Histamine Releasing Urticaria Test (CURT)

The Histamine Releasing Urticaria Test (CURT) is a functional laboratory test used in the assessment of chronic spontaneous urticaria (CSU). It helps identify a subgroup of patients with autoimmune CSU, in whom circulating serum factors – most commonly IgG autoantibodies against FcεRIα or IgE – induce basophil activation and histamine release.

Histamine release analyser (HistaReader) used for functional assessment of histamine release in autoimmune chronic spontaneous urticaria.

This autoimmune endotype is recognised in EAACI/GA²LEN/EuroGuiDerm/APAAACI urticaria guidelines and is often referred to as type IIb autoimmune chronic spontaneous urticaria.

Identifying this subgroup has practical implications for disease stratification and treatment planning, particularly in patients with severe, persistent, or treatment-refractory symptoms.

Clinical background – EAACI/GA²LEN terminology

According to EAACI / GA²LEN guidelines:

– Chronic spontaneous urticaria is defined as the spontaneous occurrence of wheals, angioedema, or both for ≥ 6 weeks, without an identifiable external trigger
– Up to 40–50% of CSU patients show evidence of autoreactivity or autoimmunity
– Type IIb autoimmune CSU is characterised by:
– Functional autoantibodies
– Basophil and mast cell activation
– Higher disease activity
– Lower total IgE (in many cases)
– Reduced response to standard-dose antihistamines

Chronic spontaneous urticaria – recurrent wheals and angioedema caused by mast cell activation without an identifiable external trigger.

CURT is one of the functional assays used to support identification of this autoimmune mechanism.

Test method – Histamine Release Assay (HR-Test)

Methodology (laboratory-based functional assay):

– Patient serum is tested in two concentrations (20% and 10%)
– Serum is incubated with IgE-depleted donor basophil leukocytes (buffy coat)
– If histamine-releasing factors are present, basophils are activated
– Released histamine is:
– Adsorbed onto glass microfibres
– Detected fluorometrically
– Results are expressed as percentage (%) of total cellular histamine released

This approach aligns with established basophil histamine release assays described in autoimmune CSU literature.

Interpretation of results

A positive CURT supports the presence of functional autoantibodies and an autoimmune CSU endotype, when interpreted in the appropriate clinical context.

CURT results must always be correlated with clinical history, examination, and other investigations. The test does not replace clinical diagnosis.

How CURT fits into chronic urticaria assessment

EAACI/GA²LEN guidelines recommend a stepwise and targeted diagnostic approach.

Baseline investigations commonly include:

– Full blood count
– CRP and/or ESR

Additional tests may include:

– Total IgE
– Anti-thyroid antibodies (e.g. anti-TPO)

Functional tests – specialist level:

– Histamine Releasing Urticaria Test (CURT)
– Basophil activation or histamine release assays
– Autologous serum skin test (ASST – less specific)

CURT is typically considered in specialist allergy or immunology settings, particularly when symptoms are severe or difficult to control.

Are allergy tests needed in chronic urticaria?

In line with EAACI/GA²LEN guidance:

– Most CSU is not IgE-mediated
– Routine screening for food or inhalant allergens is not recommended
– Targeted allergy testing may be considered only when clinical history strongly suggests an allergic mechanism

Important distinctions

– CURT does not diagnose food allergy
– CURT is not a test for histamine intolerance
– CURT does not measure histamine levels directly, but functional histamine release from basophils

Histamine Releasing Urticaria Test in London

The Histamine Releasing Urticaria Test (CURT) is available in London as part of specialist assessment for chronic spontaneous urticaria. Testing is arranged and interpreted by consultant allergists and immunologists, following EAACI/GA²LEN international guidelines.

Patients are typically referred for CURT when chronic urticaria is:
– Persistent despite treatment
– Associated with angioedema
– Clinically suggestive of an autoimmune mechanism

Testing is performed on a blood sample, with results reviewed alongside clinical findings to guide individualised management plans.