urticaria
URTICARIA
Treatment Guideline Chart
Urticaria is characterized by the appearance of wheals (hives) and/or angioedema.
The intensity of the pruritus varies but may be severe enough to disrupt sleep, work or school.
It is classified acute if the urticaria has been present for ≤6 weeks and chronic if >6 weeks. It can be spontaneous (no definite triggering factor) or inducible (a specific definite triggering factor is identified).
It can be triggered by immunological or non-immunological mechanism.

Urticaria Diagnosis

Classification

  • Urticaria is classified as acute or chronic, and as spontaneous (no definite triggering factor) or inducible (a specific definite triggering factor is identified)
    • A specific cause is more likely to be identified in acute cases
  • Can be triggered by immunological or non-immunological mechanism

Acute Urticaria

  • Lesions occurring ≤6 weeks in duration and usually without angioedema
  • More common in children and young adults and tends to have a triggering event

Chronic Urticaria

  • More common in adults (3rd and 4th decades of life), symptoms last >6 weeks
  • A patient can have >1 form of chronic urticaria including >1 form of chronic inducible urticaria

Chronic Spontaneous Urticaria

  • Presence of wheals, angioedema or both for >6 weeks due to factors that are not identifiable or idiopathic
  • Known causes include autoimmunity Type I (autoallergic) with IgE autoantibodies to self-antigens and autoimmunity Type IIb with mast cell-directed activating autoantibodies 
  • May recur after achieving months or years of full remission

Chronic Inducible Urticaria

  • Cold urticaria
  • Delayed pressure urticaria
  • Heat urticaria
  • Symptomatic dermographism
    • Daily lesions and recurrent episodic lesions are not differentiated
  • Solar urticaria
  • Vibratory angioedema
  • Aquagenic urticaria
  • Cholinergic urticaria
  • Contact urticaria

Autoimmune Chronic Spontaneous Urticaria (ACU)

  • Proposed gold standard for diagnosis of ACU (combination of all 3 parameters):
    • Positive bioassay [eg basophil histamine release assay (BHRA), basophil activation marker expression] and
    • Positive autoreactivity [eg positive autologous serum skin test (ASST)] and
    • Positive immunoassay for specific IgG autoantibodies against FcεRIα and/or anti-IgE

Diagnosis

  • Diagnosis is based on patient’s history and physical examination

Physical Examination

Look for typical lesions of urticaria

  • Wheals which typically are fleeting, lasting within 30 minutes-24 hours, have a central swelling of variable size surrounded by erythema and associated with itching, sometimes burning sensation
  • Angioedema characterized by a sudden evident swelling of the lower dermis and subcutis or mucous membranes, that is sometimes painful which may last up to 72 hours
  • Lesions may appear on any part of the body

Stroke the arm to test for dermographism/dermatographism

  • Discontinue antihistamine therapy for at least 2-3 days and immunosuppressive therapy for at least a week before testing

DIAGNOSTIC TESTS

Acute Urticaria 

  • Routine laboratory work-ups are not required except when the cause of the urticaria points to a type I food hypersensitivity or other triggering factors like medications [eg nonsteroidal anti-inflammatory drugs (NSAIDs)]

Chronic Urticaria

  • Diagnostic examinations are based on the patient’s history and physical examination
  • Assess disease activity of chronic urticaria
    • Several guidelines recommend using the Urticaria Activity Score (UAS7) system in assessing disease severity and treatment effectivity in patients with wheals
    • Summation of scores of symptoms during a 7-day period
      • 0 = no wheals, no pruritus
      • 1 = mild wheals (<20 wheals within 24 hours) + mild pruritus (nontroublesome) 
      • 2 = moderate wheals (20-50 wheals within 24 hours) + moderate pruritus (troublesome but does not interfere with daily activities or sleep) 
      • 3 = intense wheals (>50 wheals within 24 hours or large confluent wheals) + intense pruritus (severely troublesome, interferes with daily activities and sleep)
    • The Chronic Urticaria Quality of Life questionnaire (CU-Q2oL) is the recommended quality of life tool to assess the quality of life impairment specific to chronic spontaneous urticaria 
    • The Angioedema-specific Quality of Life tool (AE-QoL), Urticaria Control Test (UCT), Angioedema Control Test (AECT) and Angioedema Activity Score (AAS) may also be used to assess patient's quality of life and disease status, which may help in treatment decisions

Chronic Spontaneous Urticaria

  • Goals of diagnostic work-up include confirming the diagnosis and ruling out differential diagnoses, identifying underlying causes, conditions that affect disease activity [eg food, drugs (NSAIDs), stress, infections], comorbidities, and consequences of chronic spontaneous urticaria (anxiety, depression, sexual dysfunction, sleep disturbances), assessing predictors of disease course and treatment response, and monitoring disease activity (UAS, UAS7, AAS), impact (CU-Q2oL, AE-QoL) and control (UCT, AECT) 
  • Further tests are requested if indicated by the patient’s history, physical examination and basic tests, most notably in patients with chronic and/or on-and-off disease presentation

Chronic Inducible Urticaria

  • Goals of diagnostic work-up include ruling out differential diagnoses, identifying subtype, and determining trigger thresholds
  • Provocation threshold measurements are used to assess disease activity and control, while the UCT is used to determine how well the disease is prevented from recurring
RECOMMENDED DIAGNOSTIC TESTS FOR URTICARIA SUBTYPES
Subtype Test Extended Diagnostic Tests1
(Based on the patient's history)
Spontaneous Urticaria
Acute spontaneous urticaria None None (except when the patient's history indicates the need for testing)
Chronic spontaneous urticaria Differential blood count, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
IgG anti-thyroid peroxidase (TPO) and total IgE (for those receiving specialist care) 
Perform tests for: Infectious illnesses, functional autoantibodies, allergy, thyroid abnormalities, presence of chronic inducible urticaria, severe systemic illnesses, others (lesional skin biopsy)
Inducible Urticaria
Cold urticaria Cold provocation and threshold test (eg ice cubes, cold water) Differential blood count and ESR or CRP, rule out other diseases/infections
Delayed pressure urticaria Pressure test (0.2-1.5 kg/cm2 for 10 and 20 minutes) and threshold test None
Heat urticaria Heat provocation and threshold test (eg warm water) None
Solar urticaria Ultraviolet (UV) and visible light of different wavelengths and threshold test Rule out other light-induced dermatoses
Symptomatic dermographism Test by stroking the arm and threshold test Differential blood count, ESR or CRP 
Vibratory angioedema Test using vibration (eg mixer, Vortex vibrator) None
Exercise-induced History of urticaria after exercise, appearing with or without food intake but not after a hot bath None
Aquagenic urticaria Provocation test/apply wet cloths set at body temperature for 20 minutes None
Cholinergic urticaria Exercise and hot bath provocation, threshold test None
Contact urticaria Cutaneous provocation test, prick/patch test (see results after 20 minutes) None
References: The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2021; The definition, diagnostic testing, and management of chronic inducible urticarias – The EAACI/GA2LEN/EDF/UNEV consensus recommendations 2016 update and revision. Allergy. 2016.
1Depends on the cause being considered

Differential Diagnosis

  • Urticaria pigmentosa
  • Urticarial vasculitis
  • Bradykinin-mediated angioedema
  • Exercise-induced anaphylaxis
  • Cryopyrin-associated periodic syndromes
  • Schnitzler's syndrome
  • Gleich's syndrome
  • Well's syndrome
  • Bullous pemphigoid (prebullous stage)
  • Mast cell activation syndrome 
  • Adult-onset Still's disease 
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