★ UCARE & ACARE
Accredited Centre of Excellence
The London Allergy and Immunology Centre is the first dual UCARE (Urticaria Centre of Reference and Excellence) and ACARE (Angioedema Centre of Reference and Excellence) accredited clinic in the UK, accredited by GA²LEN since November 2017. This confirms our capability to prescribe and monitor omalizumab and specialist biologic therapies for urticaria and angioedema to the highest international standards.
Contents
What is Urticaria?
Urticaria — commonly known as hives, nettle rash, or welts — is a skin condition characterised by the sudden appearance of itchy, raised, blotchy swellings called wheals. It is very common, affecting approximately 20% of people at some point in their lives. Urticaria occurs when mast cells in the skin release histamine and other inflammatory mediators, causing local swelling, redness, and intense itching.
Angioedema is a deeper form of swelling that affects the lower layers of the skin and subcutaneous tissue, most commonly the eyelids, lips, tongue, hands, feet, and genitals. It may occur alongside urticaria or independently. The swelling of angioedema is caused by either histamine (as in urticaria) or by bradykinin — a distinction that is critical for treatment, as bradykinin-mediated angioedema does not respond to antihistamines or adrenaline.
Urticaria — Key Features
- Raised, itchy wheals that can appear anywhere on the body
- Individual wheals typically last less than 24 hours and resolve without a mark
- New wheals may appear as old ones fade
- Driven by histamine release from skin mast cells
Angioedema — Key Features
- Deep, often non-itchy swelling of eyelids, lips, tongue, throat, hands
- May feel tight, painful, or burning rather than itchy
- Usually resolves over 1–3 days
- Throat swelling can rarely compromise the airway — seek emergency help if breathing is affected
Prevalence
- Acute urticaria: affects up to 20% of people at some point in their lives
- Chronic spontaneous urticaria: affects 0.5–1% of the population at any one time
- More common in women than men (2:1 ratio)
- Peak incidence in adults aged 20–40 years
Classification of Urticaria
The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline (2022) classifies urticaria as follows. Understanding which type you have determines both the investigation required and the most appropriate treatment.
| Type | Definition | Duration / Notes |
|---|---|---|
| Acute Urticaria | Spontaneous wheals and/or angioedema lasting fewer than 6 weeks | Usually resolves spontaneously. Often triggered by infection, food, or medication. Allergy testing may be warranted if a specific trigger is suspected. |
| Chronic Spontaneous Urticaria (CSU) | Spontaneous wheals and/or angioedema occurring on most days, lasting more than 6 weeks, with no identifiable external trigger | The most common chronic form. Affects 0.5–1% of the population. In about half of patients, remission occurs within 1–5 years; in others it may persist for many years. Autoimmune mechanisms are the most common cause. |
| Chronic Inducible Urticaria (CINDU) | Urticaria consistently triggered by specific physical stimuli | Includes: symptomatic dermographism (skin writing), cold contact urticaria, heat contact urticaria, solar urticaria, delayed pressure urticaria, cholinergic urticaria (exercise/heat), aquagenic urticaria, and vibratory urticaria. Each has a specific provocation test. |
Important: Urticaria is not the same as allergic urticaria. In chronic urticaria, IgE-mediated allergy is rarely the cause. Routine allergy tests (skin prick tests, RAST/IgE) are not indicated in most patients with CSU unless the clinical history specifically suggests an allergic trigger — such as consistent occurrence after a specific food or medication exposure. Most CSU is driven by autoimmune mechanisms, not allergy.
Symptoms
▲ Wheals (Hives)
- Pale, pink, or red raised swellings
- Surrounded by a red flare
- Intensely itchy
- Vary in size from a few millimetres to several centimetres
- Each weal resolves within 24 hours, leaving no mark; new wheals may appear elsewhere
▲ Angioedema
- Deep, pale or pink swelling — usually of eyelids, lips, tongue, or hands
- May not be itchy; may feel tight, painful, or burning
- Takes longer to resolve — typically 1–3 days
- Throat angioedema: difficulty swallowing, voice change — seek emergency care
▲ Impact on Quality of Life
- Sleep disturbance from nocturnal itching
- Anxiety and depression are common in chronic cases
- Interference with work, school, and social activities
- Fear of reactions in public, impact on intimate relationships
When to seek emergency help: Call 999 if swelling of the tongue or throat causes difficulty breathing, a change in voice quality, or stridor. Throat angioedema in patients with hereditary angioedema (C1 inhibitor deficiency) carries a significant risk of fatal airway obstruction. In histaminergic angioedema occurring alongside anaphylaxis features (bronchospasm, collapse), adrenaline and 999 are required.
Causes & Triggers of Urticaria
In the majority of patients with chronic spontaneous urticaria, no external cause can be identified. This is the normal finding and does not mean investigation was inadequate. The most common underlying mechanism is autoimmune: the patient’s own immune system produces antibodies (typically IgG anti-FcεRI or anti-IgE) that bind to and activate skin mast cells, triggering histamine release without any external trigger.
Autoimmune (Type IIb)
IgG autoantibodies against the high-affinity IgE receptor (FcεRI) on mast cells, or against IgE itself, cause direct mast cell activation. This accounts for the majority of truly chronic cases. Identified by the histamine-release test (BHRA) or basophil activation test.
Infections
The most common identified trigger for acute urticaria in children and adults. Viral upper respiratory tract infections, dental infections, urinary tract infections, Helicobacter pylori, and some parasitic infections. Treating the underlying infection may lead to resolution of urticaria.
Medications
Aspirin and NSAIDs worsen urticaria in NSAID-sensitive patients (NECD). ACE inhibitors cause or worsen angioedema. Opiates (codeine, morphine) cause direct mast cell degranulation. Some patients with CSU report worsening with alcohol.
Food & Additives
IgE-mediated food allergy is rarely the cause of chronic urticaria. In a small proportion of patients, foods containing high salicylates, azo dyes (e.g. tartrazine E102), and benzoate preservatives (E210–E219) may aggravate CSU. This is a pharmacological effect, not true allergy. A food diary and supervised elimination diet can clarify this in selected patients.
Physical Triggers (CINDU)
Cold, heat, pressure, sunlight, exercise (cholinergic urticaria), vibration, or water contact trigger urticaria reliably and reproducibly. These form the chronic inducible urticarias (CINDU), each with a specific diagnostic provocation test.
Stress & Hormonal Factors
Psychological stress can worsen CSU flares, as can hormonal changes — some women report exacerbation premenstrually. These are aggravating factors rather than primary causes and are important to identify for management.
Diagnosis at Our Specialist Clinic
The EAACI/GA²LEN/EuroGuiDerm guideline (2022) recommends a structured diagnostic approach. Investigations are targeted to the clinical history — not all tests are needed for every patient.
Detailed Clinical History & Symptom Diary
Duration, frequency, distribution, and duration of individual wheals; associated angioedema; potential triggers; medications (especially NSAIDs, ACE inhibitors, opiates); prior infections; family history; impact on quality of life measured with validated tools (UAS7, UCT, DLQI).
Targeted Blood Tests
Routine allergy tests are not indicated for CSU unless history suggests a specific IgE-mediated trigger. Standard initial bloods include: full blood count (for eosinophilia), CRP/ESR (for systemic inflammation), thyroid function and anti-thyroid antibodies (thyroid autoimmunity associated with CSU), and where relevant, C1 inhibitor level and function (to exclude hereditary angioedema).
Urticaria Histamine Release Test (BHRA)
Measures the ability of patient serum to trigger histamine release from donor basophils. A positive result identifies autoimmune Type IIb CSU — the most common mechanism — and can guide treatment decisions, particularly in selecting patients for omalizumab. Available at our clinic.
Provocation Tests for Chronic Inducible Urticaria
Where CINDU is suspected: dermographometer (symptomatic dermographism), TempTest or ice cube test (cold urticaria), UV provocation (solar urticaria), heat provocation, treadmill/bike exercise challenge (cholinergic urticaria), pressure test (delayed pressure urticaria). Each test confirms the specific subtype and establishes a threshold.
Skin Biopsy (Selected Patients)
A skin biopsy is occasionally indicated to exclude urticarial vasculitis — suggested by wheals lasting more than 24 hours that leave bruising or hyperpigmentation, or are associated with systemic symptoms. Also used to assess for mastocytosis or other histopathological diagnoses when CSU does not respond to standard treatment.
Treatment Pathway — EAACI/GA²LEN Step-Up Algorithm
The international guideline recommends a stepwise approach, escalating treatment when adequate control is not achieved after 2–4 weeks at each step. The goal is complete disease control — no wheals, no itch, no angioedema — not simply symptom suppression.
First-Line: Second-Generation H1 Antihistamines (Standard Dose)
A modern, non-sedating second-generation antihistamine — cetirizine 10 mg, loratadine 10 mg, fexofenadine 120–180 mg, or desloratadine 5 mg — taken daily. If symptoms are well controlled, continue for at least one month before considering dose reduction. The older, sedating “first-generation” antihistamines (chlorphenamine, hydroxyzine) are not recommended as first-line therapy due to central nervous system side effects and impairment of performance.
Up-Dosing: Increase to Up to 4× Licensed Antihistamine Dose
If standard-dose antihistamine provides insufficient control after 2–4 weeks, the dose may be increased up to four times the licensed dose (e.g. cetirizine up to 40 mg daily), under specialist supervision. Evidence suggests this improves response in a proportion of patients with limited additional side effects. This step requires specialist oversight and is not recommended without consultant guidance.
Add-On: Omalizumab (Xolair®) 300 mg — First-Line Biologic
MHRA-licensed in the UK for CSU in patients aged 12 and older inadequately controlled on H1 antihistamines. Given as a subcutaneous injection of 300 mg every 4 weeks. In Phase III trials (ASTERIA I and II), 36–44% of patients achieved complete symptom control (UAS7 = 0). Omalizumab acts by binding free IgE, reducing IgE receptors on mast cells and basophils, and normalising mast cell reactivity. Well tolerated, suitable during pregnancy, and carries a very low risk of anaphylaxis. Available at our clinic. Reassessed after 6 months of treatment.
Add-On: Ciclosporin — For Antihistamine & Omalizumab Refractory CSU
Low-dose ciclosporin (an immunosuppressant) is recommended as a third-line add-on for patients with CSU refractory to both high-dose antihistamines and omalizumab. Used for as short a time as possible due to risk of hypertension, renal impairment, and drug interactions. Requires regular blood pressure and blood test monitoring. Used under strict specialist supervision at our clinic.
Short courses of oral corticosteroids (maximum 10 days) may be used at any step to manage severe acute flares. They are not recommended as long-term treatment for CSU due to significant side effects. Cimetidine and ranitidine (H2 antihistamines) occasionally used as add-ons are no longer routinely recommended in the 2022 guideline update.
New Biologic Therapies for CSU — 2025 Major Updates
The CSU treatment landscape transformed significantly in 2025 with two major new approvals, expanding options for patients who do not achieve adequate control with antihistamines and omalizumab. Omalizumab is effective in approximately 80% of patients after 6 months; the remaining 20–27% represent a significant unmet need now being addressed by these new agents.
Dupilumab (Dupixent®)
Anti-IL-4Rα — First New CSU Biologic in Over a Decade
FDA-approved in April 2025 for CSU in patients aged 12 and older inadequately controlled on H1 antihistamines — marking the first new targeted CSU therapy in over a decade. Dupilumab targets the IL-4/IL-13 signalling pathway, key drivers of Type 2 inflammation in CSU. In the Phase III LIBERTY-CSU CUPID-A and CUPID-C trials, dupilumab achieved complete symptom control (UAS7 = 0) in approximately 30% of biologic-naïve patients at Week 24. It is particularly beneficial for patients with atopic comorbidities (eczema, asthma, food allergy) and is now under EMA review for European and UK licensing. EMA and MHRA consideration for the UK is anticipated.
Also effective for: Atopic eczema, severe asthma (eosinophilic), nasal polyps (CRSwNP), food allergy (EAACI 2025). A powerful option for patients with multiple type-2 inflammatory conditions.
Enquire at your consultation about current UK availability.
Remibrutinib (Rhapsido®)
First Oral BTK Inhibitor for CSU
Remibrutinib became the first oral Bruton’s tyrosine kinase (BTK) inhibitor approved for antihistamine-refractory CSU in 2025. It targets the BTK signalling pathway in mast cells, inhibiting IgE-receptor-mediated activation. In the Phase III REMIX-1 and REMIX-2 trials, symptom improvement was evident as early as Week 2, with complete response rates of 28–36% and a favourable safety profile. As an oral once-daily tablet, remibrutinib offers a significant practical advantage over injectable biologics for patients who prefer non-injectable therapy. Under regulatory review by EMA/MHRA.
Enquire at your consultation about current UK availability.
Omalizumab (Xolair®) 300 mg
Anti-IgE — UK Standard of Care for Refractory CSU
Still the UK standard-of-care biologic for antihistamine-refractory CSU, MHRA-licensed for adults and adolescents aged 12+. Subcutaneous injection every 4 weeks. Achieves complete control in 36–44% of patients; clinically meaningful improvement in a further significant proportion. Well tolerated, pregnancy-safe, fast-acting (often within the first 1–4 weeks). Available privately at our clinic. We are a UCARE-accredited centre with extensive experience in omalizumab prescribing and monitoring for CSU.
Available now at our Harley Street, City, and East London clinics.
Dupilumab in omalizumab-resistant CSU: A 2025 prospective study (Hayama et al., World Allergy Organ J) found that switching from omalizumab to dupilumab improved Urticaria Control Test (UCT) scores in 75% of omalizumab-resistant CSU patients at 24 weeks, despite dupilumab not meeting its primary endpoint in the broader CUPID-B trial (which included many non-omalizumab-naïve patients). Real-world experience suggests dupilumab may offer meaningful benefit for selected omalizumab non-responders.
Types of Angioedema — Why the Distinction Matters
Not all angioedema is the same. The mediator driving the swelling — histamine or bradykinin — determines the correct treatment. Giving antihistamines or adrenaline to bradykinin-mediated angioedema will not work and may delay appropriate life-saving treatment.
| Type | Mediator | Associated With | Treatment |
|---|---|---|---|
| Histaminergic angioedema | Histamine | CSU, acute allergic reactions, food allergy, drug allergy. Usually occurs with urticaria wheals. | Antihistamines, corticosteroids, adrenaline (if anaphylaxis), omalizumab for CSU-associated |
| ACE inhibitor-induced angioedema | Bradykinin | Use of ACE inhibitors (ramipril, lisinopril, perindopril, etc.). Tongue and lip swelling most common. Can occur any time during treatment, even after years. | Stop ACE inhibitor immediately. Antihistamines and adrenaline are not effective. Icatibant (bradykinin B2 receptor antagonist) may be used for severe attacks. Switch to an ARB (not an ACE inhibitor). |
| Hereditary angioedema (HAE) | Bradykinin | C1 inhibitor deficiency (Type 1) or dysfunction (Type 2). Rare — 1:50,000–100,000. Autosomal dominant inheritance. Recurrent attacks without urticaria. | Specific HAE treatments only (see below). Antihistamines and adrenaline are not effective. Laryngeal attacks are life-threatening. |
| Idiopathic angioedema | Unknown | Recurrent angioedema with no identifiable cause and normal C1 inhibitor. The most common form of isolated angioedema without urticaria. | Antihistamines as first-line; omalizumab for antihistamine-refractory cases. Requires specialist investigation to exclude HAE and ACE inhibitor cause. |
Hereditary Angioedema (HAE) — Diagnosis & Treatment
Hereditary angioedema (HAE) is a rare but potentially life-threatening condition. Laryngeal attacks — affecting the throat and upper airway — carry a risk of fatal asphyxiation if not treated promptly with specific HAE medications. Every patient with confirmed or suspected HAE must be under the care of a specialist and must carry appropriate on-demand treatment at all times.
HAE is caused by deficiency (Type 1 — the most common, accounting for ~85% of cases) or dysfunction (Type 2) of C1 esterase inhibitor (C1-INH), a protein that regulates the contact activation pathway and kallikrein-kinin system. Without adequate C1-INH, uncontrolled bradykinin production causes recurrent episodes of swelling of the skin, gastrointestinal tract, and upper airway. Attacks typically last 2–5 days and can be triggered by stress, trauma, infection, hormonal changes (oestrogen), and dental or surgical procedures.
Diagnosis
Blood tests: C1 inhibitor level and function (both must be measured), and C4 complement level (chronically low in Types 1 and 2). Genetic testing where needed. Diagnosis should be repeated to confirm, as single measurements can be misleading. All offspring and first-degree relatives of affected patients should be tested.
Treatment — Current UK Landscape (2024–2025)
On-Demand Attack Treatment
- Plasma-derived C1 inhibitor (C1-INH) — e.g. Berinert, Cinryze. First-line for all attacks. Intravenous.
- Icatibant (Firazyr®) — Bradykinin B2 receptor antagonist. Self-administered subcutaneous injection. First-line for attacks in adults, adolescents, and children over 2 years.
- Recombinant C1-INH (Ruconest®) — Intravenous. Alternative on-demand option.
- All patients must carry on-demand medication for at least two attacks at all times.
Long-Term Prophylaxis
- Lanadelumab (Takhzyro®) — Plasma kallikrein inhibitor. Subcutaneous injection every 2–4 weeks. Recommended as first-line long-term prophylaxis (EAACI/WAO guideline, 89% agreement, evidence level A). Markedly reduces attack frequency.
- Berotralstat (Orladeyo®) — Oral plasma kallikrein inhibitor. Once-daily capsule. First-line prophylaxis (EAACI 81% agreement, evidence level A). UK-licensed and available.
- Intravenous C1-INH (Cinryze®) — Twice-weekly IV infusion. Established first-line option.
- Attenuated androgens (danazol) are only recommended as second-line due to significant side effects.
Short-Term Prophylaxis
Required before known trigger events — dental procedures, surgery, endoscopy, childbirth, stressful life events. Intravenous plasma-derived C1-INH is first-line for short-term prophylaxis. Discuss pre-procedure planning with your consultant well in advance of any planned procedure.
2024 UK update: A UK Delphi consensus (Yong et al., Clin Exp Immunol, 2024) confirms that lanadelumab and berotralstat are now established first-line long-term prophylaxis options in the UK, governed by NHS England commissioning policies and NICE technology appraisals. Our consultants can assess HAE eligibility and initiate or manage these therapies privately.
Self-Management — What You Can Do
Alongside medical treatment, the following measures may help reduce urticaria flares and improve daily comfort:
Avoid Known Aggravators
- Aspirin, ibuprofen, and other NSAIDs
- ACE inhibitors (discuss with your GP if prescribed)
- Opioid painkillers (codeine, morphine)
- Alcohol (direct mast cell effect)
- Sudden temperature changes and tight clothing
Symptom Relief
- Cool compresses or cool baths to reduce itching
- Loose, breathable, non-synthetic clothing
- Non-perfumed emollients for dry, itchy skin
- Keep antihistamines with you at all times
- Avoid scratching — it worsens wheals via dermographism
Food & Dietary Factors
- Keep a food and symptom diary if you suspect dietary triggers
- Consider a low-salicylate, low-preservative diet if advised by your consultant
- Discuss with a specialist dietitian before eliminating food groups
- Do not undertake unguided elimination diets — this can cause nutritional deficiencies
Stress & Wellbeing
- Stress is a recognised aggravating factor — discuss with your consultant
- Psychological support or CBT can help with chronic urticaria anxiety
- Use validated scores (UAS7, UCT) to monitor and communicate disease activity
- Consider patient support groups (e.g. Urticaria UK)
Frequently Asked Questions
Important Notice
This page provides general educational information only and is not a substitute for individual medical advice. All treatment decisions are made by a qualified consultant following a full assessment. In a medical emergency — including throat swelling or breathing difficulty — call 999 immediately.
References
- Zuberbier T, Abdul Latiff AH, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734–766. doi:10.1111/all.15090
- Agache I, Akdis CA, et al. EAACI Biologicals Guidelines — Omalizumab for the treatment of chronic spontaneous urticaria. Allergy. 2022;77(1):17–38. doi:10.1111/all.15030
- Sanofi / Regeneron. Dupixent (dupilumab) FDA approval for chronic spontaneous urticaria in patients aged 12 and older. April 2025. LIBERTY-CSU CUPID Phase 3 trial data.
- Hayama K, Ito-Watanabe M, Fujita H. Effectiveness of transitioning from omalizumab to dupilumab in chronic spontaneous urticaria patients with inadequate response to omalizumab. World Allergy Organ J. 2025;18(8):101098. doi:10.1016/j.waojou.2025.101098
- Remibrutinib (Rhapsido®; Novartis). First oral BTK inhibitor FDA approval for antihistamine-refractory CSU, 2025. Phase III REMIX-1 and REMIX-2 trial data.
- Türk M, Yilmaz I, Ertas R, Kocaturk E. Efficacy of omalizumab, dupilumab, and remibrutinib in chronic spontaneous urticaria: Phase data and placebo response. Allergy. 2025;80(8):2410–2413.
- Maurer M, Magerl M, et al. EAACI/WAO Guideline for the management of hereditary angioedema. Allergy. 2022. doi:10.1111/all.15214
- Yong PFK, Annals R, et al. Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus. Clin Exp Immunol. Published online March 2024. doi:10.1093/cei/uxae018
- National Institute for Health and Care Excellence (NICE). Omalizumab for chronic spontaneous urticaria. Technology Appraisal TA339. NICE, London.
Page reviewed: June 2026 | London Allergy and Immunology Centre | privateallergy.uk