Drug Provocation Tests in Patients with a History Suggesting an Immediate Drug Hypersensitivity Reaction

15 June 2004 | Volume 140 Issue 12 | Pages 1001-1006

Background: Drug hypersensitivity reactions are common and can be life-threatening. Confirmation of the diagnosis should be rigorous and based on clinical history and a physical examination, possibly followed by skin tests and drug provocation tests.

Objective: To describe the outcome of drug provocation tests in evaluating patients with histories suggesting drug allergy.

Design: Retrospective analysis of clinic case series.

Setting: The department for drug allergy at a university hospital.

Patients: 898 consecutive patients with suspected immediate drug allergy referred to the clinic between September 1996 and August 2001. Patients with severe skin reactions and those with positive results on skin tests for ß-lactams were excluded.

Intervention: Single-blinded administration of increasing doses of the suspected drug, up to the usual daily dose, under strict hospital surveillance.

Results: 1372 drug provocation tests were performed using various drugs, including ß-lactams (30.3%), aspirin (14.5%), other nonsteroidal anti-inflammatory drugs (11.7%), paracetamol (8.9%), macrolides (7.4%), and quinolones (2.4%). There were 241 (17.6%) positive drug provocation test results. Drug provocation reproduced the same symptoms, albeit milder and of a shorter duration, in the following patients: 13 (5.4%) with a history of anaphylactic shock, 17 (7.0%) with a history of anaphylaxis without shock, 10 (4.1%) with a history of laryngeal edema, 19 (7.9%) with a history of bronchospasm, 160 (66.4%) with a history of urticaria, and 22 (9.1%) with a history of maculopapular eruption. All adverse reactions were completely reversed by prednisolone, H₁-antihistamines, and epinephrine as needed.

Limitations: Falsely negative results on drug provocation tests may have occurred because of loss of sensitization, rare cofactors not included in the diagnostic procedure, and tolerance induction during provocation.

Conclusions: Drug provocation tests in individuals with suspected drug allergy performed in carefully controlled settings can confirm drug hypersensitivity.

Editors' Notes Context Physicians face a difficult decision when patients need to take a drug to which they have had a possible hypersensitivity reaction. Contribution The authors gave the implicated drug or drugs to 898 patients referred for evaluation of possible drug hypersensitivity. Of 1372 tests performed, 17.6% confirmed hypersensitivity. None of the 241 positive test results involved a reaction that clinicians could not readily control with prednisolone, epinephrine, or antihistamine. Implications When administered by experienced clinicians in a carefully monitored setting, drug provocation tests are a safe method for confirming immediate hypersensitivity. –The Editors

 

Author and Article Information

From Hôpital Arnaud de Villeneuve, Montpellier, France.

Acknowledgments: The authors thank Ms. Anna Bedbrook for help with the English language.

Grant Support: In part by the University Hospital of Montpellier institutional grant, Projet Hospitalier de Recherche Clinique—7679.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Pascal Demoly, MD, PhD, Exploration des Allergies, Maladies Respiratoires, INSERM U454–IFR3, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex 5, France; e-mail, demoly{at}montp.inserm.fr.

Current Author Addresses: Drs. Messaad, Sahla, Benahmed, Godard, Bousquet, and Demoly: Exploration des Allergies, Maladies Respiratoires, INSERM U454–IFR3, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex 5, France.

Author Contributions: Conception and design: P. Demoly.

Analysis and interpretation of the data: D. Messaad, P. Demoly.

Drafting of the article: D. Messaad, P. Demoly.

Critical revision of the article for important intellectual content: J. Bousquet, P. Demoly.

Final approval of the article: D. Messaad, H. Sahla, S. Benahmed, J. Bousquet, P. Demoly.

Provision of study materials or patients: H. Sahla, S. Benahmed, P. Demoly.

Obtaining of funding: P. Demoly.

Administrative, technical, or logistic support: P. Godard.

Collection and assembly of data: D. Messaad.

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