Urticaria and Angioedema: MCCQE1 Study Guide

Introduction

Urticaria (hives) and Angioedema are common presentations in Canadian primary care and emergency departments. For the MCCQE1, candidates must demonstrate the ability to distinguish between acute and chronic forms, identify life-threatening presentations (anaphylaxis), and apply evidence-based Canadian management guidelines.

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Canadian Context: Approximately 20% of the Canadian population will experience urticaria at some point in their lives. The Canadian Society of Allergy and Clinical Immunology (CSACI) provides specific guidelines for management that differ slightly from US or European protocols, particularly regarding antihistamine dosing.

MCCQE1 Objectives

According to the Medical Council of Canada, a candidate should be able to:

Diagnose: Differentiate urticaria/angioedema from other dermatoses and identify potential triggers (allergic vs. non-allergic).
Assess: Recognize signs of anaphylaxis and airway compromise immediately.
Manage: Formulate a management plan including avoidance of triggers and pharmacotherapy based on Canadian guidelines.

Definitions and Pathophysiology

Understanding the underlying mechanism is crucial for determining the etiology and treatment.

Core Definitions

Urticaria: Superficial dermal swelling (wheals) accompanied by pruritus (itching). Lesions are migratory and typically resolve within 24 hours without scarring.
Angioedema: Swelling of the deep dermis and subcutaneous or submucosal tissues. Often painful rather than pruritic.

Key Mediators

Understanding the mediator helps in selecting the treatment (e.g., Antihistamines do not work for Bradykinin-mediated angioedema).

Classification

Classification is based on duration and triggers. This is the first step in the diagnostic algorithm.

Duration

Acute Urticaria: Duration < 6 weeks. Often identifiable trigger (infection, food, medication).
Chronic Urticaria: Duration > 6 weeks. Often idiopathic or autoimmune.

Clinical Presentation and History Taking

As a CanMEDS Communicator, gathering a precise history is more diagnostic than laboratory testing.

Comparison of Features

Feature	Urticaria (Hives)	Angioedema
Location	Superficial Dermis	Deep Dermis / Subcutaneous
Sensation	Intense Pruritus (Itch)	Pain, Burning, Tightness
Appearance	Erythematous wheals with central pallor	Skin-colored or slightly erythematous swelling
Resolution	Individual lesions fade < 24 hrs	Can last up to 72 hours
Mucosal Involvement	Rare	Common (Lips, Tongue, Larynx, Bowel wall)

Red Flags (MCCQE1 High Yield)

If any of these are present, immediate assessment for anaphylaxis or systemic disease is required:

Respiratory distress (stridor, wheeze)
Hypotension or syncope
Severe abdominal pain (intestinal angioedema)
Fever, arthralgia, or weight loss (suggests Urticarial Vasculitis)
Lesions lasting > 24 hours or leaving bruising/pigmentation (suggests Urticarial Vasculitis)

Diagnostic Approach

Step 1: Rule out Anaphylaxis

Assess ABCs (Airway, Breathing, Circulation). If unstable $\rightarrow$ IM Epinephrine immediately.

Step 2: Characterize the Lesion

Is it Urticaria, Angioedema, or both?

Both: Likely Histaminergic (Allergic or Idiopathic).
Angioedema ONLY: Consider Bradykinin-mediated (ACE Inhibitors, Hereditary Angioedema).

Step 3: Identify Triggers (The 5 I’s)

Ingestants (Foods, Additives)
Inhalants (Pollens, Dander - usually cause rhinitis/asthma too)
Injectants (Drugs, Insect stings)
Infections (Viral URTI is the #1 cause of acute urticaria in children; H. pylori, parasites in chronic)
Internal Disease (Thyroid disease, Autoimmune, Malignancy - rare)

Step 4: Investigations

Acute Urticaria: No investigations needed if history is clear.
Chronic Spontaneous Urticaria (CSU):
- CBC + Diff (Eosinophilia?)
- CRP/ESR (Systemic inflammation?)
- TSH (Thyroid autoimmunity is associated with CSU)
- Note: Extensive allergy testing is not recommended unless history suggests a specific trigger (Choosing Wisely Canada).

Management Guidelines (Canadian Context)

Management follows a stepwise approach endorsed by the CSACI.

1. Acute Urticaria

Avoidance: Stop suspected drugs (NSAIDs, Opioids, ACEi) or foods.
Pharmacotherapy:
- First-line: Second-generation H1-antihistamines (non-sedating).
  - Examples: Cetirizine, Loratadine, Desloratadine, Bilastine, Rupatadine.
- Avoid: First-generation antihistamines (Diphenhydramine) due to sedation and anticholinergic side effects, especially in the elderly.
- Steroids: Short course of Prednisone (e.g., 20-40mg for 3-5 days) for severe acute cases only.

2. Chronic Spontaneous Urticaria (CSU)

The goal is complete symptom control.

Step 1: Standard Dose

Start with a standard daily dose of a 2nd generation H1-antihistamine (e.g., Cetirizine 10mg daily).

Step 2: Updosing

If uncontrolled after 2-4 weeks, increase dose up to 4-fold (e.g., Cetirizine 40mg daily).

Specific Canadian Guideline Recommendation

Step 3: Add-on Therapy

If still uncontrolled, add Omalizumab (Anti-IgE). Fourth line is Cyclosporine.

3. Angioedema Specifics

Histaminergic: Treat as Urticaria + consider Epinephrine if airway involved.
ACE-Inhibitor Induced:
- Stop ACE inhibitor immediately.
- Note: Swelling may recur for weeks after stopping.
- Antihistamines and Steroids are usually ineffective.
- Ensure airway protection (intubation if necessary).
Hereditary Angioedema (HAE):
- Deficiency/Dysfunction of C1-Esterase Inhibitor.
- Acute Attack: C1-INH concentrate (Berinert) or Icatibant (Bradykinin receptor antagonist).
- Prophylaxis: Danazol (attenuated androgen) or C1-INH.

Canadian Guidelines & “Choosing Wisely”

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Choosing Wisely Canada: Do not perform screening panels for food allergies (IgE testing) in patients with chronic urticaria. Food allergy rarely causes chronic hives. Testing should only be done if there is a convincing history of immediate reaction to a specific food.

Key CSACI Recommendations:

Do not use first-generation antihistamines (Diphenhydramine/Hydroxyzine) as first-line treatment for chronic urticaria.
Updosing second-generation antihistamines (up to 4x) is safe and effective before switching to biologics.

Key Points to Remember for MCCQE1

ACE Inhibitors: Can cause angioedema years after starting therapy. Always check the medication list.
Urticarial Vasculitis: Suspect if wheals last > 24 hours, are painful/burning rather than itchy, or leave residual hyperpigmentation (bruising). Biopsy is diagnostic.
Viral Infections: The most common cause of acute urticaria in children.
NSAIDs/Aspirin: Can exacerbate chronic urticaria in 30% of patients.
C1-Esterase Inhibitor Level: Order this (and C4) if patient has recurrent angioedema without urticaria. C4 is almost always low in untreated HAE.

Sample Question

Scenario: A 34-year-old female presents to her family physician complaining of daily hives for the past 8 weeks. The hives are intensely pruritic, migratory, and appear on her trunk and extremities. She denies any lip or tongue swelling, difficulty breathing, or abdominal pain. She has no known allergies. She started taking Cetirizine 10 mg daily two weeks ago, but the hives persist and interfere with her sleep. Physical examination reveals multiple erythematous wheals with central pallor on her arms and back. Dermographism is negative. Systemic review is otherwise unremarkable.

Question: According to Canadian guidelines, which of the following is the most appropriate next step in management?

A. Add oral Prednisone 20 mg daily for 7 days
B. Switch to Diphenhydramine 50 mg every 6 hours
C. Increase Cetirizine to 20 mg twice daily (40 mg total daily)
D. Order serum specific IgE testing for common food allergens
E. Refer immediately to a dermatologist for skin biopsy

Explanation

The correct answer is:

C. Increase Cetirizine to 20 mg twice daily (40 mg total daily)

Detailed Explanation:

C is correct: This patient has Chronic Spontaneous Urticaria (CSU) (duration > 6 weeks). According to the CSACI guidelines, the first-line treatment is a second-generation H1-antihistamine. If symptoms are not controlled with standard dosing, the recommended second step is to increase the dose of the second-generation antihistamine up to four times the standard dose (e.g., Cetirizine 40 mg/day). This is preferred over adding steroids or switching to sedating antihistamines.
A is incorrect: Systemic corticosteroids are not recommended for long-term management of CSU due to side effects. They may be used for short-term exacerbations (rescue), but updosing antihistamines is the correct next step in the algorithm.
B is incorrect: First-generation antihistamines like Diphenhydramine are sedating and impair cognitive function (REM sleep interference, driving impairment). Guidelines recommend against their routine use as first-line or maintenance therapy.
D is incorrect: Food allergy is extremely rare as a cause of chronic urticaria. Indiscriminate testing (Choosing Wisely) leads to false positives and unnecessary dietary restrictions. Testing is only indicated if there is a clear history relating symptoms to ingestion.
E is incorrect: Skin biopsy is indicated for suspected Urticarial Vasculitis (painful, persistent >24h, bruising). This patient has classic urticaria features (migratory, pruritic), so biopsy is not indicated at this stage.

References

Canadian Society of Allergy and Clinical Immunology (CSACI). Guideline for the Management of Urticaria. https://csaci.ca
Betschel S, et al. The Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol. 2014.
Choosing Wisely Canada. Allergy and Clinical Immunology. https://choosingwiselycanada.org/allergy-and-clinical-immunology/
Medical Council of Canada. MCCQE Part I Objectives: Urticaria and Angioedema. https://mcc.ca
Kanani A, et al. Urticaria and Angioedema: An Update on Classification and Management. Clinical & Experimental Allergy.