methimazole and Lupus-Erythematosus--Systemic

Topics: Animals; Antibodies; Antiphospholipid Syndrome; CD4 Antigens; Disease Models, Animal; Fatty Acids, Omega-3; Immunosuppression Therapy; Immunotherapy; Lupus Erythematosus, Systemic; Methimazole; Mice; Mice, Inbred BALB C; Nutritional Status; Tamoxifen

Two cases of propylthiouracil-associated acute hepatitis, one case of fatal methimazole-associated hepatocellular necrosis and one case of propylthiouracil-associated lupus-like syndrome are described. The literature related to antithyroid drug side effects and the mechanisms for their occurrence are reviewed and the efficacy and complications of thyroidectomy and radioiodine compared to those of antithyroid drugs. It is concluded that in most circumstances 131I is the therapy of choice for hyperthyroidism.

Topics: Adult; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Methimazole; Necrosis; Propylthiouracil

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Topics: Adult; Anti-Inflammatory Agents; Antirheumatic Agents; Antithyroid Agents; Blister; Drug Therapy, Combination; Female; Graves Disease; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Methimazole; Mycophenolic Acid; Prednisolone; Skin

Clinical recognition of drug-induced vasculitic and lupus-like syndromes is very important because continued use of the offending drug can lead to irreversible and life-threatening vasculitic organ damage (e.g. end-stage renal disease or pulmonary haemorrhage). Withdrawal of the drug often leads to spontaneous recovery, meaning that immunosuppressive therapy can be avoided. The presence of myeloperoxidase-antineutrophil cytoplasmic antibodies, IgM anticardiolipin antibody, and antihistone antibodies in combination was found to be characteristic of drug-induced vasculitic syndromes caused by the antithyroid drugs propylthiouracil and methimazol. Clinically, skin vasculitis and arthralgias predominated and renal vasculitis was rare.

Topics: Acute Kidney Injury; Antibodies, Anticardiolipin; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Autoimmune Diseases; Churg-Strauss Syndrome; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Immunoglobulin M; Kidney; Lupus Erythematosus, Systemic; Methimazole; Propylthiouracil; Skin; Thrombophilia; Vasculitis, Leukocytoclastic, Cutaneous

(NZB x NZW)F1 mice spontaneously develop with age an autoimmune disease that resembles the human disease, systemic lupus erythematosus (SLE). The present study demonstrates that methimazole (MMI), an agent used in the treatment of autoimmune thyroid disease, is effective in mitigating the development of this SLE-like autoimmune disease in (NZB x NZW)F1 mice. MMI significantly reduces the incidence and severity of proteinuria and deposition of immune complexes in the kidney. Previous studies have demonstrated that development of an experimentally induced SLE, which was prevented by MMI treatment, depended on the expression of MHC class I molecules. We now report that class I levels on both T cells and B cells from old (NZB x NZW)F1 MHC class I are markedly elevated relative to those from young F1 mice. Furthermore, treatment of (NZB x NZW)F1 mice with MMI reduced MHC class I expression on their PBL concomitant with amelioration of disease, raising the possibility that class I molecules may play a role in the generation of spontaneous autoimmune disease in these mice.

Topics: Aging; Animals; Autoantibodies; Autoimmune Diseases; Disease Models, Animal; DNA; Female; Histocompatibility Antigens Class I; Lupus Erythematosus, Systemic; Methimazole; Mice; Mice, Inbred BALB C; Mice, Inbred NZB

Topics: Animals; Antirheumatic Agents; Estrogen Antagonists; Female; Histocompatibility Antigens Class II; Lupus Erythematosus, Systemic; Male; Methimazole; Methotrexate; Mice; Mice, Inbred Strains; Tamoxifen

Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal anti-DNA Ab, bearing a major Id 16/6Id. Immunized mice initially produce Abs to 16/6Id, DNA and nuclear Ags, and subsequently develop various clinical manifestations including leukopenia and renal immune complex disease. MHC class I Ags play a critical role in the induction and progression of experimental SLE. The present study reports that ocular changes also occur in mice with experimental SLE. The ocular disease is characterized by bilateral subacute and chronic inflammation of the eyelids (blepharitis) with immune complex IgG deposition and hypertrophic meibomian glands. The severity of ocular changes was strain dependent: most severe in 129 mice, less intense in BALB/c animals and only minimal in C3H.SW mice. No blepharitis developed in mice deficient in MHC class I expression. Further, the disease was strongly inhibited in BALB/c mice treated with methimazole, an agent that has been shown to repress transcription of MHC class I. In these cases, there was no IgG deposition and a decreased infiltration of inflammatory cells in the eyelids. These observations thus suggest that, similar to the observation with experimental SLE, MHC class I is critical in the onset of this experimental autoimmune blepharitis. The new experimental eye disease described here provides an animal model for chronic blepharitis in humans, a common condition for which such a model has been sought.

Topics: Animals; Blepharitis; Female; Histocompatibility Antigens Class I; Lupus Erythematosus, Systemic; Methimazole; Mice; Mice, Inbred BALB C; Mice, Mutant Strains

Experimental SLE can be induced in mice by immunization with a human mAb to DNA (16/6Id). Immunized mice develop Abs to the 16/6Id immunogen, DNA, and nuclear Ags. Subsequently, clinical manifestations of disease develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. MHC class I Ags play a critical role in the induction of experimental SLE, as demonstrated by the finding that class I-deficient mice are resistant to disease induction. This finding suggested that agents that reduce MHC class I expression might mitigate experimental SLE in normal mice. These studies report that methimazole, which has been shown to repress class I transcription in some cell lines, reduces class I expression on PBLs in vivo and prevents the development of clinical manifestations of SLE in 16/6Id-immunized mice. These data suggest that methimazole, which has been used in the treatment of Graves' disease, may be useful in the clinical treatment of SLE and other autoimmune diseases.

Topics: Animals; Antibodies, Antinuclear; Antibodies, Monoclonal; DNA; Histocompatibility Antigens Class I; Immunization; Lupus Erythematosus, Systemic; Methimazole; Mice; Mice, Inbred BALB C

A 17-year-old Japanese woman developed a lupus erythematosus-like syndrome during treatment for Graves' disease with thiamazole and propylthiouracil. Erythema, arthralgia, and low grade fever developed during therapy with thiamazole; purplish-red erythema developed during therapy with propylthiouracil. Antinuclear antibodies, anti-single-stranded DNA antibodies, and anti-double-stranded DNA antibodies were positive throughout the administration of these two drugs. Eruptions and other symptoms improved after their discontinuation. The titers of autoantibodies also decreased two months after withdrawal. The patient had HLA DR4.

Topics: Adolescent; Antibodies, Antinuclear; DNA; DNA, Single-Stranded; Female; Graves Disease; Humans; Immunoglobulin M; Lupus Erythematosus, Systemic; Methimazole; Propylthiouracil; Skin Tests

We present two cases of systemic lupus erythematosus (SLE) associated with both Basedow's disease and fatty liver. The first case is a 46-year-old Japanese female who was admitted because of high fever and general fatigue. She had been diagnosed as having Basedow's disease and treated with thiamazole for over 4 years. Since thiamazole-induced lupus was unlikely because of high titer anti-nuclear antibody and anti-DNA antibody and low levels of complements, a diagnosis of SLE was made. The upper abdominal ultrasound study and the specimen obtained by liver biopsy performed before initiating steroid therapy demonstrated marked fatty liver. SLE itself is considered as an etiology of fatty liver in this case. The second case was a 25-year-old Japanese female with SLE. She had been treated with prednisolone for 13 years and was complicated with Basedow's disease 10 years later. Fatty liver was also demonstrated in this patient on ultrasonography, and was thought to be resulted from long-term steroid hormone administration.

Topics: Adult; Fatty Liver; Female; Graves Disease; Humans; Lupus Erythematosus, Systemic; Methimazole; Middle Aged; Prednisolone

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Child; Female; Goiter, Nodular; Graves Disease; Humans; Immunoassay; Iodine Radioisotopes; Lupus Erythematosus, Systemic; Male; Methimazole; Middle Aged; Thyroiditis, Autoimmune

In 16 untreated patients with hyperthyroidism due to Graves' disease, serum antidouble stranded DNA antibody, measured by RIA, was positive (greater than 20 U/ml) in 14. In methimazole-treated patients with T3-suppressible thyroid uptake, anti-DNA antibody was found in 9% (3 of 35). The frequency of positive tests in methimazole-treated patients with T3-nonsuppressible thyroid uptake and in surgically treated patients was 24% (5 of 21) and 57% (4 of 7), respectively. Among anti-DNA antibody-negative (less than 9 U/ml) and weakly positive (10-19 U/ml) patients, those with T3-suppressible thyroid uptake had lower anti-DNA antibody titers than those with T3-nonsuppressible thyroid uptake. Among 32 patients with Hashimoto's thyroiditis, anti-DNA antibody was positive in 7. None of the patients with simple goiter had positive or weakly positive anti-DNA antibody results. Although the quantity of antibodies did not correlate well in individual patients, the rates of positive TSH binding-inhibiting immunoglobulin and anti-DNA antibody tests were roughly comparable in these patient groups. None of these patients with thyroid disease associated with anti-DNA antibody had clinical or other serological evidence suggestive of systemic lupus erythematosus or related collagen vascular disorders. The finding of anti-DNA antibody provides a new aspect of immunological abnormality associated with hyperthyroidism of Graves' disease.

Topics: Antibodies, Antinuclear; Autoimmune Diseases; Female; Goiter; Graves Disease; Humans; Lupus Erythematosus, Systemic; Male; Methimazole; Thyroiditis, Autoimmune; Thyroxine; Triiodothyronine

We have experienced two cases (Case 1: 21-year-old female, Case 2: 26-year-old female) of systemic lupus erythematosus (SLE) associated with hyperthyroidism. Case 1 had been treated with methimazole (MMI) and betamethasone for approximately two years. Although thyroid function improved with the treatment, laboratory data of SLE deteriorated. She was successfully treated with betamethasone alone. Case 2, who had severe side effect (severe hemorrhage due to gastric ulcer) during prednisolone treatment for SLE, was found to have an additional hyperthyroidism. She was treated with intermittent prednisolone administration alone. Physical findings as well as laboratory data of both SLE and hyperthyroidism improved by the therapy.

Topics: Adult; Betamethasone; Female; Humans; Hyperthyroidism; Lupus Erythematosus, Systemic; Methimazole; Prednisolone

A patient with Graves' disease who experienced various allergic reactions to both PTU and MMI is reported. She developed fever, skin rash, lymphadenopathy, liver damage and moderate leukopenia during PTU administration. Furthermore, she developed an MMI-induced lupus-like syndrome characterized by generalized lymphadenopathy, migrating, polyarthritis and myalgia, and results of tests for anti-DNA antibody and anti-nuclear antibody, and LE were positive. All these abnormalities reverted to normal upon discontinuation of medication after subtotal thyroidectomy.

Topics: Adult; Autoantibodies; Dexamethasone; Female; Graves Disease; Humans; Lupus Erythematosus, Systemic; Methimazole; Propranolol; Propylthiouracil; Thyroidectomy

Topics: Adolescent; Arthritis, Rheumatoid; Female; Humans; Hyperthyroidism; Indians, North American; Lupus Erythematosus, Systemic; Methimazole; Neutrophils