis. Objective: The aim of the present study was to determine the negative predictive values (NPV) of DPTs with NSAIDs in pediatric patients and to evaluate their attitudes toward NSAID use after a negative DPT result. Methods: The study included all patients who had undergone DPTs between January 1, 2014, and December 31, 2018, in our pediatric allergy clinic for suspected NSAID hypersensitivity reaction and who had a negative result for the suspected agent. Those patients who could be contacted were asked whether the patient had used the same drug again since the DPT and, if so, whether he or she had a reaction. Patients who were reported to have had a reaction were invited to the clinic for reevaluation. Based on the findings from this retesting, the NPVs of the DPTs with NSAIDs were calculated. Results: During the 5-year study period, DPT results were negative for 230 suspected agents in 215 patients. Of these, 143 patients (66.5%) were able to be contacted. A total of 108 patients (75.5%) had used the tested NSAIDs at least once after the provocation test, and five patients (4.6%) reported a reaction on reexposure. Four of these patients declined reevaluation, one patient exhibited no reaction in a second DPT. Therefore, the NPV was calculated as 96.3% (94.3% for ibuprofen, and 100% for paracetamol). Conclusion: The NPVs of DPTs with NSAIDs, especially of paracetamol DPT, is high in children. This finding should reassure the parents of patients who may require NSAID therapy again.

Context: Ketoprofen is widely used to remove pain. A steady increase on allergic reactions and photoallergic contact dermatitis related to ketoprofen has been reported when there is topical use. However, there are few documented cases of hypersensitivity when it is administered systemically. Objective: Present a case of hypersensitivity reaction after systemic administration of ketoprofen for pain control in nephritis crisis. Case description: A 43-years-old Caucasian man diagnosed with renal colic (kidney lithiasis), who was initially treated with 100 mg of tramadol (IV), followed by 4 mg of thiocolchicoside (IM) which caused no relief. Then 100 mg of ketoprofen was administered (IV). Right after the patient began to show hypersensitivity reaction type I characterized by intense coughing, rhinitis, angioedema, periorbital edema, rash, and scleral jaundice. Discussion and conclusion: Maybe it was a case of drug-induced liver disease, however therapeutic dosages of all administered drugs only once. The mechanisms involved were not investigated, but may be the result of allergic and immunologic aspects caused by ketoprofen and facilitated by a history of hypersensitivity to other NSAIDs as reported by the patient. As for jaundice can be attributed to drug toxicity since laboratory parameters did not reveal any evidence of liver disease.

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug's reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics. The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms. The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge. A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

A 47-year-old Japanese man was diagnosed with pancolitis-type ulcerative colitis. He was treated with mesalamine in a pH-dependent release form. On day 16 of administration, he was admitted because of fever and abdominal pain. We diagnosed his symptoms to be the side effects of mesalamine. Hyposensitization using unmodified and a time-dependent release form mesalamine was performed. On day 7 of mesalamine hyposensitization, a colonoscopy was performed. The patient presented with the same allergic symptoms 9 h after the administration of an oral sodium phosphate solution. Eventually, he was orally administered a course of salazosulfapyridine (SASP) at an initial dose of 2.5 mg/day, which was increased to 2000 mg/day. It is generally recognized that SASP intolerance is an indication to switch from SASP to mesalamine. The need to switch treatment from mesalamine to SASP is, therefore, rare because allergic reactions to mesalamine do not occur frequently. We report a very rare case which was presented with abdominal pain and myalgia because of intolerance to mesalamine in whom hyposensitization with and introduction of SASP were successful.

Introduction: CRS is a complex systemic disease affecting more than 10% of the population. There are two main types of CRS phenotypes: CRSwNP and CRSsNP. In the Caucasian population, the prevalence of inflammation markers typical of the Th1 profile is observed in CRSsNP, whereas Th2 and Th17 in CRSwNP. Th2 inflammation is observed in the CRSwNP phenotype with concomitant allergies, asthma or hypersensitivity to NSAIDs., Objectives: The aim of the study was to evaluate, based on the authors' own material, whether allergies, asthma or hypersensitivity to NSAIDs were a risk factor for the development of a specific CRS phenotype. An attempt was also made to investigate the influence of comorbidities on the extent of sinus endoscopic procedures, which depended on the severity of inflammation., Methods: In the years 2006-2015, ESS was performed on 2217 patients with different CRS phenotypes. Patients with an allergy, bronchial asthma and hypersensitivity to NSAIDs were subjected to analysis., Results: Based on logistic regression, it was found that among the mentioned comorbidities, only asthma (P < 0.0001) and hypersensitivity to NSAIDs (P = 0.0007) significantly affect the occurrence of the phenotype with polyps, whereas the impact of allergies is statistically insignificant (P = 0.1909). The relationship between the type of ESS and CRS phenotypes is statistically significant (P < 0.0001)., Conclusions: Bronchial asthma and hypersensitivity to NSAIDs have a statistically significant effect on the occurrence of the CRSwNP phenotype. This effect was not observed in allergies. The impact of allergies, asthma and hypersensitivity on the phenotype was observed in the group of patients subjected to the most extensive surgery (ESS 4).

Adverse drug reactions are frequently reported in pediatric patients. In this review article, the authors discuss pediatric drug allergies with emphasis on the most common culprits, beta-lactam antibiotics and non-steroidal anti-inflammatory drugs. The authors also discuss reactions to non-beta-lactam antibiotics and chemotherapeutics. Skin testing has not yet been validated for many drugs, although notable exceptions include penicillin and carboplatin. The gold standard for diagnosis in most cases remains drug challenge, and the need for penicillin skin testing prior to oral provocation challenge has been questioned in recent studies. Successful desensitizations have also been reported with several drugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/noncase study was performed among individual case safety reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while noncases were ICSRs without HSRs. NSAIDs were categorized into (i) NSAIDs with high COX-2 selectivity (coxibs), (ii) noncoxib NSAIDs with COX-2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified 13 229 cases and 106 444 noncases. In the first 5 years after marketing, poor-selectivity NSAIDs and acetic acid derivatives were associated with the highest ROR of HSRs (age- and sex-adjusted ROR 2.12, 95% CI 1.98-2.28; and ROR 2.21, 95% CI 1.83-2.66, respectively) compared with coxibs, and sulfonamide NSAIDs were associated with the highest ROR of HSRs compared with nonsulfonamide NSAIDs (age- and sex-adjusted ROR 1.38, 95% CI 1.29-1.47). After the first 5 years of marketing, most of the RORs returned to approximately 1., (© 2019 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Background: The aim of the study was to explore the frequency and the clinical and diagnostic characteristics of a single nonsteroidal anti-inflammatory drug-induced hypersensitivity (SNIUAA) subgroup., Methods: In the hospital information system we identified patients who performed the oral provocation test (OPT) with analgesics between 2004 and 2016. We divided patients into phenotype groups based on clinical history and OPT results., Results: Altogether, 248 patients (44.3% of phenotyped patients) were diagnosed with SNIUAA. The most common offending drug in SNIUAA was diclofenac (52.4%), followed by pyrazolones (30.7%). In the group with selective diclofenac hypersensitivity, there was a larger percentage (40.0%) of patients with anaphylaxis. Compared to other phenotypes, significantly fewer patients had OPT performed with the suspected drug in SINUAA; however, in 69.4% of patients in this group, OPT with acetylsalicylic acid was performed., Conclusion: SNIUAA was the most common phenotype of nonsteroidal anti-inflammatory drug hypersensitivity in our cohort. Diclofenac was the most common cause of the hypersensitivity reaction and also the most common cause of anaphylactic reaction. In the group of patients with a positive history after taking diclofenac or pyrazolone, fewer OPTs with the suspected drug were performed, but more often OPT with aspirin to prove that hypersensitivity is selective.

An 18-year-old man diagnosed with ileocolonic Crohn's disease with circumferential strictures of the ascending colon started treatment with mesalazine and subsequently underwent right hemicolectomy. After surgery, the patient was started on adalimumab, and the clinical course was favorable. Nine months postoperatively, colonoscopy revealed granular mucosa with circumferential and continuous involvement from the transverse colon down to the rectum, findings which resembled ulcerative colitis. Mesalazine allergy was suspected, and the inflammatory findings resolved after discontinuing mesalazine. In patients of inflammatory bowel disease receiving mesalazine with an atypical clinical course, the possibility of mesalazine allergy must be borne in mind.

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.

Background: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children are becoming a great concern. Most studies have focused on adults, with noted discrepancies observed in the classification of hypersensitivity reactions to NSAIDs in children when compared with adults., Objective: To phenotype a group of children with hypersensitivity reactions to NSAIDs, including paracetamol, and analyze the degree of agreement with the entities reported in adults and how they fit the proposed classifications., Methods: The study comprised 116 children aged 0.5 to 14 years, with a clinical history indicative of hypersensitivity reactions to NSAIDs. They all underwent a single-blind oral provocation test with acetyl salicylic acid, except in those cases when this was the suspected drug, in which case the challenge was done first with ibuprofen. If positive, cross-intolerance was established and if negative, an oral provocation test with the culprit drug was performed to establish a selective response or exclude allergy., Results: Of the 26% diagnosed as hypersensitive to NSAIDs, 83% were cross-intolerant and 17% selective reactors. The highest significant differences between reactors and nonreactors were observed in the time to reaction after drug intake and the clinical entity (P < .0001), followed by drug involved and age (P < .01)., Conclusions: From the total number of cases confirmed with NSAID hypersensitivity, 83% were cross-intolerant. In cross-intolerant reactions, both cutaneous and respiratory manifestations are common. Acetyl salicylic acid challenge as the first approach proved to be safe and useful to establish the diagnosis., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of hypersensitivity reactions. Several distinct clinical syndromes are described regarding NSAID hypersensitivity. Such a reaction is generally caused by a non-immunological mechanism. In susceptible patients, COX-1 inhibition leads to an imbalance in lipid mediators such as leukotrienes and prostaglandins. It is essential to distinguish multiple nonspecific NSAID hypersensitivity from single NSAID hypersensitivity, since the management of these respective syndromes is essentially different. This review provides an overview on all the aspects of NSAID hypersensitivity reactions, from pathophysiology to clinical symptoms, leading practical recommendations.

Background: Nonsteroidal anti-inflammatory drugs (NSAID)-induced hypersensitivity reactions can be clinically apparent with asthma, rhinosinusitis, anaphylaxis or rash. Although natural anti-inflammatory products can have similar components, they are not subjected to rigorous quality control standards., Case Report: The case is presented of a 22-year-old female with NSAID allergy who attended with facial and laryngeal angioedema associated with pruritus in eyelids and pharynx. She developed these symptoms fifteen minutes after taking an over-the-counter (OTC) natural anti-inflammatory product. She received treatment with epinephrine, antihistamines and corticosteroids., Conclusion: Different natural anti-inflammatory products are freely available both OTC and online. Some contain dangerous substances that can cause important, and even lethal. side effects. Allergologists, dermatologists and general practitioners should be able to recognize that the consumption of these products, which is widely spread, can cause angioedema.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the second-most frequent drug type to cause hypersensitivity reactions in children. Asthma is one of the risk factors for NSAID hypersensitivity (NSAID-H) in adult patients. There are limited number of studies evaluating NSAID-H among children with asthma. Our aim was to assess the frequency of confirmed NSAID-H and evaluate the classification of NSAID-H in children with asthma., Methods: Patients followed with a diagnosis of asthma in our Pediatric Allergy Clinic were evaluated for NSAID-H. Patients were questioned whether they had used NSAIDs, and if they experienced any reaction with these drugs. A control group was also questioned for reactions to NSAID use., Results: 976 children with asthma and 2,000 healthy children as a control group were included in this study. The mean age of the patients with asthma was 10.61 ± 4.21 years and 59.5% were male. Ten (1%) had a reaction history to NSAIDs. NSAID-H was confirmed in 9 (0.9%) who were tested with the suspected drugs. Six of these were classified as "single NSAID-induced urticaria/angioedema or anaphylaxis" and 3 were classified as "NSAIDs-exacerbated respiratory disease." In the control group, only 1 subject had a reaction history to acetylsalicylic acid and no reaction developed in the provocation test., Conclusions: In our study, NSAID-H was found more frequent in children with asthma than in the control group. Children with asthma should be evaluated for reactions to NSAIDs during hospital visits., (© S. Karger AG, Basel.)

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, are among the most commonly used drugs worldwide. They account for a large number of adverse drug reactions (ADRs). The prevalence of NSAID-induced reactions is increasing. Distinguishing between a predicted side effect of a drug and a potentially life-threatening hypersensitivity reaction is essential to manage the affected patient. However, most clinicians find it difficult to diagnose these types of reactions despite published classification schemes. In this overview, we provide an in-depth review of NSAID classification, types of NSAID reactions, diagnostic tactics, and management strategies to provide the reader with a greater understanding of NSAID-induced reactions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy., Methods: Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk., Results: The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures., Conclusions: The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders., Methods: The GA 2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires., Results: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis., Conclusion: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

5-Aminosalicylic acid preparations have been used as first-line drugs for treatment of ulcerative colitis (UC). However, some patients with UC present with exacerbation of symptoms because of allergy to mesalazine. Diagnosis of mesalazine allergy in active UC may be challenging because its symptoms mimic those of UC. Here we describe a 13-year-old boy with mesalazine allergy who achieved remission when his medication was changed from mesalazine to salazosulfapyridine. During his clinical course mesalazine was prescribed twice, and on each occasion exacerbation of the symptoms occurred. We considered a diagnosis of mesalazine allergy, and this was confirmed by a drug lymphocyte stimulation test; the result for salazosulfapyridine was negative. On the basis of criteria involving simple mucosal biopsy combined with endoscopy for predicting patients with UC who would ultimately require surgery, we considered that the UC in this case might be susceptible to steroid treatment, and we therefore treated the patient with salazosulfapyridine and prednisolone. Shortly afterwards, remission was achieved and the patient has remained in good condition on salazosulfapyridine alone. When treating patients with mesalazine, the possibility of allergy should always be borne in mind, especially when the clinical course is inconsistent with the results of biopsy.

Background: An allergic reaction following a dental procedure is a rare event. A local anaesthetic (LA) may initially be suspected as a causative agent but allergy to dental LA solutions is extremely rare., Case Report: This report concerns a 13 year old child who underwent dental treatment and was exposed to Lignospan Special(®) LA, mouthwash, latex gloves, ibuprofen medication, and a Magnum(®) (almond) ice cream all within 45 min. He subsequently developed acute symptoms of nasal rhinorrhoea, facial flushing, peri-orbital and lip angioedema, followed by throat tightness and wheeze (respiratory compromise). His acute reaction was treated by his medical practitioner with oral anti-histamines, steroid and nebulised salbutamol. The child was referred to a local allergist. The child underwent detailed allergic investigations including skin prick tests, blood tests, incremental local anaesthetic challenge and ibuprofen challenge. The patient was diagnosed with NSAID exacerbated respiratory disease (NERD), a hypersensitivity reaction to ibuprofen., Follow-Up: The patient was advised to avoid NSAIDs and to wear a medic-alert (allergy) bracelet. A detailed written report was sent to the patient's dentist and GP., Conclusions: In the context of a suspected reaction post dental procedure, local anaesthetic should be considered a possible allergen but other important considerations include analgesics, antibiotics, and latex. All genuine allergic reactions need to be investigated. This report highlights NERD as a possible adverse outcome following dental treatment.

Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent agents involved in hypersensitivity drug reactions, with NSAID-induced urticaria and/or angioedema (NIUA) being the most common entity. Mast cells are key players in NIUA and are activated by thymic stromal lymphopoietin (TSLP). This cytokine functions through recognition by its receptor, composed of IL7Rα (interleukin-7 receptor alpha) and TSLPR (TSLP receptor). These genes have been previously associated with other inflammatory diseases., Methods: We assessed the genetic association between single nucleotide polymorphisms (SNPs) in TSLP, IL7R and TSLPR and NIUA in Spanish individuals, using genotyped and imputed data. A total of 369 unrelated NIUA patients and 580 NSAID-tolerant control subjects were included, and 6 SNPs in TSLP, 6 in IL7R and 3 in TSLPR were genotyped. Further variants were imputed using Mach and the 1,000 Genomes Project (Phase 3) data. Association testing and statistical analyses were performed with Mach2dat and R., Results: A total of 139 SNPs were tested for association following quality control. Two SNPs in TSLP (rs1816678 and rs764917) showed a nominal association (p = 0.033 and 0.024, respectively) with NIUA, although these results were not statistically significant after correcting for multiple comparisons., Conclusions: Although TSLP, IL7R and TSLPR are important genes involved in the development of the inflammatory response, we found no significant genetic association with NIUA in our population for common SNPs in these genes., (© 2016 S. Karger AG, Basel.)

In theory, all medicines can elicit allergic reactions. However, there are large differences in the frequency and clinical presentation of these reactions. Antibiotics, antiepileptic agents and NSADs trigger allergic reactions most frequently. The risk of drug allergy and of a complicated clinical course depends on the individual degree of immune activation, the dose, duration of treatment, route of administration, patient sex as well as HLA-traits, which are increasingly being identified. This article presents the commonest types of immune-mediated drug-related hypersensitivity reactions and discusses red flags which are associated with a complicated clinical course.

This study is aimed at investigating the association of HLA-DRB1, HLA-DQA1, and HLA-DQB1 variability with the response to aspirin desensitization (AD). A total of 16 patients with aspirin-exacerbated respiratory diseases (AERD, 81.3% were female) with median age of 29 ± 4.3 years were included in this study. Following 6 months, Sino-Nasal Outcome Test-22 (SNOT-22), medication, symptom scores, and forced expiratory volume in 1 s (FEV1) (all p < 0.001) improved significantly. However, only seven patients (43.7%) had clinically significant improvement in all of the medication and symptom scores and FEV1, who were considered responders to AD. Responders to AD had significantly higher symptom scores compared with non-responders at baseline (20 ± 1.18 vs 10 ± 1.27; p = 0.003). HLADQB1*0302 was significantly lower in non-responders than in responders to AD (0.12 [0.02-0.76]; p = 0.022). Sensitivity and specificity of HLA-DQB1*0302 to predict response to AD was 71.4% (95% CI: 35.8-91.7) and 81.8% (95% CI: 52.3-94.8). This study introduces HLA-DQB1*0302 as a genetic marker for favorable response to AD.

Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance., Methods: This is a prospective, single-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization., Results: Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis., Conclusion: We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol.

We introduce the reader to systems biology, using adverse drug reactions (ADRs), specifically hypersensitivity reactions to multiple non-steroidal anti-inflammatory drugs (NSAIDs), as a model. To disentangle the different processes that contribute to these reactions - from drug intake to the appearance of symptoms - it will be necessary to create high-throughput datasets. Just as crucial will be the use of systems biology to integrate and make sense of them. We review previous work using systems biology to study related pathologies such as asthma/allergy, and NSAID metabolism. We show examples of their application to NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high-throughput technology and speculate on their use to improve our understanding of this and other drug-induced pathologies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The article below shows different forms, patomechanisms and diagnostics criteria of hypersensitivity to NSAIDs based on available literature as well as up to date outlook on implementing low salicylate diet as a treatment.

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.

Drug hypersensitivity is an adverse reaction that was brought-about by a specific immunologic response. Some of these reactions are Linked with significant morbidity and mortality. Nowadays, hypersensitivity reactions to most drugs can be well defined and the risk of re-exposure to the culprit drug and/or related drugs can be properly assessed. Medical history, skin, blood and challenge tests, conducted in an allergy clinic, enable the prediction and prevention of repeated events as well as unnecessary avoidance of needed compounds. Non-steroidal anti-inflammatory drugs [NSAID] are the second most prevalent group of drugs that provoke hypersensitivity responses occurring either immediately or later. Immediate type responses to NSAID could be divided into 2 groups, each related to a different mechanism. The most common reaction is not allergic but rather it is mediated by the inhibition of the cyclooxygenase I enzyme pathway. Accordingly, this reaction is not selective to a single chemical compound but rather cross-reacts with other members of this "family" of drugs, depending on their biochemical properties. The clinical distinction between those two subtypes of immediate reaction is hard and sometimes utterly impossible. Moreover, the clinical appearance of an immediate reaction may vary from rhinitis, asthma, new appearance or augmentation of chronic urticaria and up to overt anaphylaxis and death. Furthermore, delayed type reactions may also be life-threatening and typically appear 24 hours and up to days following initiation of therapy. In the current review, we present the recommendations of the Israel Association for Allergy and Clinical Immunology for the evaluation and treatment of patients suspected to suffer from hypersensitivity to NSAIDs.

NSAIDs are the most commonly used medications worldwide and are responsible for almost 25% of adverse drug reactions. Such reactions can have different manifestations and can be immunologic or non-immunologic. The diagnosis is primarily based on the medical history, which can be difficult in patients receiving multiple medications. Because skin testing and blood tests are not valid for NSAIDs reactions, confirmation requires an appropriately-designed challenge. The latter could be avoided when the history is obvious and the reaction is life-threatening. The challenge route can be oral, nasal, or bronchial. Avoidance of the causative NSAID, often associated with the avoidance of the cross-reacting preparations, is the cornerstone of management. In most cases, a safe substitute can be used. When treatment with the causative NSAID is necessary, titrated desensitization can be performed. This review discusses the classes of NSAIDs, mechanisms of their adverse reactions, manifestations, diagnosis, and management.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most commonly involved in hypersensitivity drug reactions. Such reactions can be due to the release of inflammatory mediators in the absence of specific immunologic recognition, or immunoglobulin E (IgE)- or T-cell-selective responses. The former include upper and lower airway symptoms in patients with chronic underlying respiratory disease, the exacerbation of chronic spontaneous urticaria, and the induction of cutaneous symptoms. The latter include selective responses to a single NSAID with good tolerance to strong cyclooxygenase-1 inhibitors, with a putative IgE or T-cell mechanism proposed. These reactions can be acute or delayed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hypersensitivity reactions to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are a challenge to the clinicians, due to their severity. In susceptible individuals, NSAIDs induce a wide spectrum of reactions with various timing and organ manifestations, involving immunological and non-immunological mechanisms. Diagnosis of hypersensitivity to NSAID is based on characteristic symptoms precipitated with ASA/NSAIDs. Oral challenge with NSAID is the "gold standard" for the diagnosis and can be performed in order to confirm hypersensitivity to the culprit drug or to confirm or exclude tolerance to an alternative drug. Diagnosis process includes understanding of the underlying mechanism, and is mandatory for prevention of future events.