Tumor necrosis factor-alpha antagonist-induced sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.

Efalizumab-induced inflammatory polyarthritis: what are the implications?

A 49-year-old female was started on efalizumab for severe psoriasis. Three weeks later, she developed rapidly progressive inflammatory polyarthritis associated with high titers of both rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibody. To our knowledge, this is the first reported case of efalizumab-induced anti-CCP-positive rheumatoid arthritis (RA). The polyarticular form of psoriatic arthritis (PsA) is associated with HLA-DR4, an antigen also associated with RA, and the presence of shared epitope alleles in PsA patients correlates with erosive disease, indicating a possible common mechanism of disease. CD4 T-cells play a prominent role in the pathogenesis of RA and PsA. Efalizumab theoretically modulates that role, appearing clinically to precipitate arthritis in a subset of PsA patients. On April 8, 2009, the makers of efalizumab announced a phased voluntary withdrawal of the drug from the US market because of progressive multifocal leukoencephalopathy cases. Further research using animal models of inflammatory polyarthritis is needed to determine the exact relationship between efalizumab and inflammatory arthritis, as well as to further explore the apparent connection between the inflammatory polyarticular form of PsA and RA.