The Journal of Allergy and Clinical Immunology
Volume 115, Issue 5 , Pages 1088-1089, May 2005

Autoimmune chronic urticaria associated with type 1 diabetes and Graves' disease

  • Riccardo Asero, MD

      Affiliations

    • Ambulatorio di Allergologia, Clinica San Carlo, Via Ospedale 21, 20037 Paderno Dugnano (MI), Italy
    • ,
  • Alessandra Orsatti, BSc

      Affiliations

    • First Division of Internal Medicine, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
    • ,
  • Alberto Tedeschi, MD

      Affiliations

    • First Division of Internal Medicine, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
    • ,
  • Maurizio Lorini

      Affiliations

    • First Division of Internal Medicine, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

published online 02 February 2005.

Article Outline

 

To the Editor:

It is now widely accepted that in many cases chronic urticaria (CU) should be regarded as an autoimmune disorder caused by circulating and functionally active IgG autoantibodies specific for FcεRI present on mast cells and basophils or for IgE.1, 2 The well-known association of CU with Hashimoto's thyroiditis or with thyroid autoimmunity represents further indirect evidence of its autoimmune origin.2 In recent years, some studies have suggested that CU might be associated also with other autoimmune conditions. In 1981, one study reported an association between hyperthyroidism and CU,3 an association observed also by Irani et al.4 Recently, we reported some cases of autoimmune CU associated with thyroid autoimmunity and Raynaud's phenomenon with anti-centromere antibodies.5 In the present study we report an unusual association between autoimmune disorders characterized by autoantibodies showing 4 distinct specificities.

A 33-year-old woman was recently seen at our allergy outpatient clinic. She had been experiencing type 1 diabetes mellitus for 8 years and Graves' disease for 7 years. During the last 6 months, she had noted the recurrence of pruritus and erythema at different sites, with typical wheals after scratching sometimes associated with angioedema of the lips. Symptoms were not associated with cold exposure, pressure, or increase in body temperature. The intradermal injection of 0.05 mL of fresh autologous serum (autologous serum skin test)1 induced a large wheal (mean diameter, 10 mm) with a flare ring, whereas no skin reaction was noted at the site at which an equivalent volume of saline was injected. Strong skin reactions to autologous serum have been associated with autoimmune CU.6

Circulating anti-insulin antibodies were determined by means of quantitative radioimmunoprecipitation assay (DLD Diagnostika, Hamburg, Germany) by using iodine 125–labeled monoiodinated insulin and anti-human IgG. On the basis of the levels found in 30 normal sera, values of greater than 0.5 U/mL were considered positive. The level of anti-insulin antibodies in the patient's serum was 4.37 U/mL.

Autoantibodies to glutamic acid decarboxylase (GAD) were detected by using an RIA (GAD Ab-RSR, Cardiff, United Kingdom) with iodine 125–labeled human recombinant GAD 65. Values of greater than 1.0 U/mL were considered positive. Our patient's serum level was 12.64 U/mL.

Thyroid-stimulating hormone (TSH) receptor antibodies were measured by using a second-generation radioreceptor assay (Dynotest TRAK Human; B.R.A.M.S., Henningsdorf, Germany) with human recombinant TSH receptor. The assay was calibrated according to World Health Organization standard 90/672. Values of greater than 1.0 U/L were considered positive. Our patient's serum level was 1.44 U/L.

Finally, an in vitro histamine release assay was carried out by using basophils from healthy donors as substrate, as previously described.7 Results were expressed as the net percentage of histamine release over total histamine content. A 5% histamine release was used as the cutoff point. Our patient's serum induced 6.5% histamine release.

In this patient we detected autoantibodies specific for FcεRI, GAD, insulin, and TSH receptor. GAD autoantibodies are a rather specific marker of type 1 diabetes and are found in up to 90% of patients at diagnosis.8 It is well known that genetic factors underlie many autoimmune disorders, and an association with specific antigens of the MHC (often of class II) has been frequently found. For CU, an association with HLA-DR4 has been reported.1

A strong association of Graves' disease with HLA-DR3 has been observed in white subjects,9 and more recent studies indicate that HLA-DR3 is in strong linkage disequilibrium with DQB1∗0201 and DQA1∗0501, both of which are strongly associated with Graves' disease.10 The association between type 1 diabetes and Graves' disease has been observed for a long time.11 HLA-DR3 and HLA-DR4 convey a high risk for type 1 diabetes, and individuals with the highest risk express both DQA1∗0501 and DQB1∗0201.12 Furthermore, these haplotypes have been identified as a risk factor for thyroid autoimmunity in patients with type 1 diabetes.13

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References 

  1. Greaves MW. Chronic urticaria. J Allergy Clin Immunol. 2000;105:664–672
  2. Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. 2004;114:465–474
  3. Small P, Lerman S. Hyperthyroidism and polycythemia vera in chronic urticaria and angioedema. Ann Allergy. 1981;46:256–259
  4. Irani C, Gordon ND, Zweiman B, Levinson AI. Chronic urticaria/angioedema and Graves' disease: coexistence of 2 antireceptor antibody-mediated diseases. J Allergy Clin Immunol. 2001;108:874
  5. Asero R, Lorini M, Tedeschi A. Association of chronic urticaria with thyroid autoimmunity and Raynaud phenomenon with anticentromere antibodies. J Allergy Clin Immunol. 2003;111:1129–1130
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  8. Kawasaki E, Takino H, ano M, Uotani S, Matsumoto K, Takeo Y, et al. Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease. Diabetes. 1994;43:80–86
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  10. Barlow ABT, Wheatcroft N, Watson P, Weetman AP. Association of HLA-DQA∗0501 with Graves' disease in English Caucasian men and women. Clin Endocrinol. 1996;44:73–77
  11. Irwin WJ. Autoimmunity in endocrine diseases. Recent Prog Horm Res. 1980;36:509–556
  12. Robles DT, Eisenbarth GS. Diabetes and related autoimmune diseases. In:  Rich R editors. Clinical immunology: principles and practice. 2nd ed.. St Louis: Mosby; 2001;p. 82.1–82.18
  13. Chuang L-M, Wu HP, Chang PR, Tsai WY, Chang HM, Tai TY, et al. HLA-DRB1/DQA1/DQB1 haplotype determines thyroid autoimmunity in patients with insulin dependent diabetes mellitus. Clin Endocrinol. 1996;45:631–636

PII: S0091-6749(04)03231-2

doi:10.1016/j.jaci.2004.12.009

The Journal of Allergy and Clinical Immunology
Volume 115, Issue 5 , Pages 1088-1089, May 2005

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