methimazole and Uveitis

A 50-year-old woman was admitted because of severe exophthalmos associated with Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks after the start of pulse therapy and she was diagnosed as having uveitis. Methylprednisolone pulse therapy was performed again for both exophthalmos and uveitis, followed by daily administration of 20 mg of prednisolone and instillation of betamethasone for 2 weeks and the uveitis was improved. Western blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1-associated uveitis (HAU) has not recurred. Six months after the beginning of administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis developed in the patient. We review 43 cases of HAU with Graves disease, including the present case, in the literature. Only 2 of 27 cases (except unknown cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has been no investigation of HAU and Graves ophthalmopathy.

Topics: Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Graves Disease; HTLV-I Infections; Humans; Magnetic Resonance Imaging; Methimazole; Methylprednisolone; Middle Aged; Prednisolone; Propylthiouracil; Severity of Illness Index; Thyroid Hormones; Time Factors; Treatment Outcome; Uveitis; Vasculitis

Methimazole (methyl-mercapto-imidazole, MMI), a compound used clinically in therapy of Graves' thyroiditis, was found to inhibit development of several autoimmune diseases in animal models. It was suggested on the basis of in vitro data that inhibition is through down-regulation of interferon-gamma (IFN-gamma)-induced expression of major histocompatibility complex class I and class II molecules. Here, we investigate the effect of MMI on experimental autoimmune uveoretinitis (EAU) and study its mechanism(s). Treatment of EAU with MMI administered in drinking water inhibited induction of the disease and associated antigen (Ag)-specific proliferation and cytokine production by draining lymph node cells (LNCs). The treatment was protective only if administered during the first but not during the second week after immunization, suggesting an effect on the induction phase of EAU. It is interesting that MMI inhibited disease in IFN-gamma knockout mice, indicating that the in vivo protective effect is IFN-gamma-independent. Flow cytometric analysis of draining LNCs extracted 5 days after immunization showed that MMI partly to completely reversed the increase in Mac-1(+)/class I(+)/class II(+) cells induced by immunization and reduced the proportion of B7-1 and CD40-positive cells, suggesting a deficit in the Ag-presenting cell (APC) population. APC from untreated mice largely restored antigen-specific proliferation of MMI-treated LNCs. We suggest that MMI inhibits EAU at least in part by preventing the recruitment and/or maturation of APC, resulting in reduced generation of Ag-specific T cells.

Topics: Animals; Antigen Presentation; Antigen-Presenting Cells; Antithyroid Agents; Autoimmune Diseases; Cytokines; Disease Models, Animal; Eye Proteins; Female; Flow Cytometry; Interferon-gamma; Lymph Nodes; Macrophage-1 Antigen; Methimazole; Mice; Mice, Inbred C57BL; Mice, Knockout; Retinitis; Retinol-Binding Proteins; Uveitis

Human T-lymphotropic virus type I (HTLV-I) is responsible for a certain form of uveitis [HTLV-I-associated uveitis (HAU)]. A previous history of Graves' disease has been reported in 9-17% of the patients with HAU. In this study, the prevalence of patients with either HTLV-I antibody or uveitis was evaluated in 819 consecutive patients with thyroid disorders between 1991 and 1992. Serum HTLV-I antibody was found in 25 of 392 patients with Graves' disease, 19 of 257 with chronic thyroiditis, and 3 of 170 with nodular goiter. Five of 25 HTLV-I-positive patients with Graves' disease developed HAU. All of these 5 patients had been treated with methylmercaptoimidazole (MMI). Within a few months before the onset of uveitis, 3 patients were hyperthyroid, and 2 were hypothyroid. In 2 of 5 patients, an exacerbation of uveitis occurred soon after the readministration of MMI for the relapse of hyperthyroidism. None of the 367 HTLV-I negative patients with Graves' disease nor 22 HTLV-I-positive patients with chronic thyroiditis or nodular goiter developed uveitis. It was therefore suggested that Graves' disease, thyroid dysfunction and/or MMI administration might be related to the development of HAU.

Topics: Adult; Aged; DNA, Viral; Female; Graves Disease; HTLV-I Antibodies; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Methimazole; Middle Aged; Polymerase Chain Reaction; Uveitis