Subject with aspirin-sensitive asthma or aspirin-induced urticaria

Where it participates (unsigned role)

1. Three aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen.

   Paracetamol → A fall in forced expiratory volume in one second source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/2666482.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b", "start_char": 0, "end_char": 1081, "text_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b"}

   experimental_model

   Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects

   exposure

   1000 to 2000 milligram acetaminophen challenges, with aspirin desensitisation and acetaminophen desensitisation

   limitations

   Three subjects, selected for a history of reacting, so the frequency of cross-reactivity cannot be read from it. The cross-desensitisation result is what identifies the shared mechanism.

   nutrient_topic

   Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

   organism

   Human

   plain_language

   Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work.

   primary_references

   [apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7

   tissue_or_cell_type

   Airway

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 454–465

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects · source_derived_draft · unverified_draft

   ### apap-cross-desensitisation-shows-shared-mechanism Three aspirin-sensitive asthmatic subjects with a history of reactions underwent double-blind placebo-controlled challenges and reacted to 1000 milligrams of acetaminophen with a greater than 20% fall in forced expiratory volume in one second, two were desensitized to aspirin and then rechallenged with 1000 milligrams of acetaminophen without reaction, and two were desensitized to acetaminophen achieving refractoriness to 1500 but not 2000 milligrams, so cross sensitivity was documented at large challenge doses and the cross desensitization suggests similar mechanisms are responsible for reactions to aspirin, non-steroidal anti-inflammatory drugs and acetaminophen. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Desensitise the patient to aspirin and they stop reacting to paracetamol, so it is the same mechanism at work. organism: Human tissue_or_cell_type: Airway experimental_model: Double-blind placebo-controlled oral challenge and desensitisation in three aspirin-sensitive asthmatic subjects limitations: Three subjects, selected for a history of reacting, so the frequency of cross-reactivity cannot be read from it. The cross-desensitisation result is what identifies the shared mechanism. exposure: 1000 to 2000 milligram acetaminophen challenges, with aspirin desensitisation and acetaminophen desensitisation evidence_span: {"source_cache": "artifacts/paracetamol-research/2666482.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b", "start_char": 0, "end_char": 1081, "text_sha256": "9c731e77d65955b683aa03e7df1252729e11b1fb8bed714b9138f22c725eac2b"} [apap-p2666482] Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma. (1989). https://pubmed.ncbi.nlm.nih.gov/2666482/ DOI: 10.1016/0091-6749(89)90174-7

   Complete structured claim and evidence

2. Of 237 challenges with various non-steroidal anti-inflammatory drugs and paracetamol in 101 intolerant patients, 19 challenges were positive and 2 patients developed anaphylactic shock, with a ratio of positive to total challenges of 7 of 83 for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for nimesulide, and the authors conclude that a positive history of intolerance to a given drug is sufficient reason to contraindicate its use even for diagnostic challenge, which should be restricted to assessing tolerability of alternatives.

   Paracetamol → Urticaria and angioedema source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/7506185.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f", "start_char": 0, "end_char": 1590, "text_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f"}

   experimental_model

   Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs

   exposure

   Challenges with aspirin, dipyrone, paracetamol, imidazole-hydroxybenzoate and nimesulide

   limitations

   Provides the denominator that the case reports lack, and records two anaphylactic shocks during challenge, which is why the authors restrict the procedure.

   nutrient_topic

   Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

   organism

   Human

   plain_language

   About one in twelve challenges with paracetamol was positive in people already intolerant of these drugs.

   primary_references

   [apap-p7506185] Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. (1993). https://pubmed.ncbi.nlm.nih.gov/7506185/ DOI: 10.2165/00003495-199300461-00065

   tissue_or_cell_type

   Whole body

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 480–491

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

   ### apap-seven-in-eighty-three Of 237 challenges with various non-steroidal anti-inflammatory drugs and paracetamol in 101 intolerant patients, 19 challenges were positive and 2 patients developed anaphylactic shock, with a ratio of positive to total challenges of 7 of 83 for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for nimesulide, and the authors conclude that a positive history of intolerance to a given drug is sufficient reason to contraindicate its use even for diagnostic challenge, which should be restricted to assessing tolerability of alternatives. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: About one in twelve challenges with paracetamol was positive in people already intolerant of these drugs. organism: Human tissue_or_cell_type: Whole body experimental_model: Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs limitations: Provides the denominator that the case reports lack, and records two anaphylactic shocks during challenge, which is why the authors restrict the procedure. exposure: Challenges with aspirin, dipyrone, paracetamol, imidazole-hydroxybenzoate and nimesulide evidence_span: {"source_cache": "artifacts/paracetamol-research/7506185.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f", "start_char": 0, "end_char": 1590, "text_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f"} [apap-p7506185] Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. (1993). https://pubmed.ncbi.nlm.nih.gov/7506185/ DOI: 10.2165/00003495-199300461-00065

   Complete structured claim and evidence

3. Of 256 patients with a history of recent pseudoallergic skin reactions caused by non-steroidal anti-inflammatory drugs who underwent elective oral challenges, 48 or 19% reacted to acetaminophen or nimesulide, with similar proportions among those with chronic urticaria at 23% and otherwise normal subjects with a history of aspirin-induced urticaria at 19% while pyrazolone-intolerant patients showed the lowest number at 4%, aspirin intolerance was a risk factor for acetaminophen or nimesulide induced urticaria with a relative risk of 5.4, a history of anaphylactoid reactions carried a relative risk of 5.7, and atopy raised reactivity to nimesulide from 9 to 23%.

   Paracetamol → Urticaria and angioedema source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/10400483.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605", "start_char": 0, "end_char": 2662, "text_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605"}

   experimental_model

   Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs

   exposure

   Increasing doses of acetaminophen and nimesulide across three patient groups

   limitations

   A large challenge series that puts a rate on the cross-reactivity and identifies risk factors. Patients were selected for a history of reacting, so the rates apply to that population and not to the general one.

   nutrient_topic

   Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

   organism

   Human

   plain_language

   One patient in five who reacts to aspirin also reacts to paracetamol, so it is not automatically the safe substitute.

   primary_references

   [apap-p10400483] Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. (1999). https://pubmed.ncbi.nlm.nih.gov/10400483/ DOI: 10.1016/s1081-1206(10)63166-3

   tissue_or_cell_type

   Skin

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 467–478

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

   ### apap-twenty-percent-cross-react Of 256 patients with a history of recent pseudoallergic skin reactions caused by non-steroidal anti-inflammatory drugs who underwent elective oral challenges, 48 or 19% reacted to acetaminophen or nimesulide, with similar proportions among those with chronic urticaria at 23% and otherwise normal subjects with a history of aspirin-induced urticaria at 19% while pyrazolone-intolerant patients showed the lowest number at 4%, aspirin intolerance was a risk factor for acetaminophen or nimesulide induced urticaria with a relative risk of 5.4, a history of anaphylactoid reactions carried a relative risk of 5.7, and atopy raised reactivity to nimesulide from 9 to 23%. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: One patient in five who reacts to aspirin also reacts to paracetamol, so it is not automatically the safe substitute. organism: Human tissue_or_cell_type: Skin experimental_model: Elective oral challenges in 256 patients with a history of pseudoallergic skin reactions to non-steroidal anti-inflammatory drugs limitations: A large challenge series that puts a rate on the cross-reactivity and identifies risk factors. Patients were selected for a history of reacting, so the rates apply to that population and not to the general one. exposure: Increasing doses of acetaminophen and nimesulide across three patient groups evidence_span: {"source_cache": "artifacts/paracetamol-research/10400483.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605", "start_char": 0, "end_char": 2662, "text_sha256": "7ea713edb6955db38992c5372794d93c0d52f841d3f8897817286f7f66d28605"} [apap-p10400483] Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. (1999). https://pubmed.ncbi.nlm.nih.gov/10400483/ DOI: 10.1016/s1081-1206(10)63166-3

   Complete structured claim and evidence