Anaphylactic reaction to methylprednisolone in multiple sclerosis: a practical approach to alternative corticosteroids
Anaphylactic reaction to methylprednisolone in multiple sclerosis: a practical approach to alternative corticosteroids
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多发性硬化症患者对甲基强的松龙的过敏反应：替代皮质类固醇的实用方法
DOI：
10.1177/1352458506070655
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
Myriam Schluep
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文献类型：
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作者：
C. Deruaz;François Spertini;F. S. Lima;R. D. Pasquier;Myriam Schluep
我们报告一例对静脉注射甲泼尼龙（IVMP）的过敏反应，这是多发性硬化症（MS）的一种罕见并发症[1 3]。一名21岁女性，在神经系统事件发生前6个月内没有感染或免疫史，在两周内出现严重的认知、皮质脊髓、颅神经和小脑缺陷。扩展残疾状态量表（EDSS）评分为4.0。脑磁共振成像（MRI）显示30个T2高信号病灶位于胼胝体、脑室周围和幕下区，其中26个在T1钆给药后增强。脑脊液（CSF）检查显示白细胞7个/mL，浆细胞1.5%，无脑屏障破坏，鞘内产生大量寡克隆免疫球蛋白G。排除了代谢、感染和自身免疫性疾病，保留了可能的MS诊断。患者接受IVMP（SoluMedrol†）1 g/天，持续3天，在接下来的12天内逐渐减少剂量。尽管最初的缓解令人满意，但患者在停用MP后病情恶化，并迅速卧床不起（EDSS 8.0）。第二次脑部MRI显示新的钆增强T1病变，但CSF保持不变。因此，这些重复的发现支持了MS的诊断，合理地排除了其他脱髓鞘疾病。尽管重新开始IVMP（1 g/天），但临床状态恶化，因此每隔一天进行一次血浆置换，反应迅速。米托蒽醌（10 mg/m2），然后开始每月一次，持续三个月，然后每三个月一次。根据方案要求，在注射米托蒽醌之前注射IVMP（Solu-Medrol†）125 mg。第二次注射后，患者的病情明显改善。在第四次注射后，她能够行走无限距离（EDSS 3.0）。然而，当患者在第5次米托蒽醌注射前接受IVMP 125 mg时，她发生了面部和耳廓瘙痒性红斑，演变为荨麻疹性斑丘疹，持续40分钟以上，然后自发消退。无过敏性反应、哮喘或既往药物过敏反应史。对5种不同的皮质类固醇（CS、HP、氢化可的松、泼尼松龙、倍他米松和地塞米松）进行了速发型过敏反应的点刺试验和皮内试验，并根据国际指南进行解释[4，5]。患者仅对MP（Solu-Medrol†）有反应。由于对地塞米松（Mephasone†）的反应性试验为阴性，因此在每次后续米托蒽醌注射前使用地塞米松代替MP，效价相同，无任何副作用。CS给药后的速发过敏反应或类速发过敏反应包括过敏性皮疹、荨麻疹、血管性水肿、支气管痉挛、低血压和可能的死亡[4，6]。可能涉及免疫和非免疫机制。在少数病例中已证实存在特异性IgE，提示为速发型I型过敏反应[1，3]。辅料和盐制剂也有牵连，这在我们的情况下被排除在外。已描述了所有CS活性成分和给药途径的反应，尽管静脉注射似乎构成最大风险，MP和氢化可的松是最常涉及的化合物[4]。先前报告了12例因CS过敏而死亡的病例，因此不能再次给予相同的CS。再引入脱敏方案可用于连续给药的药物，但不建议用于MS，因为CS用作脉冲治疗。此外，这些协议也并非没有风险。因此，如果不能避免使用CS，应通过点刺或皮内注射进行皮肤试验，以找到无交叉反应性的替代CS [7]。在我们的病例中，只有MP的皮肤试验呈阳性，表明该化合物具有特异性。然而，应该记住，皮肤试验的假阴性结果相对频繁，特别是在免疫抑制患者中，因此，应在受控环境中引入新化合物[6]。
Sir We report a case of anaphylactic reaction to intravenous methylprednisolone (IVMP), a rare complication in multiple sclerosis (MS) [1 3]. A 21-year-old female, with no history of infection or immunization during the six months prior to the neurological event, developed, over two weeks, severe cognitive, corticospinal, cranial nerves and cerebellar deficits. The Expanded Disability Status Scale (EDSS) score was 4.0. Cerebral magnetic resonance imaging (MRI) revealed 30 T2 hyperintense lesions located in the corpus callosum, periventricular and infratentorial areas with 26 enhancing after T1 gadolinium administration. Cerebrospinal fluid (CSF) examination showed 7 leukocytes/mL with 1.5% plasmocytes, no brainbarrier disruption, and a strong intrathecal production of oligoclonal immunoglobulin G. Metabolic, infectious and autoimmune disorders were ruled out, and the diagnosis of possible MS was retained. The patient received IVMP (SoluMedrol†) 1 g/day for three days, tapering the dose over the next 12 days. Although the response was initially satisfactory, the patient worsened after stopping MP and became rapidly bedridden (EDSS 8.0). A second cerebral MRI showed new gadolinium-enhancing T1 lesions, but the CSF remained unchanged. The diagnosis of MS was thus sustained by these repetitive findings, excluding reasonably other demyelinating disorders. Although IVMP (1 g/day) was restarted, the clinical status worsened and, therefore, plasma exchange was performed every other day with a rapid favorable response. Mitoxantrone (10 mg/m) was then initiated on a monthly basis for three months, then every three months. As requested per protocol, mitoxantrone injections were preceded by IVMP (Solu-Medrol†) 125 mg. Significant improvement in the patient’s condition was noted after the second injection. She was able to walk for an unlimited distance after the fourth injection (EDSS 3.0). However, while the patient was receiving IVMP 125 mg before her fifth mitoxantrone injection, she developed a facial and troncular itching erythema, which evolved towards urticarial maculo-papules persisting over 40 minutes before spontaneous resolution. There was no history of atopy, asthma or previous allergic reaction to drugs. Prick and intradermal tests for immediate allergic reaction were performed for five different corticosteroids (CS; HP, hydrocortisone, prednisolone, betamethasone and dexamethasone) and interpreted according to international guidelines [4,5]. The patient was only reactive to MP (Solu-Medrol†). Since tests for reactivity to dexamethasone (Mephasone†) were negative, dexamethasone was used instead of MP at an equivalent potency before each subsequent mitoxantrone injection without any side-effects. Anaphylactic or anaphylactoid reactions following CS administration include pruritic rashes, urticaria, angioedema, bronchospasm, hypotension and possibly death [4,6]. Immunologic and non-immunologic mechanisms are probably involved. Specific IgE has been demonstrated in a few cases, suggesting an immediate, type I allergic reaction [1,3]. Excipients and salt formulations have also been implicated, which was ruled out in our case. Reactions have been described for all CS active ingredients and administration routes, although iv injection seems to pose the greatest risk, and MP and hydrocortisone are the compounds most frequently involved [4]. Twelve cases of death due to CS allergy have been previously reported, therefore re-administration of the same CS is not an option. Reintroduction-desensitization protocols may be applied for drugs that are administered continuously, but are not advised in MS, since CS are used as pulse therapy. In addition, these protocols are also not devoid of risk. Thus, if the use of CS cannot be avoided, skin tests, by prick or intradermal injection, should be performed to find a substitutive CS devoid of cross-reactivity [7]. In our case, only the skin test for MP was positive, indicating a specificity for this compound. Still, it should be borne in mind, that false negative results with skin tests are relatively frequent, especially in immunosuppressed patients, and the introduction of a new compound should, therefore, be performed in a controlled environment [6].