Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders.
BACKGROUND
Previous studies show skin reactions after exposure to acetaminophen and/or nimesulide to occur in about 10% of patients with a history of urticaria induced by aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). This fact is surprising since cross-reactivity among different NSAIDs should not occur among subjects without a history of chronic urticaria.


OBJECTIVE
To detect risk factors for intolerance to alternative drugs such as acetaminophen and nimesulide in different groups of patients with a history of adverse skin reactions (urticaria/angioedema, or anaphylaxis) after the ingestion of aspirin and other NSAIDs.


METHODS
Two hundred fifty-six patients with a history of recent pseudoallergic skin reactions caused by NSAIDs underwent elective oral challenges with increasing doses of both acetaminophen and nimesulide. Patients were divided into three groups: A = 69 subjects with chronic urticaria, B = 163 otherwise normal subjects with a history of urticaria after the ingestion of aspirin, and C = 24 otherwise normal subjects with a history of urticaria after the ingestion of pyrazolones but aspirin-tolerant.


RESULTS
Forty-eight (19%) patients reacted to acetaminophen and/or nimesulide. Similar numbers of patients with chronic urticaria (23%) and of normal subjects with a history of aspirin-induced urticaria (19%) did not tolerate one of the alternative drugs challenged. Pyrazolones-intolerant patients showed the lowest number of reactors (4%). Aspirin intolerance represented a risk factor for acetaminophen- and/or nimesulide-induced urticaria (RR = 5.4). A history of anaphylactoid reactions induced by NSAID represented a risk factor for urticaria after the ingestion of the alternative study drugs (RR = 5.7). Atopic status was associated with a higher risk of reactivity to nimesulide: this drug induced urticaria in 11/47 (23%) atopics versus 18/209 (9%) non-atopics (P < .005; RR = 3.2). A history of intolerance to antibacterial drugs was not associated with a higher prevalence of reactivity against acetaminophen and/or nimesulide.


CONCLUSIONS
In at least 20% of patients with a history of urticaria/angioedema or anaphylaxis induced by aspirin or other NSAIDs, but without a history of chronic urticaria, cross-reactivity with other NSAIDs occurs. Atopy as well as a history of aspirin-induced anapylactoid reactions seem to represent relevant risk factors for intolerance to alternative NSAIDs. In view of these findings, aspirin-intolerant patients with such clinical features should be submitted to peroral tolerance tests with at least two alternative substances in order to avoid potentially severe reactions.
Allergy Clinic, Caduti Bollatesi Hospital, Bollate, Italy.
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D000082:Acetaminophen / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D006969:Hypersensitivity, Immediate / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012871:Skin Diseases / Q000139:chemically induced*; D013449:Sulfonamides / Q000009:adverse effects*; D014581:Urticaria / Q000139:chemically induced
D018712:Analgesics, Non-Narcotic; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D000082:Acetaminophen; C012655:nimesulide