Fouda Ghada E, Bavbek Sevim
Allergy and Immunology Center, Al-Azhar University, Cairo, Egypt.
Division of Immunology and Allergy, Department of Chest Diseases, Ankara University School of Medicine, Ankara, Turkey.
Front Pharmacol. 2020 Sep 8;11:572863. doi: 10.3389/fphar.2020.572863. eCollection 2020.
Rituximab is a chimeric monoclonal antibody (mAb) against CD20 molecule which is expressed on human B cells. It has been used for the treatment of various lymphoid malignancies, lymphoproliferative diseases, and rheumatologic disorders. Rituximab is generally well tolerated. However, increased use of rituximab has been associated with hypersensitivity reactions (HSRs), which can be classified as infusion-related, cytokine-release, type I (IgE/non-IgE), mixed, type III, and type IV reactions. Immediate infusion-related reactions to rituximab are quite common and decrease in frequency with subsequent infusions. However, in about 10% of patients, severe infusion-related reactions develop, which prevent its use. Some of the immediate infusion reactions are due to a cytokine-release but some reactions raise concerns for type I (IgE/non-IgE) hypersensitivity. Recent studies have shown the presence of serum anti-rituximab antibodies, either represented by the IgG or IgE isotype. In some cases, clinical manifestations of IgE-mediated reactions and cytokine-release reactions partially overlap, which is called a mixed reaction. Classified as Type III reaction, rituximab-induced serum sickness reactions have been reported in patients with autoimmune diseases and hematological malignancies. The classic serum sickness triad (fever, rash, and arthralgia) has been observed in patients mainly with an underlying rheumatologic condition. Severe delayed type IV hypersensitivity reactions including non-severe maculopapular rash to severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been rarely reported following rituximab injection. Comprehensive reviews focused on rituximab-induced HSRs are scarce. We aimed to review clinical presentations, underlying mechanisms of rituximab hypersensitivity, as well as management including rapid drug desensitization.
利妥昔单抗是一种针对人B细胞上表达的CD20分子的嵌合单克隆抗体（mAb）。它已被用于治疗各种淋巴系统恶性肿瘤、淋巴增殖性疾病和风湿性疾病。利妥昔单抗一般耐受性良好。然而，利妥昔单抗使用的增加与超敏反应（HSR）有关，超敏反应可分为输液相关反应、细胞因子释放反应、I型（IgE/非IgE）反应、混合反应、III型反应和IV型反应。利妥昔单抗的即刻输液相关反应相当常见，且随着后续输液频率会降低。然而，约10%的患者会发生严重的输液相关反应，这使得利妥昔单抗无法使用。一些即刻输液反应是由于细胞因子释放，但有些反应引发了对I型（IgE/非IgE）超敏反应的担忧。最近的研究表明存在血清抗利妥昔单抗抗体，以IgG或IgE同种型表示。在某些情况下，IgE介导的反应和细胞因子释放反应的临床表现部分重叠，这被称为混合反应。利妥昔单抗诱导的血清病反应被归类为III型反应，已在自身免疫性疾病和血液系统恶性肿瘤患者中报道。经典的血清病三联征（发热、皮疹和关节痛）主要在患有潜在风湿性疾病的患者中观察到。利妥昔单抗注射后很少报告严重的迟发性IV型超敏反应，包括从非严重的斑丘疹到严重反应如史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症。关于利妥昔单抗诱导的HSR的综合综述很少。我们旨在综述利妥昔单抗超敏反应的临床表现、潜在机制以及包括快速药物脱敏在内的管理方法。
