MILAN, ITALY—Some patients with a history of urticaria or angioedema in response to nonsteroidal anti-inflammatory drugs (NSAIDs) show a propensity to react to other, often unrelated compounds. The mechanisms of multiple-drug reactivity are not well understood but may be due to patient-related factors that lead to histamine release from mast cells.

“Most patients with multiple-NSAID intolerance show circulating histamine releasing factors (their autologous serum skin test is markedly positive),” said Riccardo Asero, MD, Specialist in Allergy and Clinical Immunology at the Ospedale Caduti Bollatesi in Milan, Italy, in an interview with RESPIRATORY REVIEWS. Dr. Asero and colleagues studied autoreactivity as a mechanism of drug-induced histamine release in patients with a history of skin reactions from ingestion of several chemically unrelated drugs.[1]

AUTOLOGOUS SKIN TESTS

Thirty-six adults with a history of acute NSAID-induced urticaria participated in the study. Of these, 22 had a history of multiple-NSAID sensitivity (MNS); 14 had a history of single-NSAID sensitivity (SNS).

Both MNS and SNS patients underwent autologous serum skin tests (ASST) with 0.05 mL of autologous serum, using saline as a negative control. A skin-prick test with 10 mg/mL of histamine was used as a positive control. Twenty atopic patients with no history of chronic urticaria or drug allergy also underwent ASST.

Twenty of 22 MNS patients versus five of 14 SNS patients had positive ASST results. None of the atopic patients had positive results. Sera from 14 MNS patients and four SNS patients, all of whom were ASST positive, were tested for their capacity to induce histamine release from basophils of normal donors in vitro. Histamine release was induced by the sera from four MNS patients but from none of samples taken from SNS patients.

ANSWERS STILL NEEDED

According to Dr. Asero, the induction of histamine release from normal basophils in vitro is “a feature that has been associated with the presence of autoantibodies to immunoglobulin E [IgE] or FceRI, the high affinity IgE receptor.” He noted, however, that the role of such antibodies has been questioned by Fagiolo et al,[2] who showed that “IgG-depleted sera lost their histamine-releasing activity in vitro but still maintained their ability to induce histamine release in vivo.”

The reason why strongly ASST-positive patients do not have chronic urticaria remains unknown. Dr. Asero and colleagues have suggested that, in some cases, circulating histamine-releasing factors alone may not cause chronic urticaria. An additional trigger—in these cases, the offending drug—is needed to cause a massive release of histamine from mast cells and basophils.

—Gale Jurasek