Localized granuloma annulare associated with autoimmune thyroid disease in a patient with a positive family history for autoimmune polyglandular syndrome type II.

Abstract

Granuloma annulare is a benign cutaneous lesion that has no proven etiology. However, the origin is most likely immunologic (1). In at least some cases there is a mechanism of inheritance (2, 3). Interestingly, there is also evidence linking granuloma annulare and autoimmune thyroiditis/insulin-dependent diabetes mellitus (IDDM) that comes from both limited epidemiologic data (4, 5) and clinical observations (1, 6, 7). Dabski et al. (4) reviewed clinical histories of 100 patients with generalized granuloma annulare who were seen at the Department of Dermatology at the Mayo Clinic from 1966 to 1986. Thyroid disease was detected in 13 of these 100 patients (hypothyroidism in six, Graves' disease in three, thyroiditis in three, thyroid adenoma in one). Concerning the 12 patients with possible autoimmune thyroid disease, information about specific antibodies was not available. Diabetes mellitus was diagnosed in 21 patients. Muhlemann & Williams (5) confirmed a definite association between granuloma annulare and IDDM (defined as IDDM by Muhlemann), analyzing retrospectively the chart reviews of a large series of patients with granuloma annulare, using age-matched population data. We present what we believe to be the first report of a patient with granuloma annulare who underwent screening for immunoendocrinopathies because of a positive family history for autoimmune polyglandular syndrome type II and was found to have autoimmune thyroiditis. A 39-year-old woman presented in 1993 with an erythematous annular skin eruption plaque situated on her right wrist. The patient's medical history revealed no pre-existing diseases and there was no family history of thyroid disease or autoimmune polyglandular syndrome. Without treatment, the skin lesion persisted during the subsequent years and two further skin lesions developed simultaneously on the back of her left and right hands. In 1999 the patient was referred to a dermatologist for evaluation. A skin biopsy was performed and the histological analysis was consistent with granuloma annulare. Meanwhile, the 15-year-old son of the patient began to develop symptoms of diabetes mellitus and an autoimmune polyglandular syndrome type II was diagnosed, with IDDM and autoimmune thyroiditis. Test results were positive for thyroperoxidase antibodies (1:534, reference range ,1:60) and anti-cytoplasmic islet cell antibodies (1:10, reference range ,1:10), whereas they were negative for anti-glutamate decarboxylase, anti-adrenal and anti-adrenal 21-hydroxylase antibodies. Thyroid-stimulating hormone (TSH) concentration was 8.89 mU/l (reference range 0.35± 5.0 mU/l), free thyroxine (T4) and free tri-iodthyronine (T3) were within normal range (free T4 13.8 pmol/l, reference range 12±20 pmol/l; free T3 4.2 pmol/l, reference range 3.3±8.8 pmol/l). Treatment with insulin and thyroxine was initiated. Because of the positive family history, our patient underwent a thyroid function test. Thyrotropin was slightly increased (4.8 mU/l, reference range 0.35± 4.5 mU/l), whereas free T4 and free T3 were within the normal ranges (11.6 pmol/l, reference range 9.5± 25 pmol/l; 3.5 pmol/l; reference range 3.5±6.5 pmol/ l respectively). Serological test results were positive for thyroperoxidase antibodies (1:912, reference range ,1:60). On the basis of these findings, an autoimmune thyroid disease was postulated and the patient was therefore referred to our endocrine division. Endocrinological assessment was negative for anti-cytoplasmic islet cell, anti-glutamate decarboxylase, anti-insulin, anti-adrenal and anti-adrenal 21-hydroxylase antibodies. Two hours after a 75 g oral glucose load, venous plasma glucose was 4.92 mmol/l (reference range ,7.8mmol/l). Treatment with levothyroxine 0.05 mg daily was initiated and the clinical course was followed for 3 months. Skin lesions were still present, but the patient developed no signs or symptoms of further immunoendocrinopathies. Endocrinological testing of the second, 16-year-old, son showed negative titers for the above-mentioned autoantibodies. Association between granuloma annulare and autoimmune thyroiditis has been reported occasionally in the literature. Interestingly, there is one reported case of autoimmune polyglandular syndrome type II and granuloma annulare, in which granuloma annulare involved the skin and visceral organs (8). The polyglandular syndrome type II is the most common of the immunoendocrinopathy syndromes and is usually defined by the occurrence in the same individual of two or more of the following: primary adrenal insufficiency, Graves' or Hashimoto's disease, IDDM, primary hypogonadismus, myasthenia gravis ISSN 0804-4643 European Journal of Endocrinology (2001) 145 101±102