Dermatology MCQ - Inflammatory Dermatoses - NSAID-exacerbated urticaria/angioedema

A 25-year-old medical student develops widespread urticarial wheals 10 minutes after taking a dose of ibuprofen for a tension headache. She has a known history of seasonal allergic rhinitis but has taken ibuprofen on at least two previous occasions without any issues. The most likely mechanism for this reaction is:

A. IgE-mediated hypersensitivity to ibuprofen
B. Direct mast cell degranulation due to the opioid properties of ibuprofen
C. Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated urticaria/angioedema
D. Serum sickness-like reaction
E. Contact urticaria from handling the tablet

Correct Answer: C. Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated urticaria/angioedema

Answer & Explanation

Explanation:

This scenario is classic for NSAID-exacerbated urticaria/angioedema, also known as NSAID-induced urticaria. The key distinguishing features are:

• Underlying Chronic Urticaria: Patients often have a background of chronic spontaneous urticaria (CSU) or a personal history of atopy (like this patient's allergic rhinitis).

• Reaction to Multiple NSAIDs: The reaction is a pharmacologic effect, not an allergic one. It is triggered by the ability of NSAIDs to inhibit cyclooxygenase-1 (COX-1), leading to a shift in arachidonic acid metabolism towards pro-inflammatory leukotrienes. This means the reaction is typically cross-reactive among all non-selective NSAIDs.

• Prior Tolerance is Possible: A patient may have tolerated a drug previously but develops a reaction once their underlying urticarial "baseline" is active or their mast cells are in a more labile state. The reaction is not to the specific drug molecule, but to its COX-1 inhibiting effect.

The other options are incorrect:

• A. IgE-mediated hypersensitivity: This is rare for NSAIDs like ibuprofen. A true IgE-mediated allergy is specific to a single drug or structurally similar drugs, would likely occur on first known exposure (though sensitization could be unknown), and would not require an underlying urticarial diathesis.

• B. Direct mast cell degranulation: Ibuprofen is not a direct mast cell degranulator. Drugs like opioids, radiocontrast media, and vancomycin are classic examples.

• D. Serum sickness-like reaction: This presents with fever, arthralgias, and rash (which can be urticarial) typically 1-2 weeks after drug exposure, not within minutes.

• E. Contact urticaria: This would cause a localized reaction only at the site of contact with the skin, not a systemic eruption of wheals.

Key Associations for Urticaria Causes

• Classification of Causes:

  • Acute Urticaria (<6 weeks): Often caused by infections (viral upper respiratory infections are common), medications (antibiotics, NSAIDs), or foods (shellfish, nuts, eggs).

  • Chronic Spontaneous Urticaria (CSU, >6 weeks): In the majority of cases (80-90%), no specific external trigger is identified. It is considered "idiopathic" or autoimmune in nature.

• Physical Urticarias: These are a subtype of chronic inducible urticarias with specific, reproducible triggers (e.g., dermatographism, cold, pressure, solar, cholinergic).

• Differential Diagnosis: It is crucial to distinguish urticaria from its mimics, especially urticarial vasculitis (lesions last >24 hours, are painful/bruising, and may have associated systemic symptoms) and mastocytosis (fixed brownish-red macules/patches that urticate with rubbing - Darier's sign).

• Management Implication: For the patient in the question, the management is to avoid all non-selective NSAIDs. She may be able to tolerate a COX-2 selective inhibitor (e.g., celecoxib) under medical supervision, as these do not typically trigger the reaction. Managing her underlying atopy and any subclinical CSU is also important.