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]