Red flags
Anaphylaxis until proven otherwise if urticaria + any of:
- Stridor, hoarseness, tongue/pharyngeal swelling
- Wheeze, persistent cough, dyspnoea
- Hypotension, presyncope, collapse
- Persistent vomiting or abdominal pain (especially insect sting anaphylaxis)
- -> IM adrenaline immediately, do not wait for skin signs to progress
Angioedema without weals
- -> think bradykinin-mediated: ACE inhibitor, hereditary/acquired C1-INH deficiency
- Antihistamines and adrenaline will not work; airway involvement is the killer
Systemic features suggesting this is not simple urticaria
- Fever, weight loss, arthralgia, night sweats
- Individual weals lasting >24h, painful/burning rather than itchy, bruising or pigmentation on resolution -> urticarial vasculitis
- Purpura, ulceration
- Mucosal involvement, skin pain, blistering, Nikolsky sign -> SJS/TEN
- Rash + fever + eosinophilia + LFT derangement 2-6 weeks after a new drug -> DRESS
Differential by mechanism
1. Mast-cell mediated, IgE-dependent (type I)
- Food (nut, seafood, egg, milk), drug (beta-lactam), venom, latex
- Acute, reproducible, minutes after exposure
- Skin prick / specific IgE useful
2. Mast-cell mediated, IgE-independent
- Direct degranulation: opiates, vancomycin (red man), radiocontrast, NSAIDs
- Complement/anaphylatoxin: C3a, C5a
- Clinically identical to type I - the history, not the appearance, separates them
3. Autoimmune / autoallergic - chronic spontaneous urticaria
- IgG anti-FcepsilonRI-alpha or IgG anti-IgE cross-links receptors
- Not IgE (type 1) mediated - hence allergy testing is unhelpful
4. Physical (inducible) urticarias
- Dermographism, cholinergic (heat/exercise/stress, small weals), cold, delayed pressure, solar, aquagenic, vibratory
- Reproducible by the stimulus - this is the test
5. Bradykinin-mediated angioedema (no weals, no itch)
- ACE inhibitor (may start years into therapy), hereditary angioedema (C1-INH), acquired C1-INH deficiency (lymphoproliferative)
6. Urticaria as a sign of systemic disease
- Urticarial vasculitis (SLE, hypocomplementaemic), Schnitzler syndrome, adult-onset Still, systemic mastocytosis, autoinflammatory (CAPS), parasitic infection, viral (esp. children), thyroid autoimmunity, occult malignancy
Focused history2 exam ›
Define the lesion first - it settles the differential
- Duration of an individual weal
- <24h, resolves without trace = urticaria
- >24h, painful, leaves bruising/pigment = vasculitis, biopsy it
- Pruritus is a required feature of chronic spontaneous urticaria - painless lesions are something else
- Duration of the illness: >=6 weeks = chronic; acute is usually infection or drug and needs no workup
- Angioedema present? Weals present? Angioedema alone -> bradykinin pathway
Trigger
- Timing relative to food, drug, sting, exercise, infection
- Physical triggers - pressure, cold, heat, exercise, sun, water, vibration
- New drugs in the last 6 weeks; ACE inhibitor at any duration; NSAIDs (both trigger and aggravate)
- Recent infection (commonest cause of acute urticaria in children)
Systemic screen
- Fever, weight loss, arthralgia, bone pain, flushing, diarrhoea (mastocytosis)
- Thyroid symptoms
- Family history of angioedema (autosomal dominant HAE)
Impact
- Sleep, work, mood - drives escalation decisions more than lesion count
- UAS7 or UCT score if available
Focused examination
- Weals: transient, raised, erythematous, blanching, itchy, migratory
- Circle a lesion and re-inspect at 24h - the single most useful bedside test
- Angioedema: deep, non-pitting, asymmetric, non-pruritic; lips, periorbital, tongue, larynx, bowel wall
- Stroke the skin - dermographism (commonest inducible urticaria)
- Airway: voice, stridor, tongue, oropharynx
- Haemodynamics: BP, HR
- Darier sign - urtication on rubbing a pigmented macule -> mastocytosis
- Lymph nodes, liver, spleen - lymphoproliferative disease (acquired C1-INH deficiency, Schnitzler)
- Joints, purpura, livedo - vasculitis
Investigation strategy1 exam ›
Acute urticaria with a clear trigger
- No investigation needed
- Serum tryptase only if anaphylaxis suspected - within 3h of the reaction, plus a baseline >24h later
Chronic spontaneous urticaria
- Minimal testing: FBE + CRP/ESR only
- Broad allergy panels and food-specific IgE are inappropriate - CSU is not IgE-mediated and false positives cause needless dietary restriction
- Consider selectively: TFT + anti-TPO, tryptase, LFT, H. pylori
- Autoantibodies present in a minority, but may be entirely normal
- High-affinity IgG anti-FcepsilonRI-alpha 35-40%
- IgG anti-IgE 5-10%
- Anti-thyroid antibodies 25-30%, usually euthyroid
- Skin biopsy if any weal lasts >24h - urticarial vasculitis
Suspected IgE-mediated allergy
- Skin prick testing or specific IgE, directed by the history
- Oral food challenge is the gold standard where testing is discordant
Angioedema without weals
- C4 first - low C4 is the screening test
- Then C1-INH level and function; C1q (low in acquired, normal in hereditary)
- Normal C4 between attacks does not fully exclude HAE - repeat during an attack
Inducible urticaria
- Provocation testing - FricTest, ice cube, exercise challenge
Management
A. Anaphylaxis - treat first, investigate later
- IM adrenaline 0.5 mg (0.5 mL of 1:1000) anterolateral thigh, repeat q5min
- Supine with legs elevated, high-flow O2, IV fluid
- IV adrenaline only peri-arrest or refractory, with monitoring - arrhythmia risk
- Glucagon if on beta-blocker
- Observe 4-12h (biphasic reaction); adrenaline autoinjector + ASCIA action plan + allergist referral
B. Acute urticaria
- Remove trigger; non-sedating H1 antihistamine at standard dose
- Short prednisolone course only if severe or with angioedema
- No role for chronic steroids
C. Chronic spontaneous urticaria - stepwise
| Step | Therapy |
|---|---|
| 1 | Second-generation H1 antihistamine, standard dose (cetirizine, loratadine, fexofenadine) |
| 2 | Updose to 4x standard - off-label but guideline-endorsed; do not add a first-generation sedating agent |
| 3 | Add an advanced systemic agent: omalizumab 300 mg SC q4wk, or (2025 approvals) dupilumab or oral BTK inhibitor remibrutinib |
| 4 | Ciclosporin; specialist-directed |
- 2026 guidance places dupilumab and remibrutinib alongside omalizumab at step 3, not behind it
- Choice by age, route (oral vs SC) and comorbid type 2 disease
- Avoid systemic corticosteroids for maintenance - rebound and cumulative harm
- Avoid NSAIDs, opiates, alcohol; treat coexisting infection
D. Bradykinin-mediated angioedema
- Cease ACE inhibitor permanently (ARB usually tolerated)
- HAE acute attack: C1-INH concentrate or icatibant; adrenaline, steroids and antihistamines do not work
- Prophylaxis: C1-INH, lanadelumab, danazol; tranexamic acid where nothing else available
- Airway plan, MedicAlert, family screening
Traps
- Absence of urticaria does not exclude anaphylaxis - up to 10-20% have no skin signs, and skin signs are the last to appear in fulminant cases
- Weal lasting >24h is not urticaria - biopsy for vasculitis
- Ordering food-specific IgE panels in chronic urticaria generates false positives and unnecessary avoidance
- ACE inhibitor angioedema can begin years after starting the drug - duration does not exonerate the drug
- Normal tryptase does not exclude anaphylaxis; a raised tryptase does not distinguish IgE from non-IgE mechanism
- Antihistamine updosing to 4x is the step most often skipped - do not jump to steroids
- Chronic urticaria is not usually allergic. Say so early - the search for "the food" wastes months
- Cholinergic urticaria (small weals with heat/exercise) is often misread as exercise-induced anaphylaxis
- In a patient on a beta-blocker, adrenaline may fail - reach for glucagon
Talk track
- "The first question is whether this is anaphylaxis - I would assess airway, breathing and circulation and give IM adrenaline if there is any respiratory or cardiovascular involvement."
- "I would then characterise the lesion: how long does an individual weal last, is it itchy, and does it leave a mark. That separates urticaria from urticarial vasculitis."
- "Weals with angioedema points to a mast-cell process. Angioedema without weals points to bradykinin - ACE inhibitor or C1-inhibitor deficiency - and needs a completely different treatment."
- "If this has been going on more than six weeks with no identifiable trigger, this is chronic spontaneous urticaria. It is autoimmune rather than allergic, so I would limit investigation to a full blood count and inflammatory markers."
- "Management is a ladder: second-generation antihistamine, updosed up to fourfold, then omalizumab, dupilumab or remibrutinib. I would avoid maintenance corticosteroids."
- "The features that would make me stop and reconsider are a weal lasting beyond a day, systemic symptoms, or angioedema without urticaria."
8 of 8 sections written · drafted 2026-09-08