Yokoyama Hisayo, Fukumoto Shinya, Koyama Hidenori, Emoto Masanori, Kitagawa Yoshihiro, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, 545-8585 Osaka, Japan.
Diabetes Res Clin Pract. 2003 Sep;61(3):161-6. doi: 10.1016/s0168-8227(03)00114-1.
The insulin analogues, aspart and lispro, have been considered safe alternatives for patients with insulin allergy, because of their decreased immunogenicity. However, recent several reports showed that neither of them was completely free from allergic reactions. We also experienced a patient with insulin allergy not only to human regular insulin but also to both of the insulin analogues. Interestingly, the insulin analogues, which readily dissociate from polymer to monomer, induced the most severe allergic reaction among several types of human insulin reagents in the present case. Allergy to crystalline zinc-insulin, the three-dimensional structure of which results in delayed dissociation and absorption, was negative on intradermal tests. However, its large subcutaneous injection caused local allergic reaction. These results suggested that the allergic reaction might depend on the rapidity of insulin monomerization and absorption, and thus that the immunogenic residue of insulin is concealed when insulin is polymerized. Based on the intradermal tests, we speculated that the antigenic epitope might be B30-Thr in the present case. We also report here the modified method of insulin desensitization using crystalline zinc-insulin with prednisolone tapering. This might be a simple and useful treatment for insulin allergy.
胰岛素类似物门冬胰岛素和赖脯胰岛素,因其免疫原性降低,被认为是胰岛素过敏患者的安全替代药物。然而,最近的几份报告显示,它们都不能完全避免过敏反应。我们也遇到过一名不仅对人常规胰岛素过敏,而且对这两种胰岛素类似物都过敏的患者。有趣的是,在本病例中,易于从聚合物解离为单体的胰岛素类似物在几种人胰岛素制剂中引起了最严重的过敏反应。对结晶锌胰岛素过敏(其三维结构导致解离和吸收延迟),皮内试验结果为阴性。然而,其大剂量皮下注射引起了局部过敏反应。这些结果表明,过敏反应可能取决于胰岛素单体化和吸收的速度,因此当胰岛素聚合时,胰岛素的免疫原性残基被隐藏。基于皮内试验,我们推测在本病例中抗原表位可能是B30-苏氨酸。我们还在此报告了使用结晶锌胰岛素并逐渐减少泼尼松龙剂量的改良胰岛素脱敏方法。这可能是一种简单而有效的胰岛素过敏治疗方法。