idiopathic, IV ATB intravenous antibiotics, M male, NR not reported, Selleck MG 132 pt(s) patient(s), RA rheumatoid arthritis, SAE serious adverse
event, + postive Our patient presented with symptoms and signs related to all three cytopenias: fatigue (due to anemia); fever that responded to broad spectrum antibiotics (due to severe neutropenia); and petechiae and gingival bleeding (due to severe thrombocytopenia). The absence of concomitant drugs (she had been receiving methotrexate and hydroxychloroquine for years) as well as the temporal relationship between the appearance of her symptoms and the first injection of etanercept, strongly suggest a causal link. Moreover, BM recovery from toxic injury corresponded to the discontinuation of etanercept, whereas methotrexate was later continued uneventfully for months. In contrast, in some of the other cases cited, drugs other than anti-TNFα could have been responsible.
Other than listing all hitherto-reported cases of TNF blocking agent-associated aplastic anemia and pancytopenia, the literature review reveals the rarity of the association, considering that hundreds of thousands of patients have been treated. The other striking feature is the complexity Selleckchem VX 770 of the pathogenesis. TNFα is a pleiotropic cytokine, part of a complex cytokine network that regulates hematopoiesis and may affect BM stem cells differently under different circumstances [17, 18]. On one hand, TNFα (and interferon γ) are overexpressed in the BM of patients with acquired aplastic anemia and can be involved in BM stem cell
apoptosis and suppression of erythropoiesis [19, 20]. Thus, treatment with TNFα antagonists can be a useful approach to the treatment of refractory aplastic anemia [21–23]. On the other hand, under different conditions, Y-27632 2HCl TNFα interacting with other cytokines directly enhances the clonal growth of BM progenitors and suppresses hematopoietic stem cell apoptosis [17, 24]. Thus, its blockade can also exert a deleterious effect on hematopoiesis [6]. Since autoimmune mechanisms are believed to have a key role in the pathogenesis of idiopathic aplastic anemia [25], the association between TNF-targeted therapies and induction of autoimmune diseases (particularly, vasculitis and lupus predominantly with infliximab and etanercept) is also a tenable mechanism [26]. In conclusion, TNFα antagonists for the treatment of RA show significant benefit and are generally safe in comparison with other disease-modifying anti-rheumatic drugs [27–29]. BM suppression resulting in severe cytopenia, transient pancytopenia, or aplastic anemia is a well established but fortunately rare SAE of anti-TNFα therapy. Since a steadily increasing number of patients are being treated for longer periods, any serious RG-7388 purchase adverse effect, however rare, may be encountered.