The impact of treatment with tumour necrosis factor-alpha antagonists on the course of chronic viral infections: a review of the literature.

Biologics that antagonize the biological activity of tumour necrosis factor (TNF)-alpha, namely infliximab, etanercept and adalimumab, are increasingly used for treatment of immune-mediated inflammatory diseases, including psoriasis, worldwide. TNF-alpha antagonists are known to increase the risk of reactivation and infection, particularly of infections with intracellular bacteria such as Mycobacterium tuberculosis. More frequently these agents are given to patients with viral infections. Viral hepatitis and human immunodeficiency virus infections are often present in these patients, with a considerable geographical variation. Other concomitant viral infections such as herpes, cytomegalovirus and varicella zoster virus may occur much more frequently than tuberculosis or leprosy. General recommendations about the management related to possible problems associated with anti-TNF-alpha treatment and these viral infections are lacking. This short review will give an overview of the most recent data available on the effects of anti-TNF-alpha therapy on viral infections with a particular focus on patient management and screening recommendations.

[Thalidomide: new uses for an old drug]. / Thalidomide: nieuwe toepassingen voor een oud geneesmiddel.

Thalidomide was withdrawn from the market in the early sixties because of its teratogenic effects. Despite forty years of research, the mechanism of thalidomide embryopathy has remained unsolved. Thalidomide has various immunomodulatory effects. Thalidomide inhibits TNF alpha production, has T-cell costimulatory properties and modulates the expression of cell surface molecules on leukocytes in vivo. Thalidomide also has anti-angiogenic activity in vivo. Angiogenesis plays an important role in the pathogenesis of both solid tumours and hematologic malignancies such as multiple myeloma and lymphoma. In clinical studies, thalidomide has been used as an inhibitor of angiogenesis. Erythema nodosum leprosum is the only registered indication for the use of thalidomide in the United States of America. Thalidomide is also effective in the treatment of chronic graft-versus-host disease, mucocutaneous lesions in Behçet's syndrome and HIV infections, and multiple myeloma.

Thalidomide: rationale for renewed use in immunological disorders.

Despite its inherent teratogenic risk, thalidomide has over the years proven to be of clinical use in a small number of mainly immunological diseases (e.g. erythema nodosum leprosum, Behçet's syndrome and rheumatoid arthritis). The mode of action of thalidomide is still poorly understood. Recent research has shown a decrease in tumour necrosis factor-alpha (TNF alpha) during thalidomide treatment in several settings. Others have found altered expression of adhesion molecules. Currently, the most interesting new fields of application are the prevention and treatment of graft-versus-host disease in allogeneic bone marrow transplantation and the treatment of aphthous ulceration in HIV-positive patients. Contraceptive measures must be instituted in women receiving thalidomide, and careful monitoring for neurological adverse effects is required in all patients.