Hypersensitivity Reactions to Multiple Iodinated Contrast Media.

Inmaculada Doña,María Salas,Almudena Testera,Gádor Bogas,Jose Julio Laguna,María José Torres,Esther Moreno

doi:10.3389/fphar.2020.575437

Abstract

The incidence of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) has risen over last years, representing an important health problem. HSRs to ICMs are classified into immediate reactions (IRs) and non-immediate reactions (NIRs) according to if they occur within 1 h or longer after ICM administration. The diagnosis of HSRs to ICM is complex as skin test (ST) sensitivity ranges widely, and drug provocation test (DPT) protocols are heterogeneous. In this manuscript, we describe the clinical characteristics of a series of patients confirmed as HSR to ICM and the diagnosis procedure carried out, looking into those cases confirmed as HSRs to multiple ICMs. For this purpose, we prospectively evaluated patients suggestive of HSRs to ICMs and classified them as IRs or NIRs. STs were carried out using a wide panel of ICMs, and in those with a negative ST, a single-blind placebo controlled DPT was performed with the culprit. If ST or DPT were positive, then tolerance was assessed with an alternative negative ST ICM. We included 101 cases (12 IRs and 89 NIRs) confirmed as allergic. Among them, 36 (35.64%) cases were allergic to more than one ICM (8 IRs and 28 NIRs). The most common ICM involved were iomeprol and iodixanol. Although not statistically significant, the percentage of patients reporting anaphylaxis was higher in patients allergic to multiple ICMs compared with patients allergic to a single ICM (50 vs. 25%). Likewise, the percentage of positive results in STs was higher in patients allergic to multiple ICMs compared with those allergic to a single ICM (for IR 62.5 vs. 25%, p > 0.05; and for NIR, 85.71 vs. 24.59%, p < 0.000). In cases allergic to more than one ICM, DPT with negative-ST ICM was positive in more than 60% (24/36) of cases. Therefore, allergy to multiple ICMs is common, associated to severe reactions in IRs, and confirmed frequently by positive STs. The allergological work-up should include DPT not only to establish the diagnosis but also to identify safe alternative ICM, even if ICM is structurally unrelated and ST is negative. More studies are needed to clarify mechanisms underlying cross-reactivity among ICMs.

Highlights

drug provocation test (DPT) is considered the gold standard for diagnosing hypersensitivity reactions (HSRs) to drugs (Aberer et al, 2003), and, in the case of HSRs to iodinated contrast media (ICM), it is recommended to be performed with the ICM giving negative results in skin test (ST) for confirming diagnosis or looking for a safe alternative (Rosado Ingelmo et al, 2016; Brockow, 2020)
A total of 87 cases reported a single episode after ICM administration, and 14 had two episodes
According to the information obtained from the clinical history, 7 out of 12 (58.33%) cases reporting immediate reactions (IRs) developed urticaria, and 5 (41.66%) symptoms compatible with anaphylaxis

Summary

Introduction

The incidence of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) has risen in parallel with their increased usage (Brockow et al, 2005; Brockow, 2020), being estimated to occur in about 0.5–2% of patients receiving ICMs (Brockow et al, 2005). Positive results in skin tests (STs), basophil activation tests, and specific IgE detection in IRs suggests a likely IgE-mediated mechanism (Laroche et al, 1998; Mita et al, 1998; Laroche et al, 1999; Trcka et al, 2008; Brockow et al, 2009; Pinnobphun et al, 2011; Salas et al, 2013; Steiner et al, 2016); and the analysis of skin biopsies obtained from positive-ST and -drug provocation tests (DPTs) in NIR patients, the monitorization of the immune response during the acute and resolution phases, and the proliferative response in lymphocyte transformation test supports a T cell involvement (Romano et al, 2002; Kanny et al, 2005; Lerch et al, 2007; Torres et al, 2008; Antunez et al, 2011; Torres et al, 2012). Its use is controversial as it is a not-risk free procedure (Aberer et al, 2003) and doses administered during the allergological work-up lack of consensus, varying from 10 to 120 cc and being injected on a single day or incrementally increased over several days (Vernassiere et al, 2004; Torres et al, 2012; Prieto-Garcia et al, 2013; Salas et al, 2013; Sese et al, 2016; Lerondeau et al, 2016; Morales-Cabeza et al, 2017; Gracia-Bara et al, 2019; Soria et al, 2019; Trautmann et al, 2019)

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