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Original Article


Nonsteroidal Anti-inflammatory Drug Hypersensitivity Syndrome. A Multicenter Study
I. Clinical Findings and In Vitro Diagnosis


AL De Weck,1 ML Sanz,1 PM Gamboa,2 W Aberer,3 M Blanca,4 S Correia,7 S Erdman,6 JM Jermann,8 G Kanny,9 M Kowalski,10 L Mayorga,4 W Medrala,5 A Merk,6 GJ Sturm,3 J Sainte-Laudy,11 MS Schneider,8 A Sczczeklik,12 JM Weber,8 A Wedi,13 and members of the ENDA group

1 Department of Allergology and Clinical Immunology, Clínica Universidad de Navarra, Collaborative center of GA2LEN, Pamplona, Spain
2 Hospital Basurto, Division of Allergy, Bilbao, Spain
3 Department of Dermatology, Medical University of Graz, Austria
4 Hopital Haya, Malaga, Spain
5 University Hospital, Allergology, Wroclaw, Poland
6 Dermatology Clinic, University Hospital Aachen, Germany
7 Allergy Division, Hospital, Setubal, Portugal
8 Bühlmann Laboratories, Allschwil, Switzerland
9 Centre Hospitalier Universitaire, Médecine, Nancy, France
10 University Hospital, Lodz, Poland
11 Centre Hospitalier Universitaire, Limoges, France
12University Hospital, Cracow, Poland
13 Dermatology Clinic, University Hospital, Hanover, Germany

J Investig Allergol Clin Immunol 2009; Vol. 19(5): 355-369



Background: We present the results obtained from the largest series of in vitro diagnostic tests ever reported in patients with clinically validated hypersensitivity to acetylsalicylic acid (ASA)/nonsteroidal anti-inflammatory drugs (NSAID) compared with various categories of controls tolerating ASA/NSAIDs. This multicenter study, which was performed within the framework of the European Network for Drug Allergy (ENDA) group, showed that the basophil activation test (BAT), particularly when used with the 3 NSAIDs aspirin (ASA), diclofenac (DIC), and naproxen (NAP), allows us to confirm the diagnosis of NSAID hypersensitivity syndrome. The results of the cellular allergen stimulation test (CAST) frequently correlate with those of the BAT, although not always. An unexpected fi nding was that basophil activation by NSAIDs is not an all-or-nothing phenomenon
restricted to clinically hypersensitive patients, but that it also occurs in a dose-related manner in some NSAID-tolerant control individuals. Therefore, NSAID hypersensitivity appears as a shift in the normal pharmacological response to NSAIDs. These fi ndings allow us to formulate a new rational hypothesis about the mechanism of NSAID hypersensitivity syndrome, a mechanism that most authors continue to describe as “unknown.”

Methods: We enrolled 152 patients with a history of hypersensitivity to NSAIDs and 136 control participants in 11 different centers between spring 2003 and spring 2006. Flowcytometric BAT was performed.

Results: The most noteworthy results of our study were that 57% of 140 patients presented very clear-cut positive BAT results to multiple NSAIDs, and 16% were entirely negative. In about 27% of cases, positive results were obtained with 1 or 2 concentrations of a single NSAID. There is clearly a correlation between the results of BAT and CAST.

Conclusions: BAT seems particularly indicated in patients with a clinical history of NSAID intolerance, and in whom a provocation test is not advisable for ethical, clinical, or other reasons. Clear-cut positive results can be considered as confirming a history of NSAID hypersensitivity, although negative results may not exclude it.

Key words: NSAID hypersensitivity syndrome. Clinical findings. In vitro diagnosis. Basophil activation test. Flowcytometry. Sulphidoleukotrienes.