Objective. To examine the rates of and risk factors for neutropenia together with the dynamics of neutrophil and other white cell subset counts in a cohort of patients treated with a tumor necrosis factor (TNF) inhibitor for inflammatory arthritis. Methods. We performed a retrospective cohort study examining the association between baseline demographics, clinical features, medications used, and development of neutropenia, and behavior of neutrophil and other white cell subset counts during TNF inhibitor therapy. Results. In 367 patients (298 [81.2%] with rheumatoid arthritis, 38 [10.4%] with ankylosing spondylitis, and 31 [8.4%] with psoriatic arthritis), 69 (18.8%) had at least one episode of neutropenia (<2.0 ؋ 10 9 /liter) during TNF inhibitor therapy, and of these, 6% developed serious infections secondary to neutropenia. There was no significant difference in disease, demographic, or drug variables between patients with and without neutropenia. However, patients with neutropenia had significantly lower baseline neutrophil counts (4.2 ؋ 10 9 /liter; 95% confidence interval [95% CI] 3.8, 4.6 versus 6.2 ؋ 10 9 /liter; 95% CI 6.0, 6.5), and a previous history of neutropenia while receiving disease-modifying antirheumatic drugs increased the risk while receiving TNF inhibitors (hazard ratio 2.97; 95% CI 1.69, 5.25). A significant drop in mean neutrophil count (1.12 ؋ 10 9 /liter; 95% CI 0.92, 1.32) was observed after 2 weeks of TNF inhibitor therapy. Other white cell subsets tended to significantly increase. Conclusion. TNF inhibitor therapy is associated with a significant reduction in peripheral blood neutrophil count, leading to 19% of patients becoming neutropenic. Risk of neutropenia is significantly higher in patients with a low baseline neutrophil count or previous history of neutropenia. We suggest that patients receiving TNF inhibitor therapy would benefit from regular complete blood cell count monitoring.

Neutrophils have been implicated in mediating much of the tissue damage associated with chronic inflammatory diseases such as rheumatoid arthritis, where they are involved in destruction of both cartilage and bone. Glucocorticoids are powerful anti-inflammatory agents, often used in the treatment of this autoimmune disease. They exert significant inhibitory effects on neutrophil activation and functions, such as chemotaxis, adhesion, transmigration, apoptosis, oxidative burst, and phagocytosis. The mechanisms by which glucocorticoids exert these effects on neutrophils are unclear. Evidence from studies of inflammation in human subjects and animal models suggests that annexin-I an endogenous, glucocorticoid-induced protein also known as lipocortin-1, has a pivotal role in modulating neutrophil activation, transmigratory, and phagocytic functions. Furthermore, we present evidence for altered neutrophil functions in rheumatoid arthritis that correspond to a significantly reduced capacity of these cells to bind annexin-I. A proposed novel pathway for glucocorticoid actions on neutrophils involving annexin-I could explain the development of chronic neutrophil activation in diseases such as rheumatoid arthritis.

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We present case histories of two patients with type 2 diabetes who were taking herbal medicines that was claimed to be effective for the management of diabetes. Both patients had purchased their herbal medicines from India. On chemical analysis, these medicines were found to contain glibenclamide. Here we discuss the use of alternative medicines in the developed world and highlight the problem that adulteration of complimentary alternative medicines with modern medicines can cause in the management of diabetes.

Baseline DAS28 is critical in classifying responders at the 6-month assessment.