Chronic idiopathic urticaria and

Autoimmune Polyglandular Syndrome

presented by

David Elpern M.D.

Williamstown, MA, USA

February 3, 2010

Dermatologist, The Skin Clinic, Williamstown, Massachusetts, USA


30 yo woman with chronic urticaria

30-year-old woman
4 months

This 30 yo veterinary technician presents with a four-month history of urticaria.  She has had two previous episodes one and two years ago, each lasting a few months.  The patient has had Type I diabetes for 16 years and has a diagnosis of Hashimoto's thyroiditis for over three years.  She is being worked up for GI pain with a question of "allergy" or sprue.  She has had a number of E.R. visits for her urticaria. One episode of urticaria in past resolved with Levoxyl (levothyroxine)-- but not this time. There is a family history of systemic lupus erythematosus. Her present medications are:  Insulin, Levoxyl, citalopram and albuterol (salbutamol).

Physical Examination

On her office visit she had a few scattered wheals on the torso.  Dermographia was negative.  Her hives are worse at home and she sent me some pictures.



Laboratory Data

Anti-thyroid peroxidase antibody   402   (normal  0 - 35)

Anti-thyroglobulin antibody < 20  (normal 0 - 40)




Chronic idiopathic urticaria - Possibly Autoimmune type. 

Reason for presentation

The patient may have "polyglandular" syndrome. Hashimoto's thyroiditis has been associated with chronic urticaria.  The relationship is speculative (see references).


What is your understanding of "autoimmune" urticaria? 

What relationship does her GI problems have with her other symptoms.

Does hormonal therapy play a role in your opinion? 


Van den Driessche A, Eenkhoorn, Van Gaal L, De Block C. Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review.Neth J Med. 2009 Nov;67(11):376-87.

Department of Diabetology and Endocrinology, Antwerp University Hospital, Edegem, Belgium.

Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin-producing beta cells and is characterised by the presence of insulitis and & and beta-cell autoantibodies. Up to one third of patients develop an autoimmune polyglandular syndrome. Fifteen to 30% of T1DM subjects have autoimmune thyroid disease (Hashimoto's or Graves' disease), 5 to 10% are diagnosed with autoimmune gastritis and/or pernicious anaemia (AIG /PA), 4 to 9% present with coeliac disease (CD), 0.5% have Addison's disease (AD), and 2 to 10% show vitiligo.

These diseases are characterised by the presence of autoantibodies against thyroid peroxidase (for Hashimoto's thyroiditis), TSH receptor (for Graves' disease), parietal cell or intrinsic factor (for AIG /PA), tissue transglutaminase (for CD), and 21-hydroxylase (for AD). Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Hashimoto's hypothyroidism may cause weight gain, hyperlipidaemia, goitre, and may affect diabetes control, menses, and pregnancy outcome. In contrast, Graves' hyperthyroidism may induce weight loss, atrial fibrillation, heat intolerance, and ophthalmopathy.

Autoimmune gastritis may manifest via iron deficiency or vitamin B12 deficiency anaemia with fatigue and painful neuropathy. Clinical features of coeliac disease include abdominal discomfort, growth abnormalities, infertility, low bone mineralisation, and iron deficiency anaemia. Adrenal insufficiency may cause vomiting, anorexia, hypoglycaemia, malaise, fatigue, muscular weakness, hyperkalaemia, hypotension, and generalised hyperpigmentation.

Here we will review prevalence, pathogenetic factors, clinical features, and suggestions for screening, follow-up and treatment of patients with T1DM and/or autoimmune polyglandular syndrome.

Dr. Robert Rudolph from Wyomissing, Pennsylvania, USA alerted us to the importance of Anti-IgE antibodies in Chronic Autoimmune Urticaria.  This reference is of possibly importance:

Kaplan AP, Greaves M. Pathogenesis of chronic urticaria. Clin Exp Allergy. 2009 Jun;39(6):777-87. Epub 2009 Apr 22.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Medical University of South Carolina, Charleston, SC, USA.

Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks with the assumption that it occurs daily or close to it. If we eliminate physical urticarias and urticarial vasculitis from consideration, the remainder can be divided into autoimmune chronic urticaria (45%) and idiopathic chronic urticaria (55%).

The autoimmune subgroup is associated with the IgG anti-IgE receptor alpha subunit in 35-40% of patients and IgG anti-IgE in an additional 5-10%. These autoantibodies have been shown to activate blood basophils and cutaneous mast cells in vitro with augmentation of basophil activation by complement and release of C5a, in particular. Binding methods (immunoblot and ELISA) yield positives in many autoimmune diseases as well as occasional normal subjects or patients with other forms of urticaria but most such sera are non-functional. Activation of basophils or mast cells causing histamine release is quite specific for chronic urticaria and defines the autoimmune subgroup.

Although pathogenicity is not formally proven, the antibodies cause wealing upon intradermal injection, and removal of the autoantibody leads to remission. A cellular infiltrate is seen to be characterized by mast cell degranulation and infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The intensity of the infiltrate and clinical severity of the disease (including accompanying angio-oedema) is more severe in the autoimmune subpopulation. This latter group also has a higher evidence of human leucocyte antigen DR alleles associated with autoimmunity and a 25% incidence of antithyroid antibodies with diagnosed hypothyroidism in some.

Hypo-responsiveness of patients' basophils to anti-IgE and hyperresponsiveness to serum defines another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune subgroups. Hypo-responsiveness to anti-IgE has been shown to be associated with elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal of the abnormality is seen with disease remission.

Further work will be needed to distinguish whether this is a cause or a consequence of persistent urticaria and to further assess the relationship (or lack thereof) of altered responsiveness (decreased or increased) with the presence or absence of activating autoantibodies.


chronic urticaria, autoimmune polyglandular syndrome

Comments from Faculty and Members

Robert Rudolph MD, FACP, Clinical Professor of Dermatology, University of Pennsylvania, Philadelphia. PA, USA on February 4, 2010

Vitiligo patients also fit under this rubric. They often have a number of auto-antibodies to various endocrine glands. I'd bet that this woman has IgE antibodies associated with her hives in this setting. THIS is the kind associated with a chronic course. If you and she are lucky, the hives have nothing to do with her other problems, and will resolve.

Any dental or vaginal infections? Is she taking stuff on her own to help reduce the hives? Any joint pains?

Ashok Sharma M.D. Consultant Dermatologist, Kuwait on February 4, 2010

The diagnosis of Autoimmune Chronic Urticaria seems quite appropriate in this patient. Confirmation may be attempted by the Autologous Serum Test which is a simple test.

My experience with such 'autoimmune' urticarias is that the course is very unpredictable. Even with proper control of their associated endocrinopathies or other autoimmune conditions (arthritis/connnective tissue diseases mainly from my experience), the urticaria, once it starts, continues in a recurrent fashion for over a year usually.

The urticaria in such patients is more severe than with patients without any associated autoimmune condition.

Although I attempt to use routine antihistamines initially, I have had to use frequently hydroxyzine (Atarax), dimenhydramine (Benadryl), systemic steroids, cyclosporin and in a couple of cases IV immunoglobulins.

Huthaifa Hasen MD, Kerbala, Iraq on February 12, 2010

Thanks for this case which open the problem of diagnosis of chronic urticaria. Autoimmune chronic urticaria actually is a vague nomencleature. It is postulated to be higher in incidence in western countries because of advanced investigational approach. Let's try a course of non-sedative antihistamine for 2 months or more e.g loratadine.

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