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A Case of Type 1 Diabetes Followed by Methimazole-Induced Hypersensitivity Syndrome

From the Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan

Address correspondence to Nobuaki Ozaki, Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho Showa-ku, Nagoya 466-8550, Japan. E-mail: n-ozaki{at}med.nagoya-u.ac.jp

Viruses have generally been considered to be a major environmental factor in the etiology of type 1 diabetes. Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe drug eruption and multiorgan involvement, and reactivation of human herpesvirus-6 (HHV-6) may contribute to its pathology (1). This is the first reported case of type 1 diabetes followed by DIHS.

Recently, we have reported a case of DIHS induced by methimazole for Graves’ disease (2). This patient developed type 1 diabetes during treatment of DIHS. Briefly, a 50-year-old Japanese male subject was diagnosed as having DIHS caused by methimazole in November 2003, based on the physical manifestations and laboratory findings including elevated anti–HHV-6 IgG titer. The administration of glucocorticoids gradually improved his clinical manifestations.

In December 2003, fasting plasma glucose was 4.9 mmol/l. His glycemic control, thereafter, gradually worsened despite treatment with nateglinide (270 mg/day). In March 2004, laboratory studies showed fasting plasma glucose to be 14.4 mmol/l; HbA_1c, 12.1%; fasting serum C-peptide, 0.35 ng/ml (normal range 0.5–2.73); and urinary excretion of C-peptide (which means integrated intrinsic insulin secretion), 17.24 mg/day (normal range 40–120). Basal level of serum C-peptide was finally undetectable. Anti-GAD antibody was 24.1 unit/ml (normal range <1.5). Response of serum C-peptide to glucagon was blunted. Thus, we diagnosed the patient as having type 1 diabetes. He started insulin injections immediately. His glycemic control gradually improved.

The coexistence of type 1 diabetes and Graves’ disease is not infrequent. The onset age of type 1 diabetes in this case is fairly later, and anti-GAD antibody titer is relatively low, although type 1 diabetes with autoimmune thyroid disease was reported to be clinically characterized as high titer (609 ± 166 units/ml) of anti-GAD antibody and later-onset age (30 years) compared with the general type 1 diabetic population (3). Therefore, these findings cannot exclude the possibility that the coexistence of type 1 diabetes and Graves’ disease may be not incidental.

It is possible that viral infections such as coxsackie B4 virus and cytomegalovirus can trigger autoimmune reactions against pancreatic ß-cells, which leads to type 1 diabetes. Molecular mimicry has been considered as a pathogenetic mechanism for autoimmune disease (4). GAD65-reactive T-cells have been postulated to recognize the peptide derived by coxsackie B4 virus, leading to autoimmune type 1 diabetes (4). Furthermore, sequence homology between GAD65 and cytomegalovirus might participate in the onset of type 1 diabetes and stiff-man syndrome (5). Interestingly, HHV-6 is closely related to cytomegalovirus genomically and antigenically, and GAD65-reactive T-cells also recognize an epitope derived by HHV-6 (5), suggesting that reactivation of HHV-6 might contribute to the onset of autoimmune type 1 diabetes by the molecular mimicry.

References

1. Sullivan JR, Shear NH: The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol137 :357 –364,2001[Free Full Text]
   
2. Ozaki N, Miura Y, Sakakibara A, Oiso Y: A case of hypersensitivity syndrome induced by methimazole for Graves’ disease. Thyroid15 :1333 –1336,2005[Medline]
   
3. Kawasaki E, Takino H, Yano M, Uotani S, Matsumoto K, Takao Y, Yamaguchi Y, Akazawa S, Nagataki S: Autoantibodies to glutamic acid decarboxylase in patients with IDDM and autoimmune thyroid disease. Diabetes43 :80 –86,1994[Abstract]
   
4. Oldstone MB: Molecular mimicry and immune-mediated diseases. FASEB J12 :1255 –1265,1998[Abstract/Free Full Text]
   
5. Hiemstra HS, Schloot NC, van Veelen PA, Willemen SJ, Franken KL, van Rood JJ, de Vries RR, Chaudhuri A, Behan PO, Drijfhout JW, Roep BO: Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci U S A98 :3988 –3991,2001[Abstract/Free Full Text]
   

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ozaki, N. Articles by Oiso, Y. Search for Related Content PubMed PubMed Citation Articles by Ozaki, N. Articles by Oiso, Y. Social Bookmarking                What's this?