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HYPERSENSITIVITY TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS:
FROM PATHOGENESIS TO CLINICAL PRACTICE / ARTIGO DE REVISÃO

most frequent cause of drug -induced hypersensitivity, Cross -reactivity between NSAIDs occurs frequently
regardless the severity of the reactions 2,3,6 . in patients with cutaneous reactions. Nevertheless, one
The overall prevalence of NSAIDs hypersensitivity third of patients are single -reactors (selective reaction).
ranges from 0.6 to 6%, depending on the analyzed popu- The NSAIDs commonly involved in this pattern are the
lation, method of assessment and type of reaction . An pyrazolones (metamizole), ibuprofen, diclofenac, AAS
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epidemiological study performed in Portugal, revealed and paracetamol/acetaminophen .
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that 2% of the general adult population has self -reported The prevalence of late reactions is barely known, in-
hypersensitivy to NSAIDs . NSAIDs have been conside- cluding maculopapular exanthema (MPE), fixed drug erup-
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red as the most common cause of anaphylaxis induced tion (FDE), contact dermatitis and photosensitivity reac-
by drugs. Considering a drug -induced anaphylaxis survey tions. Severe and potential life -threating skin reactions,
during a 4 -year period in Portuguese allergy departments, such as Stevens -Johnson syndrome/toxic epidermal
NSAIDs were responsible for 48% of all cases (aspirin, necrolysis (SJS/TEN), acute generalized exanthematous
diclofenac and ibuprofen are the main culprits) . Similar pustulosis (AGEP) and drug reaction with eosinophilia
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results were found in a 6 -year observational study per- and systemic symptoms (DRESS) are extremely rare .
formed in a Spanish tertiary hospital, in which NSAIDs All NSAIDs can be involved. Owing to their chemical
were responsible for 49% of the anaphylactic reactions structure, some groups (naproxen, diclofenac, ketorolac
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(dipyrone, aspirin and diclofenac as main culprits) . Com- and ibuprofen) have been more frequently implicated in
paring to a previous study describing a decade review of anaphylactic reactions.
reactions reported to the Portuguese Pharmacovigilance Although rare, cases of paracetamol hypersensiti-
Authority, NSAIDs were the culprit drugs in 13% of vity have been reported, including anaphylaxis, namely
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cases (after antibiotics) . In the same study, a subgroup in children 12,13 . Ibuprofen is the most frequent elicitor
analysis in the pediatric population showed that NSAIDs/ of urticaria/angioedema or anaphylaxis in children, al-
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acetaminophen accounted for 7% of the reported cases . though paracetamol and pyrazolones have also been
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Additionally, and according to the Online Latin American implicated . Despite the low frequency of delayed
Survey on Anaphylaxis (OLASA), NSAIDs were the cul- reactions in children, FDE has been reported with ibu-
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prit agents in 73% of the drug -induced anaphylaxis . profen, naproxen, dipyrone, oxicams, nimesulide, and
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Hypersensitivity reactions to NSAIDs appear to be other NSAIDs .
more prevalent among asthmatic patients ranging from 4 In adults, the drugs more frequently involved in IgE-
to 21%. Chronic rhinosinusitis with nasal polyps, severe -mediated/immediate reaction are pyrazolones, followed
asthma, female gender and/or atopy are associated with by ibuprofen and diclofenac .
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higher prevalence of NSAIDs hypersensitivity . In a large study with 659 adolescent/adult patients, it
Cutaneous manifestations are less frequent (0.3%) in was described that 76% had cross -intolerance and the
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the general population without allergic disease . On the remaining were selective responders . Among patients
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other hand, in chronic urticaria, NSAIDs might cause a with cross -intolerance, urticaria and angioedema were
disease exacerbation in up to 40% of patients. This is a the main symptoms and in a less extent airway involve-
dose -dependent effect, more prone to occur in cases ment, whereas in selective responders there was a pre-
with poorly controlled chronic urticaria. Despite most dominance of urticaria and/or angioedema, followed by
of patients suffering from spontaneous chronic urticaria, anaphylaxis .
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other types of urticaria might be affected, such as cho- In extremely rare occasions (0.008%) cyclooxygenase
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linergic urticaria . 2 selective inhibitors (coxibs) might also be implicated .
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