Treatment of late reactions to contrast media

Uitgangsvraag

What is the optimal treatment for late hypersensitivity reactions to contrast media?

Aanbeveling

Warn patients who have had a previous hypersensitivity reaction to contrast media, that a late hypersensitivity reaction may be possible, usually a skin reaction.

 

Patients should contact their general practitioner if they have a late hypersensitivity reaction after CM administration.

 

Consider informing the radiology department about the occurrence and symptoms of a late hypersensitivity reaction after CM administration.

 

When the symptoms of a late hypersensitivity reaction are mild, a wait-and-see approach can be justified.

 

Treat late hypersensitivity reactions symptomatically.

 

Consider treatment of skin reactions with oral or topical corticosteroids.

 

When severe symptoms develop, such as generalized pustulosis or painful cutaneous blisters, refer the patient to a dermatologist.

Overwegingen

There are no solid data on different management strategies of late hypersensitivity reactions to CM, especially no studies with a control group.

 

In many patients there are nonspecific symptoms, such as headache, nausea, dizziness, gastro-intestinal upset, mild fever and arm pain (Bellin, 2011; Christiansen, 2000; Egbert, 2014). Skin rashes with erythema and swelling and headache are the most frequent true late hypersensitivity reactions or symptoms (loh, 2010). Most rashes are macular or maculopapular exanthemas, which usually occurs 2-10 days after first exposure to CM and 1 to 2 days after re-exposure to the same CM. Most reactions are mild to moderate in severity, are usually self-limiting and resolve within 1 week.

 

Treatment is symptomatic, based on the type of reaction presented. More than 90% of the late hypersensitivity reactions involve the skin only. Usually oral antihistamines and topical corticosteroid crèmes or emollients treat these late skin reactions.. Antipyretics may be given for fever, and anti-emetics for nausea or GI symptoms.

 

Very rarely the patient may develop a severe reaction with generalized pustulosis or blistering of the skin, for which specialized dermatology care needs to be sought (Egbert, 2014).

 

It seems therefore to be rational to follow the recommendations from the ESUR v10 guideline (Bellin, 2011; ESUR, 2018) and/or the ACR Manual on Contrast Media v10.3 (ACR 2018)

Inleiding

Late (non-immediate) adverse reactions are heterogeneous. Because of the self-limiting character of most cutaneous adverse reactions to CM, the traditional mainstay of treatments follows that of cutaneous adverse reactions to other drugs: withdrawal of the drug and preventative measures for reuse of them, combined with symptomatic treatment.

 

Severe cutaneous reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS) may warrant specific therapeutic interventions by a dermatologist.

Samenvatting literatuur

Not applicable. There were no studies investigating the research question.

Zoeken en selecteren

To answer the clinical question a systematic literature analysis was performed.

 

P (Patients): patients with late hypersensitivity reaction after contrast media administration;

I (Intervention): diagnosis, treatment, management, steroid, cyclosporine, topical, emollients;

C (Comparison): conservative treatment or comparison of interventions above;

O (Outcomes): recovery, course, outcome, sequels, mortality, morbidity hospitalization.

 

Relevant outcome measures

The working group considered mortality and recovery critical outcome measures for the decision making process and course, sequel, morbidity and hospitalisation important outcomes for the decision making process.

 

Methods

The databases Medline (OVID), Embase and the Cochrane Library were searched from 1st of January 1985 to 3th of January 2018 using relevant search terms for systematic reviews (SRs), randomized controlled trials (RCTs) and observational studies (OBS). Search terms are shown under the Tab “Literature Search”. The literature search procured 480 hits: 11 SR, 72 RCTs and 336 OBS. Based on title and abstract a total of 12 studies were selected. After examination of full text all studies were excluded and 0 studies definitely included in the literature summary.

Referenties

  1. American College of Radiology. ACR Manual of contrast media, v10.3. Available at: https://www.acr.org/Clinical-Resources/Contrast-Manual. Accessed: 11 July 2019.
  2. Bellin MF, Stacul F, Webb JAW, et al. Late adverse reactions to iodine-based contrast media – an update. Eur Radiol 2011; 21: 2305-2310.
  3. Christiansen C, Pichler WJ, Skotland T. Delayed allergy-like reactions to X-ray contrast media: mechanistic considerations. Eur Radiol 2000; 10: 1965-1975.
  4. Egbert RE, De Cecco CN, Schoepf UJ, McQuiston AD, Meinel FG, Katzberg RW., Delayed adverse reactions to the parenteral administration of iodinated contrast media. AJR Am J Roentgenol 2014; 203: 1163-1170.
  5. ESUR Contrast Media Safety Committee. ESUR Guidelines on contrast safety, v10. Available at: http://www.esur-cm.org. Accessed: 11 july 2019.
  6. Loh S, Bagheri S, Katzberg RW, Fung MA, Li CS. Delayed adverse reaction to contrast-enhanced CT: a prospective single-center study comparison to control group without enhancement. Radiology 2010; 255:764–771.

Evidence tabellen

Exclusion Table

Author and Year

Reason for exclusion

Bellin (2011)

Does not fulfill selection criteria. No control group. Descriptive.

Brockow K (2011)

Does not fulfill selection criteria. No control group. Descriptive.

Christiansen C (2000)

Does not fulfill selection criteria. No control group. Descriptive.

Egbert (2014)

Does not fulfill selection criteria. No control group. Descriptive.

Fok (2017)

Does not fulfill selection criteria. No control group. Descriptive.

Goksel (2011)

Does not fulfill selection criteria. No control group. Descriptive.

Hasdenteufel (2011)

Does not fulfill selection criteria. No control group. Descriptive.

Hash (1999)

Does not fulfill selection criteria. No control group. Descriptive.

Idée JM (2015)

Does not fulfill selection criteria. No control group. Descriptive.

Mikkonen (1995)

Does not fulfill selection criteria. No control group. Descriptive.

Newmark JL (2012)

Does not fulfill selection criteria. No control groep. Descriptive.

Rosado Ingelmo (2016)

Does not fulfill selection criteria. No control group. Descriptive.

Scherer K (2010)

Does not fulfill selection criteria. No control group. Descriptive.

Seitz CS (2009)

Does not fulfill selection criteria. No control group. Descriptive.

Stovsky MD (1995)

Does not fulfill selection criteria. No control group. Descriptive.

Webb JAW (2003)

Does not fulfill selection criteria. No control group. Descriptive.

Autorisatiedatum en geldigheid

Laatst beoordeeld :

Laatst geautoriseerd :

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]

Responsible authors)[2]

Authorisation Year

Next evaluation of validity of guideline

Frequency of evaluation of validity[3]

Who surveys the actuality of this guideline[4]

Relevant factors for changing recommendations[5]

Late reactions

NVvR

2019

2024

5 years

NVvR

New treatment options described and deemed effective


[1] Name of module

[2] Responsible authors (per module)

[3] Time frame: Once every 6 months, year , two years, five years, longer

[4] Responsible scientific society

[5] 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

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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