Diagnostic value of skin testing for hypersensitivity reactions to contrast media

Laatst beoordeeld: 24-06-2020

Uitgangsvraag

What is the diagnostic value of skin testing for hypersensitivity reactions to contrast media?

Aanbeveling

Do not perform skin tests routinely after every hypersensitivity reaction to a contrast medium.

 

Refer the patient to a specialist in drug allergy to perform skin tests within 6 months after the hypersensitivity reaction in the following patient groups:

  • Severe hypersensitivity reactions to a contrast medium.
  • Hypersensitivity reactions with increased tryptase levels.
  • Hypersensitivity reactions to 2 or more different contrast media of the same type (for example 2 different iodine-based CM) or to 2 or more types of contrast media (for example iodine-based CM and gadolinium-based CA).

Specify the used contrast agent in the referral.

 

Refer the patient to a specialist in drug allergy to perform skin tests in all patients with breakthrough hypersensitivity reactions despite premedication with corticosteroids and H1-antihistamines.

Overwegingen

As hypersensitivity reactions to CM have traditionally been classified as non-allergic reactions, skin tests have been regarded as inappropriate tools in patients having experienced such reactions. However, increasing evidence suggests that immunological mechanisms may be involved in CM-induced hypersensitivity reactions to a much larger degree, partly based on the positive skin tests in patients with both immediate and nonimmediate hypersensitivity reactions after CM exposure.

 

Implementing the results of skin tests might be a more valid alternative to prophylactic medication for prevention of the recurrence of CM reactions (Rosado Ingelmo, 2016). Skin tests have good sensitivity when performed within 6 months after the hypersensitivity reaction. After this time, sensitivity decreases. Therefor a speedy referral to a drug allergy specialist is recommended.

 

Few studies were found that met the inclusion criteria and were all with iodinated contrast media. Even though, no hard evidence is available on skin testing for gadolinium based CA, the hypersensitivity reactions are more often IgE-mediated in reactions after gadolinium-based CA and very similar in symptomatology to hypersensitivity reactions after iodine-based CM and therefore it seems logical to extend skin testing to hypersensitivity reactions to all CM (Clement, 2018).

 

Since included studies were considerable heterogeneous regarding to study setup and applied skin tests, no pooled outcomes of diagnostic test properties could be assessed which limits the recommendations that can be made on the current literature study.

 

If a previous reaction had shown a delayed cutaneous response it is unknown if premedication and or skin testing would reduce the risk of subsequent reactions. Delayed skin reactions may be life threatening notably when blistering has occurred. Skin testing in such cases may not be safe.

 

Performing and Reporting Skin Testing for Contrast Media

Most hospitals nowadays have contracts with just a few contrast media vendors. For skin testing of contrast media, however, it is important to test a panel of contrast agents (ICM and/or GBCA), including the culprit contrast agent and potential alternatives. Such a panel could be individualized for the specific hospital (group) where the patient comes from.

 

In order to facilitate establishment of such a local panel of iodine-based and gadolinium-based agents for allergologic skin testing, we have listed the available agents in The Netherlands and their indications below.

 

(See for physicochemical characteristics of GBCA also Table 1 in the Introduction to Safe Use of Gadolinium).

 

Table 2 Contrast agents in The Netherlands registered with the Medicine Evaluation Board

Iodine-based contrast media

Name

Commercial Name

Company

Main Indication

Iopromide

Ultravist

Bayer Healthcare

Intravascular CT/Angio

Iopamidol

Iopamiro

Bracco Imaging

Intravascular CT/Angio

Iomeprol

Iomeron

Bracco Imaging

Intravascular CT/Angio

Iohexol

Omnipaque

GE Healthcare

Intravascular CT/Angio

Iodixanol

Visipaque

GE Healthcare

Intravascular CT/Angio

Ioversol

Optiray

Guerbet

Intravascular CT/Angio

Iobitridol

Xenetix

Guerbet

Intravascular CT/Angio

 

 

 

 

Amidotrizoate meglumine

Gastrografine

Bayer Healthcare

Gastrointestinal RF/CT

Iopamidol

Gastromiro

Bracco Imaging

Gastrointestinal RF/CT

Ioxithalamate meglumine

Telebrix Gastro

Guerbet

Gastrointestinal RF/CT

 

Gadolinium-based contrast agents

Name

Commercial Name

Company

Allowed Indication

Gadobutrol

Gadovist

Bayer Healthcare

Total Body MRI

Gadoteridol

ProHance

Bracco Imaging

Total Body MRI

Gadoterate meglumine

Dotarem/Artirem

Guerbet

Total Body MRI

 

Clariscan

GE Healthcare

Total Body MRI

 

Dotagraf

Bayer Healthcare

Total Body MRI

Gadoxetate disodium

Primovist

Bayer Healthcare

Liver MRI

Gadobenate dimeglumine

MultiHance

Bracco Imaging

Liver MRI

Gadopentetate meglumine

Magnevist

Bayer Healthcare

MR Arthrography

 

See also: https://www.geneesmiddeleninformatiebank.nl/nl/

 

When reporting skin tests, it is optimal that the allergologist gives a clear written recommendation in the electronic patient dossier about:

  1. The possible ICM and/or GBCA that can be used in future CM-enhanced studies
  2. The use of or need for premedication in future CM-enhanced studies

Inleiding

Hypersensitivity reactions to contrast media (CM) have traditionally been classified as non-allergic reactions, and skin tests have been regarded as inappropriate tools in patients having experienced such reactions. However, during the last few years several investigators have reported positive skin tests in patients with both immediate and non-immediate hypersensitivity reactions after CM exposure, which indicates that immunological mechanisms may be involved much more frequently. In this chapter the diagnostic value of cutaneous tests for CM hypersensitivity reactions is assessed, which may serve as a more valid alternative to prophylactic medication for CM reactions. Furthermore, the working group evaluates whether these skin tests should be recommended in clinical practice, and under which conditions.

Conclusies

Acute Hypersensitivity Reactions: Negative Predictive value

Very Low

 GRADE

The negative predictive value of the cutaneous test is estimated to be 80 to 97%. The sensitivity and specificity for the cutaneous test for immediate hypersensitivity reaction to contrast media is unknown in patients suspected of contrast media hypersensitivity.

 

Sources: (Caimmi, 2010; Kim, 2013; Salas, 2013; Sesé, 2016)

 

Late Hypersensitivity Reactions: Negative Predictive value

Very Low

 GRADE

The negative predictive value of the cutaneous test is estimated to be 65%. The sensitivity and specificity for the cutaneous test for non-immediate hypersensitivity reaction to contrast media is unknown in patients suspected of contrast media hypersensitivity.

 

Sources: (Torres, 2012)

Samenvatting literatuur

1. Skin testing for acute (immediate) hypersensitivity reactions to contrast media

The diagnostic properties of cutaneous tests for acute (immediate) hypersensitivity reactions (HSR) to Contrast Media (CM) were evaluated in 4 studies (Caimmi, 2010; Kim, 2013; Salas, 2013; Sesé, 2016).

 

Caimmi (2010) studied 159 patients. Patients were tested with the culprit iodine-based contrast medium (ICM) and a set of other ICM if they were positive for the culprit ICM or if its name was unknown. In order to know which ICM was involved, either patients already knew which drug had supposedly caused the reaction and provided us the name, or we contacted the hospital in which the reaction had occurred. The ICM used were: amidotrizoate, ioxithalamate, iopamidol, iohexol, ioversol, iopromide, iomeprol, iobitridol, iodixanol and ioxaglate. Skin tests were performed firstly as prick tests with the undiluted commercially available solution and then, if negative, by intradermal tests (IDT) at a 1: 10 dilution. Prick tests were considered positive if, after 15 min, the size of the weal was at least 3 mm in diameter. For IDT, positivity was considered when the size of the initial weal increased by at least 3 mm in diameter after 15 to 20 min, considering as non-irritant a maximum dilution of 1/10. The negative predictive value was defined as the proportion of patients with negative skin test results to at least one ICM at first testing who had a further injection with that ICM without reacting. One hundred participated (75.5% participation rate). Seventy-one of them (5 9.2%) were females of a median age of 56 (45–65) years. The majority of the reactions were immediate (101 out of 120, 84.2%), and in two cases, it was not possible to assess whether the reaction was immediate or non-immediate. For immediate reactions, 42 (41.6%) were of grade 1, 34 (33.7%) of grade 2, 20 (19.8%) of grades 3 and five (4.9%) of grade 4. Only one (5.9%) of the 17 non-immediate reactions was moderate, all the others were mild (16 to 94.1%).

 

Kim (2013) retrospectively included 1048 patients. The mean (SD) age was 55.1 (14.5) years; 501 (47.8%) were male. Intradermal test with the RCM that was to be used in the

pending nonionic CM-enhanced CT was performed just before the CT examinations. The nonionic CM used in our contrast CT scans was iopromide, iomeprol, iohexol, and iodixanol. Intradermal tests were conducted on the volar surface of the forearm with a negative control, saline. A 1:10 solution of contrast medium (0.03 to 0.05 mL), which has been accepted as a non-irritating concentration, was gently injected into the skin to produce a small superficial bleb of 2 to 4 mm. Skin test positivity was determined when the diameter of the wheal increased by at least 3 mm, and surrounding erythema was observed after 15 to 20 minutes. If a patient had a negative response to skin tests, CT was performed as scheduled (provocation). Of the 376 patients previously exposed to CM, 61 (16.2%) had a history of at least 1 mild CM-associated reaction: 56 (91.8%) had immediate and 5 (8.2%) non-immediate reactions.

 

Salas (2013) included 90 patients with a history of immediate HSR after contrast media (CM). Immediate HSR was classified according to the Ring and Messmer scale.

 

Skin Test (ST) was carried out using the following CM: iobitridol, iomeprol, iodixanol, iohexol, ioversol, iopromide and ioxaglate. Prick tests were performed using undiluted CM and IDT using 10-fold dilutions. In those with a negative ST, a single-blind placebo-controlled provocation test was performed with the CM involved, as described. In patients with a positive ST and/or provocation test, a basophil activation test (BAT) was performed with iohexol (3; 0.3 mg/ml), iodixanol (3; 0.3 mg/ml), iomeprol (3.5; 0.35 mg/ml) and ioxaglate (5.8; 0.58 mg/ml) (based on dose–response curves and cytotoxicity studies). The median age of the subjects evaluated was 54.50 ± 27 years; 63 (60%) were women. The CM involved in the reaction was iomeprol in 26 cases (28.89%), iodixanol in 19 (21.11%), iohexol in 11 (12.22%), iopromide in 9 (10.00%) and unknown in 25 (27.78%). According to the clinical history, most cases developed reactions with skin involvement (65.65% urticaria/ angioedema and 30% generalized erythema), and only 4.44% had airway or cardiovascular involvement. Regarding symptom severity, 69 cases (76.71%) had grade I reactions, 18 (20%) grade II and 3 (3.33%) grade III. No patients had grade IV reactions.

 

Sesé (2016) included 37 patients with a definite history of immediate HSR due to Iodine-based Contrast Media (ICM). Immediate HSR was classified according to the Ring and Messmer scale. Skin tests were performed at least 6 weeks after the HSR on the volar forearm with the suspected ICM and with four other ICM. Skin prick tests (SPTs) involved freshly prepared undiluted ICM commercial solutions, and intradermal tests (IDTs) were performed successively with 100-fold and then 10-fold solution diluted in 0.9% sterile saline. Saline and chlorhydrate histamine were negative and positive controls, respectively. In total, 37 patients (24 women, mean age 49.3 years at the time of the reaction) completed the tests. The clinical severity of the reaction was grade I for 26 (70%), grade II for 4 (11%), and grade III for 7 (19%); 35 (95%) reported skin or mucosal symptoms, including pruritus (n = 11), facial erythema (n = 6), generalized erythema (n = 20), urticaria (n = 7), and angioedema (n = 5).

 

2. Skin testing for late (delayed) hypersensitivity reactions to contrast media

The diagnostic property of cutaneous tests for late (non-immediate) hypersensitivity reactions (HSR) to Iodinated Contrast Media (ICM) was evaluated in one study (Torres, 2012). Torres included a total of 161 subjects with a history of a non-immediate reaction imputable to at least one CM was evaluated. One patient who developed Stevens–Johnson syndrome was not included. The median age was 58.5 years (IR: 48.85 to 66.5) with 82 men (50.9%). According to the information obtained from the clinical history, the CM involved in the reaction were iomeprol in 53 (32.9%), iodixanol in 46 (28.6%), iohexol in 27 (16.8%), iobitridol in 4 (2.5%), ioversol in 3 (1.9%), iopromide in 3 (1.9%), ioxaglate in 2 (1.2%) and unknown in 23 (14.3%). According to the clinical history, 108 cases (67.1%) developed symptoms compatible with exanthema and 53 (32.9%) with delayed urticaria. Regarding symptom severity, 16 cases (9.9%) had mild reactions, 143 (88.8%) moderate reactions, and 2 severe reactions (1.2%) consisting of desquamative exanthema. Concerning the number of episodes, 132 cases (82%) had one episode and 29 cases (18%) two episodes.

 

Results

1. Skin testing for acute hypersensitivity reactions

Negative predictive value

The rate of a positive skin test in the study of Sesé (2016) was 13.5% (95% CI 4 to 29%) and increased to 20% (95% CI 4 to 48%) for patients who consulted during the year after the HSR. Among the 32 patients with negative skin test results, 31 were challenged successfully, 15 with the culprit ICM. One grade I reaction occurred 2 h after challenge (generalized pruritus, erythema, and eyelid oedema lasting < 1 h) and was considered a positive intravenous challenge result. At 2 h after provocation test, two patients reported generalized and isolated pruritus that regressed with antihistamine therapy and was not considered a positive IPT result. None of five patients with positive skin test to ICM were re-exposed to contrast media during radiologic examination, positive predictive could not be calculated. For an immediate HSR to ICM, the negative predictive value for skin tests with low dose was 80% (95% CI 44 to 97%).

 

Kim (2013) showed that among the 1046 patients who had negative responses on skin tests, 52 (5.0%) showed immediate-type adverse reactions after CT using radio contrast media. However, most reactions were mild and cutaneous, such as pruritus, urticaria, and mild angioedema. Only 1 patient (0.1%) had a grade II moderate immediate reaction accompanied by breathing difficulty and mild laryngeal oedema, which were relieved with an antihistamine. The negative predictive value of the pre-screening skin test for immediate hypersensitivity reactions before contrast media administration was 95.0%. The negative predictive value of the skin test for immediate hypersensitivity reactions in patients with a history of contrast media hypersensitivity reactions was 80.3% (n= 49/61) and that in patients without a history was 95.9% (n= 945/985).

 

Results of Salas (2013) showed that five subjects (5.56%) had a positive skin test: three by prick test (one to iodixanol, one to iomeprol and one to iohexol) and five by intradermal testing (four to iohexol, three iodixanol and two to iomeprol). In cases with a negative skin test to all CM tested (N = 74), provocation test was carried out with the culprit CM if known, being positive in three cases; one to iodixanol, one to iomeprol and one to iodixanol, iohexol plus iomeprol. In total, 11 patients with a negative ST refused to undergo a provocation test, resulting in a negative predictive value to immediate hypersensitivity reactions of 95.26%. Eight (8.9%) cases were confirmed as having IHR, 5 (62.5%) by ST and 3 (37.5%) by provocation test. Five from those confirmed as IHR (62.5%) had a positive BAT.

 

The results of Caimmi (2010) revealed that ICM skin tests were positive in 21 patients (17.5%). Seventeen of them (80.9%) had a history of immediate reaction (four with grade 1, eight grade 2, four grade 3 and one grade 4). Prick tests were all negative. IDT were positive at 20 min for 15 patients with an immediate history and for the patient with unknown chronology. Caimmi (2010) found one single false negative; the negative predictive value of ICM skin tests was 96.6% (95% CI: 89.9 to 103.2).

 

Quality of evidence

The quality of certainty of evidence was graded as very low due to high risk of bias (see Tab Rob assessment, downgraded by two points) and low number of patients (imprecision downgraded by one point).

 

2. Skin testing for delayed hypersensitivity reactions

Negative predictive value

In the total group of cases evaluated (N = 161), 34 subjects (21.1%) developed a delayed reading of the intradermal tests positive (13 at 1/10 dilution and 29 undiluted). Of these, 27 were skin-test positive to just one CM, 6 to two CM and 1 to three. The immediate reading of the intradermal tests was negative in all cases. The skin test was positive to iomeprol in 21 cases (50%), to iodixanol in 7 (16.7%), to iobitridol in 5 (11.9%), to ioxaglate in 4 (9.5%), to iohexol in 3 (7.1%) and to iopromide in 1 (2.4%). In the 34 cases with a positive intradermal test, 10 also had a positive patch test. No positive patch tests were detected in the patients with negative intradermal results. In the patients with a negative skin test to all the CM tested (N = 127), a provocation test was carried out with the CM involved. Provocation test was positive in 44 cases (34.6%), 19 to one CM and 3 to two CM. Thirty-eight cases (76%) were positive to iodixanol, 8 (16%) to iomeprol and 4 (8%) to iohexol. The time interval between administration and symptom development was: 1 to 6 h (13 cases), 7 to 12 h (27 cases), 13 to 24 h (68 cases), 25 to 48 h (41 cases) and > 48 h (12 cases).

 

Quality of evidence

The quality of certainty of evidence was graded as very low due to high risk of bias (see Tab Rob assessment, downgraded by two points) and low number of patients (imprecision downgraded by one point).

 

Positive rates of cutaneous tests

The positive rate of cutaneous tests was reported in 12 studies. Since these studies do not compare cutaneous tests with a provocation test, they are not in line with the PICO. However, studies on positive rates of skin tests in patients with HSR to ICM contain important clinical information. Therefore, we have additionally synthesized literature evaluating positive rates of cutaneous tests in patients with HSR to ICM. Since these studies do not describe comparative research, we did not create risk of bias and evidence tables for these studies.

In patients with immediate HSR to ICM, the pooled positive rate of skin tests was 17% (95% CI, 11–26%; I2= 45%) and was identical to that of IDT (Table 1). The pooled positive rate of SPTs was 3% (95%CI= (1-5%); I2= 0%). The pooled positive rates of IDT were shown to rise as the severity of reactions increased: pooled positive rate for mild HSR is 12% (95%CI= (6 to 23%); I2= 38%); moderate HSR 16% (95%CI= (10 to 24%); I2 = 6%) and for severe HSR, 52% (95%CI= (31 to 74%), I2= 42%). Table 1 presents a detailed overview of positive rates across studies. Figure 1 presents an overview of per-test cross-reactivity rates between pairs of ICM in skin test positive patients with HSR to ICM.

 

Table 1 Positive rates of cutaneous tests in patients with immediate HSR to ICM

 

 

Positive rate of skin tests, %

Test Site

Positive rate of IDT, %

Severity of HSR

 

 

SPTa

IDTb

SPTa

IDTb

Mild

Moderate

Severe

Dewachter, 2001

ICMc

50 (2/4)

100 (4/4)

Forearm

Back

-

-

100 (4/4)

Trcka, 2008

ICMc

-

4 (4/96)

Not specified

Not specified

0 (0/40)

7 (3/44)

8 (1/12)

Brockow, 2009

ICMc

3 (4/122)

26 (32/121)

Forearm

Forearm

26 (24/92)

-

28 (8/29)

Caimmi, 2010

ICMc

0 (0/101)

15 (15/101)

Not specified

Not specified

-

-

-

Dewachter, 2011

ICMc

4 (1/24)

46 (12/26)

Forearm

Back

33 (3/9)

40 (4/10)

71 (5/7)

Goksel, 2011

ICMc

0 (0/14)

14 (2/14)

Forearm

Forearm

14 (1/7)

14 (1/7)

-

Pinnobphun, 2011

ICMc

0 (0/63)

24 (15/63)

Not specified

Not specified

23 (12/53)

0 (0/5)

60 (3/5)

Kim, 2013

ICMc

3 (1/32)

26 (12/46)

Not specified

Forearm

13 (4/31)

25 (2/8)

57 (4/7)

Kim, 2014

ICMc

2 (1/51)

65 (33/51)

Forearm

Forearm

-

18 (2/11)

78 (31/40)

Renaudin, 2013

ICMc

14 (1/7)

57 (4/7)

Not specified

Not specified

-

-

57 (4/7)

Prieto-Garcia, 2013

ICMc

0 (0/106)

10 (11/106)

Not specified

Not specified

9 (6/66)

14 (4/29)

9 (1/11)

Salas, 2013

ICMc

3 (3/90)

6 (5/90)

Not specified

Forearm

0 (0/69)

11 (2/18)

100 (3/3)

Sesé, 2016

ICMc

3 (1/37)

13.5% (5/37)

Forearm

Not specified

11 (4/37)

3 (1/37)

-

aSPT = Skin Prick Test; bIDT= Intradermal Test; cIodine-based Contrast Media

 

F1

Figure 1 Cross-reactivity rates between pairs of ICM in skin test-positive patients with HSR to ICM. (from meta-analysis Yoon et al. Allergy 2015)

Cross-reactivity was extracted based on the results of intradermal test with 10-1 diluted ICM and patch test with undiluted ICM. If available, results of drug provocation test and graded challenge were also used. The number of † is the number of pooled studies. Pooled cross-reactivity rate is categorized and expressed in grey scale: white, pooled point estimate is ≤10%, and its upper limit of 95% CI is ≤30%; light grey, pooled point estimate is 11% and 15%, or pooled point estimate is ≤10 with its upper limit of 95% CI is >30%; grey, pooled point estimate ranged from 16% and 25%; dark grey, pooled point estimate ranged from 26% and 50%.

 

HSR, hypersensitivity reaction; ICM, iodinated contrast media; CI, confidence interval.

Zoeken en selecteren

To answer our clinical question a systematic literature analysis was performed for the following research question:

What is the diagnostic value of cutaneous testing for hypersensitivity reactions to contrast media?

 

P (patient category): patients with hypersensitivity reactions after radiological examinations with contrast media;

I (intervention): cutaneous tests: skin test, patch test (PT), Intradermal test (IDT), skin prick test (SPT) or scratch test;

C (comparison) clinical diagnosis of hypersensitivity reaction after contrast administration;

R (Reference) drug provocation test;

O (outcome) correctly confirmed diagnosis of hypersensitivity reaction to contrast media (sensitivity, specificity, area under the curve, positive predictive value, negative predictive value).

 

Relevant outcome measures

The working group considered sensitivity and specificity critical outcome measures for the decision-making process; and considered the area under the curve and the positive and negative predictive values important outcome measures.

 

Search and select (method)

The databases Medline (OVID), Embase and the Cochrane Library were searched from January 1985 to 4th of January 2018 using relevant search terms for systematic reviews (SRs), randomized controlled trials (RCTs) and observational studies (OBS). The literature search resulted in 358 hits: 7 SRs, 33 RCTs and 318 OBS.

 

Studies were selected based on the following criteria:

  • adult patients with hypersensitivity reaction to contrast media;
  • evaluation of diagnostic properties of cutaneous tests to contrast media;
  • application of a provocation test to confirm results of cutaneous testing;
  • reports predefined outcome measures: sensitivity, specificity, area under the curve, positive predictive value, negative predictive value;
  • no reports of case series or exploratory findings (n ≥ 10).

 

Based on title and abstract a total of 37 studies were selected. After examination of full text a total of 33 studies were excluded and five studies were definitely included in the literature summary. Reason for exclusion is reported in exclusion table.”). Cross-referencing leads to the inclusion of one additional study.

 

Five studies were included in the literature analysis; the most important study characteristics and results were included in the evidence tables. The evidence tables and assessment of individual study quality are included. Since study setup, and applied cutaneous tests differed across the studies, we were not able to pool the outcome of the diagnostic test properties.

 

A total of 13 studies did not fulfil the predefined selection criteria, but described the positive rates of cutaneous tests in patients that had a hypersensitivity reaction after CM administration. The positive rates in these studies are also described under Positive rates of cutaneous tests. Because these studies did not fulfil the selection criteria, and did not include a comparison to a reference test, only descriptive data of these studies was shown, and evidence tables and risk of bias tables of these studies are not included.

Referenties

  1. Brockow K, Romano A, Aberer W, Bircher AJ, Barbaud A, Bonadonna P, Faria E, Kanny G, Lerch M, Pichler WJ, Ring J, Rodrigues Cernadas J, Tomaz E, Demoly P, Christiansen C; European Network of Drug Allergy and the EAACI interest group on drug hypersensitivity. Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study. Allergy. 2009 Feb;64(2):234-41. doi: 10.1111/j.1398-9995.2008.01832.x. PubMed PMID: 19178403.
  2. Caimmi S, Benyahia B, Suau D, Bousquet-Rouanet L, Caimmi D, Bousquet PJ, Demoly P. Clinical value of negative skin tests to iodinated contrast media. Clin Exp Allergy. 2010 May;40(5):805-10. doi: 10.1111/j.1365-2222.2010.03493.x. Epub 2010 Mar 12. PubMed PMID: 20337646.
  3. Clement O, Dewachter P, Mouton-Faivre C, Nevoret C, Guilloux L, Bloch Morot E, Katsahian S, Laroche D; investigators of the CIRTACI study. Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study. EClinicalMedicine 2018; 1: 51-61.
  4. Dewachter P, Mouton-Faivre C, Felden F. Allergy and contrast media. Allergy. 2001 Mar;56(3):250-1. PubMed PMID: 11251409.
  5. Dewachter P, Laroche D, Mouton-Faivre C, Bloch-Morot E, Cercueil JP, Metge L, Carette MF, Vergnaud MC, Clément O. Immediate reactions following iodinated contrast media injection: a study of 38 cases. Eur J Radiol. 2011; 77: 495-501.
  6. Goksel O, Aydın O, Atasoy C, Akyar S, Demirel YS, Misirligil Z, Bavbek S. Hypersensitivity reactions to contrast media: prevalence, risk factors and the role of skin tests in diagnosis--a cross-sectional survey. Int Arch Allergy Immunol. 2011;155(3):297-305. doi: 10.1159/000320760. Epub 2011 Feb 3. PubMed PMID: 21293150.
  7. Kim MH, Lee SY, Lee SE, Yang MS, Jung JW, Park CM, Lee W, Cho SH, Kang HR. Anaphylaxis to iodinated contrast media: clinical characteristics related with development of anaphylactic shock. PLoS One. 2014 Jun 16;9(6):e100154. doi:10.1371/journal.pone.0100154. eCollection 2014. PubMed PMID: 24932635; PubMed Central PMCID: PMC4059752.
  8. Kim SH, Jo EJ, Kim MY, Lee SE, Kim MH, Yang MS, Song WJ, Choi SI, Kim JH, Chang YS. Clinical value of radiocontrast media skin tests as a prescreening and diagnostic tool in hypersensitivity reactions. Ann Allergy Asthma Immunol. 2013 Apr;110(4):258-62. doi: 10.1016/j.anai.2013.01.004. Epub 2013 Feb 4. PubMed PMID: 23535089.
  9. Pinnobphun P, Buranapraditkun S, Kampitak T, Hirankarn N, Klaewsongkram J. The diagnostic value of basophil activation test in patients with an immediate hypersensitivity reaction to radiocontrast media. Ann Allergy Asthma Immunol. 2011 May;106(5):387-93. doi: 10.1016/j.anai.2010.12.020. Epub 2011 Feb 5. PubMed PMID: 21530870.
  10. Prieto-García A, Tomás M, Pineda R, Tornero P, Herrero T, Fuentes V, Zapatero L, de Barrio M. Skin test-positive immediate hypersensitivity reaction to iodinated contrast media: the role of controlled challenge testing. J Investig Allergol Clin Immunol. 2013;23(3):183-9. PubMed PMID: 23967757.
  11. Renaudin JM, Beaudouin E, Ponvert C, Demoly P, Moneret-Vautrin DA. Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy. 2013 Jul;68(7):929-37. doi:10.1111/all.12168. Epub 2013 Jun 6. PubMed PMID: 23741979.
  12. Rosado Ingelmo A, Doña Diaz I, Cabañas Moreno R, Moya Quesada MC, García-Avilés C, García Nuñez I, et al. Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media. J Investig Allergol Clin Immunol. 2016;26(3):144-155.
  13. Salas M, Gomez F, Fernandez TD, Doña I, Aranda A, Ariza A, Blanca-López N, Mayorga C, Blanca M, Torres MJ. Diagnosis of immediate hypersensitivity reactions to radiocontrast media. Allergy. 2013 Sep;68(9):1203-1206.
  14. Sesé L, Gaouar H, Autegarden JE, Alari A, Amsler E, Vial-Dupuy A, Pecquet C, Francès C, Soria A. Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose. Clin Exp Allergy. 2016 Mar;46(3):472-8. doi: 10.1111/cea.12703. PubMed PMID: 26750091.
  15. Torres MJ, Gomez F, Doña I, Rosado A, Mayorga C, Garcia I, Blanca-Lopez N, Canto G, Blanca M. Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity reactions to iodinated contrast media. Allergy. 2012 Jul;67(7):929-35. doi: 10.1111/j.1398-9995.2012.02840.x. Epub 2012 May 15. PubMed PMID: 22583135.
  16. Trcka J, Schmidt C, Seitz CS, Bröcker EB, Gross GE, Trautmann A. Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-mediated allergy? AJR Am J Roentgenol. 2008 Mar;190(3):666-70. doi: 10.2214/AJR.07.2872. PubMed PMID: 18287437.

Evidence tabellen

Evidence table for diagnostic test accuracy studies

Study reference

Study characteristics

Patient characteristics

Index test (Test of interest)

Reference test

Follow-up

Outcome measures and effect size

Comments

Caimmi, 2010

 

Type of study[1]:

Case-control cohort

 

Setting: Hospital

 

Country: France

 

Conflicts of interest:

None

Inclusion criteria:

NR

Exclusion criteria:

NR

N=159

 

Median age [range]: 56 years [45-65]

 

 

 

Sex: 60% F

 

Describe index test:

Skin test

 

Cut-off point(s): Skin

test positivity was determined when the diameter of the wheal increased by at least 3 mm, and surrounding erythema was observed after 15 to 20 minutes

 

Comparator test[2]:

NR

Cut-off point(s):

NR

Describe reference test[3]:

Provocation Negative skin test

 

 

Cut-off point(s): NR

 

 

Time between the index test en reference test:

NR

 

For how many participants were no complete outcome data available?

N (100%)

 

 

Outcome measures and effect size (include 95%CI and p-value if available)4:

Negative predictive value skintest:

96.6% (95% CI: 89.9–103.2)

Clinical testing for ICM hypersensitivity has a negative predictive value of 96.6% (95% CI: 89.9–103.2) and none of the reactions in skin-test-negative patients were severe. Multi-centric large surveys are still needed for confirmation

Kim, 2013

Type of study:

Prospective follow-up.

 

Setting: Hospital

 

Country: Korea

 

Conflicts of interest:

NR

Inclusion criteria:

We prospectively enrolled patients who were to undergo CT

using RCM at Seoul National University Bundang Hospital from July

to November 2010.

 

Exclusion criteria:

Patients who did not consent to the study or who had been

administered premedications, such as steroids, antihistamines, or

other medications that may have affected the skin test results, were

excluded from the study

 

N=1048

 

Mean age ± SD: 55.1 years (14.5)

 

Sex: 48% M

Describe index test:

Skin test

 

Cut-off point(s):

Skin

test positivity was determined when the diameter of the wheal increased by at least 3 mm, and surrounding erythema was observed after 15 to 20 minutes

 

Cut-off point(s):

NR

Describe reference test:

Provocation to CM by Negative skin test

 

 

Cut-off point(s): NR

 

 

Time between the index test en reference test:

 

For how many participants were no complete outcome data available?

N (100%)

 

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

Negative predictive value skintest:

80%

RCM skin testing for screening is of no clinical utility in predicting hypersensitivity reactions.

RCM skin testing may have modest utility in retrospectively evaluating severe adverse reactions.

Salas, 2013

Type of study:

Retrospective study

 

Setting: Hospital

 

Country: Spain

 

Conflicts of interest: None

 

Inclusion criteria:

NR

Exclusion criteria: NR

 

N=90

 

Mean age: 54.5 years (SD 27)

 

Sex: 60% F

 

Describe index test:

Skin test

 

Cut-off point(s): NR

 

 

Comparator test: basophil

activation test (BAT)

 

Cut-off point(s): NR

 

Describe reference test:

Provocation test

 

 

Cut-off point(s): NR

 

 

Time between the index test en reference test: NR

 

For how many participants were no complete outcome data available?

N=11 (17%)

 

Reasons for incomplete outcome data described? NR

Outcome measures and effect size (include 95%CI and p-value if available):

 

Negative predictive value skintest:

91%

ST or DPT. BAT proved a valuable method for diagnosis confirmed hypersensitivity to RCM in 9%.

Sesé, 2016

Type of study:

Retrospective study

 

Setting: Hospital

 

Country: France

 

Conflicts of interest: None

Inclusion criteria:

NR

Exclusion criteria: NR

 

N=37

 

Mean age: 54.5 years (SD 27)

 

Sex: 65% F

 

Describe index test:

Skin test

 

Cut-off point(s): least

3 mm in diameter with erythema

 

 

Comparator test: NR

 

Cut-off point(s): NR

Describe reference test:

Provocation test

 

 

Cut-off point(s): NR

 

 

Time between the index test en reference test: NR

 

For how many participants were no complete outcome data available?

(100%)

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

Negative predictive value skintest:

80%

For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44–97%).

Torres, 2012

Type of study:

Retrospective study

 

Setting: Hospital

 

Country: Spain

 

Conflicts of interest: NR

Inclusion criteria:

NR

Exclusion criteria: NR

 

N=161

 

Mean age: 58.5 years (IR: 48-67))

 

Sex: 51% M

 

Describe index test:

Skin test

 

Cut-off point(s): least

3 mm in diameter with erythema

 

 

Comparator test: NR

 

Cut-off point(s): NR

Describe reference test:

Provocation test

 

 

Cut-off point(s): NR

 

 

Time between the index test en reference test: NR

 

For how many participants were no complete outcome data available?

(100%)

 

Outcome measures and effect size (include 95%CI and p-value if available):

 

Negative predictive value skintest:

65.4%

Patients with nonimmediate reactions to CM were identified by skin testing in 43.6% and by DPT in 56.4%. The method to confirm the diagnosis differed depending on the CM involved

 

Risk of bias assessment diagnostic accuracy studies (QUADAS II, 2011)

Study reference

Patient selection

 

Index test

Reference standard

Flow and timing

Comments with respect to applicability

Caimmi, 2010

 

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Yes

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

No

 

If a threshold was used, was it pre-specified?

No

 

 

 

Is the reference standard likely to correctly classify the target condition?

Yes

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

No

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

 

Are there concerns that the included patients do not match the review question?

Unclear

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

Unclear

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW/HIGH/UNCLEAR

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: HIGH

 

Kim, 2013

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Unclear

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Unclear

 

 

 

Is the reference standard likely to correctly classify the target condition?

Yes

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

No

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

 

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW/HIGH/UNCLEAR

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: LOW /HIGH/UNCLEAR

 

Salas, 2013

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Unclear

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Unclear

 

 

 

Is the reference standard likely to correctly classify the target condition?

Yes

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

No

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

Unclear

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW/HIGH/UNCLEAR

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: LOW /HIGH/UNCLEAR

 

Sesé, 2016

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Unclear

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Unclear

 

 

 

Is the reference standard likely to correctly classify the target condition?

Yes

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

No

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW/HIGH/UNCLEAR

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: LOW /HIGH/UNCLEAR

 

Torres, 2012

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Unclear

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Unclear

 

 

 

Is the reference standard likely to correctly classify the target condition?

Yes

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

No

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW/HIGH/UNCLEAR

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: LOW /HIGH/UNCLEAR

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: LOW /HIGH/UNCLEAR

 

Judgments on risk of bias are dependent on the research question: some items are more likely to introduce bias than others, and may be given more weight in the final conclusion on the overall risk of bias per domain:

Patient selection:

Consecutive or random sample has a low risk to introduce bias.

A case control design is very likely to overestimate accuracy and thus introduce bias.

Inappropriate exclusion is likely to introduce bias.

 

Index test:

This item is similar to “blinding” in intervention studies. The potential for bias is related to the subjectivity of index test interpretation and the order of testing.

 Selecting the test threshold to optimise sensitivity and/or specificity may lead to overoptimistic estimates of test performance and introduce bias.

 

Reference standard:

When the reference standard is not 100% sensitive and 100% specific, disagreements between the index test and reference standard may be incorrect, which increases the risk of bias.

This item is similar to “blinding” in intervention studies. The potential for bias is related to the subjectivity of index test interpretation and the order of testing.

 

Flow and timing:

If there is a delay or if treatment is started between index test and reference standard, misclassification may occur due to recovery or deterioration of the condition, which increases the risk of bias.

 

If the results of the index test influence the decision on whether to perform the reference standard or which reference standard is used, estimated diagnostic accuracy may be biased.

All patients who were recruited into the study should be included in the analysis, if not, the risk of bias is increased.

 

Judgement on applicability:

Patient selection: there may be concerns regarding applicability if patients included in the study differ from those targeted by the review question, in terms of severity of the target condition, demographic features, presence of differential diagnosis or co-morbidity, setting of the study and previous testing protocols.

 

Index test: if index tests methods differ from those specified in the review question there might be concerns regarding applicability.

Reference standard: the reference standard may be free of bias but the target condition that it defines might differ from the target condition specified in the review question

 

Table: Exclusion after revision of full text

Author and year

Reason for exclusion

Ahn, 2015

Study does not meet the PICO criteria; no reference test was used to confirm response on skintest (provocation test)

Barbaud, 2014

Literature overview does not meet the PICO criteria

Berti, 2016

Study does not meet the PICO criteria

Brockow, 1999

Case report (n=1)

Brockow, 2009

Case report study (n=1)

Cabenas, 2017

Evalaution of the diagnostic properties of the Lymphocytic transformation test (i) for drug-induced reactions.

Carr, 2016

Literature overview does not meet the PICO criteria

Chiriac, 2011

Study does not meet the PICO criteria; no provocation test to confirm skin test results

Chirumbolo, 2013

Study does not meet the PICO criteria; diagnostic properties of the Basophil activation test (BAT)

Della-Torre, 2015

Study does not meet the PICO criteria; no reference test was used to confirm response on skintest (provocation test)

Goksel, 2011

Study does not meet the PICO criteria; no provocation test to confirm skin testing results

Gómez, 2013

Literature overview (no systematic review)

Hasdenteufel, 2011

Study does not meet the PICO criteria; no provocation test to confirm skin testing results

Kim, 2014

Study does not meet the PICO criteria; case control study on clinical outcome and characteristics following skin testing.

Kvedariene, 2006

Study does not meet the PICO criteria; comparison of patients with postive and negative ICM skin tets (no diagnostic evaluation)

Lerch, 2007

Caseseries report (n=2)

Lerondeau, 2016

Letter to the Editor

Mangodt, 2015

Study does not meet the PICO criteria; diagnostic properties of Basophil Activation Test

Morales-Cabeza, 2017

No evaluation of diagnostic properties of tests but evaluating the clinical and allergologic features of IHRs to ICMs.

Nyfeler, 1997

Study does not meet the PICO criteria; no evaluation of radiocontrast media reaction

Ohtoshi, 2014

Study does not meet the PICO criteria; no provocation test to confirm Patch testing results

Prieto-García, 2013

Study describes characteristics and does not analyze diagnostic properties of skin tests

Ramirez, 2014

Study does not meet the PICO criteria. The study objective was to determine risk factors for hypersensitivity reaction to CM.

Renaudin, 2013

Study does not meet the PICO criteria; no provocation test to confirm Patch testing results

Seitz, 2009

Study does not meet the PICO criteria; no evaluation of diagnostic properties of skin tests

Soyyiǧit, 2016

Study does not meet the PICO criteria (no provocation test)

Steiner, 2016

Literature overview to evaluate the suitability of Basophil Acivation Test as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions (no data collection)

Tepetam, 2016

Study does not meet the PICO criteria; no reference test was used to confirm response on skintest (provocation test)

Trcka, 2008

Study does not meet the PICO criteria; no evaluation of diagnostic properties of skin tests

Vernassiere, 2004

Study does not meet the PICO criteria; no evaluation of diagnostic properties of skin tests

Waton, 2009

Study does not meet the PICO criteria; diagnostic properties of drug skin tests (no CMR)

Yoon, 2015

Included cases series en exploratory findings in analyses


[1] In case of a case-control design the patient characteristics should be described per group (cases en controls). NB; case control studies will overestimate the accuracy (Lijmer et al., 1999).

[2] Comparator test is comparable to the C from the PICO of an intervention question. Severla tests can also be compared. Add this as comparator test 2 etcetera. Attention: the comparator test can never be the  reference standard.

[3] The reference standard is the test that definitely demonstrates if one has the disease or not. Ideally the reference standard is the Gold standard (100% sensitive and 100% specific). Attention: the reference standard can never be the  comparator test.

4 Describe the statistical parameters fort he comparison of the index test with the reference test, and fort he ocmparison between index tests.

Autorisatiedatum en geldigheid

Laatst beoordeeld : 24-06-2020

Laatst geautoriseerd : 24-06-2020

The board of the Radiological Society of the Netherlands will determine at the latest in 2024 if this guideline (per module) is still valid and applicable. If necessary, a new working group will be formed to revise the guideline. The validity of a guideline can be shorter than 5 years, if new scientific or healthcare structure developments arise, that could be seen as a reason to commence revisions. The Radiological Society of the Netherlands is considered the keeper of this guideline and thus primarily responsible for the actuality of the guideline. The other scientific societies that have participated in the guideline development share the responsibility to inform the primarily responsible scientific society about relevant developments in their field.

 

Module[1]

Control holder(s)[2]

Year of authorisation

Next assessment actuality guideline[3]

Frequency of assessing actuality[4]

Who monitors actuality[5]

Relevant factors for changes in recommendations[6]

Cutaneous tests

NVvR

2019

2024

5 years

NVvR

New tests or new information on diagnostic parameters of tests available


[1] Name of module

2 Responsible authors (per module)

3 Year in which the guideline should be assessed for updating

4 Time frame: Once every 6 months, one year, two years, five years, or longer

5 Responsible scientific society

6 Variety of reasons: new drugs, new therapies, et cetera

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Radiologie
Geautoriseerd door:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
  • Nederlandse Vereniging van Spoedeisende Hulp Artsen
  • Nederlandse Vereniging voor Cardiologie
  • Nederlandse Vereniging voor Dermatologie en Venerologie
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging van Ziekenhuisapothekers
  • Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde
  • Nederlandse Vereniging voor Intensive Care
  • Patiëntenfederatie Nederland
  • Nederlandse Vereniging voor Allergologie en Klinische Immunologie

Algemene gegevens

The guideline development was assisted by the Knowledge Institute of the Federation Medical Specialists and was financed by the Quality Funds for Medical Specialists (Stichting Kwaliteitsgelden Medisch Specialisten: SKMS).

Doel en doelgroep

Goal

The aim of the Part 2 of Safe Use of Contrast Media guidelines is to critically review the present recent evidence with the above trend in mind and tries to formulate new practical guidelines for all hospital physicians to provide the safe use of contrast media in diagnostic and interventional studies. The ultimate goal of this guideline is to increase the quality of care, by providing efficient and expedient healthcare to the specific patient populations that may benefit from this healthcare and simultaneously guard patients from ineffective care. Furthermore, such a guideline should ideally be able to save money and reduce day-hospital waiting lists.

 

Users

This guideline is intended for all hospital physicians that request or perform diagnostic or interventional radiologic or cardiologic studies for their patients in which CM are involved.

Samenstelling werkgroep

A multidisciplinary working group was formed for the development of the guideline in 2016. The working group consisted of representatives from all relevant medical specialization fields that are involved with intravascular contrast administration.

 

All working group members have been officially delegated for participation in the working group by their scientific societies. The working group has developed a guideline in the period from May 2016 until July 2019.

 

The working group is responsible for the complete text of this guideline.

 

Working group

  • A.J. van der Molen, radiologist, Leiden University Medical Centre, Leiden (chairman)
  • R.W.F. Geenen, radiologist, Noordwest Ziekenhuisgroep (NWZ), Alkmaar
  • T. Leiner, radiologist, University Medical Centre Utrecht, Utrecht (until November 2018)
  • H.M. Dekker, radiologist, Radboud University Medical Centre, Nijmegen
  • I.A. Dekkers, clinical epidemiologist and radiologist in training, Leiden University Medical Centre, Leiden
  • K. van der Putten, nephrologist, Tergooi, Hilversum
  • J.G.R. de Monchy, allergologist, DC-Klinieken, Amsterdam
  • H.R.H. de Geus, internist-intensivist, Erasmus Medical Centre, Rotterdam
  • S.W. Zielhuis, hospital pharmacist, Medical Centre Leeuwarden, Leeuwarden
  • O.R.M. Wikkeling, vascular surgeon, Heelkunde Friesland Groep, location: Nij Smellinghe Hospital, Drachten
  • I. Brummer, emergency physician, Treant Healthcare Group, Emmen
  • M. van der Vlugt, cardiologist, Radboud University Medical Centre, Nijmegen (until April 2018)
  • M. Gotte, cardiologist, Free University Medical Centre, Amsterdam (from July 2018)
  • S.H. Kardaun, dermatologist, University Medical Centre Groningen, Groningen (until March, 2018)

 

Methodological support

  • I.M. Mostovaya, senior advisor, Knowledge Institute of the Federation Medical Specialists
  • J. Buddeke, advisor, Knowledge Institute of the Federation Medical Specialists (from April 2018)
  • W. Harmsen, advisor, Knowledge Institute of the Federation Medical Specialists (from April 2018)

Belangenverklaringen

The working group members have provided written statements about (financially supported) relations with commercial companies, organisations or institutions that are related to the subject matter of the guideline. Furthermore, inquiries have been made regarding personal financial interests, interests due to personal relationships, interests related to reputation management, interest related to externally financed research and interests related to knowledge valorisation. The statements on conflict of interest can be requested at the administrative office of the Knowledge Institute of Medical Specialists and are summarised below.

 

Last name

Function

Other positions

Personal financial interests

Personal relations

Reputation management

Externally financed research

Knowledge valorisation

Other interests

Signed

Van der Putten

Internist nephrologist

None

None

None

None

None

None

None

14-10-2015

Van der Vlugt

Cardiologist

None

None

None

Chairman of the working group Cardiac MRI & CT and Nuclear imaging of the Netherlands Society of Cardiology

None

None

None

03-01-206

Roodheuvel

Emergency physician

Instructor OSG/VvAA for courses on echography – paid position

Member of department for burn treatment – unpaid.

None

None

None

None

None

None

21-12-2015

Geenen

Radiologist

Member of commission prevention of PC-AKI

None

None

None

None

None

Has held several presentation about contrast media on invitation (GE, BAYER)

25-3-2016

Zielhuis

Hospital pharmacist

None

In the past (2013-2015) has participated in an advisory panel on expensive medication for the companies AbbVie and Novartis. Has received an expense allowance for this. Both forms do not produce contrast media that this guideline is about. Currently not active in an advisory panel.

None

None

None

None

None

8-1-2016

De Geus

Internist-Intensivist Erasmus MC Rotterdam

None

None

None

None

None

None

None

Ja, 31-03-2016

Dekkers

Radiologist in training and PhD-candidate

None

None

Not applicable

Not applicable

Not applicable

Not applicable

Not applicable

Ja, 8-7-2016

Wikkeling

Vascular surgeon

None

None

None

None

None

None

Not applicable

19-7-2016

Dekker

Radiologist

None

Not applicable

Not applicable

Not applicable

Not applicable

Not applicable

Not applicable

10-7-2016

Van der Molen

Chairman
Radiologist at LUMC

None

None

None

None

None

Not applicable

One-off royalties Springer Verlag (2014)
Reference work Safety of contrast medicine
One-off payment by Guerbet for (2014)
reference card management of CM reactions (educative material)

Incidental payments for presentations or being day chairman at contrast safety congress (2016 Netherlands + Europe
all firms: GE, Guerbet, Bracco, Bayer

6-9-2016

Kardaun

Dermatologist - researcherUniversitair Medisch Centrum Groningen: unpaid

Replacing dermatologist in clinical practice - unpaid
Member of scientific advisory board of Lareb (Dutch center for pharmacovigilance): unpaid

None

None

None

None

None

None

24-2-2016

Brummer

Emergency physician
Treant zorggroep location Emmen and Stadskanaal

None

None

None

None

None

None

None

23-2-2018

Inbreng patiëntenperspectief

It was challenging to find representation for the patient’s perspective, since the guideline does not discuss a specific group of patients with a disease. The Dutch Kidney Patients Association was invited to participate in an advisory board to the working group, but declined since this subject was not specific enough for them to give adequate input; The Dutch Kidney Patients Association did provide written feedback for specific modules during the commentary phase. The Dutch Kidney Patients Association and the Patient Federation of the Netherlands was invited to participate in the invitational conference in which the framework of the guideline was discussed. Furthermore, the concept guideline has been submitted for feedback during the comment process to the Patient Federation of the Netherlands and the Dutch Kidney Patient Association.

Methode ontwikkeling

Evidence based

Implementatie

In the different phases of guideline development, the implementation of the guideline, and the practical enforceability of the guideline were taken into account. The factors that could facilitate or hinder the introduction of the guideline in clinical practice have been explicitly considered. The implementation plan can be found with the Related Products. Furthermore, quality indicators were developed to enhance the implementation of the guideline. The indicators can also be found with the Related Products.

Werkwijze

AGREE

This guideline has been developed conforming to the requirements of the report of Guidelines for Medical Specialists 2.0 by the advisory committee of the Quality Counsel. This report is based on the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II) (www.agreetrust.org), a broadly accepted instrument in the international community and on the national quality standards for guidelines: “Guidelines for guidelines” (www.zorginstituutnederland.nl).

 

Identification of subject matter

During the initial phase of the guideline development, the chairman, working group and the advisor inventory the relevant subject matter for the guideline. Furthermore, an Invitational Conference was organized, where additional relevant subjects were discussed. A report of this meeting can be found in Related Products.

 

Clinical questions and outcomes

During the initial phase of guideline development, the chairman, working group and advisor identified relevant subject matter for the guideline. Furthermore, input was acquired for the outline of the guideline during an Invitational Conference. The working group then formulated definitive clinical questions and defined relevant outcome measures (both beneficial land harmful effects). The working group rated the outcome measures as critical, important and not important. Furthermore, where applicable, the working group defined relevant clinical differences.

 

Strategy for search and selection of literature

For the separate clinical questions, specific search terms were formulated and published scientific articles were sought after in (several) electronic databases. Furthermore, studies were scrutinized by cross-referencing for other included studies. The studies with potentially the highest quality of research were looked for first. The working group members selected literature in pairs (independently of each other) based on title and abstract. A second selection was performed based on full text. The databases, search terms and selection criteria are described in the modules containing the clinical questions.

 

Quality assessment of individual studies

Individual studies were systematically assessed, based on methodological quality criteria that were determined prior to the search, so that risk of bias could be estimated. This is described in the “risk of bias” tables.

 

Summary of literature

The relevant research findings of all selected articles are shown in evidence tables. The most important findings in literature are described in literature summaries. When there were enough similarities between studies, the study data were pooled.

 

Grading quality of evidence and strength of recommendations

The strength of the conclusions of the scientific publications was determined using the GRADE-method. GRADE stands for Grading Recommendations Assessment, Development and Evaluation (see http://www.gradeworkinggroup.org/) (Atkins, 2004).

 

GRADE defines four gradations for the quality of scientific evidence: high, moderate, low or very low. These gradations provide information about the amount of certainty about the literature conclusions. (http://www.guidelinedevelopment.org/handbook/).

 

Formulating conclusions

For diagnostic, etiological, prognostic or adverse effect questions, the evidence was summarized in one or more conclusions, and the level of the most relevant evidence was reported. For intervention questions, the conclusion was drawn based on the body of evidence (not one or several articles). The working groups weighed the beneficial and harmful effects of the intervention.

 

Considerations

Aspects such as expertise of working group members, patient preferences, costs, availability of facilities and organisation of healthcare aspects are important to consider when formulating a recommendation. These aspects were discussed in the paragraph Considerations.

 

Formulating recommendations

The recommendation answers the clinical question and was based on the available scientific evidence and the most relevant considerations.

 

Constraints (Organisation of healthcare)

During the development of the outline of the guideline and the rest of the guideline development process, the Organisation of healthcare was explicitly taken into account. Constraints that were relevant for certain clinical questions were discussed in the Consideration paragraphs of those clinical questions. The comprehensive and additional aspects of the Organisation of healthcare were discussed in a separate chapter.

 

Development of quality indicators

Internal (meant for use by scientific society or its members) quality indicators are developed simultaneously with the guideline. Furthermore, existing indicators on this subject were critically appraised; and the working group produces an advice about such indicators. Additional information on the development of quality indicators is available by contacting the Knowledge Institute for the Federation Medical Specialists. (secretariaat@kennisinstituut.nl).

 

Knowledge Gaps

During the development of the guideline, a systematic literature search was performed the results of which help to answer the clinical questions. For each clinical question the working group determined if additional scientific research on this subject was desirable. An overview of recommendations for further research is available in the appendix Knowledge Gaps.

 

Comment- and authorisation phase

The concept guideline was subjected to commentaries by the involved scientific societies. The commentaries were collected and discussed with the working group. The feedback was used to improve the guideline; afterwards the working group made the guideline definitive. The final version of the guideline was offered for authorization to the involved scientific societies and was authorized.

 

References

Brouwers MC, Kho ME, Browman GP, et al. AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182(18):E839-E842.

Medisch Specialistische Richtlijnen 2.0. Adviescommissie Richtlijnen van de Raad Kwalitieit, 2012. Available at: https://richtlijnendatabase.nl/over_deze_site/richtlijnontwikkeling.html.

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available at: http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106-10. Erratum published in: BMJ 2008;336(7654).

Ontwikkeling van Medisch Specialistische Richtlijnen: stappenplan. Kennisinstituut van Medisch Specialisten.

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