Diagnostik des Analgetika-Intoleranz-Syndroms mittels funktioneller Zelltestung (Analgetika-Intoleranz-Test: AIT)

Abstract

Hypersensitivity reactions to aspirin - first described by Widal et al. in 1922, and reactions to other nonsteroidal anti-inflammatory drugs (NSAIDs), show a classic triad of symptoms: chronic rhinitis with nasal polyps, bronchial asthma, and intolerance to aspirin. In angloamerican literature intolerance to NSAIDs is known as Samter's syndrome. Hypersensitivity to NSAIDs, predominantly cyclooxygenase-1 (COX-1) but also COX-2 inhibitors, is unlikely to be mediated by IgE-dependent mechanisms. In recent years, it has become increasingly clear that aspirin hypersensitivity is likely to be mediated by a deviation of the arachidonic acid metabolic pathway toward excessive leukotriene (LT) production, which then produces all the clinical features of analgesic-induced asthma (AIA). Up to now, the diagnosis of AIA was based on anamnesis and provocative tests. In most cases, the clear history should enable the physician to make a diagnosis. In doubtful cases, carefully controlled challenge testing with aspirin or other NSAIDs is necessary. The methods of nasal, bronchial and oral provocative tests are extensive, not only in private practice, and mostly unpleasant and painful for the patient. In some cases, like nasal obstruction, non-compliance or severe asthma, it is even not possible to perform provocative tests. This study was initiated to test the qualification of a functional cellular in vitro test (analgesic intolerance test: AIT) for the diagnosis of AIA. Therefore, the results of conventional diagnosis and AIT results obtained from 50 patients, suspected to suffer from AIA, were compared. The 38 patients of the control-group had no indications to AIA, neither in the anamnesis nor in the clinical findings, such as nasal polyposis and bronchial asthma. The conventional diagnosis was based on nasal and oral provocative tests (negative nasal test lead to an oral test), which were not performed in patients reporting from relapsing severe intolerance reactions to NSAIDs. The AIT detects the relation of peptide LT and prostaglandine (PG)E 2 produced by leucocytes upon stimulation as described recently [21]. The sensitivity of the test was determined to be 100%, the specificity 73.3%. The negative predictive value was 100% but the positive predictive value was only 71%, which is explained by patients with a negative conventional diagnosis but a positive AIT. These patients were characterized by a modified arachidonic acid metabolism with an increased LT production compared to the control group. A follow-up study has to clarify whether these patients suffer from a clinically irrelevant AIA which may change to a manifest AIA, or the AIT shows false positive results. In summary, the objective AIT is not yet sufficient to diagnose analgesic intolerance even though the first results are satisfyingly. Nevertheless, the test might be useful as a screening method reducing the need of provocative tests. Additional studies including more patients have to be performed to ameliorate the validity of the test because ofthe test's advantages such as easy handling and extremely low risk for the patient.