Urticaria and Angioedema — DCE Clinical Case

Long case

Patient scenario

Mrs KR is a 34-year-old primary school teacher who presents with a 2-year history of daily transient pruritic wheals over her trunk and proximal limbs, each lesion lasting 8 to 12 hours and resolving completely without bruising. She describes intermittent swelling of her lips, without airway symptoms, two to three times a month. Her symptoms impair her sleep and her teaching. She has coexisting Hashimoto thyroiditis (diagnosed 5 years ago) on levothyroxine 100 micrograms daily, with a normal latest TSH. She takes cetirizine 10 mg daily with partial relief. She has noticed her wheals worsen markedly after taking ibuprofen for menstrual pain. She is otherwise well, takes no other regular medications, does not smoke, and drinks alcohol moderately. There is no family history of skin disease or angioedema. She is distressed by the chronicity and asks whether she has a food allergy. [1]

Examination findings

The patient is comfortable, afebrile, and normotensive. 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; the lesions blanch on diascopy. There is no angioedema of the lips, eyelids, or tongue at this visit. Firm stroking of the skin of the back with the wooden end of a cotton swab produces a wheal-and-flare within 5 minutes, consistent with symptomatic dermographism. There is a smooth, firm, non-tender goitre of the thyroid with no bruit and no eye signs. Cardiovascular, respiratory, and abdominal examination is unremarkable. There is no lymphadenopathy. [1]

Candidate's opening statement (SASPOP)

"Doctor, my patient is Mrs KR, a 34-year-old woman who presents with a 2-year history of daily transient pruritic wheals over her trunk and limbs with intermittent lip swelling, who works as a primary school teacher, and whose symptoms impair her sleep and teaching. She has coexisting Hashimoto thyroiditis on levothyroxine with a normal TSH, and her wheals worsen with ibuprofen. Her problems are: chronic spontaneous urticaria with associated angioedema; symptomatic dermographism; Hashimoto thyroiditis; NSAID-exacerbated urticaria; and impaired quality of life." [1]

Problem list

1. Chronic spontaneous urticaria (CSU) with associated histamine-mediated angioedema and symptomatic dermographism.
2. Hashimoto thyroiditis on levothyroxine (the associated autoimmune thyroid disease).
3. NSAID-exacerbated urticaria (pharmacologic COX-1 mechanism).
4. Impaired quality of life (sleep disturbance, reduced work productivity, patient concern about food allergy). [1]

Integrated management plan

Investigations — limited and guideline-directed. Full blood count with differential (to exclude eosinophilia), CRP (to screen for urticarial vasculitis or systemic disease — normal here), and thyroid function with anti-TPO antibodies (the thyroid association). I will NOT order an extensive food allergy panel because CSU is not an IgE-mediated food allergy; broad panels produce false positives, drive unnecessary elimination diets, and delay guideline-directed treatment. I will confirm with the patient that she is taking cetirizine regularly every day, not PRN. [1]

Treatment ladder (EAACI/GA2LEN 2022). Step 1: she is on standard-dose cetirizine 10 mg daily with partial relief. Step 2: up-titrate the cetirizine to up to 40 mg daily (up to four-fold), stepwise over 2 to 4 weeks; if cetirizine sedates her, switch to fexofenadine (up to 720 mg daily), the least sedating. Step 3: if she remains symptomatic on up to 4-fold H1, add omalizumab 300 mg subcutaneously every 4 weeks — the licensed, guideline-preferred add-on (ASTERIA II; 65 to 70 per cent response). Step 4: if refractory to omalizumab, add ciclosporin 2.5 to 4 mg per kg per day, specialist-supervised, with blood pressure and renal monitoring. [1]

Trigger avoidance. Avoid all non-selective NSAIDs permanently (the ibuprofen is clearly exacerbating). Use paracetamol for pain; a COX-2 selective inhibitor (celecoxib) is an alternative if an anti-inflammatory is needed, following a supervised oral challenge if there is doubt. Avoid ACE inhibitors if any blood pressure management is needed in the future (to avoid bradykinin-mediated angioedema in this predisposed patient). [1]

Supportive care. Acknowledge the quality-of-life impact; screen for anxiety and depression; involve psychology if warranted. Counsel that CSU usually remits over months to years (about half remit within 1 to 5 years). Explain plainly that the disease is autoimmune mast cell activation, not a food allergy, to prevent unnecessary elimination diets. Avoid first-generation sedating antihistamines for chronic use because they impair cognition and increase falls. [1]

Communication. Explain the diagnosis to the patient in plain language: "Your immune system is making antibodies that switch on the mast cells in your skin, releasing histamine and producing the wheals and itch. It is not an allergy to a food or something in your environment. The good news is that it usually goes away on its own, and we have a stepwise treatment that controls the symptoms in almost everyone." [1]

Discussion questions

Examiner: "How would the management change if a wheal lasted more than 24 hours and left bruising?" Then the diagnosis would be urticarial vasculitis, not CSU. I would perform a 4 mm punch skin biopsy of a fresh lesion for histology (looking for leukocytoclasia) and immunofluorescence, check complement (C3, C4, CH50), and screen for SLE (ANA, dsDNA) and cryoglobulins, because urticarial vasculitis may be part of a systemic connective tissue disease or hypocomplementaemic urticarial vasculitis syndrome. The management would shift from the antihistamine ladder to immunosuppression and treatment of any underlying disease. [1]

Examiner: "Why is omalizumab effective if CSU is an autoimmune disease?" Omalizumab binds free IgE, which lowers FceRI expression on mast cells and basophils, reducing the cells' responsiveness to the activating autoantibodies. It may also have direct effects on mast cell signalling. The ASTERIA I, II, and GLACIAL trials established 300 mg every 4 weeks as the effective dose. [1]

Examiner: "When would you check a serum tryptase in this patient?" If the presentation were atypical (recurrent unexplained anaphylaxis, severe refractory disease, or a history of a severe reaction to hymenoptera venom). A persistently elevated tryptase (above 20 micrograms per litre) would suggest systemic mastocytosis or a clonal mast cell disorder, warranting bone marrow evaluation (KIT D816V mutation, CD25, tryptase stain). In straightforward CSU with a normal examination and response to the ladder, a tryptase is not routinely required. [1]

Short case — focused skin examination

Instruction

"Examine this patient's skin. She has a chronic pruritic eruption." [1]

Systematic examination routine

1. General inspection. Confirm the patient is comfortable and assess for distress, airway compromise, or signs of systemic disease.
2. Describe the lesions. Identify the morphology — erythematous, well-demarcated wheals with central pallor; note the size, distribution (any site, spares mucosa, often symmetrical), and the defining features: each lesion blanches on diascopy, has no overlying scale, no purpura, and no residual pigmentation.
3. Establish lesion duration. Ask the patient to document how long each individual wheal lasts. Urticaria: less than 24 hours, complete resolution. Urticarial vasculitis: more than 24 hours, bruising or pigmentation, painful.
4. Test for dermographism. Firmly stroke the skin of the back or forearm with the wooden end of a cotton swab (or a calibrated dermographometer). A wheal-and-flare forming along the stroke line within 5 to 10 minutes confirms symptomatic dermographism, the most common inducible urticaria.
5. Examine for angioedema. Inspect the lips, eyelids, tongue, and genitalia for non-pitting swelling.
6. Screen for associated disease. Examine the thyroid (goitre, eye signs of Graves), the joints (arthritis suggesting urticarial vasculitis or a connective tissue disease), and the abdomen (hepatosplenomegaly).
7. Exclude mimics. Look for the burrows of scabies (web spaces), the flexural lichenification of atopic dermatitis, the target lesions of erythema multiforme, the tense bullae of bullous pemphigoid (especially in the elderly), and the pigmented macules of urticaria pigmentosa (mastocytosis, positive Darier sign). [1]

Key signs this patient demonstrates

• Multiple transient erythematous wheals with central pallor, blanching, no scale or purpura, no residual pigmentation — consistent with urticaria.
• A positive dermographism test — confirming the inducible component.
• A smooth non-tender goitre with no eye signs — consistent with Hashimoto thyroiditis. [1]

Presentation template

"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 measuring 1 to 3 cm, with no overlying scale, purpura, or residual pigmentation; the lesions blanch on pressure. There is no angioedema of the face or mucosa at this visit. Firm stroking of the skin of the back produces a wheal-and-flare within 5 minutes, consistent with symptomatic dermographism. There is a smooth, firm, non-tender goitre of the thyroid with no bruit and no eye signs. The remainder of the examination is unremarkable. These findings are consistent with chronic spontaneous urticaria with symptomatic dermographism and an associated thyroid abnormality. I would take a focused history, measure a blood count, CRP, and thyroid function with anti-TPO antibodies, and initiate a stepwise second-generation antihistamine regimen per the international EAACI guideline." [1]

Discussion — the angioedema branch point

Examiner: "How would your differential change if the swelling were NOT accompanied by urticaria?" Angioedema without urticaria or pruritus is bradykinin-mediated. I would consider hereditary angioedema (C1-INH deficiency — childhood onset, family history, low C4 between attacks), ACE inhibitor-induced angioedema (related to the drug, normal C4, more common in Black patients), and acquired C1-INH deficiency (older adult, low C4, low C1q, driven by a B-cell lymphoproliferative disorder). The pivotal point is that adrenaline, antihistamines, and corticosteroids are NOT effective in bradykinin-mediated angioedema — the treatment is C1-INH concentrate or icatibant for HAE, and permanent cessation of the ACE inhibitor for drug-induced disease. [1]

Examiner: "What is the single most important safety warning you would give a patient with cold contact 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]