NSAID hypersensitivity guideline

Here’s a refined clinical guideline for NSAID hypersensitivity based on the most current EAACI/ENDA & GA₂LEN consensus:

📌 1. Classification (EAACI/ENDA)

NSAID hypersensitivity is categorized into five phenotypes—important to distinguish because they dictate management strategy  :

1. NERD – NSAID-exacerbated respiratory disease
   
• Presents with asthma and/or nasal polyps; airway symptoms occur 30–180 min after COX-1 NSAIDs.
2. 
   
3. NECD – NSAID-exacerbated cutaneous disease
   
• Urticaria/angioedema in chronic urticaria patients, triggered by most NSAIDs.
4. 
   
5. NEUD – NSAID-induced urticaria/angioedema
   
• Acute hives/angioedema in otherwise healthy individuals.
6. 
   
7. SNIUAA – Single NSAID–induced urticaria/angioedema/anaphylaxis
   
• IgE-mediated; reaction only to specific NSAID(s).
8. 
   
9. SNIDR – Single NSAID–induced delayed reaction
   
• T‑cell–mediated delayed rashes (e.g., SJS/TEN, DRESS)  .
10. 
    

🧪 2. Diagnostic Algorithm (Seven Steps) ()

1. Differentiate pharmacological toxicity (type A) from hypersensitivity (type B).
2. Take comprehensive history: substance(s) used, reaction onset, clinical pattern, underlying conditions.
3. Assign phenotype based on timing and symptoms.
4. Decide if in vitro testing or oral provocation testing (OPT) is needed.
5. For selective reactions (SNIUAA or SNIDR), consider skin tests, basophil activation tests.
6. If cross-reactive phenotypes (NERD, NECD, NEUD), OPT to identify safe alternatives is crucial.
7. Refer to allergy specialist when necessary.

💡 3. Management Overview

Cross‑reactive Types (NERD, NECD, NEUD)

• Avoid all COX‑1 NSAIDs.
• Use safe alternatives: selective COX‑2 inhibitors (cet alluxib) and low-dose paracetamol.
• Consider aspirin desensitization for NERD when NSAID therapy is needed  .

Selective Types (SNIUAA, SNIDR)

• Avoid only the culprit NSAID(s); other NSAIDs may be tolerable.
• Confirm cross-reactivity via testing before prescribing alternatives  .

Severe Delayed Reactions (SNIDR)

• Avoid the offending drug permanently.
• Manage acute episodes supportively, and if needed, refer for drug desensitization or alternative therapies.

🧭 4. Additional Notes

• NERD (AERD): often includes chronic sinusitis, nasal polyps, and adult-onset asthma. Management may involve inhaled steroids, leukotriene receptor antagonists, surgery, and aspirin desensitization  .
• Peak practice integration: This classification is adopted widely in Europe and North America for evaluation and risk stratification  .

✅ Summary Table

Phenotype	Mechanism	Avoidance	Safe Alternatives	Testing
NERD	COX‑1 inhibition, leukotriene excess	All COX‑1 NSAIDs	Selective COX‑2, paracetamol	OPT if needed
NECD/NEUD	COX‑1 mediated cutaneous	All COX‑1 NSAIDs	COX‑2, paracetamol	OPT
SNIUAA	IgE‑mediated	Specific NSAID	Others tolerated	Skin tests, OPT
SNIDR	T‑cell–mediated delayed	Specific NSAID	Avoid similar	Patch/skin tests

📝 What to Do Next

1. Identify which phenotype fits your patient based on their history.
2. Use the 7‑step algorithm to confirm the diagnosis.
3. Counsel on avoidance, ensure they have a list of safe NSAIDs or alternatives.
4. For complex cases, refer to allergy/immunology for further evaluation, testing, and possible desensitization.

If you’d like a detailed protocol for aspirin desensitization, drug challenge procedures, or pediatric-specific guidance, I can provide those as well!