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Abstract：
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications, and are among the leading causes of drug hypersensitivity. NSAIDs hypersensitivity reactions are classified by symptom involvement and NSAIDs subclass cross-reactivity. Reactions varying from cutaneous involvement to respiratory symptoms can be triggered by multiple NSAIDs subclasses. Anaphylaxis, while rare, can be induced by a single NSAID, with tolerability of other structurally unrelated subclasses. Reactions that fall outside of these traditional categories are deemed \"blended reactions\". We report a unique case of possible anaphylaxis to acetylsalicylic acid (ASA) and ibuprofen, two structurally dissimilar NSAIDs, indicating a severe blended reaction outside of the typical NSAIDs hypersensitivity reaction categories.
METHODS: An otherwise healthy 45 year old woman was referred to the Allergy and Immunology clinic after developing acute onset dyspnea, lip swelling, and generalized urticaria with ibuprofen use requiring treatment with intramuscular epinephrine in the emergency department. She previously tolerated ibuprofen, naproxen, and acetaminophen and had no history of urticaria, angioedema, asthma, or nasal polyps. She underwent an oral challenge to ASA whereby she developed urticaria and throat irritation with rebound symptoms requiring 2 doses of intramuscular epinephrine. On subsequent visits she passed treatment dose acetaminophen and celecoxib challenges. She was counseled to avoid all other NSAIDs and ASA desensitization was offered should this medication be clinically indicated in the future.
CONCLUSIONS: NSAIDs hypersensitivity reactions can be triggered by individual NSAIDs with tolerance of other subclasses or by multiple structurally unrelated NSAIDs due to COX-1 inhibition. Determining the type of reaction (NERD, NECD, NIUA, SNIUAA, or SNIDHR) allows for appropriate oral challenges and safe alternative therapy recommendations. However, not all clinical reactions fit perfectly into these categories. Patients may also develop blended reactions. Our case highlights a severe blended reaction to multiple unrelated NSAIDs, including likely anaphylaxis to ASA. We note the utility of drug provocation tests (DPTs) to identify safe alternative medication options, as well as the importance of performing DPTs in settings properly equipped to assess and manage severe hypersensitivity reactions including anaphylaxis.
METHODS: An otherwise healthy 45 year old woman was referred to the Allergy and Immunology clinic after developing acute onset dyspnea, lip swelling, and generalized urticaria with ibuprofen use requiring treatment with intramuscular epinephrine in the emergency department. She previously tolerated ibuprofen, naproxen, and acetaminophen and had no history of urticaria, angioedema, asthma, or nasal polyps. She underwent an oral challenge to ASA whereby she developed urticaria and throat irritation with rebound symptoms requiring 2 doses of intramuscular epinephrine. On subsequent visits she passed treatment dose acetaminophen and celecoxib challenges. She was counseled to avoid all other NSAIDs and ASA desensitization was offered should this medication be clinically indicated in the future.
CONCLUSIONS: NSAIDs hypersensitivity reactions can be triggered by individual NSAIDs with tolerance of other subclasses or by multiple structurally unrelated NSAIDs due to COX-1 inhibition. Determining the type of reaction (NERD, NECD, NIUA, SNIUAA, or SNIDHR) allows for appropriate oral challenges and safe alternative therapy recommendations. However, not all clinical reactions fit perfectly into these categories. Patients may also develop blended reactions. Our case highlights a severe blended reaction to multiple unrelated NSAIDs, including likely anaphylaxis to ASA. We note the utility of drug provocation tests (DPTs) to identify safe alternative medication options, as well as the importance of performing DPTs in settings properly equipped to assess and manage severe hypersensitivity reactions including anaphylaxis.
摘要：
背景：非甾体抗炎药（NSAIDs）是最常用的药物之一，并且是药物超敏反应的主要原因之一。NSAIDs超敏反应根据症状参与和NSAIDs亚类交叉反应性来分类。从皮肤受累到呼吸道症状的反应可以由多个NSAIDs亚类触发。过敏反应,虽然罕见，可以由单一的NSAID诱导，具有其他结构无关的亚类的耐受性。超出这些传统类别的反应被认为是“混合反应”。我们报告了一个独特的病例，可能对乙酰水杨酸（ASA）和布洛芬的过敏反应，两种结构上不同的非甾体抗炎药，表明典型的NSAIDs超敏反应类别之外的严重混合反应。
方法：一名健康的45岁女性在急性发作呼吸困难后转诊到过敏和免疫学诊所，嘴唇肿胀,和布洛芬使用的全身性荨麻疹需要在急诊科肌内肾上腺素治疗。她以前耐受布洛芬,萘普生,和对乙酰氨基酚，没有荨麻疹病史，血管性水肿,哮喘,或者鼻息肉.她接受了ASA的口服挑战，从而出现荨麻疹和喉咙刺激，并出现反弹症状，需要2剂肌内肾上腺素。在随后的访问中，她通过了对乙酰氨基酚和塞来昔布的治疗剂量挑战。建议她避免所有其他NSAIDs，如果将来临床上需要这种药物，则提供ASA脱敏。
结论：NSAIDs超敏反应可由对其他亚类具有耐受性的单个NSAIDs或由COX-1抑制导致的多种结构无关的NSAIDs引发。确定反应类型(NERD，NECD,NIUA,SNIUAA,或SNIDHR）允许适当的口服挑战和安全的替代疗法建议。然而,并非所有的临床反应都完全符合这些类别。患者也可能出现混合反应。我们的案例突出了对多种无关的非甾体抗炎药的严重混合反应，包括ASA可能的过敏反应。我们注意到药物激发试验（DPT）的实用性，以确定安全的替代药物选择，以及在配备适当的环境中进行DPT的重要性，以评估和管理包括过敏反应在内的严重超敏反应。
方法：一名健康的45岁女性在急性发作呼吸困难后转诊到过敏和免疫学诊所，嘴唇肿胀,和布洛芬使用的全身性荨麻疹需要在急诊科肌内肾上腺素治疗。她以前耐受布洛芬,萘普生,和对乙酰氨基酚，没有荨麻疹病史，血管性水肿,哮喘,或者鼻息肉.她接受了ASA的口服挑战，从而出现荨麻疹和喉咙刺激，并出现反弹症状，需要2剂肌内肾上腺素。在随后的访问中，她通过了对乙酰氨基酚和塞来昔布的治疗剂量挑战。建议她避免所有其他NSAIDs，如果将来临床上需要这种药物，则提供ASA脱敏。
结论：NSAIDs超敏反应可由对其他亚类具有耐受性的单个NSAIDs或由COX-1抑制导致的多种结构无关的NSAIDs引发。确定反应类型(NERD，NECD,NIUA,SNIUAA,或SNIDHR）允许适当的口服挑战和安全的替代疗法建议。然而,并非所有的临床反应都完全符合这些类别。患者也可能出现混合反应。我们的案例突出了对多种无关的非甾体抗炎药的严重混合反应，包括ASA可能的过敏反应。我们注意到药物激发试验（DPT）的实用性，以确定安全的替代药物选择，以及在配备适当的环境中进行DPT的重要性，以评估和管理包括过敏反应在内的严重超敏反应。
