Selective Responders Research Articles

Assessment of pediatric patients with suspected nonsteroidal anti-inflammatory drug hypersensitivity.

Background: Beta-lactam antibiotics are the most common cause of hypersensitivity reactions to medications, followed by nonsteroidal anti-inflammatory drugs (NSAID). Objective: The aim of this study was to classify children with hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAID-H) according to the latest updates. Methods: ENDA recommendations were used to evaluate all patients with suspected NSAID-H. Children were classified as either selective responders (SR) or cross-intolerant based on the results of the drug provocation test (DPT). Results: Sixty-seven patients with suspected NSAID-H were evaluated in this study. NSAID-H was confirmed in 20 patients (29.9%). Among the 20 patients diagnosed with NSAID-H, 15 were classified according to the 2018 EAACI/ENDA Position Paper. Twelve patients (80%) were classified as cross-intolerant and 3 (20%) as SRs. NSAID-H was confirmed in 4 of 37 patients (10.8%) ages <10 years and 16 of 30 patients (53.3%) ages >10 years (p < 0.001). Twelve patients ages >10 years were classified. Cross-intolerance was detected in nine patients (66.6%). In patients >10 years of age, NSAID-induced urticaria/angioedema (NIUA) (16.7%) was the most common type in the group with classifiable cross-intolerant. In addition, NSAID-exacerbated respiratory disease was detected in one patient. Conculsion: Ibuprofen is the most common NSAID-H drug used in children. NIUA is the most common reaction. In pediatric allergy, hypersensitivity to NSAIDs is a challenging diagnostic issue. Hypersensitivity to NSAIDs poses a challenging diagnostic issue in pediatric allergies. The oral challenge test is the main diagnostic tool; however, in clinical practice, performing multiple challenge tests is difficult.

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children

BackgroundHypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. MethodsAll patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. ResultsWe evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA2LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18–7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16–7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50–10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. ConclusionsThis study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

Characteristics of subjects experiencing hypersensitivity to non-steroidal anti-inflammatory drugs: patterns of response

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known. To analyse a large group of subjects with confirmed hypersensitivity reactions to NSAIDs. The drugs involved, the clinical entities induced and the time interval between drug intake and appearance of the reaction were studied. In cases where the diagnosis was not confirmed, a drug provocation test was carried out. Atopy status was also assessed with prick test and total IgE in serum. A total of 659 patients were finally considered to have had hypersensitivity reactions to NSAIDs; 76% had cross-intolerance (CI) and 24% were selective responders (SR). The most important drugs involved in CI were propionic acid derivatives, in most cases ibuprofen, and in SR pyrazolones. In CI, the most frequent clinical entity was urticaria and angio-oedema and to a lesser extent airway involvement. The skin and airways were both involved in an important proportion of cases. The most frequent entities in SR were urticaria and/or angio-oedema followed by anaphylaxis. Atopy was significantly associated in the CI group (P<0.005). Cutaneous hypersensitivity reactions by CI to NSAIDs are the most frequent entities induced by these compounds. In addition to aspirin, other NSAIDs are taking on a predominant role. Atopy can be a predisposing factor in patients with CI.

Non Steroids Anti-inflammatory Drugs (NSAIDs) Intolerance Versus Allergy: Patterns of Response and Drug Involved

RATIONALE: Few detailed studies with a large series of patients providing information of the participation of these mechanisms and the involvement of the different drugs are available in hypersensitivity to NSAIDs.METHODS: We studied 182 confirmed cases by other skin and/or in vitro testing or drug provocation test. Cases were defined as cross intolerance (CI) if they had symptoms with two or more NSAIDs and selective responders (SR) if they had symptoms only to one compound and good tolerance to others NSAID was confirmed. Cases pre-existing urticaria were excluded.RESULTS: From the total group, 130 patients (71.4%) were CI and 52 (28.6%) SR. Both CI and SR female predominated over male, although not significant. The drug involved were ibuprofen (20%) and pyrazolones (19.8%), SAA (16.3%) and diclofenac (12%) with the remaining drugs including paracetamol and selective COX-2 inhibitors less than 10% of patients. Symptoms limited to skin appeared in 70.9% of cases, limited to airways 8.9% and in the 19.2% both airways and skin were involved. Respiratory airways involvement was most frequent in CI (10% vs 1%, p < 0.001). Anaphylaxis appeared in 25% SR vs 15% CI (p < 0.001). Urticaria was the most frequent involved (22.3% CI vs 7.7% SR, p < 0.002). From SR non immediate reactions occurred in 30.9%.CONCLUSIONS: CI was the most frequent group with predominant urticaria vs respiratory involvement. The contribution of SR was relevant (1/4 cases) what indicated that specific immunological mechanisms take part in these reactions. RATIONALE: Few detailed studies with a large series of patients providing information of the participation of these mechanisms and the involvement of the different drugs are available in hypersensitivity to NSAIDs. METHODS: We studied 182 confirmed cases by other skin and/or in vitro testing or drug provocation test. Cases were defined as cross intolerance (CI) if they had symptoms with two or more NSAIDs and selective responders (SR) if they had symptoms only to one compound and good tolerance to others NSAID was confirmed. Cases pre-existing urticaria were excluded. RESULTS: From the total group, 130 patients (71.4%) were CI and 52 (28.6%) SR. Both CI and SR female predominated over male, although not significant. The drug involved were ibuprofen (20%) and pyrazolones (19.8%), SAA (16.3%) and diclofenac (12%) with the remaining drugs including paracetamol and selective COX-2 inhibitors less than 10% of patients. Symptoms limited to skin appeared in 70.9% of cases, limited to airways 8.9% and in the 19.2% both airways and skin were involved. Respiratory airways involvement was most frequent in CI (10% vs 1%, p < 0.001). Anaphylaxis appeared in 25% SR vs 15% CI (p < 0.001). Urticaria was the most frequent involved (22.3% CI vs 7.7% SR, p < 0.002). From SR non immediate reactions occurred in 30.9%. CONCLUSIONS: CI was the most frequent group with predominant urticaria vs respiratory involvement. The contribution of SR was relevant (1/4 cases) what indicated that specific immunological mechanisms take part in these reactions.