Red flags
- Angioedema of the lips/tongue/airway, stridor, or wheeze - anaphylaxis pathway, IM adrenaline, not antihistamines
- Individual wheals lasting >24h, leaving bruising/pigmentation, or painful/burning rather than itchy - suggests urticarial vasculitis, biopsy required
- Systemic features (fever, arthralgia, weight loss) with urticaria - consider autoinflammatory syndrome or systemic disease, not simple chronic spontaneous urticaria (CSU)
- Angioedema without urticaria and poor response to antihistamines/adrenaline - consider bradykinin-mediated angioedema (HAE, ACE-inhibitor)
Differential by mechanism
Acute urticaria (<6 weeks)
- IgE-mediated allergic - food, drug, latex, insect sting - temporal link within minutes-hours
- Viral infection - commonest cause in children
- Direct mast cell degranulation - opioids, NSAIDs, radiocontrast
Chronic urticaria (>6 weeks, most days)
- Chronic spontaneous urticaria (CSU) - no identifiable external trigger; autoimmune mechanism (anti-IgE or anti-FcERI autoantibodies) in a significant subset
- Chronic inducible urticaria - reproducible physical trigger: dermographism, cold, cholinergic (heat/exercise/sweat), pressure, solar, aquagenic
- Urticarial vasculitis - immune complex-mediated small vessel vasculitis, wheals >24h, resolves with bruising, biopsy shows leukocytoclastic vasculitis
Angioedema without wheals (distinct mechanism - see angioedema note)
- Bradykinin-mediated (HAE, ACE-inhibitor) - does not respond to the CSU treatment ladder
Focused history
- Duration (acute vs chronic >6 weeks) and frequency (daily/near-daily in CSU)
- Individual wheal duration - CSU wheals resolve within 24h without bruising; longer duration suggests vasculitis
- Identifiable triggers - food/drug timing, cold/heat/pressure/exercise association (inducible subtypes)
- Associated angioedema, systemic symptoms, medication review (NSAIDs, ACE-inhibitors, opioids)
- Impact on sleep/quality of life - relevant to severity scoring (UAS7)
Focused examination
- Wheal morphology - blanching, itchy, well-demarcated, evanescent (CSU) vs fixed/bruising (vasculitis)
- Dermographism - stroke skin firmly, observe for a wheal at 5-10 minutes
- Angioedema distribution if present (lips, eyelids, tongue, extremities)
- Signs of an underlying systemic trigger if suspected (thyroid exam, lymphadenopathy)
Investigation strategy
- Acute urticaria with an obvious trigger - no investigation needed
- CSU - investigation is generally NOT indicated if history/examination unremarkable; extensive routine allergy testing (IgE panels) is low yield and not recommended by current international guidelines
- Consider FBE, CRP/ESR, TFTs as baseline if CSU is prolonged/atypical
- Skin biopsy if wheals last >24h, bruise, or are painful - excludes urticarial vasculitis
- Autologous serum skin test - research/specialist setting, identifies autoimmune CSU phenotype, not routine
- Cold stimulation test, exercise challenge etc. for suspected inducible subtypes
Management
Stepwise ladder for CSU (2026 international guideline update)
1. Standard-dose second-generation non-sedating antihistamine (e.g. cetirizine, fexofenadine)
2. Up-titrate to 4x standard dose if inadequate response at 2-4 weeks - a key updated step, higher than licensed dose but guideline-endorsed
3. Add omalizumab (anti-IgE) - preferred third-line add-on therapy over ciclosporin given superior safety profile
4. Ciclosporin - for refractory disease not responding to omalizumab
Acute urticaria/anaphylaxis overlap
- If airway/systemic involvement -> treat as anaphylaxis (IM adrenaline first), see anaphylaxis approach note
- Isolated acute urticaria - non-sedating antihistamine, identify/avoid trigger
Inducible urticaria
- Trigger avoidance/modification (e.g. gradual cold/heat desensitisation) plus antihistamine ladder as above
Urticarial vasculitis
- Manage per underlying cause; may need immunosuppression (not antihistamine-responsive) - rheumatology/dermatology input
Traps
- Ordering broad allergy panels for chronic spontaneous urticaria - low yield, not evidence-based, delays effective antihistamine up-titration
- Treating urticarial vasculitis (wheals >24h) with escalating antihistamines when it needs biopsy and a different pathway entirely
- Under-dosing antihistamines - staying at standard dose when guideline-endorsed up-titration to 4x dose is appropriate before moving to omalizumab
- Missing bradykinin-mediated angioedema (no wheals, poor antihistamine/adrenaline response) and persisting with the urticaria ladder
Talk track
1. Duration of the individual wheal is the discriminator
- "If each wheal is gone within 24 hours and doesn't bruise, I'm not chasing vasculitis or ordering a big allergy panel."
2. Up-titrate before you escalate to biologics
- "Before reaching for omalizumab, I push the antihistamine to four times the standard dose - that's now a guideline step, not off-label creativity."
8 of 8 sections written · drafted 2026-09-14