Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy

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The Management of Graves’ Disease in Children, with Special Emphasis on Radioiodine Treatment

OBJECTIVE:To evaluate the literature for published cases of drug-induced vasculitis with cutaneous and/or systemic manifestations.DATA SOURCES:The MEDLINE database was searched from 1965 to December 1999 for articles focusing on drugs and vasculitis, using various search terminologies (e.g., Churg-Strauss syndrome, Goodpasture's syndrome, Henoch-Schonlein purpura, various drugs suspected to induce vasculitis). Cases were included when they met the established criteria as described in the methodology.DATA SYNTHESIS:Drugs found to be most frequently associated with vasculitis were propylthiouracil, hydralazine, colony-stimulating factors, allopurinol, cefaclor, minocycline, D-penicillamine, phenytoin, isotretinoin, and methotrexate. The interval between the first exposure and appearance of symptoms was reported to be extremely variable (hours to years). Vasculitis has occurred after drug dosage increases and after rechallenge with the suspected drug. In the majority of cases, vasculitis has resolved after d...

Cutaneous and systemic manifestations of drug-induced vasculitis.

Publisher Summary This chapter discusses the adverse effects associated with the use of thyroid and antithyroid drugs. These include use of thyroid hormone, antithyroid drugs, and iodine preparations. Hyperthyroidism developing during therapy with normal amounts of thyroid hormones and persisting after stopping levothyroxine therapy can occasionally be observed. This is because of the activation of a previously silent autoimmune disorder (Graves' disease or TSI hyperthyroidism). The optimal intake of iodine remains a controversial topic. A nutritional intake below 50 μg/day is associated with an increased incidence of goiter and hypothyroidism. The Food and Nutritional Board of the National Academy of Sciences, USA, therefore, proposed 100 μg/day as the desirable lower limit of intake. The upper tolerance limit is defined as 1000 μg/day with 300 μg as the upper desirable limit. A high-normal intake (>300 μg/day) may be associated with an increased incidence of goiter and Hashimoto thyroiditis and a decreased remission rate after medical treatment for Graves' disease. The problem of iodine-induced or iodine related hyperthyroidism is very frequent.

Thyroid and antithyroid drugs

I. Physiology of Pregnancy FOLLOWING implantation, a series of hormonal and metabolic events occur that help to shield the fetus from unfavorable changes in the maternal environment. From an endocrine standpoint these changes are controlled by steroid production in the fetal adrenals and gonads and in the placenta, as well as polypeptide hormones produced by the fetal pituitary and placenta. There is a constant hormonal interplay among fetus, mother, and placenta during pregnancy. Human CG (hCG) concentrations rapidly increase ensuring a supply of progesterone necessary for the maintenance of pregnancy before placental production is assured. These endocrine changes, including chorionic somatomammotropin production, also alter fuel metabolism, perhaps ensuring substrate for fetal growth (1). Serum PRL levels increase as do levels of CRH as a result of pituitary and hypothalamic stimulation (2). Maternal blood volume increases by 40% above nonpregnant values due to hormonal changes and venous distension tha...

Thyroid function and hyperfunction during gestation.

A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy. ( JAMA 243:458-461, 1980)

William B. Tyler

Papers

Propylthiouracil-Induced Cutaneous Vasculitis: Case Presentation and Review of the Literature