Apraxine Matveï, Van den Eynde Marc, De Cuyper Astrid, Pirson Françoise
Department of Pulmonology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Department of Pulmonology, GHdC, Charleroi, Belgium.
Allergy Asthma Clin Immunol. 2022 Dec 22;18(1):107. doi: 10.1186/s13223-022-00752-5.
Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA.
Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly.
These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner's attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.
抗肿瘤药物的超敏反应（HSR）问题日益严重，尤其是当这些反应导致治疗中断，有时甚至没有任何等效的治疗选择时。对亚叶酸（FA）的超敏反应较为罕见，FA特别用于与奥沙利铂和5-氟尿嘧啶联合治疗消化道癌。仅有七篇文献报道了对FA的超敏反应，主要通过在化疗中停用FA后症状消失得以证实。仅有两篇论文描述了过敏试验。由于诊断困难，患者通常在停用FA之前会接受几个疗程的化疗，症状逐渐加重。
在此，我们记录了两例对FA的超敏反应病例，最初误诊为对奥沙利铂过敏。首例患者描述了连续几个疗程中，先是背部肌肉疼痛，然后是寒战和面部水肿，尽管进行了预处理，最后出现弥漫性红斑伴唇部水肿。过敏评估显示急性类胰蛋白酶水平升高，FA皮内试验呈阳性，提示为免疫球蛋白E（IgE）介导的机制。第二例患者在输注FA期间除了出现心动过速和血氧饱和度下降外，还伴有下背部肌肉疼痛和寒战。皮肤试验为阴性，类胰蛋白酶水平正常。停用FA后，症状未再出现，患者得以继续化疗。FA超敏反应的机制仍不清楚。症状的发生顺序提示为IgE介导的机制，但过敏评估中未得到证实。可能涉及非IgE介导的肥大细胞/嗜碱性粒细胞活化，特别是通过补体激活或通过Mas相关G蛋白偶联受体X2（MRGPRX2）。
这两例对FA的过敏反应记录了与两种不同超敏反应机制相关的临床表现。本文提供了回顾关于FA超敏反应的有限文献的机会。通过这些病例，我们希望引起从业者对FA作为严重超敏反应潜在药物的关注，特别是在停用最可疑的化疗药物后症状仍然存在的情况下。我们还想强调过敏试验的重要性。
