Specialist Allergy Investigation
Histamine Releasing Urticaria Test (CURT)
A specialist functional laboratory test for identifying autoimmune chronic spontaneous urticaria – aligned with EAACI/GA²LEN/EuroGuiDerm international guidelines.
At a Glance
| Test type: | Functional serum basophil histamine release assay |
| Sample: | Peripheral blood (serum) |
| Positive threshold: | ≥ 16.5% histamine release |
| Clinical target: | Type IIb autoimmune chronic spontaneous urticaria |
| Setting: | Specialist allergy / immunology clinic, London |
What Is the Histamine Releasing Urticaria Test (CURT)?
The Histamine Releasing Urticaria Test (CURT) is a specialist functional laboratory assay used in the investigation of chronic spontaneous urticaria (CSU). It detects circulating serum factors – most commonly IgG autoantibodies directed against the high-affinity IgE receptor (FcεRIα) or against IgE itself – that are capable of activating basophils and triggering histamine release.
When present, these autoantibodies identify a patient as having type IIb autoimmune CSU – a distinct endotype recognised in the EAACI/GA²LEN/EuroGuiDerm/APAAACI international urticaria guidelines. This group is clinically important because they typically experience more severe disease and often respond less predictably to standard antihistamines and biological therapies such as omalizumab.
The basophil histamine release assay (BHRA), of which CURT is a validated implementation, remains – according to a 2026 publication in Clinical & Experimental Allergy – the single best available biomarker for identifying type IIb autoimmune CSU.
Histamine release analyser (HistaReader) used for functional assessment of histamine release in autoimmune chronic spontaneous urticaria.
Chronic Spontaneous Urticaria – Understanding the Endotypes
Chronic spontaneous urticaria is defined as the recurring occurrence of wheals (hives), angioedema, or both, lasting for six weeks or longer, without a clearly identifiable external trigger. It affects approximately 1% of the population at any given time and can be profoundly debilitating.
Contemporary research has established two principal antibody-mediated mechanisms underlying CSU:
Type I (Autoallergic) CSU
Mediated by IgE autoantibodies targeting self-antigens such as thyroid peroxidase (TPO) and interleukin-24.
Typically: Elevated total IgE • Allergic comorbidities • Rapid, robust response to omalizumab
CURT / BHRA: Usually negative
Type IIb (Autoimmune) CSU
Mediated by IgG autoantibodies (less frequently IgA or IgM) against IgE or its high-affinity receptor FcεRI.
Typically: Low total IgE • Higher disease severity • Poorer antihistamine response • Variable omalizumab response • Autoimmune comorbidities
CURT / BHRA: Positive
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.
A January 2026 review in Frontiers in Allergy confirms that whilst type IIb autoimmune CSU is diagnosed in fewer than 10% of CSU patients when strict criteria are applied, it is consistently associated with a more severe disease course, concurrent autoimmune conditions (particularly autoimmune thyroiditis and vitiligo), and reduced responsiveness to both antihistamines and omalizumab.
It is also important to note that both mechanisms can coexist in the same patient, and a proportion of CSU cases lack detectable autoimmune markers entirely, reflecting the broader concept of autoreactivity encompassing the full spectrum of CSU pathophysiology.
How the CURT Test Works – Laboratory Method
CURT is performed using a validated, fluorometric basophil histamine release assay. The procedure involves the following steps:
Serum Collection
A blood sample is taken from the patient and processed to extract serum. No special preparation is required.
Serum Dilution
The patient’s serum is tested at two concentrations (20% and 10%) to assess dose-dependent histamine-releasing activity.
Incubation with Donor Basophils
Each serum dilution is incubated with IgE-depleted donor basophil leucocytes (obtained from buffy coat). Using IgE-depleted cells ensures that any histamine release is attributable to IgG autoantibodies against FcεRI or IgE – rather than to simple IgE cross-linking.
Histamine Detection
Released histamine is adsorbed onto glass microfibres and detected fluorometrically using the HistaReader analyser. Results are expressed as a percentage of total cellular histamine released.
This methodology is consistent with basophil histamine release assays described throughout the peer-reviewed autoimmune CSU literature, including the 2025 World Allergy Organisation Journal (Bernstein et al., 2025, WAO J 18:101068) and the 2026 Frontiers in Allergy review (Calzari et al., 2026).
Interpreting Your CURT Result
Results are reported as the maximum percentage of histamine released across both serum concentrations tested:
| Maximum Histamine Release | Result | Clinical Implication |
|---|---|---|
| < 16.5% | Negative | No significant histamine-releasing activity detected. Type IIb autoimmune mechanism is less likely. |
| ≥ 16.5% | Positive | Consistent with circulating histamine-releasing serum factors (functional autoantibodies). Supports type IIb autoimmune CSU endotype when correlated with clinical findings. |
Important: A positive CURT result must always be interpreted alongside a full clinical history, physical examination, and complementary investigations. CURT is a supportive diagnostic tool – it does not replace clinical diagnosis. Results are reviewed and explained by your consultant allergist or immunologist.
Clinical Significance – Why CURT Matters
Identifying the autoimmune endotype of CSU has significant practical consequences for disease stratification, patient counselling, and treatment selection. Recent literature – including publications from 2025 and 2026 – has helped clarify both the utility and the limitations of BHRA/CURT testing:
Treatment Stratification
A 2026 Frontiers in Allergy review confirmed that patients with a positive BHRA and other type IIb biomarkers (low IgE, anti-TPO positivity, eosinopenia) show poorer responses to omalizumab but may respond better to ciclosporin. Knowing the endotype therefore directly informs treatment choice.
Diagnostic Precision
The 2025 World Allergy Organisation Journal (Bernstein et al.) identifies BHRA alongside total IgE and anti-TPO IgG as the most clinically meaningful biomarkers for differentiating type IIb from type I CSU – particularly prior to commencing biological therapy.
Omalizumab & BHRA
A 2026 Clinical & Experimental Allergy study confirmed that whilst intracellular basophil histamine content correlates with type IIb features, BHRA positivity itself remains the best single biomarker for identifying this endotype – although it is not currently reliable for predicting the speed or degree of omalizumab response.
Novel Therapies
With new biologics and targeted therapies under investigation for refractory CSU – including anti-FcεRI approaches and BTK inhibitors – endotyping via BHRA/CURT is expected to become increasingly important for patient selection in clinical trials and future prescribing.
Where CURT Fits in the Diagnostic Pathway
EAACI/GA²LEN guidelines advocate a stepwise, targeted approach to investigating CSU. CURT is a specialist-level investigation, typically considered after initial assessments have been completed:
| Stage | Investigations | Purpose |
|---|---|---|
| Baseline | Full blood count • CRP • ESR | Exclude systemic inflammation; assess basophil and eosinophil counts |
| Additional | Total IgE • Anti-TPO antibodies • D-dimer (in selected cases) | Support endotype characterisation; assess for autoimmune thyroid disease |
| Specialist | CURT / BHRA • Basophil activation test (BAT) • Autologous serum skin test (ASST – less specific) | Identify type IIb autoimmune endotype; guide biological therapy decisions |
CURT is typically considered in patients whose urticaria is persistent despite optimised antihistamine treatment, associated with angioedema, or clinically suggestive of an autoimmune mechanism. It is arranged and interpreted exclusively within a specialist allergy or immunology setting.
Is Allergy Testing Needed in Chronic Urticaria?
A common source of confusion is the relationship between urticaria and allergy. The EAACI/GA²LEN guidelines are clear on this point:
Most
CSU is not IgE-mediated and not caused by food or inhalant allergens
Not
Recommended to routinely screen for food or aeroallergen sensitisation in CSU
Only
Targeted allergy tests are warranted when clinical history strongly suggests an allergic trigger
Important Distinctions – What CURT Does Not Test
It is important to be clear about what CURT is and is not designed to detect:
CURT does not diagnose food allergy. It is not an allergy test to foods, medications, or environmental allergens. Patients with suspected food allergy should undergo specific IgE testing and clinical assessment.
CURT is not a test for histamine intolerance. Histamine intolerance relates to deficiency of the enzyme diamine oxidase (DAO) and is a separate, poorly characterised entity distinct from autoimmune urticaria.
CURT does not measure serum histamine levels directly. It measures the functional capacity of patient serum to trigger histamine release from donor basophils – a fundamentally different and more clinically informative measurement.
CURT is not a standalone diagnostic test. A positive result supports a clinical diagnosis of type IIb autoimmune CSU but must always be interpreted in context. A negative result does not exclude CSU or other autoimmune mechanisms.
Histamine Releasing Urticaria Test in London
The Histamine Releasing Urticaria Test (CURT) is available in London as part of a comprehensive 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 their chronic urticaria demonstrates one or more of the following features:
Persistent Symptoms
Urticaria continuing despite optimised antihistamine therapy
Associated Angioedema
Recurrent swelling of the face, lips, tongue, or limbs alongside hives
Autoimmune Profile
Low total IgE, elevated CRP/ESR, anti-TPO positivity, or concurrent autoimmune conditions
Biological Therapy Planning
Prior to initiating or reviewing response to omalizumab or ciclosporin
Testing is performed on a blood sample. Results are reviewed alongside the full clinical picture to produce an individualised management plan specific to each patient’s endotype, disease activity, and treatment history.
Frequently Asked Questions
References & Further Reading
1. Bernstein JA, Ansotegui I, Asero R, et al. Diagnostic testing for chronic spontaneous urticaria with or without angioedema: The do’s, don’t and maybe’s. World Allergy Organ J. 2025;18:101068.
2. Zhang SF, Thomsen SF. Evaluating basophil histamine content as a biomarker for omalizumab responsiveness in chronic spontaneous urticaria. Clin Exp Allergy. 2026. doi:10.1111/cea.70327.
3. Calzari P, Favale EM, Cugno M, Marzano AV, Ferrucci SM. Predictors of early treatment response to antihistamines and omalizumab in chronic spontaneous urticaria. Front Allergy. 2026;6:1728559.
4. Frontiers in Allergy. Clinical and molecular aspects of managing chronic spontaneous urticaria: identifying endotypes, phenotypes, and determinants of treatment response and resistance. Front Allergy. 2026;6:1706705.
5. Frontiers in Allergy. Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a narrative review. Front Allergy. 2025;6:1688464.
6. Zuberbier T, Maurer M, et al. EAACI/GA²LEN/EuroGuiDerm/APAAACI guidelines for the definition, classification, diagnosis and management of urticaria. Allergy. 2022;77(3):734–766.
Medical Disclaimer: The information on this page is provided for general educational purposes and does not constitute medical advice. Diagnosis and management of chronic urticaria should always be undertaken by a qualified medical professional. If you have concerns about urticaria or any other medical condition, please consult your GP or a specialist.