Urticaria and angioedema — formative SAQs

SAQ 1 (10 marks, 15 minutes)

Stem. A seven-year-old girl is brought to your clinic with itchy wheals on most days for the past eight weeks. Her mother reports that individual lumps come and go within a few hours and leave no mark, and that the rash is worse at night and disrupts her sleep. She is otherwise well, with no fever, weight loss, joint pain or bruising. She takes no regular medication. Outline your assessment, the diagnosis you would and would not make, the investigation you would and would not perform, and your stepwise management plan. [3]

Model answer — SAQ 1

The history meets the definition of chronic spontaneous urticaria: daily wheals for six weeks or more, with individual lesions resolving within twenty-four hours and leaving normal skin. The first step is to confirm the diagnosis clinically by confirming the three hallmarks of a wheal — transient (under twenty-four hours), normal skin after resolution, and itchy — and to screen for alarm features that would demand a different pathway. [1]

I would ask specifically about alarm features: individual lesions lasting over twenty-four hours, bruising or residual hyperpigmentation, pain rather than itch, fever, weight loss, arthralgia and night sweats. Their absence — as in this case — supports a clinical diagnosis of chronic spontaneous urticaria without extensive laboratory testing. I would also ask about NSAID intake, new medications, recent infections, physical triggers, stress, and a family history of urticaria, angioedema or autoimmunity. [1] [4]

I would not order a routine battery of allergy tests. The international guideline is explicit that routine specific IgE panels and skin prick testing are not indicated in chronic spontaneous urticaria without a history of reproducible food or allergen triggering, because false-positive results lead to unnecessary elimination diets and parental anxiety. Targeted testing — for example thyroid function and antibodies in refractory disease, or provocation testing for a suspected inducible trigger — is question-driven, not routine. [1] [4]

My management plan follows the four-step ladder. Step 1 is a standard-dose non-sedating second-generation H1 antihistamine (for example cetirizine, levocetirizine or loratadine at the local weight-based dose), continued daily rather than as needed. Step 2, if symptoms are not controlled within two weeks, is up-titration of the same antihistamine to two, then three, then up to four times the standard daily dose, with documentation and specialist input. Step 3 is omalizumab, for which pivotal trials demonstrated efficacy in chronic spontaneous urticaria, with age-cut-offs that vary by jurisdiction. Step 4 is specialist immunomodulation — cyclosporine or, increasingly, dupilumab — under allergy, immunology or dermatology guidance. I would also assess quality of life, because treatment intensity should track impact, and I would set expectations: most childhood chronic spontaneous urticaria resolves within one to five years. [1] [3] [7]

Marking grid — SAQ 1

Common pitfalls — SAQ 1

• Ordering a broad specific IgE panel or skin prick test battery without a compatible food-trigger history.
• Failing to screen for alarm features before accepting the chronic spontaneous urticaria label, thereby missing urticarial vasculitis.
• Stopping at the standard antihistamine dose without up-titration before declaring treatment failure.
• Using a first-generation antihistamine long-term despite sedation and anticholinergic burden.
• Not assessing quality of life, so treatment intensity does not match the child's burden.

SAQ 2 (10 marks, 15 minutes)

Stem. A ten-year-old boy is referred for recurrent episodes of facial and lip swelling over the past year. The swelling is not itchy, lasts two to three days, and occurs without any wheals. His father describes similar episodes in his own youth and one emergency intubation for throat swelling. The boy is currently well between attacks. Outline your approach to the diagnosis, the single most important initial investigation, the mechanism and the treatment, and explain why antihistamines will not help. [9]

Model answer — SAQ 2

This is recurrent angioedema without wheals, which raises the bradykinin pathway rather than the histamine pathway. The combination of angioedema without urticaria, a family history of similar swelling and a history of airway compromise in a relative makes hereditary angioedema the leading diagnosis. The first step is to confirm the clinical suspicion with complement studies. [9] [10]

The single most important initial investigation is a serum C4 level. C4 is low both during and between attacks in hereditary angioedema types I and II (C1-inhibitor deficiency and dysfunction), and a normal C4 effectively excludes these forms. If the C4 is low, I would proceed to C1-inhibitor antigenic (quantitative) and functional assays: type I shows low antigenic and functional levels, while type II shows normal or high antigenic level with low functional activity. The dedicated paediatric hereditary angioedema guideline structures the diagnostic algorithm and the on-demand treatment options by age and weight. [9]

The mechanism is bradykinin-mediated vascular leak. In hereditary angioedema, deficiency or dysfunction of C1-inhibitor allows unopposed plasma kallikrein activity, which generates bradykinin. Bradykinin binds vascular B2 receptors and produces deep-tissue angioedema without itch or wheals. This is fundamentally different from the histamine-driven vasodilation of ordinary urticaria, which is why the swelling is not itchy and does not accompany wheals. [10]

Treatment is entirely separate from the urticaria ladder. Antihistamines, adrenaline and corticosteroids do not work because they target the histamine pathway, not the bradykinin pathway. Acute attacks are treated with C1-inhibitor concentrate (plasma-derived or recombinant) or icatibant, a bradykinin B2-receptor antagonist, in weight-based paediatric doses. Long-term prophylaxis may use lanadelumab (a kallikrein inhibitor) or C1-inhibitor concentrate. The child needs an on-demand treatment plan with a home supply where feasible, a medical-alert device, education of the family and school, and family screening from childhood. I would refer to an allergy or immunology service for long-term co-management. [9] [10]

Marking grid — SAQ 2

Common pitfalls — SAQ 2

• Treating recurrent angioedema without wheals with escalating antihistamines and corticosteroids while the airway is at risk.
• Not checking a C4 level, or checking complement only during an attack when it is (correctly) low between attacks anyway.
• Giving adrenaline as definitive treatment for a hereditary angioedema laryngeal attack — it is supportive but not definitive.
• Failing to take a family history, missing the hereditary pattern and the airway event in a relative.
• Not arranging an on-demand treatment plan, medical-alert device and family screening from childhood.