Samter triad

Pathophysiology: NSAIDs inhibit cyclooxygenase-1 (COX-1), shunting arachidonic acid metabolism toward the 5-lipoxygenase pathway, leading to overproduction of cysteinyl leukotrienes (LTC4, LTD4, LTE4). These leukotrienes cause bronchoconstriction, mucus secretion, and vascular permeability, triggering acute respiratory reactions (bronchospasm, rhinorrhea, nasal congestion) within minutes to hours of NSAID ingestion. This is a pseudoallergic/non-IgE-mediated reaction, distinguishing it from true drug allergy.

Clinical features: The triad includes (1) asthma (often severe, adult-onset), (2) chronic rhinosinusitis with recurrent nasal polyposis, and (3) hypersensitivity to aspirin/NSAIDs (COX-1 inhibitors). Patients typically develop nasal symptoms first, followed by asthma, then NSAID sensitivity, often in their 20s-40s. Reactions to NSAIDs can range from mild rhinitis to severe bronchospasm and anaphylactoid reactions.

Diagnosis: Clinical history plus aspirin challenge testing (gold standard, done in controlled settings). Nasal polyps confirmed via nasal endoscopy/imaging; asthma diagnosed via spirometry.

Management: Avoidance of aspirin/NSAIDs (COX-1 inhibitors); acetaminophen and COX-2 selective inhibitors (e.g., celecoxib) are generally better tolerated. Leukotriene receptor antagonists (montelukast) or 5-lipoxygenase inhibitors (zileuton) are used for symptom control. Aspirin desensitization therapy can be performed in specialized settings and may improve long-term outcomes, especially for polyp recurrence. Nasal corticosteroids, sinus surgery for polyps, and biologics (e.g., dupilumab) may also be used in refractory cases.

High-yield board association: Classic vignette is an adult with asthma and nasal polyps who develops bronchospasm/anaphylactoid reaction after taking ibuprofen or aspirin for a headache.