The classification organizes the hypersensitivity reactions to NSAIDs into the following five categories: •
NSAIDs-exacerbated respiratory disease (NERD) is an acute (immediate to several hours) exacerbation of
bronchoconstriction and other symptoms of asthma in individuals with a history of asthma and/or
nasal congestion,
rhinorrhea or other symptoms of
rhinitis and
sinusitis in individuals with a history of rhinosinusitis after ingestion of various NSAIDs, particularly those that act by inhibiting the
COX-1 enzyme. NERD does not appear to be due to a true allergic reaction to NSAIDs but rather at least in part to the more direct effects of these drugs to promote the production and/or release of certain mediators of allergy. That is, inhibition of cellular COX activity deprives tissues of its anti-inflammatory product(s), particularly
prostaglandin E2 while concurrently shuttling its substrate, arachidonic acid, into other metabolizing enzymes, particularly
5-lipoxygenase (
ALOX5) to overproduce pro-inflammatory
leukotriene and
5-hydroxyicosatetraenoic acid metabolites and
15-lipoxygenase (
ALOX15) to overproduce pro-inflammatory
15-hydroxyicosatetraenoic acid metabolites, including
eoxins; the condition is also associated with a reduction in the anti-inflammatory metabolite,
lipoxin A4, and increases in certain pro-allergic chemokines such as
eotaxin-2 and
CCL7. • NSAIDs-exacerbated cutaneous disease (NECD) is an acute exacerbation of
wheals and/or
angioedema in individuals with a history of chronic
urticaria. NECD also appears due to the non-allergic action of NSAIDs in inhibiting the production of COX anti-inflammatory metabolites while promoting the production 5-lipoxygenase and 15-lipoxygenase pro-inflammatory metabolites and the overproduction of certain pro-allergic
chemokines, e.g.
eotaxin-1,
eotaxin-2,
RANTES, and
interleukin-5. • NSAIDs-induced urticarial disease (NEUD) is the acute development of
wheals and/or
angioedema in individuals with no history of chronic NSAIDs-induced
urticaria or related diseases. The mechanism behind NEUD is unknown but may be due to the non-allergic action of NSAIDs in promoting the production and/or release of allergy mediators. • Single NSAID-induced urticarial/angioedema or anaphylaxis (SNIUAA) is the acute development of
urticarial,
angioedema, or
anaphylaxis in response to a single type of NSAID and/or a single group of NSAIDs with a similar structure but not to other structurally unrelated NSAIDs in individuals with no history of underlying relevant chronic diseases. SNIUAA is due to a true
IgE-mediated
allergy reaction. • Single NSAID-induced delayed reactions (SNIDR) are a set of delayed onset (usually more than 24 hour) reactions to NSAIDs. SNIDR are most commonly skin reactions that may be relatively mild moderately severe such as
maculopapular rash,
fixed drug eruptions,
photosensitivity reactions, delayed
urticaria, and
contact dermatitis or extremely severe such as the
DRESS syndrome,
acute generalized exanthematous pustulosis, the
Stevens–Johnson syndrome, and
toxic epidermal necrolysis (also termed Lyell's syndrome). SNIDR result from the drug-specific stimulation of
CD4+ T lymphocytes and CD8+
cytotoxic T cells to elicit a
delayed type hypersensitivity reaction. ==References==