The accuracy of the diagnosis of suspected paracetamol (acetaminophen) hypersensitivity: results of a single-blinded trial


Pascal Demoly, MD, PhD, Maladies Respiratoires, INSERM U454, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex, France. E-mail:


Background Hypersensitivity to paracetamol (acetaminophen) is rare and very few clinical data are available in the literature.

Materials and methods Eighty-four patients (28 males and 56 females, 5–70 years old) with a suspicion of paracetamol hypersensitivity were referred to our drug allergy clinic between May 1996 and May 2000. The reaction had occurred 1–96 months prior to the consultation. Single-blinded placebo-controlled oral challenges were carried out in 82 patients, under strict hospital surveillance.

Results Most of the patients experienced skin eruptions 82/84 (97.6%), with 10 cases of anaphylactic shock (11.9%). Twenty-six (30.9%) reactions were immediate (occurring within the first hour after drug intake), 53 (63.1%) non-immediate and five could not remember. Oral provocation tests (OPT) demonstrated drug hypersensitivity in 11 patients only. The two patients not tested (due to a history of life-threatening reaction) were included in the positive group. Thus, 13 (15.5%) patients had paracetamol hypersensitivity and 71 (84.5%) had not. All the 13 positive patients had skin eruptions, five with anaphylactic shock. 9/13 had immediate reactions. Using OPT, 10 out of 11 had the same clinical reaction but more delayed. In both groups, whether hypersensitive to paracetamol or not: atopy was similar (7/13–53.8% and 31/71–43.7%), sex ratio was not different (M/F 0.3 and 0.5), 3/13 (23.1%) and 0/71 (0%) had aspirin/ibuprofen hypersensitivity.

Conclusion The clinical history of paracetamol (acetaminophen) hypersensitivity is rarely sufficient to set a firm diagnosis and only OPT can confirm this. Careful OPT reproduces the same symptoms (not more severe in our hands) with the same or slightly more delayed chronology. Atopy and sex are not risk factors.