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The pathophysiology of anaphylaxis, the difference between anaphylactic and anaphylactoid reactions, and their management.
This week we continue with our discussion anaphylaxis, and will focus on the diagnosis of drug allergy.

1.  How do you diagnose drug allergy?
2.  Can you give some examples of anaphylactoid reactions? How do you diagnose these reactions?

本周我们继续讨论过敏反应，主要关注药物过敏的诊断。

1.  如何诊断药物过敏？
2.  请举几个类过敏反应的例子，如何诊断？

参考答案：

1.  如何诊断药物过敏？

诊断药物过敏需要临床病史、诊断检测试验和诱发试验[1]。药物过敏发生前常有同一物质或类似物质的接触或致敏。Ⅰ型介导的超敏反应或过敏发生迅速，常在使用特定药物或物质、抗原后的几分钟内即可发生。反应包括较轻的皮肤反应如瘙痒和荨麻疹，严重者则危及生命，如心血管性虚脱。诊断试验包括血清标本检测、放射免疫测定法及皮肤过敏试验[1]。

纤维蛋白溶酶（一种肥大细胞脱颗粒作用释放的酶），在接触到过敏物质后30min到5h达到高峰，而根据过敏反应严重程度的不同在数天到数周内恢复正常[1]。比较高峰值与基础值，如存在显著差别则可确定诊断过敏。体外试验如放射免疫测定法可检测不良反应出现时药物反应的血清IgE抗体。体内试验包括皮内试验（即单刺试验）和激发试验，是诊断过敏的金标准。但是，因在组胺释放后体内试验可出现假阳性，因此解释结果需要谨慎。激发试验可用于单刺试验阴性或结果不确定的患者。进行激发试验时，明确激发药物或物质的确切剂量很重要，并需以最小的速度增加剂量。体内试验可导致过敏反应的发生，因此只能在抢救设备完善的情况下由变态反应学家实施。

2.  请举几个类过敏反应的例子，你是如何诊断的？

如我们以前的讨论，类过敏性反应为非免疫学机制导致的全身反应，临床表现可与过敏反应相同[2-4]。如X线照片造影剂反应、阿司匹林（ASA）反应和非类固醇类抗炎药物反应等。鼻炎的标准三联症包括鼻息肉、哮喘和阿司匹林敏感，可在使用ASA后出现类过敏反应的患者发生。使用ASA后可使花生四烯酸的代谢产物向5-lipooxygenase通路转移，导致合成白三烯（强效支气管收缩剂）[1，2]。

现在认为X线照片造影剂的反应机制可能与补体激活有关，可在首次接触时发生。发生率为4.6%-8.5%，但随着近年来低渗透性的新型造影剂的使用，其发生率呈下降趋势。放射性造影剂的类过敏反应可再次发生，且遗传性过敏症为危险因素之一。诊断依靠临床表现，当前尚无有效的检查手段。可通过提前给药降低或预防反应的发生，如抗组织胺类和皮质激素[1]。

How do you diagnose drug allergy?

The diagnosis of drug allergy is based in the clinical history, diagnostic tests and provocation tests (1). True drug allergy is often preceded by prior exposure, or sensitization, to the same or to a similar substance. Type I mediated hypersensitivity reactions, or anaphylaxis, occur within minutes after the administration of a certain medication or substance, the antigen, and lead to an immediate response. This response ranges from mild cutaneous reactions, such as pruritus and urticaria, to life threatening cardiovascular collapse. Diagnostic tests include serum blood samples, radioimmunoassays and intradermal tests (1).

Serum tryptase, an enzyme released on mast cell degranulation, often peaks between 30 minutes to 5 hours after exposure, and often returns to baseline within days to weeks depending on the severity of the episode (1). Peak samples could then be compared to baseline samples, and a diagnosis of anaphylaxis is confirmed if a significant difference is present. In vitro tests, such as radioimmunoassay, detect serum IgE antibodies to the drug responsible for the adverse reaction. In vivo tests consist of intradermal (e.g. skin prick tests) and provocation tests, and are the gold standard in the diagnosis of anaphylaxis. However, in vivo tests should be interpreted with caution as false positive results may occur secondary to non-specific histamine release. Provocation tests may be used in cases in which there is no available skin prick test or when the result is ambivalent. When conducting provocation tests, it is essential to know the exact quantity of the drug or agent, and to give very small incremental doses. In vivo tests can lead to an anaphylactic reaction, and therefore should be only administered by a trained allergist in the presence of resuscitation equipment.

Can you give some examples of anaphylactoid reactions? How do you diagnose these reactions?

As we discussed earlier this week, anaphylactoid reactions are systemic reactions caused by a non-immunologic mechanism. The clinical presentation may be identical to an anaphylactic reaction (2-4). Examples include reactions to radiographic contrast agents and to aspirin (ASA) and nonsteroidal anti-inflammatory drugs. The classic triad of rhinitis with nasal polyps, asthma and aspirin sensitivity may be present in patients with anaphylactoid reactions to ASA (2). The administration of ASA shifts the metabolism of arachidonic acid towards the 5-lipooxygenase pathway, leading to the synthesis of leukotrienes, potent bronchoconstrictors (1-2).

The mechanism of reactions to radiographic contrast agents is believed to be related to complement activation and could occur on the first exposure. The incidence is between 4.6%-8.5% of procedures, but it may decrease in the next few years when newer contrast agents with low osmolarity become more popular. An anaphylactoid reaction to radiocontrast media tends to recur and atopy tends to be a risk factor. Its diagnosis is based on the clinical presentation, and there are no available tests at the present time. This reaction can be ameliorated or prevented by the use of premedications such as antihistamines and corticosteroids (1).

References:

1.  Vervloet D. Adverse reactions to drugs. BMJ 1998;1511-14.
2.  Vervloet D, Pradal M, Castelain M. Drug allergy. Pharmacia & Upjohn. Uppsala, Sweden 1999, 2nd edition.
3.  Weiss ME, Adkinson NF, Hirshman CA. Evaluation of allergic drug reactions in the perioperative period. Anesthesiology 1989;71:483-86.
4.  Grupe S. Supplement to the Journal of Allergy and Clinical Immunology. J Allergy Clin Immunol 1998;101:S465-S528.


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