Urticaria and other allergic presentations

At a glance

• Urticaria is mast cell-driven: wheals, angioedema or both. About 1 in 5 people have acute urticaria at some point.
• Individual wheals are itchy, blanch and resolve within 24 hours without a mark. Anything else suggests a mimic.
• Acute (6 weeks or less) is usually idiopathic or triggered by infection and needs no tests. Chronic (over 6 weeks) is mostly autoimmune, rarely allergic, and treated by a step-up algorithm.
• The first job in any acute allergic presentation is to decide whether it is anaphylaxis. Urticaria with airway, breathing, circulation or severe gut involvement is treated with IM adrenaline: see the anaphylaxis note.
• The 2026 GA2LEN-led International Urticaria Guideline replaced the 2022 EAACI/GA2LEN/EuroGuiDerm/APAAACI version. It keeps the four-step backbone and adds dupilumab and remibrutinib.

Causes

Classification

Type	Subtypes and triggers
Acute spontaneous	Idiopathic (about half), viral URTI (the commonest identifiable cause, especially in children), drugs (NSAIDs, beta-lactams, opioids, contrast), IgE-mediated food or sting allergy
Chronic spontaneous (CSU)	Type I autoallergy (IgE against autoantigens such as TPO), type IIb autoimmunity (IgG against IgE or its receptor), or both; many unexplained
Chronic inducible (CIndU)	Symptomatic dermographism (the commonest), cold, delayed pressure, heat, solar, cholinergic, contact, aquagenic, vibratory

• Type IIb CSU tends to have a raised CRP, low basophil and eosinophil counts, low total IgE and raised IgG anti-TPO. It responds poorly or slowly to omalizumab and better to ciclosporin.
• CSU is associated with autoimmune thyroid disease. Thyroid antibodies are a marker; treating hypothyroidism rarely clears the hives.
• Food is almost never the cause of CSU. Elimination diets and broad IgE panels cause harm without benefit.

Other allergic presentations

Presentation	Key features	Where to read more
Anaphylaxis	Skin features plus airway, breathing, circulation or GI compromise; or isolated hypotension or bronchospasm	Anaphylaxis
Isolated angioedema	Deep swelling without wheals: think bradykinin (ACE inhibitor, hereditary)	Angioedema
Mammalian meat allergy	Hives or anaphylaxis 4 to 6 hours after red meat; tick bite history (alpha-gal)	Anaphylaxis
Pollen-food syndrome	Itchy mouth within minutes of raw fruit or nuts in someone with hay fever; cooked forms tolerated	Allergic rhinitis
Allergic rhinoconjunctivitis	Sneezing, rhinorrhoea, itchy eyes, often seasonal	Allergic rhinitis
Allergic contact dermatitis	Eczema at the contact site 24 to 72 hours after exposure (type IV); patch testing, not prick testing

Focused history

• Timing: how long each wheal lasts (mark one with a pen), and how long the whole illness has gone on.
• Angioedema: present in about half of CSU. Swelling without wheals points elsewhere: ask about ACE inhibitors, gliptins, sacubitril and family history.
• Triggers: onset within 1 to 2 hours of a food, sting or drug suggests IgE-mediated allergy. Rubbing, cold, heat, exercise, sweating, pressure or sun suggests an inducible form.
• Drugs and cofactors: NSAIDs, opioids, alcohol and stress aggravate CSU.
• Systemic symptoms: fever, joint pain, bone pain or weight loss suggest urticarial vasculitis, an autoinflammatory syndrome or Schnitzler syndrome.
• Impact: sleep, work and mood. In an early UK quality-of-life study, CSU scored as badly as triple-vessel coronary disease.

Focused examination

• Look at the wheals: size, distribution, whether they blanch, and any purpura or residual pigmentation (vasculitis).
• Stroke the skin firmly with a blunt object: a linear wheal within minutes is dermographism.
• Darier sign (rubbing a brown macule raises a wheal) suggests cutaneous mastocytosis.
• Lymphadenopathy, hepatosplenomegaly or arthritis prompt a search for systemic disease.

Pitfall: most patients arrive between crops. Ask them to bring photos.

Red flags

Feature	Think of
Wheals lasting over 24 hours, burning, bruising	Urticarial vasculitis (biopsy, C3, C4, C1q, anti-C1q, ANA)
Recurrent fever, bone pain, raised CRP, IgM paraprotein	Schnitzler syndrome
Childhood-onset rash with fever triggered by cold, family history	Cryopyrin-associated periodic syndrome
Flushing, collapse, persistently raised baseline tryptase	Mastocytosis
Angioedema without wheals, abdominal attacks	Hereditary or ACE inhibitor angioedema
Itchy urticated plaques in an older person, later blisters	Prodromal bullous pemphigoid
Target lesions fixed for days, mucosal involvement	Erythema multiforme or a severe drug reaction

Investigations

• Acute urticaria: no routine tests. Test only for a suspected IgE trigger (skin prick or specific IgE to that food, drug or venom), guided by history.
• CSU, every patient: FBC with differential and CRP and/or ESR. Raised inflammatory markers push you towards vasculitis or autoinflammatory disease.
• CSU, specialist: total IgE and IgG anti-TPO, which help predict omalizumab response (low IgE predicts a poor or slow response). TSH if thyroid disease is suspected clinically.
• CIndU: provocation testing (ice cube test for cold urticaria, dermographometer, exercise or warm bath for cholinergic), with threshold measurement.
• Skin biopsy for wheals lasting over 24 hours.
• Tryptase if anaphylaxis or mastocytosis is suspected.

Measuring disease activity and control

• UAS7: wheal score (0 to 3) plus itch score (0 to 3) each day, summed over 7 days. Range 0 to 42. A UAS7 of 28 or more is severe.
• UCT: four questions over 4 weeks, scored 0 to 16. 12 or more is well controlled. The target is complete control (UCT 16, UAS7 0).
• AAS and AECT do the same jobs for angioedema.

Management

Avoid identifiable triggers (NSAIDs, opioids, physical stimuli). Then step up, reassessing every 2 to 4 weeks, and step down once control has held for some months, because most CSU remits within 2 to 5 years. The 2026 guideline asks for the need for ongoing or alternative treatment to be re-evaluated every 3 to 6 months.

Step	2026 International Guideline	Notes
1	Second-generation H1 antihistamine, standard dose, taken daily	Cetirizine, loratadine, fexofenadine, desloratadine, bilastine. No preferred agent
2	Up-dose the same antihistamine up to 4-fold	Off-label. Don't exceed 4-fold or combine two agents
3	Add omalizumab 300 mg every 4 weeks	Off-label up-dosing to 600 mg and/or every 2 weeks if partial response
4	Dupilumab or remibrutinib, in place of omalizumab, or instead of it where cost or access dictates	Both "suggested" (weaker) as add-ons to antihistamine in CSU unresponsive to high-dose antihistamine, the same population as omalizumab. Prior omalizumab failure isn't required. Not combined with omalizumab
5	Ciclosporin 3 to 5 mg/kg/day	For refractory disease; monitor BP and renal function

• Corticosteroids: a short rescue course (up to about 10 days) for a severe flare. Long-term use is strongly recommended against.
• First-generation (sedating) antihistamines are not recommended: impaired driving and cognition, and deaths in overdose. Avoid them in older people.
• H2 antagonists and montelukast: the 2026 guideline makes no recommendation for H2 antagonists, and montelukast sits outside the algorithm on weak evidence and neuropsychiatric risk. They still matter in Australia because PBS rules count them.
• Remibrutinib (oral BTK inhibitor, 25 mg twice daily) works within 1 to 2 weeks in the REMIX-1 and REMIX-2 trials. TGA-registered May 2026, not PBS-listed.
• Dupilumab reduced itch and wheals in omalizumab-naive CSU (LIBERTY-CSU CUPID). FDA approval for CSU came in 2025; it is PBS-listed in Australia only for atopic dermatitis and asthma.

PBS omalizumab for severe CSU

• Section 100 item, prescribed by a clinical immunologist, allergist, dermatologist or general physician with CSU expertise.
• Daily itch and hives for at least 6 weeks despite H1 antihistamines.
• At least 2 weeks of "standard therapy": maximally tolerated H1 antihistamine plus one of an H2 antagonist, montelukast 10 mg daily or doxepin (unless contraindicated or not tolerated).
• A current UAS7 of at least 28 and itch score above 8, measured on that therapy. (The restriction PBAC considered in 2015 required the assessment to be no more than 1 month old; the 2026 form asks only for the current score.)
• The 2026 form also accepts patients who can't take H1 antihistamines, or the standard-therapy combination, because of a contraindication or intolerance severe enough to stop treatment.
• Initial authority covers 12 weeks. A patient who stops and relapses re-applies as a new patient. Biosimilar omalizumab continuations are streamlined.

Pitfall: writing "failed antihistamines" without documenting the add-on agent and the UAS7. The authority will be refused.

Special populations

• Pregnancy: loratadine first, then cetirizine. Up-dose cautiously. Omalizumab has reassuring registry data. Avoid sedating antihistamines in the third trimester and when breastfeeding.
• Renal impairment: halve cetirizine and levocetirizine doses at low eGFR; fexofenadine and bilastine need less adjustment.
• Children: viral acute urticaria is common and self-limiting.

Pitfalls

• Missing anaphylaxis because the patient "only has hives". Check airway, breathing, circulation and the gut.
• Ordering food IgE panels for CSU. Positive results are common and almost always irrelevant.
• Calling every NSAID-induced flare a drug allergy.
• Giving repeated or depot corticosteroids for chronic urticaria.
• Missing urticarial vasculitis because nobody asked how long each wheal lasts.
• Treating isolated angioedema on an ACE inhibitor as urticaria. Antihistamines don't touch bradykinin.