NSAID (or nonsteroidal anti-inflammatory drug) hypersensitivity reactions encompass a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID
nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual. Hypersensitivity reactions are
idiosyncratic reactions to a drug.[1] Although the term NSAID was introduced to signal a comparatively low risk of adverse effects,[2] NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity.[3]
Classification
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.[4][5][6][7][8]
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.[9][10]
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.[11]
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.[3][12]
^
abcKowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. (October 2013). "Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs". Allergy. 68 (10): 1219–32.
doi:
10.1111/all.12260.
PMID24117484.
S2CID32169451.
^Claesson HE (September 2009). "On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation and Hodgkin lymphoma". Prostaglandins & Other Lipid Mediators. 89 (3–4): 120–5.
doi:
10.1016/j.prostaglandins.2008.12.003.
PMID19130894.
^Ledford DK, Wenzel SE, Lockey RF (2014). "Aspirin or other nonsteroidal inflammatory agent exacerbated asthma". The Journal of Allergy and Clinical Immunology: In Practice. 2 (6): 653–7.
doi:
10.1016/j.jaip.2014.09.009.
PMID25439353.
^Choi JH, Kim MA, Park HS (February 2014). "An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease". Current Opinion in Allergy and Clinical Immunology. 14 (1): 1–6.
doi:
10.1097/ACI.0000000000000021.
PMID24300420.
S2CID205433452.
^Mullol J, Picado C (May 2013). "Rhinosinusitis and nasal polyps in aspirin-exacerbated respiratory disease". Immunology and Allergy Clinics of North America. 33 (2): 163–76.
doi:
10.1016/j.iac.2012.11.002.
PMID23639706.
^Simon RA, Dazy KM, Waldram JD (March 2015). "Update on aspirin desensitization for chronic rhinosinusitis with polyps in aspirin-exacerbated respiratory disease (AERD)". Current Allergy and Asthma Reports. 15 (3): 508.
doi:
10.1007/s11882-014-0508-7.
PMID25663486.
S2CID23740152.
^Rozieres A, Vocanson M, Saïd BB, Nosbaum A, Nicolas JF (August 2009). "Role of T cells in nonimmediate allergic drug reactions". Current Opinion in Allergy and Clinical Immunology. 9 (4): 305–10.
doi:
10.1097/ACI.0b013e32832d565c.
PMID19474707.
S2CID20616655.
NSAID (or nonsteroidal anti-inflammatory drug) hypersensitivity reactions encompass a broad range of allergic or allergic-like symptoms that occur within minutes to hours after ingesting aspirin or other NSAID
nonsteroidal anti-inflammatory drugs. Hypersensitivity drug reactions differ from drug toxicity reactions in that drug toxicity reactions result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual. Hypersensitivity reactions are
idiosyncratic reactions to a drug.[1] Although the term NSAID was introduced to signal a comparatively low risk of adverse effects,[2] NSAIDs do evoke a broad range of hypersensitivity syndromes. These syndromes have recently been classified by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity.[3]
Classification
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.[4][5][6][7][8]
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.[9][10]
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.[11]
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.[3][12]
^
abcKowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. (October 2013). "Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs". Allergy. 68 (10): 1219–32.
doi:
10.1111/all.12260.
PMID24117484.
S2CID32169451.
^Claesson HE (September 2009). "On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation and Hodgkin lymphoma". Prostaglandins & Other Lipid Mediators. 89 (3–4): 120–5.
doi:
10.1016/j.prostaglandins.2008.12.003.
PMID19130894.
^Ledford DK, Wenzel SE, Lockey RF (2014). "Aspirin or other nonsteroidal inflammatory agent exacerbated asthma". The Journal of Allergy and Clinical Immunology: In Practice. 2 (6): 653–7.
doi:
10.1016/j.jaip.2014.09.009.
PMID25439353.
^Choi JH, Kim MA, Park HS (February 2014). "An update on the pathogenesis of the upper airways in aspirin-exacerbated respiratory disease". Current Opinion in Allergy and Clinical Immunology. 14 (1): 1–6.
doi:
10.1097/ACI.0000000000000021.
PMID24300420.
S2CID205433452.
^Mullol J, Picado C (May 2013). "Rhinosinusitis and nasal polyps in aspirin-exacerbated respiratory disease". Immunology and Allergy Clinics of North America. 33 (2): 163–76.
doi:
10.1016/j.iac.2012.11.002.
PMID23639706.
^Simon RA, Dazy KM, Waldram JD (March 2015). "Update on aspirin desensitization for chronic rhinosinusitis with polyps in aspirin-exacerbated respiratory disease (AERD)". Current Allergy and Asthma Reports. 15 (3): 508.
doi:
10.1007/s11882-014-0508-7.
PMID25663486.
S2CID23740152.
^Rozieres A, Vocanson M, Saïd BB, Nosbaum A, Nicolas JF (August 2009). "Role of T cells in nonimmediate allergic drug reactions". Current Opinion in Allergy and Clinical Immunology. 9 (4): 305–10.
doi:
10.1097/ACI.0b013e32832d565c.
PMID19474707.
S2CID20616655.