Drug of the week series- Week 1

MBBS
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A 38-year-old female presents to the emergency with acute-onset wheezing, chest tightness, and rhinorrhea. She reports that her symptoms began roughly 45 minutes after taking a dose of aspirin for a tension headache.

Her past medical history is significant for chronic rhinosinusitis and adult-onset asthma.
Upon ENT examination: Presence of nasal polyps

Questions:

  1. What would be your diagnosis?
  2. What is the pathophysiology of the above condition ?

MBH/PS

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The diagnosis is Aspirin-Exacerbated Respiratory Disease (AERD) / Samter’s Triad.

It is characterized by:

Asthma

Nasal polyps

Aspirin/NSAID sensitivity

Pathophysiology

Aspirin inhibits the COX-1 enzyme, which decreases prostaglandin production and increases leukotriene formation.

\text{COX-1 inhibition} \rightarrow \uparrow \text{Leukotrienes} \rightarrow \text{Bronchoconstriction}

Excess leukotrienes cause bronchoconstriction, nasal inflammation, and wheezing.

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Diagnosis: Aspirin-Exacerbated Respiratory Disease (AERD)

This patient shows a classic clinical triad: chronic rhinosinusitis, asthma and NSAID hypersensitivity. The symptom onset within 30 - 120 min of aspirin ingestion is the high characteristic of AERD. (In this case onset of symptom is 45min)

Pathophysiology

Pathophysiology
Pathophysiology1536×1024 240 KB

Under normal conditions COX-1 converts arachidonic acid to PGE. Aspirin inhibits COX-1 and COX-2 resulting in decreased PGE. Loss of PGE moves to the other pathway 5-LOX pathway. This shows massive surge in pro-inflammatory agents (LTC4, LTD4, LTE4).

They cause:

  • Bronchospasm - wheezing and chest tightness
  • Mucosal edema - rhinorrhea
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Absolutely right :white_check_mark:

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Perfect :white_check_mark:

Well explained doc.

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Answers:-

  1. Diagnosis:- Aspirin-Exacerbated Respiratory Disease (AERD) AKA Samter’s Triad. It is defined by the coexistence of three conditions: Asthma (usually adult-onset), Chronic Rhinosinusitis with Nasal Polyposis and Aspirin Sensitivity

  2. Pathophysiology:-AERD is not a true Ig E-mediated allergy. Instead, it is a due to metabolic shift involving the arachidonic acid pathway.

    When a patient with AERD takes aspirin or another NSAID that inhibits the Cyclooxygenase-1 (COX-1) enzyme, the following occurs: -

    · Shunting: By blocking the COX pathway, arachidonic acid is diverted (shunted) toward the Lipoxygenase (LOX) pathway leading to Leukotriene Overproduction. This leads to a massive increase in the production of cysteinyl which are potent bronchoconstrictors and pro-inflammatory mediators.

    · Prostaglandin Depletion: Simultaneously, there is a loss of Prostaglandin E2 which normally acts to stabilize mast cells and eosinophils.

    · The result is intense airway inflammation, mucus production (rhinorrhea), and bronchospasm (wheezing).

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Thank you Dr. Priya

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Very very informative and good explanation!