Multiple drug hypersensivity: insight into the underlying mechanism and correlation with autoimmune diseases

SUMMARY

Background: Subjects with drug hypersensitivity are sometimes simultaneously reactive to several drugs. This nosological entity is defined as multiple drug hypersensivity (MDH). Urticaria and angioedema are the commonest clinical manifestations of hypersensitivity drug reactions (HDR). These clinical signs are also pathognomonic of chronic idiopathic urticaria (CIU), whose pathogenetic mechanisms are still largely unknown. The diagnostic algorithm of CIU includes autologous serum skin test (ASST) and autologous plasma skin test (APST), which demonstrated a high positive and negative predictive value, in multiple nonsteroidal anti-inflammatory drugs (NSAIDs) intolerance. Objective: to explore the underlying mechanism of MDH and to assess the correlation between such tests and autoimmune diseases (AD). Methods: Twenty eight subjects with MDH referred to our Allergy/ Immunology Unit were enrolled from May 2006 to May 2007. Eight healthy subjects served as controls. In addition to common diagnostic tools used in the diagnostic algorithm of MDH, enrolled subjects also underwent ASST and APST. Results: Patients were predominantly female (23 female vs 5 male; mean age 52.2 years). In 61% of cases MDH was associated with either CIU or AD. NSAIDs and antibiotics were the major causes of HDR, both implied in 54% of subjects. The proportions of MDH-subjects with positive ASST and APST were 46.4% and 28.6%, respectively. All patients with MDH+AD+CIU (4/4) presented a positive ASST. Conclusions: In patients with MDH, ASST proved to be frequently positive, as previously described for multiple NSAIDs intolerance. In ASST-positive subjects, the activity of several drugs appears to add up FceRIspecific autoantibodies in the induction of the release of allergic mediators.