Puig Lluís
Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Curr Probl Dermatol. 2018;53:49-63. doi: 10.1159/000479475. Epub 2017 Nov 7.
Paradoxical reactions during treatment with a biologic agent can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition, which usually remains under control (even though there may be a change in morphology or phenotype). Paradoxical reactions were initially described as isolated case reports or case series in patients treated with anti-tumor necrosis factor (TNF) α agents, first in inflammatory rheumatic diseases, later in psoriasis and inflammatory bowel disease. Paradoxical reactions have subsequently been reported with other biological drugs or classes (e.g., tocilizumab), even though in some cases insufficient efficacy or phenotype switch may be difficult to differentiate from true paradoxical reactions. This chapter will deal with the most frequently reported variants of paradoxical reactions: palmoplantar pustular and psoriasiform reactions, psoriatic arthritis, hidradenitis, inflammatory bowel disease, uveitis, pyoderma gangrenosum, granulomatous reactions, and vasculitis. The underlying pathomechanism in these complex diseases with involvement of multiple immunological pathways is most likely a cytokine imbalance, and substitution of the anti-TNFα agent by an alternative anti-p40 or anti-IL-17A biologic may be extremely helpful. Paradoxical reactions can cause serious handicap, and early recognition and treatment of these drug class effects is of paramount importance, especially when the primary disease is relatively devoid of therapeutic alternatives and its reactivation may have catastrophic consequences. Close surveillance of patients treated with newly available biologic drugs is necessary to detect and describe new paradoxical reactions.
在治疗患者的另一种通常处于可控状态的疾病(即使形态或表型可能发生变化)时,出现或加重通常对这类药物有反应的病理状况。矛盾反应最初是作为接受抗肿瘤坏死因子(TNF)α制剂治疗患者的孤立病例报告或病例系列被描述的,最初见于炎性风湿性疾病,后来见于银屑病和炎性肠病。随后,其他生物药物或类别(如托珠单抗)也有矛盾反应的报告,尽管在某些情况下,疗效不足或表型转换可能难以与真正的矛盾反应区分开来。本章将探讨最常报告的矛盾反应变体:掌跖脓疱和银屑病样反应、银屑病关节炎、化脓性汗腺炎、炎性肠病、葡萄膜炎、坏疽性脓皮病、肉芽肿反应和血管炎。这些涉及多种免疫途径的复杂疾病的潜在病理机制很可能是细胞因子失衡,用替代的抗p40或抗IL - 17A生物制剂替代抗TNFα制剂可能非常有帮助。矛盾反应可导致严重残疾,尽早识别和治疗这些药物类别效应至关重要,尤其是当原发性疾病相对缺乏治疗选择且其复发可能产生灾难性后果时。对接受新上市生物药物治疗的患者进行密切监测,对于发现和描述新的矛盾反应是必要的。