Test Details
Methodology
See individual tests.
Result Turnaround Time
7 - 10 days
Use
This test is used for diagnostic evaluation of patients with possible chronic urticaria.
Special Instructions
Component (Test No.) 505800 currently is not approved for use in New York state.
This test may exhibit interference when sample is collected from a person who is consuming a supplement with a high dose of biotin (also termed as vitamin B7 or B8, vitamin H, or coenzyme R). It is recommended to ask all patients who may be indicated for this test about biotin supplementation. Patients should be cautioned to stop biotin consumption at least 72 hours prior to the collection of a sample.
Specimen Requirements
Test Includes
- Complete Blood Count (CBC) With Differential, Reflex to Peripheral Smear Review [005009]
- Sedimentation Rate, Modified Westergren [005215]
- C-Reactive Protein (CRP), Quantitative [006627]
- Alanine Aminotransferase (ALT/SGPT) [001545]
- Thyroid-stimulating Hormone (TSH) [004259]
- Thyroid Peroxidase (TPO) Antibodies [006676]
- Chronic Urticaria PD-BAT (CSU-BAT) [505800]
Limitations
For Test No. 505800: This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.
Custom Additional Information
Chronic spontaneous urticaria (CSU) is a debilitating mast cell-driven disease characterized by recurrent wheals and/or angioedema.1-3 Chronic spontaneous urticaria (CSU) is a disorder where symptoms of urticaria occur without an identifiable provoking factor and persist for more than six weeks.1,2 CSU is thought to result from the pathogenic activation of mast cells and basophils causing them to release histamine and other proinflammatory mediators.2,4 CSU frequently occurs in patients with autoimmune conditions including autoimmune hypothyroidism, rheumatoid arthritis, type I diabetes mellitus, Sjögren syndrome, celiac disease and systemic lupus erythematosus.5-8 The exact mechanisms leading to activation of mast cells in CSU are, as of yet, not fully characterized, but autoimmunity is thought to play a key role.2,9-15
There are two identified autoimmune endotypes of CSU with different types of autoantibodies that have been associated with the activation of skin mast cells.3,9,16-19 In both type I and type IIb endotypes, mast cells are the primary drivers and basophils are important secondary contributors. Type I and type IIb CSU patients share the same phenotype but may differ in disease course, clinical features and response to treatment.3 In contrast to classical type I hypersensitivity and allergy, which involve the development of IgE to exogenous allergens, type I CSU is characterized by IgE antibodies directed to self-antigens (also called autoallergens).7,11,20 Autoallergic chronic spontaneous urticaria is present in more than 50% of patients with chronic spontaneous urticaria.21 The beneficial effects of the anti-IgE drug omalizumab in many CSU patients further points to a role of type I autoimmunity in CSU.9,22,23 Type IIb autoimmunity, related to the presence of IgG autoantibodies against the high affinity Fc epsilon receptor I (FcεRI) or, less frequently, to IgE itself, also has been implicated as a causative mechanism for CSU.2,8,9,11-13 The type IIb endotype is present in 8% to 40% of patients with CSU and is characterized by higher disease severity, basopenia, eosinopenia, concomitant autoimmune diseases, low levels of total IgE, elevated levels of thyroid peroxidase antibodies (TPO-ab), poor response to antihistamines and to omalizumab and a good response to cyclosporine.3 A recent study found that the majority of patients with a type IIb profile also had a type I profile, suggesting there is greater overlap and heterogeneity in these “endotypes” than previously recognized.21
Studies suggest that patients with type 1 (autoallergic) CSU have clinical characteristics that distinguish them from those with type IIb (autoimmune) disease.8,9,13,16-25 Differentiating factors include time since the onset of disease (longer in type IIb CSU) and concomitant autoimmune diseases (more common in type IIb CSU).8,13,25-29 Type I CSU generally presents a less aggressive course, a better response to antihistamines and a good response to omalizumab treatment, if necessary.13,24 Type IIb CSU patients tend to have a more difficult course and often require immunosuppressive drugs to achieve remission.
CSU is primarily a diagnosis of exclusion where lab testing can be performed if clinically indicated.2,31-33 The most recent practice parameter update from the Journal of Allergy and Clinical Immunology (JACI) and a position paper from the European Journal of Allergy and Clinical Immunology suggest selective labs as initial workup for CSU.2,31 Both guidelines agree that few tests are needed, and other papers have reiterated this point.34-37 The JACI Practice Parameter suggests performing a CBC with differential, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), liver enzymes and TSH as initial workup of chronic urticaria.31 The more recently published international EAACI/GA2LEN/Euro-GuiDerm/APAAACI urticaria guideline suggests that the CSU diagnostic work-up should include a CBC and ESR and/or CRP along with total IgE, TPO-ab and for CSU basophile activation testing (CSU-BAT) for in patients in specialist care.2
The type IIb endotype is associated with reduced eosinophil and basophil counts along elevated markers of inflammation (ESR and/or CRP).2,38,39 It should be noted that these inflammation biomarkers are nonspecific and can be seen in urticarial vasculitis and urticarial autoinflammatory diseases.2,32,33 Patients with type IIb CSU tend to have very low total IgE (<18 IU/L) and elevated levels of TPO-ab.13,40-50 An elevated CSU-BAT result also supports the diagnosis of a type IIb CSU endotype. The therapeutic algorithm for CSU, suggested by the international guidelines, calls for treatment escalation to omalizumab and cyclosporine if the antihistamines fail to provide relief.2 High disease activity, reduced eosinophil and basophil counts and elevated levels of CRP are predictors of a poor or no response to antihistamines. Low serum levels of total IgE are predictive of poor response to omalizumab.51 A positive CSU-BAT result is also predictive of a poor response to omalizumab, but a good response to cyclosporine (see individual test description of Test No. 505800 for more information).51-53
The Chronic Urticaria Evaluation Profile is not comprehensive, and further testing may be required in patients without a clear diagnosis. It may be important to differentiate CSU from other conditions that can manifest with wheals and/or angioedema but have distinct pathophysiology and/or clinical presentation.2,33,54 These conditions include urticarial vasculitis, mastocytosis, mast cell diseases (maculo-papular cutaneous mastocytosis, indolent systemic mastocytosis with involvement of the skin and mast cell activation syndrome), autoinflammatory syndromes (e.g., cryopyrin-associated periodic syndromes or Schnitzler’s syndrome), adult-onset Still’s disease, hereditary angioedema, urticarial drug eruption, eczematous urticarial dermatitis, Well’s syndrome, bullous pemphigoid (prebullous stage), insect bite reactions and erythema multiforme.2,31,33,53-55 Testing for infections such as H. pylori, hepatitis B, hepatitis C or underlying malignancy may be warranted if there is clinical suspicion, although these tests are not routinely performed. Other laboratory tests that may be considered include tryptase and food/inhalant allergy testing if indicated by the patient’s history and physical examination.2,35,39 Although there is no specific guideline-based recommendation to routinely test for antinuclear antibodies (ANA), individual patient factors and clinical judgement can influence the decision to test for ANA or other autoimmune markers.56 Skin biopsy should only be performed in patients who are suspected to have a condition other than CSU.2
Specimen
Serum and whole blood (EDTA)
Volume
4 mL serum and 4 mL whole blood (EDTA)
Container
Lavender-top (EDTA) tube and gel-barrier tube or red-top tube
Storage Instructions
See individual tests.
Causes for Rejection
Specimens that are inadequately labeled, lipemic, hemolyzed, cloudy or microbiologically contaminated
Collection Instructions
CBC+ESR: Invert lavender-top tube eight to 10 times immediately after tube is filled at the time of collection.
Other tests: If a red-top tube is used, transfer separated serum to a plastic transport tube.
Stability Requirements
See individual tests.
Footnotes
1. Lang DM. Chronic Urticaria. N Engl J Med. 2022 Sep 1;387(9):824-831. PubMed 36053507
2. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022 Mar;77(3):734-766. PubMed 34536239
3. Kolkhir P, Munoz M, Asero R, et al. Autoimmune chronic spontaneous urticaria. J Allergy Clin Immunol. 2022 Jun;149(6):1819-1831. PubMed 35667749
4. Kaplan A, Lebwohl M, Gimenez-Arnau AM, Hide M, Armstrong AW, Maurer M. Chronic spontaneous urticaria: focus on pathophysiology to unlock treatment advances. Allergy. 2023 Feb;78(2):389-401. PubMed 36448493
5. Baldini E, Odorisio T, Tuccilli C, et al. Thyroid diseases and skin autoimmunity. Rev Endocr Metab Disord. 2018 Dec;19(4):311-323. PubMed 29948572
6. Kolkhir P, Borzova E, Grattan C, Asero R, Pogorelov D, Maurer M. Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review. Autoimmun Rev. 2017 Dec;16(12):1196-1208. PubMed 29037900
7. Altrichter S, Peter HJ, Pisarevskaja D, Metz M, Martus P, Maurer M. IgE mediated autoallergy against thyroid peroxidase--a novel pathomechanism of chronic spontaneous urticaria? PLoS One. 2011 Apr 12;6(4):e14794. PubMed 21532759
8. Confino-Cohen R, Chodick G, Shalev V, Leshno M, Kimhi O, Goldberg A. Chronic urticaria and autoimmunity: associations found in a large population study. J Allergy Clin Immunol. 2012 May;129(5):1307-1313. PubMed 22336078
9. Bracken SJ, Abraham S, MacLeod AS. Autoimmune Theories of Chronic Spontaneous Urticaria. Front Immunol. 2019 Mar 29;10:627. PubMed 30984191
10. Kaplan AP, Greaves M. Pathogenesis of chronic urticaria. Clin Exp Allergy. 2009 Jun;39:777-787. Epub 2009 Apr 22. PubMed 19400905
11. Kolkhir P, Church MK, Weller K, Metz M, Schmetzer O, Maurer M. Autoimmune chronic spontaneous urticaria: what we know and what we do not know. J Allergy Clin Immunol. 2017 Jun;139(6):1772-1781.e1. PubMed 27777182
12. Konstantinou GN, Asero R, Ferrer M, et al. EAACI taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria. Allergy. 2013 Jan;68(1):27-36. PubMed 23157716
13. Schoepke N, Asero R, Ellrich A, et al. Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: Results of the PURIST Study. Allergy. 2019 Dec;74(12):2427-2436. Epub 2019 Jul 29. PubMed 31228881
14. Sabroe RA, Fiebiger E, Francis DM, et al. Classification of anti-FcεRI and anti-IgE auto-antibodies in chronic idiopathic urticaria and correlation with disease severity. J Allergy Clin Immunol. 2002 Sep;110(3):492-499. PubMed 12209101
15. Maurer M, Altrichter S, Schmetzer O, Scheffel J, Church MK, Metz M. Immunoglobulin E-Mediated Autoimmunity. Front Immunol. 2018 Apr 9;9:689. eCollection 2018. PubMed 29686678
16. Zuberbier T, Ensina LF, Giménez-Arnau A, et al. Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment. Lancet. 2024 Jul 27;404(10450):393-404. Epub 2024 Jul 11. PubMed 39004090
17. Moñino-Romero S, Hackler Y, Okas TL, et al. Positive Basophil Tests Are Linked to High Disease Activity and Other Features of Autoimmune Chronic Spontaneous Urticaria: A Systematic Review. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2411-2416. Epub 2023 Jun 5. PubMed 37286132
18. Gimenez-Arnau AM, DeMontojoye L, Asero R, et al. The pathogenesis of chronic spontaneous urticaria: the role of infiltrating cells. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2195-2208. Epub 2021 Apr 3. PubMed 33823316
19. Hide M, Kaplan AP. Concise update on the pathogenesis of chronic spontaneous urticaria (CSU). J Allergy Clin Immunol. 2022 Dec;150(6):1403-1404. Epub 2022 Sep 5. PubMed 36070827
20. Asero R, Ferrer M, Kocaturk E, Maurer M. Chronic spontaneous urticaria: the role and relevance of autoreactivity, autoimmunity, and autoallergy. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2302-2308. Epub 2023 Mar 1. PubMed 36868473
21. Xiang YK, Kolkhir P, Scheffel J, et al. Most patients with autoimmune chronic spontaneous urticaria also have autoallergic urticaria, but not viceVersa. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2417-2425.e1. Epub 2023 Feb 16. PubMed 36805105
22. Deza G, Bertolín-Colilla M, Sánchez S, et al. Basophil FcɛRI expression is linked to time to omalizumab response in chronic spontaneous urticaria. J Allergy Clin Immunol. 2018 Jun;141(6):2313-2316.e1. Epub 2018 Mar 5. PubMed 29518420
23. Gericke J, Metz M, Ohanyan T, et al. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria. J Allergy Clin Immunol. 2017 Mar;139(3):1059-1061.e1. Epub 2016 Nov 9. PubMed 27838346
24. Larenas-Linnemann D. Biomarkers of Autoimmune Chronic Spontaneous Urticaria. Curr Allergy Asthma Rep. 2023 Dec;23(12):655-664. Epub 2023 Dec 8. PubMed 38064133
25. Sanchez J, Sanchez A, Cardona R. Clinical characterization of patients with chronic spontaneous urticaria according to anti-TPO IgE levels. J Immunol Res. 2019 Dec 7;2019:4202145. eCollection 2019. PubMed 31886301
26. de Montjoye L, Darrigade AS, Gimenez-Arnau A, et al. Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria. Eur Ann Allergy Clin Immunol. 2021 Mar;53(2):55-66. Epub 2021 Mar 1. PubMed 31965967
27. HOssein Zadeh Attar M, Merk HF, Kotliar K, et al. The CD63 basophil activation test as a diagnostic tool for assessing autoimmunity in patients with chronic spontaneous urticaria. Eur J Dermatol. 2019 Dec 1;29(6):614-618. PubMed 31903951
28. Kikuchi Y, Fann T, Kaplan AP. Antithyroid antibodies in chronic urticaria and angioedema. J Allergy Clin Immunol. 2003 Jul;112(1):218. PubMed 12847508
29. Matsui Y, Heiner DC, Beall GN. IgE and IgE autoantibodies in patients with autoimmune thyroid disorders and their relatives. Proc Soc Exp Biol Med. 1978 May;158(1):73-76. PubMed 580805
30. Diakow MN, Fakus JR. Chronic Urticaria. Medscape website: https://emedicine.medscape.com/article/1050052-overview. Updated October 13, 2021. Accessed January 2025.
31. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014 May;133(5):1270-1277. PubMed 24766875
32. Maurer M, Magerl M, Metz M, Siebenhaar F, Weller K, Krause K. Practical algorithm for diagnosing patients with recurrent wheals or angioedema. Allergy. 2013 Jun;68(6):816-819. Epub 2013 May 6. PubMed 23646863
33. Metz M, Altrichter S, Buttgereit T, et al. The Diagnostic Workup in Chronic Spontaneous Urticaria-What to Test and Why. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2274-2283. Epub 2021 Apr 20. PubMed 33857657
34. Greiner B, Nicks S, Adame M, McCracken J. Pathophysiology, Diagnosis, and Management of Chronic Spontaneous Urticaria: A Literature Review. Clin Rev Allergy Immunol. 2022 Dec;63(3):381-389. Epub 2022 Sep 1. PubMed 36048326
35. Hon KL, Leung AKC, Ng WGG, Loo SK. Chronic Urticaria: An Overview of Treatment and Recent Patents. Recent Pat Inflamm Allergy Drug Discov. 2019;13(1):27-37. PubMed 30924425
36. Pedersen NH, Sørensen JA, Ghazanfar MN, Zhang DG, Vestergaard C, Thomsen SF. Biomarkers for Monitoring Treatment Response of Omalizumab in Patients with Chronic Urticaria. Int J Mol Sci. 2023 Jul 11;24(14):11328. PubMed 37511088
37. Saini SS, Kaplan AP. Chronic Spontaneous Urticaria: The Devil's Itch. J Allergy Clin Immunol Pract. 2018 Jul-Aug;6(4):1097-1106. PubMed 30033911
38. Kolkhir P, Church MK, Altrichter S, et al. Eosinopenia, in chronic spontaneous urticaria, is associated with high disease activity, autoimmunity, and poor response to treatment. J Allergy Clin Immunol Pract. 2020 Jan;8(1):318-325.e5. Epub 2019 Aug 28. PubMed 31472293
39. Kolkhir P, Gimenez-Arnau AM, Kulthanan K, Peter J, Metz M, Maurer M. Urticaria. Nat Rev Dis Primers. 2022 Sep 15;8(1):61. PubMed 36109590
40. Chuang KW, Hsu CY, Huang SW, Chang HC. Association between serum total IgE levels and clinical response to omalizumab for chronic spontaneous urticaria: a systematic review and metaanalysis. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2382-2389.e3. Epub 2023 May 30. PubMed 37263348
41. Asero R. Clinical variables of severe chronic spontaneous urticaria from total IgE standpoint: a retrospective study. Eur Ann Allergy Clin Immunol. 2022 Jan;54(1):30-33. Epub 2021 Feb 8. PubMed 33555151
42. Altrichter S, Fok JS, Jiao Q, et al. Total IgE as a marker for chronic spontaneous urticaria. Allergy Asthma Immunol Res. 2021 Mar;13(2):206-218. PubMed 33474856
43. Asero R, Ferrucci S, Casazza G, Marzano AV, Cugno M. Total IgE and atopic status in patients with severe chronic spontaneous urticaria unresponsive to omalizumab treatment. Allergy. 2019 Aug;74(8):1561-1563. Epub 2019 Mar 11. PubMed 30801715
44. Kolkhir P, Kovalkova E, Chernov A, et al. Autoimmune Chronic Spontaneous Urticaria Detection with IgG Anti-TPO and Total IgE. J Allergy Clin Immunol Pract. 2021 Nov;9(11):4138-4146.e8. Epub 2021 Aug 4. PubMed 34363991
45. Ertas R, Ozyurt K, Atasoy M, Hawro T, Maurer M. The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change. Allergy. 2018 Mar;73(3):705-712. Epub 2017 Nov 27. PubMed 29083482
46. Weller K, Ohanyan T, Hawro T, et al. Total IgE levels are linked to the response of chronic spontaneous urticaria patients to omalizumab. Allergy. 2018 Dec;73(12):2406-2418. Epub 2018 Sep 25. PubMed 30076605
47. Kolkhir P, Altrichter S, Hawro T, Maurer M. C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria. Allergy. 2018 Apr;73(4):940-948. Epub 2017 Dec 7. PubMed 29130488
48. Ertas R, Ozyurt K, Ozlu E, et al. Increased IgE levels are linked to faster relapse in patients with omalizumab-discontinued chronic spontaneous urticaria. J Allergy Clin Immunol. 2017 Dec;140(6):1749-1751. Epub 2017 Sep 1. PubMed 28870460
49. Magen E, Waitman DA, Dickstein Y, Davidovich V, Kahan NR. Clinical laboratory characteristics of ANA-positive chronic idiopathic urticaria. Allergy Asthma Proc. 2015 Mar-Apr;36(2):138-144. PubMed 25715242
50. Shin YS, Suh DH, Yang EM, Ye YM, Park HS. Serum specific IgE to thyroid peroxidase activates basophils in aspirin intolerant urticaria. J Korean Med Sci. 2015 Jun;30(6):705-709. Epub 2015 May 13. PubMed 26028921
51. Fok JS, Kolkhir P, Church MK, Maurer M. Predictors of treatment response in chronic spontaneous urticaria. Allergy. 2021 Oct;76(10):2965-2981. Epub 2021 Feb 27. PubMed 33539587
52. Marcelino J, Baumann K, Skov PS, et al. What Basophil Testing Tells Us About CSU Patients - Results of the CORSA Study. Front Immunol. 2021 Sep 28;12:742470. eCollection 2021. PubMed 34650565
53. Straesser MD, Oliver E, Palacios T, et al. Serum IgE as an immunological marker to predict response to omalizumab treatment in symptomatic chronic urticaria. J Allergy Clin Immunol Pract. 2018 Jul-Aug;6(4):1386-1388.e1. Epub 2017 Nov 23. PubMed 29175369
54. Bernstein JA, Ziaie N, Criado R, Criado PR, Rea S, Davis M. Chronic urticaria and angioedema: masqueraders and misdiagnoses. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2251-2263. Epub Jun 26. PubMed 37380071
55. Schettini N, Corazza M, Schenetti C, Pacetti L, Borghi A. Urticaria: a narrative overview of differential diagnosis. Biomedicines. 2023 Apr 4;11(4):1096. PubMed 37189714
56. Arunkajohnsak S, Jiamton S, Tuchinda P, et al. Do antinuclear antibodies influence the clinical features of chronic spontaneous urticaria?: a retrospective cohort study. Biomed Res Int. 2022 Nov 29;2022:7468453. eCollection 2022. PubMed 36483629