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SEVERE ANAPHYLACTOID SHOCK SECONDARY TO GADOLINIUM CONTRAST MEDIA
Figure 1. Cysteinyl leukotriene receptor 1 (CysLTR1) expression and monocyte chemoattractant protein 1 (MCP-1) production in interleukin 4 (IL-4)–primed A549 cells. A549 cells were preincubated with IL-4 (10 ng/mL) for 24 hours and then were stimulated with 100nM CysLT D4 (LTD4) for 6 hours. A, Expression of CysLTR1 was examined in IL-4 –primed A549 cells using semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR) (for messenger RNA levels) and flow cytometry (for protein levels). A thin solid line represents the isotype control; a thick solid line, the control; and a thick dotted line, IL-4 treatment. The RT-PCR results were shown by total RNA extracted in a typical experiment using primers for MCP-1 and ACTB (-actin) gene transcripts. Similar results were obtained in 3 identical experiments. B, Production of MCP-1 from IL-4 –primed A549 cells. Results are presented as mean ⫾ SD (error bar) of MCP-1 secretion in IL-4 –treated A549 cells in triplicate. C, Mean ⫾ SD (error bars) production of MCP-1 in IL-4 –primed A549 cells after LTD4 stimulation. D, Inhibitory action of MK571 on MCP-1 production in IL-4 –primed A549 cells after LTD4 stimulation. Results are shown as the mean ⫾ SD (error bars) of MCP-1 secretion from LTD4-treated A549 cells in 2 independent experiments performed in duplicate. *P ⬍ .05 (Mann-Whitney test) relative to controls.
SEVERE ANAPHYLACTOID SHOCK SECONDARY TO GADOLINIUM CONTRAST MEDIA Anaphylactoid reactions to gadolinium contrast media are rare, with the current literature reporting an incidence of 0.01%.1,2 We report a case of a severe anaphylactoid reaction to gadoteridol. A 58-year-old nonatopic woman with a history of breast cancer and hypertension, treated with a -blocker drug, underwent magnetic resonance imaging of her abdomen with her first exposure to gadolinium. She received an injection of ProHance gadoteridol and immediately developed nausea and vomiting. Shortly thereafter, she became unresponsive and experienced respiratory and cardiac arrest. Cardiopulmonary resuscitation was initiated, and she was intubated (with noted difficulty exhaling). She received a total of 4 mg of epinephrine and 1 mg of atropine for pulseless electrical activity
Disclosures: Authors have nothing to disclose.
VOLUME 103, OCTOBER, 2009
before her pulse was detected. On physical examination, she had no urticaria, angioedema, wheezing, or laryngeal edema. The patient had negative results on a workup for other causes of pulseless electrical activity, including a cardiology evaluation. Laboratory test results were significant only for transient metabolic acidosis due to lactic acidosis from the prolonged hypoxia. Her total serum IgE level was 98.6 IU/mL. A serum tryptase level was not obtained. The patient recovered quickly and was extubated the same day. She was told to avoid all gadolinium agents in the future and was referred to the Allergy Immunology Clinic at the VA Greater Los Angeles Healthcare System, Los Angeles, California. Confirmatory skin testing to gadolinium was considered and was not performed because of the severity of the patient’s reaction and her -blocker medication. The severity of our patient’s reaction is seen in comparison to the adverse reactions to gadolinium in 2 previously reported case series.1,2 Most of the reactions in these 2 case series were mild
359
nonallergic reactions or mild to moderate allergic reactions. Severe reactions requiring epinephrine were reported in only 3 of the total 81 patients with adverse reactions. Two of these patients developed chest tightness, respiratory distress, and periorbital edema; 1 patient developed anaphylactoid shock requiring intubation. However, none of these 3 patients with severe reactions experienced cardiac arrest. Gadolinium agents are used as contrast media for magnetic resonance imaging to achieve better tissue enhancement. In the United States, there are 5 gadolinium agents that are commonly used: ProHance, Magnevist, Omniscan, Optimark, and Multihance. They can be separated into macrocyclic molecules and open-chain molecules based on their structure. ProHance is the only macrocyclic molecule listed. Dotarem and Gadovist are macrocyclic molecules that are used in Europe. Anaphylactoid reactions have been reported in both macrocyclic and open-chain gadolinium. Adverse reactions to gadolinium agents are much less frequent than adverse reactions to iodinated contrast media. Mild reactions to gadolinium occur approximately 1% of the time.3 The most common mild reactions to gadolinium are pruritis, nausea, urticaria, and angioedema. The gadolinium agents listed are not differentiable in terms of these mild reactions.3,4 The incidence of severe anaphylactoid reaction to gadolinium is approximately 0.01%.1,2 Even though these numbers are low, millions of radiologic examinations with gadolinium agents are completed each year in the United States. Anaphylactoid reactions to gadolinium can occur on the first exposure to this agent. Patients with allergies, asthma, or drug sensitivities are at increased risk of anaphylactoid reactions. No premedication regimen has been established to decrease the risk of anaphylaxis. However, if a patient had a systemic reaction to gadolinium in the past and additional gadolinium is required, steroids and antihistamines are routinely given. Skin testing may be beneficial in patients with a history of systemic reactions to gadolinium. Case reports from Europe have been published with positive skin test results to gadolinium agents in 5 patients with anaphylactoid reactions to gadolinium.5– 8 Work done by Hasdenteufel et al6 has shown 2 patients with anaphylactoid reactions to macrocyclic gadolinium agents who, after a negative skin test result, were able to tolerate an IV challenge of an open-chain gadolinium agent. This distinction may provide an alternative agent for future imaging
360
studies in patients with a history of a systemic reaction to macrocyclic gadolinium. In conclusion, although the risk of an anaphylactoid reaction is low, gadolinium agents are not innocuous, as demonstrated clearly by the magnitude of the reaction in this patient and by other reports. Radiologists should be keenly aware of the potential for profound systemic reactions, including anaphylactoid shock. If a reaction occurs, skin testing may be useful in confirming the diagnosis of gadolinium sensitivity. Differentiating between open-chain molecules and macrocyclic molecules of gadolinium may also be beneficial in planning future patient care. CAROLINE WATSON SIMONS, MD* SARALEEN BENOUNI, MD* GARY GIBBON, MD* WILLIAM KLAUSTERMEYER, MD* *Division of Allergy and Immunology VA Greater Los Angeles Healthcare System/University of California Los Angeles Los Angeles, California [email protected] 1. Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR Am J Roentgenol. 1996;167:847– 849. 2. Li A, Wong CS, Wong MK, Lee CM, Au Yeung MC. Acute adverse reactions to magnetic resonance contrast media: gadolinium chelates. Br J Radiol. 2006;79: 368 –371. 3. Runge VM. Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging. 2000;12:205–213. 4. Kirchin MA, Runge VM. Contrast agents for magnetic resonance imaging: safety update. Top Magn Reson Imaging. 2003;14:426 – 435. 5. Hasdenteufel F, Luyasu S, Renaudin J, et al. Anaphylactic shock after first exposure to gadoterate meglumine: two case reports documented by positive allergy assessment. J Allergy Clin Immunol. 2008;121:527–528. 6. Hasdenteufel F, Luyasu S, Renaudin J, et al. Reply. J Allergy Clin Immunol. 2008;122:216 –217. 7. Beaudouin E, Kanny G, Blanloeil Y, Guilloux L, Renaudin JM, Moneret-Vautrin DA. Anaphylactic shock induced by gadoterate meglumine (DOTAREM). Allerg Immunol (Paris). 2003;35:382–385. 8. Kalogeromitros D, Makris M, Aggelides X, et al. Anaphylaxis to gadobenate dimeglumine (Multihance): a case report. Int Arch Allergy Immunol. 2007;144:150 –154.
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
SEVERE ANAPHYLACTOID SHOCK SECONDARY TO GADOLINIUM CONTRAST MEDIA Anaphylactoid reactions to gadolinium contrast media are rare, with the current literature reporting an incidence of 0.01%.1,2 We report a case of a severe anaphylactoid reaction to gadoteridol. A 58-year-old nonatopic woman with a history of breast cancer and hypertension, treated with a -blocker drug, underwent magnetic resonance imaging of her abdomen with her first exposure to gadolinium. She received an injection of ProHance gadoteridol and immediately developed nausea and vomiting. Shortly thereafter, she became unresponsive and experienced respiratory and cardiac arrest. Cardiopulmonary resuscitation was initiated, and she was intubated (with noted difficulty exhaling). She received a total of 4 mg of epinephrine and 1 mg of atropine for pulseless electrical activity
Disclosures: Authors have nothing to disclose.
VOLUME 103, OCTOBER, 2009
before her pulse was detected. On physical examination, she had no urticaria, angioedema, wheezing, or laryngeal edema. The patient had negative results on a workup for other causes of pulseless electrical activity, including a cardiology evaluation. Laboratory test results were significant only for transient metabolic acidosis due to lactic acidosis from the prolonged hypoxia. Her total serum IgE level was 98.6 IU/mL. A serum tryptase level was not obtained. The patient recovered quickly and was extubated the same day. She was told to avoid all gadolinium agents in the future and was referred to the Allergy Immunology Clinic at the VA Greater Los Angeles Healthcare System, Los Angeles, California. Confirmatory skin testing to gadolinium was considered and was not performed because of the severity of the patient’s reaction and her -blocker medication. The severity of our patient’s reaction is seen in comparison to the adverse reactions to gadolinium in 2 previously reported case series.1,2 Most of the reactions in these 2 case series were mild
359
nonallergic reactions or mild to moderate allergic reactions. Severe reactions requiring epinephrine were reported in only 3 of the total 81 patients with adverse reactions. Two of these patients developed chest tightness, respiratory distress, and periorbital edema; 1 patient developed anaphylactoid shock requiring intubation. However, none of these 3 patients with severe reactions experienced cardiac arrest. Gadolinium agents are used as contrast media for magnetic resonance imaging to achieve better tissue enhancement. In the United States, there are 5 gadolinium agents that are commonly used: ProHance, Magnevist, Omniscan, Optimark, and Multihance. They can be separated into macrocyclic molecules and open-chain molecules based on their structure. ProHance is the only macrocyclic molecule listed. Dotarem and Gadovist are macrocyclic molecules that are used in Europe. Anaphylactoid reactions have been reported in both macrocyclic and open-chain gadolinium. Adverse reactions to gadolinium agents are much less frequent than adverse reactions to iodinated contrast media. Mild reactions to gadolinium occur approximately 1% of the time.3 The most common mild reactions to gadolinium are pruritis, nausea, urticaria, and angioedema. The gadolinium agents listed are not differentiable in terms of these mild reactions.3,4 The incidence of severe anaphylactoid reaction to gadolinium is approximately 0.01%.1,2 Even though these numbers are low, millions of radiologic examinations with gadolinium agents are completed each year in the United States. Anaphylactoid reactions to gadolinium can occur on the first exposure to this agent. Patients with allergies, asthma, or drug sensitivities are at increased risk of anaphylactoid reactions. No premedication regimen has been established to decrease the risk of anaphylaxis. However, if a patient had a systemic reaction to gadolinium in the past and additional gadolinium is required, steroids and antihistamines are routinely given. Skin testing may be beneficial in patients with a history of systemic reactions to gadolinium. Case reports from Europe have been published with positive skin test results to gadolinium agents in 5 patients with anaphylactoid reactions to gadolinium.5– 8 Work done by Hasdenteufel et al6 has shown 2 patients with anaphylactoid reactions to macrocyclic gadolinium agents who, after a negative skin test result, were able to tolerate an IV challenge of an open-chain gadolinium agent. This distinction may provide an alternative agent for future imaging
360
studies in patients with a history of a systemic reaction to macrocyclic gadolinium. In conclusion, although the risk of an anaphylactoid reaction is low, gadolinium agents are not innocuous, as demonstrated clearly by the magnitude of the reaction in this patient and by other reports. Radiologists should be keenly aware of the potential for profound systemic reactions, including anaphylactoid shock. If a reaction occurs, skin testing may be useful in confirming the diagnosis of gadolinium sensitivity. Differentiating between open-chain molecules and macrocyclic molecules of gadolinium may also be beneficial in planning future patient care. CAROLINE WATSON SIMONS, MD* SARALEEN BENOUNI, MD* GARY GIBBON, MD* WILLIAM KLAUSTERMEYER, MD* *Division of Allergy and Immunology VA Greater Los Angeles Healthcare System/University of California Los Angeles Los Angeles, California [email protected] 1. Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR Am J Roentgenol. 1996;167:847– 849. 2. Li A, Wong CS, Wong MK, Lee CM, Au Yeung MC. Acute adverse reactions to magnetic resonance contrast media: gadolinium chelates. Br J Radiol. 2006;79: 368 –371. 3. Runge VM. Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging. 2000;12:205–213. 4. Kirchin MA, Runge VM. Contrast agents for magnetic resonance imaging: safety update. Top Magn Reson Imaging. 2003;14:426 – 435. 5. Hasdenteufel F, Luyasu S, Renaudin J, et al. Anaphylactic shock after first exposure to gadoterate meglumine: two case reports documented by positive allergy assessment. J Allergy Clin Immunol. 2008;121:527–528. 6. Hasdenteufel F, Luyasu S, Renaudin J, et al. Reply. J Allergy Clin Immunol. 2008;122:216 –217. 7. Beaudouin E, Kanny G, Blanloeil Y, Guilloux L, Renaudin JM, Moneret-Vautrin DA. Anaphylactic shock induced by gadoterate meglumine (DOTAREM). Allerg Immunol (Paris). 2003;35:382–385. 8. Kalogeromitros D, Makris M, Aggelides X, et al. Anaphylaxis to gadobenate dimeglumine (Multihance): a case report. Int Arch Allergy Immunol. 2007;144:150 –154.
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY