Special Article

Controversies in Drug Allergy: Radiographic

Contrast Media
Mario Sánchez-Borges, MDa,*, Werner Aberer, MDb,*, Knut Brockow, MDc, Gulfem E. Celik, MDd,
Josefina Cernadas, MDe, Paul A. Greenberger, MDf, Marie-Soleil Masse, MDg, Rik Schrijvers, MDh, and
Axel Trautmann, MDi Caracas, Venezuela; Graz, Austria; Munich, Würzburg, Germany; Ankara, Turkey; Porto, Portugal; Chicago,
Ill; Montréal, Canada; and Leuven, Belgium

This article is one of a series of international consensus documents developed from the International Drug Allergy Symposium held at
the Joint Congress of the American Academy of Allergy, Asthma & Immunology/World Allergy Organization on March 1, 2018, in
Orlando, Florida, USA. The symposium was sponsored by The Journal of Allergy and Clinical Immunology, The Journal of Allergy
and Clinical Immunology: In Practice, and The World Allergy Organization Journal and chaired by Mariana Castells, MD, PhD, and
Pascal Demoly, MD, PhD.

The risk for developing immediate or delayed hypersensitivity Key words: Anaphylaxis; Drug allergy; Premedication; Radio-
reactions to radiocontrast media (RCM) interferes with the graphic contrast media; RCM; Skin testing
diagnosis and treatment of a number of patients requiring imaging
diagnostic methods for many common diseases. A group of experts Worldwide more than 75 million X-ray examinations are
met in Orlando, Florida, in March 2018 to analyze the similarities performed per year using radiographic contrast media (RCM).
and differences in the management of RCM reactions in different RCMs are categorized based on ion content (Table I), and
areas of the world. This paper presents a summary of the currently nonionic RCMs are preferred more in clinical practice
recommendations provided by this consensus group, highlighting owing to their lower hypersensitivity profile.1-4
controversial issues and unmet needs that require further The prevalence of hypersensitivity reactions to monomeric ionic
research. Ó 2019 American Academy of Allergy, Asthma & RCM has been reported to vary between 3.8% and 12.7%, and
Immunology (J Allergy Clin Immunol Pract 2019;7:60-4) severe reactions occur in 0.02% to 0.04% of intravenous applica-
tions.5 For nonionic RCM, the observed prevalence is 0.7% to 3%.6
Two types of hypersensitivity reactions to RCM have been
recognized: immediate and nonimmediate (delayed).7 Immediate
a
Allergy and Clinical Immunology Department, Centro Médico Docente La Trinidad reactions can be caused by IgE and non-IgE mechanisms. Im-
b
and Clínica El Avila, Caracas, Venezuela mediate, anaphylaxis-like reactions may be caused by an effect of
Department of Dermatology and Venerology, Medical University of Graz, Graz, the RCM on the mast cell membrane leading to mediator release
Austria
c
Department of Dermatology and Allergy Biederstein, Technische Universität
or, possibly, by direct complement activation. IgE-mediated
München, Munich, Germany allergic hypersensitivity reactions may have been underreported
d
Department of Chest Diseases, Division of Immunology and Allergy, Ankara in the past,1-4,8-13 due to the lack of allergy testing.
University School of Medicine, Ankara, Turkey Macular or maculopapular exanthema seems to account for
e
Department of Allergy and Clinical Immunology, Medical University, H. S. Joao,
Porto, Portugal
the great majority of RCM-induced nonimmediate reactions.
f
Department of Medicine, Division of Allergy and Immunology, Northwestern Although the mechanisms of these exanthematous reactions have
University Feinberg School of Medicine, Chicago, Ill not been fully elucidated, T-cell involvement has been suggested
g
Department of Medicine, Service of Allergy and Clinical Immunology, Centre in delayed hypersensitivity to RCMs (Figure 1).14 Previous
Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada reactions to RCM are the main risk factor for developing
h
Laboratory of Clinical Immunology, Department of Microbiology and Clinical
Immunology, KU Leuven, Leuven, Belgium
hypersensitivity reactions to RCM. Other factors that have been
i
Department of Dermatology and Allergy, University Hospital Würzburg, Würzburg, associated with an increased risk to develop hypersensitivity
Germany reactions to RCM are atopy and asthma (Table II).
* These authors were topic co-leaders.
No funding was received for this work.
Conflicts of interest: P. A. Greenberger has received consultancy fees from Allergy CONTROVERSIAL AREAS
Therapeutics; receives royalties from Up To Date and Wolters Kluwer Lippincott,
The role of the basophil activation test
Williams and Wilkins; and has provided expert witness testimony. The rest of the
authors declare that they have no relevant conflicts of interest. The usefulness of the basophil activation test (BAT) to study
Received for publication June 27, 2018; accepted for publication June 27, 2018. reactions to RCM has been investigated in some centers, but still
Corresponding author: Mario Sánchez-Borges, MD, Clínica El Avila, 6a. transversal remains a research tool and needs further validation.2 For RCM,
Urb. Altamira, piso 8, consultorio 803, Caracas 1060, Venezuela. E-mail: BAT sensitivity varies from 46% to 62%, and although speci-
[email protected].
2213-2198
ficity is high (88% to 100%), the results do not correlate with
Ó 2019 American Academy of Allergy, Asthma & Immunology symptom severity. Further research is required before routine
https://doi.org/10.1016/j.jaip.2018.06.030 usage of this diagnostic method can be recommended.12,15

60
J ALLERGY CLIN IMMUNOL PRACT SÁNCHEZ-BORGES ET AL 61
VOLUME 7, NUMBER 1

Figure 2 presents an algorithm suggested by some experts for

Abbreviations used the management of patients with immediate reactions to RCM
BAT- Basophil activation test that includes a role for the drug provocation test (DPT).
DPT- Drug provocation test
RCM- Radiographic contrast media The role of premedication
Premedication with corticosteroids, antihistamines, and sym-
pathomimetics to prevent severe reactions to RCM was proposed
The role of skin testing
years ago by Greenberger and Patterson28 in North America
Skin tests with RCM for diagnostic purpose are not routinely
(Table IV) and is the standard of care in all US institutions. The
performed outside specialized centers, although diagnostic
premedication regime has provided a significant reduction of
sensitivity and specificity of prick tests with undiluted RCM and
severe reactions using a pretreatment protocol with prednisone
intradermal tests with 1:10 dilution seem to be quite high. A
and diphenhydramine or prednisone, diphenhydramine, and
multicenter study demonstrated that up to 50% of the imme-
ephedrine.
diate reactors and up to 47% of nonimmediate reactors were skin
A recent large study increasing the median of days of oral
test positive when patients were tested within 2 to 6 months after
corticosteroid to 6 had substantial increased costs, side effects as
the initial reaction, whereas the skin test positivity decreased to
well as longer hospital stay.29
18% and 22% when tested after this time interval.11,16,17
Although premedication protocols are used around the world
The initial evaluation for immediate reactions includes skin
by radiologists, in Europe the value of premedication is consid-
testing with culprit RCM if the involved RCM is known. After
ered controversial, because it provides patients and physicians a
this step, if the test is positive or the RCM is unknown, a broad
false sense of security. Cases of “breakthrough reactions” despite
panel of RCM is tested. In patients who develop nonimmediate
premedication in untested patients have been reported.30,31
reactions, prick and intradermal tests with late readings, as well as
Although it has gained wide acceptance, it is not generally rec-
patch tests, are used in Europe (Table III).10,16-22
ommended by European colleagues because they consider that
The differences in recommendations on skin testing are re-
the evidence is weak and although it may be useful to reduce
flected in the different guidelines published by various national
mild immediate nonallergic reactions, its efficacy for immediate
and international scientific societies such as the 2010 Practice
moderate-to-severe and nonimmediate reactions has not been
Parameters from the American Academy of Allergy, Asthma and
confirmed.30,32
Immunology, the American College of Allergy, Asthma and
Immunology and the Joint Council of Allergy, Asthma and
Immunology,23 the American College of Radiology Contrast CONSENSUS RECOMMENDATIONS
Media Manual,24 and the International Consensus Document Current recommendations of this panel can be summarized as
on Drug Allergy.25 follows:
There are additional issues that are not currently elucidated
and make difficult to comment on test results. For example, in a 1. Skin testing for RCM immediate hypersensitivity may
study by Schrijvers et al,26 29% of patients were atopic and that potentially identify safe alternative(s) for re-exposure. How-
could influence skin testing results. Although the mechanism of ever, this still needs to be confirmed with additional pro-
immediate reactions seems mediated by IgE, transient positivity spective studies. The opinion of most members of the expert
has been observed and needs to be better understood. panel is that the evaluation of patients with RCM-induced
The role of cross reactions between different RCMs has been anaphylaxis or exanthema should always include appropriate
highlighted in a paper by Lerondeau et al,27 and confirmed by skin tests ensuring that patients with IgE-mediated or
Schrijvers et al,26 and should help identify safe alternative(s) for delayed-type allergy are not missed. Allergy testing may also
re-exposure relating to nonimmediate reactions. Present evidence identify alternative RCM that could be tolerated in future
suggests that cross-reactivity seems less understood in case of skin radiologic investigations.
testeproven immediate sensitization compared with non- 2. Considering that DPT involves the risk of severe reactions,
immediate RCM reactions. the expert group recommends that this is performed only in
Figures 2 and 3 present algorithms suggested by some experts selected cases using a skin testenegative RCM to identify
for the skin testebased management of patients with immediate alternative RCMs for further radiologic investigations.
and nonimmediate reactions to RCM. 3. Although recommendations on premedication are not stan-
dardized, anesthesiology specialists in the USA have been
The role of the drug provocation test using premedication guidelines for the last 20 years with good
Provocation tests with RCM have been used mainly in outcomes. Its use can be reserved to decrease reaction fre-
patients with a history of severe reactions to identify alternative quency or severity in high-risk patients (eg, those who have
RCMs. Increasing amounts of a skin testenegative RCM with a experienced previous anaphylactic reactions to RCM, masto-
different structure are administered under direct monitoring cytosis) including those who experienced severe immediate-
where emergency care equipment is ready. For example, doses of type reactions without evidence of an IgE-mediated mecha-
5, 15, 30, and 50 mL at 30- to 45-minute intervals for imme- nism. It is important to highlight that physicians using RCM
diate reactions and at 1-hour intervals for nonimmediate re- routinely should be trained to early recognize and treat
actions, with observation times at 3, 6, and 24 hours. anaphylaxis appropriately.33,34
However, dose titration is empiric, and there are no data to 4. Because skin tests and BAT are negative in the majority of
support that the procedure is safer than giving 1/10 and 9/10 of a control subjects, the negative predictive value is likely to be
target dose. Furthermore, more than 3 doses may induce high. However, the positive predictive value is unknown,
desensitization and provide a false sense of security. although some experts suggest that it is high especially for
62 SÁNCHEZ-BORGES ET AL J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019

TABLE I. Radiocontrast media currently available for diagnosis

Class Combination Iodine content (mg/mL) Osmolality (mOsm/kg)

Ionic monomers with high osmolality Sodium iothalamate 54% 325 1843
Meglumin diatrizoate 65% 306 1530
Ionic dimers with low osmolality Meglumin ioxaglate 39.5% 320 580
Sodium ioxaglate 19.6% 320 580
Nonionic monomers Iopamidol 61.2% 300 616
Iohexol 64.6% 300 640
Ioversol 63.6% 300 645
Iopromid 62.3% 300 610
Nonionic dimers Iotrolan 64.1% 300 320
Iodixanol 65.2% 300 290

TABLE II. Risk factors for hypersensitivity reactions to RCM

Radiocontrast Media Risk factor OR (95% CI)
37
Atopy 5.0
Asthma 8.74 (2.36-32.35)38
2.0 (0.8-5.1)39
Female gender 1.6 (1.3-2.0)39
Immediate Nonimmediate
Severe cardiovascular disease 7.71 (1.04-57.23)38
Repeated administration of RCM NA40
Previous reactions to RCM 15.9 (7.8-32.3)39
Drug allergy 1.4 (1.0-1.9)39
Mastocytosis NA41
T-cell mediated
CI, Confidence interval; OR, odds ratio; RCM, radiocontrast media.

Non
IgE-mediated
immunologic TABLE III. Skin test concentrations recommended for iodinated
radiocontrast media*
Readings
Direct effects of RCM Nonimmediate
the RCM Test concentration Immediate reactions reactions†

• On the mast Skin-prick test Undiluted 20 min 48 h, 72 h

cells Intradermal test 1:10 20 min 48 h, 72 h
• On other 1:1z Not recommended 24 h
cells Patch test Undiluted Not recommended 48 h, 72 h
(vessels,
bradikynin…) RCM, Radiocontrast media.
*Modified from Brockow and Sánchez-Borges.18
†For nonimmediate reactions, readings at 96 h and 7 d could also be applied.
zFor nonimmediate reactions, intradermal tests with the undiluted RCM and readings
FIGURE 1. Mechanisms of hypersensitivity reactions to at >24 h are associated with a higher sensitivity.
radiocontrast media. RCM, Radiocontrast media.

expert group considers that premedication in those patients

immediate reactions.25,35,36 Although provocation testing with a high risk for severe repeat reactions and a negative
outside the context of radiological imaging to verify negative allergy workup may help many patients and the benefits of
in vivo and in vitro test results has been used, it is not rec- premedication generally outweigh the potential harm. For
ommended because no controlled studies have provided evi- patients who have suffered Drug reaction with eosinophilia
dence of utility and can put patients at risk for a reaction and systemic symptoms (DRESS) or Stevens-Johnson syn-
outside a controlled environment. drome (SJS)/toxic epidermal necrolysis (TEN) associated with
5. There is no standardized premedication regime, with differ- RCM, the contrast media is contraindicated and a nonecross-
ences between the North American and European recom- reactive alternative will need careful evaluation. Premedication
mendations. Allergists and radiologists differ in the approach, is contraindicated in these patients and further exposure to the
and consensus multidisciplinary strategies (and even care same contrast can be lethal.
pathways) should be established to overcome differences be-
tween specialists. Recently, there has been some concern Unmet needs
related to adverse effects induced by systemic corticosteroids, There are several issues that need further research to improve
even when taken for short periods of time.29 However, the the knowledge in this field and consequently the quality of
J ALLERGY CLIN IMMUNOL PRACT SÁNCHEZ-BORGES ET AL 63
VOLUME 7, NUMBER 1

TABLE IV. Premedication for prophylaxis of reactions to radio-

Posive history of
contrast media*
Immediate reacon
Time before
injection (h) Pretreatment Recommended dose

13 Corticosteroid: prednisone 50 mg PO
RCM 7 Corticosteroid: prednisone 50 mg PO
RCM
known 1 Corticosteroid: prednisone 50 mg PO
unknown
1 Anti-H1 antihistamine: 1 mg/kg PO or IM
+ - diphenhydramine
IM, Intramuscular route; PO, oral administration.
Skin test with a ID test Skin prick and ID tests *Modified from Greenberger and Patterson.28
panel of RCM dil 1:10 with a panel
If posive: +
avoid this one - patients to assess the impact (efficacy/safety) of different pre-
If negave: medication protocols on clinical outcomes are needed.
Consider DPT
consider DPT
or Hypersensive Non
or
premedicaon rechallenge hypersensive REFERENCES
or alternave 1. Kim MH, Lee SY, Lee SE, Yang MS, Jung JW, Park CM, et al. Anaphylaxis to
RCM iodinated contrast media: clinical characteristics related with development of
anaphylactic shock. PLoS One 2014;9:e100154.
2. Salas M, Gomez F, Fernandez TD, Doña I, Aranda A, Ariza A, et al. Diagnosis
FIGURE 2. Skin testebased management of patients with im- of immediate hypersensitivity reactions to radiocontrast media. Allergy 2013;
mediate reactions to radiocontrast media. DPT, Drug provocation 68:1203-6.
test; RCM, radiocontrast media. 3. Goksel O, Aydın O, Atasoy C, Akyar S, Demirel YS, Misirligil Z, et al. Hy-
persensitivity reactions to contrast media: prevalence, risk factors and the role of
skin tests in diagnosis—a cross-sectional survey. Int Arch Allergy Immunol
Posive history of 2011;155:297-305.
4. Brockow K, Ring J. Anaphylaxis to radiographic contrast media. Curr Opin
Nonimmediate reacon
Allergy Clin Immunol 2011;11:326-31.
5. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K.
Adverse reactions to ionic and nonionic contrast media. A report from the
Patch and intradermal tests
Japanese Committee on the Safety of Contrast Media. Radiology 1990;175:
with reading at 48 and 72 hours 621-8.
6. Li X, Liu H, Zhao L, Liu J, Cai L, Liu L, et al. Clinical observation of adverse
+ - drug reactions to non-ionic iodinated contrast media in population with un-
derlying diseases and risk factors. Br J Radiol 2017;90:20160729.
7. Brockow K. Immediate and delayed reactions to radiocontrast media: is there an
Rechallenge
Rechallenge with allergic mechanism? Immunol Allergy Clin North Am 2009;29:453-68.
with alternave, 8. Laroche D, Namour F, Lefrançois C, Aimone-Gastin I, Romano A, Sainte-
culprit RCM
skin test Laudy J, et al. Anaphylactoid and anaphylactic reactions to iodinated contrast
negave RCM material. Allergy 1999;54(suppl 58):13-6.
9. Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an
indicator of mast-cell activation in systemic anaphylaxis and mastocytosis.
N Engl J Med 1987;316:1622-6.
Rechallenge
Not 10. Laroche D, Aimone-Gastin I, Dubois F, Huet H, Gérard P, Vergnaud MC, et al.
with alternave, Mechanisms of severe, immediate reactions to iodinated contrast material.
hypersensive
skin test Radiology 1998;209:183-90.
negave RCM 11. Brockow K, Romano A, Aberer W, Bircher AJ, Barbaud A, Bonadonna P, et al.
Skin testing in patients with hypersensitivity reactions to iodinated contrast
media—a European multicenter study. Allergy 2009;64:234-41.
RCM are contraindicated in paents with Stevens Johnson 12. Pinnobphun P, Buranapraditkun S, Kampitak T, Hirankarn N,
Syndrome, Toxic epidermal necrolysis or DRESS. Klaewsongkram J. The diagnostic value of basophil activation test in patients
with an immediate hypersensitivity reaction to radiocontrast media. Ann Allergy
Asthma Immunol 2011;106:387-93.
FIGURE 3. Skin testebased management of patients with non- 13. Mita H, Tadokoro K, Akiyama K. Detection of IgE antibody to a radiocontrast
medium. Allergy 1998;53:1133-40.
immediate reactions to radiocontrast media (RCM). RCM are 14. Kanny G, Pichler W, Morisset M, Franck P, Marie B, Kohler C, et al. T cell-
contraindicated in patients with Stevens-Johnson syndrome, toxic mediated reactions to iodinated contrast media: evaluation by skin and
epidermal necrolysis, or DRESS. DRESS, Drug reaction with lymphocyte activation tests. J Allergy Clin Immunol 2005;115:179-85.
eosinophilia and systemic symptoms. 15. Mayorga C, Celik G, Rouzaire P, Whitaker P, Bonadonna P, Rodrigues-
Cernadas J, et al. In vitro tests for drug hypersensitivity reactions: an ENDA/
EAACI Drug Allergy Interest Group position paper. Allergy 2016;71:1103-34.
patient’s care. Prospective investigations are needed that help 16. Rosado Ingelmo A, Doña Diaz I, Cabañas Moreno R, Moya Quesada MC,
clarify the clinical usefulness of skin testing with RCM to García-Avilés C, García Nuñez I, et al. Clinical practice guidelines for diagnosis
confirm or exclude an RCM allergy diagnosis and to select and management of hypersensitivity reactions to contrast media. J Investig
alternative RCMs in patients with a history of reactions. Beyond Allergol Clin Immunol 2016;26:144-53.
17. Brockow K, Garvey LH, Aberer W, Atanaskovic-Markovic M, Barbaud A,
tryptase, good diagnostic tools to evaluate the mechanism of Bilo MB, et al. Skin test concentrations for systemically administered drugs—an
RCM hypersensitivity reactions in real time are needed. Finally, ENDA/EAACI Drug Allergy Interest Group position paper. Allergy 2013;68:
controlled prospective multicentric studies with large numbers of 702-12.
64 SÁNCHEZ-BORGES ET AL J ALLERGY CLIN IMMUNOL PRACT
JANUARY 2019

18. Brockow K, Sánchez-Borges M. Hypersensitivity to contrast media and dyes. 30. Lasser EC, Berry CC, Mishkin MM, Williamson B, Zheutlin N, Silverman JM.
Immunol Allergy Clin North Am 2014;34:547-64. Pretreatment with corticosteroids to prevent adverse reactions to nonionic
19. Gall H, Pillekamp H, Peter RU. Late-type allergy to the X-ray contrast medium contrast media. AJR Am J Roentgenol 1994;162:523-6.
Solutrast (iopamidol). Contact Dermatitis 1999;40:248-50. 31. Tramer MR, von Elm E, Loubeyre P, Hauser C. Pharmacological prevention of
20. Caimmi S, Benyahia B, Suau D, Bousquet-Rouanet L, Caimmi D, Bousquet PJ, serious anaphylactic reactions due to iodinated contrast media: systematic re-
et al. Clinical value of negative skin tests to iodinated contrast media. Clin Exp view. BMJ 2006;333:675-81.
Allergy 2010;40:805-10. 32. Trcka J, Schmidt C, Seitz CS, Bröcker E-B, Gross GE, Trautmann A.
21. Kvedariene V, Martins P, Rouanet L, Demoly P. Diagnosis of iodinated contrast Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-
media hypersensitivity: results of a 6-year period. Clin Exp Allergy 2006;36: mediated allergy? AJR Am J Roentgenol 2008;190:666-70.
1072-7. 33. Dawson P, Sidhu PS. Is there a role for corticosteroid prophylaxis in patients at
22. Torres MJ, Gomez F, Doña I, Rosado A, Mayorga C, Garcia I, et al. Diagnostic increased risk of adverse reactions to intravascular contrast agents? Clin Radiol
evaluation of patients with nonimmediate cutaneous hypersensitivity reactions 1993;48:225-6.
to iodinated contrast media. Allergy 2012;67:929-35. 34. Bartlett MJ, Bynevelt M. Acute contrast reaction management by radiologists: a
23. Joint Task Force on Practice Parameters; American Academy of Allergy, local audit study. Australas Radiol 2003;47:363-7.
Asthma and Immunology; American College of Allergy, Asthma and 35. O’Neill JM, McBride KD. Cardiopulmonary resuscitation and contrast media
Immunology; Joint Council of Allergy, Asthma and Immunology. Drug al- reactions in a radiology department. Clin Radiol 2001;56:321-5.
lergy: an updated practice parameter. Ann Allergy Asthma Immunol 2010; 36. Yoon SH, Lee SY, Kang HR, Kim JY, Hahn S, Park CM, et al. Skin tests in
105:259-73. patients with hypersensitivity reaction to iodinated contrast media: a meta-
24. ACR Manual on Contrast Media. Version 10.3. ACR Committee on Drugs and analysis. Allergy 2015;70:625-37.
Contrast Media. American College of Radiology; 2017. 37. Ansell G, Tweedie MC, West CR, Evans P, Couch L. The current status of
25. Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, reactions to intravenous contrast media. Invest Radiol 1980;15(suppl):S32-9.
et al. International consensus on drug allergy. Allergy 2014;69:420-37. 38. Lang DM, Alpern MB, Visintainer PF, Smith ST. Elevated risk of
26. Schrijvers R, Breynaert C, Ahmedali Y, Bourrain JL, Demoly P, Chiriac A. Skin anaphylactoid reaction from radiographic contrast media is associated with
testing for suspected iodinated contrast media hypersensitivity. J Allergy Clin both beta-blocker exposure and cardiovascular disorders. Arch Intern Med
Immunol Pract 2018;6:1246-54. 1993;153:2033-40.
27. Lerondeau B, Trechot P, Waton J, Poreaux C, Luc A, Schmutz JL, et al. 39. Pradubpongsa P, Dhana N, Jongjarearnprasert K, Janpanich S, Thongngarm T.
Analysis of cross-reactivity among radiocontrast media in 97 hypersensitivity Adverse reactions to iodinated contrast media: prevalence, risk factors and
reactions. J Allergy Clin Immunol 2016;137:833-5. outcome—the results of a 3-year period. Asian Pac J Allergy Immunol 2013;31:
28. Greenberger PA, Patterson R. The prevention of immediate generalized re- 299-306.
actions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 40. Cochrane ST. Anaphylactoid reactions to radiocontrast media. Curr Allergy
1991;87:867-72. Asthma Rep 2005;5:28-31.
29. Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, et al. Short 41. Bonadonna P, Pagani M, Aberer W, Bilò MB, Brockow K, Oude Elberink H,
term use of oral corticosteroids and related harms among adults in the United et al. Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI posi-
States: population based cohort study. BMJ 2017;357:j1415. tion paper. Allergy 2015;70:755-63.