eMedicine Specialties > Allergy and Immunology > Urticaria and Angioedema

Urticaria: Differential Diagnoses & Workup

Author: Javed Sheikh, MD, Assistant Professor of Medicine, Harvard Medical School; Clinical Director, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center; Clinical Director, Center for Eosinophilic Disorders, Beth Israel Deaconess Medical Center
Coauthor(s): Umer Najib, MD, Clinical Research Fellow, Department of Medicine, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center
Contributor Information and Disclosures

Updated: Jun 5, 2009

Differential Diagnoses

Angioedema
Erythema Multiforme (Stevens-Johnson Syndrome)
Mastocytosis, Systemic

Other Problems to Be Considered

Bullous pemphigoid
Dermatitis herpetiformis
Chronic pruritus (nonurticarial)
Hypersensitivity vasculitis and/or urticarial vasculitis
Urticaria pigmentosa or other mast cell releasability syndromes
Pruritic urticarial papules and plaques of pregnancy (PUPPP), also referred to as polymorphic eruption of pregnancy (PEP)

Workup

Laboratory Studies

  • Skin tests or radioallergosorbent assay test (specific IgE)
    • Selected allergy tests can be performed if food allergy or stinging insect hypersensitivity is suspected. This may be helpful for some cases of acute urticaria but is rarely helpful in the evaluation of chronic urticaria.12 Skin testing can be performed to detect hypersensitivity to a limited number of antibiotics. Testing for pollen or other inhalants is generally not helpful unless a severe allergy may be causing the urticaria, such as a severe allergy to pollens, cats, or latex (these may manifest as contact urticaria).
    • Routine allergy testing with a large battery of screening tests is not recommended.
    • A few research centers perform an autologous serum skin test, but it is not a well-established procedure currently.
  • Screening laboratory studies
    • Which laboratory tests, if any, to order for routine screening is very controversial.
    • Many specialists order only a few select screening studies for patients who have chronic urticaria lasting at least 6 weeks with no apparent etiology.
    • Some choose to perform no testing at all. Laboratory testing for acute urticaria is not indicated, unless a particular medical condition is suspected.38
    • Common screening laboratory tests that may be ordered are as follows:
      • CBC with differential
      • Total eosinophil count
      • Sedimentation rate
      • Urinalysis
      • Liver function tests
    • Evaluation of the complement system, including total hemolytic complement (CH50), C3, and C4 should be considered in patients with prominent angioedema and in patients with urticarial lesions lasting more than 24 hours. These tests are of no value in patients with classic chronic urticaria.
    • Thyroid studies, including thyroid autoantibody levels (antimicrosomal, antithyroglobulin) can be considered, particularly in women or in patients with a family history of thyroid disease or other autoimmune diseases, although the clinical significance of finding positive titers in a euthyroid individual is still unclear.
    • Order laboratory tests only if an abnormal result is found on the initial screening tests or if a specific medical condition is suspected. Evaluation for possible occult infection can be considered, but evidence that infections cause chronic urticaria is limited.
    • Other tests to consider if the history and physical examination findings are suggestive of specific problems include the following:
      • Chemistry panel
      • Stool analysis for ova and parasites
      • H pylori workup39
      • Hepatitis B and C workup
      • Sinus radiography (if symptomatic)
      • Antinuclear antibody (ANA)
      • Rheumatoid factor
      • Cryoglobulin levels
      • Other imaging studies
    • Assays for serum histamine–releasing factors and evaluation for specific autoantibodies (anti-IgE receptor/anti-FcεR1 and anti-IgE) have performed by some research centers, and can now be ordered through certain commercial laboratories.40,41 Currently, 2 reference labs in the United States commercially offer such a test: IBT Reference Laboratory (with the test referred to as the “CU IndexTM ”) and Clinical Reference Laboratories at National Jewish Medical and Research Center (with the test referred to as the “Anti-FcεRI antibody”).42,43 The role of a positive versus negative test finding on these assays is still unclear, as current evidence does not make clear whether a positive result should change management.
    • Patients with cold urticaria should be evaluated for cold agglutinins and cryoproteins because these are found in 5% of cases. The presence of a cryoglobulin suggests an underlying cause such chronic hepatitis (B or C) or lymphoreticular malignancy. These tests, however, are generally unnecessary in routine CIU.

Other Tests

  • Physical challenge tests can be performed if a physical urticaria is suspected. These include challenge with an ice cube, heat, pressure, light, scratching of the skin (dermographism), exercise, and vibration. With the exception of testing for dermographism, these tests are usually performed only by specialty centers.

Procedures

  • Skin biopsy is not indicated on a routine basis, but it should be considered if the urticaria does not respond to usual treatment or if any atypical features, such as those of vasculitis or cutaneous lymphoma, are present.14

More on Urticaria

Overview: Urticaria
Differential Diagnoses & Workup: Urticaria
Treatment & Medication: Urticaria
Follow-up: Urticaria
Multimedia: Urticaria
References
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References

  1. Kaplan AP. Urticaria angioedema. In: Adkinson Jr NFY, Busse WW, Bochner BS, Holgate ST, Simons FER (Eds). Allergy: principles and practice. Philadelphia: Mosby; 2003:1537 – 1558.

  2. Kaplan AP. Chronic urticaria and angioedema. N Engl J Med. 2002;346:175-179.

  3. Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. Jun 3 1993;328(22):1599-604. [Medline].

  4. Brodell LA, Beck LA, Saini SS. Pathophysiology of chronic urticaria. Ann Allergy Asthma Immunol. Apr 2008;100(4):291-7; quiz 297-9, 322. [Medline].

  5. Jacques P, Lavoie A, Bedard PM, Brunet C, Hebert J. Chronic idiopathic urticaria: profiles of skin mast cell histamine release during active disease and remission. J Allergy Clin Immunol. Jun 1992;89(6):1139-43. [Medline].

  6. Sheikh J. Autoantibodies to the high-affinity IgE receptor in chronic urticaria: how important are they?. Curr Opin Allergy Clin Immunol. Oct 2005;5(5):403-7. [Medline].

  7. Sabroe RA, Francis DM, Barr RM, Black AK, Greaves MW. Anti-Fc(episilon)RI auto antibodies and basophil histamine releasability in chronic idiopathic urticaria. J Allergy Clin Immunol. Oct 1998;102(4 Pt 1):651-8. [Medline].

  8. Vonakis BM, Saini SS. New concepts in chronic urticaria. Curr Opin Immunol. Dec 2008;20(6):709-16. [Medline].

  9. Luquin E, Kaplan AP, Ferrer M. Increased responsiveness of basophils of patients with chronic urticaria to sera but hypo-responsiveness to other stimuli. Clin Exp Allergy. Apr 2005;35(4):456-60. [Medline].

  10. Brodell LA, Beck LA, Saini SS. Pathophysiology of chronic urticaria. Ann Allergy Asthma Immunol. Apr 2008;100(4):291-7; quiz 297-9, 322. [Medline].

  11. Vonakis BM, Vasagar K, Gibbons SP Jr, Gober L, Sterba PM, Chang H. Basophil FcepsilonRI histamine release parallels expression of Src-homology 2-containing inositol phosphatases in chronic idiopathic urticaria. J Allergy Clin Immunol. Feb 2007;119(2):441-8. [Medline].

  12. Kaplan AP. What the first 10,000 patients with chronic urticaria have taught me: A personal journey. J Allergy Clin Immunol. Dec 9 2008;[Medline].

  13. Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. Sep 2004;114(3):465-74; quiz 475. [Medline].

  14. Davis MD, Brewer JD. Urticarial vasculitis and hypocomplementemic urticarial vasculitis syndrome. Immunol Allergy Clin North Am. May 2004;24(2):183-213, vi. [Medline].

  15. Gaig P, Olona M, Munoz Lejarazu D, Caballero MT, Dominguez FJ, Echechipia S. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214-20. [Medline].

  16. O'Donnell BF, Lawlor F, Simpson J, Morgan M, Greaves MW. The impact of chronic urticaria on the quality of life. Br J Dermatol. Feb 1997;136(2):197-201. [Medline].

  17. Kaplan AP. Urticaria and angioedema. In: Middleton E, et al, (Eds). Allergy: Principles and Practices. St. Louis, Mo: Mosby-Year Book; 1998:1104-1118.

  18. Charlesworth EN. Urticaria and angioedema: a clinical spectrum. Ann Allergy Asthma Immunol Jun. 1996;76(6):484-495.

  19. Wong RC, Fairley JA, Ellis CN. Dermographism: a review. J Am Acad Dermatol. Oct 1984;11(4 Pt 1):643-52. [Medline].

  20. Sheila MA, Stephen CD. Urticaria. Prim Care Clin Office Pract. 2008;35:141-157.

  21. Hirschmann JV, Lawlor F, English JS, Louback JB, Winkelmann RK, Greaves MW. Cholinergic urticaria. A clinical and histologic study. Arch Dermatol. Apr 1987;123(4):462-7. [Medline].

  22. Greaves M. Chronic urticaria. J Allergy Clin Immunol. Apr 2000;105(4):664-72. [Medline].

  23. Goodman DL, McDonnell JT, Nelson HS, et al. Chronic urticaria exacerbated by the anti-oxidant food preservatives. J Allergy Clin Immunol. 1990;86:570-575.

  24. Di Lorenzo G, Pacor ML, Mansueto P, Martinelli N, Esposito-Pellitteri M, Lo Bianco C. Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria. Int Arch Allergy Immunol. Nov 2005;138(3):235-42. [Medline].

  25. Sheikh J. Advances in the treatment of chronic urticaria. Immunol Allergy Clin North Am. May 2004;24(2):317-34, vii-viii. [Medline].

  26. Valsecchi R, Pigatto P. Chronic urticaria and Helicobacter pylori. Acta Derm Venereol. Nov 1998;78(6):440-2. [Medline].

  27. Ozkaya-Bayazit E, Demir K, Ozguroglu E, Kaymakoglu S, Ozarmagan G. Helicobacter pylori eradication in patients with chronic urticaria. Arch Dermatol. Sep 1998;134(9):1165-6. [Medline].

  28. Di Campli C, Gasbarrini A, Nucera E, Franceschi F, Ojetti V, Sanz Torre E. Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Dig Dis Sci. Jun 1998;43(6):1226-9. [Medline].

  29. Schnyder B, Helbling A, Pichler WJ. Chronic idiopathic urticaria: natural course and association with Helicobacter pylori infection. Int Arch Allergy Immunol. May 1999;119(1):60-3. [Medline].

  30. Leznoff A, Josse RG, Denburg J, Dolovich J. Association of chronic urticaria and angioedema with thyroid autoimmunity. Arch Dermatol. Aug 1983;119(8):636-40. [Medline].

  31. Sabroe RA, Grattan CE, Francis DM, Barr RM, Kobza Black A, Greaves MW. The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br J Dermatol. Mar 1999;140(3):446-52. [Medline].

  32. Grattan CE, Francis DM, Hide M, Greaves MW. Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. Clin Exp Allergy. Nov 1991;21(6):695-704. [Medline].

  33. Ferrer M, Kinet JP, Kaplan AP. Comparative studies of functional and binding assays for IgG anti-Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria. J Allergy Clin Immunol. May 1998;101(5):672-6. [Medline].

  34. Tong LJ, Balakrishnan G, Kochan JP, Kinet JP, Kaplan AP. Assessment of autoimmunity in patients with chronic urticaria. J Allergy Clin Immunol. Apr 1997;99(4):461-5. [Medline].

  35. Rumbyrt JS, Katz JL, Schocket AL. Resolution of chronic urticaria in patients with thyroid autoimmunity. J Allergy Clin Immunol. Dec 1995;96(6 Pt 1):901-5. [Medline].

  36. Leznoff A, Sussman GL. Syndrome of idiopathic chronic urticaria and angioedema with thyroid autoimmunity: a study of 90 patients. J Allergy Clin Immunol. Jul 1989;84(1):66-71. [Medline].

  37. Irinyi B, Szeles G, Gyimesi E, Tumpek J, Heredi E, Dimitrios G. Clinical and laboratory examinations in the subgroups of chronic urticaria. Int Arch Allergy Immunol. 2007;144(3):217-25. [Medline].

  38. Beltrani VS. Urticaria: reassessed. Allergy Asthma Proc. May-Jun 2004;25(3):143-9. [Medline].

  39. Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy for patients infected with Helicobacter pylori who have chronic urticaria. J Am Acad Dermatol. Nov 2003;49(5):861-4. [Medline].

  40. Soundararajan S, Kikuchi Y, Joseph K, Kaplan AP. Functional assessment of pathogenic IgG subclasses in chronic autoimmune urticaria. J Allergy Clin Immunol. Apr 2005;115(4):815-21. [Medline].

  41. Kikuchi Y, Kaplan AP. Mechanisms of autoimmune activation of basophils in chronic urticaria. J Allergy Clin Immunol. Jun 2001;107(6):1056-62. [Medline].

  42. Yasnowsky KM, Dreskin SC, Efaw B, Schoen D, Vedanthan PK, Alam R. Chronic urticaria sera increase basophil CD203c expression. J Allergy Clin Immunol. Jun 2006;117(6):1430-4. [Medline].

  43. Sheikh J. Effect of omalizumab on patients with chronic urticaria: issues with the determination of autoimmune urticaria. Ann Allergy Asthma Immunol. Jan 2008;100(1):88; author reply 88-9. [Medline].

  44. Wong JT, Nagy CS, Krinzman SJ, Maclean JA, Bloch KJ. Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema. J Allergy Clin Immunol. May 2000;105(5):997-1001. [Medline].

  45. Grattan CE. Aspirin sensitivity and urticaria. Clin Exp Dermatol. Mar 2003;28(2):123-7. [Medline].

  46. O'Donnell BF, Barr RM, Black AK, Francis DM, Kermani F, Niimi N. Intravenous immunoglobulin in autoimmune chronic urticaria. Br J Dermatol. Jan 1998;138(1):101-6. [Medline].

  47. Grattan CE, Francis DM, Slater NG, Barlow RJ, Greaves MW. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet. May 2 1992;339(8801):1078-80. [Medline].

  48. Grattan CE, O'Donnell BF, Francis DM, Niimi N, Barlow RJ, Seed PT. Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria. Br J Dermatol. Aug 2000;143(2):365-72. [Medline].

  49. Vena GA, Cassano N, Colombo D, Peruzzi E, Pigatto P. Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. J Am Acad Dermatol. Oct 2006;55(4):705-9. [Medline].

  50. Werni R, Schwarz T, Gschnait F. Colchicine treatment of urticarial vasculitis. Dermatologica. 1986;172(1):36-40. [Medline].

  51. Ruzicka T, Goerz G. Systemic lupus erythematosus and vasculitic urticaria. Effect of dapsone and complement levels. Dermatologica. 1981;162(3):203-5. [Medline].

  52. Nettis E, Dambra P, D'Oronzio L, Loria MP, Ferrannini A, Tursi A. Comparison of montelukast and fexofenadine for chronic idiopathic urticaria. Arch Dermatol. Jan 2001;137(1):99-100. [Medline].

  53. Asero R, Tedeschi A, Lorini M. Leukotriene receptor antagonists in chronic urticaria. Allergy. May 2001;56(5):456-7. [Medline].

  54. Gober LM, Sterba PM, Eckman JA, Saini SS. Effect of anti-IgE (omalizumab) in chronic idiopathic urticaria (CIU) patients. J Allergy Clin Immunol. 2008;121:AB#566.

  55. Najib U, Sheikh J. An update on acute and chronic urticaria for the Primary Care Provider. Postgrad Med. Jan 2009;121(1): ISSN – 0032-5481, e-ISSN:1941-9260.

  56. Breneman DL. Cetirizine versus hydroxyzine and placebo in chronic idiopathic urticaria. Ann Pharmacother. Oct 1996;30(10):1075-9. [Medline].

  57. Finn AF Jr, Kaplan AP, Fretwell R, Qu R, Long J. A double-blind, placebo-controlled trial of fexofenadine HCl in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. Nov 1999;104(5):1071-8. [Medline].

  58. Goldsobel AB, Rohr AS, Siegel SC, Spector SL, Katz RM, Rachelefsky GS. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. Nov 1986;78(5 Pt 1):867-73. [Medline].

  59. Bleehen SS, Thomas SE, Greaves MW, Newton J, Kennedy CT, Hindley F. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: a multi-centre randomized double-blind study. Br J Dermatol. Jul 1987;117(1):81-8. [Medline].

  60. Toubi E, Blant A, Kessel A, Golan TD. Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy. Mar 1997;52(3):312-6. [Medline].

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Further Reading

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Keywords

urticaria, hives, acute urticaria, chronic urticaria, chronic idiopathic urticaria, CIU, angioedema, welts, pruritus, dermographism, erythema, itching, delayed pressure urticaria, urticarial vasculitis, anaphylaxis

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Contributor Information and Disclosures

Author

Javed Sheikh, MD, Assistant Professor of Medicine, Harvard Medical School; Clinical Director, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center; Clinical Director, Center for Eosinophilic Disorders, Beth Israel Deaconess Medical Center
Javed Sheikh, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and American College of Allergy, Asthma and Immunology
Disclosure: UCB Honoraria Speaking and teaching; Sanofi-Aventis Honoraria Speaking and teaching; GlaxoSmithKline Grant/research funds Clinical Trial funding; GlaxoSmithKline Consulting fee Review panel membership; Novartis Honoraria Speaking and teaching; Genentech Honoraria Speaking and teaching; MedPointe Pharmaceuticals  Speaking and teaching

Coauthor(s)

Umer Najib, MD, Clinical Research Fellow, Department of Medicine, Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Stephen C Dreskin, MD, PhD, Director of Allergy, Asthma, and Immunology Practice, Professor of Medicine, Departments of Internal Medicine and Immunology, University of Colorado Health Sciences Center
Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American Association of Neuropathologists, American Association of Ophthalmic Pathologists, American Association of Oral and Maxillofacial Surgeons, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology
Disclosure: Genentech Consulting fee Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Stephen C Dreskin, MD, PhD, Director of Allergy, Asthma, and Immunology Practice, Professor of Medicine, Departments of Internal Medicine and Immunology, University of Colorado Health Sciences Center
Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American Association of Neuropathologists, American Association of Ophthalmic Pathologists, American Association of Oral and Maxillofacial Surgeons, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology
Disclosure: Genentech Consulting fee Consulting

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD, Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians
Disclosure: Abbott Consulting fee Consulting; Alcon Consulting fee Consulting; Glaxo Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering Consulting fee Consulting; Teva  Consulting; Meda Honoraria Speaking and teaching

 
 
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