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Dermatology
Allergy
Immunology

Chronic Urticaria

High EvidenceUpdated: 2025-12-22

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Red Flags

  • Angioedema affecting airway (stridor, tongue swelling) - Anaphylaxis
  • Urticarial vasculitis signs (painful, bruising, >24h duration)
  • Systemic symptoms (fever, joint pain)
  • Triggers identifying anaphylaxis risk (e.g., peanut + exercise)
Overview

Chronic Urticaria

1. Overview

Chronic Urticaria (CU) is defined as the daily or near-daily occurrence of wheals (hives), angioedema, or both for more than 6 weeks. Unlike acute urticaria, it is rarely due to an external allergy. The most common form is Chronic Spontaneous Urticaria (CSU), which is an autoimmune-driven skin condition.

Key Classification

  1. Chronic Spontaneous Urticaria (CSU): No specific trigger. 60-70% of cases. Autoimmune.
  2. Chronic Inducible Urticaria (CIndU): Specific physical trigger. 20-30% of cases.
    • Dermographism (stroking)
    • Cholinergic (sweat/heat)
    • Cold/Solar/Pressure urticaria

Clinical Features of a Wheal

  • Central swelling (edema)
  • Surrounding erythema (flare)
  • Intense itching (pruritus)
  • Transient: Individual lesions disappear <24 hours without scarring

Epidemiology

FactorDetails
Prevalence0.5-1% of population
GenderFemale predominance (2:1)
AgePeak 20-40 years
Duration1-5 years average (can be longer)
2. Pathophysiology
┌─────────────────────────────────────────────────────────────────────────────┐
│                    CHRONIC URTICARIA PATHOPHYSIOLOGY                        │
├─────────────────────────────────────────────────────────────────────────────┤
│                                                                             │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                 MAST CELL ACTIVATION (The Driver)                   │   │
│   │  • Skin mast cells degranulate spontaneously                        │   │
│   │  • Release: Histamine, Leukotrienes, Prostaglandins, PAF            │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                                    ↓                                        │
│               ┌────────────────────┴─────────────────────┐                  │
│               ↓                                          ↓                  │
│   ┌───────────────────────────┐          ┌──────────────────────────┐       │
│   │ TYPE I AUTOIMMUNITY       │          │ TYPE II AUTOIMMUNITY     │       │
│   │ ("Auto-allergic")         │          │ (Auto-antibodies)        │       │
│   │                           │          │                          │       │
│   │ • IgE antibodies against  │          │ • IgG antibodies against │       │
│   │   self-antigens (e.g. TPO)│          │   IgE or FcεRI receptor  │       │
│   │ • Cross-link FcεRI        │          │ • "Autoimmune Urticaria" │       │
│   │ • 40-50% cases            │          │ • 30-40% cases           │       │
│   └───────────────────────────┘          └──────────────────────────┘       │
│                                    ↓                                        │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                    CLINICAL EFFECTS                                 │   │
│   │  • Histamine → Vasodilation (Redness)                               │   │
│   │  • Histamine → Vascular permeability (Swelling/Wheal)               │   │
│   │  • Histamine → Sensory nerve simulation (Itch)                      │   │
│   │  • Bradykinin? → Angioedema (deeper swelling)                       │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                                                                             │
└─────────────────────────────────────────────────────────────────────────────┘

Autoimmune Associations

CSU is strongly linked to other autoimmune diseases, particularly Hashimoto's Thyroiditis (up to 30% have antithyroid antibodies). Screening for thyroid disease is mandatory.

3. Clinical Features

History Taking

The "6 Ss" Trigger Check (to rule out Inducible):

  1. Scratching (Dermographism)
  2. Sweating (Cholinergic)
  3. Sun (Solar)
  4. Shivering (Cold)
  5. Stress (Pressure - delayed)
  6. Shower (Aquagenic)

Excluding Vasculitis:

  • Do individual lesions last >24 hours?
  • Is it painful/burning rather than itching?
  • Does it leave a bruise (purpura) when it fades?
  • (If YES to above → think Urticarial Vasculitis)

Medication Review:

  • NSAIDs/Codeine: "Pseudo-allergens" - worsen existing urticaria directly via mast cells.
  • ACE Inhibitors: Common cause of isolated Angioedema (Bradykinin-mediated).

Physical Examination

  • Wheals: Check for "migratory" nature (draw a circle around one, check later).
  • Dermographism: Stroke back with tongue depressor. Wheal forms in <5 mins.
  • Angioedema: Swelling of lips, eyelids, hands. Non-pitting.
4. Diagnosis

Diagnostic Approach

Diagnosis is clinical. Extensive allergy testing is NOT recommended as CSU is rarely allergic.

Investigations

Routine Baseline (EAACI Guidelines):

  1. FBC + ESR/CRP: Rule out systemic inflammation/infection.
  2. Differential Blood Count: Checking for eosinophilia.
  3. Total IgE: Often elevated.
  4. Anti-TPO Assessment: Thyroid autoimmune screen.

Extended (Only if history suggests):

  • Challenge tests: Ice cube test (Cold urticaria), Exercise (Cholinergic).
  • Skin Biopsy: ONLY if vasculitis suspected (painful, persistent, purpuric lesions).
5. Management Algorithm
┌─────────────────────────────────────────────────────────────────────────────┐
│                    CHRONIC URTICARIA MANAGEMENT (EAACI)                     │
├─────────────────────────────────────────────────────────────────────────────┤
│                                                                             │
│   DIAGNOSIS CONFIRMED (Wheals &gt;6 weeks, Vasculitis excluded)                │
│                          ↓                                                  │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                 STEP 1: STANDARD ANTIHISTAMINE                      │   │
│   │  • 2nd Generation (Non-sedating) H1-Antihistamine daily             │   │
│   │  • E.g., Cetirizine 10mg, Fexofenadine 180mg, Loratadine 10mg       │   │
│   │  • Assess for 2-4 weeks                                             │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                          ↓ Inadequate control                               │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                 STEP 2: HIGH DOSE ANTIHISTAMINE                     │   │
│   │  • INCREASE dose of same antihistamine up to 4-FOLD                 │   │
│   │  • E.g., Cetirizine 40mg daily, Fexofenadine 720mg daily            │   │
│   │  • (Off-label but strong guideline recommendation)                  │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                          ↓ Inadequate control after 2-4 weeks               │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                 STEP 3: BIOLOGIC THERAPY                            │   │
│   │  • Add OMALIZUMAB (Anti-IgE Monoclonal Antibody)                    │   │
│   │  • 300mg SC every 4 weeks                                           │   │
│   │  • Highly effective (&gt;70% response)                                 │   │
│   │  • Very safe profile                                                │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                          ↓ Inadequate control                               │
│   ┌─────────────────────────────────────────────────────────────────────┐   │
│   │                 STEP 4: IMMUNOSUPPRESSION                           │   │
│   │  • Add Cyclosporine A (3-5 mg/kg/day)                               │   │
│   │  • Requires monitoring (BP, Renal function)                         │   │
│   └─────────────────────────────────────────────────────────────────────┘   │
│                                                                             │
└─────────────────────────────────────────────────────────────────────────────┘

Important Management Principles

  1. Daily Dosing: Antihistamines must be taken daily, not "as needed" (PRN). The goal is receptor occupancy.
  2. Avoid Sedating H1: (e.g., Chlorphenamine, Hydroxyzine) No longer recommended for long-term use due to REM sleep disruption and driving impairment.
  3. Short-course Steroids: Prednisolone (e.g., 20-40mg for 3-7 days) ONLY for severe exacerbations. NOT for maintenance.

Omalizumab

  • Mechanism: Binds free IgE, reducing receptor expression on mast cells.
  • Efficacy: Transformative. ~40% distinct complete remission, ~70% significant improvement.
  • Onset: Fast (days to weeks).
6. Angioedema Without Wheals

If patient has Angioedema ONLY (swelling without itchy hives), consider:

  1. ACE Inhibitor Induced: Can happen years after starting. Stop ACEi.
  2. Hereditary Angioedema (HAE): C1 esterase inhibitor deficiency.
    • Test: C4 level (Low in HAE).
    • Red flag: Laryngeal edema, abdominal pain, family history.
    • Treatment: Antihistamines/Steroids/Adrenaline DO NOT WORK. Needs C1-inhibitor or Icatibant.
7. Prognosis
  • Natural History: Generally self-limiting but prolonged.
  • Duration: 50% resolve within 1 year. 20% persist >5 years.
  • Quality of Life: Impact comparable to ischemic heart disease (sleep disturbance, itching, social isolation).
8. Complications
  • Sleep Deprivation: Due to nocturnal itch.
  • Psychological: Anxiety/Depression.
  • Systemic toxicity: From inappropriate long-term steroid use (avoid!).
9. Special Considerations

Pregnancy

  • Safety: Cetirizine and Loratadine are generally considered safe (Category B).
  • Step-up: Up-dosing is usually avoided; standard dose preferred.
  • Omalizumab: Emerging data suggests safety, but use with caution.

Children

  • Guidelines similar to adults.
  • Doses adjusted for weight/age.
  • Cetirizine/Loratadine syrups available.
10. Key Clinical Pearls

Exam-Focused Points

  1. Not Allergic: Counsel patients that finding an "allergy" (food/detergent) is unlikely. It is autoimmune.
  2. 4x Dose: Don't say "antihistamines failed" until you have tried up to 4x standard dose daily.
  3. ACE Inhibitors: Always check drug history in angioedema.
  4. C4 Level: The screening test for Hereditary Angioedema (in isolated angioedema).
  5. Vasculitis: Pain + Bruising + >24h persistence = Urticarial Vasculitis (Needs biopsy).
  6. Avoid NSAIDs: Can worsen CSU in 30% of patients. Paracetamol is safe.

Common Exam Scenarios

  • Patient with 3 months of hives. Wants allergy test. (Explain autoimmune nature, start daily antihistamine).
  • Patient on fexofenadine 180mg still itching. (Increase to 360mg bd).
  • Patient with lip swelling, no hives, taking Ramipril. (Stop Ramipril, monitor).
11. Patient Explanation

What is Chronic Urticaria?

"Chronic urticaria is a condition where your skin's immune cells (mast cells) are 'twitchy' and release histamine too easily, causing hives and swelling.

Unlike acute hives from a peanut allergy, this is not caused by something you are eating or touching. It is an internal 'autoimmune' issue - your immune system is activating your skin cells by mistake."

Will it Go Away?

"Yes, for most people it eventually burns itself out and goes away, but this can take months to years. Our goal is to suppress the symptoms completely with medication so you can live a normal life while we wait for it to resolve."

Is the Medication Safe?

"Yes. Modern antihistamines are very safe even at high doses (up to 4 tablets a day). They do not cause damage to your body. Is it much safer to take high-dose antihistamines than to take steroid tablets."

12. Evidence & Guidelines

Key Guidelines

GuidelineOrganizationYearKey Points
Urticaria GuidelineEAACI / WAO2018/2021The global gold-standard. 4-step algorithm.
BSACI GuidelineBritish Society (Allergy)2015Similar to EAACI.

Landmark Trials

GLACIAL and ASTERIA Trials (2013):

  • Pivotal Phase 3 trials for Omalizumab in CSU.
  • Established efficacy and safety in patients refractory to H1-antihistamines.
  • Led to FDA/EMA approval.

Up-Dosing Studies:

  • Confirms that Increasing antihistamine dose improves control in ~60% of non-responders.

Evidence-Based Recommendations

RecommendationEvidence Level
Non-sedating H1 antihistamines 1st lineHigh
Up-dosing H1 to 4-foldHigh
Omalizumab for refractoryHigh
Systemic Steroids for maintenanceStrong recommendation AGAINST
Routine Allergy TestingStrong recommendation AGAINST
13. References
  1. Zuberbier T, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1311-1344. (Updated 2021).
  2. Kaplan AP. Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations. Allergy Asthma Immunol Res. 2017;9(6):477-482.
  3. Maurer M, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368(10):924-935.
  4. Powell RJ, et al. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy. 2015;45(3):547-565.

Last updated: 2025-12-22

At a Glance

EvidenceHigh
Last Updated2025-12-22

Red Flags

  • Angioedema affecting airway (stridor, tongue swelling) - Anaphylaxis
  • Urticarial vasculitis signs (painful, bruising, &gt;24h duration)
  • Systemic symptoms (fever, joint pain)
  • Triggers identifying anaphylaxis risk (e.g., peanut + exercise)

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines