methimazole and Vasculitis

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

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

The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism.

Topics: Adult; Antithyroid Agents; Febrile Neutropenia; Female; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Thyroidectomy; Vasculitis

We report on a case of diffuse alveolar haemorrhage in a Chinese woman due to methimazole-induced antineutrophil cytoplasmic antibodies. A literature search for anti-thyroid drugs associated with antineutrophil cytoplasmic antibody-induced diffuse alveolar haemorrhages is reviewed. Diffuse alveolar haemorrhage is a rare complication of thiourea agents and the treatment often requires corticosteroids or other immunosuppressants, together with withdrawal of the causative agent.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Comorbidity; Female; Graves Disease; Hemorrhage; Humans; Lung Diseases; Methimazole; Pulmonary Alveoli; Vasculitis

To study the relationship between methimazole (MMI) and antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis.. Thirty-three cases with Graves' disease were tested for serum ANCA before and after taking MMI. At the same time, clinicopathological data of two patients with Graves' disease who had antineutrophil cytoplasmic antibody-positive vasculitis during treatment with MMI were analyzed.. Two patients developed antineutrophil cytoplasmic antibody-positive vasculitis during the medication with MMI for 5-6 years; their major clinical manifestations were hematuria and renal failure. Renal biology showed renal vasculitis and vascular necrosis. The disease was relieved after treatment with immunosuppressor. Serum ANCA in the 33 cases was negative before taking MMI. In 3 cases serum ANCA became positive after taking MMI for 2 months, 3 months and 2 years, respectively. The positive rate is 9% (3/33). The major finding was microscopic hematuria. ANCA positive rate was significantly higher after taking MMI than that before taking MMI (chi2) = 5.3, P < 0.05). Microscopic hematuria disappeared after general treatment.. There may be a relationship between methimazole and development of antineutrophil cytoplasmic antibody-positive vasculitis. Renal impairment can occur. The signs and symptoms of the vasculitis can disappear after proper treatment.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Child; Female; Graves Disease; Humans; Kidney; Male; Methimazole; Vasculitis

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Antithyroid Agents; Autoantigens; Autoimmune Diseases; Churg-Strauss Syndrome; Cyclophosphamide; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Granulomatosis with Polyangiitis; Graves Disease; Hashimoto Disease; Humans; Hyperthyroidism; Immunoprecipitation; Kidney; Lung; Male; Methimazole; Middle Aged; Myeloblastin; Nephelometry and Turbidimetry; Peroxidase; Polyarteritis Nodosa; Prednisone; Pregnancy; Pregnancy Complications; Propylthiouracil; Retrospective Studies; Serine Endopeptidases; Skin; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Female; Fluorescent Antibody Technique, Indirect; Graves Disease; Humans; Lupus Erythematosus, Cutaneous; Methimazole; Skin Diseases, Vesiculobullous; Treatment Outcome; Vasculitis

A 30-year-old female patient, diagnosed as having Graves' disease in 1996, was treated with propylthiouracil (PTU) for 4 years. She developed a low-grade fever from December 1999. As myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) vasculitis is one of the adverse effects of PTU, we examined serum MPO-ANCA level and found it was positive, but cytoplasmic-ANCA (c-ANCA) was negative. There were no symptoms that indicated other diseases associated with MPO-ANCA. She was confirmed to be at 6 weeks gestation, and thyroid hormone levels were elevated at that time. We discontinued PTU and gave methyl-mercaptoimidazole (MMI), and the titer of MPO-ANCA fell along with fever. Therefore we estimated the case as probable MPO-ANCA positive vasculitis induced by PTU. MMI was also suspended because of the development of hepatic dysfunction. After thyroid function was normalized by administration of potassium iodide, she underwent subtotal thyroidectomy, and delivered a 2350 g infant at 38 weeks' gestation, which was less than the normal birth weight of 2400 g. MPO-ANCA is considered to be one reason of low birth weight infant including hyperthyroidism. It is necessary to consider the appearance of the possibility of MPO-ANCA positive vasculitis in patients who are treated with PTU.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Female; Graves Disease; Humans; Infant, Low Birth Weight; Infant, Newborn; Methimazole; Peroxidase; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Propylthiouracil; Thyroidectomy; Vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with antithyroid drugs. We describe the case of an 18-year-old girl who developed antimyeloperoxidase ANCA (MPO-ANCA)-positive vasculitis manifesting as a skin lesion and hemoptysis with hypoxic respiratory failure after taking methimazole. An open lung biopsy was consistent with acute capillaritis. Both skin and sural nerve biopsy showed lymphocytic vasculitis. Administration of steroid and plasmapheresis produced a good clinical response.

Topics: Adolescent; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Female; Hemorrhage; Humans; Lung Diseases; Methimazole; Peroxidase; Skin Diseases, Vascular; Vasculitis

A 24-year-old woman with Graves' disease treated with methimazole for 4 years, developed recalcitrant ulcers on the lower legs. Histological studies demonstrated vasculitis in deep dermal vessels accompanied by C3 deposition. Laboratory investigation revealed lupus-like abnormalities (leucocytopenia, positive antinuclear and antidouble strand (ds) DNA antibodies, and positive ANCA). The leg ulcers dramatically improved after methimazole was withdrawn. In addition, leucocytopenia and the immunological abnormalities soon faded. Although lupus-like syndrome is well known to be induced by antithyroid drugs, vasculitis is a rare complication. To the best of our knowledge, this is the first report describing ANCA-associated vasculitis caused by methimazole.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Antithyroid Agents; Autoantibodies; Biomarkers; Female; Graves Disease; Humans; Lupus Vulgaris; Methimazole; Skin Ulcer; Vasculitis