Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated.

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Clinical use of anti-TNF therapy and increased risk of infections

OBJECTIVE: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents. METHODS: A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case-control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference. RESULTS: 38 cases of lymphoma, 31 non-Hodgkin's lymphoma (NHL) (26 B cell and five T cell), five Hodgkin's lymphoma (HL) and two Hodgkin's-like lymphoma were collected. Epstein-Barr virus was detected in both of two Hodgkin's-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3-7.1) and 3.6 (2.3-5.6) versus 0.9 (0.4-1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio 4.7 (1.3-17.7) and 4.1 (1.4-12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2). CONCLUSION: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

https://ard.bmj.com/content/annrheumdis/69/2/400.full.pdf

Lymphoma in patients treated with anti-TNF. Results of the 3-year prospective French RATIO registry.

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.

The impact of treatment with tumour necrosis factor‐α antagonists on the course of chronic viral infections: a review of the literature

Tumor necrosis factor (TNF) blockers are widely used to treat rheumatoid arthritis and other chronic inflammatory diseases. Many studies have demonstrated an increased risk of opportunistic infections such as tuberculosis and fungal infection in patients treated with TNF blockers, which is thought to be related to the primary role of TNF both in host defense and in the immune response. Little is known, however, about the association between TNF blockade and the development of viral infection. Owing to the critical role of TNF in the control of viral infection, depletion of this cytokine with TNF blockers could facilitate the development or reactivation of viral infection. A number of large observational studies have found an increased risk of herpes zoster in patients receiving TNF blockers for the treatment of rheumatoid arthritis. This Review draws attention to the risk of several viral infections, including HIV, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human papillomavirus, in patients receiving TNF-blocking therapy for chronic inflammatory conditions. In addition, implications for clinical practice and possible preventative approaches are discussed.

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Tumor necrosis factor blockade and the risk of viral infection

Summary
Background Anti-Tumour necrosis factor (TNF) therapy is now well established in the treatment of inflammatory bowel disease and the risk of opportunistic infection is recognized. However, specific considerations regarding screening, detection, prevention and treatment of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease are not widely adopted in practice.

Aim  To provide a detailed and comprehensive review of the relevance of chronic viral infections in the context of anti-TNF therapy in inflammatory bowel disease.

Methods  Literature search was conducted using Medline, Pubmed and Embase using the terms viral infection, hepatitis, herpes, CMV, EBV, HPV, anti-TNF, infliximab, adalimumab, certolizumab pegol and etanercept. Hepatitis B and C and HIV had the largest literature associated and these have been summarized in Tables.

Results  Particular risks are associated with the use of anti-TNF drugs in patients with hepatitis B infection, in whom reactivation is common unless anti-viral prophylaxis is used. Reactivation of herpes zoster is the most common viral problem associated with anti-TNF treatment, and may be particularly severe. Primary varicella infection may present with atypical features in patients on anti-TNF.

Conclusion  Appreciation of risks of chronic viral disease associated with anti-TNF therapy may permit early recognition, prophylaxis and treatment.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2036.2009.04112.x

Review article: chronic viral infection in the anti-tumour necrosis factor therapy era in inflammatory bowel disease.

This study investigated the utilization of turmeric (Curcuma aromatica Salab.) for tofu manufacture and its effects on the quality characteristics and shelf-life. Various concentration (0.000%, 0.005%, 0.010%, and 0.015%) of turmeric were used to evaluate the shelf-life during tofu storage for 12 days at . The pH decreased with an increasing storage period, but the 0.010% and 0.015% tofu showed lower pH value than the 0.000% tofu, the acidity decreased with an increasing storage period. The water content of the turmeric tofu decreased with an increasing storage period. The turbidity gradually increased until 6 days of storage, and then rapidly increased at 12 days of storage. The microbial count of the 0.015% tofu was lowest during the storage period. In measuring the turmeric tofu color, the L- and a--values decreased during the storage period, while the b--value increased. In the texture analysis, hardness, gumminess, and brittleness of the turmeric tofu decreased 12 days of storage. Cohesiveness and springiness increased with an increasing storage period. In the sensory evaluation, Smoothness, after taste, and overall taste were highest for the 0.010% tofu. For the overall acceptability, the 0.010% tofu (with 0.45% mixed coagulant) attained the highest score.

Physicochemical Quality Characteristics of Tofu Prepared with Turmeric(Curcuma aromatica Salab.)

We describe the case of a 64-year-old female patient with rheumatoid arthritis (RA), who presented with lymphoproliferative disease (LPD) soon after the administration of etanercept, and regressed very shortly after the withdrawal of it. The occurrence was also associated with the Epstein–Barr virus (EBV) infection. The case of our patient may provide the evidence that etanercept plays an etiologic role in LPD in patients with RA.

Spontaneous regression of EBV-associated diffuse lymphoproliferative disease in a patient with rheumatoid arthritis after discontinuation of etanercept treatment.

[Purpose] Many assumptions have been made about taping and several studies have considered tape application methods; however, the true effect of taping on muscle strength remains unclear. Most previous studies compared application techniques using Kinesio tape (KT), but studies that compared muscle strength using non-elastic tape (NT) are limited. Moreover, no studies have applied KT and NT in the same way to assess grip strength in normal subjects. The purpose of this study was to evaluate the immediate effect of application of two tapes with different elastic properties on maximal grip strength in healthy adults. [Subjects and Methods] Twenty healthy adults were divided into two groups (KT and NT). Maximal grip strength was measured with a dynamometer. Forearm extensor muscles of the dominant hand were then taped and subjects were immediately asked to perform hand grip movement with maximum strength in the same standardized manner. [Results] In the KT group, maximal grip strength was significantly increased compared to the initial value; however, in the NT group, there was no significant difference in maximal grip strength. [Conclusion] This study suggests that only Kinesio tape can increase maximal grip strength immediately after application on the extensor region of the forearm.

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Effects of kinesio tape compared with non-elastic tape on hand grip strength.

[Purpose] Kinesio taping is a therapeutic method used in the treatment of various musculoskeletal and neuromuscular deficits, but there is limited evidence of the effects of trunk kinesio taping in neurologic patients. Therefore, this study aimed to determine the effects of trunk kinesio taping on balance ability and gait function in persons after a stroke. [Subjects and Methods] Twenty-five post-stroke patients were included in this study. Kinesio tape was applied to four trunk muscles. Before and after the taping, in all subjects, the balance ability was measured using the Wii Balance Board, and gait function was assessed using the GAITRite system. [Results] The difference in gait function before and after trunk taping was not statistically significant. However, a variability of balance ability showed statistically significant differences. [Conclusion] These results suggest that taping may be a helpful method during rehabilitation programs for stroke patients. Its application to the trunk muscles is especially useful for improving balance ability.

The effects of trunk kinesio taping on balance ability and gait function in stroke patients.

This study was investigated the utilization of pomegranate(P) as coagulants for 새려 manufacture, the quality characteristics and shelf-life on tofu made by P1(fruit juice of pomegranate 1%) and P2(fruit juice of pomegranate 2%) and P3(fruit juice of pomegranate 3%) and P4(fruit juice of pomegranate 4%) and P5(fruit juice of pomegranate 5%) were investigated and compared to G.D.L(C). And also, total microbe and tatal acid of the tofu were determined during storage at . The results are summarized as follow P3(493.3g/500ml) compared to C(485g/500ml) showed the highest yield. Turbidity of tofu was increased as the proportion of pomegranate was increased, while pH of tofu was increased as the proportion of pomegranate was decreased. value of C tofu was highest, value of tofu was increased as the proportion of pomegranate was increased and value of C tofu was higher than those of other tofus. The hardness of tofu coagulated with pomegranate showed higher than that of coagulated G.D.L. The cohesiveness of P4, P5 showed higher than C tofu, but those of other tofus showed lower than C tofu. The springiness of tofu showed in the order of P4>P5>P3>P2>P1, gumminess of P5 tofu was highest. The Brittleness of tofu was increased as the proportion of pomegranate increased. The pH value of tofu coagulated with pomegranate increased during storage at . During the storage period of tofu, pH and total acid showed a maximum change in C tofu. Generally the total plate counts of bacteria of all tofu increased during storage at , and those of tofu with added pomegranate were shown to be lower than C tofu. The results of S.E.M(scanning electron microscopes), the lower hardness showed the more soft and the smaller particle, The particle of C tofu was small and uniformity but the size of P4, P5 tofu showed coarse. In the sensory evaluation of all tofu, sleekness, nutty, chewiness and smoothness, appearance and overall quality was the highest in C tofu. In the sensory evaluation of tofus coagulated with pomegranate. overall quality was the highest in P2.

Ji-Young Kim

Papers

Physicochemical Quality Characteristics of Tofu Prepared with Turmeric(Curcuma aromatica Salab.)

Spontaneous regression of EBV-associated diffuse lymphoproliferative disease in a patient with rheumatoid arthritis after discontinuation of etanercept treatment.

Effects of kinesio tape compared with non-elastic tape on hand grip strength.

The effects of trunk kinesio taping on balance ability and gait function in stroke patients.

Quality Characteristics and Shelf-life of Tofu Coagulated by Furie Juice of Pomegranate