Urticaria and Angioedema — Viva Defence

Long case viva — chronic spontaneous urticaria

Candidate's opening statement (SASPOP)

"Doctor, my patient is a 34-year-old woman with a 2-year history of daily transient pruritic wheals and intermittent lip swelling, who works as a primary school teacher and who has coexisting Hashimoto thyroiditis on levothyroxine. Her symptoms impair her sleep and her teaching. Her problems are: chronic spontaneous urticaria with angioedema; Hashimoto thyroiditis; NSAID-exacerbated urticaria; and impaired quality of life." [1]

Problem list

1. Chronic spontaneous urticaria (CSU) with associated angioedema — mast-cell-driven, autoimmune subgroup likely.
2. Hashimoto thyroiditis (the associated autoimmune thyroid disease, present in 15 to 25 per cent).
3. NSAID-exacerbated urticaria (worsens with ibuprofen; pharmacologic COX-1 mechanism).
4. Impaired quality of life — sleep disturbance, reduced work productivity. [1]

Integrated management plan

Investigations — limited. Full blood count, CRP, thyroid function with anti-TPO antibodies. NO extensive allergy panel (CSU is not IgE-mediated food allergy; broad panels produce false positives). Confirm regular daily cetirizine dosing. [1]

Treatment ladder. Step 2: up-titrate cetirizine to up to 40 mg daily (up to 4-fold), the standard second step in the EAACI guideline and the step most often missed. If cetirizine sedates, switch to fexofenadine up to 720 mg daily. Step 3 if refractory: add omalizumab 300 mg SC every 4 weeks (ASTERIA II; 65 to 70 per cent response). Step 4 if refractory: add ciclosporin 2.5 to 4 mg per kg per day, specialist-supervised, with blood pressure and renal monitoring. [1]

Trigger avoidance. Avoid non-selective NSAIDs permanently (use paracetamol; celecoxib if an anti-inflammatory is needed). Treat thyroid dysfunction on its merits. [1]

Supportive. Acknowledge the quality-of-life impact; screen for anxiety and depression; counsel that CSU usually remits over months to years; avoid first-generation sedating antihistamines. [1]

Examiner probing questions

Examiner: "Why is her thyroid relevant?" Hashimoto thyroiditis and positive anti-TPO antibodies are associated with CSU in 15 to 25 per cent of patients, reflecting a shared autoimmune predisposition. The thyroid must be screened and dysfunction treated on its merits. Levothyroxine for euthyroid patients with positive antibodies is sometimes tried but evidence of benefit in CSU is limited. [1]

Examiner: "Why does the ibuprofen worsen her urticaria?" Non-selective NSAIDs inhibit cyclo-oxygenase-1, shunting arachidonic acid down the lipoxygenase pathway and increasing leukotriene production. Leukotrienes activate mast cells. About 20 to 30 per cent of CSU patients NSAID-exacerbate, and the effect class-shares across non-selective NSAIDs but not COX-2 selective inhibitors. This is pharmacologic, not IgE-mediated. [1]

Examiner: "Why is omalizumab effective in CSU if the disease is autoimmune?" Omalizumab binds free IgE, lowering the expression of FceRI on mast cells and basophils and reducing the cells' responsiveness to the activating autoantibodies. It also may have direct effects on mast cell signalling. The ASTERIA I, II, and GLACIAL trials showed 300 mg every 4 weeks significantly reduced itch and wheal activity. [1]

Examiner: "When would you suspect urticarial vasculitis instead of CSU?" If an individual wheal lasts more than 24 hours, leaves bruising or pigmentation, is painful rather than pruritic, or is accompanied by arthralgia, fever, or renal involvement. Then I biopsy a fresh lesion (4 mm punch, histology and immunofluorescence) and check complement and autoimmune screen. [1]

Branching scenario — hereditary angioedema

Examiner: "Now consider a 19-year-old man, the patient's nephew, who presents to ED with acute tongue and lip swelling and stridor. He has had similar episodes since childhood, and his father (the patient's brother) has the same. What is the diagnosis and what is your immediate management?"

This is hereditary angioedema with a laryngeal attack. The key points: [1]

• Childhood onset of recurrent non-urticarial, non-pruritic angioedema with a family history — autosomal dominant C1-INH deficiency.
• The swelling is bradykinin-mediated, so adrenaline, antihistamines, and corticosteroids are NOT effective.
• Immediate management: C1 inhibitor concentrate 20 units per kg IV or icatibant 30 mg SC, given at once. Secure the airway with senior anaesthetic and ENT support — prepare for a difficult airway (awake fibre-optic intubation, surgical airway tray at the bedside).
• Do NOT rely on repeated adrenaline while the airway closes. [1]

Examiner: "What screening test confirms the diagnosis between attacks?" C4, which is low both during and between attacks because of continuous classical pathway consumption. A normal C4 between attacks effectively excludes HAE. Confirm with C1-INH antigenic level (low in type 1) and functional level (low in type 1 and type 2). The functional assay is essential because type 2 HAE has a normal antigenic level. C1q is normal in hereditary HAE and low in acquired C1-INH deficiency. [1]

Examiner: "What long-term prophylaxis would you offer?" Modern first-line: lanadelumab 300 mg SC every 2 weeks (the HELP trial showed an 87 per cent reduction in monthly attack rate) or berotralstat 150 mg orally daily. Attenuated androgens (danazol) are second-line because of virilisation and hepatotoxicity, and are contraindicated in pregnancy. Avoid ACE inhibitors and oestrogen permanently. Give short-term prophylaxis with C1-INH concentrate 1000 units IV before dental or surgical procedures. [1]

Examiner: "How would you advise the family?" HAE is autosomal dominant with incomplete penetrance. First-degree relatives should be offered screening with C4 and C1-INH function. Provide a written action plan, a medical alert, and the on-demand medication for home self-treatment. Offer genetic counselling. [1]

Branching scenario — ACE inhibitor angioedema

Examiner: "And what if the swelling occurred in a 62-year-old man of African descent on lisinopril for three years, with a normal C4?"

That is ACE inhibitor-induced angioedema — the most common cause of bradykinin-mediated angioedema in adults. ACE inhibitors inhibit kininase II (one of the two main bradykinin-degrading enzymes), raising bradykinin levels. The C4 is normal (excluding HAE). It is more common in Black patients and can occur years after starting. The management is to stop the ACE inhibitor permanently and never rechallenge, secure the airway, and switch to an angiotensin receptor blocker or calcium channel blocker. Icatibant and C1-INH concentrate may be used in severe cases (mixed evidence). [1]

Short-case discussion — skin examination

Examiner: "Examine this patient's skin. She has chronic urticaria."

My routine: general inspection for wheals and distribution; inspect individual lesions for the defining features (erythematous, well-demarcated, central pallor, blanch on pressure, no scale, no purpura, no residual pigmentation); confirm each lesion lasts less than 24 hours; examine for angioedema (lips, eyelids, tongue); test for dermographism by stroking the skin firmly with the wooden end of a cotton swab — a wheal forming within 5 to 10 minutes is positive; examine for thyroid enlargement and eye signs; and look specifically for the features of urticarial vasculitis (purpura, residual pigment, livedo, arthralgia) which would redirect me to biopsy. [1]

Presentation: "On general inspection the patient is comfortable. The skin shows multiple discrete, well-demarcated, erythematous wheals with central pallor on the trunk and proximal limbs, each 1 to 3 cm, with no overlying scale, purpura, or residual pigmentation, and the lesions blanch on pressure. There is no angioedema of the face or mucosa. Firm stroking of the skin of the back produces a wheal within 5 minutes, consistent with dermographism. There is a smooth, firm, non-tender goitre with no eye signs. These findings are consistent with chronic spontaneous urticaria with symptomatic dermographism and an associated thyroid abnormality. I would take a limited history, measure a blood count, CRP, and thyroid function with anti-TPO antibodies, and initiate a stepwise second-generation antihistamine regimen." [1]

Examiner: "What is the single most important safety warning in cold urticaria?" Cold water immersion can trigger massive histamine release, hypotension, and anaphylaxis — cold urticaria is a documented cause of drowning. Warn the patient explicitly to avoid cold water immersion, never to swim alone, and to carry adrenaline. [1]